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Durlobactam

May 23, 2025 9:13 am / Leave a comment

Durlobactam

CAS 1467829-71-5

WeightAverage: 277.25
Monoisotopic: 277.03685626

Chemical FormulaC₈H₁₁N₃O₆S

Ingredient	UNII	CAS	InChI Key
Durlobactam sodium	F78MDZ9CW9	1467157-21-6	WHHNOICWPZIYKI-IBTYICNHSA-M

FDA 5/23/2023, Xacduro, To treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex
Press Release
Drug Trials Snapshots

(2S,5R)-2-CARBAMOYL-3-METHYL-7-OXO-1,6-DIAZABICYCLO(3.2.1)OCT-3-EN-6-YL SULFATE

SULFURIC ACID, MONO((2S,5R)-2-(AMINOCARBONYL)-3-METHYL-7-OXO-1,6-DIAZABICYCLO(3.2.1)OCT-3-EN-6-YL) ESTER
ETX 2514, ETX-2514, ETX2514, WHO 10824
Durlobactam is a non-beta-lactam, beta-lactamase inhibitor used to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.

Durlobactam is a beta-lactamase inhibitor used in combination with sulbactam to treat susceptible strains of bacteria in the genus Acinetobacter^[1] It is an analog of avibactam.

The combination therapy sulbactam/durlobactam was approved for medical use in the United States in May 2023.^[1]

PATENT

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US9309245	No	2016-04-12	2033-04-02
US9623014	No	2017-04-18	2033-04-02
US9968593	No	2018-05-15	2035-11-17
US10376499	No	2019-08-13	2035-11-17

SYN

https://doi.org/10.1021/acs.jmedchem.4c02079
J. Med. Chem. 2025, 68, 2147−2182

Durlobactam (1) is a copackaged antibiotic combination being developed by Entasis Therapeutics for the treatment of infections caused by Acinetobacter baumannii-calcoaceticus. 13,14
Entasis Therapeutics obtained the worldwide development rights for durlobactam (1) from AstraZeneca in 2015.13 The drug combination was approved by the USFDA in 2023 for use in patients 18 years of age and older as an intravenous infusion.13 Acinetobacter baumannii is a critical bacterial pathogen that has
become highly resistant to various β-lactam antibiotics for Gram-negative infections, including penicillin.15,16 The inventors targeted β-lactam resistance via coadministration of a β-lactamase inhibitor to restore the activity of β-lactam antibiotics. Sulbactam is a β-lactam antibiotic that inhibits penicillin binding proteins (PBP 1 and 3) essential for cell wall synthesis. Durlobactam is a β-lactamase inhibitor that protects sulbactam from degradation by Ambler class A, C, and D serine β-lactamases produced byAcinetobacter baumannii-calcoaceticus. Durlobactam binds covalently with these β-lactamases by
carbamoylating the active site serines, thus safeguarding sulbactam from enzymatic degradation.17,18 The covalent bond between durlobactam and the active site serine isreversible due to the ability of sulfated amine of durlobactam to recyclize back into urea. This allows durlobactam to exchange from one
enzyme molecule to another via a mechanism known as acylation exchange

(13) Keam, S. J. Sulbactam/Durlobactam: first approval. Drugs 2023, 83, 1245−1252.
(14) El-Ghali, A.; Kunz Coyne, A. J.;Caniff, K.; Bleick,C.; Rybak, M. J.Sulbactam-durlobactam: a novel β-lactam-β-lactamase inhibitor combination targeting carbapenem-resistant Acinetobacter baumannii
infections. Pharmacotherapy 2023, 43, 502−513.
(15) O’Donnell, J.; Tanudra, A.; Chen, A.; Miller, A. A.; McLeod, S.M.; Tommasi, R. In vitro pharmacokinetics/pharmacodynamics of the β-lactamase inhibitor, durlobactam, in combination with sulbactam against Acinetobacter baumannii-calcoaceticus complex. Antimicrob.Agents Chemother. 2024, 68, e00312-23.
(16) Arya, R.; Goldner, B. S.; Shorr, A. F. Novel agents in development for multidrug-resistant Gram-negative infections: potential new options facing multiple challenges. Curr. Opin. Infect. Dis. 2022, 35, 589−594.
(17) Shapiro, A. B.; Moussa, S. H.; McLeod, S. M.; Durand-Réville, T.; Miller, A. A. Durlobactam, a new diazabicyclooctane β-lactamase inhibitor for the treatment of Acinetobacter infections in combination
with Sulbactam. Front. Microbiol. 2021, 12, No. 709974.
(18) Iyer, R.; Moussa, S. H.; Durand-Reville, T. F.; Tommasi, R.; Miller, A. Acinetobacter baumannii OmpA is a selective antibiotic permeant porin. ACS Infect. Dis. 2018, 4, 373−381.

The route below was chosen as it was demonstrated on a multikilogram scale (Scheme 1), although some reagents (e.g.,triphosgene) are not typical for large-scale manufacturing.20,22 The synthesis commenced with the condensation of glyoxylic acid monohydrate (1.1) with (S)-tert-butylsulfinamide (1.2) to generate a solution of 2-(tert-butylsulfinylimino)acetic acid 1.3. In parallel, commercially available trans-crotyl alcohol (1.4) was treated with diboronic acid (1.5) in the presence of a palladium catalyst to produce a solution of crotylboronic acid 1.6. These two solutions were mixed to afford chiral α-amino acid 1.7 in
58% overall yield. Diastereo- and enantioselectivity were not reported for the transformation.
Conversion of 1.7 into durlobactam sodium (1) is described in Scheme 2. First, the carboxylic acid 1.7 was converted to an amide and the sulfinamide was removed to afford amino amide 1.8 as an HCl salt. The primary amine in 1.8 was subsequently alkylated with allyl bromide (1.9) and the resulting allyl amine
was protected with Boc anhydride to provide olefin metathesis precursor 1.10. Bisolefin 1.10 was then subjected to Grubbs first-generation catalyst (Grubbs-I) to generate a tetrahydropyridine precursor, which participated in a one-pot nitroso-ene reaction with N-Boc hydroxylamine (1.11) to produce allyl
hydroxylamine 1.12 in 61% overall yield. This key transformation efficiently installed the amine stereocenter required for formation of the bridged urea. Next, the hydroxyl moiety in 1.12 was protected as the TBS ether and the two Boc groups were removed with ZnBr2 to unveil bis-amine 1.13. The intramolecular urea formation was accomplished by the treatment with triphosgene to generate diazabicyclooctene 1.14 in 50% yield over 3 steps. The TBS ether was then removed, and the hydroxyl urea intermediate was treated with sulfur trioxide-pyridine complex and tetrabutylammonium
hydrogen sulfate to afford durlobactam tetrabutylammonium salt 1.15. Finally, tetrabutylammonium durlobactam 1.15 was converted to a calcium salt and subsequently to the targeted sodium salt providing 1. The authors mentioned that the salt formations were required to improve the purity of the final API
(>99%), however, the yields of these steps were not reported.22

(19) McGuire, H.; Bist, S.; Bifulco, N.; Zhao, L.; Wu, Y.; Huynh, H.; Xiong, H.; Comita-Prevoir, J.; Dussault, D.; Geng, B.; et al. Preparation of oxodiazabicyclooctenyl hydrogen sulfate derivatives for use as betalactamase inhibitors. WO 2013150296, 2013.
(20) Basarab, G. S.; Moss, B.; Comita-Prevoir, J.; Durand-Reville, T. F.; Gauthier, L.; O’Donnell, J.; Romero, J.; Tommasi, R.; Verheijen, J.C.; Wu, F.; et al. Preparation of substituted 2-(1,6-diazabicyclo[3.2.1]-
oct-3-en-6-yloxy)acetates as beta-lactamase inhibitors. WO2018053215, 2018.
(21) Durand-Reville, T. F.;Comita-Prevoir, J.; Zhang, J.; Wu, X.; MayDracka, T. L.; Romero, J. A. C.; Wu, F.; Chen, A.; Shapiro, A. B.; Carter, N. M.; et al. Discovery of an orally available diazabicyclooctane
inhibitor (ETX0282) of class A, C, and D serine β-lactamases. J. Med.Chem. 2020, 63, 12511−12525.
(22) Durand-Reville, T. F.; Wu, F.; Liao, X.; Wang, X.; Zhang, S.Preparation of Durlobactam crystalline forms. WO 2023206580, 2023

syn

https://www.mdpi.com/1424-8247/15/3/384

Synthesis of Durlobactam

Chemically, durlobactam is [(2S,5R)-2-carbamoyl-3-methyl-7-oxo-1,6-diazabicyclo [3.2.1] oct-3-en-6-yl] hydrogen sulfate which can be prepared from the key intermediate hydroxyurea 6-hydroxy-3-methyl-7-oxo-1,6-diaza-bicyclo [3.2.1] oct-3-ene-2-carboxylic acid amide I, which is the structural isomer of III prepared to synthetize ETX-1317 [101]. Then, according to Scheme 15, compound 1 obtained in the synthesis of III (Scheme 14) was reacted with penta-1,3-diene in place of isoprene, and, by an aza-Diels−Alder reaction, compound 2 was obtained.

Scheme 15. Synthesis of durlobactam (C₈H₁₁N₃O₆S, MW = 277.36, IUPAC name, [(2S,5R)-2-carbamoyl-3-methyl-7-oxo-1,6-diazabicyclo [3.2.1] oct-3-en-6-yl] hydrogen sulphate.

Compound 2 underwent deprotection of the tert-butyl sulfinyl group to afford 3, subsequently Boc protected, to give compound 4. The saponification of the ester followed by amide coupling using ammonium acetate afforded compound 5. The reaction of alkene 5 with N-Boc-hydroxylamine in the presence of oxygen or air gave the desired compound 6 in a single step. Compound 6 was then protected with TBS group, using TBSCl to afford 7, which was Boc deprotected using zinc bromide obtaining compound 8. Cyclization of the diamine 8 with tri-phosgene provided the corresponding cyclic urea 9, which was TBS deprotected with HFPy to give the key intermediate I. This compound was then immediately sulfated with the DMF:SO₃ complex to obtain the sulfate, which was isolated as its tetrabutylammonium salt 10 by reacting with tetrabutylammonium acetate. The tetrabutylammonium salt was converted to durlobactam in the form of sodium salt by passing 10 through a column filled with Indion 225 sodium resin.

REF

https://sioc-journal.cn/Jwk_yjhx/EN/abstract/abstract350784.shtml

References

^ Jump up to:^a ^b “FDA Approves New Treatment for Pneumonia Caused by Certain Difficult-to-Treat Bacteria”. U.S. Food and Drug Administration (Press release). 24 May 2023. Retrieved 24 May 2023. This article incorporates text from this source, which is in the public domain.


Clinical data
Other names	ETX2514
Routes of administration	Intravenous
Drug class	Antibacterial, beta-lactamase inhibitor
ATC code	None
Legal status
Legal status	US: ℞-only co-packaged with sulbactam
Identifiers
showIUPAC name
CAS Number	1467829-71-5
PubChem CID	89851852
DrugBank	DB16704 DBSALT003190
ChemSpider	57617784 71060725
UNII	PSA33KO9WA F78MDZ9CW9
KEGG	D11591 D11592
ChEMBL	ChEMBL4298137 ChEMBL4297378
Chemical and physical data
Formula	C₈H₁₁N₃O₆S
Molar mass	277.25 g·mol⁻¹
3D model (JSmol)	Interactive image
showSMILES
showInChI

Edelinontrine

May 23, 2025 3:03 am / Leave a comment

Edelinontrine

CRD740, PF04447943, cas 1082744-20-4

Molecular Weight	395.46
Formula	C₂₀H₂₅N₇O₂

6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(oxan-4-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one

Edelinontrine (PF-04447943) is a potent inhibitor of human recombinant PDE9A (IC₅₀=12 nM) with >78-fold selectivity, respectively, over other PDE family members (IC₅₀>1000 nM).

PF-04447943 is a potent, selective brain penetrant PDE9 inhibitor (Ki of 2.8, 4.5 and 18 nM) for human, rhesus and rat recombinant PDE9 respectively and high selectivity for PDE9 versus PDEs1-8 and 10-11. PF-04447943 was being developed by Pfizer for the treatment of cognitive disorders. PF-04447943 attenuates a scopolamine-induced deficit in a novel rodent attention task. PF-04447943 enhances synaptic plasticity and cognitive function in rodents. PF-04447943 has completed Phase II clinical trials in subjects with mild to moderate AD in 2013 but this research was discontinued. Pfizer completes a phase I trial in Sickle cell anaemia.

SCHEME

SUDECHAIN

MAIN

Patent

WO2023114995 PFIZER

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023114995&_cid=P20-MB07JE-44537-1

PAPER

Journal of Medicinal Chemistry (2012), 55(21), 9045-9054

PATENT

WO2008139293

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2008139293&_cid=P20-MB07LY-46583-1

EXAMPLE 111

6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyiτolidin-3-yl]-1-αetrahydro-2H- pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one

///////Edelinontrine, CRD740, PF04447943, CRD 740, PF 04447943, PHASE 1

Sulbactam

May 22, 2025 1:11 pm / Leave a comment

Sulbactam

Ingredient	UNII	CAS	InChI Key
Sulbactam benzathine	49MU89FVBV	83031-43-0	YSEPFTSCLHUBNH-HFKSPEPWSA-N
Sulbactam sodium	DKQ4T82YE6	69388-84-7	NKZMPZCWBSWAOX-IBTYICNHSA-M

68373-14-8 (free acid)

WeightAverage: 233.242
Monoisotopic: 233.035793157

Chemical FormulaC₈H₁₁NO₅S

(2S,5R)-3,3-dimethyl-4,4,7-trioxo-4λ⁶-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Betamaze, Penicillanic Acid Sulfone, Sulbactamum, CP 45899, CP-45899, CP45899

FDA 2023, Xacduro, 5/23/2023, To treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex
Press Release
Drug Trials Snapshots

Sulbactam is a β-lactamase inhibitor. This drug is given in combination with β-lactam antibiotics to inhibit β-lactamase, an enzyme produced by bacteria that destroys the antibiotics.^[1]

It was patented in 1977 and approved for medical use in 1986.^[2]

Sulbactam is a beta (β)-lactamase inhibitor and a derivative of the basic penicillin nucleus. When given in combination with β-lactam antibiotics, sulbactam produces a synergistic effect as it blocks the enzyme responsible for drug resistance by hydrolyzing β-lactams.

PATENT

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US9309245	No	2016-04-12	2033-04-02
US9623014	No	2017-04-18	2033-04-02
US9968593	No	2018-05-15	2035-11-17
US10376499	No	2019-08-13	2035-11-17

doi:10.1016/S0040-4039(00)89275-8

SYN

European Journal of Medicinal Chemistry

Volume 265, 5 February 2024, 116124

https://doi.org/10.1016/j.ejmech.2024.116124

On May 23, 2023, the FDA granted approval to Xacduro for the treatment of Baumannii-sensitive strains causing hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia in
patients aged 18 years or older [4]. Xacduro consists of Sulbactam and Durlobactam. Sulbactam, a medication with a similar structure to Penicillin, has the ability to eliminate Acinetobacter baumannii. On the other hand, Durlobactam shields Sulbactam from being broken down by enzymes that may be produced by Acinetobacter baumannii [5].
The production process of Sulbactam started with 6-aminopenicilanic acid (6-APA) (SULB-001) as the starting material (Scheme 1) [6]. It underwent bromination reaction with sodium nitrite and bromine
in the presence of sulfuric acid. Then, SULB-002 was oxidized by potassium permanganate to obtain sulfone SULB-003. Finally, the sulfonewas catalytically hydrogenated and dehalogenated in the presence of Raney nickel to get Sulbactam

[5] A. El-Ghali, A.J. Kunz Coyne, K. Caniff, C. Bleick, M.J. Rybak, Sulbactamdurlobactam: a novel β-lactam-β-lactamase inhibitor combination targeting
carbapenem-resistant Acinetobacter baumannii infections, Pharmacotherapy 43
(2023) 502–513.
[6] Z.M. Song, W. Liu, J. Yang, Y. Sun, Improvement on the synthetic process of
sulbactam, Chin. J

PATENT

https://patents.google.com/patent/CN101967155A/en

Embodiment 1

In the four-hole boiling flask of 2000ML, add 600ML methylene dichloride and 180ML2.5N sulfuric acid, stirring is cooled to below 0 ℃, add 28ML bromine and 25g Sodium Nitrite, 0 ± 0.2 ℃, gradation adds 40g 6-APA, and controlled temperature is lower than 5 ℃, stirring reaction 1h, be cooled to then below 0 ℃, 20% aqueous solution of sodium bisulfite of dropping below 0 ℃ leaves standstill phase-splitting to the color fade of bromine, water 100ML dichloromethane extraction 3 times, merge organic phase, with 100ML saturated sodium-chloride water solution washing 2 times, obtain 6, the 6-dibromo penicillanic acid;

To go up 6, the 6-dibromo penicillanic acid changes in the 2000ML beaker mutually. and add 250ML distilled water and stir, be cooled to below 5 ℃, drip 4NNaHCO ₃The aqueous solution leaves standstill phase-splitting to pH=7, organic phase extracts 3 times with the 80ML deionized water, merge water, water changes in the 2000ML four-hole boiling flask, stirring is cooled to 0 ℃, and beginning dropping oxidizing agent (44g KMn04+10.8ML H3P04+700MLH20 stirring and dissolving) dripped in 30 minutes, controlled temperature is lower than 10 ℃ in the dropping process, keep 0～5 ℃ then, stirring reaction 1h adds the 500ML ethyl acetate, drip 6N sulfuric acid to pH=1.25, be cooled to 0 ℃, slowly add the color fade of 27.5% hydrogen peroxide (about 45g) to KMn04, during continue to keep pH=1.25 with 6N sulfuric acid, controlled temperature is lower than 10 ℃, reaction 10mi n filters, and adds sodium-chlor in the filtrate to no longer dissolving, leave standstill the branch phase of anhydrating, water 250ML ethyl acetate extraction 4 times merge organic phase, and wash 2 times with the 100ML saturated sodium-chloride water solution, organic phase contains 6, the acid of 6-dibromo sulbactam;

To go up 6,6-dibromo sulbactam acid organic phase changes in the 2000ML four-hole boiling flask, adds 350ML water, is cooled to below 5 ℃, uses 4N NaHCO ₃The aqueous solution is transferred pH to 5.0, and add 25ML methyl alcohol, add the 26g zinc powder in batches, and drip 6N sulfuric acid maintenance pH:4.5～5.5, after adding zinc powder, keep stirring reaction 4h below 5 ℃, keep pH=4.5～5.5 with 6N sulfuric acid simultaneously, filter, with 25ML ethyl acetate and 25ML water washing, merging filtrate is transferred pH to 2.0 with 6N sulfuric acid, add sodium-chlor to water insoluble till, leave standstill the branch phase of anhydrating, water merges organic phase with 150ML ethyl acetate extraction 4 times, washs to redness with the 50ML-100ML5% potassium permanganate solution earlier at organic layer and does not take off, again with 150ML saturated sodium-chloride water solution washing 2 times, layering, organic layer add the 2g activated carbon decolorizing, the 15g anhydrous magnesium sulfate drying, suction filtration, be evaporated to feed liquid and be creamy white, cool to 0 ℃ after centrifuging, after the oven dry product Sulbactam (sulbactam acid) 32g, the product yield is 74%, the product colour pure white was placed 30 days the color no change under the room temperature.

Embodiment 2

In the reactor of 2000L, add 600L methylene dichloride and 180L2.5N sulfuric acid, stirring is cooled to below 0 ℃, add 28L bromine and 25Kg Sodium Nitrite, 0 ± 0.2 ℃, gradation adds 40Kg 6-APA, and controlled temperature is lower than 5 ℃, stirring reaction 1h, be cooled to then below 0 ℃, 20% aqueous solution of sodium bisulfite of dropping below 0 ℃ leaves standstill phase-splitting to the color fade of bromine, water 100L dichloromethane extraction 3 times, merge organic phase, with 100L saturated sodium-chloride water solution washing 2 times, obtain 6, the 6-dibromo penicillanic acid;

Will on obtain 6, the 6-dibromo penicillanic acid changes in the 2000L reactor mutually. add the 250L tap water and stir, be cooled to below 5 ℃, drip 4NNaHCO ₃The aqueous solution leaves standstill phase-splitting to pH=7, organic phase extracts 3 times with the 80L deionized water, merge water, water changes in the 2000L reactor, stirring is cooled to 0 ℃, and beginning dropping oxidizing agent (44Kg KMn04+10.8L H3P04+700LH20 stirring and dissolving) dripped in 30 minutes, controlled temperature is lower than 10 ℃ in the dropping process, keep 0～5 ℃ then, stirring reaction 1h adds the 500L ethyl acetate, drip 6N sulfuric acid to pH=1.25, be cooled to 0 ℃, slowly add 28% hydrogen peroxide (about 44Kg) color fade to KMn04, during continue to keep pH=1.25 with 6N sulfuric acid, controlled temperature is lower than 10 ℃, reaction 10mi n filters, and adds sodium-chlor in the filtrate to no longer dissolving, leave standstill the branch phase of anhydrating, water 250L ethyl acetate extraction 4 times merge organic phase, and wash 2 times with the 100L saturated sodium-chloride water solution, organic phase contains 6, the acid of 6-dibromo sulbactam;

To go up organic phase and contain 6, the acid of 6-dibromo sulbactam changes in the 2000L reactor, adds 350L water, is cooled to below 5 ℃, uses 4N NaHCO ₃The aqueous solution is transferred pH to 5.0, and add 25L methyl alcohol, add the 26Kg zinc powder in batches, and drip 6N sulfuric acid maintenance pH:4.5～5.5, after adding zinc powder, keep stirring reaction 4h below 5 ℃, keep pH=4.5～5.5 with 6N sulfuric acid simultaneously, filter, with 25L ethyl acetate and 25L water washing, merging filtrate is transferred pH to 2.0 with 6N sulfuric acid, add sodium-chlor to water insoluble till, leave standstill the branch phase of anhydrating, water merges organic phase with 150L ethyl acetate extraction 4 times, washs to redness with the 30-50L10% potassium permanganate solution earlier at organic layer and does not take off, again with 150L saturated sodium-chloride water solution washing 2 times, layering, organic layer add the 2Kg activated carbon decolorizing, the 15Kg anhydrous magnesium sulfate drying, suction filtration, be evaporated to feed liquid and be creamy white, cool to 0 ℃ after centrifuging, after the oven dry product Sulbactam (sulbactam acid) 31.5Kg, the product yield is 72.8%, the product colour pure white was placed 30 days the color no change under the room temperature.

