| Identification | Back Directory | [Name]
Benzamide, 4-[4-[[[6-methoxy-2-(2-methoxyimidazo[2,1-b]-1,3,4-thiadiazol-6-yl)-4-benzofuranyl]oxy]methyl]-2-thiazolyl]-N,N-dimethyl- | [CAS]
1478711-48-6 | [Synonyms]
BMS-986141
Benzamide, 4-[4-[[[6-methoxy-2-(2-methoxyimidazo[2,1-b]-1,3,4-thiadiazol-6-yl)-4-benzofuranyl]oxy]methyl]-2-thiazolyl]-N,N-dimethyl- | [Molecular Formula]
C27H23N5O5S2 | [MOL File]
1478711-48-6.mol | [Molecular Weight]
561.63 |
| Hazard Information | Back Directory | [Uses]
BMS-98614 is an orally active, selective thrombin receptor protease-activated receptor-4 (PAR-4) antagonist with an IC50 value of 0.4 nM. BMS-98614 has excellent antithrombotic effect[1][2]. | [in vivo]
BMS-986141 (compound 49) shows a slight but significant prolongation of KBT (kidney bleeding time) and demonstrates excellent anti-thrombotic efficacy at 0.5 mg/kg in cynomolgus monkey[1][2].
| Animal Model: | Monkey arterial thrombosis (AT) and mesenteric bleeding time (MBT) models[2] | | Dosage: | 0.05, 0.1, 0.5 mg/kg | | Administration: | p.o., 2 hours | | Result: | Inhibited PAR4-AP-induced platelet aggregation in human and monkey blood with IC50 of 1.8 and 1.3 nM, respectively.
Reduced the thrombus weight by 36%, 63% and 88% at concentrations of 0.05, 0.1 and 0.5 mg/kg, respectively in AT model.
Increased MBT by 1.2 times.
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| Animal Model: | Rat, dog and monkey[1] | | Dosage: | 0.5, 1, 2 mpk | | Administration: | i.v., 0.5 mpk, 10 min or p.o., 2 mpk for rat, 1 mpk for dog and monkey | | Result: | The pharmacokinetic parameters of BMS-986141 (compound 49)
| Parameters | rat | dog | monkey | | t1/2(h) | 3.7 ± 0.4 | 13 | 75 ± 12 | | CL (mL/min/kg) | 14.3 ± 0.4 | 8.5 | 12 ± 2 | | Vss(L/kg) | 2.7 ± 0.3 | 2.7 | 14 ± 5 | | F (%) | 31 | 25 | 36 | |
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| [IC 50]
PAR4: .4 nM (IC50) | [References]
[1] E Scott Priestley, et al. Discovery of Two Novel Antiplatelet Clinical Candidates (BMS-986120 and BMS-986141) That Antagonize Protease-Activated Receptor 4. J Med Chem. 2022 Jul 14;65(13):8843-8854. DOI:10.1021/acs.jmedchem.2c00359
[2] P Wong, et al. Favorable therapeutic index of an orally-active small-molecule antagonist of the platelet protease-activated receptor-4, BMS-986141, compared with the P2Y12 antagonist ticagrelor in cynomolgus monkeys. European Heart Journal, Volume 41, Issue Supplement_2, November 2020. |
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| Company Name: |
BOC Sciences
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| Tel: |
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| Website: |
https://www.bocsci.com |
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