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Glasmacinal
Glasmacinal
CAS 2097822-02-9
MF C37H62N2O10 MW694.90
[(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4,10,13-tetrahydroxy-3,5,6,8,10,12,14-heptamethyl-15-oxo-1-oxa-6-azacyclopentadec-11-yl]oxy]-6-methyloxan-3-yl] benzoate
- (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[[2-O-Benzoyl-3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,6,8,10,12,14-heptamethyl-1-oxa-6-azacyclopentadecan-15-one
- 1-Oxa-6-azacyclopentadecan-15-one, 11-[[2-O-benzoyl-3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyl]oxy]-2-ethyl-3,4,10,13-tetrahydroxy-3,5,6,8,10,12,14-heptamethyl-, (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-
(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-{[2-O-benzoyl-3,4,6-trideoxy-3-(dimethylamino) -β-D-xylo-hexopyranosyl]oxy}-2-ethyl3,4,10,13-tetrahydroxy-3,5,6,8,10,12,14-heptamethyl-1-oxa-6-
azacyclopentadecan-15-one
non-antibacterial macrolide, anti-inflammatory, EP 395, M3T8D3P634
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US234729681&_cid=P12-MKVZ26-57135-1
Example 2: (2S,3R,4S,6R)-4-(dimethylamino)-2-[[(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4,10,13-tetrahydroxy-3,5,6,8,10,12,14-heptamethyl-15-oxo-1-oxa-6-azacyclopentadec-11-yl]oxy]-6-methyl-tetrahydropyran-3-yl] benzoate)
To a mixture of (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-2-ethyl-3,4,10,13-tetrahydroxy-3,5,6,8,10,12,14-heptamethyl-1-oxa-6-azacyclopentadecan-15-one (Example 1) (0.5 g, 0.8500 mmol) and Triethylamine (428.2 mg, 4.23 mmol) in DCM (5 ml), cooled on ice, was added Benzoyl chloride (356.9 mg, 2.54 mmol). The reaction mixture was allowed to reach room temperature. After 3 days good conversion to the desired benzoylated product was obtained and the mixture was portioned between DCM and saturated sodium hydrogen carbonate solution. The organic phase was dried over magnesium sulphate and concentrated to a white foam. The product was purified using reversed phase chromatography (see general information)
PAT
- Azithromycin Derivatives With Epithelial Barrier Enhancement PropertiesPublication Number: US-2018354981-A1Priority Date: 2015-11-19
- Azithromycin derivatives with epithelial barrier enhancement propertiesPublication Number: US-10723752-B2Priority Date: 2015-11-19Grant Date: 2020-07-28
- Azithromycin Derivatives With Epithelial Barrier Enhancement PropertiesPublication Number: US-2020317710-A1Priority Date: 2015-11-19
- Azithromycin derivatives with epithelial barrier enhancement propertiesPublication Number: US-12049477-B2Priority Date: 2015-11-19Grant Date: 2024-07-30
- Azithromycin derivatives with epithelial barrier enhancement propertiesPublication Number: US-11236120-B2Priority Date: 2015-11-19Grant Date: 2022-02-01
- Compounds
- Publication Number: US-2022106349-A1
- Priority Date: 2015-11-19
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Advect Process Systems Ltd. https://advectprocess.com
ADVECT PROCESS SYSTEMS CANADA LTD
51 Beechwood Rd., Cambridge, ON Canada N1S 3S1, Call Now +1 306 850 6737, Mail Now, ask@advectprocess.com
///////glasmacinal, ANAX, ADVECT, non-antibacterial macrolide, anti-inflammatory, EP 395, M3T8D3P634
Frespaciguat
Frespaciguat
CAS 2101645-33-2
MF C27H22ClF5N6O3 MW 608.9 g/mol
3-[4-[(5S)-4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]propanoic acid
3-{4-[(5S)-4-amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)-1H-indazol-3-yl]-5-methyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl}propanoic acid
guanylate cyclase activator, MK5475, MK 5475, sGC activator 1, 6DXN080KGB
Frespaciguat (development code MK-5475) is an experimental inhaled soluble guanylate cyclase stimulator developed by Merck for pulmonary arterial hypertension.[1][2][3][4]
Frespaciguat is a small molecule drug. The usage of the INN stem ‘-ciguat’ in the name indicates that Frespaciguat is a guanylate cyclase activator and stimulator. Frespaciguat is under investigation in clinical trial NCT05612035 (Frespaciguat (MK-5475) INSIGNIA-PH-COPD: A Study of the Efficacy and Safety of Frespaciguat (an Inhaled sGC Stimulator) in Adults With PH-COPD). Frespaciguat has a monoisotopic molecular weight of 608.14 Da.
- Frespaciguat (MK-5475) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD) (MK-5475-006)CTID: NCT04370873Phase: Phase 1Status: CompletedDate: 2025-05-28
- A Study of the Efficacy and Safety of Frespaciguat (MK-5475) in Participants With Pulmonary Arterial Hypertension (INSIGNIA-PAH: Phase 2/3 Study of an Inhaled sGC Stimulator in PAH) (MK-5475-007)CTID: NCT04732221Phase: Phase 2/Phase 3Status: CompletedDate: 2025-05-25
- Frespaciguat (MK-5475) in Participants With Hypoxemia Due to COVID-19 Pneumonia (MK-5475-009)CTID: NCT04425733Phase: Phase 1Status: WithdrawnDate: 2025-05-15
- Frespaciguat (MK-5475) INSIGNIA-PH-COPD: A Study of the Efficacy and Safety of Frespaciguat (an Inhaled sGC Stimulator) in Adults With PH-COPDCTID: NCT05612035Phase: Phase 2Status: Active, not recruitingDate: 2025-10-07
- A Study of Single Doses of Frespaciguat (MK-5475) on Pulmonary Vascular Resistance (MK-5475-002)CTID: NCT03744637Phase: Phase 1Status: CompletedDate: 2025-06-04
SYN
US10030027,
https://patentscope.wipo.int/search/en/detail.jsf?docId=US199416000&_cid=P12-MKUJSJ-89968-1
Example 10B
(S)-3-(4-{4-Amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)-1H-indazol-3-yl]-5-methyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-5-yl}phenyl)propanoic acid
Step A—(S)-Methyl 3-(4-{4-Amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)-1H-indazol-3-yl]-5-methyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-5-yl}phenyl)propanoate
Step B—(S)-3-(4-{4-Amino-2-[6-chloro-1-(3,3,4,4,4-pentafluorobutyl)-1H-indazol-3-yl]-5-methyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-5-yl}phenyl)propanoic acid
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2025006295&_cid=P12-MKUJNS-84717-1
EXAMPLE 2
[0038] To an autoclave was charged anisole (12.78 L), indazole ester (IV) (2.13 kg, 5.64 mol), and hexamethyldisilazane (4.55 kg, 28.2 mol). The mixture was cooled to 0-5 oC and the vessel was placed under slight positive pressure with no N2 sweeping. A solution of H2O (203.21 g, 11.27 mol) in sulfolane (6.39 L) was added while keeping at < 10 oC in order to minimize NH3 gas escaping. The resulting mixture was cooled to -10 oC, then TfOH (1.692 kg, 11.27 mol) was slowly added at < 22 oC. The vessel was sealed and the mixture was heated at 120-130 °C for 24 h. The upper vessel was kept warm so that solid ammonium triflate did not deposit there.
[0039] After cooling the mixture to rt, the batch (biphasic) was further cooled to 0-10 oC.2.4 equiv 1N KOH (13.53 L, 14.207 kg, 13.53 mol) was slowly added at < 25 oC. After agitating for 30 min, and letting settle at rt, the bottom aqueous layer was removed (pH~14). The organic layer was washed with 18% brine (10.5 L). The aqueous layer was removed (pH ~12). To the organic phase was added ¼ (101 mL, 149 g) of 1.1 equiv methanesulfonic acid (402 mL, 595 g, 6.20 mol), then seeded with 0.2 wt% amidine MSA type A (8.5 g). The rest of MSA (447 g, 302 mL) was then slowly added over 1 h. During MSA addition, the temperature was controlled at < 25 oC. The resulting slurry, after aging at 22 oC for 15 h, was filtered, then displacement washed with 2 x 3 vol 2-MeTHF (2 x 6.4 L), and vacuum dried under N2 at < 30 °C for 24 h. The product (III) was obtained (4.62 kg, 10.58 mol, 93 % yield) as an off-white to light beige solid.
