FLAGS AND HITS
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
FACEBOOK
...................................................................Join me on twitter
..................................................................Join me on google plus
GoogleplusMYSELF
Soquelitinib
Soquelitinib
CAS 2226636-04-8
MF C25H30N4O4S2, 514.7 g/mol
N-[5-({4-methoxy-2-methyl-5-[(3R)-3-methyl-4-(prop-2-enoyl)-1,4-diazepane-1-carbonyl]phenyl}sulfanyl)-1,3-thiazol-2-yl]cyclopropane-1-carboxamide
tyrosine kinase inhibitor, antineoplastic, CPI818, CPI-000818, CPI596, CP I818, CPI 000818, CP I596, 6I5H17AN3I,
Soquelitinib (CPI-818) is an experimental drug which acts as a selective inhibitor of the enzyme interleukin-2-inducible T-cell kinase (ITK). It is in clinical trials for the treatment of T-cell lymphoma.[1][2]
Soquelitinib is an orally available, small-molecule, irreversible inhibitor of interleukin-2 inducible T-cell kinase (ITK) with potential immunomodulatory and antineoplastic activities. Upon oral administration, soquelitinib selectively and covalently binds to the cysteine residue at position 442 (CYS-442) of ITK, thereby disrupting ITK-mediated signal transduction, while sparing tyrosine-protein kinase TXK (resting lymphocyte kinase, RLK) activity. This may abrogate T-cell receptor (TCR) signaling through ITK and inhibit TCR-induced proliferation of malignant T-cells. Additionally, inhibiting ITK activation may prevent the upregulation of GATA-3, a transcription factor that drives T-helper 2 (Th2) cell differentiation and is overexpressed in certain T-cell lymphomas. Thus, selective inhibition of ITK may inhibit Th2 responses without affecting T-helper 1 (Th1)-dependent immunity. ITK, a member of the Tec family of non-receptor protein tyrosine kinases plays a significant role in the T-cell development, differentiation and production of pro-inflammatory cytokines.
- Safety, Tolerability, and Preliminary Efficacy of Soquelitinib in Participants With Moderate to Severe ADCTID: NCT06345404Phase: Phase 1Status: RecruitingDate: 2025-07-22
- Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS PatientsCTID: NCT06730126Phase: Phase 2Status: RecruitingDate: 2025-05-31
- Soquelitinib vs Standard of Care in Participants With Relapsed/Refractory Peripheral T-cell Lymphoma Not Otherwise Specified, Follicular Helper T-cell Lymphomas, or Systemic Anaplastic Large-cell LymphomaCTID: NCT06561048Phase: Phase 3Status: RecruitingDate: 2025-04-17
- A Dose Escalation Study Evaluating CPI-818 in Relapsed/Refractory T-Cell LymphomaCTID: NCT03952078Phase: Phase 1Status: Active, not recruitingDate: 2025-04-16
Syn
- US11008314,
- https://patentscope.wipo.int/search/en/detail.jsf?docId=US278926237&_cid=P10-MISM56-82578
- SIMILAR
Syn
- WO2018089261 COMPD 44
- https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2018089261&_cid=P10-MISM0C-78029-1
SYN
Embodiment B23. A method for an Th2/ITK-mediated disease in a patient in need thereof, the method comprising administering to the patient about 250 mg to about 1,000 mg per day of a compound of Formula (A) or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (A) is:
REF
https://www.nature.com/articles/s44386-024-00002-1
Pat
- Compounds and methods for modulating interleukin-2-inducible t-cell kinasePublication Number: US-2022363676-A1Priority Date: 2016-11-03
- Compounds and methods for modulating Interleukin-2-inducible T-cell kinasePublication Number: US-11897874-B2Priority Date: 2016-11-03Grant Date: 2024-02-13
- Itk inhibitors for increasing th1 cell activityPublication Number: WO-2023196278-A1Priority Date: 2022-04-05
- Compounds and methods for modulating interleukin-2-inducible t-cell kinasePublication Number: US-2019375743-A1Priority Date: 2016-11-03
- Compounds and methods for modulating interleukin-2-inducible t-cell kinasePublication Number: WO-2018089261-A2Priority Date: 2016-11-03
- Compounds and methods for modulating interleukin-2-inducible t-cell kinasePublication Number: US-11008314-B2Priority Date: 2016-11-03Grant Date: 2021-05-18
- Compounds and methods for modulating interleukin-2-inducible t-cell kinasePublication Number: EP-3534899-B1Priority Date: 2016-11-03Grant Date: 2022-06-01
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
References
- Khodadoust MS, Feldman TA, Yoon DH, Yannakou CK, Radeski D, Kim YH, et al. (November 2020). “Cpi-818, an oral interleukin-2-inducible T-cell kinase inhibitor, is well-tolerated and active in patients with T-cell lymphoma”. Blood. 136: 19–20. doi:10.1182/blood-2020-137782.
