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US 7,022,703 B2Granted
Acetylenic compound useful in treating inflammatory disorders
AssigneeJanssen Pharmaceutica NV
InventorsScott Beers, Elizabeth A. Malloy, Michael P. Wachter
Life of this patent
Estimating the term…
Abstract
This invention is directed to acetylenic compounds as inhibitors of a nicotinamide adenine dinucleotide oxidase hydride donor useful in treating or ameliorating a reactive oxygen species mediated inflammatory disorder.
Claims33
A compound of Formula (I):
- wherein:
- A is (C5-6)cycloalkyldiyl, cyclic heteroalkyldiyl, aryldiyl or heteroaryldiyl;
- B is aryldiyl or heteroaryldiyl;
- E is aryldiyl or heteroaryldiyl;
- R1 is (C3-8)cycloalkyl-(R8)q, cyclic heteroalkyl-(R9)q, aryl-(R8)q, heteroaryl-(R9)q or NR5R6;
- R5 is hydrogen, (C1-12)alkanyl-R7, C(O)H, C(O)—(C1-12)alkanyl-R7, CO2H, C(O)O—(C1-12)alkanyl-R7, (C3-8)cycloalkyl-(R8)q, cyclic heteroalkyl-(R9)q, aryl-(R8)q or heteroaryl-(R9)q;
- wherein cyclic heteroalkyl-(R9)q and heteroaryl-(R9)q are attached to the nitrogen atom of NR5R6 via a ring carbon atom;
- R6 is hydrogen or (C1-8)alkanyl-R7;
- R7 is hydrogen, (C1-8)alkoxy-(R10)s, C(O)H, C(O)—(C1-8)alkanyl-(R10)s, C(O)—Ra, CO2H, C(O)O—(C1-8)alkanyl-(R10)s, C(O)O—Ra, OC(O)—(C1-8)alkanyl-(R10)s, OC(O)—Ra, NH2, NH(C1-8alkanyl-(R10)s), N(C1-8alkanyl-(R10)s)2, cyano, (halo)1-3, hydroxy or Ra;
- Ra is (C3-8)cycloalkyl-(R11)q, cyclic heteroalkyl-(R12)q, aryl-(R11)q or heteroaryl-(R12)q;
- (R8)q is hydrogen, (C1-8)alkanyl-(R10)s, (C1-8)alkoxy-(R10)s, C(O)H, C(O)—(C1-8)alkanyl-(R10)s, CO2H, C(O)O—(C1-8)alkanyl-(R10)s, NH2, NH(C1-8alkanyl-(R10)s), N(C1-8alkanyl-(R10)s)2 or halogen;
- (R9)q is hydrogen, (C1-8)alkanyl-(R10)s, C(O)H, C(O)—(C1-8)alkanyl-(R10)s, CO2H or C(O)O—(C1-8)alkanyl-(R10)s when attached to a nitrogen atom;
- wherein (R9)q is hydrogen, (C1-8)alkanyl-(R10)s, (C1-8)alkoxy-(R10)s, C(O)H, C(O)—(C1-8)alkanyl-(R10)s, CO2H, C(O)O—(C1-8)alkanyl-(R10)s, NH2, NH(C1-8alkanyl-(R10)s), N(C1-8alkanyl-(R10)s)2 or halogen when attached to a carbon atom;
- (R10)s is hydrogen, (C1-8)alkoxy, NH2, NH(C1-8alkanyl), N(C1-8alkanyl)2, (halo)1-3 or hydroxy;
- (R11)q is hydrogen, (C1-8)alkanyl, (C1-8)alkoxy, NH2, NH(C1-8alkanyl), N(C1-8alkanyl)2 or halogen;
- (R12)q is hydrogen or (C1-8)alkanyl;
- R2 is hydrogen, (C1-8)alkanyl-R7, (C1-8)alkoxy-R7, C(O)H, C(O)—(C1-8)alkanyl-R7, CO2H, C(O)O—(C1-8)alkanyl-R7, NH2, NH(C1-8alkanyl-R7), N(C1-8alkanyl-R7)2, cyano, halogen, hydroxy or Ra;
- R3 and R4 are independently hydrogen, (C1-8)alkanyl-R7, C(O)H, C(O)—(C1-8)alkanyl-R7, CO2H, C(O)O—(C1-8)alkanyl-R7, (C3-8)cycloalkyl-(R8)q or aryl-(R8)q when attached to a nitrogen atom;
- wherein R3 and R4 are independently hydrogen, (C1-8)alkanyl-R7, (C1-8)alkoxy-R7, C(O)H, C(O)—(C1-8)alkanyl-R7, CO2H, C(O)O—(C1-8)alkanyl-R7, NH2, NH(C1-8alkanyl-R7), N(C1-8alkanyl-R7)2, cyano, halogen, hydroxy, (C3-8)cycloalkyl-(R8)q, cyclic heteroalkyl-(R9)q, aryl-(R8)q or heteroaryl-(R9)q when attached to a carbon atom;
- q is 1, 2, 3, 4 or 5;
- and,
- s is 1 or 2;
- and enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof.
20 more elements
A compound of Formula (Ia):
- wherein
- R1a is NR5aR6a;
- R5a is hydrogen, (C1-10)alkanyl-R7a or aryl;
- R6a is hydrogen or (C1-4)alkanyl-R7a;
- R7a is hydrogen, OC(O)—Ra1, NH2, NH(C1-4alkanyl), N(C1-4alkanyl)2 or Ra1;
- Ra1 is cyclic heteroalkyl-(R12a)q or aryl;
- (R12a)q is hydrogen or (C1-4)alkanyl;
- R2a is hydrogen or (C1-4)alkanyl-R7a;
- R3a and R4a are independently hydrogen, (C1-4)alkanyl-R7a or halogen;
- and,
- q is 1;
- and enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof.
9 more elements
Dependencies are inferred from the claim text.