PAT
- 4-amino-2-(1h-pyrazolo[3,4-b]pyridin-3-yl)-6-oxo-6,7-dihydro-5h-pyrrolo[2,3-d]pyrimidine derivatives and the respective (1h-indazol-3-yl) derivatives as cgmp modulators for treating cardiovascular diseasesPublication Number: EP-3394067-B1Priority Date: 2015-12-22Grant Date: 2020-04-01
- Soluble guanylate cyclase stimulatorPublication Number: TW-201734017-APriority Date: 2015-12-22
- 4-Amino-2- (1h-pyrazolo [3,4-b] pyridin-3-yl) -6-oxo-6,7-dihydro-5h-pyrrolo [2,3-d] pyrimidine derivatives and respectively (1h- indazol-3-yl) are derived as cgmp activators for the treatment of cardiovascular diseasePublication Number: IL-260020-APriority Date: 2015-12-22
- Soluble guanylate cyclase stimulatorsPublication Number: TW-I724079-BPriority Date: 2015-12-22Grant Date: 2021-04-11
- cGMP modulators for the treatment of cardiovascular diseasePublication Number: CN-108738320-BPriority Date: 2015-12-22Grant Date: 2021-11-19
- 4-Amino-2-(1H-pyrazolo[3,4-b]pyridin-3-yl)-6-oxo-6,7-dihydro- 5H-pyrrolo[2,3-d]pyrimidine derivatives and their respective (1H-indazol-3-yl) derivativesPublication Number: CN-108738320-APriority Date: 2015-12-22
- 4-amino-2-(1H-pyrazolo[3,4-B]pyridin-3-yl)-6-oxo-6,7-dihydro-5H-pyrrolo[ as a cGMP modulator for the treatment of cardiovascular disease 2,3-D]pyridine derivatives and respective (1H-indazol-3-yl) derivativesPublication Number: KR-102191312-B1Priority Date: 2015-12-22Grant Date: 2020-12-15
- Soluble guanylate cyclase stimulatorsPublication Number: US-10030027-B2Priority Date: 2015-12-22Grant Date: 2018-07-24
- 4-Amino-2- (1H-pyrazolo [3,4-b] pyridin-3-yl) -6-oxo-6,7-dihydro-5H-pyrrolo [2,3-d] pyrimidine derivatives and cardiovascular disease (1H-indazol-3-yl) derivatives as cGMP modulators for treatingPublication Number: JP-2018538333-APriority Date: 2015-12-22
- Soluble guanylate cyclase stimulatorsPublication Number: US-2018305366-A1Priority Date: 2015-12-22
- Processes for preparing crystalline soluble guanylate cyclase stimulatorsPublication Number: WO-2025006294-A2Priority Date: 2023-06-26
- Processes for preparing soluble guanylate cyclase stimulatorsPublication Number: WO-2025006295-A1Priority Date: 2023-06-26
- 4-Amino-2- (1H-pyrazolo [3,4-b] pyridin-3-yl) -6-oxo-6,7-dihydro-5H-pyrrolo [2,3-d] pyrimidine derivatives and cardiovascular disease (1H-indazol-3-yl) derivatives as cGMP modulators for treatingPublication Number: JP-6454448-B2Priority Date: 2015-12-22Grant Date: 2019-01-16
- Soluble guanylate cyclase stimulatorsPublication Number: US-10428076-B2Priority Date: 2015-12-22Grant Date: 2019-10-01
- Soluble guanylate cyclase stimulatorsPublication Number: US-2017174693-A1Priority Date: 2015-12-22
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ADVECT PROCESS SYSTEMS CANADA LTD
51 Beechwood Rd., Cambridge, ON Canada N1S 3S1, Call Now +1 306 850 6737, Mail Now, ask@advectprocess.com
| Legal status | |
|---|---|
| Legal status | Investigational |
| Identifiers | |
| IUPAC name | |
| CAS Number | 2101645-33-2 |
| PubChem CID | 129242560 |
| ChemSpider | 129394387 |
| UNII | 6DXN080KGB |
| ChEMBL | ChEMBL5944803 |
| Chemical and physical data | |
| Formula | C27H22ClF5N6O3 |
| Molar mass | 608.95 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
References
- Bajwa, Ednan K.; Cislak, Dawn; Palcza, John; Feng, Hwa-ping; Messina, Eric J.; Reynders, Tom; Denef, Jean-François; Corcea, Vasile; Lai, Eseng; Stoch, S. Aubrey (January 2023). “Effects of an inhaled soluble guanylate cyclase (sGC) stimulator MK-5475 in pulmonary arterial hypertension (PAH)”. Respiratory Medicine. 206 107065. doi:10.1016/j.rmed.2022.107065. PMID 36521262.
- Patel, Mahesh J.; Bajwa, Ednan K.; Cislak, Dawn; Palcza, John; Reynders, Tom; Barthson, Jenny; Lai, Eseng; Stoch, S. Aubrey (9 September 2023). “A randomized study to evaluate the effects of single-dose MK-5475 co-administered with sildenafil on systemic hemodynamics”. European Respiratory Journal PA1208. doi:10.1183/13993003.congress-2023.PA1208.
- El-Kersh, Karim; Jalil, Bilal A. (July 2023). “Pulmonary hypertension inhaled therapies: An updated review”. The American Journal of the Medical Sciences. 366 (1): 3–15. doi:10.1016/j.amjms.2023.03.002. PMID 36921672.
- Tawa, Masashi; Okamura, Tomio (August 2022). “Factors influencing the soluble guanylate cyclase heme redox state in blood vessels”. Vascular Pharmacology. 145 107023. doi:10.1016/j.vph.2022.107023. PMID 35718342.
/////////frespaciguat, ANAX, ADVECT, guanylate cyclase activator, MK5475, MK 5475, sGC activator 1, 6DXN080KGB
Fosrolapitant
Fosrolapitant
CAS 2573694-38-7
MF C27H29F6N2O8P MW654.5 g/mol
phosphonooxymethyl (5S,8S)-8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-2-oxo-8-phenyl-1,9-diazaspiro[4.5]decane-9-carboxylate
(phosphonooxy)methyl (5S,8S)-8-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}methyl)-2-oxo-8-phenyl-1,7-diazaspiro[4.5]decane-7-carboxylate
neurokinin 1 (NK1) receptor antagonist, HR20013, HR 20013, M5QGY92X8B
Fosrolapitant (HR20013) is a novel, intravenous, highly selective neurokinin-1 (NK-1) receptor antagonist used for the prevention of chemotherapy-induced nausea and vomiting (CINV), particularly for cisplatin-based regimens. As a prodrug, it is rapidly converted to rolapitant, offering a long half-life (~180 h). It is often combined with palonosetron and dexamethasone for high efficacy.
Fosrolapitant is a small molecule drug. The usage of the INN stem ‘-pitant’ in the name indicates that Fosrolapitant is a neurokinin NK1 (substance P) receptor antagonist. Fosrolapitant has a monoisotopic molecular weight of 654.16 Da.
Key Aspects of Fosrolapitant:
- Mechanism: Acts as an NK-1 receptor antagonist to prevent nausea/vomiting.
- Administration: Intravenous (IV) formula, often combined as a fixed-dose with palonosetron (HR20013).
- Metabolism: Completely converted to rolapitant in the body, which has a prolonged half-life of approximately 180 hours.
- Clinical Efficacy: In trials (e.g., PROFIT trial), it demonstrated high effectiveness in preventing CINV in patients receiving highly emetogenic chemotherapy.
- Safety Profile: Common adverse events in trials included constipation (22.7%), increased blood pressure (18.2%), abdominal distension (13.6%), and injection site reactions (9.1%).
Fosrolapitant is designed to improve convenience and patient compliance in managing acute and delayed nausea and vomiting associated with cancer treatments.
HR20013 for Nausea and Vomiting Associated With Moderate Emetic Risk Anticancer Agents
CTID: NCT06554184
Phase: Phase 3
Status: Completed
Date: 2025-11-17
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2020259675&_cid=P20-MKT4GS-85082-1
Under N2 protection, compound 3 (1.95 g, 2.543 mmol, 1 eq) dissolved in dichloromethane (40 mL) was added to a 100
mL single-necked flask. Trifluoroacetic acid (1.45 mL, 19.52 mmol, 8 eq) was slowly added under ice water cooling. The mixture was stirred until the reaction was complete, concentrated, and 2.29 g of oil was obtained. After separation and purification, 1.39 g of white foamy solid was obtained, with a yield of 83.5%.
[0129]
1H-NMR(400MHz，CD 3OD):δ(ppm)7.89(s，2H)，7.86(s，1H)，7.41-7.27(m，5H)，5.66(d，J＝12Hz，1H)，5.50-5.47(m，1H)，4.60(d，J＝8Hz，1H)，4.20-3.88(m，3H)，2.51-2.10(m，5H)，1.86-1.66(m，3H)，1.44-1.31(m，4H).
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US380158929&_cid=P20-MKT480-75882-1
Example 1
STEP 1
Compound 1 (2.43 g, 4.86 mmol, 1 eq) was weighed and dissolved in dichloromethane (36 mL) in a 100 mL three-necked flask under N 2 atmosphere. Diisopropylethylamine (5 g, 38.76 mmol, 8 eq) was added and the mixture was cooled to −30° C. Trimethylchlorosilane (1.36 g, 12.52 mmol, 2.6 eq) was added and the mixture was stirred at room temperature for 2 h. The reaction mixture was cooled to −25° C. A solution of chloromethyl chloroformate (0.77 g, 6 mmol, 1.23 eq) in dichloromethane was added dropwise and the mixture was stirred under controlled temperature at −20° C.˜−5° C. until completion of the reaction. The reaction solution was poured into ice water, put to separation, and extracted with dichloromethane. Water and 1 N hydrochloric acid solution were added and put to separation. The organic layer was then successively washed with brine, saturated aqueous solution of sodium bicarbonate and brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 3.0 g yellow jelly with a yield of 104%.
| Compound 3 (1.95 g, 2.543 mmol, 1 eq) was added into a 100 mL single-necked flask and dissolved in dichloromethane (40 mL) under N 2 atmosphere. Trifluoroacetic acid (1.45 mL, 19.52 mmol, 8 eq) was added slowly under ice water cooling. The reaction mixture was stirred until completion of the reaction, and then concentrated to give 2.29 g oil which was then purified purified to give 1.39 g white foamy solid with a yield of 83.5%. |
PAT
- Use of nk1 antagonist prodrug compound in combination with 5-ht3 receptor antagonistPublication Number: US-2024016822-A1Priority Date: 2020-12-25
- Use of nk1 antagonist prodrug compound in combination with 5-ht3 receptor antagonistPublication Number: EP-4268818-A1Priority Date: 2020-12-25
- Neurokinin-1 antagonistPublication Number: EP-3991730-A1Priority Date: 2019-06-28
- Neurokinin-1 antagonistPublication Number: WO-2020259675-A1Priority Date: 2019-06-28
- Neurokinin-1 antagonistsPublication Number: TW-202115064-APriority Date: 2019-06-28
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/////fosrolapitant, neurokinin 1 (NK1) receptor antagonist, HR20013, HR 20013, M5QGY92X8B
Filricianine
Filricianine
CAS 2140857-94-7
MF C45H52N2O12S3, 909.1
3H-Indolium, 3-(3-carboxypropyl)-2-[2-[3-[2-[1,3-dihydro-3,3-dimethyl-1-(3-sulfopropyl)-2H-indol-2-ylidene]ethylidene]-2-(4-sulfophenoxy)-1-cyclohexen-1-yl]ethenyl]-3-methyl-1-(3-sulfopropyl)-, inner salt
3-[(2Z)-3-(3-carboxypropyl)-2-[(2E)-2-[3-[(E)-2-[3,3-dimethyl-1-(3-sulfopropyl)indol-1-ium-2-yl]ethenyl]-2-(4-sulfophenoxy)cyclohex-2-en-1-ylidene]ethylidene]-3-methylindol-1-yl]propane-1-sulfonate
3-[(3RS)-3-(3-carboxypropyl)-2-{(1Ξ)-2-[(3Ξ)-3-{(2Ξ)-2-[3,3-dimethyl-1-(3-sulfopropyl)- 1,3-dihydro-2H-indol-2-ylidene]ethylidene}-2-(4-sulfophenoxy)cyclohex-1-en-1-yl]ethen-1-yl}-3-methyl-3H-indol-1-ium-1-yl]propane-1-sulfonate
diagnostic imaging agent, CI4MD9KLX8
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////////filricianine, diagnostic imaging agent, CI4MD9KLX8
Fanregratinib
Fanregratinib
CAS 1628537-44-9
MF C27H33ClN6O2, 509.0 g/mol
4-chloro-3-[2-[2-[4-[(3S,5R)-3,5-dimethylpiperazin-1-yl]anilino]pyrimidin-5-yl]ethyl]-5-methoxy-N-methylbenzamide
- 4-Chloro-3-(2-(2-((4-((3s,5r)-3,5-dimethylpiperazin-1-yl)phenyl)amino)pyrimidin-5-yl)ethyl)-5-methoxy-N-methylbenzamide
- 4-chloro-3-(2-(2-(4-((3S,5R)-3,5-dimethylpiperazin-1-yl)phenylamino)pyrimidin-5-yl)ethyl)-5-methoxy-N-methylbenzamide
- 4-chloro-3-[2-[2-[4-[(3S,5R)-3,5-dimethylpiperazin-1-yl]anilino]pyrimidin-5-yl]ethyl]-5-methoxy-N-methylbenzamide
- Benzamide, 4-chloro-3-[2-[2-[[4-[(3R,5S)-3,5-dimethyl-1-piperazinyl]phenyl]amino]-5-pyrimidinyl]ethyl]-5-methoxy-N-methyl-, cis-
- Benzamide, 4-chloro-3-[2-[2-[[4-[(3R,5S)-3,5-dimethyl-1-piperazinyl]phenyl]amino]-5-pyrimidinyl]ethyl]-5-methoxy-N-methyl-, rel-
- cis-4-Chloro-3-[2-[2-[[4-[(3R,5S)-3,5-dimethyl-1-piperazinyl]phenyl]amino]-5-pyrimidinyl]ethyl]-5-methoxy-N-methylbenzamide
- rel-4-Chloro-3-[2-[2-[[4-[(3R,5S)-3,5-dimethyl-1-piperazinyl]phenyl]amino]-5-pyrimidinyl]ethyl]-5-methoxy-N-methylbenzamide
fibroblast growth factor receptor tyrosine kinase inhibitor, antineoplastic, 8RWL2B2CLS
- OriginatorHutchison MediPharma
- DeveloperHutchison MediPharma; HUTCHMED
- ClassAntineoplastics; Small molecules
- Mechanism of ActionType 1 fibroblast growth factor receptor antagonists; Type 3 fibroblast growth factor receptor antagonists; Type-2 fibroblast growth factor receptor antagonists
- PreregistrationCholangiocarcinoma
- Phase IIMesothelioma
- Phase I/IISolid tumours
- 29 Dec 2025Preregistration for Cholangiocarcinoma (Late-stage disease, Metastatic disease, Second-line therapy or greater, Inoperable/Unresectable) in China (PO)
- 29 Dec 2025Updated efficacy data from a phase II trial in Cholangiocarcinoma released by HUTCHMED
- 03 Nov 2025HUTCHMED announces intention to submit new drug application to NMPA for Cholangiocarcinoma in first half of 2026
FANREGRATINIB is a small molecule drug with a maximum clinical trial phase of II and has 1 investigational indication.
Fanregratinib is a small molecule drug. The usage of the INN stem ‘-gratinib’ in the name indicates that Fanregratinib is a fibroblast growth factor receptor (FGFR) inhibitor. Fanregratinib has a monoisotopic molecular weight of 508.24 Da.
Fanregratinib is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) types 1, 2, and 3 (FGFR1/2/3), with potential antineoplastic activity. Upon administration, fanregratinib binds to and inhibits FGFR1/2/3, which may result in the inhibition of FGFR1/2/3-related signal transduction pathways. This inhibits proliferation in FGFR1/2/3-overexpressing tumor cells. FGFR, a family of receptor tyrosine kinases (RTKs) upregulated in many tumor cell types, plays a key role in cellular proliferation, migration and survival.
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=US159751913&_cid=P10-MKQ98D-55657-1
Example 9
Synthesis of Compounds 79-91, 146-155
Compound 79
4-chloro-3-(2-(2-((4-((3S,5R)-3,5-dimethylpiperazin-1-yl)phenyl)amino)pyrimidin-5-yl)ethyl)-5-methoxy-N-methylbenzamide
(C) 4-chloro-3-(2-(2-(4-((3S,5R)-3,5-dimethylpiperazin-1-yl)phenylamino)pyrimidin-5-yl)ethyl)-5-methoxy-N-methylbenzamide
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2014139465&_cid=P10-MKQ9F3-62190-1
Example 9: Synthesis of Compounds 78-103
Compound 78
4-chloro-3-(2-(2-((4-((3S,5/f)-3,5-dimethylpiperazin-l-yl)phenyl)amino)pyrimidin-5
-yl)ethyl)-5-methoxy-N-methylbenzamide
(A) Methyl 4-chloro-3-((JE)-2-(2-(4-((3S,5R)-3,5-dimethylpiperazin-l-yl)
phenylamino)pyrimidin-5-yl)vinyl)-5-methoxybenzoate
A mixture of (E)-methyl 4-chloro-3-(2-(2-chloropyrimidin-5-yl)vinyl)-5-methoxy benzoate (150mg, 0.442 mmol), 4-((35′,5i?)-3,5-dimethylpiperazin-l-yl)aniline (109 mg, 0.531 mmol) and TFA (0.1 mL, 1.326 mmol) in propan~2-oi (5 mL) was stirred at 150 °C for 1 h under microwave. The resulting mixture was concentrated, basified with ammonia water, purified via ISCO (DCM/MeOH) to afford the title compound as a
yellow solid (130 mg, 57.9% yield). MS (m/z): 508.2(M+H)+.
(B) 4-chloro-3-((£)-2-(2-(4-((3S,5R)-3,5-dimethylpiperazin-l-yl)phenylamino)pyrim idin-5-yl)vinyl)-5-methoxy-N-methylbenzamide
A mixture of methyl 4-chloro-3-((E)-2-(2-(4-((35′,5i?)-3,5-dimethylpiperazin-l-yl) phenylamino)pyrimidin-5-yl)vinyl)-5-methoxybenzoate (250 mg, 0.492 mmol) and methylamine (6 mL, 35% solution in ethanol) was stirred at 145 °C for 22 min under microwave. The resulting mixture was concentrated, purified via ISCO (DCM/MeOH) to afford the title compound as a yellow solid (145 mg, 58.1%> yield). MS (m/z):
506.9(M+H)+.
(C) 4-chloro-3-(2-(2-(4-((3S,5R)-3,5-dimethylpiperazin-l-yl)phenylamino)pyrimidin -5-yl)ethyl)-5-methoxy-N-methylbenzamide
A mixture of 4-chloro-3-((E)-2-(2-(4-((35*,5i?)-3,5-dimethylpiperazin-l-yl)
phenylamino)pyrimidin-5-yl)vinyl)-5-methoxy-N-methylbenzamide (120 mg, 0.237 mmol), 4-methylbenzenesulfonohydrazide (528 mg, 2.84 mmol) and sodium acetate (233 mg, 2.84 mmol) in THF (6mL) and water (6mL) was stirred overnight at 100 °C under nitrogen atmosphere. The resulting mixture was concentrated. The residue was partitioned between 2N HC1 (15 mL) and EA (15 mL). The aqueous layer was then adjusted to pH=8 with 30% NaOH and extracted with DCM (2* 15 mL). The combined extracts were concentrated and the residue was purified via ISCO (eluted with MeOH in H20 0-100%) to afford the title compound as a yellow solid (50 mg, 41.5% yield). MS (m/z): 509.0(M+H)+. 1H NM (400 MHz, CD3OD) δ 8.1 1 (s, 2H), 7.44 (d, J = 9.1 Hz, 2H), 7.37 (d, J = 2.0 Hz, 1H), 7.30 (d, J = 2.0 Hz, 1H), 6.95 (d, J = 9.1 Hz, 2H), 3.93 (s, 3H), 3.53 – 3.44 (m, 2H), 3.10 – 2.99 (m, 4H), 2.90 (s, 3H), 2.82 (t, J = 7.6 Hz, 2H), 2.25 (t, J = 7.5 Hz, 2H), 1.16 (d, J = 6.4 Hz, 6H).
PAT
- Novel pyrimidine and pyridine compounds and their usagePublication Number: WO-2014139465-A1Priority Date: 2013-03-15
- Novel pyrimidine and pyridine compounds and usage thereofPublication Number: WO-2014139145-A1Priority Date: 2013-03-15
- Pyrimidine and pyridine compounds and their usePublication Number: BR-112015020772-B1Priority Date: 2013-03-15
- Pyrimidine and pyridine compounds and their usagePublication Number: US-9701680-B2Priority Date: 2013-03-15Grant Date: 2017-07-11
- Novel pyrimidine and pyridine compounds and usage thereofPublication Number: US-2016052926-A1Priority Date: 2013-03-15
- Novel pyrimidine and pyridine compounds and their usagePublication Number: EP-2970120-A1Priority Date: 2013-03-15
- Novel pyrimidine and pyridine compounds and their usagePublication Number: EP-2970120-B1Priority Date: 2013-03-15Grant Date: 2018-09-12
- Novel pyrimidine and pyridine compounds and their usagePublication Number: US-2016024021-A1Priority Date: 2013-03-15
- The salts of a compound and the crystalline forms thereofPublication Number: WO-2021073494-A1Priority Date: 2019-10-14
- The salts of a compound and the crystalline forms thereofPublication Number: US-2023121346-A1Priority Date: 2019-10-14
- The salts of a compound and the crystalline forms thereofPublication Number: TW-202128669-APriority Date: 2019-10-14
- Salts of compounds and crystalline forms thereofPublication Number: CN-114555558-APriority Date: 2019-10-14
- SALTS OF THE COMPOUND 4-CHLORO-3-(2-(2-((4-((3S,5R)-3,5-DIMETHYLPIPERAZIN-1-YL)PHENYL)AMINO)PYRIMIDIN-5-YL)ETHYL)-5 -METHOXY-N-METHYLBENZAMIDE AND CRYSTALLINE FORMS THEREOFPublication Number: AR-120202-A1Priority Date: 2019-10-14
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/////////fanregratinib, fibroblast growth factor receptor tyrosine kinase inhibitor, antineoplastic, 8RWL2B2CLS
Evetifator
Evetifator
CAS 2278265-85-1
MF C20H19ClF3N3O4 MW457.8 g/mol
2-(4-chlorophenoxy)-N-[3-[5-[3-(trifluoromethoxy)cyclobutyl]-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentanyl]acetamide
2-(4-chlorophenoxy)-N-(3-{5-[(1s,3s)-3-(trifluoromethoxy)cyclobutyl]-1,3,4-oxadiazol-2-yl}bicyclo [1.1.1]pentan-1-yl)acetamide
eukaryotic translation initiation factor 2B (eIF2B) activator, DNL-343, DNL 343, FYL3Y9D7SK
Evetifator (also known as DNL343) is a potent, selective, and brain-penetrant small molecule activator of eukaryotic initiation factor 2B (eIF2B). As of 2026, it is primarily being investigated for the treatment of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS).
Key Characteristics and Function
- Mechanism of Action: It acts as an eIF2B activator. eIF2B is a critical regulator of protein synthesis; by activating it, the drug aims to address the Integrated Stress Response (ISR) which, when chronically activated, leads to neurodegeneration.
- Pharmacological Profile:
- Potency: It shows an
IC50cap I cap C sub 50𝐼𝐶50 of 3.2 nM in cellular reporter assays.
- Brain Penetration: It is specifically designed to cross the blood-brain barrier to target the central nervous system (CNS).
- Potency: It shows an
- A Study to Evaluate the Bioavailability and Safety of DNL343 in Healthy VolunteersCTID: NCT04581772Phase: Phase 1Status: CompletedDate: 2021-06-11
- A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 in Healthy VolunteersCTID: NCT04268784Phase: Phase 1Status: CompletedDate: 2022-02-07
- HEALEY ALS Platform Trial – Regimen G DNL343CTID: NCT05842941Phase: Phase 2/Phase 3Status: CompletedDate: 2025-02-04
- A Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral SclerosisCTID: NCT05006352Phase: Phase 1Status: CompletedDate: 2024-09-19
- HEALEY ALS Platform Trial – Master ProtocolCTID: NCT04297683Phase: Phase 2/Phase 3Status: Active, not recruitingDate: 2025-12-31
SYN
WO 2019/032743
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2019032743&_cid=P10-MKOU1U-66006-1
EXAMPLE 3
2-(4-chlorophenoxy)-N-[3-[5-[cis-3-(trifluoromethoxy)cyclobutyl]-1,3,4-oxadiazol-2-yl]-1- bicyclo[1.1.1]pentanyl]acetamide
[0257] 2-(4-chlorophenoxy)-N-[1-(hydrazinecarbonyl)-3-bicyclo[1.1.1]pentanyl]acetamide (200 mg, 0.65 mmol), 3-cis-(trifluoromethoxy)cyclobutanecarboxylic acid (131 mg, 0.71 mmol; 8:1 to 10:1 ratio of cis- to trans-) and triethylamine (NEt3) (0.45 mL, 3.23 mmol) were dissolved in EtOAc (2.6 mL) and T3P solution (0.58 mL, 1.94 mmol, 50 % in EtOAc) was added. The resulting reaction mixture was heated to 100 °C overnight, cooled to rt and was diluted with sat. aq. NaHCO3 solution (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3 × 10 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude reaction mixture was purified employing reverse-phase prep-HPLC to deliver the desired product as a clear oil. 1H-NMR (400 MHz; CDCl3): δ 7.33-7.29 (m, 2H), 7.03 (s, 1H), 6.91-6.87 (m, 2H), 4.76-4.69 (m, 1H), 4.44 (s, 2H), 3.39-3.30 (m, 1H), 2.92-2.84 (m, 2H), 2.74-2.68 (m, 2H), 2.67 (s, 6H). LC-MS m/z: = 458.20 [M+H]+.
[0258] Alternatively, a mixture of 2-(4-chlorophenoxy)acetic acid (50 mg, 0.27 mmol), 2-(4-chlorophenoxy)acetic acid (50 mg, 0.27 mmol), NEt3 (123 mg, 1.21 mmol) and T3P (185 mg, 0.29 mmol, 50% purity) in DCM (1 mL) was stirred at 0 °C for 1 h. To the mixture was added 1-[5-[3-cis-(trifluoromethoxy)cyclobutyl]-1,3,4-oxadiazol-2-yl]bicyclo[1.1.1]pentan-3-amine HCl salt (8:1 to 10:1 favoring the cis- diastereomer) (70 mg, 0.24 mmol) at 0 °C. The mixture was stirred at 25 °C for 12 h. To the reaction was added sat. aq. NaHCO3 (4 mL). The aqueous phase was extracted with DCM (5 mL, 3 mL). The combined organic phase was washed with brine (10 mL), dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide the title compound.
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022133236&_cid=P10-MKOTTO-58939-1
2-(4-chlorophenoxy)-N-[3-[5-[cA-3-(trifluoromethoxy)cyclobutyl]-l,3,4-oxadiazol-2-yl]-l-bicyclo[l.l.l]pentanyl]acetamide, designated herein as Compound I, has the following formula:
Example 1. Synthesis of Compound I
2-(4-chlorophenoxy)-/V-[l-(hydrazinecarbonyl)-3-bicyclo[l.l.l]pentanyl]acetamide
[0131] To a suspension of methyl 3-[[2-(4-chlorophenoxy)acetyl]amino]bicyclo[l.l.l]pentane-l-carboxylate (270 mg, 0.87 mmol) in EtOH (0.25-0.1M) was added hydrazine hydrate (131 mg, 2.6 mmol) in EtOH (3.5 mL) and the reaction mixture was heated at 90 °C overnight. The reaction mixture
was cooled to rt often causing the product to crystallize out of solution. This solid was collected by removal of the supernatant. If the product did not crystallize, the solution was concentrated, and the crude product was sufficiently pure to use in subsequent steps.
LC-MS m/z: = 310.1 [M+H]+.