- Hsu LY, Rosenbaum JT, Verner E, Jones WB, Hill CM, Janc JW, et al. (December 2024). “Synthesis and characterization of soquelitinib a selective ITK inhibitor that modulates tumor immunity”. npj Drug Discovery. 1 (1) 2: 1–4. doi:10.1038/s44386-024-00002-1.
| Identifiers | |
|---|---|
| IUPAC name | |
| CAS Number | 2226636-04-8 |
| PubChem CID | 134517711 |
| DrugBank | DB18749 |
| ChemSpider | 129629996 |
| UNII | 6I5H17AN3I |
| KEGG | D12762 |
| Chemical and physical data | |
| Formula | C25H30N4O4S2 |
| Molar mass | 514.66 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
//////////////Soquelitinib, tyrosine kinase inhibitor, antineoplastic, CPI818, CPI-000818, CPI596, CP I818, CPI 000818, CP I596, 6I5H17AN3I,
Sitokiren
Sitokiren
CAS 1399849-02-5,
MF C22H32N6O4, 444.5 g/mol
methyl N-[3-[3-[(1R)-1-[cyclopropyl-[(2R)-morpholine-2-carbonyl]amino]ethyl]-6-methylpyrazolo[5,4-b]pyridin-1-yl]propyl]carbamate
methyl [3-(3-{(1R)-1-[(2R)-N-cyclopropylmorpholine-2-carboxamido]ethyl}-6-methyl-1H-pyrazolo[3,4-
b]pyridin-1-yl)propyl]carbamate
renin inhibitor, SPH 3127, C2M78A9V6Z
Sitokiren, also known as SPH3127, isa highly potent, orally active direct renin inhibitor developed by Mitsubishi Tanabe Pharma Corp. that was initially investigated for hypertension and cardiovascular diseases. Recent research has shown it also has a strong anti-inflammatory effect, particularly in the gut, making it a potential candidate for treating conditions like inflammatory bowel disease (IBD).
What it is
- Direct renin inhibitor: Sitokiren directly inhibits the enzyme renin, which is the rate-limiting step in the renin-angiotensin-aldosterone system (RAAS).
- Chemical properties: It is a small molecule with the chemical formula
C22H32N6O4
- Developed by: Mitsubishi Tanabe Pharma Corp..
- Alternative name: SPH3127 is another name for sitokiren.
How it works
- Blocks the RAAS: By inhibiting renin, it prevents the RAAS from over-activating.
- Potential benefits: This inhibition may help in managing blood pressure and has also shown promise in suppressing inflammation in the gut, which is a key factor in IBD.
Current research and potential applications
- Hypertension: Sitokiren was initially developed for its potential to treat hypertension, and preclinical models have shown it to be more potent than the approved drug aliskiren.
- Inflammatory bowel disease (IBD): Studies using sitokiren in mouse models have demonstrated its ability to reduce inflammation and protect against damage in colitis, suggesting it could be a novel therapeutic for IBD.
SPH-3127 is under investigation in clinical trial NCT05359068 (Study to Evaluate the Efficacy and Safety of SPH3127 in Patients With Mild-moderate Essential Hypertension).
