Discovery of ((1S,3R)-1-isopropyl-3-((3S,4S)-3-methoxy-tetrahydro-2H-pyran-4-ylamino)cyclopentyl)(4-(5-(trifluoromethyl)pyridazin-3-yl)piperazin-1-yl)methanone, PF-4254196, a CCR2 antagonist with an improved cardiovascular profile.
Bioorg Med Chem Lett
; 21(9): 2626-30, 2011 May 01.
Article
en En
| MEDLINE
| ID: mdl-21315584
ABSTRACT
We describe the systematic optimization, focused on the improvement of CV-TI, of a series of CCR2 antagonists. This work resulted in the identification of 10 (((1S,3R)-1-isopropyl-3-((3S,4S)-3-methoxy-tetrahydro-2H-pyran-4-ylamino)cyclopentyl)(4-(5-(trifluoromethyl)pyridazin-3-yl)piperazin-1-yl)methanone) which possessed a low projected human dose 35-45mg BID and a CV-TI=3800-fold.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Piperazinas
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Piridazinas
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Modelos Moleculares
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Receptores CCR2
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Antiinflamatorios
Límite:
Humans
Idioma:
En
Año:
2011
Tipo del documento:
Article