2-(4-chlorophenoxy)-N-[3-[5-[cis-3-(trifluoromethoxy)cyclobutyl]-1,3,4-oxadiazol-2-yl]-1-bicyclo[1.1.1]pentanyl]acetamide
[0132] 2-(4-chlorophenoxy)-N-[1-(hydrazinecarbonyl)-3-bicyclo[1.1.1]pentanyl]acetamide (200 mg, 0.65 mmol), 3-cis-(trifluoromethoxy)cyclobutanecarboxylic acid (131 mg, 0.71 mmol; 8:1 to 10:1 ratio of cis- to trans-) and triethylamine (NEt3) (0.45 mL, 3.23 mmol) were dissolved in EtOAc (2.6 mL) and T3P solution (0.58 mL, 1.94 mmol, 50 % in EtOAc) was added. The resulting reaction mixture was heated to 100 ºC overnight, cooled to rt and was diluted with sat. aq. NaHCO3 solution (10 mL) and EtOAc (10 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (3 x 10 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude reaction mixture was purified employing reverse-phase prep-HPLC to deliver the desired product as a clear oil.1H-NMR (400 MHz; CDCl3): δ 7.33-7.29 (m, 2H), 7.03 (s, 1H), 6.91-6.87 (m, 2H), 4.76-4.69 (m, 1H), 4.44 (s, 2H), 3.39-3.30 (m, 1H), 2.92-2.84 (m, 2H), 2.74-2.68 (m, 2H), 2.67 (s, 6H). LC-MS m/z: = 458.20 [M+H]+.
[0133] Alternatively, a mixture of 2-(4-chlorophenoxy)acetic acid (50 mg, 0.27 mmol), NEt3 (123 mg, 1.21 mmol) and T3P (185 mg, 0.29 mmol, 50% purity) in DCM (1 mL) was stirred at 0 °C for 1 h. To the mixture was added 1-[5-[3-cis-(trifluoromethoxy)cyclobutyl]-1,3,4-oxadiazol-2-yl]bicyclo[1.1.1]pentan-3-amine HCl salt (8:1 to 10:1 favoring the cis- diastereomer) (70 mg, 0.24 mmol) at 0 °C. The mixture was stirred at 25 °C for 12 h. To the reaction was added sat. aq. NaHCO3 (4 mL). The aqueous phase was extracted with DCM (5 mL, 3 mL). The combined organic phase was washed with brine (10 mL), dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide the title compound.
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023250107&_cid=P10-MKOTXL-62392-1
Example 14: Preparation of 2-(4-chlorophenoxy)-N-(3-(5-((ls,3s)-3-(trifluoromethoxy)cyclobutyl)- l,3,4-oxadiazol-2-yl)bicyclo[l.l.l]pentan-l-yl)acetamide (I)
[0377] XI- la, 2-(4-chlorophenoxy)acetic acid (XII- la), and 2-MeTHF were charged to a reactor under N2 condition and cooled to 0 ~ 5 °C. TEA was added while maintaining an internal temperature of not more than about 10 °C under N2 condition and rinsed with 2-methyltetrahydrafuran (2-MeTHF). The contents were agitated at about 0 ~ 5 °C for not less than about 20 minutes. Diphenylphosphinic chloride in 2-MeTHF solution is added slowly while maintaining an internal temperature of not more than about 10 °C under N2 condition and rinsed with 2-MeTHF. The contents were warmed to about 20 ~ 25 °C and then agitated for not less than about 1 hour until the reaction was completed. The contents were cooled to about 0 ~ 5 °C and then aqueous 10% K2CO3 was added while maintaining an internal temperature of not more than about 10 °C. After phase separation, the organic layer was successively washed with aqueous 10% K2CO3 and 5% K2CO3. The organic layer was concentrated to a target volume 3 V. 2-MeTHF was added and then the contents were concentrated to a target volume 3 V to control the water content to not more than about 0.3 w/w%. IPA was added and then the contents were heated to about 60 ~ 70 °C to
dissolve all solids. The contents were filtered at about 60 ~ 70 °C through cartridge filter and rinsed with pre-heated IPA (60 ~ 70 °C). The filtrate was concentrated to a target volume 4 V. IPA was added and concentrated to a target volume 4 V to control the residual 2-MeTHF relative to IPA to not more than 1 % by GC. The contents were adjusted to about 20 ~25 °C. n-Heptane was added and then heated to about 60 ~ 80 °C to dissolve all solids. The contents were adjusted to about 62 ~ 70 °C. Seed crystal was charged and agitated for not less than about 0.5 hour. n-Heptane was added while maintaining an internal temperature of about 60 ~ 65 °C. The contents were cooled to about 0 ~ 5 °C over 12 hour (5 °C per hour). The slurry was agitated for not less than 2 hours. The slurry was filtered and washed with precooled IPA/n-heptane mixture. The wet cake was dried at 25 °C under vacuum. If any individual impurity except 2-(4-chlorophenoxy)-N-(3-(5-(trans-3-(trifluoromethoxy)cyclobutyl)-l,3,4-oxadiazol-2-yl)bicyclo[l.l.l]pentan-l-yl)acetamide was more than 0.12%, recrystallization was performed.
[0378] ’H NMR (600 MHz, MeCN-d3): 7.65 (s, 1H), 7.3
PAT
- Compounds, compositions and methodsPublication Number: JP-2023052166-APriority Date: 2017-08-09
- Compounds, compositions, and methodsPublication Number: CN-111094233-BPriority Date: 2017-08-09Grant Date: 2024-03-15
- Modulators of eukaryotic initiation factor 2B, compositions and methodsPublication Number: US-11236100-B2Priority Date: 2017-08-09Grant Date: 2022-02-01
- Compounds, compositions, and methodsPublication Number: CN-118239938-APriority Date: 2017-08-09
- Solid forms of a compoundPublication Number: US-2024059662-A1Priority Date: 2020-12-18
- Modulators of eukaryotic initiation factor 2B, compositions and methodsPublication Number: US-2022411433-A1Priority Date: 2017-08-09
- COMPOUNDS, COMPOSITIONS AND METHODSPublication Number: WO-2019032743-A1Priority Date: 2017-08-09
- Modulators of eukaryotic initiation factor 2B, compositions and methodsPublication Number: US-11851440-B2Priority Date: 2017-08-09Grant Date: 2023-12-26
- Compounds, compositions and methodsPublication Number: US-2021147435-A1Priority Date: 2017-08-09
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//////evetifator, ANAX, eukaryotic translation initiation factor 2B (eIF2B) activator, DNL-343, DNL 343, FYL3Y9D7SK
Evategrel
Evategrel
CAS 2760609-74-1
MF C21H26ClNO7S MW 472.0 g/mol
(2Z)-2-[(4R)-1-[(1S)-1-(2-chlorophenyl)-2-methoxy-2-oxoethyl]-4-(propan-2-yloxycarbonyloxymethylsulfanyl)piperidin-3-ylidene]acetic acid
(Z)-[(4R)-1-[(1S)-1-(2-chlorophenyl)-2-methoxy-2-oxoethyl]-4-{[({[(propan-2-yl)oxy]carbonyl}oxy)methyl]sulfanyl}piperidin-3-ylidene]acetic acid
platelet aggregation inhibitor, CG-0255, CG 0255, 9FKJ76ZX22
Evategrel (CG-0255) is a promising new antiplatelet drug, a thioether prodrug, designed to improve upon clopidogrel (Plavix) by offering faster action, consistent potency, and overcoming resistance, with both oral and intravenous (IV) formulations available for emergency use. It works by rapidly converting to the same active metabolite as clopidogrel (H4) through simple hydrolysis, bypassing the CYP enzymes that can cause variability and resistance with clopidogrel. Clinical trials show it’s well-tolerated, potent, and has potential to become a superior P2Y12 inhibitor for preventing blood clots in cardiovascular conditions.
Key Features
- Fast & Potent: Achieves significant platelet inhibition (IPA) within 15-30 minutes.
- Consistent Activation: Relies on liver carboxylesterases, avoiding CYP2C19 variability, leading to less individual response difference.
- Dual Formulation: First P2Y12 inhibitor with both IV (for emergencies/surgery) and oral forms.
- Overcomes Resistance: Specifically designed to address clopidogrel resistance issues.
- Low Drug-Drug Interactions: Expected to have minimal interactions.
How it Works
- Prodrug: Evategrel is inactive when administered.
- Hydrolysis: Liver esterase enzymes quickly break it down (hydrolyze it) in a single step.
- Active Metabolite: This process creates H4, the same active antiplatelet molecule as clopidogrel’s active form.
- Platelet Inhibition: H4 blocks the P2Y12 receptor on platelets, preventing them from clumping (aggregating).
Development & Potential
- Developed by China-based CureGene.
- Shows promise as a “best-in-class” P2Y12 antagonist, potentially benefiting patients with acute coronary syndromes (ACS) or those undergoing PCI (percutaneous coronary intervention).