SPH3127 is a small-molecule renin inhibitor developed by Shanghai Pharmaceuticals for hypertension and kidney disease. It is believed to be more potent than aliskiren.[1][2][3]
SYN
https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.2c00834
Methyl N-[3-(3-{(1S)-1-[cyclopropyl-((2R)-morpholine-2-carbonyl)amino]ethyl}-6-methyl
pyrazolo[3,4-b]pyridin-1-yl)propyl]carbamate (18-diastereomer). This isomer was separated
from a mixture of the corresponding diastereomers using NH-silica gel column chromatography
as the more polar isomer. 1H NMR (400 MHz, DMSO-d6) : 0.20 (m, 1H), 0.51−0.74 (m, 3H),
1.70 (d, J = 7.0 Hz, 3H), 1.94 (m, 2H), 2.57 (s, 3H), 2.60−2.75 (m, 3H), 2.79 (m, 1H), 2.87 (dd,J = 2.4, 12.5 Hz, 1H), 3.00 (m, 2H), 3.47 (m, 1H), 3.51 (s, 3H), 3.79 (d, J = 10.9 Hz, 1H),
4.30−4.46 (m, 2H), 4.66 (dd, J = 2.1, 9.4 Hz, 1H), 5.84 (q, J = 7.0 Hz, 1H), 7.02 (d, J = 8.2 Hz,
1H), 7.16 (m, 1H), 7.83 (d, J = 8.2 Hz, 1H). MS (APCI) m/z: 445.1 [M + H]+. Purity and
diastereomeric excess measured by chiral HPLC: 98.37%, 81.23% de (column: Chiralpak IC (4.6
mm × 250 mm, elution: hexane/EtOH/diethylamine, 50:50:0.1 (v/v), flow rate: 0.5 mL/min,
column temperature: 25 °C, retention time: 29.40 min).
SYN
SYN
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022047730&_cid=P12-MIR63I-81994-1
PAT
Nitrogen-containing saturated heterocyclic compound
Publication Number: US-9278944-B2
Priority Date: 2011-03-16
Grant Date: 2016-03-08
https://patentscope.wipo.int/search/en/detail.jsf?docId=US95781978&_cid=P12-MIR64F-82901-1
PAT
- Salt of morpholine derivative and crystalline form thereof, as well as preparation method, pharmaceutical composition and use of the samePublication Number: EP-3398946-B1Priority Date: 2015-12-29Grant Date: 2022-05-04
- Nitrogen-containing saturated heterocyclic compoundPublication Number: EP-2687518-B1Priority Date: 2011-03-16Grant Date: 2017-11-01
- Nitrogen-containing saturated heterocyclic compoundPublication Number: US-10155731-B2Priority Date: 2011-03-16Grant Date: 2018-12-18
- Nitrogen-containing saturated heterocyclic compoundPublication Number: US-2014011807-A1Priority Date: 2011-03-16
- Nitrogen-containing saturated heterocyclic compoundPublication Number: US-2016145220-A1Priority Date: 2011-03-16
- Methods to treat inflammatory bowel diseasePublication Number: US-2023398123-A1Priority Date: 2020-09-04
- Salt of morpholine derivative and crystalline form thereof, as well as preparation method, pharmaceutical composition and use of the samePublication Number: EP-3398946-A1Priority Date: 2015-12-29
- Salts of morpholine derivative, crystal forms thereof, processes for producing the same, pharmaceutical compositions including the same, and use thereofPublication Number: US-10519150-B2Priority Date: 2015-12-29Grant Date: 2019-12-31
- Salts of morpholine derivative, crystal forms thereof, processes for producing the same, pharmaceutical compositions including the same, and use thereofPublication Number: US-2019016718-A1Priority Date: 2015-12-29
- Salt of morpholine derivative and its crystal form, manufacturing method thereof, pharmaceutical composition and use thereofPublication Number: TW-I705065-BPriority Date: 2015-12-29Grant Date: 2020-09-21
- Methods to treat inflammatory bowel diseasePublication Number: WO-2022047730-A1Priority Date: 2020-09-04
- Application of nitrogen-containing saturated heterocyclic compoundPublication Number: WO-2022048614-A1Priority Date: 2020-09-04
- Methods to treat inflammatory bowel diseasePublication Number: WO-2022048618-A1Priority Date: 2020-09-04
