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DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 36Yrs Exp. in the feld of Organic Chemistry,Working for AFRICURE PHARMA as ADVISOR earlier with GLENMARK PHARMA at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google, NO ADVERTISEMENTS , ACADEMIC , NON COMMERCIAL SITE, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution, ........amcrasto@gmail.com..........+91 9323115463, Skype amcrasto64 View Anthony Melvin Crasto Ph.D's profile on LinkedIn Anthony Melvin Crasto Dr.

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA, ROW2TECH, NIPER-G, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc He has total of 32 International and Indian awards

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Recent Posts

Zoliflodacin

December 26, 2025 3:12 am / Leave a comment


Zoliflodacin

  • CAS 1620458-09-4
  • AZD-0914
  • AZD0914
  • FWL2263R77
  • ETX0914

MF C22H22FN5O7 MW 487.4 g/mol

FDA 2025, APPROVALS 2025, 12/12/2025, Nuzolvence

(4′R,6′S,7′S)-17′-fluoro-4′,6′-dimethyl-13′-[(4S)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]spiro[1,3-diazinane-5,8′-5,15-dioxa-2,14-diazatetracyclo[8.7.0.02,7.012,16]heptadeca-1(17),10,12(16),13-tetraene]-2,4,6-trione

Spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5(6H),5′(2′H)-pyrimidine]-2′,4′,6′(1′H,3′H)-trione, 11-fluoro-1,2,4,4a-tetrahydro-2,4-dimethyl-8-[(4S)-4-methyl-2-oxo-3-oxazolidinyl]-, (2R,4S,4aS)-

(2R,4S,4aS)-11-Fluoro-2,4-dimethyl-8-[(4S)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione

To treat uncomplicated urogenital gonorrhea due to Neisseria gonorrhoeae

Zoliflodacin, sold under the brand name Nuzolvence, is an antibiotic used for the treatment of antibiotic-resistant Neisseria gonorrhoeae (gonorrhea).[2] Zoliflodacin is being developed as part of a public-private partnership between Innoviva Specialty Therapeutics and the Global Antibiotic Research & Development Partnership (GARDP).[3] Zoliflodacin is taken by mouth.[2]

The most common side effects include low white blood cell counts, headache, dizziness, nausea, and diarrhea.[2]

Zoliflodacin was approved for medical use in the United States in December 2025.[2]

SYN

SYN

SYN

US8889671, 5

SYN

WO-2022204231-A2

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=US106042502&_cid=P11-MJMADN-82597-1

(2R,4S,4aS)-11-Fluoro-2,4-dimethyl-8-[(4S)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione

   Example 5 was prepared from Intermediate 21. The title compound was isolated by reverse phase HPLC (10 mM ammonium acetate in water, CH 3CN) as the first eluting of two components. 1H NMR (400 MHz, DMSO-d 6) δ: 0.9 (d, 3H), 1.15 (d, 3H), 1.4 (d, 3H), 2.9 (d, 1H), 3.1 (t, 1H), 3.5-3.6 (m, 2H), 3.8 (m, 1H), 3.9 (d, 1H), 4.0 (d, 1H), 4.2 (q, 1H), 4.6-4.7 (m, 2H), 7.6 (s, 1H), 11.5 (s, 1H), 11.8 (s, 1H). MS (ES) MH +: 488.4 for C 22H 22FN 5O 7, [α] D 20=−92 (c=1; MeOH).
      Also isolated from the synthesis of Example 5 as the second eluting component from HPLC purification was (2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[(4S)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione
1H NMR (400 MHz, DMSO-d 6) δ: 0.9 (d, 3H), 1.15 (d, 3H), 1.4 (d, 3H), 2.9 (d, 1H), 3.1 (t, 1H), 3.6-3.7 (m, 2H), 3.8-4.0 (m, 1H), 3.9 (d, 1H), 4.1 (d, 1H), 4.2 (q, 1H), 4.6-4.7 (m, 2H), 7.6 (s, 1H), 11.5 (s, 1H), 11.8 (s, 1H). MS (ES) MH +: 488.4 for C 22H 22FN 5O 7, [α] D 20=+224 (c=1; MeOH).

Alternative Synthesis of Example 5

      A solution of Intermediate 22 (1.14 g, 2.71 mmol) and pyrimidine-2,4,6(1H,3H,5H)-trione (0.346 g, 2.71 mmol) in acetic acid (8 mL) and of water (2 mL) was heated at 110° C. for 2 hours. The solvent was removed and the reaction mixture was purified using Super Critical Fluid Chromatography (Chiralpak IC column with 30% methanol and 70% CO 2 mobile phase). The first eluting compound was further purified by dissolving in acetonitrile (30 mL) and diluting with water (60 mL) to give the title compound as a solid. (0.910 g, 69.0% yield). 1H NMR (300 MHz, DMSO-d 6) δ: δ 0.9 (d, 3H), 1.15 (d, 3H), 1.4 (d, 3H), 2.9 (d, 1H), 3.1 (t, 1H), 3.6-3.7 (m, 2H), 3.8 (m, 1H), 3.9 (d, 1H), 4.1 (d, 1H), 4.2 (q, 1H), 4.6-4.75 (m, 2H), 7.6 (s, 1H), 11.4 (s, 1H), 11.8 (s, 1H). MS (ES) MH +: 488 for C 22H 22FN 6O 7.
      Also isolated from the synthesis of Alternative Synthesis of Example 5 as the second component eluting from the HPLC purification was (2R,4R,4aR)-11-fluoro-2,4-dimethyl-8-[(4S)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione:

 1H NMR (300 MHz, DMSO-d 6) δ: 1.0 (d, 3H), 1.3 (d, 3H), 1.4 (d, 3H), 3.1 (d, 1H), 3.5-4.3 (m, 7H), 4.5-4.8 (m, 2H), 7.6 (s, 1H), 11.5 (br. s., 1H), 11.7 (br. s., 1H). MS (ES) MH +: 488 for C 22H 22FN 5O 7.

SYN

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/mic90

2.3.2 Chemical synthesis

The synthesis of zoliflodacin described below was reported in 2015 [47]. The first step, starting from 2,3,4-trifluorobenzaldehyde, consists of the protection of the aldehyde function to an acetal group. After deprotonation using n-BuLi, formylation is performed with DMF to introduce an aldehyde group, which is then converted to oxime using hydroxylamine. Chlorination with N-chlorosuccinimide (NCS), followed by reaction with L-alaninol and intramolecular SNAr allows the formation of the benzisoxazole ring. The oxazolidinone moiety is obtained using 1,1′-carbonyldiimidazole (CDI). The deprotection of the aldehyde is then performed in acidic conditions followed by another SNAr at the ortho position of the aldehyde using (2R,6S)-2,6-dimethylmorpholine. Finally, a Knoevenagel condensation between the aldehyde and hexahydropyrimidine-2,4,6-trione is performed, followed by an intramolecular rearrangement consisting in an [1-5] hydride shift and then intramolecular cyclization leading to zoliflodacin (Fig. 5).

PAT

str1

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Medical uses

Zoliflodacin is indicated for the treatment of uncomplicated urogenital gonorrhea in people who weigh at least 77 pounds (35 kg).[2]

Susceptible bacteria

Zoliflodacin has shown in vitro activity against the following species of bacteria:[4] Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, and Chlamydia trachomatis

Adverse effects

Animal studies showed that zoliflodacin might cause birth defects, pregnancy loss, or male fertility problems.[2]

Mechanism of action

It has a mechanism of action which involves inhibition of bacterial type II topoisomerases.[4][5][6]

History

Compound PNU-286607, discovered in a high-throughput screen for compounds with antibiotic activity.

