Orally bioavailable, indole-based nonpeptide GnRH receptor antagonists with high potency and functional activity
| Autor: | Mark T. Goulet, Rosemary Sisco, Xiaolan Shen, Jisong Cui, An-Hua Mao, Bindhu V. Karanam, Kang Cheng, Gerard R. Kieczykowski, Tsuei-Ju Wu, Kathryn A. Lyons, Rena Ning Ren, Stella H. Vincent, George R. Mount, Yi Tien Yang, Josephine R. Carlin, Wallace T. Ashton, Joel B. Yudkovitz |
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| Rok vydání: | 2001 |
| Předmět: |
Indoles
Stereochemistry medicine.drug_class Clinical Biochemistry Pharmaceutical Science Administration Oral Biological Availability Carboxamide Biochemistry Chemical synthesis Structure-Activity Relationship Dogs Oral administration Drug Discovery medicine Moiety Animals Molecular Biology Indole test Bicyclic molecule Chemistry Organic Chemistry Antagonist Luteinizing Hormone Macaca mulatta Tryptamines Bioavailability Rats Models Animal Molecular Medicine Receptors LHRH |
| Zdroj: | Bioorganicmedicinal chemistry letters. 11(19) |
| ISSN: | 0960-894X |
| Popis: | Stereospecific introduction of a methyl group to the indole-3-side chain enhanced activity in our tryptamine-derived series of GnRH receptor antagonists. Further improvements were achieved by variation of the bicyclic amino moiety of the tertiary amide and by adjustment of the tether length to a pyridine or pyridone terminus. These modifications culminated in analogue 24, which had oral activity in a rat model and acceptable oral bioavailability and half-life in dogs and monkeys. |
| Databáze: | OpenAIRE |
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