Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-06-20
1999-03-30
McKane, Joseph
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514364, 514210, 514211, 514213, 5142242, 5142305, 514373, 514375, 514412, 540202, 540476, 540552, 540583, 546114, 546115, 546168, 546152, 546131, 546217, 546500, A61K 3147, C07D21512
Patent
active
058890220
DESCRIPTION:
BRIEF SUMMARY
This is a National Stage filing under 37 U.S.C. .sctn. 371 of PCT/EP94/04181, filed Dec. 12, 1994.
The present invention relates to novel indole, indoline and quinoline derivatives, processes for their preparation, and pharmaceutical compositions containing them.
EPA 0 533 266/7/8 disclose a series of benzanilide derivatives which are said to possess 5HT.sub.1D receptor antagonist activity. These compounds are alleged to be of use in the treatment of various CNS disorders such as depression.
A structurally distinct class of compounds have now been discovered and have been found to exhibit 5HT.sub.1D antagonist activity. In a first aspect, the present invention therefore provides a compound of formula (I) or a salt thereof: ##STR2## in which P is a 5-7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkenyl, C.sub.1-6 alkoxy, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO.sub.2 R.sup.9, CONR.sup.10 R.sup.11, NR.sup.10 R.sup.11 where R.sup.9, R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl; or together with the nitrogen atom to which they are attached form an optionally substituted 5- to 7-membered heterocyclic ring containing one or two heteroatoms selected from oxygen, nitrogen or sulphur; R.sup.12 is hydrogen or C.sub.1-6 alkyl, or A is CR.sup.5 =CR.sup.6 or CR.sup.5 R.sup.6 where R.sup.5 and R.sup.6 are independently hydrogen or C.sub.1-6 alkyl; R.sup.14 are independently hydrogen or C.sub.1-6 alkyl or B is (CR.sup.13 R.sup.14).sub.r --D where r is 0, 1, 2 or 3 and D is oxygen, sulphur or CR.sup.13 .dbd.CR.sup.14.
C.sub.1-6 alkyl groups, whether alone or as part of another group, may be straight chain or branched.
Suitably R.sup.1, R.sup.2 and R.sup.3 are independently hydrogen, halogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkenyl, C.sub.1-6 alkoxy, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO.sub.2 R.sup.9, CONR.sup.10 R.sup.11, NR.sup.10 R.sup.11 where R.sup.9, R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl. Preferably R.sup.1 and R.sup.2 are both C.sub.1-6 alkyl, particularly methyl. Preferably R.sup.3 is hydrogen.
Suitably P is a 5 to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur. Examples of suitable heterocyclic rings include thienyl, furyl, pyrrolyl, triazolyl, diazolyl, imnidazolyl, oxadiazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, pyxidyl, pyrimidyl and pyrazinyl. The heterocyclic rings can be linked to the remainder of the molecule via a carbon atom or, when present, a nitrogen atom. Preferably P is oxadiazolyl.
Suitably R.sup.4 is hydrogen, halogen, hydroxy, C.sub.1-6 alkyl or C.sub.1-6 alkoxy. Preferably R.sup.4 is C.sub.1-6 alkoxy such as methoxy. Preferably n is 1.
Suitably R.sup.5 and R.sup.6 are independently hydrogen or C.sub.1-6 alkyl. Preferably R.sup.5 and R.sup.6 are both hydrogen.
Suitably R.sup.7 and R.sup.8 are independently hydrogen, C.sub.1-6 alkyl or aralkyl such as benzyl. Examples of R.sup.7 and R.sup.8 heterocyclic rings include morpholine, piperazine and piperidine. Optional substituents for such rings include C.sub.1-6 alkyl. Preferably R.sup.7 and R.sup.8 are both C.sub.1-6 alkyl, in particular methyl.
Suitably A oxygen, S(O).sub.n where n is 0, 1 or 2, or A is NR.sup.12 where R.sup.12 is hydrogen or C.sub.1-6 alkyl, or A is CR.sup.5 .dbd.CR.sup.6 or CR.sup.5 R.sup.6 where R.sup.5 and R.sup.6 are independently hydrogen or C.sub.1-6 alkyl. Preferably A is oxygen.
Suitably B is (CR.sup.13 R.sup.14).sub.q where q is 2, 3 or 4 and R.sup.13 and R.sup.14 are independently hydrogen or C.sub.1-6 alkyl or B is (CR.sup.13 R.sup.14).sub.r --D where r is 0, 1, 2 or 3 and D is oxygen, sulphur or CR.sup.13 .dbd.CR.sup.14. Preferably R.sup.13 and R.sup.14 are both hydrogen such that the group B forms part of an indole, indoline or tetrahydroquinoline ring.
Suitably m is 1 to 4, preferably m is 1 or 2.
The groups --A(CR.sup.5 R.sup.6).sub.m NR
REFERENCES:
patent: 5354766 (1994-10-01), Naka et al.
Gaster Laramie Mary
Wyman Paul Adrian
Lentz Edward T.
McKane Joseph
Myers, Jr. Richard S.
SmithKline Beecham p.l.c.
Venetianer Stephen
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