Sulfonamide derivatives as 5HT.sub.7 receptor antagonists

Details Sulfonamide derivatives as 5HT.sub.7 receptor antagonists Sulfonamide derivatives as 5HT.sub.7 receptor antagonists

1999-06-23

2000-02-15

Powers, Fiona T.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

546143, 546146, 546148, A01N 4342

Patent

active

060253673

DESCRIPTION:

BRIEF SUMMARY
This invention relates to compounds having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of CNS disorders.
EPA 0 021 580 and EPA 0 076 072 describe sulphonamide derivatives which are disclosed as having antiarrhythmic activity. A structurally distinct class of compounds has now been discovered, which have been found to have 5HT.sub.7 receptor antagonist activity. 5HT.sub.7 receptor antagonists are believed to be of potential use in the treatment of certain CNS disorders such as anxiety, depression, sleep disorders, and schizophrenia.
The present invention therefore provides, in a first aspect, a compound of formula (I) or a salt thereof: ##STR1## wherein: Ar is an optionally substituted mono- or bicyclic aromatic or heteroaromatic ring; heteroaromatic ring; membered ring containing one or two heteroatoms optionally substituted by C.sub.1-6 alkyl; form a 5-8 membered ring containing one or two heteroatoms optionally substituted by C.sub.1-6 alkyl;
C.sub.1-6 alkyl groups, whether alone or as part of another group, may be straight chain or branched.
Optional substituents for aromatic and heteroaromatic groups include C.sub.1-6 alkyl optionally substituted by NR.sup.7 R.sup.8, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkylthio, cyano, nitro, halogen, CF.sub.3, C.sub.2 F.sub.5, NR.sup.7 R.sup.8, CONR.sup.7 R.sup.8, NR.sup.7 COR.sup.8, S(O).sub.p NR.sup.7 R.sup.8, CHO, OCF.sub.3, SCF.sub.3, SOR.sup.9, SO.sub.2 R.sup.9, OSO.sub.2 R.sup.9, COR.sup.9, CH.sub.2 OR.sup.9, CO.sub.2 R.sup.9 or OR.sup.9 where p is 1 or 2 and R.sup.7, R.sup.8 and R.sup.9 are independently hydrogen, C.sub.1-6 alkyl, optionally substituted aryl or optionally substituted arylC.sub.1-6 alkyl. More than one substituent can be present and in the case of multiple substituents these can be the same or different.
Preferably Ar is an optionally substituted bicyclic aromatic group. Most preferably Ar is naphthyl.
Preferably Ar' is an optionally substituted monocyclic aromatic group. Most preferably Ar' is phenyl.
Examples of groups where R.sup.1 is C.sub.1-6 alkyl are ethyl and most preferably methyl. When groups R.sup.1 and R.sup.3 are combined to form a heterocycle the preferred examples have 5 or most preferably 6 membered rings.
Preferably R.sup.2 is hydrogen or methyl;
The preferred group when R.sup.3 is C.sub.1-6 alkyl is methyl. When groups R.sup.1 and R.sup.3 are combined to form a heterocycle the preferred examples have 5 or most preferably 6 membered rings.
Preferably R.sup.4 is hydrogen;
Preferably R.sup.5 and R.sup.6 are hydrogen;
Preferably q and r have values such that they form part of a 5- or 6-membered ring. Most preferably q and r have values such that they form part of a 6-membered ring i.e. the sum of q and r is 3.
Particular compounds of the invention include: hydroisoquinoline 2-(2-(3-Chloro-4-methylphenyl)-piperidin-2-yl)-ethyl-1,2,3,4 tetrahydroisoquinoline
The compounds of the formula (I) can form acid addition salts with acids, such as conventional pharmaceutically acceptable acids, for example maleic, hydrochloric. hydrobromic, phosphoric, acetic, fumaric, salicylic, citric, lactic, mandelic, tartaric and methanesulfonic.
Compounds of formula (I) may also form solvates such as hydrates, and the invention also extends to these forms. When referred to herein, it is understood that the term `compound of formula (I)` also includes these forms.
Certain compounds of formula (I) are capable of existing in stereoisomeric forms including diastereomers and enantiomers and the invention extends to each of these stereoisomeric forms and to mixtures thereof including racemates. The different stereoisomeric forms may be separated one from the other by the usual methods, or any given isomer may be obtained by stereospecific or asymmetric synthesis. The invention also extends to any tautomeric forms and mixtures thereof.
The present invention also provides a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt t

REFERENCES:
patent: 4485108 (1984-11-01), Jozic
patent: 5294621 (1994-03-01), Russell
Kitagawa et al., Biochim. Biophys. Acta, 987 (1989) 235-8.

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