Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-02-02
1998-11-10
Bernhardt, Emily
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
5142358, 514255, 544121, 544357, 544364, 544366, 544370, 544371, 544365, 544379, 544393, A61K 31495, C07D40714, C07D40914, C07D295155
Patent
active
058344713
DESCRIPTION:
BRIEF SUMMARY
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. These compounds are alleged 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 antagonist activity. In a first aspect, the present invention therefore provides a compound of formula (I) or a salt thereof: ##STR1## in which P is a phenyl or a 5 or 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from oxygen, nitrogen or sulphur, substituted phenyl or an optionally substituted 5-7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur, trifluoromethyl or cyano;
C.sub.1-6 alkyl groups, whether alone or as part of another group, may be straight chain or branched.
Suitably P is a phenyl or a 5 or 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from oxygen, nitrogen or sulphur. Examples of rings P include pyridyl, thienyl, furyl and pyrrolyl rings. Preferably P is phenyl, thienyl, furyl or pyridyl.
Suitably R.sup.1 is halogen, C.sub.1-6 alkyl, C.sub.1-6 cycloalkyl, optionally substituted phenyl or an optionally substituted 5-7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur. The group R.sup.1 can be an aromatic or saturated heterocyclic ring. When R.sup.1 is an aromatic heterocyclic ring, examples of such rings include pyridyl, thienyl, furyl, pyrrolyl, oxadiazolyl, pyrazolyl, triazolyl, diazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, pyrimidyl and pyrazinyl. When R.sup.1 is a saturated ring examples include piperidine, morpholine and piperazine rings. Optional substituents for R.sup.1 include halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, hydroxy, cyano, nitro, amino, CO.sub.2 R.sup.5 where R.sup.5 is hydrogen or C.sub.1-6 alkyl or CONR.sup.6 R.sup.7 where R.sup.6 and R.sup.7 are independently hydrogen or C.sub.1-6 alkyl.
Preferably R.sup.1 is halogen, butyl, cyclohexyl, pyridyl, pyrazolyl, triazolyl, imidazolyl, morpholinyl, piperazinyl or thienyl.
Suitably R.sup.2 is hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy or nitro. Preferably R.sup.2 is hydrogen, C.sub.1-6 alkoxy, for example methoxy, C.sub.1-6 alkyl, for example methyl, or nitro.
Suitably R.sup.3 is hydrogen, halogen, hydroxy, C.sub.1-6 alkyl or C.sub.1-6 alkoxy. Preferably R.sup.3 is C.sub.1-6 alkoxy such as methoxy.
Preferably n is 1 and the group R.sup.3 is para to the amide linkage.
Suitably R.sup.4 is hydrogen or C.sub.1-6 alkyl. Preferably R.sup.4 is C.sub.1-6 alkyl such as methyl.
Particularly preferred compounds include: mide, mide, boxamide, oxamide, hene-4-carboxamide, boxamide, benzamide, benzamide, zamide, robenzamide, -1-yl)benzamide, pharmaceutically acceptable salt thereof.
Preferred salts of the compounds of formula (I) are pharmaceutically acceptable salts. These include acid addition salts such as hydrochlorides, hydrobromides, phosphates, acetates, fumarates, maleates, tartrates, citrates, oxalates, methanesulphonates and p-toluenesulphonates.
Certain compounds of formula (I) are capable of existing in steroisomeric forms. It will be understood that the invention encompasses all geometric and optical isomers of the compounds of formula (I) and the mixtures thereof including racemates. Tautomers of compounds of formula (I) and mixtures thereof also form an aspect of the invention.
In a further aspect the present invention provides a process for the preparation of a compound of formula (I) which comprises.
(a) reaction of a compound of formula (II): ##STR2## in which R.sup.1, R.sup.2 and P are as defined in formula (I) and L is a leaving group, with a compound of formula (III): ##STR3## in which R.sup.3, R.sup.4 and n are as defined in formula (I);
(b) for compounds of formula (I) in which R.sup.1 is a phenyl or heteroc
REFERENCES:
patent: 5340810 (1994-08-01), Clitherow et al.
patent: 5356893 (1994-10-01), Bradshaw et al.
John W. Clitherow, et al., "Evolution of a Novel Series of Selective 5-HT1D Antagonists", Journal of Medicinal Chemistry, vol. 37, No. 15, pp. 2253-2257 (Jul. 22, 1994).
Saxena et al.. Pharmac. Ther.vol.66,p.339-368, 1995.
Duckworth David Malcolm
Jenkins Sarah Margaret
Jennings Andrew John
Bernhardt Emily
Dustman Wayne J.
Kinzig Charles M.
SmithKline Beecham p.l.c.
Venetianer Stephen
LandOfFree
Amide derivatives as 5HT.sub.1D receptor antagonists does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Amide derivatives as 5HT.sub.1D receptor antagonists, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Amide derivatives as 5HT.sub.1D receptor antagonists will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1517003