- Application of nitrogen-containing saturated heterocyclic compoundPublication Number: EP-4209218-A1Priority Date: 2020-09-04
- Application of nitrogen-containing saturated heterocyclic compoundPublication Number: US-2023330093-A1Priority Date: 2020-09-04
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
References
- Iijima, Daisuke; Sugama, Hiroshi; Takahashi, Yoichi; Hirai, Miki; Togashi, Yuko; Xie, Jianshu; Shen, Jingkang; Ke, Ying; Akatsuka, Hidenori; Kawaguchi, Takayuki; Takedomi, Kei; Kashima, Akiko; Nishio, Masashi; Inui, Yosuke; Yoneda, Hikaru; Xia, Guangxin; Iijima, Toru (25 August 2022). “Discovery of SPH3127: A Novel, Highly Potent, and Orally Active Direct Renin Inhibitor”. Journal of Medicinal Chemistry. 65 (16): 10882–10897. doi:10.1021/acs.jmedchem.2c00834. PMID 35939295. S2CID 251400126.
- Zhang, Leduo; Mao, Yu; Gao, Zhiwei; Chen, Xiaoyan; Li, Xin; Liu, Yanjun; Xia, Guangxin (February 2020). “The Nonclinical Pharmacokinetics and Prediction of Human Pharmacokinetics of SPH3127, a Novel Direct Renin Inhibitor”. European Journal of Drug Metabolism and Pharmacokinetics. 45 (1): 15–26. doi:10.1007/s13318-019-00573-9. PMID 31494843. S2CID 201848935.
- Jing, Shan; Xu, Ranchi; Yang, Kexu; Liu, Wenfang; Zhang, Leduo; Ke, Ying; Xia, Guangxin; Lin, Yang (April 2021). “Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SPH3127: A Phase I, Randomized, Double-Blind, Placebo-Controlled Trial”. Clinical Therapeutics. 43 (4): 735.e1–735.e14. doi:10.1016/j.clinthera.2021.01.025. PMID 33653620. S2CID 232104329.
| Legal status | |
|---|---|
| Legal status | Investigational |
| Identifiers | |
| IUPAC name | |
| CAS Number | 1399849-02-5 |
| PubChem CID | 117877477 |
| ChemSpider | 76799450 |
| UNII | C2M78A9V6Z |
| ChEMBL | ChEMBL4110551 |
| Chemical and physical data | |
| Formula | C22H32N6O4 |
| Molar mass | 444.536 g·mol−1 |
| 3D model (JSmol) | Interactive image |
| SMILES | |
| InChI | |
////Sitokiren, renin inhibitor, SPH 3127, C2M78A9V6Z
Setidegrasib
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
- Combination of anticancer agents comprising a bifunctional compound with g12d mutant kras inhibitory activityPublication Number: WO-2024033537-A1Priority Date: 2022-08-12
- Combination of anticancer agents comprising a bifunctional compound with g12d mutant kras inhibitory activityPublication Number: WO-2024033538-A1Priority Date: 2022-08-12
- Quinazoline compound for inducing degradation of g12d-mutation kras proteinPublication Number: WO-2022173032-A1Priority Date: 2021-02-15
- Quinazoline compound for inducing degradation of g12d-mutation kras proteinPublication Number: EP-4293024-A1Priority Date: 2021-02-15
- Quinazoline compound for inducing degradation of g12d mutant kras proteinPublication Number: US-2024182483-A1Priority Date: 2021-02-15
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
- [1]. Yoshinari, et al. Preparation of quinazoline-linked (4R)-4-hydroxy-L-prolinamide compounds for inducing degradation of G12D-mutation KRAS protein: World Intellectual Property Organization, WO2022173032[P]. 2022-08-18.[2]. Yoshinari T, et al. Discovery of KRAS(G12D) selective degrader ASP3082. Commun Chem. 2025 Aug 23;8(1):254. [Content Brief]
////////Setidegrasib, antineoplastic, ASP-3082, ASP 3082, 3NQ4ME292X, KRAS G12D inhibitor 17
Sendegobresib
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. |
PAT
PAT
PAT
- Enhanced hyt-induced protein degradation using lipid nanoparticle deliveryPublication Number: US-2023414723-A1Priority Date: 2020-10-26
