109683-67-2Relevant academic research and scientific papers
Design, synthesis, and physicochemical properties of a novel, conformationally restricted 2,3-dihydro-1,3,4-thiadiazole-containing angiotensin converting enzyme inhibitor which is preferentially eliminated by the biliary route in rats
Bennion,Brown,Cook,Manners,Payling,Robinson
, p. 439 - 447 (2007/10/02)
Two novel series of dihydrothiadiazole ring containing inhibitors of angiotensin converting enzyme have been designed and synthesized. The compounds are highly potent enzyme inhibitors and, as a consequence of conformational restriction, chemically stable with respect to undesirable cyclization reactions. The most interesting compound from this series, 5a (FPL 63547), is the monoethyl ester prodrug of the highly potent ''aminocarboxy'' inhibitor 5b (FPL 63674). It produces an antihypertensive effect of long duration in animal models after oral dosing. Unlike other ACE inhibitors, 5b is eliminated almost entirely by biliary clearance in the rat. The favorable pharmacological properties of 5a and 5b are rationalized in terms of their unique physicochemical profiles. The clear preference for biliary clearance seen with 5b is consistent with its lipophilicity and its high degree of net ionization at physiological pH, which results from the very low pK(a) of the C-terminus carboxylic acid function. FPL 63547 is presently undergoing clinical investigation in man.
1,3,4-THIADIAZOLES
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, (2008/06/13)
There are described compounds of formula I, STR1 in which Y is S, O or NR 9,n is 0 or 1,R. sub.9 is hydrogen or alkyl C 1 to 10,R 3 is hydrogen, alkyl C 1 to 10, cycloalkyl C3 to 10, CF 3, SR 10, a 5 or 6 membered heterocyclic group containing one or more S, O or N atoms, NR 4 R 5, phenyl or phenylalkyl C7 to 12, the phenyl, phenylalkyl and heterocyclic groups optionally being fused to a further phenyl group, the heterocyclic group and any phenyl group optionally being substituted by alkyl C 1 to 6, halogen, alkoxy C 1 to 6, nitro, nitrile, CF 3, SR. sub.6, NR 7 R 11 or hydroxy,R 6, R 7 and R 11, which may be the same or different, are each hydrogen or alkyl C 1 to 10,R. sub.4 and R 5, which may be the same or different, are each hydrogen, alkyl C 1 to 10 or phenyl, R 10 is alkyl C 1 to 10, X 1 is S or O, andA is a chain comprising from 2-16 atoms, which chain carries an O or S containing substitutent at a position 2-6 atoms away from the group C=X 1,and pharmaceutically acceptable salts, esters and amides thereof, p1 there are also described method of making the compounds and pharmaceutical formulations, e.g. for the treatment of hypertension, containing them.
