Pyrrolidine and piperidine analogues of SC-57461A as potent, orally active inhibitors of leukotriene A4 hydrolase

Bioorganic and Medicinal Chemistry Letters

Volumn 12, Issue 23, 2002, Pages 3383-3386

  Penning, Thomas D ^a   Chandrakumar, Nizal S ^a   Desai, Bipin N ^a   Djuric, Stevan W ^a   Gasiecki, Alan F ^a   Liang, Chi Dean ^a   Miyashiro, Julie M ^a   Russell, Mark A ^a   Askonas, Leslie J ^a   Gierse, James K ^a   Harding, Elizabeth I ^a   Highkin, Maureen K ^a   Kachur, James F ^a   Kim, Suzanne H ^a   Villani Price, Doreen ^a   Pyla, E Yvonne ^a   Ghoreishi Haack, Nayereh S ^a   Smith, Walter G ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HYDROLASE INHIBITOR; LEUKOTRIENE A4 HYDROLASE; PYRROLIDINE DERIVATIVE; SC 56938; SC 57461A; UNCLASSIFIED DRUG; BETA ALANINE; DRUG DERIVATIVE; ENZYME INHIBITOR; EPOXIDE HYDROLASE; PIPERIDINE DERIVATIVE; SC 57461; SC56938;

ANIMAL EXPERIMENT; ARTICLE; CHROMATOGRAPHY; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; HUMAN; IC 50; IN VITRO STUDY; MOUSE; NONHUMAN; SUBSTITUTION REACTION; ANIMAL; CHEMISTRY; DRUG ANTAGONISM; ORAL DRUG ADMINISTRATION; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; BETA-ALANINE; ENZYME INHIBITORS; EPOXIDE HYDROLASES; HUMANS; INHIBITORY CONCENTRATION 50; MICE; PIPERIDINES; PYRROLIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 18644372612     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(02)00760-6     Document Type: Article

References (7)

1. Penning T.D. Curr. Pharm. Des. 7:2001;163.
2. Penning T.D., Chandrakumar N.S., Chen B.B., Chen H.Y., Desai B.N., Djuric S.W., Docter S.H., Gasiecki A.F., Haack R.A., Miyashiro J.M., Russell M.A., Yu S.S., Corley D.G., Durley R.C., Kilpatrick B.F., Parnas B.L., Askonas L.J., Gierse J.K., Harding E.I., Highkin M.K., Kachur J.F., Kim S.H., Krivi G.G., Villani-Price D., Pyla E.Y., Smith W.G., Ghoreishi-Haack N.S. J. Med. Chem. 43:2000;721.
3. Penning T.D., Russell M.A., Chen B.B., Chen H.Y., Liang C.D., Mahoney M.W., Malecha J.W., Miyashiro J.M., Yu S.S., Askonas L.J., Gierse J.K., Harding E.I., Highkin M.K., Kachur J.F., Kim S.H., Villani-Price D., Pyla E.Y., Ghoreishi-Haack N.S., Smith W.G. J. Med. Chem. 45:2002;3482.
4. Askonas L.J., Kachur J.F., Villani-Price D., Liang C.D., Russell M.A., Smith W.G. J. Pharmacol. Exp. Ther. 300:2002;577.
5. Kachur J.F., Askonas L.J., Villani-Price D., Ghoreishi-Haack N., Won-Kim S., Liang C.D., Russell M.A., Smith W.G. J. Pharmacol. Exp. Ther. 300:2002;583.
6. Pharmacokinetic data is available for 2, which had an oral bioavailability of 25% and a half-life of 1.1 h in mouse. However, the pharmacodynamic half-life as demonstrated in the mouse ex vivo assay exceeded 24 h, possibly due to its extensive distribution.
7. Askonas, L. J.; Kachur, J. F.; Villani-Price, D.; Harding, E. I.; Pyla, E. Y.; Highkin, M. K.; Liang, D. C.; Desai, B. N.; Russell, M. A.; Smith, W. G. 8th International Congress of the Inflammation Research Association, Hersey, PA, 1996; Abstract 84.