- Compounds for targeted degradation of brd9Publication Number: WO-2021178920-A1Priority Date: 2020-03-05
- Compounds for targeted degradation of brd9Publication Number: US-2022098194-A1Priority Date: 2020-03-05
- Compounds for targeted degradation of brd9Publication Number: US-2023060334-A1Priority Date: 2020-03-05
- Compounds for targeted degradation of BRD9Publication Number: US-11691972-B2Priority Date: 2020-03-05Grant Date: 2023-07-04
- Selected compounds for targeted degradation of brd9Publication Number: US-2024245677-A1Priority Date: 2021-09-09
- Exosome-based cancer assaysPublication Number: US-11938164-B2Priority Date: 2021-04-07Grant Date: 2024-03-26
- Exosome-based cancer assaysPublication Number: US-2022331390-A1Priority Date: 2021-04-07
- Exosome-based cancer assaysPublication Number: WO-2022216765-A1Priority Date: 2021-04-07
- Enhanced hyt-induced protein degradation using lipid nanoparticle deliveryPublication Number: WO-2022093809-A1Priority Date: 2020-10-26
- Directed degron molecules and applications thereofPublication Number: WO-2023081400-A1Priority Date: 2021-11-04
- Directed degron molecules and applications thereofPublication Number: WO-2023081400-A9Priority Date: 2021-11-04
- Directed degron molecules and applications thereofPublication Number: EP-4426687-A1Priority Date: 2021-11-04
- Selected compounds for targeted degradation of brd9Publication Number: WO-2023039208-A1Priority Date: 2021-09-09
- Selected compounds for targeted degradation of brd9Publication Number: EP-4398904-A1Priority Date: 2021-09-09
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
/////////Sendegobresib, antineoplastic, AW8PEP3VZ3, CFT 8634, ORPHAN DRUG
Segigratinib, Ratangratinib
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
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
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
- Indazole compounds as fgfr kinase inhibitor, preparation and use thereofPublication Number: EP-3184521-A1Priority Date: 2014-08-19
- Indazole compounds as FGFR kinase inhibitor, preparation and use thereofPublication Number: US-10562900-B2Priority Date: 2014-08-19Grant Date: 2020-02-18
- Indazole compounds as fgfr kinase inhibitor, preparation and use thereofPublication Number: US-2017275291-A1Priority Date: 2014-08-19
- Indazole compounds as fgfr kinase inhibitor, preparation and use thereofPublication Number: WO-2016026445-A1Priority Date: 2014-08-19
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
////////segigratinib, antineoplastic, 3D 185, Ratangratinib, 3D-185, G0Z5E4YTB4, HH 185
Segatroxaban
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
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2009103440&_cid=P10-MILGON-12468-1
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2014174102&_cid=P10-MILGJE-09654-1
SYN
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
- Tartrate salt of 5-chloro-thiophene-2-carboxylic acid [(S)-2-[2-methyl-3-(2-oxo-pyrrolidin-1-yl)-benzenesulfonylamino]-3-(4-methyl-piperazin-1-yl)-3-oxo-propyl]amidePublication Number: US-9637479-B2Priority Date: 2013-04-26Grant Date: 2017-05-02
- Tartrate salt of 5-chloro-thiophene-2-carboxylic acid [(s)-2-[methyl-3-(2-oxo-pyrrolidin-1-yl)-benzenesulfonylamino]-3-(4-methyl piperazin-1 -yl)-3-oxo-propryl]amidePublication Number: WO-2014174102-A1Priority Date: 2013-04-26
- Chlorothiophene-amides as inhibitors of coagulation factors xa and thrombinPublication Number: EP-2254881-A1Priority Date: 2008-02-21
