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ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

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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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Setidegrasib

December 3, 2025 10:09 am / Leave a comment


Setidegrasib

CAS 2821793-99-9

MF C60H65FN12O7S MW1117.30

(2S,4R)-1-[(2S)-2-[4-[4-[[6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-(oxan-4-yloxy)quinazolin-8-yl]oxymethyl]phenyl]triazol-1-yl]-3-methylbutanoyl]-4-hydroxy-N-[(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide

Kirsten rat sarcoma viral oncogene homologue (KRAS) degradation
inducer, antineoplastic, ASP-3082, ASP 3082, 3NQ4ME292X, KRAS G12D inhibitor 17

Setidegrasib (KRAS G12D inhibitor 17, ASP3082) is a PROTAC KRAS degrader (DC50: 37 nM). Setidegrasib induces the degradation of G12D-mutation KRAS protein. Setidegrasib suppresses p-ERK, p-AKT, p-S6 levels in AsPC-1 cells. Setidegrasib exhibits anti-tumor activity in various cancer xenograft models in mice. Setidegrasib can be used for the study of KRAS(G12D)-mutated solid tumors. (Blue: VHL ligase ligand (HY-168699); Black: linker (HY-168698); Pink: G12D ligand (HY-168700)).


Setidegrasib is a small molecule drug. The usage of the INN stem ‘-rasib’ in the name indicates that Setidegrasib is a Ras protein inhibitor. Setidegrasib has a monoisotopic molecular weight of 1116.48 Da.

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022173032&_cid=P21-MIPU3D-50779-1

PAT

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////////Setidegrasib, antineoplastic, ASP-3082, ASP 3082, 3NQ4ME292X, KRAS G12D inhibitor 17

Sendegobresib

December 2, 2025 2:59 am / Leave a comment


Sendegobresib

CAS 2704617-96-7

MFC37H45F3N6O5, 710.79

2,6-PIPERIDINEDIONE, 3-((4-(4-((4S)-1-((4-(1,6-DIHYDRO-1,4,5-TRIMETHYL-6-OXO-3-PYRIDINYL)-2,6-DIMETHOXYPHENYL)METHYL)-3,3-DIFLUORO-4-PIPERIDINYL)-1-PIPERAZINYL)-3-FLUOROPHENYL)AMINO)-, (3S)-

(3S)-3-[4-[4-[(4S)-1-[[2,6-dimethoxy-4-(1,4,5-trimethyl-6-oxo-3-pyridinyl)phenyl]methyl]-3,3-difluoropiperidin-4-yl]piperazin-1-yl]-3-fluoroanilino]piperidine-2,6-dione

bromodomain-containing protein 9 (BRD9) degradation inducer, antineoplastic, AW8PEP3VZ3, CFT 8634, ORPHAN DRUG

Sendegobresib is an orally bioavailable heterobifunctional protein degrader of bromodomain-containing protein 9 (BRD9; sarcoma antigen NY-SAR-29; rhabdomyosarcoma antigen MU-RMS-40.8), with potential antineoplastic activity. Sendegobresib is comprised of an E3 ligase-binding moiety and a BRD9-binding moiety. Upon oral administration, sendegobresib targets and binds to BRD9 with its BRD9-binding moiety. Upon BRD9 binding, the E3 ligase-binding moiety binds to cereblon (CRBN), a component of the CRL4-CRBN E3 ubiquitin ligase complex, which directs proteins for destruction, resulting in the proteasome-mediated degradation of BRD9. This leads to an inhibition of the growth of tumor cells that rely on BRD9 for survival. BRD9, a component of one form of the Brg/Brahma-Associated Factor (BAF) complex, is needed for the survival of certain cancer cells due to mutations.

A Study to Assess the Safety and Tolerability of CFT8634 in Locally Advanced or Metastatic SMARCB1-Perturbed Cancers, Including Synovial Sarcoma and SMARCB1-Null Tumors

CTID: NCT05355753

Phase: Phase 1

Status: Terminated

Date: 2024-12-17

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US355912448&_cid=P11-MINYJY-62955-1

Synthesis of Compound 172

Step-1: To a stirred solution of compound tert-butyl piperazine-1-carboxylate (85.40 g, 536.82 mmol) in DMF (500 mL) was added cesium carbonate (262.4 g, 805.4 mmol) and stirred for 15 min before adding 1,2-difluoro-4-nitro-benzene (100 g, 536.82 mmol). The reaction mixture stirred at RT for 16 h while monitoring by TLC. After completion, the reaction mass was quenched with ice flakes and the precipitated solid was filtered, dried under vacuum to afford tert-butyl 4-(2-fluoro-4-nitro-phenyl) piperazine-1-carboxylate 172-3 (152 g, 88.85% yield, 97.94% purity) as a yellow solid.
      Step-2: To a stirred solution of tert-butyl 4-(2-fluoro-4-nitrophenyl)piperazine-1-carboxylate 172-3 (50.0 g, 153.69 mmol) in 20 ml dioxane was added 4M dioxane HCl (30 ml) and reaction mixture stirred for 2 h at RT while monitoring by TLC. The solvent was evaporated to dryness under reduced pressure and crude solid was triturated with diethyl ether (75 ml) and n-pentane (100 ml) to afford HCl salt of 1-(2-fluoro-4-nitrophenyl) piperazine 172-4 (36.0 g, 136.2 mmol, 88.62% yield, 99% purity). LCMS (ES +): m/z 226.10 [M+H] +
      Step-3: To stirred solution of 1-(2-fluoro-4-nitro-phenyl)piperazine 172-4 (8.0 g, 35.52 mmol) in toluene (200 ml) and ACN (100 ml) was added NaOAc (7.28 g, 88.80 mmol), followed by AcOH (8 ml) and molecular sieves 4 Å (10 g) and stirred for 15 min. After 15 min tert-butyl 3,3-difluoro-4-oxo-piperidine-1-carboxylate (11.49 g, 48.84 mmol, co-distilled with toluene before use) was added and the reaction mixture was allowed to reflux for 12 h, while monitoring by LCMS and TLC. After completion, reaction mixture was cooled to room temperature and filtered through Celite bed. The filtrate was concentrated under vacuum to dryness to afford crude residue 3,3-difluoro-4-(4-(2-fluoro-4-nitrophenyl)piperazin-1-yl)-3,6-dihydropyridine-1(2H)-carboxylate 172-6 (12.2 g, 98.89% purity) which was used for next step without any purification. LCMS (ES +): m/z 443.75 [M+H] +
      Step-4: The compound 172-6 (8 g, 18.08 mmol) was dissolved in a mixture of methanol (20 mL), DCE (20 mL) and AcOH (2 ml), allowed to stir for 15 min, before adding sodium cyanoborohydride (5.68 g, 90.41 mmol). After addition, the reaction mixture was stirred for 24 h at room temperature, while monitoring by LCMS and TLC. The reaction mixture was filtered through Celite bed and filtrate was concentrated under vacuum. Crude compound purified by (silica gel mesh 100-200, and product eluted with 30% ethyl acetate in pet ether-neat ethyl acetate) column chromatography to afford tert-butyl-3,3-difluoro-4-[4-(2-fluoro-4-nitro-phenyl)piperazin-1-yl]piperidine-1-carboxylate 172-7 (7.2 g, 15.39 mmol, 85.11% yield, 98% purity). LCMS (ES +): m/z 445.35 [M+H] +
      Step-5: To the stirred solution of tert-butyl 3,3-difluoro-4-(4-(2-fluoro-4-nitrophenyl)piperazin-1-yl)piperidine-1-carboxylate 172-7 (5 g, 11.25 mmol) in ethyl acetate (100 mL) was added 10% Palladium on carbon wet (3.59 g, 33.75 mmol) at RT. The reaction mixture was stirred at RT under H 2 balloon pressure for 12 h was monitored by TLC. After the completion of the reaction, the reaction mixture was filtered-off through Celite and washed with ethyl acetate (200 mL). The filtrate was concentrated to obtain the crude product which was triturated with pentane, decanted the organic layer and the solidified product was filtered, dried well to afford tert-butyl 4-[4-(4-amino-2-fluoro-phenyl)piperazin-1-yl]-3,3-difluoro-piperidine-1-carboxylate 172-8 (3 g, 61.48% yield, 95.56% purity) as pale pink solid. LCMS (ES +): m/z 415.56 [M+H] +
      Step-6: To a stirred solution of tert-butyl 4-[4-(4-amino-2-fluoro-phenyl)piperazin-1-yl]-3,3-difluoro-piperidine-1-carboxylate 172-8 (5 g, 12.06 mmol) in DMF (20 mL) taken in a seal tube was added 3-bromopiperidine-2,6-dione (6.95 g, 36.19 mmol) at rt followed by the addition of sodium bicarbonate (6.08 g, 72.38 mmol) and the reaction mixture was allowed to stir at 90° C. for 12 h. After the completion of the reaction, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (200 mL) and filtered off through Celite. The filtrate washed with water (2×100 mL), brine (1×25 mL), dried over anhydrous Na 2SO 4, filtered and concentrated to get the crude product. The crude product was purified by column chromatography using silica gel (100/200 mesh) and the product eluted at 2-3% MeOH/DCM) to afford (tert-butyl 4-(4-(4-((2,6-dioxopiperidin-3-yl)amino)-2-fluorophenyl)piperazin-1-yl)-3,3-difluoropiperidine-1-carboxylate 172-9 (4.2 g, 56.31% yield, 91.08% purity) as a purple solid. LCMS (ES +): m/z 526.48 [M+H] +
      Step-7: To the stirred solution of tert-butyl 4-[4-[4-[(2,6-dioxo-3-piperidyl)amino]-2-fluoro-phenyl]piperazin-1-yl]-3,3-difluoro-piperidine-1-carboxylate 172-9 (7 g, 13.32 mmol) in 1,4-dioxane (30 mL) was added 4M HCl in dioxane (30.35 mL, 665.95 mmol, 30.35 mL) at 0° C. The reaction mixture was stirred at 0° C. for 30 minutes, slowly warmed to RT and stirred at RT for 6 h. After the completion of the reaction, the reaction mixture was concentrated and the residual mass was triturated with diethyl ether (3×100 mL) and the solid precipitated out was dried well to afford 3-[4-[4-(3,3-difluoro-4-piperidyl)piperazin-1-yl]-3-fluoro-anilino]piperidine-2,6-dione 172-10 as HCl salt (5.54 g, 90.05% yield, 91.71% purity) as pale blue solid. LCMS (ES +): m/z 426.22 [M+H] +
      Step 8: To a stirred solution of 3-[4-[4-(3,3-difluoro-4-piperidyl)piperazin-1-yl]-3-fluoro-anilino]piperidine-2,6-dione HCl 172-10 (5.65 g, 12.23 mmol) in DCE:MeOH (60:60 ml) were added 4 Å molecular sieves (3 g), acetic acid (0.797 g, 13.27 mmol) and sodium acetate (3.27 g, 39.82 mmol). The resulting solution was stirred for 10 min, then added 2,6-dimethoxy-4-(1,4,5-trimethyl-6-oxo-3-pyridyl)benzaldehyde 172-11 (4 g, 13.27 mmol) and heated the reaction mixture at 70° C. for 5 h then cooled it at RT and added Silia Bond Cyanoborohydride (3.85 g, 66.37 mmol). The stirring was continued at RT for 16 h, while monitoring the reaction by LCMS and TLC. After 16 h, the reaction mass was filtered through Celite, concentrated and purified by (Devisil silica gel, and product eluted with 1% to 5% MeOH in CH 2C2) column flash chromatography to afford compound was dissolved in dry DCM (10 ml) and TFA (5 ml) was added at 0° C., stirred it for 30 min. After 30 min, reaction crude was concentrated to dryness and obtained crude was washed with diethyl ether (3×20 ml) to afford 3-[4-[4-[1-[[2,6-dimethoxy-4-(1,4,5-trimethyl-6-oxo-3-pyridyl)phenyl]methyl]-3,3-difluoro-4-piperidyl]piperazin-1-yl]-3-fluoro-anilino]piperidine-2,6-dione TFA Compound 172 (3.21 g, 3.83 mmol, 28.85% yield, 98.40% purity) as a light green solid. 1H NMR (400 MHz, DMSO-d 6) δ 10.78 (s, 1H), 9.97 (s, 1H), 7.52 (s, 1H), 6.84 (t, J=9.3 Hz, 1H), 6.66 (s, 2H), 6.51 (d, J=15.0 Hz, 1H), 6.42 (d, J=8.5 Hz, 1H), 4.28-4.24 (m, 3H), 3.86 (s, 7H), 3.47 (s, 6H), 2.90 (bs, 9H), 2.76-2.68 (m, 1H), 2.53-2.54 (m, 1H), 2.08 (d, J=10.7 Hz, 9H), 1.91-1.87 (m, 1H). LCMS (ES +): m/z 711.20 [M+H] +

PAT

WO-2021178920

PAT

WO-2022216765

PAT

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/////////Sendegobresib, antineoplastic, AW8PEP3VZ3, CFT 8634, ORPHAN DRUG

Segigratinib, Ratangratinib

December 1, 2025 3:03 am / Leave a comment


Segigratinib, Ratangratinib

CAS 1882873-93-9

MF C27H28Cl2N6O3 MW 555.5 g/mol

N-[6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-(3,3-dimethylpiperazin-1-yl)benzamide

N-[6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[5,4-b]pyridin-3-yl]-4-(3,3-dimethylpiperazin-1-yl)benzamide
fibroblast growth factor receptor tyrosine kinase inhibitor, antineoplastic, 3D 185, Ratangratinib, 3D-185, G0Z5E4YTB4, HH 185

Ratangratinib is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) types 1, 2, and 3 (FGFR1/2/3) and colony stimulating factor 1 receptor (CSF1R; CSF-1R; CD115; M-CSFR), with potential immunomodulatory and antineoplastic activities. Upon administration, ratangratinib binds to and inhibits FGFR1/2/3, which may result in the inhibition of FGFR1/2/3-mediated signal transduction pathways. This inhibits proliferation in FGFR1/2/3-overexpressing tumor cells. 3D185 also targets and binds to CSF1R, thereby blocking CSF1R activation and CSF1R-mediated signaling. This inhibits the activities of tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), and prevents immune suppression in the tumor microenvironment (TME). This enhances antitumor T-cell immune responses and inhibits the proliferation of 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. CSF1R, also known as macrophage colony-stimulating factor receptor (M-CSFR) and CD115 (cluster of differentiation 115), is a cell-surface receptor that plays major roles in tumor cell proliferation and metastasis.

Efficacy and Safety of 3D185 Monotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma

CTID: NCT05039892

Phase: Phase 2

Status: Not yet recruiting

Date: 2025-05-20

SYN

WO-2016026445-A1

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2016026445&_cid=P20-MIMK7T-68502-1

N-(6-(2,6-dichloro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)-6-(3,3-dimethylpiperazin-1-yl)nicotinamide


1H NMR(DMSO-d6,400MHz)δppm 13.39(s,1H),10.86(s,1H),8.81(d,1H,J＝2.0Hz),8.40(d,1H,J＝8.0Hz),8.16(dd,1H,J 1＝2.4Hz,J 2＝2.4Hz),7.08(t,2H,J＝8.4Hz),6.90(d,1H,J＝9.2Hz),3.99(s,6H),3.60(t,2H,J＝4.0Hz),3.43(s,2H),2.82(t,2H,J＝4.4Hz),1.04(s,6H).LCMS:556.2[M+H] +，RT＝1.21min。

SYN

US10562900,

https://patentscope.wipo.int/search/en/detail.jsf?docId=US204149576&_cid=P20-MIMK4B-66027-1

1H NMR (d-MeOD, 400 MHz) δ ppm 8.52 (d, J=8.0 Hz, 1H), 8.03 (d, J=8.0 Hz, 2H), 7.15-7.13 (m, 3H), 6.94 (s, 1H), 3.99 (s, 6H), 3.58-3.57 (m, 2H), 3.44-3.40 (m, 4H), 10.50 (s, 6H).

PAT

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////////segigratinib, antineoplastic, 3D 185, Ratangratinib, 3D-185, G0Z5E4YTB4, HH 185

Segatroxaban

November 30, 2025 8:36 am / Leave a comment


Segatroxaban

CAS 1184300-63-7

MF C24H30ClN5O5S2 MW568.11

5-chloro-N-{(2S)-2-[2-methyl-3-(2-oxopyrrolidin-1-yl)benzene1-sulfonamido]-3-(4-methylpiperazin-1-yl)-3-oxopropyl}thiophene-2-carboxamide

2-THIOPHENECARBOXAMIDE, 5-CHLORO-N-((2S)-2-(((2-METHYL-3-(2-OXO-1-PYRROLIDINYL)PHENYL)SULFONYL)AMINO)-3-(4-METHYL-1-PIPERAZINYL)-3-OXOPROPYL)-5-CHLORO-N-((2S)-2-(((2-METHYL-3-(2-OXO-1-PYRROLIDINYL)PHENYL)SULFONYL)AMINO)-3-(4-METHYL-1-PIPERAZINYL)-3-OXOPROPYL)-2-THIOPHENECARBOXAMIDE5-CHLOROTHIOPHENE-2-CARBOXYLIC ACID N-((S)-2-(((2-METHYL-3-(2-OXOPYRROLIDIN-1-YL)PHENYL)SULFONYL)AMINO)-3-(4-METHYLPIPERAZIN-1-YL)-3-OXOPROPYL)AMIDE5-CHLORO-N-((2S)-2-(2-METHYL-3-(2-OXOPYRROLIDIN-1-YL)BENZENE-1-SULFONAMIDO)-3-(4-METHYLPIPERAZIN-1-YL)-3-OXOPROPYL)THIOPHENE-2-CARBOXAMIDE
blood coagulation factors Xa and IIa (thrombin) inhibitor, 53FM6EUY9U, SAR107375, SAR 107375

SYN

WO-2009103440

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2009103440&_cid=P10-MILGON-12468-1

SYN

WO-2014174102-A1

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2014174102&_cid=P10-MILGJE-09654-1

SYN

WO-2023031083-A1

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023031083&_cid=P10-MILGQR-13553-1

PAT

Chlorothiophene-amides as inhibitors of coagulation factors xa and thrombin

Publication Number: WO-2009103440-A1

Priority Date: 2008-02-21

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Rupitasertib

November 29, 2025 3:11 am / Leave a comment


Rupitasertib

CAS 1379545-95-5

MF C21H19ClF3N5O 449.9 g/mol

4-({(1S)-2-(azetidin-1-yl)-1-[4-chloro-3-(trifluoromethyl)phenyl]ethyl}amino)quinazoline-8-carboxamide

4-[[(1S)-2-(azetidin-1-yl)-1-[4-chloro-3-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxamide
serine/ threonine kinase inhibitor, antineoplastic, EMD SERONO, Gastric cancer; HER2 positive breast cancer; Solid tumours, M2698 HCl, M2698 hydrochloride, MSC2363318A, MSC 2363318A, MSC-2363318A, M2698, M-269, M 2698. Rupitasertib HCl, 0DXG50I4WD

  • OriginatorEMD Serono
  • DeveloperEMD Serono; Evexta Bio
  • ClassAntineoplastics; Small molecules
  • Mechanism of Action70 kDa ribosomal protein S6 kinase inhibitors; Proto-oncogene protein c-akt inhibitors
  • PreclinicalGlioblastoma; HER2 negative breast cancer
  • No development reportedGastric cancer; HER2 positive breast cancer; Solid tumours
  • 28 Oct 2025No recent reports of development identified for preclinical development in Gastric-cancer in France (PO)
  • 28 Jun 2025No recent reports of development identified for phase-I development in HER2-positive-breast-cancer(Combination therapy, Late-stage disease, Metastatic disease) in USA (PO)
  • 28 Jun 2025No recent reports of development identified for phase-I development in Solid-tumours(Combination therapy, Late-stage disease) in USA (PO)
  • First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies
  • CTID: NCT01971515
  • Phase: Phase 1
  • Status: Completed
  • Date: 2018-09-19

Rupitasertib is an orally available inhibitor of the serine/threonine protein kinases ribosomal protein S6 Kinase (p70S6K) and Akt (protein kinase B), with potential antineoplastic activity. Upon administration, rupitasertib binds to and inhibits the activity of p70S6K and Akt. This prevents the activation of the PI3K/Akt/p70S6K signaling pathway and inhibits tumor cell proliferation in cancer cells that have an overactivated PI3K/Akt/p70S6K signaling pathway. Constitutive activation and dysregulated signaling of the PI3K/Akt/p70S6K pathway are frequently associated with tumorigenesis of many tumor types; targeting multiple kinases in this pathway is more efficacious than targeting a single kinase.

An optimized S6K inhibitor to overcome limitations of PAM pathway inhibitors

In just over 20 years, protein kinase inhibitors have changed the face of oncology and opened the new eras of targeted therapies and precision medicine. However, with few exceptions, no patient can be cured by one of these drugs alone. Today, scientists seek to develop novel kinase inhibitors[1] with improved efficacy and the potential to overcome resistances. The dual S6K AKT1/3 inhibitor rupitasertib (formerly DIACC3010, acquired from Merck KGaA, Darmstadt, Germany) has both of these characteristics and reaches brain metastases. After successfully completing a Phase I trial in patients with advanced/refractory solid tumors, including breast cancer, the drug candidate will be evaluated in a Phase 2/3 trial in ER+ HER2 breast cancer, which is expected to start in 2024.

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2012069146&_cid=P10-MIJPKI-12294-1

Example 4 was prepared following the general synthesis of A-E starting with (S)-2- amino-2-(3,4-di-fluoro-phenyl)-ethanol.LCMS [384.20 (M+1)]. 1H NMR (DMSO-d6, ppm) 1.92 (2H), 2.75 (1H), 2.93 (1H), 3.15 (4H), 5.43 (1H), 7.34 (2H), 7.53 (1H), 7.68 (1H), 7.81 (1H), 8.58 (4H), 10.30 (1H).

4-[(S)-2-Azetidin-1-yl-1-(4-chloro-3-trifluoromethylphenyl)-ethylamino]-guinazoline-8- carboxylic acid amide (5)

IC50 P70S6K [nM]: 0.9

pS6 MDA-MB-468 [nM]: 11

Akt1 IC50 [nM]: 1.4

Aurora B IC50 [nM]: 100

PAT

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////////////Rupitasertib, antineoplastic, EMD SERONO, Gastric cancer; HER2 positive breast cancer; Solid tumours, M2698 HCl, M2698 hydrochloride, MSC2363318A, MSC 2363318A, MSC-2363318A, M2698, M-269, M 2698. Rupitasertib HCl, 0DXG50I4WD

Rogocekib

November 28, 2025 3:06 am / Leave a comment


Rogocekib

CAS 2144751-78-8

MF C19H17FN8O2 MW 408.39

1-({5-[(1R)-1-fluoroethyl]-1,3,4-oxadiazol-2-yl}methyl)-6-(4-methoxypyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-methyl1H-imidazo[4,5-b]pyridine

2-[(1R)-1-fluoroethyl]-5-[[6-(4-methoxypyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-methylimidazo[4,5-b]pyridin-1-yl]methyl]-1,3,4-oxadiazole
dual specificity protein kinase CLK (CDC2-like kinase)inhibitor, antineoplastic, CTX 712, XE88VQP94E

Rogocekib is an orally effective CLK 2 inhibitor, with an IC50 of 1.4 nM, showing anti-tumor activity.

Rogocekib is an orally bioavailable inhibitor of CLK family kinases, with potential antineoplastic activity. Upon oral administration, rogocekib binds to and inhibits the activity of CLK family kinases, thereby inhibiting the phosphorylation of serine/arginine-rich (SR) domain-containing splicing factors (SFs). This modulates RNA splicing, prevents the expression of certain tumor-associated genes, and inhibits tumor cell proliferation. In many cancer cells, core spliceosome proteins, including SF3B1, U2 small nuclear ribonucleoprotein auxiliary factor 1 (U2AF1), serine/arginine-rich splicing factor 2 (SRSF2) and U2 small nuclear ribonucleoprotein auxiliary factor subunit-related protein 2 (ZRSR2), are mutated and aberrantly activated leading to a dysregulation of mRNA splicing. CLK family kinases, an evolutionarily conserved group of kinases, phosphorylates various SR proteins including SR domain-containing SFs.

SYN

https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00412

(R)-2-fluoropropanoic acid (21)
(R)-Ethyl 2-fluoropropanoate (20) (95 g, 791 mmol) was suspended in 10% sulfuric acid (950 mL), and heated and
refluxed for 3 h. After cooled, sodium chloride was added to saturate the aqueous layer, and the aqueous layer
was extracted with TBME (900 mL x4). The obtained organic layer was dried over MgSO4, and concentrated under
reduced pressure to give the title compound (124 g, 791 mmol calcd as quant., containing TBME).
1H NMR (300 MHz, DMSO-d6) δ 1.35-1.56 (3H, m), 4.91-5.21 (1H, m), 13.19 (1H, brs).
(S)-2-amino-3-phenylpropane-1-ol (R)-2-fluoropropanoate (22)
To a solution of (S)-2-amino-3-phenylpropan-1-ol (119 g, 787 mmol) in EtOH (360 mL) and MeCN (1090 mL) was
added dropwise a solution of 21 (791 mmol, theoretically calcd as quant.) in MeCN (1090 mL) at 65° C to 70° C.
The mixture was stirred at 60° C for 1 h, and further stirred at room temperature for 1 h. Precipitated crystals were
collected by filtration, and washed with MeCN (500 mL) to obtain white crystals (170 g, 699 mmol, 89%).
The obtained crystals(140 g, 575 mmol) were dissolved in EtOH (700 mL) at 60° C, and to the solution was added
MeCN (4200 mL) at 58° C to 65° C. The mixture was stirred at 60° C for 1 h. The mixture was cooled to room
temperature, and then stirred overnight at room temperature. The obtained solid was collected by filtration, and
washed with MeCN to obtain give the title compound (109 g, 448 mmol, 78%) as a white crystal.
(R)-2-((6-bromo-2-methyl-1H-imidazo[4,5-b]pyridin-1-yl)methyl)-5-(1-fluoroethyl)-1,3,4-oxadiazole ((R)-19b)
22 (109 g, 448 mmol) was dissolved in 1M HCl aq. (1500 mL) and brine (1500 mL) and extracted with TBME (1000
mL x4). The organic layer was dried over MgSO4 and concentrated in vacuo to give free salt of 22 (i.e., 21) as a
colorless oil. 50 wt% T3P in EtOAc (419 mL, 704 mmol) was added to a suspension of the above material, 17a (100
g, 351.97 mmol), and DIPEA (246 mL, 1408 mmol) in BuOAc (3000 mL) at room temperature. After being stirred at
50 °C for 30 min, 50 wt% T3P in EtOAc (210 mL, 351.97 mmol) was added to the mixture and then the mixture was
heated and refluxed for 3 h. After cooling, to the mixture was added sat NaHCO3 aq. (3000 mL), then the insoluble

material was removed by filtration. The filtrate was extracted with EtOAc (1500 mL x2). The organic layer was
separated, washed with water and brine, then passed through NH silica gel eluted with EtOAc. The residue was
concentrated in vacuo and the resulting precipitate was washed with IPE (3000 mL) to give the title compound
(57.8 g, 170 mmol, 48.3%) as an off-white solid.
1H NMR (300 MHz, DMSO-d6) δ 1.62-1.79 (3H, m), 2.62 (3H, s), 5.83-6.14 (3H, m), 8.38 (1H, d, J = 1.9 Hz), 8.45 (1H,
d, J = 1.9 Hz). MS m/z 340.0, 341.9 [M+H]+
.
1-((5-((1R)-1-fluoroethyl)-1,3,4-oxadiazol-2-yl)methyl)-6-(4-methoxypyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-methyl1H-imidazo[4,5-b]pyridine ((R)-19, CTX-712)
A mixture of (4-methoxypyrrolo[2,1-f][1,2,4]triazin-5-yl)boronic acid (79 g, 409.39 mmol), (R)-19b (100 g, 294
mmol), Pd(Amphos)Cl2 (2.00 g, 2.97 mmol), 2 M Cs2CO3 aq. (295 mL, 590 mmol) and DME (2000 mL) was stirred at
80 °C for 1 h. After cooled to 50 °C, the mixture was diluted with THF (1000 mL). The mixture was poured into
NaHCO3 aq. (1600 mL) and extracted with EtOAc (1000 mL x3). The organic layer was separated, washed with 5%
ammonia aq. (1600 mLx2) and brine (1600 mL), dried over MgSO4 and concentrated in vacuo to give a yellow solid.
To the solution of obtained solid in THF (8000 mL) and water (200 mL) was added NH silica gel (2400 g) and stirred
for 3.5 h at room temperature. The insoluble material was removed by filtration and washed with THF (15 L). The
filtrate was concentrated in vacuo to give a yellow solid. The solid was washed with TBME to give the title
compound (98 g, 240 mmol, 82 %) as a pale yellow solid. A mixture of the above material (115 g, 270 mmol) and
activated carbon (Ecosorb, 33 g) in EtOH/water = 9/1 (2200 mL) and water (1100 mL) was stirred at 55 °C for 1 h.
The insoluble material was removed by filtration, and washed EtOH (550 mL). The resultant solution was diluted
with water (1600 mL) at 55 °C and stirred at room temperature overnight. After cooled to 5 °C, the mixture was
stirred for 3 h. The solid was collected by filtration and washed with EtOH/water = 1/1 (1000 mL) to give a
colorless crystal (88 g, 207 mmol, 77% as a water adduct).
1H NMR (300 MHz, DMSO-d6) δ 1.58-1.82 (3H, m), 2.67 (3H, s), 3.96 (3H, s), 5.83-6.18 (3H, m), 7.06 (1H, d, J = 2.7
Hz), 8.06 (1H, d, J = 2.7 Hz), 8.23 (2H, t, J = 1.0 Hz), 8.59 (1H, d, J = 2.0 Hz). MS m/z 409.1 [M+H]+
.

PAT

Patent document 1: 

WO 2010/016526

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2010016526&_cid=P10-MIIA44-38372-1

WO 2011/096535

SYN

WO-2023190967

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023190967&_cid=P10-MII9ZT-35263-1

SYN

WO-2024048541

SYN

WO2017188374

https://patentscope.wipo.int/search/en/detail.jsf?docId=JP275206879&_cid=P10-MII9SJ-29591-1

https://data.epo.org/publication-server/rest/v1.2/publication-dates/2025-02-05/patents/EP4501328NWA1/document.pdf

PAT

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///////rogocekib, CTX 712, XE88VQP94E

Riselcaftor

November 27, 2025 8:31 am / Leave a comment


Riselcaftor

CAS 2799652-36-9

MF C29H28N2O5S MW 516.61

(2R,4R)-2-(2-methoxy-5-methylphenyl)-N-(2-methylquinoline-5-sulfonyl)-4-phenyloxolane-2-
carboxamide

(2R,4R)-2-(2-methoxy-5-methylphenyl)-N-(2-methylquinolin-5-yl)sulfonyl-4-phenyloxolane-2-carboxamide
cystic fibrosis transmembrane regulator (CFTR)protein modulator, 726GWJ6KQQ

Riselcaftor (Example 33) is a CFTR modulator, with an EC50 of 20.1 nM in human bronchial epithelial cells. Riselcaftor can be used for research of cystic fibrosis.

SYN

US20220211692

https://patentscope.wipo.int/search/en/detail.jsf?docId=US367940046&_cid=P11-MIH63N-23616-1

Example 33

(2R,4R)-2-(2-methoxy-5-methylphenyl)-N-(2-methylquinoline-5-sulfonyl)-4-phenyloxolane-2-carboxamide

      The enantiomers of Example 32D (140 mg) were separated by chiral preparative supercritical fluid chromatography (ES Industries AD-H column (21×250 mm, 5 micron) 12.8 mg/mL in 10:1 methanol/diethylamine, 56 g/minutes CO 2, RT 11.8 minutes) to provide the title compound (84.7 mg, 0.164 mmol, 60.2% yield). 1H NMR (500 MHz, dimethyl sulfoxide-d 6) δ ppm 12.07 (s, 1H), 8.80 (d, J=8.9 Hz, 1H), 8.27 (d, J=7.3 Hz, 1H), 8.24 (d, J=8.5 Hz, 1H), 7.90 (t, J=7.9 Hz, 1H), 7.48 (d, J=8.9 Hz, 1H), 7.28-7.22 (m, 3H), 7.21-7.16 (m, 1H), 7.11-7.06 (m, 2H), 7.06-7.01 (m, 1H), 6.63 (d, J=8.3 Hz, 1H), 4.15 (t, J=7.9 Hz, 1H), 3.73 (t, J=8.7 Hz, 1H), 3.21-3.14 (m, 1H), 3.11 (s, 3H), 3.05 (dd, J=13.4, 7.0 Hz, 1H), 2.71 (s, 3H), 2.22 (s, 3H), 1.85 (t, J=11.8 Hz, 1H). MS(APCI+) m/z 517 (M+H) +.

PAT

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……

[1]. David J. Hardee, et al. Modulators of the Cystic Fibrosis Transmembrane Conductance Regulator Protein and Methods of Use. Patent. US20220211692 A1

//////Riselcaftor, 726GWJ6KQQ

Pudafensine

November 26, 2025 2:40 am / Leave a comment


Pudafensine

CAS 1320346-14-2

MFC17H19NO4 MW 301.34 g/mol

7-{[(1R,3s,5S)-8-azabicyclo[3.2.1]octan-3-yl]oxy}-3-methoxy2H-1-benzopyran-2-one
monoamine reuptake inhibitor, erectile dysfunction, neuropathic pain, NS18313, NS 18313, L9NG7US8GE, IP2015, IP 2015

Pudafensine is a monoamine reuptake inhibitor being developed as a potential treatment for erectile dysfunction (ED) and neuropathic pain. As a drug candidate, it works by preferentially inhibiting the reuptake of dopamine and serotonin. It is designed to be a first-line treatment for patients with organic ED who are not adequately served by existing therapies like PDE5 inhibitors. 

How it works

  • Pudafensine is a monoamine reuptake inhibitor that increases the levels of dopamine and serotonin in the brain by preventing their reabsorption into neurons.
  • It has been shown in animal models and human trials to improve erectile function and reduce pain, including neuropathic pain. 

Potential uses

  • Erectile Dysfunction (ED): Pudafensine is being investigated for its potential to help men with organic ED who do not respond well to or cannot tolerate current treatments. Phase IIb clinical trial results are expected in late 2023.
  • Neuropathic Pain: A clinical trial on pain involving pudafensine indicated it reduced allodynia and was well-tolerated with a favorable safety profile compared to pregabalin. 