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023144782&_cid=P10-MKNELX-27983-1
Synthesis Example 1
Steps 11 and 12. Synthesize la-1 and la-2
The solution of 1–13 (1.8 g, 3.4 mmol) in TFA (10 mL) was stirred at room temperature for 30 minutes. After stirring, the reaction mixture was added to a saturated NaHCO3 solution (100 mL), followed by collection with EtOAc (100 mL * 3). The combined organic layers were washed with saturated NaHCO3 , dried over Na2SO4 , and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by reversed-phase column chromatography (C18, CH3CN / H2O = 80/20 ) to give la (550 mg, 34% yield). la was further purified by chiral column chromatography to give la-1 and la-2.
the:
LC-MS [M+l]+ = 472.1
57.59 (s, 1H), 7.38 (d, J = 4 Hz, 1H), 7.32-7.26 (m, 2H), 5.86 (s, 1H), 5.22 (dd, 12.2, 2.6 Hz, 1H), 5.00-4.83 (m, 3H), 4.50 (dd, J = 66.2, 11.9 Hz, 1H), 3.82 (s, 1H), 3.70 (d, J = 4.9 Hz, 3H), 3.52 (dd, J = 37.9, 12.9 Hz, 1H), 2.92-2.64 (m, 2H), 2.45-2.30 (m, 1 H), 1.95-1.84 (m, 1H), 1.30 ( 6.2 Hz, 6H)O
la-1：
NMR (400 MHz, CDC13) 6 7.65 (s, 1H), 7.46 – 7.43 (m, 1H), 7.33 (dd, J = 6.3, 2.7 Hz, 2H), 5.91 (s, 1H), 5.27 (d, J = 12.3 Hz, 1H), 5.04 – 4.87 (m, 3H), 4.49 (d, J = 13.7 Hz, 1H), 3.88 (s, 1H), 3.75 (s, 3H), 3.58 (d, J = 14.0 Hz, 1H), 2.87 (s, 2H), 2.44 (s, 1H), 1.95 (dd, J = 14.2, 3.3 Hz, 1H), 1.35 (d, J = 6.2 Hz, 6H)O
la-2:
NMR (400 MHz, CDCh) 5 7.63 (s, 1H), 7.44 (dt, J = 8.2, 3.1 Hz, 1H), 7.35 – 7.31 (m,
2H), 5.92 (s, 1H), 5.25 (d, J = 12.3 Hz, 1H), 5.07 (s, 1H), 4.94 (td, J = 12.5, 6.5 Hz, 2H), 4.68 (d, J = 13.4 Hz, 1H), 3.87 (s, 1H), 3.76 (s, 3H), 3.50 (d, J = 13.4 Hz, 1H), 2.90 (s, 1H), 2.75 (d, J = 12.3 Hz, 1H), 2.44 (s, 1H), 1.96 (d, 7 = 13.2 Hz, 1H), 1.34 (d, J = 6.3 Hz, 6H) =
PAT
- Pharmaceutical composition of antiplatelet drug, and use thereofPublication Number: WO-2023144782-A1Priority Date: 2022-01-28
- Antiplatelet drugs and uses thereofPublication Number: US-2023295089-A1Priority Date: 2020-07-29
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/////////evategrel, platelet aggregation inhibitor, CG-0255, CG 0255, 9FKJ76ZX22
Enrupatinib
Enrupatinib
CAS 2222689-47-4
MF C27H26N6O3 MW 482.5 g/mol
6-[3-methoxy-4-[(6-methyl-3-pyridinyl)methoxy]anilino]-3-morpholin-4-ylquinoxaline-5-carbonitrile
colony-stimulating factor 1 receptor (CSF1R) inhibitor, antineoplastic, EI 1071, EI-1071, 9L35RVQ9J6
ENRUPATINIB is a small molecule drug with a maximum clinical trial phase of II and has 1 investigational indication.
EI-1071 is a selective Colony Stimulating Factor-1 Receptor kinase inhibitor.
- A Study to Evaluate the Safety, Tolerability and Amount of EI-1071 in Blood in Healthy VolunteersCTID: NCT04238364Phase: Phase 1Status: CompletedDate: 2025-02-25
- A Phase 2 Study to Assess the Safety of EI-1071 and the Effects of EI-1071 on Neuroinflammation in Alzheimer’s Disease PatientsCTID: NCT06745583Phase: Phase 2Status: RecruitingDate: 2025-07-28
- OriginatorElixiron Immunotherapeutics
- Developer4B Technologies; Elixiron Immunotherapeutics
- ClassAntidementias; Antineoplastics; Small molecules
- Mechanism of ActionMacrophage colony-stimulating factor receptor antagonists
- Phase IIAlzheimer’s disease
- Phase IAmyotrophic lateral sclerosis; Giant cell tumour of tendon sheath
- No development reportedBreast cancer; Colorectal cancer
- 27 Jul 2025Pharmacodynamics data from preclinical studies in Alzheimer’s disease presented at the Alzheimer’s Association International Conference 2025 (AAIC-2025)
- 20 Dec 2024Phase-II clinical trials in Alzheimer’s disease (Treatment-experienced) in Taiwan (PO) (NCT06745583)
- 28 Jul 2024Adverse event data from a phase I trial in Alzheimer’s disease presented at the Alzheimer’s Association International Conference 2024 (AAIC-2024)
SYN
PAT
PAT
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2018071348&_cid=P12-MKLZ1L-03304-1
PAT
- Solid dispersion, pharmaceutical composition, and preparation method and use thereforPublication Number: WO-2025067450-A1Priority Date: 2023-09-28
- Method of enhanced absorption of quinoxaline type iii receptor tyrosine kinase inhibitorsPublication Number: WO-2025019622-A2Priority Date: 2023-07-18
- Quinoxaline compounds as type iii receptor tyrosine kinase inhibitorsPublication Number: US-2019308949-A1Priority Date: 2016-10-10
- Quinoxaline Compounds as Type III Receptor Tyrosine Kinase InhibitorsPublication Number: CN-110325515-APriority Date: 2016-10-10
- Quinoxaline compounds as type III receptor tyrosine kinase inhibitorsPublication Number: JP-7206188-B2Priority Date: 2016-10-10Grant Date: 2023-01-17
- quinoxaline compounds as type III tyrosine kinase receptor inhibitorsPublication Number: BR-112019007271-A2Priority Date: 2016-10-10
- Quinoxaline compounds as type III receptor tyrosine kinase inhibitorsPublication Number: AU-2017342928-A1Priority Date: 2016-10-10
- QUINOXALINE COMPOUNDS AS TYPE III RECEPTOR TYROSINKINASE INHIBITORSPublication Number: RU-2019113764-APriority Date: 2016-10-10
- Quinoxaline compounds as type iii receptor tyrosine receptor inhibitorsPublication Number: IL-265829-APriority Date: 2016-10-10
- Quinoxaline compounds as type iii receptor tyrosine kinase inhibitorsPublication Number: CA-3039919-A1Priority Date: 2016-10-10
- Quinoxaline compounds as type iii receptor tyrosine kinase inhibitorsPublication Number: WO-2018071348-A1Priority Date: 2016-10-10
- Quinoxaline compounds as inhibitors of type III receptor tyrosine kinasePublication Number: CN-110325515-BPriority Date: 2016-10-10Grant Date: 2023-06-20
- Quinoxaline compounds as type III receptor tyrosine kinase inhibitorsPublication Number: US-10689362-B2Priority Date: 2016-10-10Grant Date: 2020-06-23
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////////enrupatinib, ANAX, colony-stimulating factor 1 receptor (CSF1R) inhibitor, antineoplastic, EI 1071, EI-1071, 9L35RVQ9J6
Emestedastat
Emestedastat
CAS 1346013-80-6
MF C19H19N5O2S MW381.5 g/mol
[(1R,3r,5S)-3-hydroxy-3-(pyrimidin-2-yl)-8-azabicyclo[3.2.1]octan-8-yl][5-(1H-pyrazol-4-yl)thiophen-3-yl]methanone
11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor, UE-2343, UE 2343, 106ELK29GH
Emestedastat (proposed brand name Xanamem; developmental code name UE-2343) is a steroidogenesis inhibitor which is under development for the treatment of major depressive disorder, Alzheimer’s disease, and fragile X syndrome.[1][2] It specifically acts as a centrally penetrant inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and thereby inhibits the synthesis of the glucocorticoid steroid hormone cortisol.[1][3][4][2] As of August 2024, emestedastat is in phase 2 clinical trials for major depressive disorder and Alzheimer’s disease and is in the preclinical stage of development for fragile X syndrome.[1][2] Clinical effectiveness for Alzheimer’s disease has been mixed.[2] It was originated by the University of Edinburgh and is being developed by Actinogen Medical.[1]
- Phase I MAD, Fed-Fasted, CSF Study of UE2343 in Healthy SubjectsCTID: NCT02616445Phase: Phase 1Status: CompletedDate: 2025-01-22
- Effect of 10 mg Xanamem on Dementia Due to Alzheimer’s DiseaseCTID: NCT06125951Phase: Phase 2Status: Active, not recruitingDate: 2025-12-02
- A Phase I Study of Oral UE2343 in Healthy SubjectsCTID: NCT01770886Phase: Phase 1Status: CompletedDate: 2013-07-17
- Xanamem™ in Healthy Elderly SubjectsCTID: NCT03830762Phase: Phase 1Status: CompletedDate: 2025-01-22
- OriginatorUniversity of Edinburgh
- DeveloperActinogen Medical
- ClassAntidementias; Azabicyclo compounds; Ketones; Pyrazoles; Pyrimidines; Small molecules; Thiophenes
- Mechanism of Action11-beta-hydroxysteroid dehydrogenase type 1 inhibitors
- Phase II/IIIAlzheimer’s disease
- Phase IIMajor depressive disorder
- No development reportedFragile X syndrome
- 15 Sep 2025Meeting similar to that of Type C will be held for Alzheimer’s disease (AD) with European Medicines Agency and subsequently with the UK MHRA and other regulators in 2026
- 27 Aug 2025Pharmacokinetics data from a phase I pharmacokinetics trial in volunteers released by Actinogen
- 28 Jul 2025No recent reports of development identified for preclinical development in Fragile-X-syndrome in Australia (PO)
Syn
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022094668&_cid=P20-MKKJLN-11715-1
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021062472&_cid=P20-MKKJLN-11715-1
PAT
- medical cognitive therapyPublication Number: CN-114761005-APriority Date: 2019-09-30
- Medicinal cognitive treatmentsPublication Number: CA-3152902-A1Priority Date: 2019-09-30
- Therapeutic editingPublication Number: AU-2020395113-A1Priority Date: 2019-12-02
- Medicinal cognitive treatmentsPublication Number: EP-4037684-A1Priority Date: 2019-09-30
- Medicinal cognitive treatmentsPublication Number: US-2023000843-A1Priority Date: 2019-09-30
- Medicinal cognitive treatmentsPublication Number: WO-2021062472-A1Priority Date: 2019-09-30
- Cognitive pharmacological treatmentPublication Number: JP-2022550221-APriority Date: 2019-09-30
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References
- “UE 2343”. AdisInsight. 28 August 2024. Retrieved 9 October 2024.
