Discovery of Two Novel Antiplatelet Clinical Candidates (BMS-986120 and BMS-986141) That Antagonize Protease-Activated Receptor 4.

Benzofurans Blood Platelets Humans Imidazoles Morpholines Platelet Aggregation Receptor, PAR-1 Receptors, Thrombin Thiazoles Thrombin Thrombosis / drug therapy

Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
14 07 2022
Historique:
pubmed: 23 6 2022
medline: 16 7 2022
entrez: 22 6 2022
Statut: ppublish

Résumé

Protease-activated receptor 4 (PAR4) is a G-protein coupled receptor that is expressed on human platelets and activated by the coagulation enzyme thrombin. PAR4 plays a key role in blood coagulation, and its importance in pathological thrombosis has been increasingly recognized in recent years. Herein, we describe the optimization of a series of imidazothiadiazole PAR4 antagonists to a first-in-class clinical candidate, BMS-986120 (

Identifiants

DOI: 10.1021/acs.jmedchem.2c00359 PMID: 35729784
pubmed: 35729784
doi: 10.1021/acs.jmedchem.2c00359
doi:

Substances chimiques

BMS-986120 0
Benzofurans 0
Imidazoles 0
Morpholines 0
Receptor, PAR-1 0
Receptors, Thrombin 0
Thiazoles 0
Thrombin EC 3.4.21.5
protease-activated receptor 4 JWE1M73YZN

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

8843-8854

Auteurs

E Scott Priestley (ES)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.
ORCID: 0000-0001-8390-1143

Jacques Banville (J)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Daniel Deon (D)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Laurence Dubé (L)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Marc Gagnon (M)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Julia Guy (J)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Philippe Lapointe (P)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Jean-François Lavallée (JF)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Alain Martel (A)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Serge Plamondon (S)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Roger Rémillard (R)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Edward Ruediger (E)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

François Tremblay (F)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Shana L Posy (SL)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.

Victor R Guarino (VR)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.

Jeremy M Richter (JM)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.
ORCID: 0000-0002-8313-7154

Jianqing Li (J)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.
ORCID: 0000-0002-8445-9796

Anuradha Gupta (A)

Department of Discovery Synthesis, Biocon Bristol-Myers Squibb R&D Centre, Syngene International Ltd., Biocon Park, Plot No. 2 & 3, Bommasandra-Jigani Road, Bangalore560099, India.
ORCID: 0000-0002-4211-1441

Muthalagu Vetrichelvan (M)

Department of Discovery Synthesis, Biocon Bristol-Myers Squibb R&D Centre, Syngene International Ltd., Biocon Park, Plot No. 2 & 3, Bommasandra-Jigani Road, Bangalore560099, India.
ORCID: 0000-0001-7201-4143

T J Balapragalathan (TJ)

Department of Discovery Synthesis, Biocon Bristol-Myers Squibb R&D Centre, Syngene International Ltd., Biocon Park, Plot No. 2 & 3, Bommasandra-Jigani Road, Bangalore560099, India.

Arvind Mathur (A)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.

Ji Hua (J)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.

Mario Callejo (M)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Jocelyne Guay (J)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

Chi Shing Sum (CS)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.

Mary Ellen Cvijic (ME)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.

Carol Watson (C)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.

Pancras Wong (P)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.

Jing Yang (J)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.

Michel Bouvier (M)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.
Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QuébecH3C 3J7, Canada.
ORCID: 0000-0003-1128-0100

David A Gordon (DA)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.

Ruth R Wexler (RR)

Bristol-Myers Squibb Research & Early Development, 3551 Lawrenceville Road, Princeton, New Jersey08540, United States.

Anne Marinier (A)

Institute for Research in Immunology and Cancer, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.
Department of Chemistry and Department of Pharmacology, Université de Montréal, P.O. Box 6128, Downtown Station, Montréal, QuébecH3C 3J7, Canada.

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Classifications MeSH

questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Benzofuranes › Discovery of Two Novel Antiplatelet Clinical...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Sang › Cellules sanguines › Plaquettes › Discovery of Two Novel Antiplatelet Clinical...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Discovery of Two Novel Antiplatelet Clinical...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Imidazoles › Discovery of Two Novel Antiplatelet Clinical...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Oxazines › Morpholines › Discovery of Two Novel Antiplatelet Clinical...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hémostase › Activation plaquettaire › Agrégation plaquettaire › Discovery of Two Novel Antiplatelet Clinical...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs activés par la protéinase › Récepteurs à la thrombine › Récepteur de type PAR-1 › Discovery of Two Novel Antiplatelet Clinical...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs activés par la protéinase › Récepteurs à la thrombine › Discovery of Two Novel Antiplatelet Clinical...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Thiazoles › Discovery of Two Novel Antiplatelet Clinical...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Thrombine › Discovery of Two Novel Antiplatelet Clinical...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Embolie et thrombose › Thrombose › Discovery of Two Novel Antiplatelet Clinical...