Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-05-08
2000-12-26
Rotman, Alan L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514326, 546 18, 5483017, 549330, 549331, 549343, 549344, A61K 31445, C07D40114, C07D23702, C07D48720, C07D49304
Patent
active
061660345
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel piperidine 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 antagonlist activity. PCT/EP/95/04889 discloses further 5HT.sub.1D receptor antagonist having a spiropiperidine structure. These compounds are said to be of use in treatment of various CNS disorders. The 5HT.sub.1D.beta. receptor has now been reclassified as the 5HT.sub.1B receptor (P. R. Hartig et al Trends in Pharmacological Science, 1996, 17, 103-105.
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 or N-oxide thereof: ##STR2## in which P.sup.1 and P.sup.2 are independently phenyl, napthyl, a 5 to 7-membered heterocyclic ring selected from the group consisting of thienyl, furyl, pyrrolyl, triazolyl, diazolyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, pyridyl, pyrimidyl and pyrazinyl, or a bicyclic heterocyclic ring selected from the group consisting of include quinoline, isoquinoline, benzofuran and benzothiophene; COC.sub.1-6 alkyl, C.sub.1-6 alkoxy, hydroxy, hydroxyC.sub.1-6 alkyl, hydroxyC.sub.1-6 alkoxy, C.sub.1-6 alkoxyC.sub.1-6 alkoxy, acyl, nitro, trifluoromethyl, cyano, SR.sup.9, SOR.sup.9, SO.sub.2 R.sup.9, SO.sub.2 NR.sup.10 R.sup.11, CO.sub.2 R.sup.10, NR.sup.10 SO.sub.2 R.sup.11, CONR.sup.10 R.sup.11, CO.sub.2 NR.sup.10 R.sup.11, CONR.sup.10 (CH.sub.2).sub.p CO.sub.2 R.sup.11, (CH.sub.2).sub.p NR.sup.10 R.sup.11, (CH.sub.2).sub.p CONR.sup.10 R.sup.11, (CH.sub.2).sub.p NR.sup.10 COR.sup.11, (CH.sub.2).sub.p CO.sub.2 C.sub.1-6 alkyl, CO.sub.2 (CH.sub.2).sub.p OR.sup.10, CONHNR.sup.10 R.sup.11, NR.sup.10 R.sup.11, N.dbd.CNR.sup.9 NR.sup.10 R.sup.11, NR.sup.10 CO.sub.2 R.sup.11, NR.sup.10 CO(CH.sub.2).sub.p NR.sup.10 R.sup.11, NR.sup.10 CONR.sup.10 R.sup.11, CR.sup.10 .dbd.NOR.sup.11, CNR.sup.10 .dbd.NOR.sup.11, or NR.sup.12 COR.sup.13 where R.sup.9, R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl, p is 1 to 4, R.sup.12 is hydrogen, C.sub.1-6 alkyl or together with R.sup.2 ' forms a group (CH.sub.2).sub.q where q is 2, 3 or 4 and R.sup.13 is hydrogen, C.sub.1-6 alkyl or an aryl group; or R.sup.1 is a 5 to 7-membered heterocyclic ring selected from the group consisting of thienyl, furyl, pyrrolyl, triazolyl, diazolyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, pyridyl, pyrimidyl and pyrazinyl optionally substituted by C.sub.1-6 alkyl; C.sub.3-6 cycloalkenyl, C.sub.1-6 alkoxy, hydroxyC.sub.1-6 alkyl, C.sub.1-6 alkylOC.sub.1-6 alkyl, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO.sub.2 R.sup.10, CONR.sup.10 R.sup.11, NR.sup.10 R.sup.11 where R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl, or R.sup.2 and R.sup.3 together form a group --(CH.sub.2).sub.r --R.sup.14 --(CH.sub.2).sub.s -- where R.sup.14 is O, S, CH.sub.2 or NR.sup.15 where R.sup.15 is hydrogen or C.sub.1-6 alkyl and r and s are independently 0, 1 or 2; ##STR3## or a group ##STR4## where B is oxygen or sulphur and D is nitrogen, carbon or a CH group; and C.sub.1-6 alkoxy or halogen, or R.sup.6 together with R.sup.7 forms a group --M-- where M is (CR.sup.16 R.sup.17).sub.t where t is 1, 2 or 3 and R.sup.16 and R.sup.17 are independently hydrogen or C.sub.1-6 alkyl or M is (CR.sup.16 R.sup.17).sub.u -J where u is 0, 1 or 2 and J is oxygen, sulphur, CR.sup.16 .dbd.CR.sup.17, CR.sup.16 .dbd.N, or N.dbd.N; R.sup.20 are independently hydrogen or C.sub.1-6 alkyl or E is S(O).sub.v where v is 0, 1 or 2; independently hydrogen or C.sub.1-6 alkyl; as defined above; and
C.sub.1-6 alkyl groups, whether alone or as part of another group, may be straight chain or branched.
When P.sup.1 and P.sup.2 are bicyclic heterocyclic rings suitable examples include quinoline, isoquinoline, benzofu
REFERENCES:
patent: 5723616 (1998-03-01), Houghton et al.
patent: 5919932 (1999-07-01), Gaster et al.
patent: 5952325 (1999-09-01), Wyman et al.
patent: 5972951 (1999-10-01), Gaster et al.
patent: 5972979 (1999-10-01), Gaster L.
Clitherow, et al., J. Med. Chem; vol. 37, No. 15, 1994, pp. 2253-2257.
Desai Rita
Kanagy James M.
Kinzig Charles M.
Rotman Alan L.
SmithKline Beecham p. l. c
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