Development status

  • Initiator Pharma is developing pudafensine as an oral tablet.
  • Phase IIb studies for erectile dysfunction and Phase II studies for neuropathic pain have been completed, with positive results.
  • The company is exploring its use in treating patients who are inadequately treated with existing medications. 

Erectile dysfunction (ED)

Pudafensine, Initiator’s most advanced drug program has successfully demonstrated efficacy in a Clinicial Phase 2a Proof-of-Concept study and in a Phase 2b study to treat patients who suffer from organic erectile dysfunction (ED) that do not respond or cannot tolerate the currently marketed drugs in the PDE5i class (e.g. Viagra®, Cialis®, Levitra®).

Pudafensine strengthens the natural erection response by having a dual-action, both a central effect initiating erection and a peripheral effect potentiating erection through smooth muscle relaxation. Pudafensine is aimed for treatment of organic erectile dysfunction in patients who have erectile dysfunction (ED) due to abnormalities of the penile arteries and/or veins. Most common risk factors for organic ED are diabetes, overweight, lack of exercise, high cholesterol, high blood pressure, and cigarette smoking. Since Initiator Pharma was founded and pudafensine acquired, all preclinical development of the drug candidate to enable an application for clinical trials (CTA) has been carried out by the company’s auspices. Pudafensine is developed as a tablet that is taken orally on-demand. It is the company’s goal to be able to create a new “First-Line” treatment (recommended treatment) for the large group of men who have organic erectile dysfunction, who are sub-optimally treated with PDE5i products or for whom PDE5i treatment is contraindicated.

In Q4 2023 positive results from the Phase IIb clinical trial with pudafensine (IP2015) was announced. The Phase 2b trial is a randomized, double-blind, placebo-controlled, parallel-dosing group trial studying the efficacy and safety of high and low doses of pudafensine (IP2015) and placebo in otherwise healthy patients suffering from moderate to severe ED. The study comprises 130 patients divided into 3 parallel arms receiving a higher and a lower dose of pudafensine and placebo, respectively, with treatment duration of 4 weeks with frequent assessments of erectile dysfunction, safety and pharmacokinetics. The study has been conducted at the MAC clinical sites in the UK.

The study demonstrated statistically significant efficacy on the primary endpoint (related to improvements in intercourse settings) compared to placebo [p=0.034] and baseline [p=0.046]. Furthermore, the results were consistent throughout the study. Several other clinical endpoints related to improved intercourse activities (obtained from the International Index of Erectile Function Questionnaire, IIEF-15) demonstrated significant effects compared to the baseline. The frequency and type of adverse effects were mild to moderate and comparable to those observed in the placebo group. There was no reporting of critical safety observations.

Neuropathic pain

Pudafensine have shown effects in a human model of pain ie. in a clinical Phase I study in healthy subjects dosed with the drug pudafensine and challenged with a pain-inducing ingredient (capsaicin).

The Phase I study was a randomized, double blind, placebo controlled study in 24 healthy male subjects, investigating the effects on pain measures (hyperalgesia, allodynia, and subjects pain rating) of single doses of pudafensine, pregabalin as an active control, and placebo. The pain was induced by intradermal capsaicin. Pudafensine demonstrated a statistically significant effect on allodynia (p=0.049) and showed a dose-dependent effect on the measured pain parameters. Pregabalin (p=0.083) and IP2015 (p=0.051) tended to reduce hyperalgesia, although the effects on hyperalgesia were not statistically significant compared to placebo-treated subjects.

Syn

US20130040985 

https://patentscope.wipo.int/search/en/detail.jsf?docId=US76705962&_cid=P22-MIFE0H-55553-1

endo-Benzoic acid 8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl ester

Benzoylchloride (84.3 g, 600 mmol) was added during 30 min at <30° C. to a mixture of tropine (70.6 g, 500 mmol), potassium tert-butoxide (67.3 g, 600 mmol) and THF (500 ml). The mixture was stirred at room temperature for 2 h. Water (1 L) was added followed by extraction with diethylether (2×500 ml). The organic phase was washed twice with water (2×200 ml) followed by a solution of saturated aqueous sodium chloride (200 ml). The ether phase was dried and hydrochloric acid in ethanol (170 ml, 3 M) was added. The precipitated hydrochloride was filtered and washed with diethylether. The free base was obtained by adding an excess of aqueous ammonia followed by extraction with a mixture of ethylacetate and diethylether. Yield 66.8 g (54%).

endo-Benzoic acid 8-aza-bicyclo[3.2.1]oct-3-yl ester

 2,2,2-Trichloroethylchloroformate (75.0 ml, 544 mmol) was added dropwise to a mixture of endo-benzoic acid 8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl ester (66.8 g, 272 mmol) and dry toluene (500 ml). The mixture was allowed to stir for 1 h at room temperature, followed by 15 h at 100° C. Water (250 ml) was added followed by stirring 1 h. The phases were separated and the organic phase was washed twice with water (2×200 ml). The mixture of the intermediate 3-benzoyloxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid trichloromethyl ester, was dried and evaporated. Acetic acid (350 ml) was added followed by addition of zinc (53.4 g, 817 mmol) over 3 h time period. Water (100 ml) was added, cooled by adding ice and made alkaline by adding concentrated aqueous ammonia (ca: 400 ml) and the mixture was extracted with dichloromethane (2×300 ml). Yield 44.5 g (61%).

endo-3-Benzoyloxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester

Di-tert-butyl-dicarbonate (39.9 g, 183 mmol) solved in THF (100 ml) was added to a stirred mixture of endo-benzoic acid 8-aza-bicyclo[3.2.1]oct-3-yl ester (44.5 g, 166.4 mmol), triethylamine (67.4 g, 666 mmol) and THF (250 ml) during 0.5 h at room temperature, followed by stirring for 1 h. Water (1 L) was added and the mixture was extracted with diethylether (2×300 ml). The collected ether phase was washed twice with water (2×200 ml), dried and evaporated. Yield 60.1 g (100%).

endo-3-Hydroxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester

  A mixture of endo-3-benzoyloxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (55.0 g, 166 mmol), potassium hydroxide (11.2 g 199 mmol) and ethanol (99%, 400 ml) was stirred for 3 days at room temperature. Potassium benzoate was separated by filtration and the filtrate was evaporated. Diethylether (200 ml) was added and remaining potassium benzoate was separated by filtration and the filtrate was evaporated. The product was triturated with petroleum. Yield 30.0 g (80%). Mp 139.5-140.8° C.

xample 1

Exo-tert-butyl-3-(3-methoxy-2-oxo-chromen-7-yl)oxy-8-azabicyclo[3.2.1]octane-8-carboxylate (Intermediate)

Triphenylphosphine (1.15 g, 4.37 mmol) was solved in toluene (20 ml) and cooled to <20° C. Diethylazodicarboxylate (40% in toluene) (2.0 ml, 4.37 mmol) was added to the mixture below 20° C., followed by stirring for 10 minutes. endo-3-Hydroxy-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.828 g, 3.64 mmol) was added and after 10 minutes 7-hydroxy-3-methoxy-chromen-2-one (0.70 g, 3.64 mmol) (prepared according to J. Med. Chem. 1999, 42, p2662-2672) was added to the mixture. The temperature raised to 25° C. due to an exothermic reaction. The mixture precipitates. The mixture was allowed to stir for 15 h at room temperature. Water (20 ml) and sodium hydroxide (0.5 ml, 4 M) was added followed by stirring. The mixture was cooled on an ice-bath, filtered and washed with water and diethylether. Yield 0.92 g (63%).

Exo-7-[(-8-azabicyclo[3.2.1]octan-3-yl)oxy]-3-methoxy-chromen-2-one hydrochloride (Compound 1.1)

Exo-tert-butyl-3-(3-methoxy-2-oxo-chromen-7-yl)oxy-8-azabicyclo[3.2.1]octane-8-carboxylate (0.92 g, 2.29 mmol) and hydrogen chloride (15 ml, 1 M) in acetic acid was mixed as a solution and stirred at room-temperature and precipitated after a few minutes. The product was filtered and washed with diethylether. Yield 0.48 g (62%). LC-ESI-HRMS of [M+H]+ shows 302.13856 Da. Calc. 302.138689 Da, dev. −0.4 ppm.

Syn

WO2011092061 

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2011092061&_cid=P22-MIFE80-61015-1

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2024008808&_cid=P22-MIFDSB-50229-1

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2024089247&_cid=P22-MIFDSB-50229-1

SYN

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2024146892&_cid=P22-MIFDSB-50229-1

PAT

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……

//////////Pudafensine, monoamine reuptake inhibitor, erectile dysfunction, neuropathic pain, NS18313, NS 18313, L9NG7US8GE, IP2015, IP 2015

Privosegtor

November 25, 2025 2:40 am / Leave a comment


Privosegtor

CAS 1361200-34-1

MF C25H38FN5O4, MW 491.6 g/mol

GLYCINAMIDE, N-(2-(2-FLUOROPHENYL)ETHYL)GLYCYL-N-(2-METHYLPROPYL)GLYCYL-N2-(3-(2-OXO-1-PYRROLIDINYL)PROPYL)-
N-(2-(2-FLUOROPHENYL)ETHYL)GLYCYL-N-(2-METHYLPROPYL)GLYCYL-N2-(3-(2-OXO-1-PYRROLIDINYL)PROPYL)GLYCINAMIDE
N-(2-(2-FLUOROPHENYL)ETHYL)GLYCYL-N-(2-METHYLPROPYL)GLYCYL-N2-(3-(2-OXOPYRROLIDIN-1-YL)PROPYL)GLYCINAMIDE

N-[2-(2-fluorophenyl)ethyl]glycyl-N-(2-methylpropyl)glycyl-N2[3-(2-oxopyrrolidin-1-yl)propyl]glycinamide
serum/ glucocorticoid-regulated kinase 2 (Sgk2) activator, Phase 2, Optic neuritis, orphan drug, BN-201, BN 201, G-79, G 79, KCN37L7EIH
  • OriginatorBionure
  • DeveloperBionure; Oculis Pharma
  • ClassAnti-inflammatories; Antiglaucomas; Eye disorder therapies; Neuroprotectants; Peptides; Small molecules
  • Mechanism of ActionBrain derived neurotrophic factor agonists; Insulin-like growth factor I stimulants; Neuron modulators; Serum-glucocorticoid regulated kinase stimulants
  • Orphan Drug StatusYes – Optic neuritis
  • Phase IIOptic neuritis
  • PreclinicalMultiple sclerosis; Neurotrophic keratopathy
  • No development reportedGlaucoma; Neuromyelitis optica
  • 06 Oct 2025Oculis Holding plans the PIONEER-2 trial in Optic neuritis in first half of 2026
  • 06 Oct 2025Oculis Holding plans the PIONEER-3 trial in Optic nerve disorders in mid-2026
  • 06 Oct 2025Oculis Holding completes End-of-phase II meeting with US FDA and receives positive feedback for registrational PIONEER program in Optic neuritis and Optic nerve disorders

OCS-05 in Patients With Optic Neuritis

CTID: NCT04762017

Phase: Phase 2

Status: Completed

Date: 2025-09-22

N-[2-[(2-amino-2-oxoethyl)-[3-(2-oxopyrrolidin-1-yl)propyl]amino]-2-oxoethyl]-2-[2-(2-fluorophenyl)ethylamino]-N-(2-methylpropyl)acetamide (BN201) is a small peptide molecule, a first-in-class neuroprotective compound. BN201 promotes the survival of cultured neural cells when subjected to oxidative stress or when deprived of trophic factors. BN201 promotes neuronal differentiation, the differentiation of precursor cells to mature oligodendrocytes in vitro, and the myelination of new axons. BN201 modulates several kinases participating in the insulin growth factor 1 pathway including serum-glucocorticoid kinase and midkine, inducing the phosphorylation of NDRG1 and the translocation of the transcription factor Foxo3 to the cytoplasm. In vivo, BN201 prevents axonal and neuronal loss, and it promotes remyelination in models of multiple sclerosis, chemically induced demyelination, and glaucoma. Bionure, a spin-off from Hospital Clínic de Barcelona that is based in California, is developing BN201 for multiple sclerosis, acute optic neuritis (AON) and glaucoma. BN201 was granted with orphan designation status for optic neuritis by the FDA. Optic neuritis is often an early sign of multiple sclerosis. The efficacy, safety, and capacity of the drug to cross the blood-brain barrier have been demonstrated in animal models, but the drug has not yet entered clinical testing.

PAT

Agonists of neurotrophin receptors and their use as medicaments

Publication Number: WO-2012028959-A1

Priority Date: 2010-08-31

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2012028959&_cid=P10-MIDYQ0-58943-1

PAT

WO-2021084013

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2021084013&_cid=P10-MIDYSN-60542-1

In another embodiment, optionally in combination with one or more features of the various embodiments described above or below throughout all the description, the compound of formula (I) is selected from the group consisting of G79 ([N-(2-(2′-fluorophenyl)ethyl)- glycyl]-[N-(2-methylpropyl)-glycyl]-N-[3-(2′-oxopyrrolidinyl)-propyl]glycinamide, BN201 , Chemical Formula: C25H38FN5O4; MW 491.5987), G-80 ([N-(2-(2′-fluorophenyl)ethyl)- glycyl]-[N-(2-methyl-propyl)glycyl]-N-[2-(4′-sulfamoyl-phenyl)ethyl]glycinamide, BN 119, Chemical Formula: C26H36FN5O5S; MW 549.658) and G81 ([N-(2-(1 -pyrrolidinyl)ethyl)- glycyl]-[N-(2-methyl-propyl)glycyl]-N-[2-(4′-sulfamoyl-phenyl)ethyl]glycinamide, BN 120, Chemical Formula: C24H4oN6OS; MW 524.6766):

G79 (BN201) G80 (BN119) G81 (BN120)

Compounds of formula (I) can be prepared as disclosed in WO2012028959.

