Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-06-03
1996-08-20
Haley, Jacqueline
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5483355, A61K 31415, C07D23361
Patent
active
055479723
DESCRIPTION:
BRIEF SUMMARY
This is a National Stage Application of PCT/EP92/02899 filed on Dec. 12, 1992 which published as WO93/13075 on Jul. 8, 1993.
This invention relates to novel 1-(arylalkylaminoalkyl)imidazole compounds having therapeutic activity useful in treating conditions associated with inflammation or allergy, to therapeutic compositions containing these novel compounds and to processes for preparing these novel compounds.
It is believed that, in response to an inflammatory stimulus, phospholipase enzymes are activated leading to the release of arachidonic acid from phospholipids. Existing non-steroidal antiinflammatory agents (NSAIA) are believed to act primarily by blocking the conversion of this released arachidonic acid into prostaglandins via the cyclo-oxygenase pathway of the arachidonic acid cascade. Many existing NSAIA are unsuitable for use by asthmatics. We have found a series of compounds which act to block the release of arachidonic acid from phospholipids. These compounds are indicated as useful antiinflammatory compounds with a potentially broader spectrum of activity than existing NSAIA, and potentially fewer gastro-intestinal side-effects. In addition the compounds may be useful in the treatment of asthma.
Compound A is disclosed in Il Farmaco, 44 (5), 495-502, 1989 as having an inhibitory effect on platelet aggregation in vitro. ##STR2##
Compound B is disclosed as a chemical intermediate in EP 0230035. No pharmacological activity is disclosed for this compound. ##STR3##
GB 2088888 discloses desensitizing compositions for photographic developers comprising imidazoles of formula C ##STR4## wherein R.sub.1 represents a hydrogen atom, a C.sub.1-20 alkyl group or a C.sub.6-20 aryl group; R.sub.2 represents a hydrogen atom, a C.sub.1-20 alkyl group, a C.sub.6-20 aryl group, an amino group, or a C.sub.1-20 alkylthio group; and R.sub.3 and R.sub.4, which may be the same or different, each represents a hydrogen atom, a C.sub.1-4 alkyl group, or a C.sub.6-20 aryl group; and R.sub.1, R.sub.2, R.sub.3 and R.sub.4 may be substituted. 1-(6-Benzylaminohexyl)-2-methylimidazole is disclosed. No pharmacological activity is disclosed for this compound.
More distantly related compounds of formula D ##STR5## in which the ring incorporating N and Z represents dialkylamino, morpholino or piperidino are disclosed in the Indian Journal of Pharmacology 1973, 5, 428 and Pfl. Krankh. 1975, 3, 149. These compounds are disclosed as potential central nervous system depressants. N-[2-(4-Morpholino)propyl]-.alpha.-ethyl-3,4-dichlorobenzylamine is alleged to have antiinflanmmtory activity but has a wide range of undesirable side-effects in mice.
The present invention provides novel compounds of formula I ##STR6## and pharmaceutically acceptable salts thereof in which R.sub.1, R.sub.2 and R.sub.3 independently represent hydrogen, halo, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group, phenoxy (optionally substituted by a C.sub.1-4 alkyl group, a C.sub.1-4 alkoxy group or halo), phenyl (optionally substituted by a C.sub.1-4 alkyl group, a C.sub.1-4 alkoxy group or halo), a C.sub.2-6 alkoxycarbonyl group, an amino group of formula --NR.sub.13 R.sub.14 (in which R.sub.13 and R.sub.14 are independently hydrogen or a C.sub.1-4 alkyl Group or R.sub.13 and R.sub.14 together with the nitrogen atom to which they are attached represent a pyrrolidine ring, a morpholine ring or a piperidine ring), a halogenated C.sub.1-4 alkoxy group, a halogenated C.sub.1-4 alkyl group, benzyloxy (optionally substituted by a C.sub.1-4 alkyl group, a C.sub.1-4 alkoxy Group or halo), hydroxy, a C.sub.1-4 hydroxyalkyl group, a (C.sub.2-6 alkoxycarbonyl)vinyl group; a group of formula --S(O(.sub.n R.sub.7 (in which R.sub.7 represents a C.sub.1-4 alkyl Group and n is 0, 1 or 2), a C.sub.2-4 carbamoylalkyl Group, a C.sub.2-6 alkoxycarbonyl C.sub.1-2 alkyl group, a carbamoyl Group of formula --CONR.sub.11 R.sub.12 (in which R.sub.11 and R.sub.12 are independently hydrogen or a C.sub.1-6 alkyl group) or R.sub.1 and R.sub.2 together with the phenyl ring to which they are
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Clegg Lawrence S.
Hunneyball Ian M.
Jones Colin G. P.
Rafferty Paul
Steele Leslie
Haley Jacqueline
The Boots Company PLC
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