- Seckl J (January 2024). “11β-Hydroxysteroid dehydrogenase and the brain: Not (yet) lost in translation”. Journal of Internal Medicine. 295 (1): 20–37. doi:10.1111/joim.13741. PMID 37941106.
- Bachurin SO, Gavrilova SI, Samsonova A, Barreto GE, Aliev G (March 2018). “Mild cognitive impairment due to Alzheimer disease: Contemporary approaches to diagnostics and pharmacological intervention”. Pharmacological Research. 129: 216–226. doi:10.1016/j.phrs.2017.11.021. PMID 29170097.
- Canet G, Hernandez C, Zussy C, Chevallier N, Desrumaux C, Givalois L (2019). “Is AD a Stress-Related Disorder? Focus on the HPA Axis and Its Promising Therapeutic Targets”. Frontiers in Aging Neuroscience. 11 269. doi:10.3389/fnagi.2019.00269. PMC 6776918. PMID 31611783.
///////////emestedastat, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor, UE-2343, UE 2343, 106ELK29GH
Direclidine
Direclidine
CAS 1803346-98-6
MF C19H30N4O2 MW346.5 g/mol
ethyl 2-[4-(2-methylpyrazol-3-yl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate
ethyl (2r,4s)-2-[4-(1-methyl-1H-pyrazol-5-yl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate
muscarinic M4 receptor positive allosteric modulator, TXB4V44U24, NBI-1117568, NBI 1117568
Direclidine (INNTooltip International Nonproprietary Name;[2] developmental code names NBI-1117568, HTL-0016878)[1] is an investigational antipsychotic drug for schizophrenia[3] that was out-licensed from Nxera Pharma to Neurocrine Biosciences, a United States-based pharmaceutical company.[4][1][5] It is an oral small molecule.[6][7]
Direclidine (NBI-1117568) is an investigational, oral drug in Phase 3 trials for schizophrenia, developed by Neurocrine Biosciences, working as a selective M4 muscarinic receptor agonist to treat psychosis by modulating dopamine indirectly. It’s an innovative small molecule with potential for neuropsychiatric disorders, showing promise in early trials and aiming to offer a new treatment approach beyond traditional antipsychotics.
Key aspects of Direclidine:
- Drug Class: Small molecule, muscarinic M4 receptor agonist, antipsychotic.
- Mechanism: Acts as a selective agonist for the M4 receptor, which indirectly helps improve dopamine levels, targeting schizophrenia symptoms.
- Developer: Originally from Nxera Pharma, licensed to Neurocrine Biosciences.
- Status: In Phase 3 clinical trials for schizophrenia.
- Significance: Offers a novel mechanism for treating schizophrenia, potentially with fewer side effects than current treatments.
- Other Uses: Also being explored for bipolar mania and other neuropsychiatric conditions.
Development Timeline & Data:
- Positive Phase 2 data was announced in August 2024, showing promise for its use in schizophrenia.
- Topline data from ongoing Phase 3 studies is expected around 2027.
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2015118342&_cid=P20-MKJ4D7-04370-1
Typical procedure for the preparation of piperidines via sodium triacetoxyborohydride reductive amination, Boc-deprotection and ethylcarbamate formation as exemplified by the preparation of Example 1 -7, ethyl 2-[4-(1 -methyl-1 H-imidazol-2-yl)piperidin-1 -yl]-6-aza s p i ro [3.4] octa n e -6 -ca rb oxy late
Example 1-7
4-(1 -Methylimidazol-2-yl)piperidine hydrochloride (0.244 g, 1 .21 mmol) and 6-Boc-2-oxo-6-azaspiro[3,4]octane (0.273 g, 1 .21 mmol) were dissolved in DCM (10 mL) at rt and titanium isopropoxide (0.4 mL, 2.42 mmol) was added. The reaction mixture was stirred at rt for 1 h. The reaction mixture was cooled to -5 °C, then STAB (0.513 g, 2.42 mmol) and acetic acid (27 pL, 480 pmol) were added and the reaction mixture was stirred overnight under nitrogen while warming to rt. The reaction mixture was quenched with the addition of NaHC03 (sat aq.) (10 mL) and diluted with DCM then filtered through a pad of celite. The layers were separated and the aqueous layer was extracted with DCM. The combined DCM layers were washed with brine, then dried over MgS04. The solvents were removed in vacuo, and the residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25g , 40-63 μΠΊ, 60 A, 50 mL per min, gradient 1 % to 10% MeOH in DCM]) to give an inseparable mixture of isomers of terf-butyl 2-[4-(1 -methyl-1 H-imidazol-2-yl)piperidine]-6-azaspiro[3.4]octane-6-carboxylate (0.330 g, 72%) as a yellow gum.
LCMS (Method A): m/z 374 (M+H)+ (ES*), at 1.68 min, UV inactive.
Terf-butyl 2-[4-(1-methyl-1 H-imidazol-2-yl)piperidine]-6-azaspiro[3.4]octane-6-carboxylate (0.326 g, 0.87 mmol) was dissolved in 4 M hydrogen chloride in dioxane (1 .2 mL, 5.2 mmol). The reaction mixture was stirred at rt for 18 h. The volatiles were then removed in vacuo and the residue dissolved DCM (17 mL) and triethylamine (0.49 mL, 3.49 mmol). Ethyl chloroformate (125 μί, 1.31 mmol) was added dropwise and the solution stirred at rt for 18 h. The mixture was then poured into NaHC03 (aq) (75 mL) and DCM (75 mL), extracted (2 x 75 mL) , and the combined DCM extracts washed with brine (20 mL) then dried over MgSO*. After concentration, the residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μΐη, 60 A, 50 mL per min, gradient 1 % to 10% MeOH in DCM]) to provide ethyl 2-[4-(1 -methyl-1 H-imidazol-2-yl)piperidine]-6-azaspiro[3.4]octane-6-carboxylate as a brown oil as a mixture of diastereomers (0.25 g, 83%). Preparative HPLC was used to separate the diastereomers, using a Phenomenex Gemini-N C18 column, 150 x 21 mm, eluting with 38 to 48% MeCN/H20 at 18 mL/min and collecting fractions by monitoring at 218 nm to give ethyl 2-[4-(1 -methyl-1 H-imidazol-2-yl)piperidine]-6-azaspiro[3.4]octane-6-carboxylate, Example 1-7 Isomer 1 , (0.044 g, 15%) as a colourless oil and ethyl 2-[4-(1 -methyl-1 /-/-imidazol-2-yl)piperidine]-6-azaspiro[3.4]octane-6-carboxylate, Example 1 -7 Isomer 2, (0.031 g, 10%) as a colourless oil. The data for Isomer 2 are in Table 3
PAT
- Pharmaceutical compoundsPublication Number: EP-4413985-A2Priority Date: 2014-02-06
- BICYCLIC AZA COMPOUNDS AS MUSCARINIC RECEPTOR AGONISTSPublication Number: FI-3406609-T3Priority Date: 2014-02-06Grant Date: 2024-09-10
- Bicyclic aza compounds as muscarinic receptor agonistsPublication Number: EP-3406609-B1Priority Date: 2014-02-06Grant Date: 2024-06-26
- Bicyclic aza compounds as muscarinic m1 receptor agonists.Publication Number: WO-2015118342-A1Priority Date: 2014-02-06
- Bicyclic aza compounds as muscarinic m1 receptor and/or m4 receptor agonistsPublication Number: US-2018179184-A1Priority Date: 2014-02-06
- Bicyclic aza compounds as muscarinic m1 receptor and/or m4 receptor agonistsPublication Number: US-2017240530-A1Priority Date: 2014-02-06
- Bicyclic aza compounds as muscarinic m1 receptor and/or m4 receptorPublication Number: US-2020325118-A1Priority Date: 2014-02-06
- Bicyclic aza compounds as muscarinic receptor agonistsPublication Number: ES-2986327-T3Priority Date: 2014-02-06Grant Date: 2024-11-11
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Overview
It is a selective muscarinic acetylcholine M4 receptor agonist that indirectly modulates dopamine as the basis for its putative improvement of schizophrenia.[6] In April 2016, the compound was out-licensed from Nxera Pharma to Allergan, an Irish pharmaceutical company, as part of Nxera’s wider muscarinic agonist portfokio. By September 2017, it had advanced to Phase I clinical trial for the indication of “neuropsychiatric symptoms associated with Alzheimer’s disease and other dementias”[8] Following Allergan’s acquisition by AbbVie, the license was returned to Nxera in January 2021.[9] In November 2021, the compound was newly out-licensed to Neurocrine Biosciences, a U.S. pharmaceutical company.[5] It has been under development as a treatment for schizophrenia, and is currently in Phase III clinical trials.[10][11]
History
- 2016
- April: The rights to develop Nxera Pharma’s muscarinic agonist portfolio, including NBI-1117568 were transferred to Allergan.[9]
- 2017
- September: Allergan initiated Phase I clinical trials for NBI-1117568 to treat “neurobehavioral symptoms related to Alzheimer’s disease and other conditions.”[8]
- 2021
- 2022
- October: Phase II clinical trial of NBI-1117568 for the treatment of adults with schizophrenia was initiated.[12]
- 2024
- 2025
- May: Neurocrine Biosciences initiated a Phase III registrational program for NBI-1117568 for the treatment of adults with schizophrenia.[14]
Clinical trials
Phase II clinical trial
The Phase II clinical trial was conducted in 15 sites across the U.S. with 200 adult patients diagnosed with schizophrenia.[15] The primary endpoint was assessed by the change in the total score of the Positive and Negative Syndrome Scale (PANSS) after six weeks of treatment. The 20 mg once-daily group showed a statistically significant improvement of 7.5 points compared to the placebo group (improvement of 18.2 points from baseline, p = 0.011, effect size = 0.61).[16] However, the 40 mg once-daily group, 60 mg once-daily group, and 30 mg twice-daily group did not show statistically significant differences compared to the placebo group (p-values: 40 mg group: 0.282, 60 mg group: 0.189, 30 mg twice-daily group: 0.090).[16]
Market reaction to phase II clinical trial
With a PANSS improvement of 7.5, NBI-111758 lagged behind xanomeline/trospium (KarXT) (Karuna Therapeutics) with 8.4 and emraclidine (Cerevel Therapeutics) with 12.7, both of which were in clinical trials at the same time. Moreover, the lack of dose-dependency led to disappointment in the stock market.[17] Neurocrine Biosciences’ share price dropped 19% on the day following the announcement of the Phase II clinical trial results.[18]
References
- “Delving into the Latest Updates on Direclidine with Synapse”. Synapse. 30 June 2025. Retrieved 27 July 2025.