Embodiment 3

In the four-hole boiling flask of 1000ML, add 300ML methylene dichloride and 90ML2.5N Hydrogen bromide, stirring is cooled to below 0 ℃, add 14ML bromine and 12.5g Sodium Nitrite, 0 ± 0.2 ℃, gradation adds 20g 6-APA, and controlled temperature is lower than 5 ℃, stirring reaction 1h, be cooled to then below 0 ℃, 20% aqueous solution of sodium bisulfite of dropping below 0 ℃ leaves standstill phase-splitting to the color fade of bromine, water 50ML dichloromethane extraction 3 times, merge organic phase, with 50ML saturated sodium-chloride water solution washing 2 times, obtain 6, the 6-dibromo penicillanic acid;

To go up 6, the 6-dibromo penicillanic acid changes in the 1000ML beaker mutually. and add 125ML distilled water and stir, be cooled to below 5 ℃, drip 4NNaHCO ₃The aqueous solution leaves standstill phase-splitting to pH=7, organic phase extracts 3 times with the 40ML deionized water, merge water, water changes in the 1000ML four-hole boiling flask, stirring is cooled to 0 ℃, and beginning dropping oxidizing agent (22g KMn04+5.4ML H3P04+300MLH20 stirring and dissolving) dripped in 30 minutes, controlled temperature is lower than 10 ℃ in the dropping process, keep 0～5 ℃ then, stirring reaction 1h adds the 250ML ethyl acetate, drip 6N sulfuric acid to pH=1.25, be cooled to 0 ℃, slowly add 25% hydrogen peroxide (about 29g) color fade to KMn04, during continue to keep pH=1.25 with 6N sulfuric acid, controlled temperature is lower than 10 ℃, reaction 10mi n filters, and adds sodium-chlor in the filtrate to no longer dissolving, leave standstill the branch phase of anhydrating, water 125ML ethyl acetate extraction 4 times merge organic phase, and wash 2 times with the 50ML saturated sodium-chloride water solution, organic phase contains 6, the acid of 6-dibromo sulbactam.

To go up organic phase and contain 6, the acid of 6-dibromo sulbactam changes in the 1000ML four-hole boiling flask, adds 175ML water, is cooled to below 5 ℃, uses 4N NaHCO ₃The aqueous solution is transferred pH to 5.0, and add 12.5ML methyl alcohol, add the 13g zinc powder in batches, and drip 6N sulfuric acid maintenance pH:4.5～5.5, after adding zinc powder, keep stirring reaction 4h below 5 ℃, keep pH=4.5～5.5 with 6N sulfuric acid simultaneously, filter, with 12.5ML ethyl acetate and 12.5ML water washing, merging filtrate is transferred pH to 2.0 with 6N sulfuric acid, add sodium-chlor to water insoluble till, leave standstill the branch phase of anhydrating, water merges organic phase with 75ML ethyl acetate extraction 4 times, washs to redness with the 15ML-35ML7% potassium permanganate solution earlier at organic layer and does not take off, again with 75ML saturated sodium-chloride water solution washing 2 times, layering, organic layer add the 1g activated carbon decolorizing, the 7.5g anhydrous magnesium sulfate drying, suction filtration, be evaporated to feed liquid and be creamy white, cool to 0 ℃ after centrifuging, after the oven dry product Sulbactam (sulbactam acid) 15.9g, the product yield is 73.5%, the product colour pure white was placed 30 days the color no change under the room temperature.

PATENT

https://patents.google.com/patent/US4420426A/en

Medical uses

The combination ampicillin/sulbactam (Unasyn) is available in the United States.^[3]

The combination cefoperazone/sulbactam (Sulperazon) is available in many countries but not in the United States.^[4]

The co-packaged combination sulbactam/durlobactam was approved for medical use in the United States in May 2023.^[5]

Mechanism

Sulbactam is primarily used as a suicide inhibitor of β-lactamase, shielding more potent beta-lactams such as ampicillin.^[6] Sulbactam itself contains a beta-lactam ring, and has weak antibacterial activity by inhibiting penicillin binding proteins (PBP) 1 and 3, but not 2.^[7]

References

^ Totir MA, Helfand MS, Carey MP, Sheri A, Buynak JD, Bonomo RA, Carey PR (August 2007). “Sulbactam forms only minimal amounts of irreversible acrylate-enzyme with SHV-1 beta-lactamase”. Biochemistry. 46 (31): 8980–8987. doi:10.1021/bi7006146. PMC 2596720. PMID 17630699.
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 492. ISBN 9783527607495.
^ “Unasyn- ampicillin sodium and sulbactam sodium injection, powder, for solution”. DailyMed. U.S. National Library of Medicine. 29 March 2023. Retrieved 25 May 2023.
^ “Sulperazon”. drugs.com.
^ “FDA Approves New Treatment for Pneumonia Caused by Certain Difficult-to-Treat Bacteria”. U.S. Food and Drug Administration (Press release). 24 May 2023. Retrieved 24 May 2023.
^ Crass RL, Pai MP (February 2019). “Pharmacokinetics and Pharmacodynamics of β-Lactamase Inhibitors”. Pharmacotherapy. 39 (2): 182–195. doi:10.1002/phar.2210. PMID 30589457. S2CID 58567725.
^ Penwell WF, Shapiro AB, Giacobbe RA, Gu RF, Gao N, Thresher J, et al. (March 2015). “Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii”. Antimicrobial Agents and Chemotherapy. 59 (3): 1680–1689. doi:10.1128/AAC.04808-14. PMC 4325763. PMID 25561334.



Clinical data
AHFS/Drugs.com	International Drug Names
MedlinePlus	a693021
Routes of administration	Intravenous, intramuscular
ATC code	J01CG01 (WHO)
Legal status
Legal status	UK: POM (Prescription only)
Pharmacokinetic data
Protein binding	29%
Elimination half-life	0.65–1.20 hrs
Excretion	Mainly kidneys (41–66% within 8 hrs)
Identifiers
showIUPAC name
CAS Number	68373-14-8
PubChem CID	130313
ChemSpider	115306
UNII	S4TF6I2330
KEGG	D08533
ChEBI	CHEBI:9321
ChEMBL	ChEMBL403
CompTox Dashboard (EPA)	DTXSID1023605
ECHA InfoCard	100.063.506
Chemical and physical data
Formula	C₈H₁₁NO₅S
Molar mass	233.24 g·mol⁻¹
3D model (JSmol)	Interactive image
Melting point	148 to 151 °C (298 to 304 °F)
showSMILES
showInChI

Eclitasertib

May 22, 2025 3:12 am / Leave a comment

Eclitasertib

CAS 2125450-76-0

5-benzyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydropyrido[3,2-b][1,4]oxazepin-3-yl]-1H-1,2,4-triazole-3-carboxamide

DNL-758
SAR-443122
Eclitasertib (DNL-758) is a potent receptor-interacting protein kinase 1 (RIPK1) inhibitor with an IC₅₀ of 0.0375 µΜ.
UNII-975AT1P9J6

Molecular Weight	378.38
Formula	C₁₉H₁₈N₆O₃

OriginatorHarvard University
DeveloperDenali Therapeutics Inc; Sanofi
Class2 ring heterocyclic compounds; Amides; Anti-inflammatories; Antipsoriatics; Antirheumatics; Oxazepines; Pyridines; Skin disorder therapies; Small molecules; Triazoles
Mechanism of ActionRIPK1 protein inhibitors

Phase IIUlcerative colitis
DiscontinuedCutaneous lupus erythematosus; Psoriasis; Rheumatoid arthritis; SARS-CoV-2 acute respiratory disease
12 Mar 2024Discontinued – Phase-I for Psoriasis (In volunteers) in USA (unspecified route) (Denali pipeline, February 2024)
12 Mar 2024Discontinued – Phase-I for Rheumatoid arthritis (In volunteers) in USA (unspecified route) (Denali pipeline, February 2024)
27 Feb 2024Efficacy and adverse events data from phase II trial in Cutaneous lupus erythematosus released by Sanofi

SAR443122, was investigated in several clinical trials to evaluate its safety and efficacy. NCT04469621 was studied in severe COVID-19 patients, while NCT05588843 is currently recruiting participants with ulcerative colitis. Additionally, NCT04781816, which was completed with results, focused on patients with cutaneous lupus erythematosus.

Eclitasertib is an orally bioavailable, small-molecule inhibitor of receptor-interacting serine/threonine-protein kinase 1 (RIPK1; receptor-interacting protein 1; RIP1), with potential anti-inflammatory and immunomodulatory activities. Upon oral administration, eclitasertib disrupts RIPK1-mediated signaling, and may attenuate inflammation and the resulting tissue damage. RIPK1, a signaling protein in the tumor necrosis factor (TNF) receptor pathway, plays a key role in inflammation and cell death in response to tissue damage and pathogen recognition.

SCHEME

SIDE CHAIN

MAIN

REF

WO2017136727

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2017136727&_cid=P22-MAYSGO-11421-1

Example 42: (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepin-3-yl)- 4H-1,2,4-triazole-3-carboxamide

Step 1: Preparation oƒ (2S)-2-(((tert-butoxy)carbonyl)amino)-3-((2-nitropyridin-3-yl)oxy)propanoic acid

[0535] Sodium hydride (60%, 2 g, 50 mmol) was added into a stirring solution of (2S)-2-(tert-butoxycarbonylamino)-3-hydroxypropanoic acid (5 g, 25.0 mmol) in N,N-dimethylformamide (100 mL). The resulting mixture was stirred at 0 °C for 2 hours. 3-Fluoro-2-nitropyridine (3.6 g, 25.3 mmol) was added and the reaction mixture was stirred at room temperature for an additional 8 hours before quenching with hydrochloric acid (3 N, 5 mL). After adjusting the pH to 3-4 with hydrochloric acid (3 N, 20 mL), the resulting mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by reversed phase chromatography with a RP-C18 column (acetonitrile/water, 1/2) to afford the title compound (3.2 g, 39%) as a light yellow oil. LC-MS (Method C): m/z = 272.1 [M+H-(t-BuO)]⁺, 1.269 min.

Step 2: Preparation oƒ (2S)-3-((2-aminopyridin-3-yl)oxy)-2-(((tert-butoxy)carbonyl)amino)propanoic acid

[0536] (2S)-2-(((tert-butoxy)carbonyl)amino)-3-((2-nitropyridin-3-yl)oxy)propanoic acid (0.45 g, 1.4 mmol) in methanol (20 mL) was aged overnight at room temperature in the presence of palladium on carbon (10%, 0.5 g) under hydrogen atmosphere (2-3 atm). The reaction mixture was filtered through Celite and the filtrate was concentrated under reduced pressure to afford the title compound (0.32 g, 78%) as a yellow oil. LC-MS (Method C): m/z = 298.1 [M+H]⁺, 0.982 min.

Step 3: Preparation oƒ tert-butyl N-((3S)-4-oxo-2H,3H,4H,5H-pyrido[3,2-b][1,4]oxazepin-3-yl)carbamate

[0537] N,N,N’,N’-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophospate (0.73 g, 1.92 mmol) and N,N-diisopropylethylamine (0.25 g, 1.93 mmol) were added to a stirring solution of (2S)-3-((2-aminopyridin-3-yl)oxy)-2-(((tert-butoxy)carbonyl)amino)propanoic acid (0.45 g, 1.51 mmol) in N,N-dimethylformamide (5 mL). After stirring for 6 hours at room temperature, the reaction mixture was quenched by the addition of water (20 mL), and extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography (methanol/dichloromethane, 1/10) to afford the title compound (0.11 g, 26%) as a white solid. LC-MS (Method C): m/z = 280.1 [M+H]⁺, 1.248 min.

tep 4: Preparation oƒ tert-butylN-((3S)-5-methyl-4-oxo-2H,3H,4H,5H-pyrido[3,2-b][1,4]oxazepin-3-yl)carbamate

[0538] Iodomethane (50 mg, 0.35 mmol) was added dropwise to a stirring solution of tert-butyl N-((3S)-4-oxo-2H,3H,4H,5H-pyrido[3,2-b][1,4]oxazepin-3-yl)carbamate (100 mg, 0.36 mmol) and cesium carbonate (120 mg, 0.36 mmol) in N,N-dimethylformamide (5 mL). After stirring for 3 hours at room temperature, the reaction mixture was diluted with water (20 mL), and extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (methanol/dichloromethane, 1/10) to afford the title compound (90 mg, 86%) as a white solid. LC-MS (Method C): m/z = 294.1 [M+H]⁺, 1.333 min.

Step 5: Preparation oƒ (3S)-3-amino-5-methyl-2H,3H,4H,5H-pyrido-[3,2-b][1,4]oxazepin-4-one hydrochloride

[0539] tert-butyl N-((3S)-5-methyl-4-oxo-2H,3H,4H,5H-pyrido[3,2-b][1,4]oxazepin-3-yl)carbamate (90 mg, 0.31 mmol) was added to a solution of hydrogen chloride in dioxane (4 M, 10 mL). The reaction mixture was stirred for 3 hours at room temperature and concentrated under reduced pressure to afford the title compound (65 mg, 93%) as a white solid, which was used directly in the next step without further purification. LC-MS (Method C): m/z = 194.1 [M+H]⁺, 0.847 min.

Step 6: Preparation oƒ (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido[3,2-b][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide

[0540] A solution of (3S)-3-amino-5-methyl-2H,3H,4H,5H-pyrido-[3,2-b][1,4]oxazepin-4-one hydrochloride (55 mg, 0.24 mmol) in N,N-dimethylformamide (1 mL) was added to a stirring solution of 5-benzyl-2H-1,2,4-triazole-3-carboxylic acid (80 mg, 0.40 mmol), 1-hydroxy-benzotrizole (70 mg, 0.53 mmol), N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (100 mg, 0.52 mmol) and N,N-

diisopropylethylamine (160 mg, 1.21 mmol) in N,N-dimethylformamide (2 mL). After stirring for 8 hours at room temperature, the reaction mixture was quenched by the addition of water (20 mL), and extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by Prep-HPLC with the following conditions: Column, XBridge Shield RP18 OBD Column, 5 μm, 19 x 150 mm; mobile phase, water (0.1% formic acid) and ACN (30.0% ACN to 60.0% over 7 min); Detector, UV 254 & 220 nm to afford the title compound. ¹H NMR (300 MHz, DMSO-d₆) δ 14.45 (s, 1H), 8.67 (d, J= 7.2 Hz, 1H), 8.37 (dd, J= 4.8, 1.8 Hz, 1H), 7.71 (dd, J= 7.8, 1.5 Hz, 1H), 7.37-7.21 (m, 6H), 4.92-4.82 (m, 1H), 4.73 (dd, J= 11.4, 9.6 Hz, 1H), 4.53 (dd, J= 9.6, 7.5 Hz, 1H), 4.14 (s, 2H), 3.37 (s, 3H). LC-MS (Method D): m/z = 379.1 [M+H]⁺, 1.611 min.

PATENT

WO2023182512

WO2023137035

WO2022208262

WO2021211919

WO2021209740

WO2021205298

WO2021205296

, WO2017136727

PAPER

European Journal of Medicinal Chemistry (2021), 220, 113484

Structure-based bioisosterism design of thio-benzoxazepinones as novel necroptosis inhibitors

Publication Name: European Journal of Medicinal Chemistry

Publication Date: 2021-08-05

PMID: 33930803

DOI: 10.1016/j.ejmech.2021.113484

PATENT

WO2021203011

[1]. Anthony A. ESTRADA, et al. Compounds, compositions and methods. WO2017136727A2.[2]. Darwish I, et al., Rip1k inhibitors. WO2021203011

//////////Eclitasertib, DNL-758, SAR-443122, DNL 758, SAR 443122, UNII-975AT1P9J6, Phase 2, Ulcerative colitis

Perfluorhexyloctane

May 21, 2025 2:49 am / Leave a comment

WeightAverage: 432.269
Monoisotopic: 432.112266666Chemical FormulaC₁₄H₁₇F₁₃

Perfluorhexyloctane

133331-77-8
MIEBO
Tetradecane, 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-
7VYX4ELWQM
NOV03, NOV 03
1-(perfluorohexyl)octane
F6H8
NOV03
Perfluorohexyloctane

1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorotetradecane

FDA APPROVED 8/16/2023, Sohonos, To reduce the volume of new heterotopic ossification in adults and pediatric patients (aged 8 years and older for females and 10 years and older for males) with fibrodysplasia ossificans progressiva
Drug Trials Snapshot

Perfluorohexyloctane is a fluoroalkane that is tetradecane in which all of the hydrogen atoms at positions 1, 2, 3, 4, 5, and 6 have been replaced by fluorine atoms. It is an ophthalmic solution used to treat the signs and symptoms of dry eye disease. It has a role as an ophthalmology drug and a nonionic surfactant. It is a fluorohydrocarbon and a fluoroalkane. It derives from a hydride of a tetradecane.

Perfluorohexyloctane (branded as Evotears, Miebo,^[a] and Novatears, among others) is a medication used for the treatment of dry eye disease.^[4] It is a semifluorinated alkane.^[4]

Perfluorohexyloctane has been available in multiple markets since 2015 under the brand names Evotears and Novatears,^[5] and was additionally approved for medical use in the United States in May 2023 under the brand name Miebo.^[4]^[6] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.^[7]

PATENT

Show 102550100 entries

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US11357738	No	2022-06-14	2036-09-29
US10058615	No	2018-08-28	2033-09-12
US10369117	No	2019-08-06	2033-09-12
US10449164	No	2019-10-22	2033-09-12
US10507132	No	2019-12-17	2037-06-21
US10576154	No	2020-03-03	2033-09-12

SYN

https://www.scientificupdate.com/process-chemistry-articles/not-a-dry-eye-in-the-house

Medical uses

Perfluorohexyloctane is indicated for the treatment of the signs and symptoms of dry eye disease.^[4]^[8]^[9]

Availability

Perfluorohexyloctane is sold as an over-the-counter medication under the brand names Evotears and Novatears in multiple countries,^[10] costing around NZ$34.00, A$30, and €30 for a one-month supply.

In the US, perfluorohexyloctane is sold under the brand name Miebo; a prescription is required.

Notes and references

^ /ˈmaɪboʊ/ MY-bow

^ “Notice: Multiple additions to the Prescription Drug List (PDL) [2024-10-18]”. Health Canada. 18 October 2024. Retrieved 25 October 2024.
^ “Miebo product information”. Health Canada. 4 September 2024. Retrieved 27 December 2024.
^ “Regulatory Decision Summary for Miebo”. Drug and Health Products Portal. 4 September 2024. Retrieved 27 December 2024.
^ Jump up to:^a ^b ^c ^d ^e “Miebo- perfluorohexyloctane solution”. DailyMed. 18 May 2023. Retrieved 8 June 2023.
^ “URSAPHARM GmbH and Novaliq GmbH Announce European Partnership Agreement” (Press release). Retrieved 15 February 2024.
^ “Bausch + Lomb and Novaliq Announce FDA Approval of Miebo (Perfluorohexyloctane Ophthalmic Solution) for the Treatment of the Signs and Symptoms of Dry Eye Disease” (Press release). Bausch + Lomb Corporation. 18 May 2023. Retrieved 8 June 2023 – via Business Wire.
^ New Drug Therapy Approvals 2023 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 10 January 2024. Retrieved 9 January 2024.
^ Ballesteros-Sánchez A, De-Hita-Cantalejo C, Sánchez-González MC, Jansone-Langine Z, de Sotomayor MA, Culig J, et al. (October 2023). “Perfluorohexyloctane in dry eye disease: A systematic review of its efficacy and safety as a novel therapeutic agent”. The Ocular Surface. 30: 254–262. doi:10.1016/j.jtos.2023.10.001. hdl:11441/151762. PMID 37813152. S2CID 263802332.
^ Sheppard JD, Evans DG, Protzko EE (November 2023). “A review of the first anti-evaporative prescription treatment for dry eye disease: perfluorohexyloctane ophthalmic solution”. The American Journal of Managed Care. 29 (14 Suppl): S251 – S259. doi:10.37765/ajmc.2023.89464. PMID 37930231. S2CID 265032840.
^ “In Australia, NovaTears Eye Drops Are Available on the Pharmaceutical Benefits Scheme (PBS) from Now On” (Press release). Retrieved 15 February 2024.


Clinical data
Trade names	Evotears Miebo (/ˈmaɪboʊ/ MY-bow) Novatears
Other names	NOV03; 1-(perfluorohexyl)octane
AHFS/Drugs.com	Monograph
MedlinePlus	a623054
License data	US DailyMed: Perfluorohexyloctane
Routes of administration	Eye drops
ATC code	None
Legal status
Legal status	CA: ℞-only^[1]^[2]^[3]US: ℞-only^[4]
Identifiers
showIUPAC name
CAS Number	133331-77-8
PubChem CID	10477896
DrugBank	DB17823
ChemSpider	8653305
UNII	7VYX4ELWQM
KEGG	D12604
ChEBI	CHEBI:229658
CompTox Dashboard (EPA)	DTXSID20440585
Chemical and physical data
Formula	C₁₄H₁₇F₁₃
Molar mass	432.269 g·mol⁻¹
3D model (JSmol)	Interactive image
showSMILES
showInChI

DIMDAZENIL

May 20, 2025 9:15 am / Leave a comment

DIMDAZENIL

CAS 308239-86-3

WeightAverage: 372.81
Monoisotopic: 372.1101515

Chemical FormulaC₁₇H₁₇ClN₆O₂

EVT-201, 308239-86-3, EVT201, 6J8AF7CLE4, EVT 201

7-Chloro-3-[5-[(dimethylamino)methyl]-1,2,4-oxadiazol-3-yl]-4,5-dihydro-5-methyl-6H-imidazo[1,5-a]

[1,4]benzodiazepin-6-one

7-chloro-3-[5-[(dimethylamino)methyl]-1,2,4-oxadiazol-3-yl]-5-methyl-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one

EVT 201 is a novel partial positive allosteric modulator of the GABAA receptor complex which is being developed as a treatment for insomnia. It is being developed by Evotec Inc.

OriginatorRoche
DeveloperEvotec SE; Zhejiang Jingxin Pharmaceutical
ClassBenzodiazepines; Chlorobenzenes; Dimethylamines; Imidazoles; Ketones; Oxadiazoles; Sleep disorder therapies; Small molecules
Mechanism of ActionGABA A receptor modulators
RegisteredInsomnia
29 Nov 2023Registered for Insomnia in China (PO) – First global approval
24 Oct 2023Efficacy and adverse events data from a phase III trial in Insomnia released by Zhejiang Jingxin Pharmaceutical
21 Oct 2023Efficacy and adverse events data from a phase II trial in Insomnia released by Zhejiang Jingxin Pharmaceutical

Dimdazenil, sold under the brand name Junoenil, is a medication used in the treatment of insomnia in China.^[1] It is a benzodiazepine derivative and a partial positive allosteric modulator of the GABA_A receptor^[2] with two- to four-fold higher functional affinity for the α₁ subunit relative to the α₂, α₃, and α₅ subunits.

Medical use

Dimdazenil shows effectiveness in the treatment of insomnia, but has less intrinsic activity in comparison to currently-marketed benzodiazepines and the Z-drugs;^[3] however, it is thought that the lower efficacy may result in fewer side effects, such as motor incoordination.^[3] In China, dimdazenil is approved for short-term treatment of insomnia.^[4]

History

Dimdazenil was originally developed by Roche, based on preclinical data, as a non-sedating anxiolytic, but was found to produce sedation in humans in phase I clinical trials. For this reason, it was subsequently licensed to Evotec, which is now developing it for the treatment of insomnia.^[3] By 2007, dimdazenil completed phase II clinical trials for this indication, with positive findings reported.^[5] In China, the drug was developed by Zhejiang Jingxin Pharmaceutical.

