Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-01-24
1996-10-22
Haley, Jacqueline
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5482664, 548466, 548468, A61K 31415, C07D40304
Patent
active
055677266
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GB93/01495 filed 15 Jul. 1993, now WO 94/02477 published 3 Feb. 1994.
The present invention relates to a class of substituted imidazole, triazole and tetrazole derivatives which act on 5-hydroxytryptamine (5-HT) receptors, being selective agonists of so-called "5-HT.sub.1 -like" receptors. They are therefore useful in the treatment of clinical conditions for which a selective agonist of these receptors is indicated.
5-HT.sub.1 -like receptor agonists which exhibit selective vasoconstrictor activity have recently been described as being of use in the treatment of migraine (see, for example, A. Doenicke et al., The. Lancet, 1988, Vol. 1, 1309-11). The compounds of the present invention, being selective 5-HT.sub.1 -like receptor agonists, are accordingly of particular use in the treatment of migraine and associated conditions, e.g. cluster headache, chronic paroxysmal hemicrania, headache associated with vascular disorders, tension headache and paediatric migraine.
EP-A-0313397 and WO-A-91/18897 describe separate classes of tryptamine derivatives substituted by various five-membered heteroaliphatic rings, which are stated to be specific to a particular type of "5-HT.sub.1 -like" receptor and thus to be effective therapeutic agents for the treatment of clinical conditions, particularly migraine, requiring this activity. However, neither EP-A-0313397 nor WO-A-91/18897 discloses or suggests the imidazole, triazole and tetrazole derivatives provided by the present invention.
EP-A-0497512, published on 5 Aug. 1992, describes a class of substituted imidazole, triazole and tetrazole derivatives which are stated to be selective agonists of 5-HT.sub.1 -like receptors and hence to be of particular use in the treatment of migraine and associated conditions.
The present invention provides a compound of formula I, or a salt or prodrug thereof: ##STR2## wherein the broken circle represents two non-adjacent double bonds in any position in the five-membered ring;
two, three or four of V, W, X, Y and Z represent nitrogen and the remainder represent carbon provided that, when two of V, W, X, Y and Z represent nitrogen and the remainder represent carbon, then the said nitrogen atoms are in non-adjacent positions within the five-membered ring;
A.sup.1 represents hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano, trifluoromethyl, --OR.sup.x, --SR.sup.x, --NR.sup.x R.sup.y, --NR.sup.x COR.sup.y, --NR.sup.x CO.sub.2 R.sup.y, --NR.sup.x SO.sub.2 R.sup.y, or --NR.sup.z CTNR.sup.x R.sup.y ;
A.sup.2 represents a non-bonded electron pair when four of V, W, X, Y and Z represent nitrogen and the other represents carbon; or, when two or three of V, W, X, Y and Z represent nitrogen and the remainder represent carbon, A.sup.2 represents hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano, trifluoromethyl, --OR.sup.x, --SR.sup.x, --NR.sup.x R.sup.y, --NR.sup.x COR.sup.y, --NR.sup.x CO.sub.2 R.sup.y, --NR.sup.x SO.sub.2 R.sup.y, or --NR.sup.z CTNR.sup.x R.sup.y ;
E represents a bond or a straight or branched alkylene chain containing from 1 to 4 carbon atoms;
F represents a group of formula ##STR3##
U represents nitrogen or C--R.sup.2 ;
B represents oxygen, sulphur or N--R.sup.3 ;
R.sup.1 represents a group of formula (i), (ii) or (iii): ##STR4## in which
M represents the residue of an azetidine, pyrrolidine or piperidine ring;
p is zero or 1 and q is an integer from 1 to 4,
R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 independently represent hydrogen or C.sub.1-6 alkyl;
R.sup.x and R.sup.y independently represent hydrogen, hydrocarbon or a heterocyclic group, or R.sup.x and R.sup.y together represent a C.sub.2-6 alkylene group;
R.sup.z represents hydrogen, hydrocarbon or a heterocyclic group;
T represents oxygen, sulphur or a group of formula .dbd.N.G; and
G represents hydrocarbon, a heterocyclic group or an electron-withdrawing group.
The present invention also provides compounds of formula I above wherein R.sup.1 represents a group of formula (i) or (ii), and the remaining substituents ar
REFERENCES:
patent: 5451588 (1995-09-01), Baker et al.
Baker Raymond
Castro Pineiro Jose L.
Guiblin Alexander R.
Matassa Victor G.
Reeve Austin J.
Haley Jacqueline
Merck Sharp & Dohme Ltd.
North Robert J.
Winokur Melvin
LandOfFree
Imidazole, Triazole and tetrazole derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Imidazole, Triazole and tetrazole derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Imidazole, Triazole and tetrazole derivatives will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2358930