A high throughput screening campaign aimed at identifying compounds with whole cell antibacterial activity performed at Pharmacia & Upjohn identified compound PNU-286607, a progenitor of Zoliflodacin, as having the desired activity.[7]

Subsequent research at AstraZeneca led to the discovery that the nitroaromatic in PNU-286607 could be replaced with a fused benzisoxazole ring,[8] which allowed for an exploration of different groups at the 3-position of the heterocycle. This work was continued at Entasis Pharmaceuticals where extensive optimization resulted in the discovery of ETX0914.[4]

Researchers tested zoliflodacin in a study with 930 participants who had uncomplicated urogenital gonorrhea.[2] Two-thirds of participants received a single 3-gram dose of zoliflodacin dissolved in water.[2] The other third received the standard treatment of ceftriaxone shot plus azithromycin pill.[2] The study measured how well the medicines cleared the bacteria 4 to 8 days after treatment.[2] The study showed 91% of participants who took zoliflodacin were cured and 96% of participants who received the standard treatment were cured.[2]

Society and culture

Zoliflodacin was approved for medical use in the United States in December 2025.[3]

The US Food and Drug Administration (FDA) granted the application for zoliflodacin fast track, qualified infectious disease product, and priority review designations for the uncomplicated urogenital gonorrhea indication.[2] The FDA approval for zoliflodacin was granted to Entasis Therapeutics.[2]

Names

Zoliflodacin is the international nonproprietary name.[9]

Zoliflodacin is sold under the brand name Nuzolvence.[3]

References

  1.  https://innovivaspecialtytherapeutics.com/wp-content/uploads/2025/12/NUZOLVENCE-zoliflodacin-Full-Prescribing-Information-December-2025.pdf [bare URL PDF]
  2.  “FDA Approves Two Oral Therapies to Treat Gonorrhea”. U.S. Food and Drug Administration (FDA) (Press release). 12 December 2025. Retrieved 13 December 2025. Public Domain This article incorporates text from this source, which is in the public domain.
  3.  Pierre G (12 December 2025). “Nuzolvence (Zoliflodacin) Receives U.S. FDA Approval”. Global Antibiotic Research & Development Partnership (GARDP). Retrieved 13 December 2025.
  4.  Basarab GS, Kern GH, McNulty J, Mueller JP, Lawrence K, Vishwanathan K, et al. (July 2015). “Responding to the challenge of untreatable gonorrhea: ETX0914, a first-in-class agent with a distinct mechanism-of-action against bacterial Type II topoisomerases”. Scientific Reports. 5 (1) 11827. Bibcode:2015NatSR…511827B. doi:10.1038/srep11827. PMC 4501059. PMID 26168713.
  5.  Bradford PA, Miller AA, O’Donnell J, Mueller JP (June 2020). “Zoliflodacin: An Oral Spiropyrimidinetrione Antibiotic for the Treatment of Neisseria gonorrheae, Including Multi-Drug-Resistant Isolates”. ACS Infectious Diseases. 6 (6): 1332–1345. doi:10.1021/acsinfecdis.0c00021. PMID 32329999.
  6.  Pisano L, Giovannuzzi S, Supuran CT (June 2024). “Management of Neisseria gonorrhoeae infection: from drug resistance to drug repurposing”. Expert Opinion on Therapeutic Patents. 34 (6): 511–524. doi:10.1080/13543776.2024.2367005. PMID 38856987.
  7.  Miller AA, Bundy GL, Mott JE, Skepner JE, Boyle TP, Harris DW, et al. (August 2008). “Discovery and characterization of QPT-1, the progenitor of a new class of bacterial topoisomerase inhibitors”. Antimicrobial Agents and Chemotherapy. 52 (8): 2806–2812. doi:10.1128/AAC.00247-08. PMC 2493097. PMID 18519725.
  8.  Basarab GS, Brassil P, Doig P, Galullo V, Haimes HB, Kern G, et al. (November 2014). “Novel DNA gyrase inhibiting spiropyrimidinetriones with a benzisoxazole scaffold: SAR and in vivo characterization”. Journal of Medicinal Chemistry. 57 (21): 9078–9095. doi:10.1021/jm501174m. PMID 25286019.
  9.  World Health Organization (2016). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 76”. WHO Drug Information. 30 (3). hdl:10665/331020.

Further reading

Clinical data
Trade namesNuzolvence
Other namesAZD0914; ETX0914
AHFS/Drugs.comNuzolvence
License dataUS DailyMed: Zoliflodacin
Routes of
administration		By mouth
Drug classAntibacterial
ATC codeNone
Legal status
Legal statusUS: ℞-only[1][2]
Pharmacokinetic data
Bioavailability97.8%
MetabolismLiver
Onset of actionFasted: 1.5–2.3 hFed: 4 h
Elimination half-life5.3–6.3 h
ExcretionFeces (79.6%)Urine (18.2%)
Identifiers
IUPAC name
PubChem CID76685216
DrugBank12817
UNIIFWL2263R77
KEGGD11726
Chemical and physical data
FormulaC22H22FN5O7
Molar mass487.444 g·mol−1
3D model (JSmol)Interactive image
SMILES
InChI

//////////Zoliflodacin, FDA 2025, APPROVALS 2025, Nuzolvence, AZD-0914, AZD 0914, FWL2263R77, ETX 0914

Iscartrelvir

December 25, 2025 2:37 am / Leave a comment


Iscartrelvir

CAS 2921711-74-0

MF 2921711-74-0, 526.4 g/mol

N-{(1S,2R)-2-[4-bromo-2-(methylcarbamoyl)-6-nitroanilino]cyclohexyl}isoquinoline-4-carboxamide
antiviral, WU-04, WU 04, W2LTV65R5E

Iscartrelvir is an investigational new drug developed by the Westlake University for the treatment of COVID-19. It targets the SARS-CoV-2 3CL protease, which is crucial for the replication of the virus responsible for COVID-19.[1][2]

Iscartrelvir is a small molecule drug. The usage of the INN stem ‘-trelvir’ in the name indicates that Iscartrelvir is a antiviral 3CL protease inhibitor. Iscartrelvir has a monoisotopic molecular weight of 525.1 Da.

PAT

WO2022150962A1

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022150962&_cid=P11-MJKTXT-76321-1

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=CN331401594&_cid=P11-MJKTO7-65334-1

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2024243841&_cid=P11-MJKTO7-65334-1

N-((1S,2R)-2-((4-bromo-2-(methylcarbamoyl)-6-nitrophenyl)amino)cyclohexyl)isoquinoline-4-carboxamide, and its structure is as follows:

Example 1: Preparation of Compound 1 

[0189]A free, amorphous compound 1, a yellow solid, was prepared according to the method disclosed in paragraphs [00121]-[00128] of WO2022150962A1, and was used in the following examples. The specific synthetic steps are shown in steps a to d:

The reagents and conditions for steps a to d are further described below: (a) 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU), N,N-diisopropylethylamine (DIPEA), CH₂Cl₂ 

or 

dichloromethane (DCM), 0°C, 2 h; (b) DIPEA, dimethylformamide (DMF), 80°C, 16 h; (c) 3M ethyl hydrochloride (HCl·EA), CH₂Cl₂ , 1 

h ; (d ) HATU, DIPEA, DMF, room temperature, 12 h. 

[0191]Step a: Synthesis of N-methyl-5-bromo-2-fluoro-3-nitrobenzamide (I-1) 

[0192]A solution of 5-bromo-2-fluoro-3-nitrobenzoic acid (0.8 g, 3.80 mmol) in dichloromethane (20 mL) was stirred at 0 °C. Then, HATU (2.0 g, 5.25 mmol), DIPEA (1.88 mL, 11.4 mmol), and methylamine hydrochloride (0.31 g, 4.5 mmol) were added to the reaction mixture. The mixture was stirred at 0 °C for 2 hours until it became clear. The mixture was extracted three times with dichloromethane, and the combined organic layers were washed with a saturated brine solution. The organic phase was then dried over anhydrous Na₂SO₄ and concentrated 

under vacuum. Finally, the mixture was purified by chromatography to give compound I-1 (0.8 g, 76% yield) as a yellow solid.

[0193]Step b: Synthesis of tert-butyl 2-((4-bromo-2-(methylcarbamoyl)-6-nitrophenyl)amino)cyclohexyl)carbamate (I-2) 

[0194]A solution of compound I-1 (0.8 g, 2.9 mmol) in 15 mL of DMF was stirred at room temperature. Then, tert-butyl ((1S,2R)-2-aminocyclohexyl)carbamate (0.75 g, 3.5 mmol) (the corresponding stereoisomer of this reagent can be used to synthesize the stereoisomer of compound I-2) and DIPEA (1.44 mL, 8.7 mmol) were added to the reaction mixture. The mixture was heated to 80 °C and stirred for 16 hours. The mixture was extracted three times with ethyl acetate, and the combined organic layers were washed with saturated salt solution. The organic phase was then dried over anhydrous Na₂SO₄ and concentrated under vacuum to give compound 

I -2 as a yellow solid, requiring no further purification.

Step c: Synthesis of 2-(2-aminocyclohexyl)amino)-5-bromo-N-methyl-3-nitrobenzamide hydrochloride (I-3) 

[0196]A solution of compound I-2 (90 mg, 0.19 mmol) (or the corresponding stereoisomer) in anhydrous dichloromethane (6 mL) was stirred at room temperature. Then, HCl (4 mL, 3 M in ethyl acetate) was added. The mixture was stirred at room temperature for 2 hours. The mixture was concentrated under vacuum to give compound I-3 as a yellow solid, requiring no further purification. 

[0197]Step d: Synthesis of N-((1S,2R)-2-((4-bromo-2-(methylcarbamoyl)-6-nitrophenyl)amino)cyclohexyl)isoquinoline-4-carboxamide 

[0198]At room temperature, a solution of the corresponding isoquinoline-4-carboxylic acid (1 equivalent) and HATU (1.5 equivalent) in anhydrous DMF (6 mL) was stirred. Then, compound I-3 and DIPEA (5.0 equivalent) were added. The mixture was stirred overnight at room temperature. The mixture was extracted three times with ethyl acetate, and the combined organic layers were washed with saturated brine. The organic phase was then dried over anhydrous Na₂SO₄ and 

concentrated under vacuum. Finally, the mixture was purified by chromatography to give compound 1 as a free amorphous solid in yellow form.

PAT

str1

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Clinical data
Other namesWPV01; WU-04
Identifiers
IUPAC name
CAS Number2921711-74-0
PubChem CID156774920
ChemSpider129307041
UNIIW2LTV65R5E
PDB ligandJ7R (PDBe, RCSB PDB)
Chemical and physical data
FormulaC24H24BrN5O4
Molar mass526.391 g·mol−1
3D model (JSmol)Interactive image
SMILES
InChI

References

  1.  Yang L, Wang Z (September 2023). “Bench-to-bedside: Innovation of small molecule anti-SARS-CoV-2 drugs in China”. European Journal of Medicinal Chemistry. 257 115503. doi:10.1016/j.ejmech.2023.115503. PMC 10193775. PMID 37229831.
  2.  Hou N, Shuai L, Zhang L, Xie X, Tang K, Zhu Y, et al. (February 2023). “Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro”. ACS Central Science. 9 (2): 217–227. doi:10.1021/acscentsci.2c01359. PMC 9885526. PMID 36844503.
  3. Resistance mechanisms of SARS-CoV-2 3CLpro to the non-covalent inhibitor WU-04Publication Name: Cell DiscoveryPublication Date: 2024-04-09PMCID: PMC11003996PMID: 38594245DOI: 10.1038/s41421-024-00673-0
  4. Identification of Ebselen derivatives as novel SARS-CoV-2 main protease inhibitors: Design, synthesis, biological evaluation, and structure-activity relationships explorationPublication Name: Bioorganic & Medicinal ChemistryPublication Date: 2023-12-15PMID: 37972434DOI: 10.1016/j.bmc.2023.117531
  5. The molecular mechanism of non-covalent inhibitor WU-04 targeting SARS-CoV-2 3CLpro and computational evaluation of its effectiveness against mainstream coronavirusesPublication Name: Physical chemistry chemical physics : PCCPPublication Date: 2023-09-13PMID: 37655706DOI: 10.1039/d3cp03828a
  6. Bench-to-bedside: Innovation of small molecule anti-SARS-CoV-2 drugs in ChinaPublication Name: European Journal of Medicinal ChemistryPublication Date: 2023-09-05PMCID: PMC10193775PMID: 37229831DOI: 10.1016/j.ejmech.2023.115503
  7. Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLproPublication Name: ACS Central SciencePublication Date: 2023-01-25PMCID: PMC9885526PMID: 36844503DOI: 10.1021/acscentsci.2c01359

////////iscartrelvir, antiviral, WU-04, WU 04, W2LTV65R5E

Zoracopan

December 24, 2025 2:52 am / Leave a comment


Zoracopan

CAS 2243483-63-6

MF C31H31BrN6O3 MW 615.52

2-Azabicyclo[3.1.0]hexane-3-carboxamide, 2-[2-[3-acetyl-7-methyl-5-(2-methyl-5-pyrimidinyl)-1H-indol-1-yl]acetyl]-N-(6-bromo-3-methyl-2-pyridinyl)-5-methyl-, (1R,3S,5R)-

(1R,3S,5R)-2-{[3-acetyl-7-methyl-5-(2-methylpyrimidin5-yl)-1H-indol-1-yl]acetyl}-N-(6-bromo-3-methylpyridin2-yl)-5-methyl-2-azabicyclo[3.1.0]hexane-3-carboxamide
complement factor D inhibitor, ALXN-2080, ALXN 2080, E7799Y8LXY

Zoracopan is a selective complement factor D (CFD) inhibitor. When administered systemically (orally or intravenously), Zoracopan accumulates and is sustained-released in ocular tissues, primarily in the choroid-retinal pigment epithelium (C-RPE) and/or iridociliary body (I-CB).

Zoracopan is a small molecule drug. The usage of the INN stem ‘-copan’ in the name indicates that Zoracopan is a complement receptor antagonist/complement inhibitor. Zoracopan is under investigation in clinical trial NCT06173596 (A Study to Evaluate Potential Drug Interactions Between ALXN2080 and Itraconazole, Fluconazole & Carbamazepine in Healthy Adults). Zoracopan has a monoisotopic molecular weight of 614.16 Da.

  • Safety and Tolerability, PK, and PD Study of Single and Multiple ALXN2080 Doses in Healthy ParticipantsCTID: NCT05428696Phase: Phase 1Status: CompletedDate: 2024-06-07
  • A Study to Evaluate Potential Drug Interactions Between ALXN2080 and Itraconazole, Fluconazole & Carbamazepine in Healthy AdultsCTID: NCT06173596Phase: Phase 1Status: CompletedDate: 2024-06-20
  • A Study to Investigate the Potential Drug Interactions Between ALXN2080 and Rosuvastatin and Metformin in Healthy Adult ParticipantsCTID: NCT06160414Phase: Phase 1Status: CompletedDate: 2025-04-24

WO2024259085

WO2024137329

SYN

US11084800,

426

https://patentscope.wipo.int/search/en/detail.jsf?docId=US289331902&_cid=P10-MJJEYB-31207-1

SYN

WO2021183555

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2018160889&_cid=P10-MJJEK1-12570-1

PAT

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[1]. Ocular drug depot for complement-mediated disorders. WO2021183555A1 – Ocular drug depot for complement-mediated disorders – Google Patents.

////zoracopan, complement factor D inhibitor, ALXN-2080, ALXN 2080, E7799Y8LXY

Zopocianine

December 23, 2025 2:32 am / Leave a comment


Zopocianine

CAS 2206660-94-6, NA SALT 2206660-95-7

MF C74H93N7O27S4, 1,640.83

L-Tyrosine, N-[[[(1S)-1,3-dicarboxypropyl]amino]carbonyl]-L-g-glutamyl-3-[2-(2-aminoethoxy)ethoxy]propanoyl-L-phenylalanyl-O-[6-[2-[1,3-dihydro-3,3-dimethyl-5-sulfo-1-(4-sulfobutyl)-2H-indol-2-ylidene]ethylidene]-2-[2-[3,3-dimethyl-5-sulfo-1-(4-sulfobutyl)-3H-indolium-2-yl]ethenyl]-1-cyclohexen-1-yl]-, inner salt

N-{[(1S)-1,3-dicarboxypropyl]carbamoyl}-L-γ-glutamyl3-[2-(2-aminoethoxy)ethoxy]propanoyl-L-phenylalanylO-[(6Ξ)-2-{(1Ξ)-2-[3,3-dimethyl-1-(4-sulfobutyl)-5-
sulfonato-3H-indol-1-ium-2-yl]ethen-1-yl}-6-{(2Ξ)-2-
[3,3-dimethyl-5-sulfo-1-(4-sulfobutyl)-1,3-dihydro-2Hindol-2-ylidene]ethylidene}cyclohex-1-en-1-yl]-Ltyrosine
diagnostic imaging agent, UD9V5S9M7A, OTL 0078, OTL 78

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/////////zopocianine, diagnostic imaging agent, UD9V5S9M7A, OTL 0078, OTL 78

Zomiradomide

December 22, 2025 2:37 am / Leave a comment


Zomiradomide

CAS 2655656-99-6

MF C45H48F3N7O6S MW871.97

  • N-[2-[4-[[6-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethyl]-2-azaspiro[3.3]heptan-2-yl]methyl]cyclohexyl]-5-(2-hydroxypropan-2-yl)-1,3-benzothiazol-6-yl]-6-(trifluoromethyl)pyridine-2-carboxamide
  • N-[2-[trans-4-[[6-[2-[[2-(2,6-Dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethyl]-2-azaspiro[3.3]hept-2-yl]methyl]cyclohexyl]-5-(1-hydroxy-1-methylethyl)-6-benzothiazolyl]-6-(trifluoromethyl)-2-pyridinecarboxamide

antineoplastic, IRAK degrader-1, AQ5UXV5646

Zomiradomide is an orally active PROTAC degrader for IRAK4 (DC50=6 nM), thereby inhibiting the NF-κB signaling pathway. Zomiradomide acts also as a molecular glue, recruiting Ikaros and Aiolos, and mediating their degradation (DC50 for Ikaros is 1 nM), thereby activating the type I IFN signaling pathway.

Zomiradomide is a small molecule protein degrader of interleukin-1 receptor-associated kinase 4 (IRAK4) and the immunomodulatory imide drug (IMiD) substrates Ikaros (IKZF1) and Aiolos (IKZF3), with potential immunomodulating and antineoplastic activities. Upon administration, zomiradomide modulates the E3 (ubiquitin) ligase and targets IRAK4, Ikaros and Aiolos for ubiquitination. This induces proteasome-mediated degradation of IRAK4, Ikaros and Aiolos. The degradation of IRAK4 inhibits IRAK4-mediated signaling and prevents the activation of IRAK4-mediated nuclear factor-kappa B (NF-kB) signaling and decreases the expression of inflammatory cytokines and certain pro-survival factors. This inhibits the proliferation of IRAK4-overactivated tumor cells, which are found in cells harboring MYD88 activating mutations or those with overactivated toll-like receptor (TLR) pathways. The degradation of the transcription factors Ikaros and Aiolos leads to a downregulation of other proteins, including interferon regulatory factor 4 (IRF4), which upregulates type I interferon signaling and further inhibits NF-kB activation. This leads to apoptosis and the inhibition of tumor cell proliferation. IRAK4, a serine/threonine-protein kinase that plays a key role in both the TLR and IL-1R signaling pathways, is activated though the adaptor protein MYD88 and links the TLR and IL-1R signaling pathway to the NF-kB pathway.

SYN

WO2022027058

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022027058&_cid=P20-MJGJKA-81687-1

Example 1. Synthesis of N-[2-[4-[[6-[2-[[2-(2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]amino]ethyl]-2- azaspiro[3.3]heptan-2-yl]methyl]cyclohexyl]-5-(1-hydroxy-1-methyl-ethyl)-1,3-benzothiazol-6-yl]-6-(trifluoromethyl)pyridine-2-carboxamide (Compound A)

[00349] To a solution of 4-[2-(2-azaspiro[3.3]heptan-6-yl)ethylamino]-2-(2,6-dioxo-3-piperidyl)isoindoline -1,3-dione (75.8 mg, 148 umol, TFA salt, Intermediate ATH) in THF (2 mL) was added TEA (15.0 mg, 148 umol), then the mixture stirred at 25 °C for 10 min. Next, HOAc (8.92 mg, 148 umol) and N-[2-(4-formylcyclohexyl)-5-(1-hydroxy-1-methyl-ethyl)-1,3-benzothiazol-6-yl]-6-(trifluoromethyl)pyridine-2-carboxamide (73.0 mg, 148 umol, Intermediate BAX) were added to the mixture and the mixture was stirred at 25 °C for 20 minutes, then NaBH(OAc)3 (62.9 mg, 297 umol) was added to the mixture at 0 °C. The reaction mixture was stirred at 0-25 °C for 2 hours. On completion, the reaction mixture was quenched with H2O (1 mL) and concentrated in vacuo. The residue was purified by prep-HPLC (column: Phenomenex Synergi C18150*25*10 um; mobile phase: [water(0.225%FA)-ACN]; B%: 31%-58%, 9 min) to give the title compound (59.1 mg, 41% yield) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ 12.54 (s, 1H), 11.09 (s, 1H), 9.06 (s, 1H), 8.49 – 8.44 (m, 1H), 8.38 (t, J = 8.0 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.88 (s, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.10 – 6.99 (m, 2H), 6.47 (t, J = 5.6 Hz, 1H), 6.07 (s, 1H), 5.05 (dd, J = 5.6, 12.8 Hz, 1H), 3.54 – 3.47 (m, 2H), 3.25 – 3.18 (m, 4H), 3.06 – 2.99 (m, 1H), 2.93 – 2.83 (m, 1H), 2.63 – 2.56 (m, 1H), 2.54 (s, 3H), 2.30 – 2.21 (m, 2H), 2.30 – 2.21 (m, 3H), 2.06 – 1.99 (m, 1H), 1.88 – 1.77 (m, 4H), 1.68 – 1.61 (m, 8H), 1.58 – 1.49 (m, 2H), 1.45 – 1.36 (m, 1H), 1.15 – 1.02 (m, 2H); LC-MS (ESI+) m/z 872.2 (M+H)+.

PAT

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[1]. Weiss Matthew M. Preparation of benzothiazole derivatives as IRAK degraders and uses thereof. World Intellectual Property Organization, WO2021127190 A1. 2021-06-24.[2]. Zeng S, et al. Current advances and development strategies of orally bioavailable PROTACs. Eur J Med Chem. 2023 Dec 5;261:115793.  [Content Brief][3]. Weiss MM, et al., Discovery of KT-413, a Targeted Protein Degrader of IRAK4 and IMiD Substrates Targeting MYD88 Mutant Diffuse Large B-Cell Lymphoma. J Med Chem. 2024 Jul 11;67(13):10548-10566.  [Content Brief]

/////////zomiradomide, antineoplastic, IRAK degrader-1, AQ5UXV5646

Zerencotrep

December 21, 2025 2:44 am / Leave a comment


Zerencotrep

CAS 1628287-16-0

MF C23H20ClF3N4O5, MW 524.88

7-[(4-chlorophenyl)methyl]-1-(3-hydroxypropyl)-3-methyl-8-[3-(trifluoromethoxy)phenoxy]purine-2,6-dione

7-[(4-chlorophenyl)methyl]-1-(3-hydroxypropyl)-3-
methyl-8-[3-(trifluoromethoxy)phenoxy]-3,7-dihydro1H-purine-2,6-dione
transient receptor potential channel 4 and 5 (TRPC4, TRPC5) inhibitor, Pico 145, HC 608, HMIMSYLCWQ

Pico145 (HC-608) is a remarkable inhibitor of TRPC1/4/5 channels, inhibits (-)-englerin A-activated TRPC4/TRPC5 channels, with IC50s of 0.349 and 1.3 nM in cells, and shows no effect on TRPC3, TRPC6, TRPV1, TRPV4, TRPA1, TRPM2, TRPM8.


Zerencotrep is a small molecule drug. The usage of the INN stem ‘-cotrep’ in the name indicates that Zerencotrep is a transient receptor potential canonical channel 5 (TRPC5) antagonist. Zerencotrep has a monoisotopic molecular weight of 524.11 Da.

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2014143799&_cid=P22-MJF454-30876-1

The following examples 7a through 7k were prepared using the method of example 6, step 1.

Example 7a 7-(4-chlorobenzyl)-l -(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-l -purine-2,6(3H,7H)-dione

The title compound was prepared using the method of example 6, step 1 and purified

preparative HPLC to give 7-(4-chlorobenzyl)-l -(3-hydroxypropyl)-3-methyl-8-(3-

(trifluoromethoxy)phenoxy)-lH-purine-2,6(3H,7H)-dione (10 mg, 17.3% yield) as white solid. lH-NMR (CD3OD) δ 7.57-7.53(t, IH), 7.46-7.44(d, 2H), 7.37-7.33(m, 4H), 7.26-7.24(d, IH), 5.49(s, 2H), 4.13-4.09(t, IH), 3.64-3.60(t, 2H), 3.42(s, 3H), 1.89-1.86(m, 2H). LCMS retention time 3.059 min; LCMS MH+ 525.

PAT

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///////////zerencotrep, Pico 145, HC 608, HMIMSYLCWQ

Zemprocitinib

December 20, 2025 2:54 am / Leave a comment


Zemprocitinib

CAS 2417414-44-7

MF C16H19N5O2S MW 345.4 g/mol

N-[3-(3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-3-yl)-1-bicyclo[1.1.1]pentanyl]propane-1-sulfonamide

N-[3-(imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)bicyclo[1.1.1]pentan-1-yl]propane-1-sulfonamide
Janus kinase inhibitor, anti-inflammatory, LNK 01001, LG6MM3RP86

Zemprocitinib (also known as LNK01001) is a selective Janus kinase (JAK) 1 inhibitor, a type of small molecule drug being developed for inflammatory and autoimmune conditions like rheumatoid arthritis, atopic dermatitis, and ankylosing spondylitis. It works by blocking the JAK1 enzyme, reducing the inflammatory signals that cause these diseases, and has shown promising results in clinical trials, with development reaching Phase 3. 

Key Aspects:

  • Drug Class: JAK1 Inhibitor.
  • Mechanism: Blocks Janus Kinase 1, a key enzyme in inflammatory pathways.
  • Developer: Initially Lynk Pharmaceuticals.
  • Potential Uses: Rheumatoid Arthritis, Atopic Dermatitis, Ankylosing Spondylitis, Psoriasis, Alopecia Areata.
  • Development Stage: Reached Phase 3 clinical trials for several indications.
  • Chemical Info: CAS: 2417414-44-7; Formula: C16H19N5O2S. 

In Summary:

Zemprocitinib is an investigational drug targeting inflammation by inhibiting JAK1, with potential to treat various autoimmune disorders, showing strong efficacy in early clinical trials for conditions like rheumatoid arthritis. 

SYN

US20220009927

https://patentscope.wipo.int/search/en/detail.jsf?docId=US347660217&_cid=P21-MJDP3D-82397-1

Example 1

Step 1. 4-Chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridine (1b)

      Compound 1a (30 g, 0.2 mol) and TsCl (45 g, 0.24 mol) were dissolved in a mixture of acetone and water (600 mL, V:V=5:1) followed by the addition of NaOH (11.8 g, 0.29 mmol) at 0° C. After stirring at RT for 1 h, the mixture was concentrated to 100 mL of solvent and cooled with ice-water. The formed solid was filtered and dried to afford title product as a white solid (52 g, 86% yield). 1H NMR (400 MHz, CDCl 3) δ 8.30 (d, J=5.6 Hz, 1H), 8.05 (d, J=8.4 Hz, 2H), 7.76 (d, J=4.0 Hz, 1H), 7.27 (d, J=8.4 Hz, 2H), 7.18 (d, J=5.2 Hz, 1H), 6.69 (d, J=4.0 Hz, 1H), 2.37 (s, 3H).

Step 2. 4-Chloro-5-nitro-1-tosyl-1H-pyrrolo[2,3-b]pyridine (1c)

      To a mixture of compound 1b (5.0 g, 16.3 mmol) and 75 mL of DCM was added tetrabutylammonium nitrate (2.9 g, 21.3 mmol) portion-wise at 0° C. followed by trifluoroacetic anhydride (3.14 mL, 22.2 mmol) slowly. After stirring for 16 hrs at RT, another portion of tetrabutylammonium nitrate (0.58 g, 4.23 mmol) and trifluoroacetic anhydride (0.8 mL, 5.7 mmol) were added at 0° C. After warmed up to room temperature, the reaction mixture was stirred for 4 hrs at RT. The reaction mixture was diluted with DCM (150 mL), washed with water (30 mL×2) and then concentrated to dryness. The residue was triturated in MeOH to afford title product as a white solid (3.15 g, 55% yield). LC-MS (Method 2): t R=1.76 min, m/z (M+H) +=351.8.

Step 3. Tert-butyl 3-((5-nitro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)amino)bicyclo[1.1.1]pentane-1-carboxylate (Id)

      Compound 1c (500 mg, 1.42 mmol), tert-butyl 3-aminobicyclo[1.1.1]pentane-1-carboxylate (313 mg, 1.71 mmol) and DIPEA (276 mg, 2.13 mmol) were dissolved in isopropanol (5 mL). The above solution was stirred at 120° C. for 2 hrs. After cooling, the formed solid was collected by filtering and dried to afford the title product as a brown solid (612 mg, 86% yield). 1H NMR (400 MHz, CDCl 3) δ 9.28 (s, 1H), 9.11 (s, 1H), 8.07 (d, J=8.0 Hz, 2H), 7.64 (d, J=5.6 Hz, 1H), 7.30 (d, J=8.0 Hz, 2H), 6.96 (d, J=5.6 Hz, 1H), 2.48 (s, 6H), 2.40 (s, 3H), 1.47 (s, 9H).

Step 4. Tert-butyl 3-((5-amino-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)amino)bicyclo[1.1.1]pentane-1-carboxylate (le)

      Compound 1d (600 mg, 1.22 mmol) was dissolved in MeOH (6 mL) followed by the addition of Pd/C (48 mg, 10% wt) in one portion. The mixture was hydrogenated (1 atm) at RT for 16 hrs. The mixture was filtered and the filtrate was concentrated. The residue was purified by prep. TLC (PE:EtOAc=1:1) to afford the title product as a white solid (258 mg, 46% yield). LC-MS (Method 2): t R=1.64 min, m/z (M+H) +=469.0.

Step 5. Tert-butyl 3-(6-tosylimidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)bicyclo[1.1.1]pentane-1-carboxylate (1f)

      Compound 1e (258 mg, 0.55 mmol), triethyl orthoformate (204 mg, 1.37 mmol) and p-toluenesulfonic acid (10 mg, 0.05 mmol) were dissolved in toluene (6 mL). The mixture was stirred for 16 hrs at 120° C. After cooling, the mixture was concentrated to dryness. The residue was purified by chromatography on silica gel (elute: PE:EtOAc=1:1) to afford the title product as a brown solid (191 mg, 73% yield). 1H NMR (400 MHz, CDCl 3) δ 8.91 (s, 1H), 8.10 (d, J=8.0 Hz, 2H), 7.82 (d, J=8.0 Hz, 2H), 7.27-7.25 (m, 2H), 6.83 (d, J=4.4 Hz, 1H), 2.71 (s, 6H), 2.35 (s, 3H), 1.51 (s, 9H).

Step 6. 3-(6-Tosylimidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6LF)-yl)bicyclo[1.1.1]pentane-1-carboxylic acid (1g)

      To a solution of compound 1f (191 mg, 0.40 mmol) in DCM (2 mL) was added TFA (1 mL). After stirring for 16 hrs at RT, the mixture was concentrated to dryness to afford crude title product as a brown solid (170 mg, 100% yield). LC-MS (Method 2): t R=1.47 min, m/z (M+H) +=423.0

Step 7. Tert-butyl (3-(6-tosylimidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6LF)-yl)bicyclo[1.1.1]pentan-1-yl)carbamate (1h)

      To a mixture of compound 1g (153 mg, 0.36 mmol) in tert-butanol (7.2 mL) was added DPPA (130 mg, 0.47 mmol) and TEA (73 mg, 0.72 mmol) under N 2. The mixture was stirred at RT for 30 minutes and then raised to 90° C. and stirred for another 16 hrs. After cooling, the mixture was concentrated to dryness. The residue was purified by chromatography on silica gel (elute: DCM:MeOH=50:1) to afford the title product as a brown solid (160 mg, 89% yield). LC-MS (Method 2): t R=1.71 min, m/z (M+H) +=494.0.

