Novel imidazole-based histamine H3 antagonists.
A novel series of imidazole containing histamine H(3) receptor ligands were investigated and found to be potent functional antagonists. After improving the stability of these molecules towards liver microsomes, these compounds were found to have no appreciable affinity for CYP P450s. Subsequent in vivo experiments showed significant brain uptake of (4-chloro-phenyl)-[2-(1-isopropyl-piperidin-4-ylmethoxy)-3-methyl-3H-imidazol-4-yl]-methanone 22.
Jablonowski
Jill A
JA
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA. jjablono@its.jnj.com
Ly
Kiev S
KS
Bogenstaetter
Michael
M
Dvorak
Curt A
CA
Boggs
Jamin D
JD
Dvorak
Lisa K
LK
Lord
Brian
B
Miller
Kirsten L
KL
Mazur
Curt
C
Wilson
Sandy J
SJ
Lovenberg
Timothy W
TW
Carruthers
Nicholas I
NI
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008024:Ligands; D008956:Models, Chemical; D011485:Protein Binding; D051381:Rats; D013329:Structure-Activity Relationship
D054828:Histamine H3 Antagonists; D007093:Imidazoles; D008024:Ligands