Pyridazine and pyridazinone derivatives as potent and selective factor XIa inhibitors.

Hu, Zilun; Wang, Cailan; Han, Wei; Rossi, Karen A; Bozarth, Jeffrey M; Wu, Yiming; Sheriff, Steven; Myers, Joseph E; Luettgen, Joseph M; Seiffert, Dietmar A; Wexler, Ruth R; Quan, Mimi L

Hu, Zilun; Wang, Cailan; Han, Wei; Rossi, Karen A; Bozarth, Jeffrey M; Wu, Yiming; Sheriff, Steven; Myers, Joseph E; Luettgen, Joseph M; Seiffert, Dietmar A; Wexler, Ruth R; Quan, Mimi L.

Afiliação

Hu Z; Bristol-Myers Squibb Company, Research and Development, 350 Carter Road, Hopewell, NJ 08540, United States. Electronic address: zilun.hu@bms.com.
Wang C; Bristol-Myers Squibb Company, Research and Development, 350 Carter Road, Hopewell, NJ 08540, United States.
Han W; Bristol-Myers Squibb Company, Research and Development, 350 Carter Road, Hopewell, NJ 08540, United States.
Rossi KA; Bristol-Myers Squibb Company, Research and Development, 350 Carter Road, Hopewell, NJ 08540, United States.
Bozarth JM; Bristol-Myers Squibb Company, Research and Development, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
Wu Y; Bristol-Myers Squibb Company, Research and Development, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
Sheriff S; Bristol-Myers Squibb Company, Research and Development, US Rt. 206 & Province Line Road, Princeton, NJ 08540, United States.
Myers JE; Bristol-Myers Squibb Company, Research and Development, US Rt. 206 & Province Line Road, Princeton, NJ 08540, United States.
Luettgen JM; Bristol-Myers Squibb Company, Research and Development, 311 Pennington-Rocky Hill Road, Pennington, NJ 08543, United States.
Seiffert DA; Bristol-Myers Squibb Company, Research and Development, US Rt. 206 & Province Line Road, Princeton, NJ 08540, United States.
Wexler RR; Bristol-Myers Squibb Company, Research and Development, 350 Carter Road, Hopewell, NJ 08540, United States.
Quan ML; Bristol-Myers Squibb Company, Research and Development, 350 Carter Road, Hopewell, NJ 08540, United States.

Bioorg Med Chem Lett ; 28(6): 987-992, 2018 04 01.

Article em En | MEDLINE | ID: mdl-29501396

ABSTRACT

ABSTRACT

Pyridazine and pyridazinone derivatives were designed and synthesized as coagulation factor XIa inhibitors. Potent and selective inhibitors with single digit nanomolar affinity for factor XIa were discovered. Selected inhibitors demonstrated moderate oral bioavailability.

Assuntos

Fator XIa/antagonistas & inibidores; Piridazinas/farmacologia; Inibidores de Serina Proteinase/farmacologia; Cristalografia por Raios X; Relação Dose-Resposta a Droga; Fator XIa/metabolismo; Humanos; Microssomos Hepáticos/efeitos dos fármacos; Microssomos Hepáticos/metabolismo; Modelos Moleculares; Estrutura Molecular; Piridazinas/síntese química; Piridazinas/química; Inibidores de Serina Proteinase/síntese química; Inibidores de Serina Proteinase/química; Relação Estrutura-Atividade

Palavras-chave

FXIa; Factor XIa inhibitors; Pyridazine; Pyridazinone; Thrombosis

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridazinas / Fator XIa / Inibidores de Serina Proteinase Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2018 Tipo de documento: Article

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