Calmodulin inhibitory activity of the malbrancheamides and various analogs.
The preparation and biological activity of various structural analogs of the malbrancheamides are disclosed. The impact of indole chlorination, C-12a relative stereochemistry, and bicyclo[2.2.2]diazaoctane core oxidation state on the ability of these analogs to inhibit calmodulin dependent phosphodiesterase (PDE1) was studied, and a number of potent compounds were identified.
Miller
Kenneth A
KA
Department of Chemistry, Colorado State University, 1301 Center Avenue, Fort Collins, CO 80523-1872, USA.
Figueroa
Mario
M
Valente
Meriah W N
MW
Greshock
Thomas J
TJ
Mata
Rachel
R
Williams
Robert M
RM
D000470:Alkaloids / Q000737:chemistry; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D002713:Chlorine / Q000737:chemistry; D002746:Chlorpromazine / Q000737:chemistry; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D010100:Oxygen / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D002147:Calmodulin; D026121:Indole Alkaloids; D007211:Indoles; C529354:malbrancheamide; D002713:Chlorine; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D010100:Oxygen; D002746:Chlorpromazine