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US 2004/0024210 A1Published application
New compounds
AssigneeProximagen Limited
InventorsGary Johansson, Annika Jenmalm-Jensen, Katarina Beierlein
Life of this patent
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Abstract
The present invention relates to compounds of the general formula (I), 1 wherein P is sulfone or sulfonamide; and A, B, W, X, Y and R3 are as defined in the description; to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the prophylaxis and treatment of medical conditions relating to obesity, type II diabetes, and/or CNS disorders, to achieve reduction of body weight and of body weight gain.
Claims57
A compound of the formula (I):
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- or a pharmaceutically acceptable salt thereof, wherein:
- ring B is
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- in which D is a five-membered heterocyclic or heteroaryl ring, said ring comprising one or two atoms selected from the group consisting of nitrogen, sulfur and oxygen, with the proviso that when D contains an oxygen atom, D is heteroaryl;
- each W is independently —N—, —(CH)—, or —C— provided that not more than three groups W are —N— in both rings A and B together;
- P is any one of formula (a), (b) or (c)
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- wherein x 0, 1, or 2 and y=0, 1, or 2;
- and P and R3 can be attached to any carbon atom that allows the substitution in one of either the A- or B-ring, or when ring A contains at least one nitrogen atom and P is (c), then P can also be attached to any nitrogen in ring B that allows the substitution;
- the dashed bonds denote that P and R3, respectively, may be attached to either the A or B ring;
- but each P or R3 may not be simultaneously bound to both rings A and B;
- R1 is
- (a) C1-6 alkyl,
- (b) C1-6 alkoxyalkyl,
- (c) straight-chained or branched C1-6 hydroxyalkyl,
- (d) straight-chained or branched C1-6 alkylhalides,
- (e) aryl carbonylmethyl,
- (f) C3-7 cycloalkyl, which is optionally partially unsaturated,
- (g) C3-7 cycloalkyl-C1-6 alkyl, wherein the cyclic ring is optionally partially unsaturated, or
- (h) a group Ar;
- wherein Ar is
- (a) phenyl,
- (b) 1-naphthyl,
- (c) 2-naphthyl,
- (d) aryl-C1-6 alkyl,
- (e) cinnamyl,
- (f) a 5 to 7-membered, optionally aromatic, partially saturated or completely saturated, mono- or bi-cyclic heterocyclic ring, each containing 1 to 4 heteroatoms, selected from oxygen, sulfur, and nitrogen,
- (g) a bicyclic ring system comprising at least one heterocyclic ring according to (f) and a group Ar,
- wherein the group Ar is substituted in one or more positions with
- (a) H, X or Y, or
- (b) a 5 to 7-membered, optionally aromatic, partially saturated or completely saturated, heterocyclic ring each containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur;
- R1 is
- (a) H,
- (b) C1-6 alkyl,
- (c) C2-6 alkoxyalkyl,
- (d) straight or branched C1-6 hydroxyalkyl, or
- (e) straight or branched C1-6 alkylhalides;
- (f) a group Ar,
- or R1 and R2 are linked to form a group —CH2CH2OCH2CH2— or
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- wherein v is 0-2,
- X and Y are independently
- (a) H,
- (b) halogen,
- (c) C1-6 alkyl,
- (d) CF3,
- (e) hydroxy,
- (f) C1-6 alkoxy,
- (g) C2-6 alkenyl,
- (h) phenyl,
- (i) phenoxy,
- (j) benzyloxy,
- (k) benzoyl,
- (l) —OCF3,
- (m) —CN,
- (n) straight or branched C1-6 hydroxyalkyl,
- (o) straight or branched C1-6 alkylhalides,
- (p) —NH2,
- (q) —NHR4,
- (r) —NR4R5,
- (s) —NO2,
- (t) —CONR4R5,
- (u) —NHSO2R4,
- (v) —NR4COR5,
- (x) —SO2NR4R5,
- (z) —C(═O)R4,
- (aa) —CO2R4, or
- (ab) —S(O)nR4, wherein n is 0, 1, 2 or 3,
- (ac) —S—(C1-6) alkyl, or
- (ad) —SCF3;
- and
- R4 and R5 are independently
- (a) H,
- (b) C1-6 alkyl,
- (c) C3-7 cycloalkyl, or
- (d) Ar, as defined above for R1;
- alternatively, R4 and R5 are linked to form a group —CH2OCH2—, —CH2CH2OCH2CH2— or (CH2)3-5;
- R3 is a group selected from any one of
- 342 343
- wherein R3 is optionally substituted on each carbon atom that allows the substitution with Rq groups, wherein Rq is independently H, or (C1-6) alkyl, and wherein two Rq groups can be present on the same carbon atom simultaneously, wherein
- q=1, 2, 3, 4, 5 or 6,
- m=1 or 2, and
- n=0, 1 or 2;
- R6 is independently
- (a) H,
- (b) linear or branched C1-6 alkyl,
- (c) benzyl,
- (d) —CH2—CH2—OH, or
- (e) —CH2—CH2—O—C1-6 alkyl;
- P and R3 can be attached to the same ring or to different rings of rings A and B;
- provided that
- when P is
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- P and R both are attached to ring A in the meta- or para-position relative to one another then R3 is selected from any one of
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- when ring B is
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- and P is
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- then P and R3 are simultaneously attached to the same ring A or B;
- when ring B is
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- and P is
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- wherein y=0, then P and R3 are attached to the different rings of rings A and B;
- when the ring system A+B is benzofurane or benzothiophene, and P is
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- and attached to position 3 in the A+B ring system, and R3 is a group selected from any one of
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- and attached to position 7 in the A+B ring system, then y=1 or 2;
- when the ring system A+B is indole, and P is
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- and P is attached to position 3 in the A+B ring system, and R3 is a group selected from any one of
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- and R3 is attached to any one of positions 5, 6 or 7 in the A+B ring system, then y=1 or 2;
- or
- when ring B is
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- and R1=Ar is partially saturated bi-cyclic heterocyclic ring containing a N atom, the N atom in Ar cannot be attached to the S atom in P;
- with the proviso that:
- when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, then R3 is not substituted in position 1 on the naphthalene ring;
- and
- with the proviso that:
- when ring D is a pyrrole ring, P is of the formula (c), then R3 is not of the formula
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- substituted in position 3 on the pyrrole ring.
124 more elements
Dependencies are inferred from the claim text.