Your browser doesn't support javascript.
loading
Development of a novel tricyclic class of potent and selective FIXa inhibitors.
Meng, Dongfang; Andre, Patrick; Bateman, Thomas J; Berger, Richard; Chen, Yi-Heng; Desai, Kunal; Dewnani, Sunita; Ellsworth, Kenneth; Feng, Daming; Geissler, Wayne M; Guo, Liangqin; Hruza, Alan; Jian, Tianying; Li, Hong; Metzger, Joe; Parker, Dann L; Reichert, Paul; Sherer, Edward C; Smith, Cameron J; Sonatore, Lisa M; Tschirret-Guth, Richard; Wu, Jane; Xu, Jiayi; Zhang, Ting; Campeau, Louis-Charles; Orr, Robert; Poirier, Marc; McCabe-Dunn, Jamie; Araki, Kazuto; Nishimura, Teruyuki; Sakurada, Isao; Hirabayashi, Tomokazu; Wood, Harold B.
Afiliación
  • Meng D; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. Electronic address: dongfang-meng@merck.com.
  • Andre P; Department of Cardiometabolic Disease, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Bateman TJ; Department of Pharmacokinetics, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Berger R; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Chen YH; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Desai K; Department of Cardiometabolic Disease, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Dewnani S; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Ellsworth K; Department of Pharmacology, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Feng D; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Geissler WM; Department of Pharmacology, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Guo L; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Hruza A; Department of Structural Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Jian T; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Li H; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Metzger J; Department of Cardiometabolic Disease, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Parker DL; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Reichert P; Department of Structural Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Sherer EC; Department of Chemistry Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Smith CJ; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Sonatore LM; Department of Pharmacology, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Tschirret-Guth R; Department of Pharmacokinetics, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Wu J; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Xu J; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Zhang T; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Campeau LC; Department of Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Orr R; Department of Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Poirier M; Department of Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • McCabe-Dunn J; Department of Process Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
  • Araki K; Discovery Research, Mochida Pharmaceutical Co., LTD, 7, Yotsuya 1-Chome, Shinjuku-ku, Tokyo 160-8515, Japan.
  • Nishimura T; Discovery Research, Mochida Pharmaceutical Co., LTD, 7, Yotsuya 1-Chome, Shinjuku-ku, Tokyo 160-8515, Japan.
  • Sakurada I; Discovery Research, Mochida Pharmaceutical Co., LTD, 7, Yotsuya 1-Chome, Shinjuku-ku, Tokyo 160-8515, Japan.
  • Hirabayashi T; Discovery Research, Mochida Pharmaceutical Co., LTD, 7, Yotsuya 1-Chome, Shinjuku-ku, Tokyo 160-8515, Japan.
  • Wood HB; Department of Discovery Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.
Bioorg Med Chem Lett ; 25(22): 5437-43, 2015 Nov 15.
Article en En | MEDLINE | ID: mdl-26318999
ABSTRACT
Using structure based drug design, a novel class of potent coagulation factor IXa (FIXa) inhibitors was designed and synthesized. High selectivity over FXa inhibition was achieved. Selected compounds were evaluated in rat IV/PO pharmacokinetic (PK) studies and demonstrated desirable oral PK profiles. Finally, the pharmacodynamics (PD) of this class of molecules were evaluated in thrombin generation assay (TGA) in Corn Trypsin Inhibitor (CTI) citrated human plasma and demonstrated characteristics of a FIXa inhibitor.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diseño de Fármacos / Factor IXa / Inhibidores Enzimáticos / Compuestos Heterocíclicos con 3 Anillos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2015 Tipo del documento: Article
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diseño de Fármacos / Factor IXa / Inhibidores Enzimáticos / Compuestos Heterocíclicos con 3 Anillos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2015 Tipo del documento: Article