- Chlorothiophene-amides as inhibitors of coagulation factors xa and thrombinPublication Number: EP-2254881-B1Priority Date: 2008-02-21Grant Date: 2012-09-12
- Chlorothiophene-amides as inhibitors of coagulation factors xa and thrombinPublication Number: US-2011112075-A1Priority Date: 2008-02-21
- Substituted S-alaninate derivativesPublication Number: US-11912692-B2Priority Date: 2021-09-03Grant Date: 2024-02-27
- Substituted s-alaninate derivativesPublication Number: WO-2023031083-A1Priority Date: 2021-09-03
- A method for detecting isomers in SAR107375 by high performance liquid chromatographyPublication Number: CN-112666269-BPriority Date: 2019-10-16Grant Date: 2022-12-30
- Tartrate salt of 5-chloro-thiophene-2-carboxylic acid [(s)-2-[methyl-3-(2-oxo-pyrrolidin-1-yl)-benzenesulfonylamino]-3-(4-methyl-piperazin-1 -yl)-3-oxo-propyl]amidePublication Number: AU-2014259378-B2Priority Date: 2013-04-26Grant Date: 2018-08-30
- Tartrate salt of 5-chloro-thiophene-2-carboxylic acid [(s)-2-[methyl-3-(2-oxo-pyrrolidin-1-yl)-benzenesulfonylamino]-3-(4-methyl-piperazin-1-yl)-3-oxo-propyl]amidePublication Number: US-2016102082-A1Priority Date: 2013-04-26
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
//////////segatroxaban, 53FM6EUY9U, SAR107375, SAR 107375
Rupitasertib
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
- Quinazoline carboxamide azetidinesPublication Number: SG-190318-A1Priority Date: 2010-11-24
- Quinazoline carboxamide azetidinesPublication Number: US-2013252942-A1Priority Date: 2010-11-24
- Quinazoline carboxamide azetidinesPublication Number: US-8946247-B2Priority Date: 2010-11-24Grant Date: 2015-02-03
- SMAC Mimetic for Treating Myelodysplastic SyndromesPublication Number: US-2015158908-A1Priority Date: 2009-07-02
- Methods of treating a ras protein-related disease or disorderPublication Number: US-2025049810-A1
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
- p70S6K/Akt dual inhibitor DIACC3010 is efficacious in preclinical models of gastric cancer alone and in combination with trastuzumabPublication Name: Scientific ReportsPublication Date: 2023-09-25PMCID: PMC10520030PMID: 37749105DOI: 10.1038/s41598-023-40612-9
- TTD: Therapeutic Target Database describing target druggability informationPublication Name: Nucleic Acids ResearchPublication Date: 2023-09-15PMCID: PMC10767903PMID: 37713619DOI: 10.1093/nar/gkad751
- Identification of Clinical Candidate M2698, a Dual p70S6K and Akt Inhibitor, for Treatment of PAM Pathway-Altered CancersPublication Name: Journal of Medicinal ChemistryPublication Date: 2021-10-01PMID: 34596404DOI: 10.1021/acs.jmedchem.1c01087
- Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancerPublication Name: Journal of Hematology & OncologyPublication Date: 2021-08-18PMCID: PMC8371902PMID: 34407844DOI: 10.1186/s13045-021-01132-z
- M2698 is a potent dual-inhibitor of p70S6K and Akt that affects tumor growth in mouse models of cancer and crosses the blood-brain barrierPublication Name: American journal of cancer researchPublication Date: 2016PMCID: PMC4859885PMID: 27186432
////////////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
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
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2023190967&_cid=P10-MII9ZT-35263-1
SYN
SYN
https://patentscope.wipo.int/search/en/detail.jsf?docId=JP275206879&_cid=P10-MII9SJ-29591-1
PAT
- Condensed Heterocyclic CompoundsPublication Number: KR-102431405-B1Priority Date: 2016-04-28Grant Date: 2022-08-10
