Aryl-triazolyl and related gpr84 antagonists and uses thereof

A compound of Formula II:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is
• or Y1;
• R2 is —(C2-4 alkynylene)-(C3-7 cycloalkyl), —(C2-4 alkynylene)-(C1-3 alkylene)-(C1-6 alkoxyl), —(C2-4 alkynylene)-(phenyl substituted with 0, 1, or 2 occurrences of R10), —(C2-4 alkynylene)-(5-6 membered heteroaryl containing 1 or 2 heteroatoms selected from nitrogen and oxygen, wherein the heteroaryl is substituted with 0, 1, or 2 occurrences of R10), —(C2-4 alkynylene)-(phenyl substituted with 0, 1, or 2 occurrences of R11), —(C2-4 alkynylene)-(5-6 membered heteroaryl containing 1 or 2 heteroatoms selected from nitrogen and oxygen, wherein the heteroaryl is substituted with 0, 1, or 2 occurrences of R11), -(3-7 membered saturated heterocyclyl containing 1 or 2 heteroatoms selected from nitrogen and oxygen, wherein the heterocyclyl is substituted with 0, 1, or 2 groups independently selected from C1-6 alkyl and C1-6 hydroxyalkyl), -(7-9 membered saturated spirocyclic heterocyclyl containing 1 or 2 heteroatoms selected from nitrogen and oxygen, wherein the spirocyclic heterocyclyl is substituted with 0, 1, or 2 groups independently selected from C1-6 alkyl and C1-6 hydroxyalkyl), -(3-7 membered saturated heterocyclylene containing 1 or 2 heteroatoms selected from nitrogen and oxygen)-(C1-4 alkylene)-(5-6 membered heteroaryl containing 1 or 2 heteroatoms selected from nitrogen and oxygen), or Y2;
• R3 represents independently for each occurrence halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxyl, C3-6 cycloalkyl, —O—C3-6 cycloalkyl, —N(R7)(R8), or Y3;
• R4 and R5 are independently C1-6 alkyl or C1-2 deuteroalkyl, or R4 and R5 are taken together with their intervening atom(s) to form a 3-5 membered saturated carbocyclic ring;
• R6 is C1-6 alkyl or C3-6 cycloalkyl;
• R7 and R8 each represent independently for each occurrence hydrogen, C1-6 alkyl, or C3-6 cycloalkyl;
• or R7 and R8 are taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocyclic ring containing 1 nitrogen atom;
• R9 is hydrogen, C1-6 alkyl, or C3-6 cycloalkyl;
• R10 represents independently for each occurrence halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxyl, or C3-6 cycloalkyl;
• R11 represents independently for each occurrence halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxyl, C3-6 cycloalkyl, or —O—C3-6 cycloalkyl;
• A1 is
• or Y4, wherein ** is a point of attachment to L2;
• A2 is phenylene or Y5, wherein the phenylene is substituted with n occurrences of R3;
• L1 is a C1-3 alkylene;
• L2 is —N(R9)—, Y6, or C1-4 alkylene substituted by C1-4 alkoxyl;
• Y1 is —C(O)N(R7)(R8), —N(R7)C(O)(R6), —CO2R7,
• or a 6-membered heteroaryl containing 1 or 2 nitrogen atoms, wherein the heteroaryl is substituted by 0, 1, or 2 occurrences of R10;
• Y2 is —C≡C—(C1-3 alkylene)-N(R7)SO2—R6, —C≡C—(C1-3 alkylene)-SO2—N(R7)(R8), —C≡C—(C0-3 alkylene)-N(R7)C(O)R6, —C≡C—(C0-3 alkylene)-C(O)N(R7)(R8), —C≡C—(C1-3 alkylene)-N(R7)(R8), —C≡C—(C1-3 alkylene)-O—(C3-6 cycloalkyl), —C≡C—(C1-3 alkylene)-O—(C1-5 haloalkyl), —C≡C—(C1-5 haloalkyl), —C≡C-(cyclobutyl), —C≡C—(C(CH3)2(OH)), —C≡C-(hydroxycyclopropyl), —C≡C—(C1-3 alkylene)-N(R7)(4-6 membered saturated heterocyclyl containing 1 oxygen atom), —C≡C—(C1-3 alkylene)-N(R7)—(C0-3 alkylene)-(5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur), —C≡C—(C1-3 alkylene)-(triazolyl optionally substituted by one phenyl which is optionally substituted by one C1-3 alkyl),
• -(azetidinylene substituted with 1 or 2 occurrences of C1-4 alkyl)-Z2, -(azetidinyl substituted with one C1-4 haloalkyl and one C1-4 alkyl), -(azetidinyl substituted with one C1-4 alkyl and one C1-3 alkylene-O—C3-6 cycloalkyl), -(azetidinyl substituted with one C1-4 haloalkyl and one C1-4 alkyl), -(azetidinyl substituted with one C1-4 alkyl and one C1-4 haloalkoxy), —(C0-3 alkylene)-CN, —(C2 alkynylene)-CN, C1-4 haloalkyl, —(C0-3 alkylene)-C(O)N(R7)(R8), —O—(C1-3 alkylene)-C(O)N(R7)(R8), —N(R7)—(C1-3 alkylene)-C(O)N(R7)(R8), C3-7 cycloalkyl, -(7-10 membered spirocyclic hydroxy-substituted saturated heterocyclyl containing 1, 2, or 3 heteroatoms selected from nitrogen and oxygen), —C(O)N(R7)—(C1-3 alkylene)-(5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from oxygen, nitrogen, and sulfur), phenyl, benzyl, (C1-4 alkylene)-(5-6 membered heteroaryl containing 1 or 2 heteroatoms selected from nitrogen and oxygen), (C0-4 alkylene)-(C3-6 cycloalkyl), C1-4 alkoxyl, C1-6 hydroxyalkyl, or hydrogen;
• Y3 is —N(R7) (C1-4 deuteroalkyl) or —N(C1-4 deuteroalkyl)2;
• wherein ** is a point of attachment to L2;
• Y5 is a 5-6 membered heteroarylene containing 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroarylene is substituted with n occurrences of R3;
• Y6 is (a) —C≡C—or -(C1-4 alkylene) (C(H) (C1-4 alkoxyl)-, (b)C2-4 alkylene substituted by 0 or 1 C3-5 cycloalkyl, (c)C1-4 alkylene substituted by —S—C1-4 alkyl, or (d)—CH2—or -O—;
• Z1 is C1-10 aliphatic, —(C0-3 alkylene)-(3-7 membered saturated heterocyclyl containing 1, 2, or 3 heteroatoms selected from nitrogen and oxygen, wherein the heterocyclyl is substituted with 1, 2, or 3 groups independently selected from C1-6 alkyl and C1-6 hydroxyalkyl), —N(R7)—(C0-3 alkylene)-(5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur), —(C0-3 alkylene)-(5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur), or C1-6 hydroxyalkyl;
• Z2 is one of the following:
• (a) 3-7 membered saturated heterocyclyl substituted 1 or 2 occurrences of R3,
• (b)—(C0-3 alkylene)-N(R7)—(C0-3 alkylene)-(5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur), or
• (c) 5-6 membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• n is 0, 1, or 2;
• wherein there is at least one occurrence of Y1, Y2, Y3, Y4, Y5, or Y6;
• and
• provided that if A1 is
• and Y6 is —CH2—or -O—, then R3 is not methyl.