Heterocyclic ureas, their preparation and their use as vanilloid receptor antagonists
AssigneeSmithKline Beecham Corporation
InventorsHarshad Kantilal Rami, Mervyn Thompson, Paul Adrian Wyman
Life of this patent
Estimating the term…
Abstract
The invention relates to compounds of formula (I) having Vanilloid Receptor (VR1) antagonist activity, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders.
Claims10
A compound of formula (I) or a pharmaceutically acceptable salt thereof:
- 6
- P is phenyl or naphthyl;
- R1 and R2 are independently selected from —H, -halo, —CN, —NO2, —OH, —CF3, —OCF3, —NR4R5, —S(O)mR6—S(O)2NR4R5, —OS(O)2R6, —OS(O)2CF3, alkyl, cycloalkyl, alkoxy, —O(CH2)nNR4R5, —C(O)CF3, —C(O)alkyl, —C(O)cycloalkyl, —C(O)alkylaryl, —C(O)aryl, —C(O)(CH2)nOR6, —C(O)(CH2)nNR4R5, —C(O)Oalkyl, —C(O)NR4R5, —(CH2)nC(O)Oalkyl, —(CH2)nOC(O)R6, —(CH2)nOR6, —(CH2)nNR4R5, —(CH2)C(O)NR4R5, —(CH2)nN(R4)C(O)R6, —(CH2)S(O)2NR4R5, —(CH2)nN(4)S(O)2R6, -ZAr, arylalkyl-, arylalkoxy-, cycloalkylalkyl-, cycloalkylalkoxy-, R6S(O)2C1-6alkyl-, R6S(O)C1-6alkoxy-, R6S(O)2N(R4)—, R6C(O)N(R4)-, R6S(O)2N(R4)C1-6alkyl-, R6C(O)N(R4)C1-6alkyl- or R6C(O)C1-6alkyl;
- R4 and R5 may be the same or different and represent H or alkyl or R4 and R5 together with the atoms to which they are attached form an optionally substituted, saturated ring having 3 to 6 atoms optionally comprising a further nitrogen atom and/or a moiety NR6;
- R1 is C1-6alkyl or aryl;
- n is 0, 1, 2 or 3;
- p is 0, 1, 2 or 3 and when p is 2 or 3 the groups R1 can be the same or different;
- q is 0, 1, 2 or 3 and when q is 2 or 3 the groups R2 can be the same or different;
- r is 1, 2 or 3;
- and
- s is 0, 1 or 2;
- and provided that the compound of formula (I) is not 1-(1-phenyl-3-pyrrolidinyl)-3-phenyl urea or 1-(1-phenyl-3-pyrrolidinyl)-3-(4-methoxyphenyl)urea.
A process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof, which process comprises coupling a compound of formula (II):
- 7
- in which R1, P and p are as defined in formula (I) with a compound of formula (III):
- 8
- in which R2, n, q, r and s are as defined in formula (I) and A and B contain appropriate functional groups which are capable of reacting together to form the urea moiety;
- and thereafter, carrying out one or more of the following optional steps:
- (i) removing any protecting groups (ii) converting R1 into another R1 or R2 into another R2;
- and
- (iii) forming a salt of a compound of formula (I) or a solvate of a compound of formula (I).
The use of a compound of formula (I′), or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate thereof in the manufacture of a medicament for the treatment or prophylaxis of diseases or disorders mediated or associated with the activity of vanilloid receptor
A method for the treatment or prophylaxis of diseases or disorders mediated or associated with the activity of vanilloid receptor, which comprises administering a non toxic, therapeutically effective amount to a patient in need thereof of a compound of formula (I′) or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable solvate.
Dependencies are inferred from the claim text.