Clonidine derivatives useful in the treatment of diarrhoea

Claim 2

A compound of formula (I): wherein A is a 2-imidazolinyl group optionally substituted on a nitrogen atom with C l-4 alkyl group; B is oxygen, sulphur; CR 1 R 2 , wherein R 1 and R 2 are the same or different and each is selected from C l-4 alkyl and hydrogen; or NR 3 , wherein R is selected from C 1-4 alkyl and hydrogen; and C is a 5 or 6 membered carbo- or heterocyclic group having a nitrogen-containing substituent and optionally also substituted by one or two groups, each selected from halogen, (C 1-4 ) alkyl, (C 1-4 ) alkoxy and hydroxy; or an N-acyl derivative and/or an acid addition salt thereof, for use in treating diarrhoea.

Claim 3

A pharmaceutical composition comprising a compound of formula (I) as defined in claim 1 in association with a pharmaceutically acceptable carrier therefor.

Claim 4

A compound as claimed in claim 1 or a composition as claimed in claim 2 wherein A is 2-imidazolinyl or an acyl derivative thereof, B is NH and C is a substituted phenyl group having a nitrogen containing substituent in the ortho or para position with respect to B.

Claim 5

A compound as claimed in claim 1 or a composition as claimed in claim 2 wherein the compound of formula (I) is p-amino Clonidine or an acid addition salt thereof.

Claim 6

A compound of formula (II): wherein R 5 is hydrogen, (C 1-4 ) alkyl or acyl; R 6 is hydrogen, (C 1-4 ) ) alkyl or acyl; R 7 is hydroxy, halogen, (C 1-4 ) alkyl, (C 1-4 ) alkoxy or a group R 8 ; R 8 is an ortho or para substituent selected from amino, mono- or di-(C 1-4 ) alkyl amino, aminomethyl, mono- or di-(C 1-4 ) alkylaminomethyl,amidino, guanidinyl or 2-imidazolidinyl optionally substituted on a nitrogen atom with (C 1-4 ) alkyl or acyl; R 9 is selected from hydroxy, halogen, (C 1-4 ) alkoxy, hydrogen and a group R 8 when in the para position. or R 9 is selected from hydroxy, halogen, (C 1-4 ) alkyl, and (C 1-4 ) alkoxy when in a meta position, or R 9 is selected from hydroxy, halogen, (C l-4 ) alkyl, (C 1-4 ) alkoxy and a group R 8 when in the ortho position, or a salt thereof, provided that when R 9 is in the ortho position and is chloro, R 7 is chloro, R 5 is hydrogen and R 6 is hydrogen, ethyl or acetyl, then R 8 is other than para-amino, or a methyl, ethyl or acetyl derivative or salt thereof.

Claim 7

A compound of formula (II): wherein R 5 is hydrogen, (C 1-4 ) alkyl or acyl; R 6 is hydrogen, (C 1-4 ) ) alkyl or acyl; R 7 is hydroxy, halogen, (C 1-4 ) alkyl, (C 1-4 ) alkoxy or a group R 8 ; R 8 is an ortho or para substituent selected from amino, mono- or di-(C 1-4 ) alkyl amino, aminomethyl, mono- or di-(C 1-4 ) alkylaminomethyl,amidino, guanidinyl or 2-imidazolidinyl optionally substituted on a nitrogen atom with (C 1-4 ) alkyl or acyl; R 9 is selected from hydroxy, halogen, (C 1-4 ) alkoxy, hydrogen and a group R 8 when in the para position. or R 9 is selected from hydroxy, halogen, (C 1-4 ) alkyl, and (C 1-4 ) alkoxy when in a meta position, or R 9 is selected from hydroxy, halogen, (C l-4 ) alkyl, (C 1-4 ) alkoxy and a group R 8 when in the ortho position, or a salt thereof, provided that when R 9 is in the ortho position and is chloro, R 7 is chloro, R 5 is hydrogen and R 6 is hydrogen, ethyl or acetyl, then R 8 is other than para-amino, or a methyl, ethyl or acetyl derivative or salt thereof.

Claim 8

2-(4-amino-2, 6-dibromophenylimino)imidazolidine; 2-(4-amino-2, 6-dimethylphenylimino)imidazolidine; 2-(4-aminomethyl-2, 6-dichlorophenylimino) imidazolidine; 2-(2, 6-dichloro-4-diethylaminomethylphenylimino),imidazolidine; 2-(2, 6-dichloro-4-imidazolino-2-iminophenylimino) imidazolidine or2-[2-6-dichloro-4-(1,3-dimethylguanidino, phenylimino]imidazolidine.

Claim 9

2-(4-amino-2, 6-dibromophenylimino)imidazolidine; 2-(4-amino-2, 6-dimethylphenylimino)imidazolidine; 2-(4-aminomethyl-2, 6-dichlorophenylimino) imidazolidine; 2-(2, 6-dichloro-4-diethylaminomethylphenylimino),imidazolidine; 2-(2, 6-dichloro-4-imidazolino-2-iminophenylimino) imidazolidine or2-[2-6-dichloro-4-(1,3-dimethylguanidino, phenylimino]imidazolidine.

Claim 10

A compound as claimed in claim 5 or 6 for use in treating the human or animal body.

Claim 11

A pharmaceutical composition comprising a compound as claimed in claim 5 or claim 6 in association with a pharmaceutically acceptable carrier therefor.

Claim 12

A process for producing a compound of formula (II) as defined in claim 5 which process comprises (a) reacting a compound of formula (IV) wherein R 7 to R 9 - are as defined with respect to formula (II) and X is a group wherein R 14 is an (C 1-4 ) alkyl group, with a compound of formula (III) wherein R 19 is hydrogen or (C 1-4 ) alkyl. (b) reacting a compound of formula (V) wherein R 7 - R 9 are as defined with respect to formula (II), and R 15 is hydrogen or a group R 6 as hereinbefore defined with respect to formula (II), with a compound of formula (VI) wherein R 20 is hydrogen, alkyl or, when R 17 and R 18 are oxo, acyl, R 16 and R 17 together form a bond and R 17 is (C 1-4 ) alkyl thio or benzylthio or R 16 is hydrogen, and R 17 and R 18 together form an oxo group; or (c) converting the corresponding compound with a nitro substituent in the ortho or para position to the required compound of formula (II); and optionally thereafter forming an acyl derivative and/or a salt thereof.

Claim 13

A process for producing a pharmaceutical composition as as claimed in claim 2 or claim 8 which process comprises bringing into association a compound of formula (I) or formula (II) and a pharmaceutically acceptable carrier therefor.