SCHEME

PATENT

CN111620834

https://patentscope.wipo.int/search/en/detail.jsf?docId=CN306317338&_cid=P10-MAWAJX-84923-1

Example 16

1M lithium bis(trimethylsilyl)amide (320 mL, 0.32 mol, 3 eq, 1 Mol/liter) was added to the flask, nitrogen was passed through, the temperature was lowered to -15°C, and the compound K1 (22.6 g, 0.11 mol, 1 eq) obtained in Example 11 was added dropwise. After the addition, the mixture was kept warm at -15°C to -5°C for 2 hours. After the addition, the compound b (26 g, 0.11 mol, 1 eq) obtained by the method of Example 15 was added dropwise. The mixture was kept warm at -15°C to -5°C for 2 hours. After the addition, the mixture was naturally heated to room temperature, and glacial acetic acid was slowly added dropwise. The temperature was controlled to be below 35°C. After completion, the temperature was raised to 55-60°C, and the reaction was kept warm for 2 hours. Then, the mixture was transferred to a rotary evaporator, and the mixture was concentrated under reduced pressure at 45-50°C in batches. The temperature was lowered to 25-30°C, and water and dichloromethane were added in batches. The layers were stirred and separated, and the organic layer was collected. The aqueous layer was extracted once more with dichloromethane, and the organic layers were combined. The layers were washed with a saturated aqueous solution of sodium bicarbonate and water. After washing, the organic layers were collected and transferred to a rotary evaporator for concentration to obtain a solid. The solid was slurried with ethanol at -15°C to -5°C for 15 minutes, filtered, rinsed with cold ethanol, and dried under reduced pressure at 55-60°C to obtain a compound of formula I (36 g, 96.6%), MS: M ⁺⁺ 1=373.1, HPLC purity 99.85%.

¹ H-NMR data:¹ H NMR (400 MHz, DMSO-d₆δ8.57(s,1H),7.69(d,J＝1.9Hz,3H),4.60(d,J＝3.7Hz,2H),3.61(s,2H),3.05(s,3H),2.16(s,6H).

¹³ C-NMR data:¹³ C NMR (101 MHz, DMSO) δ 163.35, 163.25, 161.50, 138.88, 134.17, 133.15, 132.81, 130.95, 128.29, 122.67, 114.56, 110.52, 61.10, 46.6 (2), 41.77, 34.48.

PATENT

WO2000069858

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2000069858&_cid=P10-MAWAOS-90001-1

EXAMPLE

a) 6-Chloro-3,4-dihydro-4-methyl-2H-l,4-benzodiazepine-2,5(lH)-dione (III).

25.0 g 6-chloro-isatoic anhydride (II) and 12.4 g sarcosine were suspended under stirring and argon atmosphere in 100 ml p-xylene and heated at reflux for two hours. The suspension was cooled to room temperature and further stirred 1 hour, then filtered off. The precipitate was washed with 25 ml p-xylene twice and dried at 50°C under vacuum. The solid so obtained (6-chloro-3,4-dihydro-4-methyl-2H-l,4-benzodiazepine-2,5( lH)-dione (II)) was digested in 75 ml deionized water at 0°C for 1 hour, filtered off, washed with 25 ml deionized water and dried under vacuum 18 hours at 80°C. Crude product: 25.2 g as a beige powder, m.p. 230-232°C

b) Ethyl 7-chloro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[ l,5-a] [ 1,4] benzodiazepine- 3-carboxylate (V).

25.0 g 6-Chloro-3,4-dihydro-4-methyl-2H-l,4-benzodiazepine-2,5( lH)-dione (III) were suspended under stirring and argon atmosphere in 200 ml toluene and 32.1 ml N,N-dimethyl-p-toluidine. The suspension was heated to 100°C and 11.2 ml phosphorus oxychloride were added over 30 minutes and stirring was pursued two and an half hours at 100°C. The dark-orange solution was cooled to 40°C and toluene was removed under reduced pressure to give 82 g of a dark-orange oil.

Meanwhile, 81.2 ml hexamethyldisilazane and 265 ml tetrahydrofuran were mixed and cooled to -35°C. 229.5 ml Butyllithium were added over 45 minutes and, after stirring 30 minutes at -35°C, a solution of 35.2 g ethyl(dimethylamino-methylenamino)acetate in 70.4 ml tetrahydrofuran was added over 30 minutes. The orange solution obtained was stirred one more hour at -35°C and a solution of the crude iminochloride in 100 ml
tetrahydrofuran was added over 1 hour at -15°C. The dark red solution was stirred one hour at -15°C, then 18 hours at room temperature (r.t.). 75 ml Acetic acid were added in 10 minutes, then 75 ml deionized water were added in one portion and the orange suspension was heated at reflux for two hours. Tetrahydrofuran was removed under reduced pressure and the residue was partitioned between 200 ml dichloromethane and 100 ml deionized water. The phases were separated and the organic phase was washed with 100 ml aqueous HC1 IN twice and with 100 ml deionized water. The aqueous phases were extracted twice with 100 ml dichloromethane. The combined organic extracts were dried (Na₂S0₄) and evaporated. The residue was digested in 200 ml n-heptane 30 minutes at r.t. and filtered off. The sticky crystals obtained were digested at reflux for 30 minutes in 213.5 ml ethanol, then stirred 3 hours to r.t. and 2 hours at -20°C. The precipitate (ethyl 7-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[ l,5-a] [ l,4]benzodiazepine-3-carboxylate (V)) was filtered off, washed three times with 20 ml ethanol and dried under reduced pressure 16 hours at 60°C. Crude product: 23.4 g as a beige powder, m.p. 225.5-226.5 °C c) 7-Chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [ 1 ,5-a] [ 1 ,4]benzodiazepine-3- carboxamide (VI).

22.8 g Ethyl 7-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[ l,5-a] [l,4]- benzodiazepine-3-carboxylate (V)were suspended under stirring and argon atmosphere in 91.2 ml 1 ,4-dioxane. 14.1 ml Formamide and 13.9 ml sodium methanolate were successively added to yield a clear light-orange solution, which turned to a white suspension after 10 minutes. This suspension was stirred two hours at 30°C. 200 ml deionized water were added in one portion and 1,4-dioxane was distilled off at 40°C under reduced pressure. The remaining white suspension was stirred two hours at 0°C and filtered. The precipitate (7-chloro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[ l,5-a] [ l,4]benzodiazepine-3-carboxamide (VI)) was washed with 50 ml deionized water three times and dried under reduced pressure for 18 hours at 80°C. Crude product: 19.43 g as a white powder. m.p.>250°C

d) 7-Chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[l,5-a] [l,4]benzodiazepine-3- carbonitrile (VII).

19.0 g 7-Chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[ l,5-a] [ l,4]benzodiazepine-3- carboxamide (VI) were suspended under stirring and argon atmosphere in 95 ml 1,4- dioxane and 6.58 phosphorous oxychloride were added in one portion. The reaction mixture was heated to reflux for one hour giving a yellow solution, which was concentrated at 50°C under reduced pressure. The residue was digested in 100 ml deionized water for two hours at r.t.. The precipitate (7-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[l,5- a] [ l ,4]benzodiazepine-3-carbonitrile (VII)) was filtered off, washed three times with 30 ml deionized water and dried under vacuum at 80°C for 18 hours. Crude product: 17.3 g as a light yellow powder, m.p. 238.5-239.5°C

_ e) 7-Chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[l,5-a] [l,4]benzodiazepine-3- carboxamidoxime (VIII).

16.8 g 7-Chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[ l,5-a] [ l,4]benzodiazepine-3- carbonitrile (VIII) were suspended under stirring and argon atmosphere in 101 ml N,N- dimethylformamide and 13.48 g hydroxylamine hydrochloride was added in one portion. 34.2 ml Sodium methanolate were then added over 60 minutes to the yellow suspension, which turned to a colorless suspension. It was stirred one more hour at r.t., then cooled to 0-2°C and 202 ml deionized water were added over 30 minutes. After stirring one more hour at 0°C, the precipitate (7-chloro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[l,5-a] [l,4]benzodiazepine-3-carboxamidoxime (VIII) was filtered off, washed twice with 40 ml deionized water and dried under vacuum at 70°C for 18 hours Crude product 17.84 g as a white powder m.p.>250°C

f) 7-Chloro-3- (5-chloromethyl- [ 1 ,2,4] oxadiazol-3-yl)-5-methyl-4,5-dihydro- imidazo [ 1 ,5-a] [ 1 ,4] benzodiazepin-6-one (IX).

8.0 g 7-chloro-5,6-dιhydro-5-methyl-6-oxo-4H-ιmιdazo[ 1,5-a] [ l,4]benzodιazepιne-3-carboxamidoxime (VIII) and 1.0 g magnesium oxide were suspended under stirring and argon atmosphere in 160 ml 1,4-dioxane. 2 7 ml Chloracetyl chloride were added in one portion and the white thick gel obtained was stirred 4 hours at r.t. and then 17 hours at reflux to give a lightly orange fluid suspension 100 ml Dioxane were distilled off and the reaction mixture was cooled to room temperature. 180 ml Deionized water were added within 15 minutes and the suspension was stirred 1 hour at r.t . The precipitate was filtered off, washed with 50 ml deionized water twice and dried under vacuum at 80°C for 18 hours Crude product: 8.3 g as a light pink powder. This crude product was dissolved in 120 ml tetrahydrofuran at reflux and 0.83 g active charcoal Darco G 60 were added. The system was refluxed 1 hour, then filtered on 25 g Dicaht-Speedex and the filter cake was washed with three portions of 50 ml warm tetrahydrofuran. The filtrate was concentrated at 40°C under reduced pressure The residue was digested in 80 ml ethanol 1 hour at reflux, then stirred 16 hours at r.t. and finally 2 hours at 2°C. The precipitate (7-chloro-3-(5-chloromethyl- [ l,2,4]oxadιazol-3-yl)-5-methyl-4,5-dιhydro-ιmιdazo [ 1,5-a] [ l,4]benzo-dιazepιn-6-one (IX)) was filtered off, washed with 2 portions of 25 ml cold tert-butyl ethvl- ether and dried under vacuum 5 hours at 80°C Crude product: 7.6 g as a light beige powder, m p. 234-238°C

g) 7-Chloro-3-(5-dimethylaminomethyl-[l,2,4]oxadiazol-3-yl)-5-methyl-4,5- dιhydro-imidazo[l,5-a] [l,4]benzodιazepin-6-one (I).

7.0 g 7-Chloro-3-(5-chloromethyl- [ l,2,4]oxadιazol-3-yl)-5-methyl-4,5-dιhydro-ιmιdazo-[ 1,5-a] [ l,4]benzodιazepιn-6-one (IX) were suspended under stirring and argon
atmosphere in 70 ml 1,4-dioxane and 25.7 ml dimethylamine (33% in ethanol) were added over 60 minutes The reaction mixture was stirred one more hour at r.t. and then the solvents were removed under reduced pressure at 35°C. The residue was partitioned between 50 ml dichloromethane and 20 ml deionized water. The phases were separated and the organic phase was washed twice with 20 ml deionized water. The aqueous phases were extracted separately with the same portion of 25 ml dichloromethane, twice. The combined organic extracts were dried (Na2SO4) and the solvent was removed under reduced pressure Crude product: 8.0 g as a light yellow foam Purification
The crude product was dissolved in 40 ml ethanol at reflux and 400 mg active charcoal Darco G 60 were added. The system was stirred 1 hour at reflux, then filtered on a hot pad of Dicalit Speedex, which was washed with two portions of 40 ml hot ethanol. The filtrate was concentrated to 14 g under reduced pressure, heated to reflux and at this temperature and 40 ml terf-butyl-methylether were added over 5 minutes. The suspension was cooled slowly to r.t., stirred 16 hours, further cooled to 2°C. After stirring 1 hour at 2°C, the precipitate was filtered off, washed with 20 ml tert-butyl-methylether and dried 1 hour at 60°C under vacuum. The so obtained powder was dissolved at reflux in 26 ml ethyl acetate. 6.5 ml Ethyl acetate were then distilled off and the turbid solution obtained was slowly cooled to r.t., then to 0°C. After 1 hour stirring at 0°C, the precipitate was filtered off, washed with 10 ml cold tert-butyl-methylether and dried under vacuum at 60°C for 16 hours. The so obtained powder (7-chloro-3-(5-dimethylaminomethyl-[ 1,2,4] oxadiazol-3-yl)-5-methyl-4,5-dihydro-imidazo[ 1,5-a] [l,4]benzodiazepin-6-one (I)) was crystallized a second time in 24.3 ml ethyl acetate according to the procedure described above. Product: 5.5 g as a white powder, m.p. 151.5-153°C

