Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-01-22
1999-07-27
Gupta, Yogendra N.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514217, 5142328, 514250, 514292, 514309, 540580, 544101, 544345, 546 81, 546 84, 546141, 546143, A61K 3147, C07D21722
Patent
active
059290854
DESCRIPTION:
BRIEF SUMMARY
This invention relates to new amidine and isothiourea derivatives, processes for their preparation, compositions containing them and their use in therapy.
According to the invention we provide a compound of formula (I) ##STR2## wherein: X represents NR.sup.6, S, O, CH.sub.2 or a bond; ring containing 1 to 4 heteroatoms selected from O, N and S optionally substituted at a carbon atom by one or more groups selected from halogen, trifluoromethyl,alkyl C1 to 6, nitro, or cyano; --(CH.sub.2).sub.d OAr or --(CH.sub.2).sub.n Ar; --(CH.sub.2).sub.b OAr or --(CH.sub.2).sub.n Ar; --(CH.sub.2).sub.c OAr or --(CH.sub.2).sub.h Ar; --(CH.sub.2).sub.q OAr, --(CH.sub.2).sub.n Ar, --(CH.sub.2).sub.t COOR.sup.8 or --(CH.sub.2).sub.t CONR.sup.9 R.sup.10 ; represent a chain --(CH.sub.2).sub.m -- or --(CH.sub.2).sub.r Y(CH.sub.2).sub.p --; containing one or two nitrogen atoms, or a five membered heterocyclic aromatic ring containing 1 to 4 heteroatoms selected from O, N and S, which phenyl ring, six membered heterocyclic aromatic ring or five membered heterocyclic aromatic ring may be optionally substituted by one or more groups selected from alkyl C1 to 6, alkoxy C1 to 6, halogen, nitro, cyano, perfluoroalkyl C1 to 6, phenyl or a five membered heterocyclic aromatic ring containing 1 to 4 heteroatoms selected from O, N and S; the range 2 to 4; hydrogen or alkyl C1 to 6; morpholinyl, tetrahydroisoquinolinyl, piperazinyl, or piperazinyl 4-substituted by group R.sup.15 ; from alkyl C1 to 6, alkoxy C1 to 6, halogen, nitro, cyano and trifluoromethyl; R.sup.2, R.sup.3 R and R.sup.5 each represent hydrogen, then R.sup.4 does not represent hydrogen or alkyl C1 to 6; 6; salts thereof.
We prefer that R.sup.1 represents S-methyl or S-ethyl, especially S-ethyl, or a ring containing one heteroatom selected from O, N and S. We particularly prefer that R.sup.1 represents thienyl, especially 2-thienyl. Unless otherwise indicated, the term "alkyl C1 to 6" referred to herein denotes a straight or branched chain alkyl group having from 1 to 6 carbon atoms or a cyclic alkyl group having from 3 to 6 carbon atoms. Examples of such groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, cyclopentyl and cyclohexyl. Unless otherwise indicated, the term "alkyl C1 to 3" referred to herein denotes a straight or branched chain alkyl group having from 1 to 3 carbon atoms. Examples of such groups include methyl, ethyl, n-propyl and i-propyl.
According to the invention, we further provide a process for the preparation of compounds of formula (I), and optical isomers and racemates thereof and pharmaceutically acceptable salts thereof, which comprises: compound of formula (II) ##STR3## wherein X, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined above, with a compound of formula (III) ##STR4## wherein R.sup.1 is as defined above and L is a leaving group; (b) preparing a compound of formula (I) by reacting a corresponding compound of formula (IV) ##STR5## wherein X, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined above and HA is an acid, with a compound of formula (V) by reacting a corresponding compound of formula (VI) ##STR6## wherein X, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined above, with a compound of formula (VII) C1 to 6, --(CH.sub.2).sub.c OH, --(CH.sub.2).sub.c OAr or --(CH.sub.2).sub.n Ar by reacting a corresponding compound of formula (I) in which R.sup.4 represents hydrogen with a compound of formula (VIII) --(CH.sub.2).sub.c OAr or --(CH.sub.2).sub.n Ar and L is a leaving group; R.sup.6 represents alkyl C1 to 6 by reacting a corresponding compound of formula (I) in which R.sup.6 represents hydrogen with a compound of formula (IX) R.sup.4 and R.sup.5 are joined to form a chain --(CH.sub.2).sub.r Y(CH.sub.2).sub.p --, Y represents NR.sup.7 and R.sup.7 represents alkyl C1 to 6 by reacting a corresponding compound of formula (I) in which R.sup.7 represents hydrogen with a compound of formula (IX); --(CH.sub.2).sub.t COOR.sup.8 and R.sup.8 represents alkyl C1 to 6 by esterifying a corresponding compound of formula
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MacDonald James
Matz James
Shakespeare William
Astra Aktiebolag
Gupta Yogendra N.
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