Indole- and benzothiophene-based histamine H3 antagonists.
Previous research on histamine H(3) antagonists has led to the development of a pharmacophore model consisting of a central phenyl core flanked by two alkylamine groups. Recent investigation of the replacement of the central phenyl core with heteroaromatic fragments resulted in the preparation of novel 3,5-, 3,6- and 3,7-substituted indole and 3,5-substituted benzothiophene analogs that demonstrate good to excellent hH(3) affinities. Select analogs were profiled in a rat pharmacokinetic model.
Santillan
Alejandro
A
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121-1126, United States.
McClure
Kelly J
KJ
Allison
Brett D
BD
Lord
Brian
B
Boggs
Jamin D
JD
Morton
Kirsten L
KL
Everson
Anita M
AM
Nepomuceno
Diane
D
Letavic
Michael A
MA
Lee-Dutra
Alice
A
Lovenberg
Timothy W
TW
Carruthers
Nicholas I
NI
Grice
Cheryl A
CA
D000818:Animals; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007536:Isomerism; D008958:Models, Molecular; D051381:Rats; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*
D051638:Ether-A-Go-Go Potassium Channels; D054828:Histamine H3 Antagonists; D007202:Indicators and Reagents; D007211:Indoles; D013876:Thiophenes; C088015:benzothiophene