Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as JAK inhibitors

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• X is CH or N;
• Y is H, cyano, halo, C1-3 alkyl, or C1-3 haloalkyl;
• Z is N;
• W is CH or N;
• when W is CH, then L is O, S, C(R6)2, C(═O), C(═O)N(R7), C(═O)O, C(═O)C(R6)2, S(═O), S(═O)2, S(═O)N(R7), S(═O)2N(R7), or C(═NR7a)N(R7);
• or
• when W is N, then L is C(R6)2, C(═O), C(═O)O, C(═O)N(R7), C(═O)C(R6)2, S(═O), S(═O)2, S(═O)N(R7), S(═O)2N(R7), or C(═NR7a)N(R7);
• R1, R2 and R3 are each independently H, hydroxy, halo, C1-3 alkyl, or C1-3 haloalkyl;
• each R5 is independently hydroxy, C1-4 alkoxy, fluorine, C1-4 alkyl, hydroxy-C1-4-alkyl, C1-4 alkoxy-C1-4-alkyl, or C1-4 fluoroalkyl;
• each R6 is, independently, H or C1-4 alkyl;
• or
• two R6 groups, together with the carbon atom to which they are attached, form a 3-, 4-, 5-, or 6-membered cycloalkyl ring;
• R7 is H or C1-4 alkyl;
• R7a is H, OH, CN, C1-4 alkoxy, or C1-4 alkyl;
• or R7 and R7a, taken together with the C(═N)N moiety to which they are attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl ring or a 5- or 6-membered heteroaryl ring;
• A is H, C1-6 alkyl, C3-10 cycloalkyl, C2-10 heterocycloalkyl, C6-10 aryl, or C1-10 heteroaryl;
• wherein said C1-6 alkyl, C3-10 cycloalkyl, C2-10 heterocycloalkyl, C6-10 aryl, and C1-10 heteroaryl are each optionally substituted with p independently selected R8 substituents;
• wherein p is 1, 2, 3, 4, or 5;
• provided when L is O, S, C(═O), C(═O)O, S(═O), or S(═O)2, then A is not H;
• each R8 is independently selected from halo, cyano, nitro, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4-alkyl, C2-10 heterocycloalkyl, C2-10 heterocycloalkyl-C1-4-alkyl, C6-10 aryl, C6-10 aryl-C1-4-alkyl, C1-10 heteroaryl, C1-10 heteroaryl-C1-4-alkyl, —ORa, —SRa, —S(═O)Rb, —S(═O)2Rb, —S(═O)2NReRf, —C(═O)Rb, —C(═O)ORa, —C(═O)NReRf, —OC(═O)Rb, —OC(═O)NReRf, —NReRf, —NRcC(═O)Rd, —NRcC(═O)ORd, —NRcS(═O)2Rd, and —NRcS(═O)2NReRf;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4-alkyl, C2-10 heterocycloalkyl, C2-10 heterocycloalkyl-C1-4-alkyl, C6-10 aryl, C6-10 aryl-C1-4-alkyl, C1-10 heteroaryl, and C1-10 heteroaryl-C1-4-alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected Rg groups;
• each Ra, Rc, Rd, Re, and Rf is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4-alkyl, C2-10 heterocycloalkyl, C2-10 heterocycloalkyl-C1-4-alkyl, C6-10 aryl, C6-10 aryl-C1-4-alkyl, C1-10 heteroaryl, and C1-10 heteroaryl-C1-4-alkyl;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4-alkyl, C2-10 heterocycloalkyl, C2-10 heterocycloalkyl-C1-4-alkyl, C6-10 aryl, C6-10 aryl-C1-4-alkyl, C1-10 heteroaryl, and C1-10 heteroaryl-C1-4-alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected Rg groups;
• each Rb is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4-alkyl, C2-10 heterocycloalkyl, C2-10 heterocycloalkyl-C1-4-alkyl, C6-10 aryl, C6-10 aryl-C1-4-alkyl, C1-10 heteroaryl, and C1-10 heteroaryl-C1-4-alkyl;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkyl-C1-4-alkyl, C2-10 heterocycloalkyl, C2-10 heterocycloalkyl-C1-4-alkyl, C6-10 aryl, C6-10 aryl-C1-4-alkyl, C1-10 heteroaryl, and C1-10 heteroaryl-C1-4-alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected Rg groups;
• each Rg is independently selected from halo, cyano, nitro, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3-alkyl, C2-7 heterocycloalkyl, C2-7 heterocycloalkyl-C1-3-alkyl, phenyl, phenyl-C1-3-alkyl, C1-7 heteroaryl, C1-7 heteroaryl-C1-3-alkyl, —ORa1, —SRa1, —S(═O)Rb1, —S(═O)2Rb1, —S(═O)2NRe1Rf1, —C(═O)Rb1, —C(═O)ORa1, —C(═O)NRe1Rf1, —OC(═O)Rb1, —OC(═O)NRe1Rf1, —NRe1Rf1, —NRc1C(═O)Rd1, —NRc1C(═O)ORd1, —NRc1S(═O)2Rd1, and —NRc1S(═O)2NRe1Rf1;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3-alkyl, C2-7 heterocycloalkyl, C2-7 heterocycloalkyl-C1-3-alkyl, phenyl, phenyl-C1-3-alkyl, C1-7 heteroaryl, and C1-7 heteroaryl-C1-3-alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected Rh groups;
• each Ra1, Rc1, Rd1, Re1, and Rf1 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3-alkyl, C2-7 heterocycloalkyl, C2-7 heterocycloalkyl-C1-3-alkyl, phenyl, phenyl-C1-3-alkyl, C1-7 heteroaryl, and C1-7 heteroaryl-C1-3-alkyl;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3-alkyl, C2-7 heterocycloalkyl, C2-7 heterocycloalkyl-C1-3-alkyl, phenyl, phenyl-C1-3-alkyl, C1-7 heteroaryl, and C1-7 heteroaryl-C1-3-alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected Rh groups;
• each Rb1 is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3-alkyl, C2-7 heterocycloalkyl, C2-7 heterocycloalkyl-C1-3-alkyl, phenyl, phenyl-C1-3-alkyl, C1-7 heteroaryl, and C1-7 heteroaryl-C1-3-alkyl;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3-alkyl, C2-7 heterocycloalkyl, C2-7 heterocycloalkyl-C1-3-alkyl, phenyl, phenyl-C1-3-alkyl, C1-7 heteroaryl, and C1-7 heteroaryl-C1-3-alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected Rh groups;
• each Rh is independently selected from cyano, halo, hydroxy, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, hydroxy-C1-4 alkyl, C1-4 alkoxy-C1-4 alkyl, cyano-C1-4 alkyl, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino;
• m is 0, 1, or 2;
• and
• n is 0, 1, 2, 3, or 4.