2,8-diazaspiro[4.5]decane compounds

A compound of Formula (I):

• or an N-oxide thereof, or a pharmaceutically acceptable salt thereof, wherein:
• R1 is 5- to 14-membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• R2 is hydrogen, halogen, C1-6 alkyl, —O(C1-6 alkyl), —NH(C1-6 alkyl) or —N(C1-6 alkyl)2, wherein each C1-6 alkyl is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• R3 is hydrogen, C1-6 alkyl, halogen, cyano, hydroxyl, —O(C1-6 alkyl), C2-6 alkenyl or C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• R4 is hydrogen, halogen, cyano, —NR43aR43b, —OR44, C1-6 alkyl or C3-6 cycloalkyl, wherein the C1-6 alkyl and C3-6 cycloalkyl are each optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• G1 is N or CR41, G2 is N or CR42, provided that one or both of G1 and G2 are N;
• R41 and R42 are independently hydrogen, halogen, cyano, —NR43aR43b, —OR44, C1-6 alkyl or C3-6 cycloalkyl, wherein the C1-6 alkyl and C3-6 cycloalkyl are each optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• each R43a and R43b is independently hydrogen or C1-6 alkyl;
• R44 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 3- to 14-membered heterocyclyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl and 3- to 14-membered heterocyclyl of R44 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;
• R5 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-14 aryl, 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl, —C(O)R14, —C(O)OR15 or —C(O)NR16aR16b, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-14 aryl, 5 to 14-membered heteroaryl and 3- to 14-membered heterocyclyl of R5 are each optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• or is taken together with R6a or R6b and the atoms to which they are attached to form a 3- to 14-membered heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• each R6a and R6b is independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 14-membered heteroaryl, 3- to 12-membered heterocyclyl, —C(O)R14, —C(O)OR15 or —C(O)NR16aR16b, wherein the C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 14-membered heteroaryl, and 3- to 12-membered heterocyclyl of R6a and R6b are each optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• or taken together with R5 and the atoms to which they are attached to form a 3- to 14-membered heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• or R6a and R6b are taken together with the carbon to which they are attached to form a carbonyl;
• each R7a and R7b is independently hydrogen or C1-6 alkyl optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• or R7a and R7b are taken together with the carbon to which they are attached to form a carbonyl;
• each R8a and R8b is independently hydrogen, halogen, hydroxyl, —O(C1-6 alkyl) or C1-6 alkyl, wherein each C1-6 alkyl is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• n is 0 to 8;
• each R9 is independently C1-6 alkyl;
• or two geminal Rg groups, if present, are taken together with the carbon to which they are attached to form a carbonyl;
• each R14 is independently hydrogen or C1-6 alkyl;
• each R15 is independently C1-6 alkyl;
• each R16a and R16b is independently hydrogen or C1-6 alkyl;
• or R16a and R16b are taken together with the nitrogen atom to which they are attached to form a 4- to 12-membered heterocyclyl optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R10;
• each R10 is independently oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-14 aryl, 5- to 14-membered heteroaryl, 3- to 14-membered heterocyclyl, halogen, cyano, —C(O)Ra, —C(O)ORb, —C(O)NRcRd, —ORb, —OC(O)Ra, —OC(O)NRcRd, —SRb, —S(O)Rc, —S(O)2Rc, —S(O)(═NH)Rc, —S(O)2NRcRd, —NRcRd, —N(Rf)C(O)Ra, —N(Rf)C(O)ORb, —N(Rf)C(O)NRcRd, —N(Rf)S(O)2Rc, —N(Rf)S(O)2NRcRd or —P(O)RgRh, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-14 aryl, 5- to 14-membered heteroaryl and 3- to 14-membered heterocyclyl of R10 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
• each Ra is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl or 3- to 12-membered heterocyclyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl and 3- to 12-membered heterocyclyl of Ra are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
• each Rb is independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl or 3- to 12-membered heterocyclyl, wherein the C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl and 3- to 12-membered heterocyclyl of Rb are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
• each Rc and Rd is independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl or 3- to 12-membered heterocyclyl;
• wherein the C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl and 3- to 12-membered heterocyclyl of Rc and Rd are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
• or Rc and Rd are taken together with the nitrogen atom to which they are attached to form a 4- to 12-membered heterocyclyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
• each Rc is independently C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl or 3- to 12-membered heterocyclyl, wherein the C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl and 3- to 12-membered heterocyclyl of Rc are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
• each Rf2 is independently hydrogen or C1-6 alkyl;
