May & Baker, Ltd.

Rhone-poulenc Sante

Edward C Coffee

Michael P Caton

Gordon L Watkins

Gordon Leonard Watkins

Terance W Hart

Helene I Butler

Clive W Bird

Geoffrey Darnbrough

The invention provides: (2S,4R,6S)-6-[(4,5-diphenylimidazol-2-yl)thiomethyl]-4-hydroxy-2-methoxy-3 ,4,5,6-tetrahydro-2H-pyran and (2R,4R,6S)-6-[(4,5-diphenylimidazol-2-yl)thiomethyl]-4-hydroxy-2-methoxy-3 ,4,5,6-tetrahydro-2H-pyran or a mixture thereof; the compounds are anti-atherosclerotic agents.

Imidazole derivatives

Prostaglandin analogues of the general formula: ##STR1## (wherein R.sup.1 represents a hydrogen atom or a straight- or branched-chain alkyl group, Y.sup.1 represents a carbonyl or hydroxymethylene group,  represents a single or double bond, A.sup.1 represents an alkylene linkage containing 2 or 3 carbon atoms and optionally bearing a methyl or ethyl substituent, R.sup.2 represents a hydrogen atom or a methyl or ethyl group and R.sup.3 represents a hydrogen atom or else R.sup.2 and R.sup.3 form an alkylene linkage containing 2 or 3 carbon atoms, optionally bearing a methyl or ethyl substituent, such that the symbols A.sup.1, R.sup.2 and R.sup.3, together with the carbon atoms through which they are connected, form a cycloalkyl ring of 6, 7 or 8 carbon atoms, optionally bearing one or two methyl or ethyl substituents, X.sup.1 represents an ethylene or trans-vinylene group, Y.sup.2 represents a carbonyl or hydroxymethylene group, and either (i) A.sup.2 represents a straight- or branched-alkylene chain containing from 1 to 3 carbon atoms, Z.sup.1 represents a direct bond or an oxygen or sulphur atom, and R.sup.4 represents a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, optionally substituted by a cycloalkyl group containing from 3 to 8 carbon atoms, or represents a cycloalkyl group containing from 3 to 8 carbon atoms, or represents a phenyl group optionally substituted by a halogen atom or by a trifluoromethyl group or by a straight- or branched-chain alkyl or alkoxy group containing from 1 to 6 carbon atoms, or (ii) A.sup.2 and Z.sup.1 both represent direct bonds and R.sup.4 represents a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, optionally substituted by a cycloalkyl group containing from 3 to 8 carbon atoms, or represents a cycloalkyl group containing from 3 to 8 carbon atoms) and cyclodextrin clathrates thereof and, when R.sup.1 represents a hydrogen atom, non-toxic salts thereof, possess useful pharmacological properties.

Prostaglandin analogues

Cyclopentane derivatives of the formula: ##STR1## wherein R.sup.1 represents hydrogen or a carboxylic acyl group, and either (i) R.sup.2 represents a group of the formula:

Cyclopentane derivatives

Compounds of the formula: ##STR1## wherein the two side chains are attached to the ring carbon atoms in the trans configuration, have pharmacological properties typical of prostaglandins, and are especially useful for the treatment of gastric ulceration and gastric hyperacidity.

Cyclopentane derivatives of the formula: ##STR1## wherein R.sup.1 represents hydrogen or a carboxylic acyl group, and either (I) R.sup.2 represents a group of the formula:

Cyclopentanone derivatives

Cyclopentane derivatives of the formula: ##STR1## wherein R.sup.1 represents alkyl of 1 through 4 carbon atoms, R.sup.2 represents hydrogen or alkyl of 1 through 3 carbon atoms, R.sup.3 represents alkoxy of 3 through 6 carbon atoms, or alkoxyalkyl in which alkoxy and alkyl moieties each contain 1 through 4 carbon atoms, R.sup.4 represents hydrogen or alkyl of 1 through 12 carbon atoms, R.sup.5 represents hydrogen or alkyl of 1 through 4 carbon atoms or a carboxylic acyl group, A represents carbonyl or a group --CH(OR.sup.5)-- wherein R.sup.5 is as hereinbefore defined, and X represents ethylene or trans-vinylene, possess pharmacological properties, for example the production of hypotension, broncodilation, inhibition of gastric acid secretion, and stimulation of uterine contraction.

Cyclopentane derivatives of the prostaglandin type of the formula: ##SPC1## (wherein R.sup.1 represents hydrogen or lower alkyl, R.sup.2 represents alkyl of 1 to 10 carbon atoms, the symbols R.sup.3 are the same and represent hydrogen, lower alkyl, lower alkenyl, phenyl(lower)alkyl or lower alkanoyl, R.sup.4 represents a carboxy or alkoxycarbonyl group, or an amido group unsubstituted or substituted on the nitrogen atom, X represents vinylene, ethylene, epoxyethylene or cyclopropylene, and n represents an integer of 5 to 8), which possess pharmacological properties in particular the production of hypotension, bronchodilation, inhibition of gastric acid secretion and stimulation of uterine contraction are prepared by a new six-stage process involving initially the reaction of an enamine of a cyclopentanone with an aldehyde to form a 2-hydroxyalkyl-2-cyclopenten-1-one, reacting the cyclopentenone with a source of hydrogen cyanide to form a hydroxyalkyl-3-oxocyclopentane-carbonitrile, reducing the carbonitrile to a 3-hydroxy-2-hydroxyalkyl-cyclopentanecarbaldehyde, reacting the carbaldehyde with an alkanoylmethylenephosphorane to convert the formyl group to ------CH=CH --CO--R.sup.2, oxidising the terminal hydroxymethyl group in the 2-position substituent to carboxy and the ring hydroxy group to oxo, and reducing the two oxo groups in the resulting cyclopentanonealkanoic acid to yield a 2-hydroxy-5-(3-hydroxyalkenyl)cyclopentyl-alkanoic acid, and optionally converting the product into another compound of the foregoing formula.

Growing community of inventors

Upminster, United Kingdom

Edward C Coffee