Substituted heterocyclic compounds and methods of use

Abstract

The present invention relates to therapeutic diazobicyclo pyridines and their use in the treatment of arthritis, rheumatoid arthritis, psoriatic arthritis or osteoarthritis, organ transplant, acute transplant or heterograft and homograft rejection, ischemic and reperfusion injury, transplantation tolerance induction, multiple sclerosis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, lupus, graft vs. host diseases, T-cell mediated hypersensitivity diseases, contact hypersensitivity, delayed-type hypersensitivity, gluten-sensitive enteropathy, Type 1 diabetes, psoriasis, contact dermatitis, Hashimoto's thyroiditis, Sjogren's syndrome, autoimmune hyperthyroidism, Graves' Disease, Addison's disease, autoimmune polyglandular disease, autoimmune alopecia, pernicious anemia, vitiligo, autoimmune hypopituatarism, Guillain-Barre syndrome, autoimmune diseases, glomerulonephritis, serum sickness, uticaria, respiratory allergies, asthma, hayfever, allergic rhinitis, skin allergies, scleracielma, mycosis fungoides, acute inflammatory responses, acute respiratory distress syndrome, dermatomyositis, alopecia areata, chronic actinic dermatitis, eczema, Behcet's disease, Pustulosis palmoplanteris, Pyoderma gangrenum, Sezary's syndrome, atopic dermatitis, systemic schlerosis, morphea, Type II diabetes and cancers where PKC theta or other PKC-family kinases are activated, overexpressed or facilitate tumor growth or survival of tumor cells, T cell leukemia, thymoma, T and B cell lymphoma, colon carcinoma, breast carcinoma and lung carcinoma or provides resistance to chemotherapeutic drugs.

1 . A compound of formula I 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein
 J is NH, N(R b ), O or S; 
 m is independently at each instance 0, 1, 2 or 3; 
 n is 1 or 2; 
 R 1  is selected from 
 
     
       
         
         
             
             
         
       
       R 2  is a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 1, 2, 3 or 4 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, and wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a ; 
       R 3  is independently at each instance H, C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R 4  is independently at each instance C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R 5  is H or C 1-6 alkyl substituted by 0, 1, 2 or 3 substituents independently selected from R d  and additionally substituted by 0 or 1 substituents selected from R f ; 
       R 6  is H. R c , R d , or a C 1-6 alkyl substituted by 1, 2 or 3 substituents independently selected from R d  and additionally substituted by 0 or 1 substituents selected from R f . 
       R a  is independently, at each instance, H or R b ; 
       R b  is independently, at each instance, phenyl, benzyl or C 1-6 alkyl, the phenyl, benzyl and C 1-6 alkyl being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alkyl, C 1-3 haloalkyl, —OC 1-4 alkyl, —NH 2 , —NHC 1-4 alkyl, and —N(C 1-4 alkyl)C 1-4 alkyl; 
       R c  is independently at each instance a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups; 
       R d  is independently at each instance C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R e  is independently at each instance R d  or H; and 
       R f  is independently at each instance a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups and the ring is substituted by 0, 1, 2 or 3 substituents selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a . 
     
   
   
       2 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 J is NH or N(R b );   m is independently at each instance 0, 1, 2 or 3;   n is 1 or 2;   R 1  is selected from   
     
       
         
         
             
             
         
       
       R 2  is a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 1, 2, 3 or 4 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, and wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a ; 
       R 3  is independently at each instance H, C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —OR a , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R 4  is independently at each instance C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —OR a , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R 5  is H or C 1-6 alkyl substituted by 0, 1, 2 or 3 substituents independently selected from R d  and additionally substituted by 0 or 1 substituents selected from R f ; 
       R 6  is H, R c , R d , or a C 1-6 alkyl substituted by 1, 2 or 3 substituents independently selected from R d  and additionally substituted by 0 or 1 substituents selected from R f . 
       R a  is independently, at each instance, H or R b ; 
       R b  is independently, at each instance, phenyl, benzyl or C 1-6 alkyl, the phenyl, benzyl and C 1-6 alkyl being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alkyl, C 1-3 haloalkyl, —OC 1-4 alkyl, —NH 2 , —NHC 1-4 alkyl and —N(C 1-4 alkyl)C 1-4 alkyl; 
       R c  is independently at each instance a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups; 
       R d  is independently at each instance C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R e  is independently at each instance R d  or H; and 
       R f  is independently at each instance a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups and the ring is substituted by 0, 1, 2 or 3 substituents selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a . 
     