7-Chloro-3-(5-dimethylaminomethyl-[l,2,4]oxadiazol-3-yl)-5-methyl-4,5-dihydro-imidazo [ 1 ,5-a] [ 1 ,4] benzodiazepin-6-one maleate (1:1)

373 mg 7-Chloro-3-(5-dimethylaminomethyl-[ l,2,4]oxadiazol-3-yl)-5-methyl-4,5-dihydro-imidazo[ 1,5-a] [ l,4]benzodiazepin-6-one (I) and 116 mg maleic acid were dissloved in 3 ml hot ethanol. The salt crystalized on cooling. The suspension was stirred for 10 min at 0°C. Filtration and drying afforded 460 mg 7-Chloro-3-(5-dimethylaminomethyl-[ l,2,4]oxadiazol-3-yl)-5-methyl-4,5-dihydro-imidazo[l,5-a] [ l,4]benzodiazepin-6-one maleate (1:1) as a white solid, m.p. 182-184°C

References

^ Huang Z, Zhan S, Chen C, Zhang R, Zhou Y, He J, et al. (February 2024). “Efficacy and safety of Dimdazenil in adults with insomnia disorder: results from a multicenter, randomized, double-blind, placebo-controlled phase III trials”. Sleep. 47 (2). doi:10.1093/sleep/zsad272. PMC 10851846. PMID 37875349.
^ Guilleminault C (2010). Sleep Medicine. Elsevier Health Sciences. pp. 574–. ISBN 978-1-4377-1836-2.
^ Jump up to:^a ^b ^c Monti JM, Pandi-Perumal SR, Möhler H (28 September 2010). GABA and Sleep: Molecular, Functional and Clinical Aspects. Springer Science & Business Media. pp. 50–51. ISBN 978-3-0346-0226-6.
^ Syed YY (March 2024). “Dimdazenil: First Approval”. Drugs. doi:10.1007/s40265-024-02020-9. PMID 38546956.
^ Plunkett JW (September 2007). Plunkett’s Biotech & Genetics Industry Almanac 2008: Biotech & Genetics Industry Market Research, Statistics, Trends & Leading Companies. Plunkett Research, Ltd. pp. 311–. ISBN 978-1-59392-087-6.

External links

Dimdazenil – AdisInsight

Clinical data

Trade names	Junoenil
Other names	EVT-201; EVT201
Legal status
Legal status	Rx in China
Identifiers
showIUPAC name
CAS Number	308239-86-3
PubChem CID	9885841
DrugBank	DB05721
ChemSpider	8061514
UNII	6J8AF7CLE4
ChEMBL	ChEMBL5095096
CompTox Dashboard (EPA)	DTXSID301032055
Chemical and physical data
Formula	C₁₇H₁₇ClN₆O₂
Molar mass	372.81 g·mol⁻¹
3D model (JSmol)	Interactive image
showSMILES
showInChI

//////////DIMDAZENIL, EVT-201, 308239-86-3, EVT201, 6J8AF7CLE4, EVT 201, CHINA 2023, INSOMNIA

Digadoglucitol

May 19, 2025 2:51 am / Leave a comment

Digadoglucitol

DA-52534

CAS 2098944-37-5

μ-[2,2′,2”,2”’,2””,2””’-({[(2S,3R,4R,5R)-2,3,4,5,6- pentahydroxyhexyl]azanediyl}bis{[2-(hydroxy-κO)propane3,1-diyl]-1,4,7,10-tetraazacyclododecane-10,1,4,7-tetraylκ4 N1 ,N4 ,N7 ,N10})hexa(acetato-κO)]digadolinium diagnostic agent

C40H69Gd2N9O19

MW 1,294.536

F2Q2ZU6CAU

Digadoglucitol free acid
USL2PB6YFS
1-[Bis[2-hydroxy-3-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl]propyl]amino]-1-deoxy-D-glucitol
2098944-28-4 FREE ACID
D-Glucitol, 1-[bis[2-hydroxy-3-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl]propyl]amino]-1-deoxy-

SCHEME

PATENT

Bracco Imaging SpA

WO2017098044

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2017098044&_cid=P12-MAUH6W-49653-1

PATENT

WO2023006722

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023006722&_cid=P12-MAUHGF-56290-1

PATENT

WO2022023240

.///////////Digadoglucitol, F2Q2ZU6CAU, X RAY CONTRAST AGENT, DA-52534, DA 52534

Tofersen

May 17, 2025 9:23 am / Leave a comment

all-P-ambo-2′-O-(2-Methoxyethyl)-5-methyl-P-thiocytidylyl-(3’→5′)-2′-O-(2-methoxyethyl)adenylyl-(3’→5′)-2′-O-(2-methoxyethyl)-P-thioguanylyl-(3’→5′)-2′-O-(2-methoxyethyl)guanylyl-(3’→5′)-2′-O-(2-methoxyethyl)-P-thioadenylyl-(3’→5′)-P-thiothymidylyl-(3’→5′)-2′-deoxy-P-thioadenylyl-(3’→5′)-2′-deoxy-5-methyl-P-thiocytidylyl-(3’→5′)-2′-deoxy-P-thioadenylyl-(3’→5′)-P-thiothymidylyl-(3’→5′)-P-thiothymidylyl-(3’→5′)-P-thiothymidylyl-(3’→5′)-2′-deoxy-5-methyl-P-thiocytidylyl-(3’→5′)-P-thiothymidylyl-(3’→5′)-2′-deoxy-P-thioadenylyl-(3’→5′)-2′-O-(2-methoxyethyl)-5-methylcytidylyl-(3’→5′)-2′-O-(2-methoxyethyl)-P-thioadenylyl-(3’→5′)-2′-O-(2-methoxyethyl)guanylyl-(3’→5′)-2′-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3’→5′)-2′-O-(2-methoxyethyl)-5-methyluridine

C₂₃₀H₃₁₇N₇₂O₁₂₃P₁₉S₁₅ : 7127.86
[2088232-70-4]

Tofersen

CAS 2088232-70-4

FDA APPROVED 4/25/2023, Qalsody

BIIB 067
BIIB067
Formula
C₂₃₀H₃₁₇N₇₂O₁₂₃P₁₉S₁₅
Molar mass
7127.85 g·mol⁻¹

Antisense Oligonucleotide Inhibitor Of The Expression Of Superoxide Dismutase 1 Gene
DNA, D((2′-O-(2-METHOXYETHYL))M5RC-SP-(2′-O-(2-METHOXYETHYL))RA-(2′-O-(2-METHOXYETHYL))RG-SP-(2′-O-(2-METHOXYETHYL))RG-(2′-O-(2-METHOXYETHYL))RA-SP-T-SP-A-SP-M5C-SP-A-SP-T-SP-T-SP-T-SP-M5C-SP-T-SP-A-SP-(2′-O-(2-METHOXYETHYL))M5RC-(2′-O-(2-METHOXYETHYL))R
IONIS SOD1Rx

To treat amyotrophic lateral sclerosis in adults who have a SOD1 gene mutation
Drug Trials Snapshot

A nucleic acid-based drug indicated for the treatment of a specific type of amyotrophic lateral sclerosis.

Tofersen, sold under the brand name Qalsody, is a medication used for the treatment of amyotrophic lateral sclerosis (ALS).^[3] Tofersen is an antisense oligonucleotide that targets the production of superoxide dismutase 1, an enzyme whose mutant form is commonly associated with amyotrophic lateral sclerosis. It is administered as an intrathecal injection.^[3]

The most common side effects include fatigue, arthralgia (joint pain), increased cerebrospinal (brain and spinal cord) fluid white blood cells, and myalgia (muscle pain).^[3]

Tofersen was approved for medical use in the United States in April 2023,^[3]^[6] and in the European Union in May 2024.^[4] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.^[7]

Clinical data

Trade names	Qalsody
AHFS/Drugs.com	Monograph
MedlinePlus	a623024
License data	US DailyMed: Tofersen
Routes of administration	Intrathecal
ATC code	N07XX22 (WHO)
Legal status
Legal status	CA: ℞-only^[1]US: ℞-only^[2]^[3]EU: Rx-only^[4]^[5]
Identifiers
CAS Number	2088232-70-4
DrugBank	DB14782
UNII	2NU6F9601K
KEGG	D11811
Chemical and physical data
Formula	C₂₃₀H₃₁₇N₇₂O₁₂₃P₁₉S₁₅
Molar mass	7127.85 g·mol⁻¹

References

^ “Register of Innovative Drugs”. Health Canada. 3 November 2006. Retrieved 17 April 2025.
^ “Qalsody- tofersen injection”. DailyMed. 25 April 2023. Archived from the original on 8 May 2023. Retrieved 10 June 2023.
^ Jump up to:^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l “FDA approves treatment of amyotrophic lateral sclerosis associated with a mutation in the SOD1 gene” (Press release). U.S. Food and Drug Administration (FDA). 25 April 2023. Archived from the original on 25 April 2023. Retrieved 25 April 2023. This article incorporates text from this source, which is in the public domain.
^ Jump up to:^a ^b ^c ^d “Qalsody EPAR”. European Medicines Agency (EMA). 22 February 2024. Retrieved 24 February 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ Jump up to:^a ^b “Qalsody PI”. Union Register of medicinal products. 3 June 2024. Retrieved 7 September 2024.
^ “FDA Grants Accelerated Approval for Qalsody (tofersen) for SOD1-ALS, a Major Scientific Advancement as the First Treatment to Target a Genetic Cause of ALS” (Press release). Biogen. 25 April 2023. Archived from the original on 25 April 2023. Retrieved 25 April 2023 – via GlobeNewswire.
^ Jump up to:^a ^b New Drug Therapy Approvals 2023 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 10 January 2024. Retrieved 9 January 2024.
^ Liu A (1 May 2019). “Biogen’s antisense ALS drug shows promise in early clinical trial”. FierceBiotech. Archived from the original on 2 February 2023. Retrieved 25 April 2023.
^ Langreth R (22 March 2023). “Biogen’s ALS Drug Gets Partial Backing From FDA Panel”. Bloomberg News. Retrieved 25 April 2023.
^ “FDA approves drug which helps to slow progression of rare form of MND”. http://www.sheffield.ac.uk. 28 April 2023. Retrieved 16 May 2024.
^ Berdyński M, Miszta P, Safranow K, Andersen PM, Morita M, Filipek S, et al. (January 2022). “SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity”. Scientific Reports. 12 (1): 103. Bibcode:2022NatSR..12..103B. doi:10.1038/s41598-021-03891-8. PMC 8742055. PMID 34996976.
^ Constantino A (25 April 2023). “FDA grants accelerated approval for Biogen ALS drug that treats rare form of the disease”. CNBC. Archived from the original on 25 April 2023. Retrieved 25 April 2023.
^ Constantino A (22 March 2023). “FDA advisors vote against effectiveness of Biogen’s ALS drug for rare and aggressive form of the disease”. CNBC. Archived from the original on 10 April 2023. Retrieved 25 April 2023.
^ Robins R (25 April 2023). “F.D.A. Approves Drug for Rare Form of A.L.S.” The New York Times. Archived from the original on 25 April 2023. Retrieved 25 April 2023.
^ “New treatment for rare motor neuron disease recommended for approval”. European Medicines Agency (EMA) (Press release). 23 February 2024. Retrieved 24 February 2024.

