US 7,566,715 B2
Substituted sulfonamide compounds useful for the prophylaxis and treatment of conditions relating to obesity, type II diabetes and/or disorders of the central nervous system
Ulf Bremberg, Uppsala (Sweden); Patrizia Caldirola, Uppsala (Sweden); Annika J. Jensen, Uppsala (Sweden); Gary Johansson, Uppsala (Sweden); Lori Sutin, Stockholm (Sweden); Andrew Mott, Knivsta (Sweden); and Jan Tejbrant, Enskede (Sweden)
Assigned to Biovitrum AB, (Sweden)
Filed on Aug. 30, 2005, as Appl. No. 11/215,173.
Application 11/215173 is a continuation of application No. 10/144677, filed on May 13, 2002, granted, now 6,969,710.
Claims priority of provisional application 60/294102, filed on May 29, 2001.
Claims priority of provisional application 60/294132, filed on May 29, 2001.
Claims priority of application No. 0101659 (SE), filed on May 11, 2001; application No. 0101660 (SE), filed on May 11, 2001; and application No. 0101958 (SE), filed on Jun. 05, 2001.
Prior Publication US 2006/0009446 A1, Jan. 12, 2006
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 241/36 (2006.01); C07D 487/02 (2006.01); A61K 31/495 (2006.01); A61K 31/40 (2006.01); A61P 25/18 (2006.01); A61P 25/22 (2006.01); A61P 25/24 (2006.01); A61P 25/28 (2006.01); A61P 3/10 (2006.01)
U.S. Cl. 514—249  [514/412; 544/349; 548/453] 20 Claims
 
1. A compound of the formula (I)

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof, wherein
X is

OG Complex Work Unit Drawing
R1 is a group Ar;
R3 is:
(a) H
(b) C1-6 alkyl,
(c) C1-6 alkoxy,
(d) straight or branched C1-6 hydroxyalkyl,
(e) straight or branched C1-6 alkylhalides; or
(f) a group Ar;
each Ar is
(a) phenyl,
(b) 1-naphthyl,
(c) 2-naphthyl,
(d) benzyl,
(e) cinnamoyl,
(f) a 5 to 7-membered, partially or completely saturated, heterocyclic ring containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfur, or
(g) a bicyclic ring system consisting of two heterocyclic rings as defined under (f), or a bicyclic ring system consisting of one benzene ring and one heterocyclic ring as defined under (f);
alternatively, R1 and R3 are linked to form a group (CH2)3-5 in formula (Ib);
optionally, the group Ar is substituted with one or more substituents selected from the group consisting of
(a) halogen,
(b) C1-6 alkyl,
(c) CF3,
(d) hydroxy,
(e) C1-6 alkoxy,
(f) C1-4 alkenyl;
(g) phenyl;
(h) phenoxy,
(i) benzyloxy,
(j) benzoyl,
(k) OCF3,
(l) CN,
(m) straight or branched C1-6 hydroxyalkyl,
(n) straight or branched C1-6 alkylhalides,
(o) NH2,
(p) NHR6,
(q) NR6R7,
(r) NO2,
(s) —CONR6R7,
(t) NHSO2R6,
(u) NR6COR7,
(v) SO2NR6R7,
(w) —C(═O)R6,
(x) —CO2R6, or
(y) S(O)nR6; wherein n is 0, 1, 2 or 3; and
(z) a 5 to 7-membered, partially or completely saturated, heterocyclic ring each containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur;
Y is
(a) H,
(b) halogen,
(c) C1-6 alkyl,
(d) CF3,
(e) hydroxy,
(f) C1-6 alkoxy,
(g) C1-4 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) NHR6,
(r) NR6R7,
(s) NO2,
(t) —CONR6R7,
(u) NHSO2R6,
(v) NR6COR7,
(x) SO2NR6R7,
(z) —C(═O)R6,
(aa) —CO2R6, or
(ab) S(O)nR6; wherein n is 0, 1, 2 or 3;
R2 and R4 are independently:
(a) —SO2R1,
(b) H,
(c) C1-6 alkyl,
(d) C1-C3 alkenyl,
(e) C1-C3 alkylaryl,
(f) Ar as defined above for R1,
(g) —C(═O)R6,
(h) —C(O)NR6R7,
(i) —C(S)NR6R7,
(j) —CO2R6;
(k) —C(S)R6;
(l) straight or branched C1-6 hydroxyalkyl, or
(m) straight or branched C1-6 alkylhalides;
alternatively, R2 and R4 are linked to form a group (CH2)3-5 in formula (Ia);
R5 is selected from the group consisting of the following chemical groups:

OG Complex Work Unit Drawing
each R6 and R7 is independently
(a) H,
(b) C1-6 alkyl,
(c) C3-7 cycloalkyl, or
(d) Ar1;
wherein each Ar1 is
(a) phenyl,
(b) 1-naphthyl,
(c) 2-naphthyl,
(d) benzyl,
(e) cinnamoyl,
(f) a 5 to 7-membered, partially or completely saturated, heterocyclic ring containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfur, or
(g) a bicyclic ring system consisting of two heterocyclic rings as defined under (f), or a bicyclic ring system consisting of one benzene ring and one heterocyclic ring as defined under (f);
optionally, the group Ar1 is substituted with one or more substituents selected from the group consisting of
(a) halogen,
(b) C1-6 alkyl,
(c) CF3,
(d) hydroxy,
(e) C1-6 alkoxy,
(f) C1-4 alkenyl;
(g) phenyl;
(h) phenoxy,
(i) benzyloxy,
(j) benzoyl,
(k) OCF3,
(l) CN,
(m) straight or branched C1-6 hydroxyalkyl,
(n) straight or branched C1-6 alkylhalides,
(o) NH2,
(p) NHR9,
(q) NR9R10,
(r) NO2,
(s) —CONR9R10,
(t) NHSO2R9,
(u) NR9COR10,
(v) SO2NR9R10,
(w) —C(═O)R9,
(x) —CO2R9, or
(y) S(O)nR9; wherein n is 0, 1, 2 or 3; and
(z) a 5 to 7-membered, partially or completely saturated, heterocyclic ring each containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur;
alternatively, R6 and R7 are linked to form a group (CH2)3-5;
R8 is
(a) H, or
(b) C1-6 alkyl; and
each R9 and R10 is independently
(a) H,
(b) C1-6 alkyl; or
(c) C3-7 cycloalkyl; or
alternatively, R9 and R10 are linked to form a group (CH2)3-5.