Design, Synthesis, and Pharmacological Evaluation of Second-Generation Soluble Adenylyl Cyclase (sAC, ADCY10) Inhibitors with Slow Dissociation Rates.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
24 11 2022
24 11 2022
Historique:
pubmed:
9
11
2022
medline:
26
11
2022
entrez:
8
11
2022
Statut:
ppublish
Résumé
Soluble adenylyl cyclase (sAC: ADCY10) is an enzyme involved in intracellular signaling. Inhibition of sAC has potential therapeutic utility in a number of areas. For example, sAC is integral to successful male fertility: sAC activation is required for sperm motility and ability to undergo the acrosome reaction, two processes central to oocyte fertilization. Pharmacologic evaluation of existing sAC inhibitors for utility as on-demand, nonhormonal male contraceptives suggested that both high intrinsic potency, fast on and slow dissociation rates are essential design elements for successful male contraceptive applications. During the course of the medicinal chemistry campaign described here, we identified sAC inhibitors that fulfill these criteria and are suitable for
Identifiants
pubmed: 36346696
doi: 10.1021/acs.jmedchem.2c01133
pmc: PMC9866367
mid: NIHMS1865332
doi:
Substances chimiques
Adenylyl Cyclases
EC 4.6.1.1
ADCY10 protein, human
EC 4.6.1.1
Contraceptive Agents, Male
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15208-15226Subventions
Organisme : NICHD NIH HHS
ID : F31 HD105363
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD100549
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061290
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY025810
Pays : United States
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