Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-09-21
1997-04-08
Chang, Ceila
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546187, 546193, 546209, 546210, A61K 31445, C07D41310, C07D41710
Patent
active
056188277
DESCRIPTION:
BRIEF SUMMARY
This invention relates to substituted phenylcarbamates and ureas, to processes for their preparation, to pharmaceutical compositions containing them and to their medical use.
European Patent Specification No. EP 0419397 describes compounds of formula ##STR3## wherein R.sup.10 is a group ##STR4## where S is 2 or 3, t is 1 or 2, u is 1 to 3, v is 1-3 and R.sup.40 and R.sup.50 are H, C.sub.1-7 alkyl or C.sub.3-6 cycloalkyl; and wherein R.sup.20 is an oxadiazole, substituted with C.sub.1-8 alkyl, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, C.sub.3-7 cycloalkyl, benzyl, phenyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, amino or alkylamino; or hydrogen or methyl and R.sup.70 is C.sub.1-6 alkyl which may be substituted with C.sub.3-7 cycloalkyl; trifluoromethyl, C.sub.1-6 alkyl or C.sub.1-6 alkoxy.
These compounds are stated to have 5-HT.sub.3 -receptor antagonist activity, anti-emetic activity and/or gastric motility enhancing activity.
The present invention relates to novel compounds which are potent and specific antagonists of 5-hydroxytryptamine (5-HT serotonin).
Thus, the present invention provides substituted phenylcarbamates and ureas of formula (I): ##STR5## wherein R.sup.1 represents a hydrogen or a halogen atom, or a C.sub.1-6 alkyl, C.sub.1-6 alkoxy or hydroxy group; selected from C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, --CH.sub.2 C.sub.2-5 alkenyl, --CH.sub.2 C.sub.2-5 alkynyl, phenyl or benzyl; ##STR6## R.sup.4 represents a group selected from cyano, hydroxyl, C.sub.1-6 alkoxy, phenoxy, C(O)C.sub.1-6 alkyl, C(O)C.sub.6 H.sub.5, CONR.sup.6 R.sup.7, --NR.sup.6 COR.sup.7, --SO.sub.2 NR.sup.6 R.sup.7 or --NR.sup.6 SO.sub.2 R.sup.7 (wherein each of R.sup.6 and R.sup.7 independently represent a hydrogen atom, a C.sub.1-6 alkyl or phenyl group); represents a hydrogen atom, a C.sub.1-6 alkyl or phenyl group); pharmaceutically acceptable salts and solvates thereof.
Suitable pharmaceutically acceptable salts of the compounds of general formula (I) include acid addition salts formed with pharmaceutically acceptable organic or inorganic acids for example, hydrochlorides, hydrobromides, sulphates, alkyl- or arylsulphonates (e.g. methanesulphonates or p-toluenesulphonates), phosphates, acetates, citrates, succinates, tartrates, fumarates and maleates.
Other acids, such as oxalic, while not in themselves pharmaceutically acceptable, may be useful in the preparation of salts useful as intermediates in obtaining the compounds of the invention and their pharmaceutically acceptable acid addition salts. The solvates may, for example, be hydrates.
References hereafter to a compound according to the invention includes both compounds of formula (I) and their quaternary ammonium derivatives, piperidine N-oxides and pharmaceutically acceptable acid addition salts together with pharmaceutically acceptable solvates.
Quaternary ammonium derivatives of compounds of formula (I) are compounds of formula ##STR7## where Q represents C.sub.1-6 alkyl (e.g. methyl).
Piperidine N-oxides of compounds of formula (I) are compounds of formula ##STR8##
The oxadiazole or thiadiazole ring R.sup.2 in the compounds of formula (I) may be a 1,2,4-oxadiazol-5-yl or -3-yl or 1,2,4-thiadiazol-5-yl or -3-yl, i.e. ##STR9## where W is --O-- or --S--.
When the oxadiazole or thiadiazole ring is substituted, the substituent will be attached to the free carbon atom in the oxadiazole or thiadiazole ring.
All optical isomers of compounds of general formula (I) and their mixtures including the racemic mixtures thereof, and all the geometric isomers of compounds of formula (I), are embraced by the invention.
Referring to the general formula (I), a C.sub.1-6 alkyl group may be a straight chain or branched chain alkyl group, for example, methyl, ethyl, propyl, prop-2-yl, butyl, but-2-yl, 2-methylprop-2-yl, pentyl, pent-3-yl or hexyl. A --CH.sub.2 C.sub.2-5 alkenyl group may be, for example, a propenyl or butenyl group. A --CH.sub.2 C.sub.2-5 alkynyl group may be, for example, a prop-2-ynyl group. C.sub.3-7 cycloalkyl may be, for example, cyclopropyl, cyclobutyl or cyclohex
REFERENCES:
patent: 5132309 (1995-01-01), Toth
patent: 5378714 (1995-01-01), Hansen
Reeves et al., Br. J. Pharmacol., 103, 1991, pp. 1067-1072.
Archibald et al., Chemical Abstracts, 93, 11, 15 Sep. 1980, 106809f.
Nilsson et al., Chemical Abstracts, 70, 3, 20 Jan. 1969, 11519x.
Peroutka et al. "the neuropharmacology of serotonin" N.Y. Aca. Sci. 600:104-112 (section of Proutka), 195-196(section of Tyers) (1990).
Gotto, et al. "The role of receptors in biology and medicine" Raven Press, p. 191 (1987).
Clark et al. "Principles of psychopharmacology" Aca. Press, pp. 166-167 (1970).
Burger A. "Medicinal Chemistry" Intersci. Publisher, p. 496 (1960).
Burger A. "Medicineal Chemistry" Wiley Intersci. p. 66, (1971).
Nikolaeva et al. "Derivatives of cyclano[b]pyrrolidinic esters" CA 112:178525u (1990).
Ram et al. "Synthesis and biological activity of certain alkyl 5-alkoxycarbonyl- 1H-benzimidazole- 2-carbamates and related derivatives" J. Med. Chem. 35:539-547 (1992).
Jones et al. "The potential anxiolytic activity of GR38032F . . . " Br. J. Pharmacol. v. 93, 985-993 1988.
Chang Ceila
Glaxo Group Limited
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