Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-10-07
1999-07-06
Higel, Floyd D.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
514299, 514304, 514361, 546121, 546126, 548131, A61K 3146, A61K 3147, C07D45106, C07D45104
Patent
active
059199326
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel amide derivatives, processes for their preparation, and pharmaceutical compositions containing them.
J. Med. Chem., vol 37, 1984, 2253-57, EPA 0 533 266/7/8, WO94/15920, WO95/04729, WO95/06637, WO95/06644, WO95/06044, WO95/26328, WO95/06079, GBA-2 276 160, GBA-2 276 162, GBA-2 276 164 and GBA-2 273 930 all disclose a series of benzanilide derivatives which are said to possess 5HT.sub.1D receptor antagonist activity. These compounds are said to be of use in the treatment of various CNS disorders.
A structurally distinct class of compounds have now been discovered and have been found to exhibit 5HT.sub.1D receptor antagonist activity. In a first aspect, the present invention therefore provides a compound of formula (I) or a salt or N-oxide thereof: ##STR1## 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, 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.a CO.sub.2 R.sup.11, (CH.sub.2).sub.a NR.sup.10 R.sup.11, (CH.sub.2).sub.a CONR.sup.10 R.sup.11, (CH.sub.2).sub.a NR.sup.10 COR.sup.11, (CH.sub.2).sub.a CO.sub.2 C.sub.1-6 alkyl, CO.sub.2 (CH.sub.2).sub.a 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 CO(CH.sub.2).sub.a 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, where R.sup.9, R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl and a is 1 to 4 or R.sup.1 is an optionally substituted 5 to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur; C.sub.3-6 cycloalkyl, 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; hydroxy, C.sub.1-6 alkyl or C.sub.1-6 alkoxy or R.sup.4 and R.sup.5 together form a group --A-- where A is (CR.sup.12 R.sup.13).sub.q where q is 2, 3 or 4 and R.sup.12 and R.sup.13 are independently hydrogen or C.sub.1-6 alkyl or A is (CR.sup.12 R.sup.13).sub.r --D where r is 0, 1, 2 or 3 and D is oxygen, sulphur or CR.sup.12 .dbd.CR.sup.13 ; nitrogen atom and optionally a further heteroatom selected from from oxygen, nitrogen or sulphur.
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, 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.a CO.sub.2 R.sub.11, (CH.sub.2).sub.a NR.sup.10 R.sup.11, (CH.sub.2).sub.a CONR.sup.10 R.sup.11, (CH.sub.2).sub.a NR.sup.10 COR.sup.11, (CH.sub.2).sub.a CO.sub.2 C.sub.1-6 alkyl, CO.sub.2 (CH.sub.2).sub.a 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 CO(CH.sub.2).sub.a 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, where R.sup.9, R.sup.10 and R.sup.11 are independently hydrogen or C.sub.1-6 alkyl and a is 1 to 4.
When R.sup.1 is an optionally substituted 5 to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur, suitable heterocyclic rings include thienyl, furyl, pyrrolyl, triazolyl, diazolyl, imidazolyl, oxadiazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, pyridyl, pyrimidyl and pyrazinyl. The heteroc
REFERENCES:
patent: 5124460 (1992-06-01), Humphrey
patent: 5132316 (1992-07-01), Hadley et al.
patent: 5138064 (1992-08-01), Murata et al.
patent: 5326776 (1994-07-01), Winn et al.
J. Med. Chem., Clitherow, et al., vol. 37, No. 15, 1994, pp. 2253-2257.
P. Saxena, Pharmoc. Ther; 1995, vol. 66, pp. 339-368.
Gaster Laramie Mary
Mulholland Keith Raymond
Dustman Wayne J.
Higel Floyd D.
King William T.
Kinzig Charles M.
SmithKline Beecham p.l.c.
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