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The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors.
Cox, Jason M; Chu, Hong D; Kuethe, Jeffrey T; Gao, Ying-Duo; Scapin, Giovanna; Eiermann, George; He, Huaibing; Li, Xiaohua; Lyons, Kathryn A; Metzger, Joseph; Petrov, Aleksandr; Wu, Joseph K; Xu, Shiyao; Sinha-Roy, Ranabir; Weber, Ann E; Biftu, Tesfaye.
Afiliación
  • Cox JM; Department of Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: jason_cox@merck.com.
  • Chu HD; Department of Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Kuethe JT; Department of Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Gao YD; Department of Structural Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Scapin G; Department of Structural Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Eiermann G; Department of Pharmacology, Screening & Protein Sciences, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • He H; Department of PPDM, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Li X; Department of PPDM, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Lyons KA; Department of PPDM, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Metzger J; Department of Cardiometabolic Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Petrov A; Department of Pharmacology, Screening & Protein Sciences, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Wu JK; Department of Cardiometabolic Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Xu S; Department of PPDM, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Sinha-Roy R; Department of Cardiometabolic Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Weber AE; Department of Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Biftu T; Department of Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Bioorg Med Chem Lett ; 26(11): 2622-6, 2016 06 01.
Article en En | MEDLINE | ID: mdl-27106708
ABSTRACT
Novel potent and selective 5,6,5- and 5,5,6-tricyclic pyrrolidine dipeptidyl peptidase IV (DPP-4) inhibitors were identified. Structure-activity relationship (SAR) efforts focused on improving the intrinsic DPP-4 inhibition potency, increasing protease selectivity, and demonstrating clean ion channel and cytochrome P450 profiles while trying to achieve a pharmacokinetic profile suitable for once weekly dosing in humans.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pirrolidinas / Dipeptidil Peptidasa 4 / Inhibidores de la Dipeptidil-Peptidasa IV / Descubrimiento de Drogas Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2016 Tipo del documento: Article
Texto completo
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PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pirrolidinas / Dipeptidil Peptidasa 4 / Inhibidores de la Dipeptidil-Peptidasa IV / Descubrimiento de Drogas Límite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2016 Tipo del documento: Article