////////////tofersen, Qalsody, FDA 2023, APPROVALS 2023, EU 2024, EMA 2024, BIIB 067, BIIB067, IONIS SOD1Rx

Deupsilocin

May 17, 2025 2:57 am / Leave a comment

Deupsilocin, Psilocin-d10

Psilocin-D10
Deupsilocin
Psilocine-d10

Molecular Formula	C12H16N2O
Molecular Weight	214.3299

KXD3HS8D6X

CAS 1435934-64-7

3-[2-[Di(methyl-d₃)amino]ethyl-1,1,2,2–d₄]-1H-indol-4-ol

3-[2-[bis(trideuteriomethyl)amino]-1,1,2,2-tetradeuterioethyl]-1H-indol-4-ol

1H-Indol-4-ol, 3-[2-[di(methyl-d3)amino]ethyl-1,1,2,2-d4]-

Mental health disorders, or mental illness, refer to a wide range of disorders that include, but are not limited to, depressive disorders, anxiety and panic disorders, schizophrenia, eating disorders, substance misuse disorders, post-traumatic stress disorder, attention deficit/hyperactivity disorder and obsessive compulsive disorder. The severity of symptoms varies such that some individuals experience debilitating disease that precludes normal social function, while others suffer with intermittent repeated episodes across their lifespan. Although the presentation and diagnostic criteria among mental illness conditions are distinct in part, there are common endophenotypes of note across the diseases, and often comorbidities exist. Specifically, there exist phenotypic endophenotypes associated with alterations in mood, cognition and behavior. Interestingly, many of these endophenotypes extend to neurological conditions as well. For example, attentional deficits are reported in patients with attention deficit disorder, attention deficit hyperactivity disorder, eating disorders, substance use disorders, schizophrenia, depression, obsessive compulsive disorder, traumatic brain injury, Fragile X, Alzheimer’s disease, Parkinson’s disease and frontotemporal dementia.
      Many mental health disorders, as well as neurological disorders, are impacted by alterations, dysfunction, degeneration, and/or damage to the brain’s serotonergic system, which may explain, in part, common endophenotypes and comorbidities among neuropsychiatric and neurological diseases. Many therapeutic agents that modulate serotonergic function are commercially available, including serotonin reuptake inhibitors, selective serotonin reuptake inhibitors, antidepressants, monoamine oxidase inhibitors, and, while primarily developed for depressive disorders, many of these therapeutics are used across multiple medical indications including, but not limited to, depression in Alzheimer’s disease and other neurodegenerative disease, chronic pain, existential pain, bipolar disorder, obsessive compulsive disorder, anxiety disorders and smoking cessation. However, in many cases, the marketed drugs show limited benefit compared to placebo, can take six weeks to work and for some patients, and are associated with several side effects including trouble sleeping, drowsiness, fatigue, weakness, changes in blood pressure, memory problems, digestive problems, weight gain and sexual problems.
      The field of psychedelic neuroscience has witnessed a recent renaissance following decades of restricted research due to their legal status. Psychedelics are one of the oldest classes of psychopharmacological agents known to man and cannot be fully understood without reference to various fields of research, including anthropology, ethnopharmacology, psychiatry, psychology, sociology, and others. Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD) and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2 A (5-HT2A) receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V, but also may bind with lower affinity to other receptors such as the sigma-1 receptor. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-HT2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics.
      Psychedelics have both rapid onset and persisting effects long after their acute effects, which includes changes in mood and brain function. Long lasting effects may result from their unique receptor affinities, which affect neurotransmission via neuromodulatory systems that serve to modulate brain activity, i.e., neuroplasticity, and promote cell survival, are neuroprotective, and modulate brain neuroimmune systems. The mechanisms which lead to these long-term neuromodulatory changes are linked to epigenetic modifications, gene expression changes and modulation of pre- and post-synaptic receptor densities. These, previously under-researched, psychedelic drugs may potentially provide the next-generation of neurotherapeutics, where treatment resistant psychiatric and neurological diseases, e.g., depression, post-traumatic stress disorder, dementia and addiction, may become treatable with attenuated pharmacological risk profiles.
      Although there is a general perception that psychedelic drugs are dangerous, from a physiologic safety standpoint, they are one of the safest known classes of CNS drugs. They do not cause addiction, and no overdose deaths have occurred after ingestion of typical doses of classical psychotic agents, such as LSD, psilocybin, or mescaline (Scheme 1). Preliminary data show that psychedelic administration in humans results in a unique profile of effects and potential adverse reactions that need to be appropriately addressed to maximize safety. The primary safety concerns are largely psychologic, rather than physiologic, in nature. Somatic effects vary but are relatively insignificant, even at doses that elicit powerful psychologic effects. Psilocybin, when administered in a controlled setting, has frequently been reported to cause transient, delayed headache, with incidence, duration, and severity increased in a dose-related manner [Johnson et al., Drug Alcohol Depend, 2012, 123 (1-3):132-140]. It has been found that repeated administration of psychedelics leads to a very rapid development of tolerance known as tachyphylaxis, a phenomenon believed to be mediated, in part, by 5-HT2A receptors. In fact, several studies have shown that rapid tolerance to psychedelics correlates with downregulation of 5-HT2A receptors. For example, daily LSD administration selectively decreased 5-HT2 receptor density in the rat brain [Buckholtz et al., Eur. J. Pharmacol., 1990, 109:421-425. 1985; Buckholtz et al., Life Sci. 1985, 42:2439-2445].

SCHEME

PATENT

Mindset Pharma Inc., US11591353

https://patentscope.wipo.int/search/en/detail.jsf?docId=US376433397&_cid=P10-MARMO8-36145-1

PATENT

WO2021155470

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021155470&_cid=P10-MARMST-39096-1

PATENT

Cybin IRL Limited, WO2023247665

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023247665&_cid=P10-MARMVV-41020-1

PATENT

WO2023078604

WO2022195011

Classic psychedelics and dissociative psychedelics are known to have rapid onset antidepressant and anti-addictive effects, unlike any currently available treatment. Randomized clinical control studies have confirmed antidepressant and anxiolytic effects of classic psychedelics in humans. Ketamine also has well established antidepressant and anti-addictive effects in humans mainly through its action as an NMDA antagonist. Ibogaine has demonstrated potent anti-addictive potential in pre-clinical studies and is in the early stages of clinical trials to determine efficacy in robust human studies [Barsuglia et al., Prog Brain Res, 2018, 242:121-158; Corkery, Prog Brain Res, 2018, 242:217-257].

Psilocybin (4-phosphoryloxy-N,N-dimethyltrypatmine (iii, Scheme 1) has the chemical formula C ₁₂H ₁₇N ₂O ₄P. It is a tryptamine and is one of the major psychoactive constituents in mushrooms of the psilocybe species. It was first isolated from psilocybe mushrooms by Hofmann in 1957, and later synthesized by him in 1958 [Passie et al. Addict Biol., 2002, 7 (4):357-364], and was used in psychiatric and psychological research and in psychotherapy during the early to mid-1960 s up until its controlled drug scheduling in 1970 in the US, and up until the 1980 s in Germany [Passie 2005; Passie et al., Addict Biol., 2002, 7 (4):357-364]. Research into the effects of psilocybin resumed in the mid-1990 s, and it is currently the preferred compound for use in studies of the effects of serotonergic hallucinogens [Carter et al. J. Cogn. Neurosci., 2005 17 (10):1497-1508; Gouzoulis-Mayfrank et al. Neuropsychopharmacology 1999, 20 (6):565-581; Hasler et al, Psychopharmacology (Berl) 2004, 172 (2):145-156], likely because it has a shorter duration of action and suffers from less notoriety than LSD. Like other members of this class, psilocybin induces sometimes profound changes in perception, cognition and emotion, including emotional lability.

In humans as well as other mammals, psilocybin is transformed into the active metabolite psilocin, or 4-hydroxy-N,N-dimethyltryptamine (iv, Scheme 1). It is likely that psilocin partially or wholly produces most of the subjective and physiological effects of psilocybin in humans and non-human animals. Recently, human psilocybin research confirms the 5HT2A activity of psilocybin and psilocin, and provides some support for indirect effects on dopamine through 5HT2A activity and possible activity at other serotonin receptors. In fact, the most consistent finding for involvement of other receptors in the actions of psychedelics is the 5-HT1 A receptor. That is particularly true for tryptamines and LSD, which generally have significant affinity and functional potency at this receptor. It is known that 5-HT1 A receptors are colocalized with 5-HT2A receptors on cortical pyramidal cells [Martin-Ruiz et al. J Neurosci. 2001, 21 (24):9856-986], where the two receptor types have opposing functional effects [Araneda et al. Neuroscience, 1991, 40 (2):399-412].

Although the exact role of the 5-HT2A receptor, and other 5-HT2 receptor family members, is not well understood with respect to the amygdala, it is evident that the 5-HT2A receptor plays an important role in emotional responses and is an important target to be considered in the actions of 5-HT2A agonist psychedelics. In fact, a majority of known 5HT2A agonists produce hallucinogenic effects in humans, and rodents generalize from one 5HT2A agonist to others, as between psilocybin and LSD [Aghajanian et al., Eur J Pharmacol., 1999, 367 (2-3):197-206; Nichols at al., J Neurochem., 2004, 90 (3):576-584]. Psilocybin has a stronger affinity for the human 5HT2A receptor than for the rat receptor and it has a lower K(i) for both 5HT2A and 5HT2C receptors than LSD. Moreover, results from a series of drug-discrimination studies in rats found that 5HT2A antagonists, and not 5HT1 A antagonists, prevented rats from recognizing psilocybin [Winter et al., Pharmacol Biochem Behav., 2007, 87 (4):472-480]. Daily doses of LSD and psilocybin reduce 5HT2 receptor density in rat brain.

Clinical studies in the 1960 s and 1970 s showed that psilocybin produces an altered state of consciousness with subjective symptoms such as “marked alterations in perception, mood, and thought, changes in experience of time, space, and self.” Psilocybin was used in experimental research for the understanding of etiopathogenesis of selective mental disorders and showed psychotherapeutic potential [Rucker et al., Psychopharmacol., 2016, 30 (12):1220-1229]. Psilocybin became increasingly popular as a hallucinogenic recreational drug and was eventually classed as a Schedule I controlled drug in 1970. Fear of psychedelic abuse led to a significant reduction in research being done in this area until the 1990 s when human research of psilocybin was revived when conditions for safe administration were established [Johnson et al., Psychopharmacol., 2008, 22 (6):603-620]. Today, psilocybin is one of the most widely used psychedelics in human studies due to its relative safety, moderately long active duration, and good absorption in subjects. There remains strong research and therapeutic potential for psilocybin as recent studies have shown varying degrees of success in neurotic disorders, alcoholism, depression in terminally ill cancer patients, obsessive compulsive disorder, addiction, anxiety, post-traumatic stress disorder and even cluster headaches. It could also be useful as a psychosis model for the development of new treatments for psychotic disorders. [Dubovyk and Monahan-Vaughn, ACS Chem. Neurosci., 2018, 9 (9):2241-2251].

Recent developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with treatment resistant, major depressive disorder and cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two recent small pilot studies of psilocybin assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level-dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain’s default mode network [Nichols D E. Pharmacol Rev., 2016 68 (2):264-355].

Preliminary studies using positron emission tomography (PET) showed that psilocybin ingestion (15 or 20 mg orally) increased absolute metabolic rate of glucose in frontal, and to a lesser extent in other, cortical regions as well as in striatal and limbic subcortical structures in healthy participants, suggesting that some of the key behavioral effects of psilocybin involve the frontal cortex [Gouzoulis-Mayfrank et al., Neuropsychopharmacology, 1999, 20 (6):565-581; Vollenweider et al., Brain Res. Bull. 2001, 56 (5):495-507]. Although 5HT2A agonism is widely recognized as the primary action of classic psychedelic agents, psilocybin has lesser affinity for a wide range of other pre- and post-synaptic serotonin and dopamine receptors, as well as the serotonin reuptake transporter [Tyls et al., Eur. Neuropsychopharmacol. 2014, 24 (3):342-356]. Psilocybin activates 5HT1 A receptors, which may contribute to antidepressant/anti-anxiety effects.

