Triazolopyridinylsulfanyl derivatives as P38 map kinase inhibitors

A method of treating a disease, disorder or condition in a mammal, said method comprising administering to said mammal a therapeutically effective amount of a compound of

• formula (I):
• or a pharmaceutically acceptable salt thereof,
• wherein:
• R1 is CH3, SCH3, SCH2CH3, CH2CH3, H or CH2SCH3;
• R1a is CH3 or CH2CH3;
• R2 is heteroaryl, heterocyclyl, aryl, or carbocyclyl;
• R3 is heteroaryl, heterocyclyl, aryl, carbocyclyl or R7;
• R7 is (C1-C6)alkyl optionally substituted with one to three substituents independently selected from OH, halo, NR5R6, (C1-C6)alkoxy, —S(O)p(C1-C6)alkyl, CO2H, CONR5R6, heteroaryl, heterocyclyl, aryl, carbocyclyl, aryloxy, carbocyclyloxy, heteroaryloxy and heterocyclyloxy;
• p is 0, 1 or 2;
• R5 and R6 are taken separately and are each independently selected from H and (C1-C4)alkyl, said (C1-C4)alkyl being optionally substituted with one to three substituents independently selected from OH and halo,
• or R5 and R6 are taken together with the nitrogen to which they are attached to form a piperazinyl, piperidinyl, morpholinyl or pyrrolidinyl group, wherein said piperazinyl, piperidinyl, morpholinyl and pyrrolidinyl groups are each optionally substituted by one to three OH);
• said aryl is independently phenyl or naphthyl, said phenyl or naphthyl being optionally substituted with one to three substituents independently selected from halo, —CN, —CO2H, OH, CONR5R6, NR5R6, R8 and R9;
• R8 is independently selected from (C1-C6)alkyl, (C1-C6)alkoxy, —CO2(C1-C6)alkyl, —S(O)p(C1-C6)alkyl, —CO(C1-C6)alkyl and (C3-C7)cycloalkyl, wherein each R8 is optionally substituted independently with one to three substituents independently selected from:
• (C1-C6)alkoxy, optionally substituted with one to three substituents independently selected from OH, halo, CO2H, CONR5R6 and NR5R6,
• —S(O)p(C1-C6)alkyl, optionally substituted with one to three substituents independently selected from OH, halo, CO2H, CONR5R6 and NR5R6,
• OH,
• halo,
• NR5R6,
• CO2H,
• CONR5R6, and
• R9;
• R9 is heteroaryl2, heterocyclyl2, aryl2, carbocyclyl2, aryl2oxy, carbocyclyl2oxy, heteroaryl2oxy or heterocyclyl2oxy;
• aryl2 is phenyl or naphthyl wherein said phenyl or naphthyl in the definition of aryl2 is optionally substituted with one to three substituents independently selected from halo, —CN, —CO2H, OH, and CONR5R6;
• carbocyclyl is a monocyclic or bicyclic, saturated or partially unsaturated ring system comprising from 3 to 10 ring carbon atoms, wherein said ring system is optionally substituted with one to three substituents independently selected from halo, —CN, —CO2H, OH, CONR5R6, R8 and R9;
• carbocyclyl2 is a monocyclic or bicyclic, saturated or partially unsaturated ring system comprising from 3 to 10 ring carbon atoms, optionally substituted with one to three substituents independently selected from halo, —CN, —CO2H, —OH and CONR5R6;
• heterocyclyl and heterocyclyl2 are each independently a 3- to 10-membered, saturated or partially unsaturated, monocyclic or bicyclic group comprising from 1 to 4 ring heteroatoms independently selected from N, O, and S;
• heteroaryl and heteroaryl2 are each independently a 5- to 10-membered, monocyclic or bicyclic aromatic group comprising from 1 to 4 ring heteroatoms independently selected from N, O, and S, provided that the total number of ring S atoms does not exceed 1, and the total number of ring O atoms does not exceed 1;
• each heterocyclyl and heteroaryl group is, independently, optionally substituted on one to three ring carbon atoms with one to three substituents independently selected from halo, —CN, —CO2H, OH, CONR5R6, R8 and R9, and independently optionally substituted on one to three ring nitrogen atoms with one to three substituents independently selected from H and (C1-C6)alkyl;
• and
• each heterocyclyl2 and heteroaryl2 group is, independently, optionally substituted on one to three ring carbon atoms with one to three substituents independently selected from halo, —CN, —CO2H, OH and CONR5R6, and independently optionally substituted on one to three ring nitrogen atoms with one substituent independently selected from H and (C1-C6)alkyl, or a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable diluent, carrier or adjuvant, wherein said disease, disorder or condition is selected from the group consisting of asthma, chronic or acute bronchoconstriction, small airways obstruction, emphysema, chronic obstructive pulmonary disease (COPD), bronchitis, bronchiectasis and COPD that includes chronic bronchitis.