Step 8. Tert-butyl (3-(imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)bicyclo[1.1.1]pentan-1-yl)carbamate (1i)

      To a solution of compound 1h (160 mg, 0.32 mmol) in MeOH (3 mL) and water (3 mL) was added NaOH (300 mg, 7.5 mmol). After stirring for 4 hrs at RT, the mixture was concentrated. The residue was diluted with water (20 mL) and extracted with EtOAc (30 mL*2). The combined organic layers were concentrated to dryness and the residue was purified by chromatography on silica gel (elute: DCM:MeOH=20:1) to afford the title product as a white solid (60 mg, 55% yield). 1H NMR (400 MHz, CDCl 3) δ 9.99 (s, 1H), 9.81 (s, 1H), 7.80 (s, 1H), 7.39 (d, J=4.4 Hz, 1H), 6.36 (d, J=4.4 Hz, 1H), 5.30 (br s, 1H), 2.80 (s, 6H), 1.50 (s, 9H).

Step 9. 3-(Imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)bicyclo[1.1.1]pentan-1-amine 2,2,2-trifluoroacetate (1j)

      To a solution of compound 1i (60 mg, 0.18 mmol) in DCM (2 mL) was added TFA (0.5 mL). After stirring for 1 hour at RT, the mixture was concentrated to dryness to afford crude title product as a brown solid (100 mg, 100% yield). LC-MS (Method 2): t R=0.309 min, m/z (M+H) +=240.0

Step 10. N-(3-(Imidazo[4,5-d]pyrrolo[2,3-b]pyridin-1(6H)-yl)bicyclo[1.1.1]pentan-1-yl)propane-1-sulfonamide (1)

      To a solution of compound 1j (40 mg, 0.16 mmol) and TEA (51 mg, 50 mmol) in DMF (1 mL) was added propane-1-sulfonyl chloride (28 mg, 0.5 mmol) at 0° C. After stirring for 3 hrs at RT, the mixture was diluted with water (20 mL) and extracted with EtOAc (20 mL*3). The combined organic layers were concentrated to dryness. The residue was purified prep. HPLC (Method A) to afford the title product as a white solid (10 mg, 18% yield). LC-MS (Method 1): t R=2.71 min, m/z (M+H) +=346.0. 1H NMR (400 MHz, DMSO-d 6) δ 11.94 (s, 1H), 8.59 (d, J=1.6 Hz, 1H), 8.40 (s, 1H), 8.13 (s, 1H), 7.51 (s, 1H), 6.70 (d, J=1.6 Hz, 1H), 3.08 (d, J=8.8 Hz, 2H), 2.70 (s, 6H), 1.74-1.72 (m, 2H), 1.73 (d, J=6.0 Hz, 3H).

PAT

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///////////Zemprocitinib, Janus kinase inhibitor, anti-inflammatory, LNK 01001, LG6MM3RP86

Zemirciclib

December 19, 2025 2:10 am / Leave a comment


Zemirciclib

CAS 2057509-72-3

MF C22H28ClN5O2, 429.9 g/mol

(1S,3R)-3-acetamido-N-[5-chloro-4-(5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)pyridin-2-
yl]cyclohexane-1-carboxamide

(1S,3R)-3-acetamido-N-[5-chloro-4-(5,5-dimethyl-4,6-dihydropyrrolo[1,2-b]pyrazol-3-yl)pyridin-2-yl]cyclohexane-1-carboxamide

(1S,3R)-3-acetamido-N-(5-chloro-4-(5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)pyridin-2-yl)cyclohexanecarboxamide

cyclin-dependent kinase inhibitor, antineoplastic, AZD 4573, UNII-E5XSP3X68B

Zemirciclib is a selective, short-acting inhibitor of the serine/threonine cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the RNA polymerase II (RNA Pol II) elongation factor positive transcription elongation factor b (PTEF-b; PTEFb), with potential antineoplastic activity. Upon intravenous administration, zemirciclib binds to and blocks the phosphorylation and kinase activity of CDK9, thereby preventing PTEFb-mediated activation of RNA Pol II, leading to the inhibition of gene transcription of various anti-apoptotic proteins. This induces cell cycle arrest and apoptosis, and leads to a reduction in tumor cell proliferation. CDK9 regulates elongation of transcription through phosphorylation of RNA polymerase II at serine 2 (p-Ser2-RNAPII). It is upregulated in various tumor cell types and plays a key role in the regulation of Pol II-mediated transcription of anti-apoptotic proteins. Tumor cells are dependent on anti-apoptotic proteins for their survival.

AZD-4573 is a small molecule drug with a maximum clinical trial phase of II and has 1 investigational indication.

  • AZD4573 in Novel Combinations With Anti-cancer Agents in Patients With Advanced Blood CancerCTID: NCT04630756Phase: Phase 1/Phase 2Status: CompletedDate: 2025-04-09
  • AZD4573 as Monotherapy or in Combinations With Anti-cancer Agents in Patients With r/r PTCL or r/r cHLCTID: NCT05140382Phase: Phase 2Status: CompletedDate: 2024-08-28
  • Study to Assess Safety, Tolerability, Pharmacokinetics and Antitumor Activity of AZD4573 in Relapsed/Refractory Haematological MalignanciesCTID: NCT03263637Phase: Phase 1Status: CompletedDate: 2021-10-22

SYN

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2017001354&_cid=P22-MJC84G-87476-1

Example 14: (1S,3R)-3-acetamido-N-(5-chloro-4-(5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)pyridin-2-yl)cyclohexanecarboxamide

PAT

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/////////Zemirciclib, cyclin-dependent kinase inhibitor, antineoplastic, AZD 4573, UNII-E5XSP3X68B

Zelenirstat

December 18, 2025 3:03 am / Leave a comment


Zelenirstat

CAS 1215011-08-7

MF C24H30Cl2N6O2S, 537.5 g/mol

2,6-dichloro-N-[1,5-dimethyl-3-(2-methylpropyl)-1Hpyrazol-4-yl]-4-[2-(piperazin-1-yl)pyridin-4-yl]benzene-1-sulfonamide
N-myristoyltransferase inhibitor, antineoplastic, PCLX 001, DDD86481, CCI 002, DDD 86481

Zelenirstat (PCLX-001) is an investigational, oral small-molecule drug that inhibits N-myristoyltransferases (NMTs), enzymes crucial for adding fatty acids to proteins, a process vital for cell signaling and membrane attachment. Developed by Pacylex Pharmaceuticals, it’s being tested for various cancers, showing promise in hematologic cancers like AML and lymphomas, as well as solid tumors, by disrupting cancer cell survival and growth, with early trials indicating good safety and potential efficacy. 

How it works:

  • Targets NMT enzymes: Zelenirstat blocks NMT1 and NMT2, preventing myristoylation (adding a fatty acid) to proteins.
  • Disrupts cancer cell processes: This inhibition interferes with essential cell signaling and stability, especially in cancer cells where NMT expression is altered, leading to cell death (apoptosis).
  • Affects mitochondrial function: It also disrupts mitochondrial complex I and oxidative phosphorylation, vital for leukemia stem cell survival, notes Pacylex Pharmaceuticals. 

Development & Status:

  • Orphan Drug Status: Granted for Acute Myeloid Leukemia (AML).
  • Clinical Trials: A Phase 1 trial demonstrated good safety and early signs of activity in patients with advanced solid tumors and lymphomas, leading to further development.
  • New Drug Class: It represents a novel approach to cancer treatment, distinct from many existing therapies. 

Potential Applications:

  • Acute Myeloid Leukemia (AML)
  • B-cell Lymphomas (like Diffuse Large B-Cell Lymphoma)
  • Colorectal Carcinoma
  • Other cancers, including breast, lung, bladder, and pancreatic cancers, show sensitivity in preclinical models. 

Zelenirstat, also known as PCLX-001, is an investigational new drug that is being evaluated for the treatment of cancer and as an antiviral agent. It is a small molecule inhibitor targets both N-myristoyltransferase 1 (NMT1) and N-myristoyltransferase 2 (NMT2) proteins, which are responsible for myristoylation. Its dual mechanism of action disrupts both cell signaling and energy production in cancer cells.

