N-arylsulfonyl aza-bicyclic derivatives as potent cell adhesion inhibitors

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof wherein:
• Ring A is cycloalkyl or heterocyclyl,
• wherein ring A is optionally substituted with one to four substituents independently selected from Rc;
• X and Y are independently selected from
• 1) halogen,
• 2) C1-3alkyl,
• 3) C1-3alkoxy;
• Z is
• 1) N,
• 2) N+—O—;
• R1 is
• 1) hydrogen,
• 2) C1-10alkyl,
• 3) aryl-C1-10alkyl;
• R2 is
• 1) hydrogen or
• 2) C1-10alkyl;
• R3 and R4 are independently selected from
• 1) hydrogen,
• 2) C1-10alkyl,
• 3) —ORd,
• 4) —CO2Rd,
• 5) —C(O)NRdRe,
• 6) —NRdRe,
• 7) —NRdS(O)mRe,
• 8) —NRdC(O)Re,
• 9) —NRdC(O)ORe,
• 10) —NRdC(O)NRdRe,
• wherein alkyl is optionally substituted with one to four substituents independently selected from Ra;
• R5 is
• 1) hydrogen,
• 2) OH,
• 3) OCH3;
• or
• 4) NH2;
• Ra is
• 1) —ORd,
• 2) —NRdS(O)mRe,
• 3) —NO2,
• 4) halogen
• 5) —S(O)pRd,
• 6) —SRd,
• 7) —S(O)2ORd,
• 8) —S(O)mNRdRe,
• 9) —NRdRe,
• 10) —O(CRfRg)nNRdRe,
• 11) —C(O)Rd,
• 12) —CO2Rd,
• 13) —CO2(CRfRg)nCONRdRe,
• 14) —OC(O)Rd,
• 15) —CN,
• 16) —C(O)NRdRe,
• 17) —NRdC(O)Re,
• 18) —OC(O)NRdRe,
• 19) —NRdC(O)ORe,
• 20) —NRdC(O)NRdRe,
• 21) —CRd(N—ORe),
• 22) CF3,
• 23) —OCF3,
• 24) C3-8cycloalkyl, or
• 25) heterocyclyl;
• wherein cycloalkyl and heterocyclyl are optionally substituted with one to four groups independently selected from Rc;
• Rc is
• 1) halogen,
• 2) amino,
• 3) carboxy,
• 4) C1-4alkyl,
• 5) C1-4alkoxy,
• 6) aryl,
• 7) aryl C1-4alkyl,
• 8) hydroxy,
• 9) CF3,
• 10) OC(O)C1-4alkyl,
• 11) OC(O)NRfRg, or
• 12) aryloxy;
• Rd and Re are independently selected from hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, Cy and Cy C1-10alkyl, wherein alkyl, alkenyl, alkynyl and Cy are optionally substituted with one to four substituents independently selected from Rc;
• or
• Rd and Re together with the atom(s) to which they are attached form a heterocyclic ring of 4 to 7 members containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and N—Rh;
• Rf and Rg are independently selected from hydrogen, C1-10alkyl, Cy and Cy—C1-10alkyl;
• or
• Rf and Rg together with the carbon to which they are attached form a ring of 5 to 7 members containing 0-2 heteroatoms independently selected from oxygen, sulfur and nitrogen;
• Rh is selected from Rf and —C(O)Rf;
• Cy is selected from cycloalkyl, heterocyclyl, aryl, and heteroaryl;
• Ar1 is selected from phenyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl and triazinyl each optionally substituted with one or two groups independently selected from Rc;
• Ar2 is 1,4-phenylene or 2,5-pyridylene;
• p is 1 or 2;
• m is 0, 1 or 2;
• n is 0, 1 or 2.