   
   
       3 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 J is NH, N(R b ), O or S;   m is independently at each instance 0, 1, 2 or 3;   n is 1;   R 1  is selected from   
     
       
         
         
             
             
         
       
       R 2  is a ring selected from phenyl, dihydroindenyl, naphthyl, tetrahydronaphthalenyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, triazinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, quinazolinyl, isoquinazolinyl, tetrahydroquinazolinyl, tetrahydroisoquinazolinyl, morpholinyl, thiophenyl, pyranyl, furyl, dihydrofuryl, tetrahydrofuryl, pyrrolyl, pyazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, indolyl, isoindolyl, indolinyl, benzodioxyl, benzofuranyl, dihydrobenzofuranyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzothiophenyl and benzimidazolyl, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, and wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —OC(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a ; 
       R 3  is independently at each instance H, C 1-8 alkyl, C 1-4 haloalkyl, halo, —OR a , —SR a  or —NR a R a ; 
       R 4  is C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —OR a , —SR a , —NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R 5  is H or C 1-6 alkyl substituted by 0, 1, 2 or 3 substituents independently selected from R d  and additionally substituted by 0 or 1 substituents selected from R f ; 
       R 6  is H, R c , R d , or a C 1-6 alkyl substituted by 1, 2 or 3 substituents independently selected from R d  and additionally substituted by 0 or 1 substituents selected from R f ; 
       R a  is independently, at each instance, H or R b ; 
       R b  is independently, at each instance, phenyl, benzyl or C 1-6 alkyl, the phenyl, benzyl and C 1-6 alkyl being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alkyl, C 1-3 haloalkyl, —OC 1-4 alkyl, —NH 2 , —NHC 1-4 alkyl, —N(C 1-4 alkyl)C 1-4 alkyl; 
       R c  is independently, at each instance, phenyl, dihydroindenyl, naphthyl, tetrahydronaphthalenyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, triazinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, quinazolinyl, isoquinazolinyl, tetrahydroquinazolinyl, tetrahydroisoquinazolinyl, morpholinyl, thiophenyl, pyranyl, furyl, dihydrofuryl, tetrahydrofuryl, pyrrolyl, pyazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, indolyl, isoindolyl, indolinyl, benzodioxyl, benzofuranyl, dihydrobenzofuranyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzothiophenyl or benzimidazolyl, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups; 
       R d  is independently, at each instance, C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R e  is independently, at each instance, R d  or H; and 
       R f  is independently, at each instance, phenyl, dihydroindenyl, naphthyl, tetrahydronaphthalenyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, triazinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, quinazolinyl, isoquinazolinyl, tetrahydroquinazolinyl, tetrahydroisoquinazolinyl, morpholinyl, thiophenyl, pyranyl, furyl, dihydrofuryl, tetrahydrofuryl, pyrrolyl, pyazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, indolyl, isoindolyl, indolinyl, benzodioxyl, benzofuranyl, dihydrobenzofuranyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzothiophenyl or benzimidazolyl, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups and the ring is substituted by 0, 1, 2 or 3 substituents selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)NR a R a , —OR a , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a . 
     
   
   
       4 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 J is NH or NCH 3 ;   m is independently at each instance 0, 1, 2 or 3;   n is 1;   R 1  is selected from   
     
       
         
         
             
             
         