Zelenirstat is a strong pan-N myristoyl transferase inhibitor, which prevents addition of myristic acid into penultimate glycine of protein with myristoylation signal, and initially has been introduced as anti-tumor drug.[1][2][3] It has completed phase I clinical trial and is going through escalation phase.[4] Its prototype DDD85646 as well as other NMT inhibitors such as IMP-1088 have strong antiviral activities against viruses that required myristoylated proteins to complete their life cycle, including hemorrhagic viruses, such as lassa and argentinian virus, and pox viruses, such as vaccinia and monkeypox.[5][6]

Zelenirstat is an orally bioavailable inhibitor of the enzyme N-myristoyl transferase (NMT), with potential antineoplastic activity. Upon oral administration, zelenirstat targets and binds to NMT, especially NMT type 2 (NMT2). This prevents NMT-mediated signaling and myristoylation. This inhibits proliferation of certain cancer cells in which NMT expression is lost. Zelenirstat also inhibits B-cell receptor (BCR) signaling and reduces the levels of Src-family tyrosine kinases (SFKs). NMTs mediate myristoylation, a key process by which the fatty acid myristate is added to proteins and allows proteins to interact with cell membranes and become part of the cell signaling system. NMT expression is lost in numerous cancers, such as blood cancer cells, thereby making these cells more sensitive to zelenirstat compared to normal cells. The loss of NMT expression may promote tumorigenesis.

Mechanism of action

Zelenirstat acts by inhibiting NMT I and II enzymes, which are required to complete the myristoylation of proteins. Without myristoylation, these proteins are targeted for proteasomal degradation.[7]

PCLX-001 is a first-in-kind N-Myristoyltransferase (NMT) inhibitor being developed by [Pacylex Pharmaceuticals](https://pacylex.com). Current studies have shown that PCLX-001 works differently than other known cancer drugs and has high activity and positive results in breast, lung, bladder and pancreas cancers.

  • Study of PCLX-001 in R/R Advanced Solid Malignancies and B-cell LymphomaCTID: NCT04836195Phase: Phase 1Status: CompletedDate: 2025-04-17
  • Study of Oral PCLX-001 in R/R Acute Myeloid LeukemiaCTID: NCT06613217Phase: Phase 1Status: RecruitingDate: 2025-03-10

REF

SYN

US9156811B2

DDD 86481

https://patentscope.wipo.int/search/en/detail.jsf?docId=US73438944&_cid=P12-MJAUPA-00022-1

INTERMEDIATE 23A

4-Bromo-2,6-dichloro-N-(3-isobutyl-1,5-dimethyl-1H-pyrazol-4-yl)-benzenesulfonamide

      Prepared from 4-bromo-2,6-dichlorobenzenesulfonyl chloride (0.68 g, 2.1 mmol) and 4-amino-1,5-dimethyl-3-isobutyl-1H-pyrazole (0.35 g, 2.1 mmol) in pyridine (5 ml) according to the method of intermediate 1, to give the title compound as a white solid (120 mg, 0.26 mmol, 12%). δH (D-6 DMSO, 300K) 7.65 (2H, s), 6.54 (1H, s), 3.70 (3H, s), 2.17 (3H, s), 1.96 (2H, d J 7.9 Hz), 1.74 (1H, m), 0.78 (6H, d J 6.6 Hz). m/z (ES +, 70V) 456.0 (MH +).

EXAMPLE DDD86481

2,6-Dichloro-N-(3-isobutyl-1,5-dimethyl-1H-pyrazol-4-yl)-4-(2-piperazin-1-yl-pyridin-4-yl)-benzenesulfonamide

      Prepared from the sulphonamide of intermediate 23A (115 mg, 0.25 mmol), 2-(1-piperazinyl)pyridine-4-boronic acid pinacol ester (80 mg, 0.28 mmol), tribasic potassium phosphate (60 mg, 0.28 mmol), and Pd(PPh 3) 4 (30 mg, 0.026 mmol) in DMF (1.6 ml) and water (0.4 ml), according to the method of intermediate 11, to give the title compound as a yellow solid (73 mg, 0.14 mmol, 54%). δH (D-6 DMSO, 300K) 8.20, (1H, d J 5.2 Hz), 8.06 (2H, s), 7.15 (1H, s), 7.02 (1H, d J 5.2 Hz), 3.60 (3H, s), 3.52 (4H, m), 2.80 (4H, m), 1.98 (3H, s), 1.92 (2H, d J 7.3 Hz), 1.70 (1H, m), 0.70 (6H, d J 6.6 Hz). m/z (ES +, 70V) 537.2 (MH +).

SYN

WO-2010026365

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2010026365&_cid=P12-MJAUOO-99381-1

PAT

N-myristoyl transferase inhibitors

Publication Number: WO-2010026365-A1

Priority Date: 2008-09-02

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References

  1.  Gamma JM, Liu Q, Beauchamp E, Iyer A, Yap MC, Zak Z, et al. (January 2025). “Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells”. Molecular Cancer Therapeutics. 24 (1): 69–80. doi:10.1158/1535-7163.MCT-24-0307. PMC 11694064. PMID 39382188.
  2.  Sangha R, Jamal R, Spratlin J, Kuruvilla J, Sehn LH, Beauchamp E, et al. (August 2024). “A first-in-human phase I trial of daily oral zelenirstat, a N-myristoyltransferase inhibitor, in patients with advanced solid tumors and relapsed/refractory B-cell lymphomas”. Investigational New Drugs. 42 (4): 386–393. doi:10.1007/s10637-024-01448-w. PMC 11327210. PMID 38837078.
  3.  Sangha RS, Jamal R, Spratlin J, Kuruvilla J, Sehn LH, Weickert M, et al. (June 2024). “Final results of a first-in-human phase I dose escalation trial of daily oral zelenirstat, a n-myristoyltransferase inhibitor, in patients with advanced solid tumors and relapsed/refractory B-cell lymphomas”. Journal of Clinical Oncology. 42 (16_suppl): 3082. doi:10.1200/JCO.2024.42.16_suppl.3082. ISSN 0732-183X.
  4.  Spratlin JL, Sangha RS, Jamal R, Beauchamp E, Berthiaume LG, Mackey JR (20 January 2024). “A first-in-human, open-label, phase I trial of daily oral zelenirstat, an NMT inhibitor, in patients with relapsed/refractory advanced cancer including gastrointestinal cancers”. Journal of Clinical Oncology. 42 (3_suppl): 129–129. doi:10.1200/jco.2024.42.3_suppl.129. Retrieved 19 January 2025.
  5.  Witwit H, Betancourt CA, Cubitt B, Khafaji R, Kowalski H, Jackson N, et al. (August 2024). “Cellular N-Myristoyl Transferases Are Required for Mammarenavirus Multiplication”. Viruses. 16 (9): 1362. doi:10.3390/v16091362. PMC 11436053. PMID 39339839.
  6.  Witwit H, Cubitt B, Khafaji R, Castro EM, Goicoechea M, Lorenzo MM, et al. (January 2025). “Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance”. Viruses. 17 (1): 92. doi:10.3390/v17010092. ISSN 1999-4915. PMC 11769280.
  7.  Witwit H, Betancourt CA, Cubitt B, Khafaji R, Kowalski H, Jackson N, et al. (August 2024). “Cellular N-Myristoyl Transferases Are Required for Mammarenavirus Multiplication”. Viruses. 16 (9): 1362. doi:10.3390/v16091362. PMC 11436053. PMID 39339839.
Clinical data
Other namesPCLX-001
Identifiers
IUPAC name
CAS Number1215011-08-7
PubChem CID58561243
DrugBankDB15567
ChemSpider35034199
UNII5HY8BYC3Q6
ChEMBLChEMBL3357685
Chemical and physical data
FormulaC24H30Cl2N6O2S
Molar mass537.50 g·mol−1
3D model (JSmol)Interactive image
SMILES
InChI

////////zelenirstat, N-myristoyltransferase inhibitor, antineoplastic, PCLX 001, DDD86481, CCI 002, DDD 86481

Zavolosotine

December 17, 2025 2:29 am / Leave a comment


Zavolosotine

CAS 2604416-66-0

MF C20H18F5N5O MW439.38

4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide

4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide

4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)- N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine3-carboxamide
somatostatin receptor agonist, 275EAX4XXX

Zavolosotine (Compound 1) is an orally active agonist for somatostatin receptor type 5 (SST5) with EC50 <1 nM. Zavolosotine inhibits insulin and glucagon secretion, increases levels of glucagon in blood in rat model.

SYN

WO2022177988

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022177988&_cid=P20-MJ9E0I-92373-1

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=US318018214&_cid=P20-MJ9DV5-88499-1

Example 4. 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide (Compound 1-71)

Step 4-1, preparation of tert-butyl (S)-(1-(2-chloro-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate: to a DMF (70 mL) solution was added 4,6-dichloronicotinaldehyde (6.8 g, 1.0 Eq, 39 mmol), tert-butyl (S)-pyrrolidin-3-ylcarbamate (7.6 g, 1.1 Eq, 41 mmol) and TEA (16 mL, 3.1 Eq, 120 mmol). The resulting mixture was stirred at 50° C. for 4 hours. The reaction crude was quenched with water (100 mL) and extracted with ethyl acetate (3×40 mL). The organic layers were combined, washed with brine, dried and concentrated under vacuum. The remaining residue was purified by silica gel chromatography eluting with ethyl acetate/petroleum ether (1/3) to afford tert-butyl (S)-(1-(2-chloro-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate (5.3 g, 42%) as a yellow solid. MS (M+H) +=326.2.
      Step 4-2, preparation of tert-butyl (S)-(1-(3-bromo-2-chloro-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate: to an AcOH (60 mL) solution of tert-butyl (S)-(1-(2-chloro-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate (5.3 g, 1.0 Eq, 16 mmol) was added NBS (3.1 g, 1.1 Eq, 17 mmol) at 10° C. The resulting mixture was stirred at the same temperature for 1 hour. The reaction mixture was quenched with saturated NaHCO 4 and extracted with ethyl acetate (3×40 mL). The organic layers were combined, washed with brine, dried and concentrated under vacuum. The remaining residue was purified by silica gel chromatography eluting with ethyl acetate/petroleum ether (1/4) to afford tert-butyl (S)-(1-(3-bromo-2-chloro-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate (3.5 g, 53%) as a yellow solid. MS (M+H) +=404.1, 406.1.
      Step 4-3, preparation of tert-butyl (S)-(1-(2-chloro-3-(3,5-difluorophenyl)-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate: to a mixture of tert-butyl (S)-(1-(3-bromo-2-chloro-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate (3.5 g, 1.0 Eq, 8.6 mmol), (3,5-difluorophenyl)boronic acid (0.88 Eq, 7.6 mmol, 1.2 g), Pd(DtBPF)Cl 2 (300 mg, 0.05 Eq, 0.46 mmol) and potassium phosphate (5.4 g, 2.9 Eq, 25 mmol) was added Toluene (140 mL) and water (14 mL) under atmospheric nitrogen. The resulting mixture was stirred at 40° C. for 2 hours. The reaction crude was concentrated under reduced pressure and the remaining residue was purified by silica gel column chromatography eluting with petroleum ether/EtOAc (3:1) to afford tert-butyl (S)-(1-(2-chloro-3-(3,5-difluorophenyl)-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate (2.7 g, 71%) as a yellow solid. MS (M+H) +=438.0, 440.0.
      Step 4-4, preparation of tert-butyl (S)-(1-(2-cyano-3-(3,5-difluorophenyl)-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate: to a mixture of tert-butyl (S)-(1-(2-chloro-3-(3,5-difluorophenyl)-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate (2.7 g, 1.0 Eq, 6.2 mmol), Pd 2(dba) 3.CHCl 3 (310 mg, 0.05 Eq, 0.31 mmol), Zn(CN) 2 (1.4 g, 1.9 Eq, 12 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) (720 mg, 0.20 Eq, 1.24 mmol) was added DMF (30 mL) under atmospheric nitrogen. The resulting mixture was heated under microwave radiation conditions at 135° C. for 1 hour. The reaction crude was quenched with water (100 mL) and extracted with EtOAc (3×40 mL). Organic layers were combined, washed with brine, dried over anhydrous Na 2SO 4, filtered and concentrated under vacuum. The remaining residue was purified by silica gel chromatography eluting with petroleum ether/EtOAc (1:1) to afford tert-butyl (S)-(1-(2-cyano-3-(3,5-difluorophenyl)-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate (2.2 g, 83%) as a yellow solid. MS (M+H) +=429.2.
      Step 4-5, preparation of (S)-4-(3-((tert-butoxycarbonyl)amino)pyrrolidin-1-yl)-6-cyano-5-(3,5-difluorophenyl)nicotinic acid: to a tert-butyl alcohol solution (20 mL) of (S)-(1-(2-cyano-3-(3,5-difluorophenyl)-5-formylpyridin-4-yl)pyrrolidin-3-yl)carbamate (2.4 g, 1.0 Eq, 5.1 mmol) was added sodium dihydrogen phosphate (2.4 g, 3.0 Eq, 15 mmol) 2-methylbut-2-ene (11.0 g, 31 Eq, 157 mmol), sodium chlorite (1.0 g, 2.2 Eq, 11 mmol) and water (6.6 mL). The resulting mixture was stirred at ambient temperature for 1 hour. The reaction mixture was quenched with saturated NaHSO 4 (50 mL) and extracted with ethyl acetate (3×40 mL). The organic layers were combined, washed with brine, dried and concentrated under vacuum to afford (S)-4-(3-((tert-butoxycarbonyl)amino)pyrrolidin-1-yl)-6-cyano-5-(3,5-difluorophenyl)nicotinic acid (2.0 g, 88%) as a yellow solid. This material was used for next step without purification. MS (M+H) +=445.2.
      Step 4-6, preparation of tert-butyl ((S)-1-(2-cyano-3-(3,5-difluorophenyl)-5-(((S)-1,1,1-trifluoropropan-2-yl)carbamoyl)pyridin-4-yl)pyrrolidin-3-yl)carbamate: to a DMF solution (2.0 mL) of (S)-4-(3-((tert-butoxycarbonyl)amino)pyrrolidin-1-yl)-6-cyano-5-(3,5-difluorophenyl)nicotinic acid (70 mg, 1.0 Eq, 0.16 mmol) was added (S)-1,1,1-trifluoropropan-2-amine hydrochloride (35 mg, 1.5 Eq, 0.23 mmol), N-ethyl-N-isopropylpropan-2-amine (4.4 Eq, 0.70 mmol, 0.12 mL) and HATU (60 mg, 1.0 Eq, 0.16 mmol). The resulting mixture was stirred at ambient temperature for 2 hours. The reaction crude was purified by Prep-HPLC using the following conditions: SunFire Prep C18 OBD Column, 19*150 mm 5 μm; mobile phase, Water (0.1% FA) and ACN (24.0% ACN up to 46.0% in 7 min); Total flow rate, 20 mL/min; Detector, UV 220 nm. This resulted in tert-butyl ((S)-1-(2-cyano-3-(3,5-difluorophenyl)-5-(((S)-1,1,1-trifluoropropan-2-yl)carbamoyl)pyridin-4-yl)pyrrolidin-3-yl)carbamate (45 mg, 53%) as a light yellow solid. MS (M+H) +=540.3.
      Step 4-7, preparation of 4-((S)-3-aminopyrrolidin-1-yl)-6-cyano-5-(3,5-difluorophenyl)-N—((S)-1,1,1-trifluoropropan-2-yl)nicotinamide: to a DCM solution (2.0 mL) of tert-butyl ((S)-1-(2-cyano-3-(3,5-difluorophenyl)-5-(((S)-1,1,1-trifluoropropan-2-yl)carbamoyl)pyridin-4-yl)pyrrolidin-3-yl)carbamate (45 mg, 1.0 Eq, 0.083 mmol) was added TFA (1.0 mL). The resulting mixture was stirred at ambient temperature for 2 hours. The reaction solution was concentrated and freeze-dried under vacuum to afford the TFA salt of 4-((S)-3-aminopyrrolidin-1-yl)-6-cyano-5-(3,5-difluorophenyl)-N—((S)-1,1,1-trifluoropropan-2-yl)nicotinamide bis(2,2,2-trifluoroacetate) (40.2 mg, 72%) as a light yellow solid. MS (M+H) +=440.2.

PAT

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[1]. FERRARA-COOK C, et al., Somatostatin receptor type 5 agonist for the treatment of hyperinsulinism. WO2022177988 .

///////////zavolosotine, somatostatin receptor agonist, 275EAX4XXX

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