Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-06-16
2001-04-17
Chang, Ceila (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C546S197000, C546S198000, C546S199000
Reexamination Certificate
active
06218405
ABSTRACT:
The present invention relates to novel heteroarylsulphonamide compounds which have affinity for 5-HT
1A
and/or D
2
-like (D
2
, D
3
and D
4
sub-types) receptors, to processes for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of central nervous system disorders, for example depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, Parkinson's disease, obesity, hypertension, Tourette's syndrome, sexual dysfunction, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, obsessive-compulsive behaviour, panic attacks, social phobias, eating disorders and anorexia, cardiovascular and cerebrovascular disorders, non-insulin dependent diabetes mellitus, hyperglycaemia, constipation, arrhythmia, disorders of the neuroendocrine system, stress, and spasticity.
The present invention provides compounds of formula I
including enantiomers and pharmaceutically acceptable salts thereof in which
A is methylene or —O—;
B is methylene or —O—;
G
1
—G
2
—G
3
represent —N(R′)—C(R″)═N—, —N═C(R″)—N(R′)—, —N(R′)—C(R″)═C(R′″)—, —C(R′″)═C(R″)—N(R′)—, —N(R′)—N═C(R″)—, —C(R″)═N—N(R′)—, —N(R′)—N═N—, —N═N—N(R′)—, —N═C(R″)—O—, —N═C(R″)—S—, —O—C(R″)═N—, —S—C(R″)═N—, —O—N═C(R″)—, —S—N═C(R″)—, —C(R″)═N—O—, —C(R″)═N—S—, —S—C(R″)═C(R′″)—, —C(R″)═C(R′″)—S—, —O—C(R″)═C(R′″)—, —C(R″)═C(R′″)—O— or —O—C(R′)(R′)—O—;
R′ is H or an alkyl group containing 1 to 3 carbon atoms;
R″ and R′″, which are the same or different, are H; halo; an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more halo; carboxy; an alkanoyl group containing 1 to 6 carbon atoms; an alkoxycarbonyl group in which the alkoxy group contains 1 to 3 carbon atoms; formyl; cyano; or a carbamoyl group or carbamoylmethyl group each optionally N-substituted by one or two alkyl groups, which may be the same or different, each containing 1 to 3 carbon atoms;
g is 0, 1 or 2;
R
1
represents an alkyl group containing 1 to 3 carbon atoms optionally substituted by one or more halo; an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo; halo; or an alkylthio group containing 1 to 3 carbon atoms optionally substituted by one or more halo; the substituents represented by R
1
being the same or different when g is 2;
R
2
is H or an alkyl group containing 1 to 3 carbon atoms;
R
3
and R
4
, which are the same or different, are H, or an alkyl group containing 1 to 3 carbon atoms;
U is an alkylene chain containing 1 to 3 carbon atoms, optionally substituted by one or more alkyl groups each containing 1 to 3 carbon atoms;
Q represents a divalent group of formula IIa, IIb or IIc
in which V is (CH
2
)
n
, wherein n is 0, 1, 2 or 3, optionally substituted by one or more alkyl groups each containing 1 to 3 carbon atoms;
V′ is an alkylene chain containing 2 to 6 carbon atoms, optionally substituted by one or more alkyl groups each containing 1 to 3 carbon atoms;
E is an alkylene chain containing 0 to 2 carbon atoms and E′ is an alkylene chain containing 1 to 4 carbon atoms provided that the total number of carbon atoms in E and E′ amounts to 3 or 4;
R
5
and R
6
, which may be the same or different, are H or an alkyl group containing 1 to 4 carbon atoms; and
T represents phenyl, 1- or 2-naphthyl, 1-naphth[2,1-d][1,2,3]oxadiazolyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 2- or 3-thienyl, 2- or 3-furyl, 2-, 3- or 7-benzo[b]furanyl, 2,3-dihydro-7-benzo[b]furanyl, 2-, 3- or 7-benzo[b]thiophenyl, 3-, 4- or 5-pyrazolyl, 1,2,3-triazol-4-yl, 1,2,3-triazol-5-yl, 1,2,4-triazol-2-yl, 5-tetrazolyl, 2-, 3- or 4-quinolinyl, 2- or 4-quinazolinyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isothiazolyl or 2-, 4- or 5-thiazolyl each of which may be optionally substituted by one or more substituents selected from a) halo, b) an alkyl group containing 1 to 4 carbon atoms optionally substituted by one or more halo, c) an alkoxy group containing 1 to 3 carbon atoms optionally substituted by one or more halo, d) an alkylthio group containing 1 to 3 carbon atoms optionally substituted by one or more halo, e) hydroxy, f) an acyloxy group containing 1 to 3 carbon atoms, g) hydroxymethyl, h) cyano, i) an alkanoyl group containing 1 to 6 carbon atoms, j) an alkoxycarbonyl group containing 2 to 6 carbon atoms, k) a carbamoyl group or carbamoylmethyl group each optionally N-substituted by one or two alkyl groups each containing 1 to 3 carbon atoms, l) a sulphamoyl or sulphamoylmethyl group each optionally N-substituted by one or two alkyl groups each containing 1 to 3 carbon atoms, m) an amino group optionally substituted by one or two alkyl groups each containing 1 to 5 carbon atoms, n) 1-pyrrolidinyl or 1-piperidinyl, o) nitro or p) acetamido.