       
       R 2  is a ring selected from phenyl, dihydroindenyl, naphthyl, tetrahydronaphthalenyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, triazinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, quinazolinyl, isoquinazolinyl, tetrahydroquinazolinyl, tetrahydroisoquinazolinyl, morpholinyl, thiophenyl, pyranyl, furyl, dihydrofuryl, tetrahydrofuryl, pyrrolyl, pyazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, indolyl, isoindolyl, indolinyl, benzodioxyl, benzofuranyl, dihydrobenzofuranyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzothiophenyl and benzimidazolyl, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, and wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a ; 
       R 3  is independently at each instance H, C 1-8 alkyl, C 1-4 haloalkyl, halo, —OR a , —SR a  or —NR a R a ; 
       R 4  is C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —OR a , —SR a , —NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R 5  is H or C 1-6 alkyl substituted by 0, 1, 2 or 3 substituents independently selected from R d  and additionally substituted by 0 or 1 substituents selected from R f ; 
       R 6  is H, R c , R d , or a C 1-6 alkyl substituted by 1, 2 or 3 substituents independently selected from R d  and additionally substituted by 0 or 1 substituents selected from R f ; 
       R a  is independently, at each instance, H or R b ; 
       R b  is independently, at each instance, phenyl, benzyl or C 1-6 alkyl, the phenyl, benzyl and C 1-6 alkyl being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alkyl, C 1-3 haloalkyl, —OC 1-4 alkyl, —NH 2 , —NHC 1-4 alkyl and —N(C 4 alkyl)C 1-4 alkyl; 
       R c  is independently, at each instance, phenyl, naphthyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, triazinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, quinazolinyl, isoquinazolinyl, tetrahydroquinazolinyl, tetrahydroisoquinazolinyl, morpholinyl, thiophenyl, pyranyl, furyl, dihydrofuryl, tetrahydrofuryl, pyrrolyl, pyazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, indolyl, isoindolyl, indolinyl, benzofuranyl, dihydrobenzofuranyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzothiophenyl or benzimidazolyl, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups; 
       R d  is independently at each instance C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R e  is independently at each instance R d  or H; and 
       R f  is independently at each instance phenyl, naphthyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, triazinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, quinazolinyl, isoquinazolinyl, tetrahydroquinazolinyl, tetrahydroisoquinazolinyl, morpholinyl, thiophenyl, pyranyl, furyl, dihydrofuryl, tetrahydrofuryl, pyrrolyl, pyazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, indolyl, isoindolyl, indolinyl, benzofuranyl, dihydrobenzofuranyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzothiophenyl or benzimidazolyl, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups and the ring is substituted by 0, 1, 2 or 3 substituents selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)NR a R a , —OR a , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a . 
     
   
   
       5 . The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 6  is H. 
   
   
       6 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 J is NH or NCH 3 ;   m is independently at each instance 0, 1, 2 or 3;   n is 1;   R 1  is selected from   
     
       
         
         
             
             
         
       
       R 2  is a ring selected from phenyl, dihydroindenyl, naphthyl, tetrahydronaphthalenyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, triazinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, quinazolinyl, isoquinazolinyl, tetrahydroquinazolinyl, tetrahydroisoquinazolinyl, morpholinyl, thiophenyl, pyranyl, furyl, dihydrofuryl, tetrahydrofuryl, pyrrolyl, pyazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, indolyl, isoindolyl, indolinyl, benzodioxyl, benzofuranyl, dihydrobenzofuranyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzothiophenyl and benzimidazolyl, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, and wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a ; 
       R 3  is independently at each instance H, C 1-8 alkyl, C 1-4 haloalkyl, halo or OR a ; 
       R 4  is H or C 1-8 alkyl; 
       R 5  is H or C 1-6 alkyl substituted by 0, 1, 2 or 3 substituents independently selected from R d  and additionally substituted by 0 or 1 substituents selected from R f ; 
       R 6  is H or C 1-6 alkyl; 
       R a  is independently, at each instance, H or R b ; 
       R b  is independently, at each instance, phenyl, benzyl or C 1-6 alkyl, the phenyl, benzyl and C 1-6 alkyl being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alkyl, C 1-3 haloalkyl, —OC 1-4 alkyl, —NH 2 , —NHC 1-4 alkyl and —N(C 1-4 alkyl)C 1-4 alkyl; 
       R d  is independently at each instance C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a    
       R e  is independently at each instance R d  or H; and 
       R f  is independently, at each instance, phenyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, triazinyl, morpholinyl, thiophenyl, pyranyl, furyl, dihydrofuryl, tetrahydrofuryl, pyrrolyl, pyazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, indolyl, isoindolyl, indolinyl, benzofuranyl, dihydrobenzofuranyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzothiophenyl or benzimidazolyl, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups and the ring is substituted by 0, 1, 2 or 3 substituents selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)NR a R a , —OR a , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a . 
     
