Synthesis of imidazopyridines and purines as potent inhibitors of leukotriene A4 hydrolase.
The synthesis and biological evaluation of a series of heterocyclic analogues of the previously reported LTA(4) hydrolase inhibitor 1b are described. Imidazopyridine and purine analogues are specifically highlighted with several demonstrating excellent potency in our in vitro assays, as well as good oral activity in a mouse ex vivo assay.
Penning
Thomas D
TD
Department of Medicinal Chemistry, Pharmacia Corporation, 4901 Searle Parkway, Skokie, IL 60077, USA. thomas.d.penning@pharmacia.com
Chandrakumar
Nizal S
NS
Desai
Bipin N
BN
Djuric
Stevan W
SW
Gasiecki
Alan F
AF
Malecha
James W
JW
Miyashiro
Julie M
JM
Russell
Mark A
MA
Askonas
Leslie J
LJ
Gierse
James K
JK
Harding
Elizabeth I
EI
Highkin
Maureen K
MK
Kachur
James F
JF
Kim
Suzanne H
SH
Villani-Price
Doreen
D
Pyla
E Yvonne
EY
Ghoreishi-Haack
Nayereh S
NS
Smith
Walter G
WG
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000097:blood; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D051379:Mice; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D011687:Purines; D011725:Pyridines; D011994:Recombinant Proteins; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase