The Boots Company Plc

Kenneth J Nichol

Antonin Kozlik

David M Weighton

John C Kerry

Maurice W Baker

John R Marshall

Roy V Davies

James Fraser

Malcolm F Sim

David L Roberts

Kenneth Barron

Lachlan MacLean

Albert E Harrison

James Edward Jeffery

Bruce Jeremy Sargent

John R Housley

Norman William Bristow

David B Yates

Raymond Parkinson

Peter E Macey

Therapeutic 1,4-thiazepines

A process to prepare compounds of formula I ##STR1## in which n=0, 1 or 2 comprising the cyclization of compounds of formula II ##STR2## in which n=0, 1 or 2. The cyclization may be effected in the presence of an organic or inorganic base or thermally at a temperature in the range 40.degree.-160.degree. C. Compounds of formula II and certain analogues thereof are disclosed as cardiovascular agents.

Chemical process

Process for the preparation of 1-methyl-3-methylthio-4-quinolone and the

Quinolones with antihypertensive activity have the general formula I, ##STR1## wherein X is the residue of an optionally substituted benzene ring; R is lower alkyl; R.sub.3 is hydrogen or lower alkyl; R.sub.1 and R.sub.2, which may be the same or different, are hydrogen, lower alkyl, or, together with the nitrogen atom to which they are attached, form a 5 to 7 membered saturated heterocyclic ring optionally containing an additional hetero atom selected from nitrogen, oxygen and sulphur and optionally substituted by 1 or more lower alkyl groups; and the dotted line between positions 2 and 3 of the quinolone nucleus represents an optional bond. The compounds are useful as antihypertensive agents. They are also indicated for use in treating heart failure and ischaemic heart disease. With the exception of the three compounds 1-methyl-4-oxo-1,4-dihydroquinoline-3-sulphonamide, 1,N-dimethyl-4-oxo-1,4-dihydroquinoline-3-sulphonamide and 6,7-dimethoxyl-methyl-4-oxo-1,4-dihydroquinoline-3-sulphonamide, the quinolones of formula I are novel. Pharmaceutical compositions containing the compounds of formula I are described. Processes for preparing the novel quinolones are also described.

Quinolone sulphonamides useful as antihypertensive agents

Compositions which contain a quinolone compound of the general formula ##STR1## wherein n is 0, 1 or 2; R.sub.1 is lower alkyl optionally substituted by hydroxy or C.sub.1-4 alkoxycarbonyl; allyl; propynyl or phenyl- lower alkyl in which the phenyl ring is optionally substituted by 1 or 2 C.sub.1-4 alkoxy groups; R.sub.2 is C.sub.1-4 alkyl with the proviso that when n is 0, R.sub.2 is methyl; and R.sub.3, R.sub.4 and R.sub.5, which may be the same or different, are hydrogen, lower alkyl, lower alkoxy, lower alkanoyl, halo, trifluoromethyl or lower alkylthio show antihypertensive activity. Compounds of general formula ##STR2## in which n, R.sub.1 R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are as described above are novel subject to the following provisos (a) when R.sub.3, R.sub.4 and R.sub.4 and R.sub.5 are hydrogen R.sub.2 is methyl and R.sub.1 is lower alkyl, R.sub.1 contains more than one carbon atom, and

4-Quinolinones having antihypertensive activity

Therapeutic activity, and in particular the ability to induce diuresis or saluresis, has been discovered in 4-hydroxy- or 4-mercapto-2-aryl-1,2-dihydrophthalazine-1-acetic acids, the tautomers of these namely 4-oxo or thio-2-aryl-1,2-tetrahydrophthalazine-1-acetic acids, and in the ester and alcohol derivatives of the acids, and in the acyl derivatives of the 4-hydroxy or mercapto compounds and in the 3-alkyl derivatives of the 4-oxo or thio compounds. Therapeutic compositions and methods using the compounds are described, as also are novel compounds.

Therapeutic agents

Novel imidazole compounds, pesticidal compositions and methods of using them, and their preparation are described. The compounds have the formula ##STR1## in which X is oxygen or sulphur, R.sup.3 is hydrogen, alkyl, alkenyl or optionally substituted alkylthio, alkenylthio, aralkylthio, alkoxyalkyl or alkylthioalkyl, R.sup.4 is alkyl or cycloalkyl, and R.sup.1 and R.sup.2 are each lower alkyl or alkenyl, R.sup.1 is lower alkyl and R.sup.2 is alkoxyalkyl or haloalkyl, or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclic ring; and salts thereof. Novel compounds are of particular value against insects e.g. aphids, and against other pests, e.g. acarids.

1-Morpholinocarbonyl imidazoles

New imidazole compounds, pesticidal compositions and methods of using them, and their preparation are described. The compounds have the formula ##STR1## in which X is oxygen or sulphur, R.sup.3 is hydrogen, alkyl or alkenyl, R.sup.4 is alkyl or cycloalkyl, and R.sup.1 and R.sup.2 are each lower alkyl or alkenyl, R.sup.1 is lower alkyl and R.sup.2 is alkoxyalkyl or haloalkyl, or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached, from a heterocyclic ring. Novel compounds are of particular value against insects e.g. aphids, and against other pests, e.g. acarids.

1-Carbonamido imidazoles

Thio derivatives of imidazol-1-yl carboxamides

Insecticidal composition comprising a compound of the formula ##SPC1## In which X is selected from the group consisting of oxygen and sulphur, R.sup.3 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sup.4 is selected from the group consisting of alkyl of 1 to 10 carbon atoms and cycloalkyl of 3 to 10 carbon atoms, form a morpholino group optionally containing 1 to 4 methyl substituents attached to carbon atoms of the ring, together with a suitable carrier. The insecticidal compositions are of particular vaule against insects, e.g., aphids, and against other pests, e.g., acarids.

Insecticidal compositions and methods of combatting insects using

Growing community of inventors

Nottinghamshire, United Kingdom

Kenneth J Nichol