   
   
       7 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 J is NH or NCH 3 ;   m is independently at each instance 0, 1, 2 or 3;   n is 1;   R 1  is   
     
       
         
         
             
             
         
       
       R 2  is a ring selected from phenyl, dihydroindenyl, naphthyl, tetrahydronaphthalenyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiophenyl, pyranyl, furyl, dihydrofuryl, tetrahydrofuryl, pyazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, indolyl, isoindolyl, indolinyl, benzodioxyl, benzofuranyl, dihydrobenzofuranyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzothiophenyl and benzimidazolyl, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, and wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a ; 
       R 3  is independently, at each instance, H, —CH 3 , —CH 2 CH 3  or —OR a ; 
       R 4  is absent; 
       R 5  is H, —CH 3 , —CH 2 CH 3 , —C(═O)CH(OH)CH 3 , —SO 2 CH 3 , —C(═O)CH(CH 3 )OC(═O)CH 3 , -propyl, -isopropyl, —CH 2 CHCF 2 , -n-butyl, -t-butyl, -isobutyl, —(CH 2 ) 2 COOH, —(CH 2 ) 2 COOCH 3 , —(CH2) 2 OPh, —CH(CH 3 )ethyl, —CH(CH3)CF 3 , -cyclopentyl or —OR a ; 
       R 6  is H, —CH 3  or —CH 2 CH 3 ; 
       R a  is independently, at each instance, H or R b ; and 
       R b  is independently, at each instance, phenyl, benzyl or C 1-6 alkyl, the phenyl, benzyl and C 1-6 alkyl being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alkyl, C 1-3 haloalkyl, —OC 1-4 alkyl, —NH 2 , —NHC 1-4 alkyl and —N(C 1-4 alkyl)C 1-4 alkyl. 
     
   
   
       8 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 J is NH or NCH 3 ;   m is independently at each instance 0, 1, 2 or 3;   n is 1;   R 1  is   
     
       
         
         
             
             
         
       
       R 2  is a ring selected from phenyl, dihydroindenyl, naphthyl, tetrahydronaphthalenyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiophenyl, pyranyl, furyl, dihydrofuryl, tetrahydrofuryl, pyazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, indolyl, isoindolyl, indolinyl, benzodioxyl, benzofuranyl, dihydrobenzofuranyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzothiophenyl and benzimidazolyl, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, and wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —C 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a ; 
       R 3  is independently at each instance H, —CH 3 , —CH 2 CH 3  or —OR a ; 
       R 4  is absent; 
       R 5  is H, —CH 3 , —CH 2 CH 3 , —C(═O)CH(OH)CH 3 , —SO 2 CH 3 , —C(═O)CH(CH 3 )OC(═O)CH 3 , -propyl, -isopropyl, —CH 2 CHCF 2 , -n-butyl, -t-butyl, -isobutyl, —(CH 2 ) 2 COOH, —(CH 2 ) 2 COOCH 3 , —(CH2) 2 OPh, —CH(CH 3 )ethyl, —CH(CH3)CF 3 , -cyclopentyl or —OR a ; 
       R 6  is H, —CH 3  or —CH 2 CH 3 ; 
       R a  is independently, at each instance, H or R b ; 
       R b  is independently, at each instance, phenyl, benzyl or C 1-6 alkyl, the phenyl, benzyl and C 1-6 alkyl being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alkyl, C 1-3 haloalkyl, —OC 1-4 alkyl, —NH 2 , —NHC 1-4 alkyl and —N(C 1-4 alkyl)C 1-4 alkyl; and 
       R e  is independently, at each instance, H, Cl, F, Br, I, CH 3 , NO 2 , NHSO 2 CH 3 , OH, CF 3  or N-Acetyl. 
     
   
   
       9 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 J is NH or NCH 3 ;   m is independently at each instance 0, 1, 2 or 3;   n is 1;   R 1  is selected from   
     
       
         
         
             
             
         
       
       R 2  is a ring selected from phenyl, dihydroindenyl, naphthyl, tetrahydronaphthalenyl, pyridyl, pyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiophenyl, pyranyl, furyl, dihydrofuryl, tetrahydrofuryl, pyazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, indolyl, isoindolyl, indolinyl, benzodioxyl, benzofuranyl, dihydrobenzofuranyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzothiophenyl and benzimidazolyl, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, and wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a ; 
       R 3  is independently at each instance H, —CH 3 , —CH 2 CH 3  or —OR a ; 
       R 4  is absent; 
       R 5  is H, —CH 3 , —CH 2 CH 3 , —C(═O)CH(OH)CH 3 , —SO 2 CH 3 , —C(═O)CH(CH 3 )OC(═O)CH 3 , -propyl, -isopropyl, —CH 2 CHCF 2 , -n-butyl, -t-butyl, -isobutyl, —(CH 2 ) 2 COOH, —(CH 2 ) 2 COOCH 3 , —(CH 2 ) 2 OPh, —CH(CH 3 )ethyl, —CH(CH3)CF 3 , -cyclopentyl or —OR a ; 
       R 6  is H, —CH 3  or —CH 2 CH 3 ; 
       R a  is independently, at each instance, H or R b ; 
       R b  is independently, at each instance, phenyl, benzyl or C 1-6 alkyl, the phenyl, benzyl and C 1-6 alkyl being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alkyl, C 1-3 haloalkyl, —OC 1-4 alkyl, —NH 2 , —NHC 1-4 alkyl and —N(C 1-4 alkyl)C 1-4 alkyl; and 
       R e  is independently, at each instance, H, Cl, F, Br, I, CH 3 , NO 2 , NHSO 2 CH 3 , OH, CF 3  or N-Acetyl. 
     