• each Rg and Rh is independently C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocyclyl or —O—C1-6 alkyl;
• wherein the C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl and 3- to 12-membered heterocyclyl of Rg and Rh are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
• or Rg and Rh are taken together with the phosphorus atom to which they are attached to form a 4- to 12-membered heterocyclyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R11;
• each R11 is independently oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, 3- to 8-membered heterocyclyl, halogen, cyano, —C(O)Ra1, —C(O)ORb1, —C(O)NRc1Rd1, —OR11, —OC(O)Ra1, —OC(O)NRc1Rd1, —SR11, —S(O)Rc1, —S(O)2Rc1, —S(O)2NRc1Rd1, —NRc1Rd1, —N(Rf1)C(O)Ra1, —N(R11)C(O)ORb1, —N(Rf1)C(O)NRc1Rd1, —N(Rf1)S(O)2Rc1, —N(Rf1)S(O)2NRc1Rd1 or —P(O)Rg1Rh1;
• wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl and 3- to 8-membered heterocyclyl of R11 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R12;
• each Ra1 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl or 3- to 8-membered heterocyclyl;
• wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl and 3- to 8-membered heterocyclyl of Ra1 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R12;
• each Rb1 is independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl or 3- to 8-membered heterocyclyl;
• wherein the C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl and 3- to 8-membered heterocyclyl of Rb1 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R12;
• each Rc1 and Rd1 is independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl or 3- to 8-membered heterocyclyl;
• wherein the C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl and 3- to 8-membered heterocyclyl of Rc1 and Rd1 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R12;
• or Rc1 and Rd1 are taken together with the nitrogen atom to which they are attached to form a 4- to 8-membered heterocyclyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R12;
• each Rc1 is independently C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl or 3- to 8-membered heterocyclyl;
• wherein the C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl and 3- to 8-membered heterocyclyl of Rc1 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R12;
• each Rf1 is independently hydrogen or C1-6 alkyl;
• each Rg1 and Rh1 is independently C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, 3- to 8-membered heterocyclyl, or —O—C1-6 alkyl;
• wherein the C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl and 3- to 8-membered heterocyclyl of Rg1 and Rh1 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R12;
• or Rg1 and Rh1 are taken together with the phosphorus atom to which they are attached to form a 4- to 8-membered heterocyclyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R12;
• each R12 is independently oxo, C1-6 alkyl, C3-6 cycloalkyl, C6 aryl, 5- to 6-membered heteroaryl, 3- to 6-membered heterocyclyl, halogen, cyano, —C(O)Ra2, —C(O)ORb2, —C(O)NRc2Rd2, —ORb2, —OC(O)Ra2, —OC(O)NRc2Rd2, —S(O)2Rc2, —S(O)2NRc2Rd2, —NRc2Rd2, —N(Rf)C(O)Ra2, —N(Rf)C(O)ORb2, —N(Rf)C(O)NRc2Rd2, —N(Rf2)S(O)2Rc2, —N(Rf)S(O)2NRc2Rd2 or —P(O)Rg2Rh2;
• wherein the C1-6 alkyl, C3-6 cycloalkyl, C6 aryl, 5- to 6-membered heteroaryl and 3- to 6-membered heterocyclyl of R12 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
• each Ra2 is independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C6 aryl, 5- to 6-membered heteroaryl or 3- to 6-membered heterocyclyl;
• wherein the C1-6 alkyl, C3-6 cycloalkyl, C6 aryl, 5- to 6-membered heteroaryl and 3- to 6-membered heterocyclyl of Ra2 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
• each Rb2 is independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl or 3- to 6-membered heterocyclyl;
• wherein the C1-6 alkyl, C3-6 cycloalkyl and 3- to 6-membered heterocyclyl of Rb2 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
• each Rc2 and Rd2 is independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl or 3- to 8-membered heterocyclyl;
• wherein the C1-6 alkyl, C3-6 cycloalkyl and 3- to 8-membered heterocyclyl of Rc2 and Rd2 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
• or Rc2 and Rd2 are taken together with the nitrogen atom to which they are attached to form a 4- to 6-membered heterocyclyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
• each Rc2 is independently C1-6 alkyl, C3-6 cycloalkyl, C6 aryl, 5- to 6-membered heteroaryl or 3- to 6-membered heterocyclyl;
• wherein the C1-6 alkyl, C3-6 cycloalkyl, C6 aryl, 5 to 6-membered heteroaryl and 3- to 6-membered heterocyclyl of Rc2 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
• each Rf2 is independently hydrogen or C1-6 alkyl;
• each Rg2 and Rh2 is independently C1-6 alkyl, C3-6 cycloalkyl, 3- to 8-membered heterocyclyl, or —O—C1-6 alkyl;
• wherein the C1-6 alkyl, C3-6 cycloalkyl, and 3- to 8-membered heterocyclyl of Rg2 and Rh2 are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
• or Rg2 and Rh2 are taken together with the phosphorus atom to which they are attached to form a 4- to 6-membered heterocyclyl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R13;
• and
• each R13 is independently oxo, halogen, hydroxyl, —O(C1-6 alkyl), cyano, C1-6 alkyl or C1-6 haloalkyl;
• provided that the compound is other than a compound in Table 1X and salts thereof.