- COMPOUND, MEDICINE, AND, USE OF THE COMPOUND OR SALT THEREOFPublication Number: BR-112018072039-B1Priority Date: 2016-04-28
- Fused Heterocyclic CompoundsPublication Number: CN-109415384-BPriority Date: 2016-04-28Grant Date: 2022-01-11
- Condensed heterocyclic compoundPublication Number: EP-3450436-B1Priority Date: 2016-04-28Grant Date: 2022-07-27
- Fused heterocyclic compoundPublication Number: US-11390634-B2Priority Date: 2016-04-28Grant Date: 2022-07-19
- condensed heterocyclic compoundPublication Number: ES-2927529-T3Priority Date: 2016-04-28Grant Date: 2022-11-08
- CONDENSED HETEROCYCLIC COMPOUNDPublication Number: HR-P20221277-T1Priority Date: 2016-04-28
- Fused heterocyclic compoundPublication Number: US-10577382-B2Priority Date: 2016-04-28Grant Date: 2020-03-03
- Fused heterocyclic compoundPublication Number: US-2019106437-A1Priority Date: 2016-04-28
- Fused heterocyclic compoundPublication Number: US-2020140462-A1Priority Date: 2016-04-28
- Fused heterocyclic compoundPublication Number: US-10981934-B2Priority Date: 2016-04-28Grant Date: 2021-04-20
- Fused heterocyclic compoundPublication Number: US-2021115067-A1Priority Date: 2016-04-28
- Medicament for treatment and/or prevention of cancerPublication Number: WO-2024048541-A1Priority Date: 2022-08-30
- Biomarker for treatment of solid cancer by imidazo[4,5-b]pyridine derivativePublication Number: WO-2023190967-A1Priority Date: 2022-03-31
- Fused heterocyclic compoundPublication Number: CA-3021185-A1Priority Date: 2016-04-28
- Condensed heterocyclic compoundPublication Number: EP-3450436-A1Priority Date: 2016-04-28
- Fused heterocyclic compoundsPublication Number: JP-WO2017188374-A1Priority Date: 2016-04-28
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
- [1]. Akinori Yoda, et al. CTX-712, a Novel Clk Inhibitor Targeting Myeloid Neoplasms with SRSF2 Mutation. Blood. (2021) 205–206[2]. Zhen Qin, et al. Development of Cdc2-like Kinase 2 Inhibitors: Achievements and Future Directions. J Med Chem. 2021 Sep 23;64(18):13191-13211. [Content Brief]
///////rogocekib, CTX 712, XE88VQP94E
Riselcaftor
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
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
PAT
- Modulators of the Cystic Fibrosis Transmembrane Conductance Regulator Protein and Methods of UsePublication Number: US-2022211692-A1Priority Date: 2021-01-06
- Modulators of the cystic fibrosis transmembrane conductance regulator protein and methods of usePublication Number: WO-2022150174-A1Priority Date: 2021-01-06
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
//////Riselcaftor, 726GWJ6KQQ
Pudafensine
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
- Compound for treatment of erectile dysfunctionPublication Number: WO-2024146892-A1Priority Date: 2023-01-03
- Compound for treatment of painPublication Number: WO-2024089247-A1Priority Date: 2022-10-28
- Compound for treatment of female sexual dysfunctionPublication Number: WO-2024008808-A1Priority Date: 2022-07-08
AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT
join me on Linkedin
Anthony Melvin Crasto Ph.D – India | LinkedIn
join me on Researchgate
RESEARCHGATE
join me on Facebook
Anthony Melvin Crasto Dr. | Facebook
join me on twitter
Anthony Melvin Crasto Dr. | twitter
+919321316780 call whatsaapp
EMAIL. amcrasto@gmail.com
……
//////////Pudafensine, monoamine reuptake inhibitor, erectile dysfunction, neuropathic pain, NS18313, NS 18313, L9NG7US8GE, IP2015, IP 2015
DR ANTHONY MELVIN CRASTO
ORGANIC SPECTROSCOPY
New Drug Approvals 
