Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-10-06
1997-06-17
Haley, Jacqueline
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514339, 5462774, 548468, C07D40114, C07D40306, A61K 3140
Patent
active
056397798
DESCRIPTION:
BRIEF SUMMARY
This application is a National Stage application of PCT/EP93/00738 filed Mar. 25, 1993 and published as WO 93/21177 on Oct. 28, 1993.
The present invention relates to indole derivatives which act on 5-hydroxytryptamine (5-HT) receptors.
More particularly the present invention relates to 3,5-disubstituted indoles which are selective agonists at the "5-HT.sub.1 -like" subtype of the 5-hydroxytryptamine receptor. Such "5-HT.sub.1 -like" receptors are present in the carotid vascular bed and their activation causes vasoconstriction with a consequent reduction in carotid blood flow. Compounds which have "5-HT.sub.1 -like" agonist activity are therefore useful in the treatment of medical conditions which are thought to result from excessive dilation of the carotid bed, such as migraine, cluster headache, chronic paroxysmal hemicrania and headache associated with vascular disorders. Certain compounds of the present invention are also agonists at central 5-HT.sub.1 receptors and are therefore useful for the treatment of depression, anxiety, eating disorders, obesity and drug abuse.
The present invention provides compounds of formula: ##STR2## and pharmaceutically acceptable salts thereof, wherein C.sub.1 -C.sub.3 alkylene; (R.sup.5 R.sup.6 NOC) C.sub.1 -C.sub.3 alkylene; (R.sup.5 R.sup.6 NO.sub.2 S)C.sub.1 -C.sub.3 alkylene; [R.sup.3 S(O).sub.m ]C.sub.1 -C.sub.3 alkylene; (R.sup.7 O) C.sub.2 -C.sub.4 alkylene; (C.sub.3 -C.sub.7 cycloalkyl) C.sub.1 -C.sub.3 alkylene; (aryl) C.sub.1 -C.sub.3 alkylene; (heteroaryl)C.sub.1 -C.sub.3 alkylene; C.sub.3 -C.sub.7 cycloalkyl optionally substituted with HO; C.sub.3 -C.sub.6 alkenyl optionally substituted with aryl; C.sub.5 -C.sub.7 cycloalkenyl; or C.sub.3 -C.sub.6 alkynyl; NOC)C.sub.1 -C.sub.3 alkylene; R.sup.8 R.sup.9 NO.sub.2 S; (R.sup.8 R.sup.9 NO.sub.2 S) C.sub.1 -C.sub.3 alkylene; R.sup.10 S (O).sub.m ; [R.sup.10 S (O).sub.m ]C.sub.1 -C.sub.3 alkylene; R.sup.12 CON (R.sup.11); [R.sup.12 CON(R.sup.11)]C.sub.1 -C.sub.3 alkylene; R.sup.10 SO.sub.2 N(R.sup.11); [R.sup.10 SO.sub.2 N(R.sup.11)]C.sub.1 -C.sub.3 alkylene; R.sup.8 R.sup.9 NOCN(R.sup.11); [R.sup.8 R.sup.9 NOCN(R.sup.11)]C.sub.1 -C.sub.3 alkylene; R.sup.10 O.sub.2 CN(R.sup.11); [R.sup.10 O.sub.2 CN(R.sup.11)]C.sub.1 -C.sub.3 alkylene; R.sup.13 (CH.sub.2).sub.n CH.dbd.CH; or R.sup.7 O; -C.sub.3 alkylene; (aryl) C.sub.1 -C.sub.3 alkylene; C.sub.3 -C.sub.7 cycloalkyl; or aryl; -C.sub.3 alkylene; (aryl)C.sub.1 -C.sub.3 alkylene; or C.sub.3 -C.sub.7 cycloalkyl; -C.sub.6 alkyl; (C.sub.3 -C.sub.7 cycloalkyl)C.sub.1 -C.sub.3 alkylene; (aryl)C.sub.1 -C.sub.3 alkylene; and C.sub.3 -C.sub.7 cycloalkyl; attached form a 4- to 7-membered heterocyclic ring which may optionally incorporate a further heteroatom linkage selected from O, S(O).sub.m, NH, N(C.sub.1 -C.sub.4 alkyl), and N(C.sub.1 -C.sub.5 alkanoyl); -C.sub.3 alkylene; (aryl)C.sub.1 -C.sub.3 alkylene; C.sub.3 -C.sub.7 cycloalkyl; or aryl; -C.sub.6 alkyl; (C.sub.3 -C.sub.7 cycloalkyl)C.sub.1 -C.sub.3 alkylene; (aryl)C.sub.1 -C.sub.3 alkylene; and C.sub.3 -C.sub.7 cycloalkyl;
which they are attached form a 4- to 7-membered heterocyclic ring which may optionally incorporate a further heteroatom linkage selected from O, S(O).sub.m, NH, N(C.sub.1 -C.sub.4 alkyl), and N(C.sub.1 -C.sub.5 alkanoyl); -C.sub.3 alkylene; (aryl)C.sub.1 -C.sub.3 alkylene; C.sub.3 C.sub.7 cycloalkyl; or aryl; -C.sub.6 alkyl; (C.sub.3 -C.sub.7 cycloalkyl)C.sub.1 -C.sub.3 alkylene; (aryl)C.sub.1 -C.sub.3 alkylene; C.sub.3 -C.sub.7 cycloalkyl; and aryl;
R.sup.13 is selected from R.sup.8 R.sup.9 NOC; R.sup.8 R.sup.9 NO.sub.2 S; R.sup.10 S(O).sub.m ; R.sup.12 CON(R.sup.11); R.sup.10 SO.sub.2 N(R.sup.11); R.sup.8 R.sup.9 NOCN(R.sub.11); and R.sup.10 O.sub.2 CN(R.sup.11); wherein R.sup.8, R.sup.9, R.sup.10, R.sup.11 and R.sup.12 are as defined above;
In the above definition, aryl means phenyl optionally substituted with one to three substituents independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, F.sub.3 C, NC, H.sub.2 NOC, and HO; heteroaryl means pyrrolyl, furyl, thienyl, ox
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Macor John Eugene
Wythes Martin James
Fuller Jr. Grover F.
Ginsburg Paul H.
Haley Jacqueline
Pfizer Inc.
Richardson Peter C.
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