MASP-2 inhibitors and methods of use

A compound of Formula (I-1):

• or a salt thereof, wherein:
• Cy1A is substituted C6-10 aryl;
• wherein the substituted C6-10 aryl is substituted with 1, 2, 3, 4 or 5 substituents each independently selected from RCy1A, halogen, C1-6 haloalkyl, CN, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)NRc11Rd11, NRc11C(O)ORa11, C(═NRe11)NRc11Rd11, C(═NORa11)NRc11Rd11, C(═NOC(O)Rb11)NRc11Rd11, C(═NRe11)NRc11C(O)ORa11, NRc11C(═NRe11)NRc11Rd11, S(O)Rb11, S(O)NRc11Rd11, S(O)2Rb11, NRc11S(O)2Rb11, S(O)2NRc11Rd11 and oxo;
• each RCy1A is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, and C3-10 cycloalkyl, wherein each C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl forming RCy1A is independently unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, CN, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rd11, NRc11C(O)NRc11Rd11, NRc11C(O)ORa11, C(═NRe11)NRc11Rd11, NRc11(═NRe11)NRc11Rd11, S(O)Rb11, S(O)NRc11Rd11, S(O)2Rb11, NRc11S(O)2Rb11, S(O)2NRc11Rd11 and oxo, and wherein each C6-10 aryl is independently unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRe11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)NRc11Rd11, NRc11C(O)ORa11, C(═NRe11)NRc11Rd11, NRc11C(═NRe11)NRc11Rd11, S(O)Rb11, S(O)NRc11Rd11, S(O)2Rb11, S(O)2NRc11IS(O)2Rb11, S(O)2NRc11Rd11 and oxo;
• each R13 is independently Cy1B, (CR13AR13B)n3Cy1B, (C1-6 alkylene)Cy1B, (C2-6 alkenylene)Cy1B, (C2-6 alkynylene)Cy1B or OCy1B, wherein the C1-6 alkylene, C2-6 alkenylene, or C2-6 alkynylene component of R13 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from the group consisting of halogen, CN, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)NRc11Rd11, NRc11C(O)ORa11, C(═NRe11)NRc11Rd11, NRc11C(═NRe11)NRc11Rd11, S(O)Rb11, S(O)NRb11, S(O)2Rb11, NRc11S(O)2Rb11, S(O)2NRc11Rd11 and oxo;
• n3 is 0, 1, or 2;
• R15 is selected from H, R13, C1-6 alkyl and OH;
• each R13A is independently H or C1-6 alkyl;
• each R13B is independently H or C1-6 alkyl;
• or
• or R13A and R13B attached to the same carbon atom, independently of any other R13A and R13B groups, together may form —(CH2)2-5—, thereby forming a 3-6 membered cycloalkyl ring;
• Cy1B is unsubstituted or substituted C6-10 aryl;
• and
• wherein the substituted C6-10 aryl is substituted with 1, 2, 3, 4 or 5 substituents each independently selected from RCy1B, halogen, C1-6 haloalkyl, CN, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)NRc11Rd11, NRc11C(O)ORa11, C(═NRe11)NRc11Rd11, C(═NORa11)NRc11Rd11, C(═NOC(O)Rb11)NRc11Rd11, C(═NRe11)NRc11C(O)ORa11, NRc11C(═NRe11)NRc11Rd11, S(O)ORb11, S(O)NRc11Rd11, S(O)2Rb11, NRc11S(O)2Rb11, S(O)2NRc11Rd11 and oxo;
• wherein each RCy1B is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl and 4-10 membered heterocycloalkyl, wherein the ring atoms of the 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl forming RCy1B consist of carbon atoms and 1, 2 or 3 heteroatoms selected from O, N and S;
• wherein each C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl forming RCy1B is independently unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, CN, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)NRc11Rd11, NRc11C(O)ORa11, C(═NRe11)NRc11Rd11, NRc11C(═NRe11)NRc11Rd11, S(O)Rb11, S(O)NRc11Rd11, S(O)2Rb11, NRc11S(O)2Rb11, S(O)2NRc11Rd11 and oxo;
• and wherein each C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl and 4-10 membered heterocycloalkyl forming RCy1B is independently unsubstituted or substituted with 1, 2 or 3 substituents independently selected from halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rda11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)NRc11Rd11, NRc11C(O)ORa11, C(═NRe11)NRc11Rd11, NRc11C(═NRe11)NRc11Rd11, S(O)Rb11, S(O)NRc11Rd11, S(O)2Rb11, NRc11S(O)2Rb11, S(O)2NRc11Rd11 and oxo;