   
   
       10 . A compound according to  claim 1 , wherein the compound is selected from: 
     5-[7-(2-Chloro-pyridin-4-yl)-imidazo[1,2-c]pyrimidin-5-yl]-(1S,4S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester; 
     (S)-{4-[5-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-Ethyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (R)-{4-[5-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (R)-{4-[5-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     {4-[5-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1,2-dimethyl-propyl)-amine; 
     (1,2-Dimethyl-propyl)-{4-[5-(5-isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-amine; 
     {4-[5-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-naphthalen-1-ylmethyl-amine; 
     {4-[5-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-naphthalen-1-ylmethyl-amine; 
     (S)-{4-[6-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-2-methylsulfanyl-pyrimidin-4-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[6-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-2-methylsulfanyl-pyrimidin-4-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-(2,2-Dimethoxy-ethyl)-{2-(5-isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-6-[2-(1-phenyl-ethylamino)-pyridin-4-yl]-pyrimidin-4-yl}-amine; 
     (S)-{4-[5-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-naphthalen-1-yl-ethyl)-amine; 
     (S)-{4-[5-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-[1,2,4]triazolo[1,5-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-naphthalen-1-yl-ethyl)-amine; 
     (S)-[2′-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-[4,4′]bipyridinyl-2-yl]-(1-phenyl-ethyl)-amine; 
     (S)-[2′-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-[4,4′]bipyridinyl-2-yl]-(1-phenyl-ethyl)-amine; 
     3-Methyl-2-(5-methyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-6-[2-(S)-(1-phenyl-ethylamino)-pyridin-4-yl]-3H-pyrimidin-4-one; 
     2-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-3-methyl-6-[2-((S)-1-phenyl-ethylamino)-pyridin-4-yl]-3H-pyrimidin-4-one; 
     (S)-{4-[5-(5-tert-Butyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[3-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-indazol-1-yl]-pyridin-2-yl}-[1-(2-fluoro-phenyl)-ethyl]-amine; 
     (S)-{4-[5-(5-Isopropyl-6-methyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     2-{2-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-6-[2-(S)-(1-phenyl-ethylamino)-pyridin-4-yl]-pyrimidin-4-ylamino}-ethanol; 
     (S)-{4-[5-(5-n-Butyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-(2,2,2-Trifluoro-1-methyl-ethyl)-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-sec-Butyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-Cyclopentyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-Methyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-Propyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-Isobutyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-Benzyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-(2-Phenoxy-ethyl)-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-(2-Phenoxy-propyl)-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[5-(5-(2-Phenoxy-propyl)-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-(4-{5-[5-(2,2-Difluoro-ethyl)-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl]-imidazo[1,2-c]pyrimidin-7-yl}-pyridin-4-yl)-(1-phenyl-ethyl)-amine; 
     (S)-{4-[2-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-thiazol-4-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     {4-[4-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-quinazolin-2-yl]-pyridin-2-yl}-(S)-(1-phenyl-ethyl)-amine; 
     (S)-{4-[2-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-thiazol-4-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[4-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-quinolin-2-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[4-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-quinolin-2-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[4-(5-Ethyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-quinolin-2-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[4-(5-Methyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-quinolin-2-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     Benzyl-(4-[5-((1S,4S)-2-5-diaza-bicyclo[2,2,1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl)-amine; 
     Benzyl-{4-[5-(5-isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-amine; 
     {4-[5-((1S,4S)-2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-(2-fluoro-benzyl)-amine; 
     (2-Fluoro-benzyl)-{4-[5-(5-isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-imidazo[1,2-c]pyrimidin-7-yl]-pyridin-2-yl}-amine; 
     Benzyl {4-[5-((1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl)imidazo[1,2-c]pyrimidin-7-yl]pyridin-2-yl}methyl amine; 
     (S)-{4-[4-(5-Methyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-quinazolin-2-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[4-(5-Ethyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-quinazolin-2-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; 
     (S)-{4-[4-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-quinazolin-2-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine; and 
     (S)-{4-[2-(5-Isopropyl-(1S,4S)-2,5-diaza-bicyclo[2.2.1]hept-2-yl)-pyrimidin-4-yl]-pyridin-2-yl}-(1-phenyl-ethyl)-amine, or a pharmaceutically acceptable salt thereof. 
   
