Optimising metabolic stability in lipophilic chemical space: The identification of a metabolically stable pyrazolopyrimidine CRF-1 receptor antagonist
摘要:
Balancing potency and metabolic stability in a target which favours lipophilic ligands is a considerable challenge. Here we describe two strategies employed to achieve this balance in a series of pyrazolopyrimidine CRF antagonists: moderation of lipophilicity, and incorporation of a metabolically stable lipophilic group. (c) 2009 Elsevier Ltd. All rights reserved.
Fischer indole cyclization has recently been described as an efficient approach to the synthesis of azaindoles bearing electron-donating groups. We now show that this cascade reaction can be very efficient for the formation of a wider range of 4- and 6-azaindoles by using microwave irradiation.
Optimising metabolic stability in lipophilic chemical space: The identification of a metabolically stable pyrazolopyrimidine CRF-1 receptor antagonist
作者:Duncan C. Miller、Wolfgang Klute、Andrew Calabrese、Alan D. Brown
DOI:10.1016/j.bmcl.2009.09.016
日期:2009.11
Balancing potency and metabolic stability in a target which favours lipophilic ligands is a considerable challenge. Here we describe two strategies employed to achieve this balance in a series of pyrazolopyrimidine CRF antagonists: moderation of lipophilicity, and incorporation of a metabolically stable lipophilic group. (c) 2009 Elsevier Ltd. All rights reserved.