• R16 is H, Cy1C, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl forming R16 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents selected from the group consisting of Cy1C, halogen, CN, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)NRc11Rd11, NRc11C(O)ORa11, C(═NRe11)NRc11Rd11, NRc11C(═NRe11)NRc11Rd11, S(O)Rb11, S(O)NRc11Rd11, S(O)2Rb11, NRc11S(O)2Rb11, S(O)2NRc11Rd11 and oxo, provided that no more than one of the substituents of R16 is Cy1C;
• Cy1C is unsubstituted or substituted C6-10 aryl, or unsubstituted or substituted C3-10 cycloalkyl;
• and
• wherein the substituted C6-10 aryl or substituted C3-10 cycloalkyl forming Cy1C are substituted with 1, 2, 3, 4 or 5 substituents each independently selected from RCy1C, halogen, C1-6 haloalkyl, CN, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)NRc11Rd11, NRc11C(O)ORa11, C(═NRe11)NRc11Rd11, C(═NORa11)NRc11Rd11, C(═NOC(O)Rb11)NRc11Rd11, C(═NRe11)NRc11C(O)ORa11, NRc11C(═NRe11)NRc11Rd11, S(O)Rb11, S(O)NRc11Ra11, S(O)2Rb11, NRc11S(O)2Rb11, S(O)2NRc11Rd11 and oxo;
• wherein each RCy1C is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl;
• Ra11, Rb11, Rc11 and Rd11 are each independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-3 alkyl, 5-10 membered heteroaryl-C1-3 alkyl, C3-7 cycloalkyl-C1-3 alkyl and 4-10 membered heterocycloalkyl-C1-3 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-3 alkyl, 5-10 membered heteroaryl-C1-3 alkyl, C3-7 cycloalkyl-C1-3 alkyl and 4-10 membered heterocycloalkyl-C1-3 alkyl forming Ra11, Rb11, Rc11 and Rd11 are each optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from C1-6 alkyl, halo, CN, ORa12, SRa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRc12Rd12, NRc12C(O)Rb12, NRc12C(O)NRc12Rd12 NRc12C(O)ORa12, C(═NRe12)NRc12Rd12, NRc12C(═NRe12)NRc12Rd12, S(O)Rb12, S(O)NRc12Rd12, S(O)2Rb12, NRc12S(O)2Rb12 S(O)2NRc12Rd12 and oxo;
• or Re11 and Rd11 attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or 5-membered heteroaryl group, each optionally substituted with 1, 2 or 3 substituents independently selected from C1-6 alkyl, halo, CN, ORa12, SRa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRc12Rd12, NRc12C(O)Rb12, NRc12C(O)NRc12Rd12 NRc12C(O)ORa12, C(═NRe12)NRc12Rd12, NRc12C(═NRe12)NRc12Rd12, S(O)Rb12, S(O)NRc12Rd12, S(O)2Rb12, NRc12S(O)2Rb12 S(O)2NRc12Rd12 and oxo;
• Ra12, Rb12, Rc12 and Rd12 are each independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-3 alkyl, 5-6 membered heteroaryl-C1-3 alkyl, C3-7 cycloalkyl-C1-3 alkyl and 4-7 membered heterocycloalkyl-C1-3 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-3 alkyl, 5-6 membered heteroaryl-C1-3 alkyl, C3-7 cycloalkyl-C1-3 alkyl and 4-7 membered heterocycloalkyl-C1-3 alkyl forming Ra12, Rb12, Rc12 and Rd12 are each optionally substituted with 1, 2 or 3 substituents independently selected from OH, CN, amino, NH(C1-6 alkyl), N(C1-6 alkyl)2, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy and oxo;
• or Rc12 and Rd12 attached to the same N atom, together with the N atom to which they are both attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or 5-membered heteroaryl group, each of which is unsubstituted or substituted with 1, 2 or 3 substituents independently selected from OH, CN, amino, NH(C1-6 alkyl), N(C1-6 alkyl)2, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy and oxo;
• and
• Re11 and Re12 are each, independently, H, CN or NO2.