May & Baker, Ltd.

Michael P Caton

Edward C Coffee

Gordon L Watkins

Trevor Parker

Gordon Leonard Watkins

Terance W Hart

Barbara Joyce Broughton

Keith A Stuttle

David J Hambling

Helene I Butler

Clive W Bird

Geoffrey Darnbrough

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

Compounds of the general formula: ##STR1## wherein R.sup.1 represents a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms or a phenoxy or benzyl group, and pharmaceutically acceptable salts and esters thereof, possess pharmacological properties of use in the fields of mammalian reproduction and cardiovascular disease.

Bicycloheptane derivatives

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

Tertiary alcohols of the formula: ##STR1## wherein Y.sup.1 represents a carbonyl or hydroxymethylene group, and either

Tertiary alcohols

Cyclopentane derivatives of the formula: ##STR1## wherein R.sup.1 represents hydrogen or a carboxylic acyl group, R.sup.2 represents hydrogen or alkyl of 1 through 12 carbon atoms, and n represents an integer from 4 through 8, are new compounds possessing pharmacological properties, more particularly the production of hypertension and inhibition of gastric acid secretion. They are also useful in the preparation of 10-hydroxyprostaglandins.

Cyclopentane derivatives and their pharmaceutical compositions

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 the R symbols represent hydrogen or alkyl, n represents 4 or 6, and the symbols A, B, X and Y have any one of the following combinations: (a) A represents methylene, B represents hydroxymethylene, X represents ethylene and Y represents hydroxymethylene; (b) A represents carbonyl, B represents methylene, X represents ethylene or trans-vinylene and Y represents hydroxymethylene or carbonyl; or (c) A represents hydroxymethylene, B represents methylene, X represents ethylene or trans-vinylene and Y represents hydroxymethylene) are new compounds, possessing pharmacological properties, in particular, the production of hypotension, bronchodilatation, inhibition of gastric acid secretion and stimulation of uterine contraction.

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.

Cyclopentane derivatives of the formula: ##SPC1## (wherein the R symbols represent hydrogen or alkyl, n represents 4 or 6, and the symbols A, B, X and Y have any one of the following combinations: (a) A represents methylene, B represents hydroxymethylene, X represents ethylene and Y represents hydroxymethylene; (b) A represents carbonyl, B represents methylene, X represents ethylene or trans-vinylene and Y represents hydroxymethylene or carbonyl; or (c) A represents hydroxymethylene, B represents methylene, X represents ethylene or trans-vinylene and Y represents hydroxymethylene) are new compounds, possessing pharmacological properties, in particular, the production of hypotension, bronchodilatation, inhibition of gastric acid secretion and stimulation of uterine contraction.

Growing community of inventors

Upminster, United Kingdom

Michael P Caton