PAT

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/////////Privosegtor, Phase 2, Optic neuritis, orphan drug, BN-201, BN 201, G-79, G 79, KCN37L7EIH

Pregabalin naproxencarbil

November 24, 2025 10:44 am / Leave a comment


Pregabalin naproxencarbil

CAS 1221072-91-8

MF C25H33NO7 MW459.5 g/mol

(3S)-3-[({[(1R)-1-{[(2S)-2-(6-methoxynaphthalen-2-yl)propanoyl]oxy}ethoxy]carbonyl}amino)methyl]-5-
methylhexanoic acid

(3S)-3-[[[(1R)-1-[(2S)-2-(6-methoxynaphthalen-2-yl)propanoyl]oxyethoxy]carbonylamino]methyl]-5-methylhexanoic acid
gabamimetic, analgesic, ZVG8DDT3FJ

  • OriginatorXgene Pharmaceutical
  • ClassAminobutyric acids; Analgesics; Antiepileptic drugs; Antipyretics; Antirheumatics; Anxiolytics; Drug conjugates; Gabapentinoids; Naphthaleneacetic acids; Neuroprotectants; Nonsteroidal anti-inflammatories; Small molecules
  • Mechanism of ActionCACNA2D1 protein modulators; Cyclooxygenase inhibitors
  • Phase II/IIIPostoperative pain
  • Phase IIAcute pain; Cancer pain; Pain
  • Phase I/IIBack pain; Neuropathic pain
  • No development reportedDiabetic neuropathies
  • 15 Jul 2025XG005 licensed to NeuroGen in China, Hong Kong, and Macau
  • 31 Dec 2024Efficacy and adverse events data from phase-II/III trial in Postoperative pain released by Xgene Pharmaceutical
  • 25 Oct 2024Xgene Pharmaceutical completes the phase II/III trial in Postoperative pain in USA (PO)

PAT

WO-2019219000

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2019219000&_cid=P22-MID0L3-49648-1

Example 1: Exemplary synthesis of the compound of Formula I and crystallization thereof

Step A: Synthesis of 1-chloroethyl 2-fluorophenyl carbonate (3)

[0306]

A suitable reaction vessel was charged with water and sodium bicarbonate followed by the starting material 2-fluoro-phenol (1) . The mixture was cooled to a temperature of about 0～5℃ and 1-chloroethyl chloroformate (2) was added slowly while maintaining the temperature at 0～5℃. The temperature was raised to about 15 ± 5℃. When the reaction was judged complete by the disappearance of 2-fluoro-phenol (criteria: ≤ 2.0%, by HPLC) the reaction was worked up. n-Heptane was added and the organic phase was separated, washed with water and brine. The solution was concentrated, then toluene was added and the solution was concentrated again. The toluene addition and the concentration cycle were repeated once more.

[0307]

Step B: Synthesis of (S) – ( (R, S) -1- ( (2-fluorophenoxy) carbonyloxy) ethyl 2- (6-methoxynaphthalen-2-yl) propanoate (4)

[0308]

To a solution of naproxen in toluene in a suitable reaction vessel, 1-chloroethyl 2-fluorophenyl carbonate (3) and cuprous oxide was added. The temperature of the mixture was raised to about 115 ±5℃. When the reaction was judged complete by the disappearance of 1-chloroethyl 2-fluorophenyl carbonate (criteria: ≤ 2.5%, by HPLC) the reaction was worked up. Methyl tert-butyl ether was added at about 50 ± 5℃. The resulting mixture was filtered and the filtrate was collected at about 25 ± 5℃. Purified water was added into the filtrate and then the mixture was cooled to about 0 ± 5℃. The mixture was alkalified with ammonium hydroxide to a pH of about 9～11 and the organic phase was separated and washed with ammonium hydroxide and brine. The solution was concentrated, then acetonitrile was added and the solution was concentrated again. The acetonitrile addition and the concentration cycle were repeated some more times until the residual toluene was not more than 10% (by GC method) .

[0309]

Step C: Synthesis of (S) -3- ( ( ( (R) -1- ( (S) -2- (6-methoxynaphthalen-2-yl) propanoyloxy) ethoxy) carbonyl-amino) methyl) -5-methylhexanoic acid (the compound of Formula I)

[0310]

To a solution of the mixture of (S) – ( (R, S) -1- ( (2-fluorophenoxy) carbonyloxy) ethyl 2- (6-methoxynaphthalen-2-yl) propanoate (4) in acetonitrile and methyl tert-butyl ether in a suitable reaction vessel, purified water and pregabalin was charged. Triethylamine was added slowly while maintaining the temperature at about 15 ± 5℃. The temperature was raised to about 25 ± 3℃ for reaction. When the reaction was judged complete by the disappearance of (S) – ( (R, S) -1- ( (2-fluorophenoxy) carbonyloxy) ethyl 2- (6-methoxynaphthalen-2-yl) propanoate (criteria: ≤ 0.5%, by HPLC) the reaction was worked up. The resulting mixture was acidified with KHSO 4to pH 3～5 and extracted with methyl tert-butyl ether. The combined organic layers were washed with purified water and brine. The organic phase was then concentrated. Isopropanol was added and the solution was concentrated again. The isopropanol addition and the concentration cycle was repeated once or more times until the total residual acetonitrile and methyl tert-butyl ether was not more than 5% (by GC method) . n-Heptane was added into the mixture at about 40～45 ℃ and stirred and then the temperature was gradually lowered at set appropriate intervals to crystallize (S) -3- ( ( ( (R) -1- ( (S) -2- (6-methoxynaphthalen-2-yl) propanoyloxy) ethoxy) carbonyl-amino) methyl) -5-methylhexanoic acid (5) from the system. When the precipitation was complete, the heterogeneous mixture was centrifuged and the solid was collected.

[0311]

The crude product of (S) -3- ( ( ( (R) -1- ( (S) -2- (6-methoxynaphthalen-2-yl) propanoyloxy) ethoxy) carbonyl-amino) methyl) -5-methylhexanoic acid (5) was added to a solution of isopropanol and water in a suitable vessel. The mixture was stirred while raising the temperature to 45 ± 3 ℃ until all the solid was dissolved, then the temperature was lowered gradually at set appropriate intervals to recrystallize (S) -3- ( ( ( (R) -1- ( (S) -2- (6-methoxynaphthalen-2-yl) propanoyloxy) ethoxy) carbonyl-amino) methyl) -5-methylhexanoic acid from the system. When the precipitation had stopped, the heterogeneous mixture was centrifuged and the expected pure (S) -3- ( ( ( (R) -1- ( (S) -2- (6-methoxynaphthalen-2-yl) propanoyloxy) ethoxy) carbonyl-amino) methyl) -5-methylhexanoic acid (Formula I) was collected.

Example 2: Alternative synthetic route of (S) -3- ( ( ( (R) -1- ( (S) -2- (6-methoxynaphthalen-2-yl) propanoyloxy) ethoxy) carbonyl-amino) methyl) -5-methylhexanoic acid

PAT

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.//////////Pregabalin naproxencarbil, gabamimetic, analgesic, ZVG8DDT3FJ

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