Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-02-21
1998-10-06
Higel, Floyd D.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
548500, 514421, C07D20936, C07D20926, A61K 3140
Patent
active
058178333
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/BP95/03226 filed Aug. 14, 1995.
The present invention relates to novel amide 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. Related compounds have also been disclosed in J Med Chem 1994, 37, 2253. These compounds are said 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 R.sup.1 is hydrogen, halogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, 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, CHO, 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, NR.sup.10 CO.sub.2 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, where R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl and p is 1 to 4; C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkenyl, C.sub.1-6 alkoxy, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, hydroxyC.sub.1-6 alkyl, C.sub.1-6 alkylOC.sub.1-6 alkyl, 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 together with the nitrogen atom to which they are attached form an optionally substituted 5-7-membered heterocyclic ring containing one or two heteroatoms selected from oxygen, nitrogen or sulphur; CR.sup.4 R.sup.5 where R.sup.4 and R.sup.5 are independently hydrogen or C.sub.1-6 alkyl, or A is NR.sup.12 where R.sup.12 is 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.4).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 is hydrogen, halogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, 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, CHO, 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 OR.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, NR.sup.10 CO.sub.2 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, where R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl and p is 1 to 4. Preferably R.sup.1 is hydrogen, cyano, COC.sub.1-6 alkyl, (CH.sub.2).sub.p NR.sup.10 COR.sup.11 or CR.sup.10 .dbd.NOR.sup.11. Most preferably R.sup.1 is hydrogen, cyano, COCH.sub.3, CH.sub.2 NHCOCH.sub.3 or CCH.sub.3 .dbd.NOCH.sub.3.
Suitably 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, hydroxyC.sub.1-6 alkyl, C.sub.1-6 alkylOC.sub.1-6 alkyl, CO.sub.2 R.sup.10, CONR.sup.10 R.sup.11, NR.sup.10 R.sup.11 w
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Clitherow, et al., Journal Of Medicinal Chemistry, vol. 37, No. 15, 1994; pp. 2253-2257.
Dustman Wayne J.
Higel Floyd D.
Kinzig Charles M.
SmithKline Beecham p.l.c.
Venetianer Stephen
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