- https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl133.pdf [bare URL PDF]
- Ye N, Wang Q, Li Y, Zhen X (March 2025). “Current emerging therapeutic targets and clinical investigational agents for schizophrenia: Challenges and opportunities”. Medicinal Research Reviews. 45 (2): 755–787. doi:10.1002/med.22086. PMID 39300769.
- “HTL 0016878”. AdisInsight. 2 September 2024. Retrieved 21 October 2024.
- “ニューロクライン社との統合失調症およびその他の精神神経疾患を対象とした新規ムスカリン受容体作動薬に関するライセンス契約締結のお知らせ” [Announcement of License Agreement with Neurocrine for Novel Muscarinic Receptor Agonist for Schizophrenia and Other Neuropsychiatric Disorders] (in Japanese). PR TIMES. 2021-11-22. Retrieved 2024-09-17.
- “ネクセラファーマ株価6.5%高 薬候補で毒性試験成功 – 日本経済新聞” [NexThera Pharma shares rise 6.5% as drug candidate passes toxicity test – Nikkei]. 日本経済新聞 電子版 (Nikkei Electronic Edition) (in Japanese). 日本経済新聞社 (Nikkei Inc.). 2024-04-17. Retrieved 2024-09-17.
- “当社提携先のニューロクライン社が、統合失調症を対象にしたNBI-1117568の第II相臨床試験の開始を発表［そーせいグループ］ | NIKKEI COMPASS – 日本経済新聞” [Our partner Neurocrine, Inc. announces initiation of Phase II clinical trial of NBI-1117568 for schizophrenia [Sosei Group] | NIKKEI COMPASS – Nikkei Newspaper]. 日経コンパス (Nikkei Compass) (in Japanese). 日本経済新聞社 (Nikkei Inc.). 2022-10-28. Retrieved 2024-09-17.
- “アルツハイマー病等の主要症状の治療薬として開発中の新薬候補、 選択的ムスカリンM4受容体作動薬の第I相臨床試験で最初の被験者への投与を実施” [First subjects dosed in Phase I clinical trial of selective muscarinic M4 receptor agonist, a potential new drug candidate for treating major symptoms of Alzheimer’s disease] (PDF) (in Japanese). ネクセラファーマ（旧そーせいグループ株式会社）. 2017-09-01. Retrieved 2024-09-17.
- “ムスカリン作動薬プログラムのグローバルな研究開発権・販売権が返還” [Global R&D and commercial rights to muscarinic agonist program returned]. プレスリリース・ニュースリリース配信シェアNo.1｜PR TIMES (in Japanese). PR Times. 2021-01-05. Retrieved 2024-09-17.
- 日経バイオテクONLINE (2024-09-02). “ネクセラファーマ、統合失調症治療薬候補 NBI-1117568の第II相臨床試験の良好な結果によりニューロクライン社より35百万米ドルのマイルストンを受領” [Nexella Pharma Receives $35 Million Milestone Payment from Neurocrine Following Positive Results of Phase II Clinical Trial of NBI-1117568, a Potential Treatment for Schizophrenia]. 日経バイオテクONLINE (in Japanese). 日本経済新聞社. Retrieved 2024-09-17.
- “ネクセラ—大幅反落、ニューロクラインの株価下落に追随売り | 個別株 – 株探ニュース” [Nexella – Sharp decline, selling follows fall in Neurocrine stock price | Individual stocks – Kabutan News]. kabutan.jp (in Japanese). MINKABU THE INFONOID, Inc. 2024-08-29. Retrieved 2024-09-17.
- “当社提携先のニューロクライン社が、統合失調症を対象にしたNBI-1117568の第Ⅱ相臨床試験の開始を発表” [Our Partner Neurocrine Announces Initiation of Phase 2 Clinical Trial of NBI-1117568 for Schizophrenia]. プレスリリース・ニュースリリース配信シェアNo.1｜PR TIMES (in Japanese). PR TIMES. 2022-10-28. Retrieved 2024-09-17.
- 日経バイオテク (Nikkei Biotech) ONLINE (2024-09-02). “ネクセラファーマ、統合失調症治療薬候補 NBI-1117568の第II相臨床試験の良好な結果によりニューロクライン社より35百万米ドルのマイルストンを受領” [Nexella Pharma Receives $35 Million Milestone Payment from Neurocrine Following Positive Results of Phase II Clinical Trial of NBI-1117568, a Potential Treatment for Schizophrenia]. 日経バイオテクONLINE (in Japanese). 日本経済新聞社. Retrieved 2024-09-17.
- “ネクセラファーマの統合失調症薬、最終治験を開始”. 日本経済新聞. 日本経済新聞社. 2025-05-01. Retrieved 2025-05-02.
- “Neurocrine Biosciences Initiates Phase 2 Clinical Study Evaluating NBI-1117568 in Adults with Schizophrenia”. ニューロクライン. 2022-10-27. Retrieved 2024-09-17.
- “ネクセラファーマ[4565]：ニューロクライン社との提携プログラムである統合失調症治療薬候補NBI-1117568の第2相臨床試験で良好な結果 2024年8月28日(適時開示) ：日経会社情報DIGITAL：日本経済新聞” [Nexella Pharma [4565]: Positive results in Phase 2 clinical trial of NBI-1117568, a candidate for the treatment of schizophrenia, a collaboration program with Neurocrine, Inc. August 28, 2024 (timely disclosure) : Nikkei Company Information DIGITAL: Nikkei Shimbun]. 日本経済新聞 電子版 (in Japanese). 日本経済新聞社. Retrieved 2024-09-17.
- “Nxera Pharma Official IR Blog 「ニューロクライン社から35百万米ドルのマイルストン受領」” [Received $35 million milestone payment from Neurocrine]. soseiheptares.blogspot.com. ネクセラファーマ. 2024-09-02. Retrieved 2024-09-19.
- “Neurocrine Stock Down 19% on Mixed Schizophrenia Study Results”. Zacks Investment Research. Zacks Investment. 2024-08-29. Retrieved 2024-09-17.
| Clinical data | |
|---|---|
| Other names | HTL-0016878; NBI-1117568; NBI-568[1] |
| Routes of administration | Oral |
| Drug class | Muscarinic acetylcholine M4 receptor agonist |
| Identifiers | |
| IUPAC name | |
| CAS Number | 1803346-98-6 |
| PubChem CID | 118295270 |
| ChemSpider | 133319625 |
| UNII | TXB4V44U24 |
| KEGG | D13221 |
| Chemical and physical data | |
| Formula | C19H30N4O2 |
| Molar mass | 346.475 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
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Development Solutions, Developing from Lab scale to PR&D, Kilo Scale-ups and Commercial Scales
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BLUE JET HEALTHCARE LTD, https://bluejethealthcare.com
Looking for a Reliable SNAC Manufacturer? Let’s Talk.
At Blue Jet Healthcare Ltd, we specialize in the scalable, high-purity production of SNAC—a critical excipient powering the next generation of oral peptide therapeutics.
With increasing demand for SNAC across global pharma pipelines, choosing the right manufacturing partner is essential. Quality, timelines, and consistency matter.
Phone No. +91 (22) 22075307 / +91 (22) 22071691
Business Development/ Contract Manufacturing: marketing1@bluejethealthcare.com, madhu.gautam71@gmail.com
/////direclidine, ANAX, BLUE JET, ADVECT, muscarinic M4 receptor positive allosteric modulator, TXB4V44U24, NBI-1117568, NBI 1117568
DR ANTHONY MELVIN CRASTO
ORGANIC SPECTROSCOPY
New Drug Approvals 