   
       11 . A compound of formula II 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein
 J is NH, N(R b ), O or S; 
 K is —C(R 3 R 3 ) m , —C(═O), —C(═O)O—, —C(═O)N(R a )—, —C(═NR a )N(R a )—, —O—, —OC(═O)—, —OC(═O)N(R a )—, —OC 2-6 alkylN(R a ), —OC 2-6 alkylO—, —S—, —S(═O)—, —S(═O) 2 —S(═O) 2 N(R a ), —N(R a )—, —N(R a )C(═O)—, —N(R a )C(═O)O—, —N(R a )C(═O)N(R a )—, —N(R a )C(═NR a )N(R a )—, —N(R a )S(═O) 2 —, —N(R a )S(═O) 2 N(R a )— or —N(R a )C 2-6 alkylN(R a ); 
 R 1  is selected from 
 
     
       
         
         
             
             
         
       
       R 2  is a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 1, 2, 3 or 4 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups, and wherein the ring is substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a ; 
       R 3  is independently at each instance H, C 1-8 alkyl, C 1-8 alkylOR a , C 1-4 haloalkyl, C 1-4 haloalkylOR a , halo, cyano, nitro, oxo, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R e , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R 4  is C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R 5  is H, C(═O)R b , S(O) p R b , C(═O)R c , S(O) p R c , or C 1-6 alkyl substituted by 0, 1, 2 or 3 substituents independently selected from R d  and additionally substituted by 0 or 1 substituents selected from R f ; 
       R a  is H, R c , R d , or a C 1-6 alkyl substituted by 1, 2 or 3 substituents independently selected from R d  and additionally substituted by 0 or 1 substituents selected from R f . 
       R a  is independently, at each instance, H or R b ; 
       R b  is independently, at each instance, phenyl, benzyl or C 1-6 alkyl, the phenyl, benzyl and C 1-6 alkyl being substituted by 0, 1, 2 or 3 substituents selected from halo, C 1-4 alkyl, C 1-3 haloalkyl, —OC 1-4 alkyl, —NH 2 , —NHC 1-4 alkyl, and —N(C 1-4 alkyl)C 1-4 alkyl; 
       R c  is independently at each instance a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, so long as the combination of O and S atoms is not greater than 2, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups; 
       R d  is independently at each instance C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  or —NR a C 2-6 alkylOR a ; 
       R e  is independently at each instance R d  or H; 
       R f  is independently at each instance a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups and the ring is substituted by 0, 1, 2 or 3 substituents selected from C 1-8 alkyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a  and —NR a C 2-6 alkylOR a ; 
       m is independently at each instance 0, 1, 2 or 3; 
       n is 1; and 
       p is 0, 1 or 2. 
     
   
   
       12 . A pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable carrier. 
   
   
       13 . A pharmaceutical composition comprising a compound according to  claim 11  and a pharmaceutically acceptable carrier. 
   
   
       14 . A method of treatment of inflammation comprising administering an effective amount of a compound according to  claim 1  to a mammal. 
   
   
       15 . A method of treating a disease or disorder associated with the activation of
 T cells, the method comprising administering an effective amount of a compound according to  claim 1  to a mammal.   
   
   
       16 . A method of treatment of arthritis, rheumatoid arthritis, psoriatic arthritis or osteoarthritis, organ transplant, acute transplant or heterograft and homograft rejection, ischemic and reperfusion injury, transplantation tolerance induction, multiple sclerosis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, lupus, graft vs. host diseases, T-cell mediated hypersensitivity diseases, contact hypersensitivity, delayed-type hypersensitivity, gluten-sensitive enteropathy, Type 1 diabetes, psoriasis, contact dermatitis, Hashimoto's thyroiditis, Sjogren's syndrome, autoimmune hyperthyroidism, autoimmune diseases, respiratory allergies, asthma, hayfever, allergic rhinitis, skin allergies, dermatomyositis, chronic actinic dermatitis, eczema and atopic dermatitis in a mammal comprising administering an effective amount of a compound according to  claim 1  to the mammal.