Depression and anxiety are two of the most common psychiatric disorders worldwide. Depression is a multifaceted condition characterized by episodes of mood disturbances alongside other symptoms such as anhedonia, psychomotor complaints, feelings of guilt, attentional deficits and suicidal tendencies, all of which can range in severity. According to the World Health Organization, the discovery of mainstream antidepressants has largely revolutionized the management of depression, yet up to 60% of patients remain inadequately treated. This is often due to the drugs’ delayed therapeutic effect (generally 6 weeks from treatment onset), side effects leading to non-compliance, or inherent non-responsiveness to them. Similarly, anxiety disorders are a collective of etiologically complex disorders characterized by intense psychosocial distress and other symptoms depending on the subtype. Anxiety associated with life-threatening disease is the only anxiety subtype that has been studied in terms of psychedelic-assisted therapy. This form of anxiety affects up to 40% of individuals diagnosed with life-threatening diseases like cancer. It manifests as apprehension regarding future danger or misfortune accompanied by feelings of dysphoria or somatic symptoms of tension, and often coexists with depression. It is associated with decreased quality of life, reduced treatment adherence, prolonged hospitalization, increased disability, and hopelessness, which overall contribute to decreased survival rates. Pharmacological and psychosocial interventions are commonly used to manage this type of anxiety, but their efficacy is mixed and limited such that they often fail to provide satisfactory emotional relief. Recent interest into the use of psychedelic-assisted therapy may represent a promising alternative for patients with depression and anxiety that are ineffectively managed by conventional methods.

Generally, the psychedelic treatment model consists of administering the orally-active drug to induce a mystical experience lasting 4-9 h depending on the psychedelic [Halberstadt, Behav Brain Res., 2015, 277:99-120; Nichols, Pharmacol Rev., 2016, 68 (2): 264-355]. This enables participants to work through and integrate difficult feelings and situations, leading to enduring anti-depressant and anxiolytic effects. Classical psychedelics like psilocybin and LSD are being studied as potential candidates. In one study with classical psychedelics for the treatment of depression and anxiety associated with life-threatening disease, it was found that, in a supportive setting, psilocybin, and LSD consistently produced significant and sustained anti-depressant and anxiolytic effects.

Psychedelic treatment is generally well-tolerated with no persisting adverse effects. Regarding their mechanisms of action, they mediate their main therapeutic effects biochemically via serotonin receptor agonism, and psychologically by generating meaningful psycho-spiritual experiences that contribute to mental flexibility. Given the limited success rates of current treatments for anxiety and mood disorders, and considering the high morbidity associated with these conditions, there is potential for psychedelics to provide symptom relief in patients inadequately managed by conventional methods.

Further emerging clinical research and evidence suggest psychedelic-assisted therapy, also shows potential as an alternative treatment for refractory substance use disorders and mental health conditions, and thus may be an important tool in a crisis where existing approaches have yielded limited success. A recent systematic review of clinical trials published over the last 25 years summarizes some of the anti-depressive, anxiolytic, and anti-addictive effects of classic psychedelics. Among these, are encouraging findings from a meta-analysis of randomized controlled trials of LSD therapy and a recent pilot study of psilocybin-assisted therapy for treating alcohol use disorder [dos Santos et al., Ther Adv Psychopharmacol., 2016, 6 (3):193-213]. Similarly encouraging, are findings from a recent pilot study of psilocybin-assisted therapy for tobacco use disorder, demonstrating abstinence rates of 80% at six months follow-up and 67% at 12 months follow-up [Johnson et al., J Drug Alcohol Abuse, 2017, 43 (1):55-60; Johnson et al., Psychopharmacol. 2014, 28 (11):983-992], such rates are considerably higher than any documented in the tobacco cessation literature. Notably, mystical-type experiences generated from the psilocybin sessions were significantly correlated with positive treatment outcomes. These results coincide with bourgeoning evidence from recent clinical trials lending support to the effectiveness of psilocybin-assisted therapy for treatment-resistant depression and end-of-life anxiety [Carhart-Harris et al. Neuropsychopharmacology, 2017, 42 (11):2105-2113]. Research on the potential benefits of psychedelic-assisted therapy for opioid use disorder (OUD) is beginning to emerge, and accumulating evidence supports a need to advance this line of investigation. Available evidence from earlier randomized clinical trials suggests a promising role for treating OUD: higher rates of abstinence were observed among participants receiving high dose LSD and ketamine-assisted therapies for heroin addiction compared to controls at long-term follow-ups. Recently, a large United States population study among 44,000 individuals found that psychedelic use was associated with 40% reduced risk of opioid abuse and 27% reduced risk of opioid dependence in the following year, as defined by DSM-IV criteria [Pisano et al., J Psychopharmacol., 2017, 31 (5):606-613]. Similarly, a protective moderating effect of psychedelic use was found on the relationship between prescription opioid use and suicide risk among marginalized women [Argento et al., J Psychopharmacol., 2018, 32 (12):1385-1391]. Despite the promise of these preliminary findings with classical psychedelic agents, further research is warranted to determine what it may contribute to the opioid crisis response given their potential toxicity. Meanwhile, growing evidence on the safety and efficacy of psilocybin for the treatment of mental and substance use disorders should help to motivate further clinical investigation into its use as a novel intervention for OUD.

Regular doses of psychedelics also ameliorate sleep disturbances, which are highly prevalent in depressive patients with more than 80% of them having complaints of poor sleep quality. The sleep symptoms are often unresolved by first-line treatment and are associated with a greater risk of relapse and recurrence. Interestingly, sleep problems often appear before other depression symptoms, and subjective sleep quality worsens before the onset of an episode in recurrent depression. Brain areas showing increased functional connectivity with poor sleep scores and higher depressive symptomatology scores included prefrontal and limbic areas, areas involved in the processing of emotions. Sleep disruption in healthy participants has demonstrated that sleep is indeed involved in mood, emotion evaluation processes and brain reactivity to emotional stimuli. An increase in negative mood and a mood-independent mislabeling of neutral stimuli as negative was for example shown by one study while another demonstrated an amplified reactivity in limbic brain regions in response to both negative and positive stimuli. Two other studies assessing electroencephalographic (EEG) brain activity during sleep showed that psychedelics, such as LSD, positively affect sleep patterns. Moreover, it has been shown that partial or a full night of sleep deprivation can alleviate symptoms of depression suggested by resetting circadian rhythms via modification of clock gene expression. It further was suggested that a single dose of a psychedelic causes a reset of the biological clock underlying sleep/wake cycles and thereby enhances cognitive-emotional processes in depressed people but also improving feelings of well-being and enhances mood in healthy individuals [Kuypers, Medical Hypotheses, 2019, 125:21-24].

In a systematic meta-analysis of clinical trials from 1960-2018 researching the therapeutic use of psychedelic treatment in patients with serious or terminal illnesses and related psychiatric illness, it was found that psychedelic therapy (mostly with LSD) may improve cancer-related depression, anxiety, and fear of death. Four randomized controlled clinical trials were published between 2011 and 2016, mostly with psilocybin treatment, that demonstrated psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress. [Ross S, Int Rev Psychiatry, 2018, 30 (4):317-330]. Thus, the use of psychedelics in the fields of oncology and palliative care is intriguing for several reasons. First, many patients facing cancer or other life-threatening illnesses experience significant existential distress related to loss of meaning or purpose in life, which can be associated with hopelessness, demoralization, powerlessness, perceived burdensomeness, and a desire for hastened death. Those features are also often at the core of clinically significant anxiety and depression, and they can substantially diminish quality of life in this patient population. The alleviation of those forms of suffering should be among the central aims of palliative care. Accordingly, several manualized psychotherapies for cancer-related existential distress have been developed in recent years, with an emphasis on dignity and meaning-making. However, there are currently no pharmacologic interventions for existential distress per se, and available pharmacologic treatments for depressive symptoms in patients with cancer have not demonstrated superiority over placebo. There remains a need for additional effective treatments for those conditions [Rosenbaum et al., Curr. Oncol., 2019, 26 (4): 225-226].

Recently, there has been growing interest in a new dosing paradigm for psychedelics such as psilocybin and LSD referred to colloquially as microdosing. Under this paradigm, sub-perceptive doses of the serotonergic hallucinogens, approximately 10% or less of the full dose, are taken on a more consistent basis of once each day, every other day, or every three days, and so on. Not only is this dosing paradigm more consistent with current standards in pharmacological care, but may be particularly beneficial for certain conditions, such as Alzheimer’s disease and other neurodegenerative diseases, attention deficit disorder, attention deficit hyperactivity disorder, and for certain patient populations such as elderly, juvenile and patients that are fearful of or opposed to psychedelic assisted therapy. Moreover, this approach may be particularly well suited for managing cognitive deficits and preventing neurodegeneration. For example, subpopulations of low attentive and low motivated rats demonstrate improved performance on 5 choice serial reaction time and progressive ratio tasks, respectively, following doses of psilocybin below the threshold for eliciting the classical wet dog shake behavioral response associated with hallucinogenic doses (Blumstock et al., WO 2020/157569 A1). Similarly, treatment of patients with hallucinogenic doses of 5HT2A agonists is associated with increased BDNF and activation of the mTOR pathway, which are thought to promote neuroplasticity and are hypothesized to serve as molecular targets for the treatment of dementias and other neurodegenerative disorders (Ly et al. Cell Rep., 2018, 23 (11):3170-3182). Additionally, several groups have demonstrated that low, non-hallucinogenic and non-psychomimetic, doses of 5HT2A agonists also show similar neuroprotective and increased neuroplasticity effects (neuroplastogens) and reduced neuroinflammation, which could be beneficial in both neurodegenerative and neurodevelopmental diseases and chronic disorders (Manfredi et al., WO 2020/181194, Flanagan et al., Int. Rev. Psychiatry, 2018, 13:1-13; Nichols et al., 2016, Psychedelics as medicines; an emerging new paradigm). This repeated, lower, dose paradigm may extend the utility of these compounds to additional indications and may prove useful for wellness applications.

Psychosis is often referred to as an abnormal state of mind that is characterized by hallucinatory experiences, delusional thinking, and disordered thoughts. Moreover, this state is accompanied by impairments in social cognition, inappropriate emotional expressions, and bizarre behavior. Most often, psychosis develops as part of a psychiatric disorder, of which, it represents an integral part of schizophrenia. It corresponds to the most florid phase of the illness. The very first manifestation of psychosis in a patient is referred to as first-episode psychosis. It reflects a critical transitional stage toward the chronic establishment of the disease, that is presumably mediated by progressive structural and functional abnormalities seen in diagnosed patients. [ACS Chem. Neurosci. 2018, 9, 2241-2251]. Anecdotal evidence suggests that low, non-hallucinogenic, doses (microdosing) of psychedelics that are administered regularly can reduce symptoms of schizophrenia an

/////////Deupsilocin, Psilocin-d10, KXD3HS8D6X, Psilocin-D10, Deupsilocin, Psilocine-d10

Demannose

May 16, 2025 10:22 am / Leave a comment

Demannose

CAS 530-26-7,
3458-28-4

180.16 g/mol

D-Mannopyranose
Carubinose
Seminose
mannopyranose
(3S,4S,5S,6R)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol
C₆H₁₂O₆

D-mannopyranose congenital glycosylation disorders

D-mannopyranose is d-Mannose in its six-membered ring form. It has a role as a metabolite. It is a D-aldohexose, a D-mannose and a mannopyranose.

SCHEME

LIT

Tetrahedron Letters (1987), 28(31), 3569-72

///////////Demannose, D-Mannopyranose, Carubinose, Seminose, mannopyranose

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