In preferred compounds of formula I, A is —O—.
In preferred compounds of formula I, B is —O—.
In more preferred compounds of formula I, both A and B are —O—.
In preferred compounds of formula I, g is 0 or 1. When g is 1, R
1
is preferably halo or an alkyl group containing 1 to 3 carbon atoms. In more preferred compounds of formula I, g is 0.
In preferred compounds of formula I, G
1
—G
2
—G
3
are —NH—CH═CH—; —O—CH═CH—; or —S—C(R″)═C(R′″)—. Preferably, R″ is H and R′″ is H or halo (more preferably chloro). More preferably G
1
—G
2
—G
3
are —NH—CH═CH—; or —S—C(R″)═C(R′″)—.
In preferred compounds of formula I, R
2
is H.
In preferred compounds of formula I, R
3
and R
4
, are both H.
In preferred compounds of formula I, U is methylene.
In preferred compounds of formula I, Q is a group of formula IIc in which V is methylene, E and E′ are both ethylene and R
6
is H.
In preferred compounds of formula I, T is phenyl or 2-, 3- or 4-pyridyl each of which may be optionally substituted by one or more substituents selected from methoxy, nitro, halo or acetamido. In more preferred compounds of formula I, T is 2-pyridyl or 4-acetamidophenyl.
In one group of preferred compounds of formula I, both A and B are —O—; g is 1, R
1
is halo or an alkyl group containing 1 to 3 carbon atoms; G
1
—G
2
—G
3
are —NH—CH═CH—; —O—CH═CH— or —S—C(R″)═C(R′″)—; R″ is H and R′″ is H or halo; R
2
is H; R
3
and R
4
, are both H; U is methylene; Q is a group of formula IIc in which V is methylene, E and E′ are both ethylene and R
6
is H; and T is phenyl or 2-, 3- or 4 pyridyl each of which may be optionally substituted by one or more substituents selected from methoxy, nitro, halo or acetamido.
In second group of preferred compounds of formula I, both A and B are —O—; g is 1, R
1
is halo or an alkyl group containing 1 to 3 carbon atoms; G
1
—G
2
—G
3
are —NH—CH═CH—; or —S—C(R″)═C(R′)—; R″ is H and R′″ is H or halo; R
2
is H; R
3
and R
4
, are both H; U is methylene; Q is a group of formula IIc in which V is methyene, E and E′ are both ethylene and R
6
is H; and T is phenyl or 2-, 3- or 4 pyridyl each of which may be optionally substituted by one or more substituents selected from methoxy, nitro, halo or acetamido.
Compounds of formula I may exist as salts with pharmaceutically acceptable acids. Examples of such salts include hydrochlorides, hydrobromides, sulphates, methanesulphonates, nitrates, maleates, acetates, citrates, fumarates, tartrates [eg (+)-tartrates, (−)-tartrates or mixtures thereof including racemic mixtures], succinates, benzoates and salts with amino acids such as glutamic acid. Compounds of formula I and their salts may exist in the f
Birch Alan Martin
Bradley Paul Anthony
Chang Ceila
Keil & Weinkauf
Knoll Aktiengesellschaft
LandOfFree
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