Home
Resources
Publications
Synthesis, Structure-Activity Relationships, and Pharmacokinetic Properties of Dihydroorotate Dehydrogenase Inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4'-(trifluoromethyl)phenyl ] Propenamide and Related Compounds

Synthesis, Structure-Activity Relationships, and Pharmacokinetic Properties of Dihydroorotate Dehydrogenase Inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4'-(trifluoromethyl)phenyl ] Propenamide and Related Compounds

E A Kuo, P T Hambleton, D P Kay, P L Evans, S S Matharu, E Little, N McDowall, C B Jones, C J Hedgecock, C M Yea, A W Chan, P W Hairsine, I R Ager, W R Tully, R A Williamson, R Westwood

J Med Chem. 1996 Nov 8;39(23):4608-21.

PMID: 8917650

Abstract:

The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in vitro DHODH potency. The most promising compound (3) has shown activity in rat and mouse collagen (II)-induced arthritis models (ED50 = 2 and 31 mg/kg, respectively) and has shown a shorter half-life in man when compared with leflunomide. Clinical studies in rheumatoid arthritis are in progress.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP455141-A	Leflunomide Related Compound A		455-14-1	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: