Quinazolinone dione compounds and uses thereof

A compound represented by Formula (IIa):

• or a salt thereof, wherein R22 is selected from:
• p is an integer selected from 1, 2, 3, 4, and 5;
• q is an integer selected from 1, 2, 3, and 4;
• each R21 is independently selected from:
• halogen, —NO2, —N3, —CN, —OR210a, —SR210a, —N(R210a)2, —C(O)R210a, —C(O)N(R210a)2, —N(R210a)C(O)R210a, —N(R210a)C(O)N(R210a)2, —OC(O)N(R210a)2, —N(R210a)C(O)OR210a, —C(O)OR210a, —OC(O)R210a, —S(O)R210a, and —S(O)2R210a;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210a, —SR210a, —N(R210a)2, —C(O)R210a, —C(O)N(R210a)2, —N(R210a)C(O)R210a, —C(O)OR210a, —OC(O)R210a, —N(R210a)C(O)N(R210a)2, —OC(O)N(R210a)2, —N(R210a)C(O)OR210a, —S(O)R210a, —S(O)2R210a, —NO2, ═O, ═S, ═N(R210a), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R29a;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210a, —SR210a, —N(R210a)2, —C(O)R210a, —C(O)N(R210a)2, —N(R210a)C(O)R210a, —N(R210a)C(O)N(R210a)2, —OC(O)N(R210a)2, —N(R210a)C(O)OR210a, —C(O)OR210a, —OC(O)R210a, —S(O)R210a, —S(O)2R210a, —NO2, ═O, ═S, ═N(R210a), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R29a;
• R2Z is selected from:
• —C(O)R210z, —C(O)N(R210z)2, —C(O)OR210z, and —CN;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210z, —SR210z, —N(R210z)2, —C(O)R210z, —C(O)N(R210z)2, —N(R210z)C(O)R210z, —C(O)OR210z, —OC(O)R210z, —N(R210z)C(O)N(R210z)2, —OC(O)N(R210z)2, —N(R210z)C(O)OR210z, —S(O)R210z, —S(O)2R210z, —NO2, ═O, ═S, ═N(R210z), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R29z;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210z, —SR210z, —N(R210z)2, —C(O)R210z, —C(O)N(R210z)2, —N(R210z)C(O)R210z, —N(R210z)C(O)N(R210z)2, —OC(O)N(R210z)2, —N(R210z)C(O)OR210z, —C(O)OR210z, —OC(O)R210z, —S(O)R210z, —S(O)2R210z, —NO2, ═O, ═S, ═N(R210z), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R29z;
• R2C is selected from:
• hydrogen;
• —C(O)R210c, —C(O)N(R210c)2, —C(O)OR210c, and —CN;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210c, —SR210c, —N(R210c)2, —C(O)R210c, —C(O)N(R210c)2, —N(R210c)C(O)R210c, —C(O)OR210c,—OC(O)R210c, —N(R210c)C(O)N(R210c)2, —OC(O)N(R210c)2, —N(R210c)C(O)OR210c, —S(O)R210c, —S(O)2R210c, —NO2, ═O, ═S, ═N(R210c), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R29c;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210c, —SR210c, —N(R210c)2, —C(O)R210c, —C(O)N(R210c)2, —N(R210c)C(O)R210c, —N(R210c)C(O)N(R210c)2, —OC(O)N(R210c)2, —N(R210c)C(O)OR210c, —C(O)OR210c, —OC(O)R210c, —S(O)R210c, —S(O)2R210c, —NO2, ═O, ═S, ═N(R210c), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R29e;
• R25 is selected from:
• hydrogen;
• halogen, —OR210d, —SR210d, —N(R210d)2, —C(O)R210d, —C(O)N(R210d)2, —N(R210d)C(O)R210d, —C(O)OR210d, —OC(O)R210d, —N(R210d)C(O)N(R210d)2, —OC(O)N(R210d)2, —N(R210d)C(O)OR210d, —S(O)R210d, —S(O)2R210d, —NO2, —N3, and —CN;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210d, —SR210d, —N(R210d)2, —C(O)R210d, —C(O)N(R210d)2, —N(R210d)C(O)R210d, —C(O)OR210d, —OC(O)R210d, —N(R210d)C(O)N(R210d)2, —OC(O)N(R210d)2, —N(R210d)C(O)OR210d, —S(O)R210d, —S(O)2R210d, —NO2, ═O, ═S, ═N(R210d), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R29d;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210d, —SR210d, —N(R210d)2, —C(O)R210d, —C(O)N(R210d)2, —N(R210d)C(O)R210d, —N(R210d)C(O)N(R210d)2, —OC(O)N(R210d)2, —N(R210d)C(O)OR210d, —C(O)OR210d, —OC(O)R210d, —S(O)R210d, —S(O)2R210d, —NO2, ═O, ═S, ═N(R210d), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R29d;
• or
• R25 together with R26 form a 3- to 10-membered heterocycle or C3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C3-10 carbocycle is optionally substituted with one or more R29d;
• R26 is selected from:
• hydrogen;
• halogen, —OR210e, —SR210e, —N(R210e)2, —C(O)R210e, —C(O)N(R210e)2, —N(R210e)C(O)R210e, —C(O)OR210e, —OC(O)R210e, —N(R210e)C(O)N(R210e)2, —OC(O)N(R210e)2, —N(R210e)C(O)OR210e, —S(O)R210e, —S(O)2R210e, —NO2, —N3, and —CN;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210e, —SR210e, —N(R210e)2, —C(O)R210e, —C(O)N(R210e)2, —N(R210e)C(O)R210e, —C(O)OR210e, —OC(O)R210e, —N(R210e)C(O)N(R210e)2, —OC(O)N(R210e)2, —N(R210e)C(O)OR210e, —S(O)R210e, —S(O)2R210e, —NO2, ═O, ═S, ═N(R210e), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R29e;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210e, —SR210e, —N(R210e)2, —C(O)R210e, —C(O)N(R210e)2, —N(R210e)C(O)R210e, —N(R210e)C(O)N(R210e)2, —OC(O)N(R210e)2, —N(R210e)C(O)OR210e, —C(O)OR210e, —OC(O)R210e, —S(O)R210e, —S(O)2R210e, —NO2, ═O, ═S, ═N(R210e), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R29e;
• or
• R26 together with R25 form a 3- to 10-membered heterocycle or C3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C3-10 carbocycle is optionally substituted with one or more R29e,
• R27 is selected from:
• hydrogen;
• —C(O)R210f, —C(O)N(R210f)2, —C(O)OR210f, —S(O)R210f, and —S(O)2R210f;
• C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR210f, —SR210f, —N(R210f)2, —C(O)R210f, —C(O)N(R210f)2, —N(R210f)C(O)R210f, —C(O)OR210f, —OC(O)R210f, —N(R210f)C(O)N(R210f)2, —OC(O)N(R210f)2, —N(R210f)C(O)OR210f, —S(O)R210f, —S(O)2R210f, —NO2, ═O, ═S, ═N(R210f), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R29f;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210f, —SR210f, —N(R210f)2, —C(O)R210f, —C(O)N(R210f)2, —N(R210f)C(O)R210f, —N(R210f)C(O)N(R210f)2, —OC(O)N(R210f)2, —N(R210f)C(O)OR210f, —C(O)OR210f, —OC(O)R210f, —S(O)R210f, —S(O)2R210f, —NO2, ═O, ═S, ═N(R210f), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R29f;
• R28 is selected from:
• hydrogen;
• —C(O)R210g, —C(O)N(R210g)2, —C(O)OR210g, —S(O)R210g, and —S(O)2R210g;
• C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR210g, —SR210g, —N(R210g)2, —C(O)R210g, —C(O)N(R210g)2, —N(R210g)C(O)R210g, —C(O)OR210g, —OC(O)R210g, —N(R210g)C(O)N(R210g)2, —OC(O)N(R210g)2, —N(R210g)C(O)OR210g, —S(O)R210g, —S(O)2R210g, —NO2, ═O, ═S, ═N(R210g), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R29g;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210g, —SR210g, —N(R210g)2, —C(O)R210g, —C(O)N(R210g)2, —N(R210g)C(O)R210g, —N(R210g)C(O)N(R210g)2, —OC(O)N(R210g)2, —N(R210g)C(O)OR210g, —C(O)OR210g, —OC(O)R210g, —S(O)R210g, —S(O)2R210g, —NO2, ═O, ═S, ═N(R210g), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more R29g;
• each R29a is independently selected from:
• halogen, —OR210a, —SR210a, —N(R210a)2, —C(O)R210a, —C(O)N(R210a)2, —N(R210a)C(O)R210a, —N(R210a)C(O)N(R210a)2, —OC(O)N(R210a)2, —N(R210a)C(O)OR210a, —C(O)OR210a, —OC(O)R210a, —S(O)R210a, —S(O)2R210a, —NO2, ═O, ═S, ═N(R210a), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210a, —SR210a, —N(R210a)2, —C(O)R210a, —C(O)N(R210a)2, —N(R210a)C(O)R210a, —N(R210a)C(O)N(R210a)2, —OC(O)N(R210a)2, —N(R210a)C(O)OR210a, —C(O)OR210a, —OC(O)R210a, —S(O)R210a, —S(O)2R210a, —NO2, ═O, ═S, ═N(R210a), —N3, and —CN;
• each R29b is independently selected from:
• halogen, —NO2, —N3, —CN, —OR210b, —SR210b, —N(R210b)2, —C(O)R210b, —C(O)N(R210b)2, —N(R210b)C(O)R210b, —N(R210b)C(O)N(R210b)2, —OC(O)N(R210b)2, —N(R210b)C(O)OR210b, —C(O)OR210b, —OC(O)R210b, —S(O)R210b, and —S(O)2R210b;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210b, —SR210b, —N(R210b)2, —C(O)R210b, —C(O)N(R210b)2, —N(R210b)C(O)R210b, —C(O)OR210b, —OC(O)R210b, —N(R210b)C(O)N(R210b)2, —OC(O)N(R210b)2, —N(R210b)C(O)OR210b, —S(O)R210b, —S(O)2R210b, —NO2, ═O, ═S, ═N(R210b), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210b, —SR210b, —N(R210b)2, —C(O)R210b, —C(O)N(R210b)2, —N(R210b)C(O)R210b, —N(R210b)C(O)N(R210b)2, —OC(O)N(R210b)2, —N(R210b)C(O)OR210b, —C(O)OR210b, —OC(O)R210b, —S(O)R210b, —S(O)2R210b, —NO2, ═O, ═S, ═N(R210b), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
• each R29e is independently selected from:
• halogen, —OR210e, —SR210e, —N(R210e)2, —C(O)R210e, —C(O)N(R210e)2, —N(R210e)C(O)R210e, —N(R210e)C(O)N(R210e)2, —OC(O)N(R210e)2, —N(R210e)C(O)OR210e, —C(O)OR210e, —OC(O)R210e, —S(O)R210e, —S(O)2R210e, —NO2, ═O, ═S, ═N(R210e), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210e, —SR210e, —N(R210e)2, —C(O)R210e, —C(O)N(R210e)2, —N(R210e)C(O)R210e, —N(R210e)C(O)N(R210e)2, —OC(O)N(R210e)2, —N(R210e)C(O)OR210e, —C(O)OR210e, —OC(O)R210e, —S(O)R210e, —S(O)2R210e, —NO2, ═O, ═S, ═N(R210e), —N3, and —CN;
• each R29d is independently selected from:
• halogen, —OR210d, —SR210d, —N(R210d)2, —C(O)R210d, —C(O)N(R210d)2, —N(R210d)C(O)R210d, —N(R210d)C(O)N(R210d)2, —OC(O)N(R210d)2, —N(R210d)C(O)OR210d, —C(O)OR210d, —OC(O)R210d, —S(O)R210d, —S(O)2R210d, —NO2, ═O, ═S, ═N(R210d), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210d, —SR210d, —N(R210d)2, —C(O)R210d, —C(O)N(R210d)2, —N(R210d)C(O)R210d, —N(R210d)C(O)N(R210d)2, —OC(O)N(R210d)2, —N(R210d)C(O)OR210d, —C(O)OR210d, —OC(O)R210d, —S(O)R210d, —S(O)2R210d, —NO2, ═O, ═S, ═N(R210d), —N3, and —CN;
• each R29e is independently selected from:
• halogen, —OR210e, —SR210e, —N(R210e)2, —C(O)R210e, —C(O)N(R210e)2, —N(R210e)C(O)R210e, —N(R210e)C(O)N(R210e)2, —OC(O)N(R210e)2, —N(R210e)C(O)OR210e, —C(O)OR210e, —OC(O)R210e, —S(O)R210e, —S(O)2R210e, —NO2, ═O, ═S, ═N(R210e), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210e, —SR210e, —N(R210e)2, —C(O)R210e, —C(O)N(R210e)2, —N(R210e)C(O)R210e,—N(R210e)C(O)N(R210e)2, —OC(O)N(R210e)2, —N(R210e)C(O)OR210e, —C(O)OR210e, —OC(O)R210e, —S(O)R210e, —S(O)2R210e, —NO2, ═O, ═S, ═N(R210e), —N3, and —CN;
• each R29f is independently selected from:
• halogen, —OR210f, —SR210f, —N(R210f)2, —C(O)R210f, —C(O)N(R210f)2, —N(R210f)C(O)R210f, —N(R210f)C(O)N(R210f)2, —OC(O)N(R210f)2, —N(R210f)C(O)OR210f, —C(O)OR210f, —OC(O)R210f, —S(O)R210f, —S(O)2R210f, —NO2, ═O, ═S, ═N(R210f), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210f, —SR210f, —N(R210f)2, —C(O)R210f, —C(O)N(R210f)2, —N(R210f)C(O)R210f, —N(R210f)C(O)N(R210f)2, —OC(O)N(R210f)2, —N(R210f)C(O)OR210f, —C(O)OR210f, —OC(O)R210f, —S(O)R210f, —S(O)2R210f, —NO2, ═O, ═S, ═N(R210f), —N3, and —CN;
• each R29g is independently selected from:
• halogen, —OR210g, —SR210g, —N(R210g)2, —C(O)R210g, —C(O)N(R210g)2, —N(R210g)C(O)R210g, —N(R210g)C(O)N(R210g)2, —OC(O)N(R210g)2, —N(R210g)C(O)OR210g, —C(O)OR210g, —OC(O)R210g, —S(O)R210g, —S(O)2R210g, —NO2, ═O, ═S, ═N(R210g), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210g, —SR210g, —N(R210g)2, —C(O)R210g, —C(O)N(R210g)2, —N(R210g)C(O)R210g, —N(R210g)C(O)N(R210g)2, —OC(O)N(R210g)2, —N(R210g)C(O)OR210g, —C(O)OR210g, —OC(O)R210g, —S(O)R210g, —S(O)2R210g, —NO2, ═O, ═S, ═N(R210g), —N3, and —CN;
• each R29z is independently selected from:
• halogen, —OR210z, —SR210z, —N(R210z)2, —C(O)R210z, —C(O)N(R210z)2, —N(R210z)C(O)R210z, —N(R210z)C(O)N(R210z)2, —OC(O)N(R210z)2, —N(R210z)C(O)OR210z, —C(O)OR210z, —OC(O)R210z, —S(O)R210z, —S(O)2R210z, —NO2, ═O, ═S, ═N(R210z), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR210z, —SR210z, —N(R210z)2, —C(O)R210z, —C(O)N(R210z)2, —N(R210z)C(O)R210z, —N(R210z)C(O)N(R210z)2, —OC(O)N(R210z)2, —N(R210z)C(O)OR210z, —C(O)OR210z, —OC(O)R210z, —S(O)R210z, —S(O)2R210z, —NO2, ═O, ═S, ═N(R210z), —N3, and —CN;
• and
• each R210a, R210b, R210c, R210d, R210e, R210f, R210g, and R210z is independently selected from:
• hydrogen;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C3-10 carbocycle, 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, 3- to 10-membered heterocycle, and C1-6 haloalkyl.

A compound represented by Formula (Id):

• or a salt thereof, wherein:
• R2 is selected from:
• u is an integer selected from 0, 1, 2, and 3;
• Z1 is selected from:
• —C(RZ)2, —, —N(RZ)—, —N+(—O−), —O—, and —S—;
• each Z2 is independently selected from:
• —C(RZ)(RZ′)-, —N(RZ)—, —N+(—O−), —O—, and —S—;
• X1 is selected from C(R1a), N, and N+(—O−);
• X2 is selected from C(R1b), N, and N+(—O−);
• X3 is selected from C(R1c), N, and N+(—O−);
• X4 is selected from C(R1d), N, and N+(—O−);
• wherein no more than two of X1, X2, X3, and X4 are N or —N+(—O−);
• Y2 is selected from C(R9bB), N, and N+(—O−);
• Y3 is selected from C(R9bC), N, and N+(—O−);
• Y4 is selected from C(R9bD), N, and N+(—O−);
• Y5 is selected from C(R9bE), N, and N+(—O−);
• wherein no more than three of Y2, Y3, Y4, and Y5 are N or —N+(—O−);
• R1a, R1b, R1c, and R1d, are each independently selected from:
• hydrogen;
• halogen, —NO2, —N3, —CN, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —C(O)OR10a, —OC(O)R10a, —S(O)R10a, and —S(O)2R10a;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —C(O)OR10a, —OC(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —S(O)R10a, —S(O)2R10a, —NO2, ═O, ═S, ═N(R10a), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9a;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —C(O)OR10a, —OC(O)R10a, —S(O)R10a, —S(O)2R10a, —NO2, ═O, ═S, ═N(R10a), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9a;
• each RZ is independently selected from:
• hydrogen;
• —CN, —C(O)R10z, —C(O)N(R10z)2, and —C(O)OR10z;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10z, —SR10z, —N(R10z)2, —C(O)R10z, —C(O)N(R10z)2, —N(R10z)C(O)R10z, —C(O)OR10z, —OC(O)R10z, —N(R10z)C(O)N(R10z)2, —OC(O)N(R10z)2, —N(R10z)C(O)OR10z, —S(O)R10z, —S(O)2R10z, —NO2, ═O, ═S, ═N(R10z), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9z;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10z, —SR10z, —N(R10z)2, —C(O)R10z, —C(O)N(R10z)2, —N(R10z)C(O)R10z, —N(R10z)C(O)N(R10z)2, —OC(O)N(R10z)2, —N(R10z)C(O)OR10z, —C(O)OR10z, —OC(O)R10z, —S(O)R10z, —S(O)2R10z, —NO2, ═O, ═S, ═N(R10z), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9z;
• each RZ′is independently selected from:
• hydrogen;
• —CN, —C(O)R10z, —C(O)N(R10z)2, and —C(O)OR10z;
• C1 alkyl substituted with substituted with one or more substituents independently selected from halogen, —OR10z, —SR10z, —N(R10z)2, —C(O)R10z, —C(O)N(R10z)2, —N(R10z)C(O)R10z, —C(O)OR10z, —OC(O)R10z, —N(R10z)C(O)N(R10z)2, —OC(O)N(R10z)2, —N(R10z)C(O)OR10z, —S(O)R10z, —S(O)2R10z, —NO2, ═O, ═S, ═N(R10z), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more R9z;
• C2-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10z, —SR10z, —N(R10z)2, —C(O)R10z, —C(O)N(R10z)2, —N(R10z)C(O)R10z, —C(O)OR10z, —OC(O)R10z, —N(R10z)C(O)N(R10z)2, —OC(O)N(R10z)2, —N(R10z)C(O)OR10z, —S(O)R10z, —S(O)2R10z, —NO2, ═O, ═S, ═N(R10z), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9z;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10z, —SR10z, —N(R10z)2, —C(O)R10z, —C(O)N(R10z)2, —N(R10z)C(O)R10z, —N(R10z)C(O)N(R10z)2, —OC(O)N(R10z)2, —N(R10z)C(O)OR10z, —C(O)OR10z, —OC(O)R10z, —S(O)R10z, —S(O)2R10z, —NO2, ═O, ═S, ═N(R10z), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9z;
• RC is selected from:
• hydrogen;
• —CN, —C(O)R10c, —C(O)N(R10c)2, —C(O)OR10c;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10c, —SR10c, —N(R10c)2, —C(O)R10c, —C(O)N(R10c)2, —N(R10c)C(O)R10c, —C(O)OR10c, —OC(O)R10c, —N(R10c)C(O)N(R10c)2, —OC(O)N(R10c)2, —N(R10c)C(O)OR10c, —S(O)R10c, —S(O)2R10c, —NO2, ═O, ═S, ═N(R10c), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9c;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10c, —SR10c, —N(R10c)2, —C(O)R10c, —C(O)N(R10c)2, —N(R10c)C(O)R10c, —N(R10c)C(O)N(R10c)2, —OC(O)N(R10c)2, —N(R10c)C(O)OR10c, —C(O)OR10c, —OC(O)R10c, —S(O)R10c, —S(O)2R10c, —NO2, ═O, ═S, ═N(R10c), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9c;
• R5 is selected from:
• hydrogen;
• halogen, —OR10d, —SR10d, —N(R10d)2, —C(O)R10d, —C(O)N(R10d)2, —N(R10d)C(O)R10d, —C(O)OR10d, —OC(O)R10d, —N(R10d)C(O)N(R10d)2, —OC(O)N(R10d)2, —N(R10d)C(O)OR10d, —S(O)R10d, —S(O)2R10d, —NO2, —N3, and —CN;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10d, —SR10d, —N(R10d)2, —C(O)R10d, —C(O)N(R10d)2, —N(R10d)C(O)R10d, —C(O)OR10d, —OC(O)R10d, —N(R10d)C(O)N(R10d)2, —OC(O)N(R10d)2, —N(R10d)C(O)OR10d, —S(O)R10d, —S(O)2R10d, —NO2, ═O, ═S, ═N(R10d), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9d;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10d, —SR10d, —N(R10d)2, —C(O)R10d, —C(O)N(R10d)2, —N(R10d)C(O)R10d, —N(R10d)C(O)N(R10d)2, —OC(O)N(R10d)2, —N(R10d)C(O)OR10d, —C(O)OR10d, —OC(O)R10d, —S(O)R10d, —S(O)2R10d, —NO2, ═O, ═S, ═N(R10d), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9d;
• or
• R5 together with R6 form a 3- to 10-membered heterocycle or C3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C3-10 carbocycle is optionally substituted with one or more substituents independently selected from R9d;
• R6 is selected from:
• hydrogen;
• halogen, —OR10e, —SR10e, —N(R10e)2, —C(O)R10e, —C(O)N(R10e)2, —N(R10e)C(O)R10e, —C(O)OR10e, —OC(O)R10e, —N(R10e)C(O)N(R10e)2, —OC(O)N(R10e)2, —N(R10e)C(O)OR10e, —S(O)R10e, —S(O)2R10e, —NO2, —N3, and —CN;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10e, —SR10e, —N(R10e)2, —C(O)R10e, —C(O)N(R10e)2, —N(R10e)C(O)R10e, —C(O)OR10e, —OC(O)R10e, —N(R10e)C(O)N(R10e)2, —OC(O)N(R10e)2, —N(R10e)C(O)OR10e, —S(O)R10e, —S(O)2R10e, —NO2, ═O, ═S, ═N(R10e), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9e;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10e, —SR10e—N(R10e)2, —C(O)R10e, —C(O)N(R10e)2, —N(R10e)C(O)R10e, —N(R10e)C(O)N(R10e)2, —OC(O)N(R10e)2, —N(R10e)C(O)OR10e, —C(O)OR10e, —OC(O)R10e, —S(O)R10e, —S(O)2R10e, —NO2, ═O, ═S, ═N(R10e), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9e;
• or
• R6 together with R5 form a 3- to 10-membered heterocycle or C3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C3-10 carbocycle is optionally substituted with one or more substituents independently selected from R9e;
• R7 is selected from:
• hydrogen;
• —C(O)R10f, —C(O)N(R10f)2, —C(O)OR10f, —S(O)R10f, and —S(O)2R10f;
• C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR10f, —SR10f, —N(R10f)2, —C(O)R10f, —C(O)N(R10f)2, —N(R10f)C(O)R10f, —C(O)OR10f, —OC(O)R10f, —N(R10f)C(O)N(R10f)2, —OC(O)N(R10f)2, —N(R10f)C(O)OR10f, —S(O)R10f, —S(O)2R10f, —NO2, ═O, ═S, ═N(R10f), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9f;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10f, —SR10f, —N(R10f)2, —C(O)R10f, —C(O)N(R10f)2, —N(R10f)C(O)R10f, —N(R10f)C(O)N(R10f)2, —OC(O)N(R10f)2, —N(R10f)C(O)OR10f, —C(O)OR10f, —OC(O)R10f, —S(O)R10f, —S(O)2R10f, —NO2, ═O, ═S, ═N(R10f), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9f;
• R8 is selected from:
• hydrogen;
• —C(O)R10g, —C(O)N(R10g)2, —C(O)OR10g, —S(O)R10g, and —S(O)2R10g;
• C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR10g, —SR10g, —N(R10g)2, —C(O)R10g, —N(R10g)C(O)R10g, —C(O)OR10g, —OC(O)R10g, —N(R10g)C(O)N(R10g)2, —OC(O)N(R10g)2, —N(R10g)C(O)OR10g, —S(O)R10g, —S(O)2R10g, —NO2, ═O, ═S, ═N(R10g), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9g;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10g, —SR10g, —N(R10g)2, —C(O)R10g, —C(O)N(R10g)2, —N(R10g)C(O)R10g, —N(R10g)C(O)N(R10g)2, —OC(O)N(R10g)2, —N(R10g)C(O)OR10g, —C(O)OR10g, —OC(O)R10g, —S(O)R10g, —S(O)2R10g, —NO2, ═O, ═S, ═N(R10g), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9g;
• each R9a is independently selected from:
• halogen, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —C(O)OR10a, —OC(O)R10a, —S(O)R10a, —S(O)2R10a, —NO2, ═O, ═S, ═N(R10a), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —C(O)OR10a, —OC(O)R10a, —S(O)R10a, S(O)2R10a, —NO2, ═O, ═S, ═N(R10a), —N3, and —CN;
• R9bB, R9bC, R9bD, and R9bE are each independently selected from:
• hydrogen;
• halogen, —NO2, —N3, —CN, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, and —S(O)2R10b;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —C(O)OR10b, —OC(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
• each R9z is independently selected from:
• halogen, —OR10z, —SR10z, —N(R10z)2, —C(O)R10z, —C(O)N(R10z)2, —N(R10z)C(O)R10z, —N(R10z)C(O)N(R10z)2, —OC(O)N(R10z)2, —N(R10z)C(O)OR10z, —C(O)OR10z, —OC(O)R10z, —S(O)R10z, —S(O)2R10z, —NO2, ═O, ═S, ═N(R10z), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10z, —SR10z, —N(R10z)2, —C(O)R10z, —C(O)N(R10z)2, —N(R10z)C(O)R10z, —N(R10z)C(O)N(R10z)2, —OC(O)N(R10z)2, —N(R10z)C(O)OR10z, —C(O)OR10z, —OC(O)R10z, —S(O)R10z, —S(O)2R10z, —NO2, ═O, ═S, ═N(R10z), —N3, and —CN;
• each R9c is independently selected from:
• halogen, —OR10c, —SR10c, —N(R10c)2, —C(O)R10c, —C(O)N(R10c)2, —N(R10c)C(O)R10c, —N(R10c)C(O)N(R10c)2, —OC(O)N(R10c)2, —N(R10c)C(O)OR10c, —C(O)OR10c, —OC(O)R10c, —S(O)R10c, —S(O)2R10c, —NO2, ═O, ═S, ═N(R10c), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10c, —SR10c, —N(R10c)2, —C(O)R10c, —C(O)N(R10c)2, —N(R10c)C(O)R10c, —N(R10c)C(O)N(R10c)2, —OC(O)N(R10c)2, —N(R10c)C(O)OR10c, —C(O)OR10c, —OC(O)R10c, —S(O)R10c, —S(O)2R10c, —NO2, ═O, ═S, ═N(R10c), —N3, and —CN;
• each R9d is independently selected from:
• halogen, —OR10d, —SR10d, —N(R10d)2, —C(O)R10d, —C(O)N(R10d)2, —N(R10d)C(O)R10d, —N(R10d)C(O)N(R10d)2, —OC(O)N(R10d)2, —N(R10d)C(O)OR10d, —C(O)OR10d, —OC(O)R10d, —S(O)R10d, —S(O)2R10a, —NO2, ═O, ═S, ═N(R10d), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10d, —SR10d, —N(R10d)2, —C(O)R10d, —C(O)N(R10d)2, —N(R10d)C(O)R10d, —N(R10d)C(O)N(R10d)2, —OC(O)N(R10d)2, —N(R10d)C(O)OR10d, —C(O)OR10d, —OC(O)R10d, —S(O)R10d, —S(O)2R10d, —NO2, ═O, ═S, ═N(R10d), —N3, and —CN;
• each R9e is independently selected from:
• halogen, —OR10e, —SR10e, —N(R10e)2, —C(O)R10e, —C(O)N(R10e)2, —N(R10e)C(O)R10e, —N(R10e)C(O)N(R10e)2, —OC(O)N(R10e)2, —N(R10e)C(O)OR10e, —C(O)OR10e, —OC(O)R10e, —S(O)R10e, —S(O)2R10e, —NO2, ═O, ═S, ═N(R10e), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10e, —SR10e, —N(R10e)2, —C(O)R10e, —C(O)N(R10e)2, —N(R10e)C(O)R10e, —N(R10e)C(O)N(R10e)2, —OC(O)N(R10e)2, —N(R10e)C(O)OR10e, —C(O)OR10e, —OC(O)R10e, —S(O)R10e, —S(O)2R10e, —NO2, ═O, ═S, ═N(R10e), —N3, and —CN;
• each R9f is independently selected from:
• halogen, —OR10f, —SR10f, —N(R10f)2, —C(O)R10f, —C(O)N(R10f)2, —N(R10f)C(O)R10f, —N(R10f)C(O)N(R10f)2, —OC(O)N(R10f)2, —N(R10f)C(O)OR10f, —C(O)OR10f, —OC(O)R10f, —S(O)R10f, —S(O)2R10f, —NO2, ═O, ═S, ═N(R10f), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10f, —SR10f, —N(R10f)2, —C(O)R10f, —C(O)N(R10f)2, —N(R10f)C(O)R10f, —N(R10f)C(O)N(R10f)2, —OC(O)N(R10f)2, —N(R10f)C(O)OR10f, —C(O)OR10f, —OC(O)R10f, —S(O)R10f, —S(O)2R10f, —NO2, ═O, ═S, ═N(R10f), —N3, and —CN;
• each R9g is independently selected from:
• halogen, —OR10g, —SR10g, —N(R10g)2, —C(O)R10g, —C(O)N(R10g)2, —N(R10g)C(O)R10g, —N(R10g)C(O)N(R10g)2, —OC(O)N(R10g)2, —N(R10g)C(O)OR10g, —C(O)OR10g, —OC(O)R10g, —S(O)R10g, —S(O)2R10g, —NO2, ═O, ═S, ═N(R10g), —N3, and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10g, —SR10g, —N(R10g)2, —C(O)R10g, —C(O)N(R10g)2, —N(R10g)C(O)R10g, —N(R10g)C(O)N(R10g)2, —OC(O)N(R10g)2, —N(R10g)C(O)OR10g, —C(O)OR10g, —OC(O)R10g, —S(O)R10g, —S(O)2R10g, —NO2, ═O, ═S, ═N(R10g), —N3, and —CN;
• and
• each R10a, R10b, R10z, R10c, R10d, R10e, R10f, and R10g is independently selected from:
• hydrogen;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C3-10 carbocycle, 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, 3- to 10-membered heterocycle, and C1-6 haloalkyl;
• wherein when X1 is C(H), X2 is C(H), X3 is C(H), and X4 is C(H);
• then R9bC is selected from:
• halogen, —NO2, —N3, —CN, —OH, —O(C2-6 alkyl), —O(C1-6 haloalkyl), —SR10b, —NH(C1-6 alkyl), —N(C1-6 alkyl)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, and —S(O)2R10b;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —C(O)OR10b, —OC(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
• wherein when R7 is —CH3, and R8 is —CH3, and X4 is N or —N+(—O−), then R1c is selected from hydrogen;
• halogen, —NO2, —N3, —CN, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —C(O)OR10a, —OC(O)R10a, —S(O)R10a, and —S(O)2R10a;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from chloro, bromo, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —C(O)OR10a, —OC(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —S(O)R10a, —S(O)2R10a, —NO2, ═O, ═S, ═N(R10a), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9a;
• C1 alkyl substituted with one —F or two —F;
• C2-6 alkyl substituted with one or more —F;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —C(O)OR10a, —OC(O)R10a, —S(O)R10a, —S(O)2R10a, —NO2, ═O, ═S, ═N(R10a), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9a;
• wherein when X1 is C(H), and X2 is C(H), and X3 is C(H), and X4 is C(H), and Z1 is —CH2—, and u is 2, and each Z2 is —CH2— or —O—, and Y2 is C(H), and Y3 is C(H), and Y4 is C(H);
• then
• R9bE is selected from:
• fluoro, chloro, iodo, —NO2, —N3, —CN, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, and —S(O)2R10b;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —C(O)OR10b, —OC(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
• and
• wherein when X1 is C(H), and X2 is C(H), and X3 is C(H), and X4 is C(H), and Z1 is —CH2—, and u is 1, and Z2 is —CH2—, and Y5 is C(H), and Y3 is C(H), and Y4 is C(H);
• then R9bB is selected from
• hydrogen;
• chloro, bromo, iodo, —NO2, —N3, —CN, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, and —S(O)2R10b;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —C(O)OR10b, —OC(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), —N3, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), —N3, —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl.

A method of treating a cardiovascular disease or a related condition comprising administering to a subject in need thereof a compound or salt of Formula (IIIa):

• (IIIa);
• or a salt thereof, wherein
• X1, X2, X3, and X4 are each independently selected from C(R1), N, and N+(—O−);
• wherein no more than two of X1, X2, X3, and X4 are N or N+(—O−);
• each R1 is independently selected from:
• hydrogen;
• halogen, —NO2, —CN, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —C(O)OR10a, —OC(O)R10a, —S(O)R10a, and —S(O)2R10a;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —C(O)OR10a, —OC(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —S(O)R10a, —S(O)2R10a, —NO2, ═O, ═S, ═N(R10a), —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9a;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —C(O)OR10a, —OC(O)R10a, —S(O)R10a, —S(O)2R10a, —NO2, ═O, ═S, ═N(R10a), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9a;
• R2 is selected from:
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —C(O)OR10b, —OC(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9b;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9b;
• R5 and R6 are each independently selected from:
• hydrogen, halogen, —OR10c, —SR10c, —N(R10c)2, —NO2, and —CN;
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, any of which is optionally substituted at each occurrence with one or more substituents independently selected from halogen, —OR10c, —SR10c, —N(R10c)2, —NO2, —CN, and C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10c, —SR10c, —N(R10c)2, —NO2, and —CN;
• and
• C3-10 carbocycle and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10c, —SR10c, —N(R10c)2, —NO2, and —CN;
• or
• R5 together with R6 form a 3- to 10-membered heterocycle or C3-10 carbocycle, wherein the 3- to 10-membered heterocycle or C3-10 carbocycle is optionally substituted with one or more substituents independently selected from R9c;
• R7 is selected from:
• hydrogen and C1-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR10d, —SR10d, —N(R10d)2, —NO2, and —CN;
• R8 is selected from:
• hydrogen;
• and
• C1 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR10e, —SR10e, —N(R10e)2, —NO2, —CN, and 3- to 10-membered heterocycle, wherein each 3- to 10-membered heterocycle is optionally substituted with one or more substituents independently selected from halogen, —OR10e, —SR10e, —N(R10e)2, —NO2, and —CN;
• C2-6 alkyl optionally substituted with one or more substituents independently selected from halogen, —OR10e, —SR10e, —N(R10e)2, —NO2, —CN, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein each C3-10 carbocycle and 3- to 10-membered heterocycle are optionally substituted with one or more substituents independently selected from halogen, —OR10e, —SR10e, —N(R10e)2, —NO2, and —CN;
• each R9a is independently selected from:
• halogen, —OH, —O(C2-6 alkyl), —O(C1-6 haloalkyl), —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —C(O)OR10a, —OC(O)R10a, —S(O)R10a, —S(O)2R10a, —NO2, ═O, ═S, ═N(R10a), and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10a, —SR10a, —N(R10a)2, —C(O)R10a, —C(O)N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)N(R10a)2, —OC(O)N(R10a)2, —N(R10a)C(O)OR10a, —C(O)OR10a, —OC(O)R10a, —S(O)R10a, —S(O)2R10a, —NO2, ═O, ═S, ═N(R10a), and —CN;
• each R9b is independently selected from:
• halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), and —CN;
• each R9c is independently selected from:
• halogen, —OR10c, —SR10c, —N(R10c)2, —C(O)R10c, —C(O)N(R10c)2, —N(R10c)C(O)R10c, —N(R10c)C(O)N(R10c)2, —OC(O)N(R10c)2, —N(R10c)C(O)OR10c, —C(O)OR10c, —OC(O)R10c, —S(O)R10c, —S(O)2R10c, —NO2, ═O, ═S, ═N(R10c), and —CN;
• and
• C1-3 alkyl, C2-3 alkenyl, and C2-3 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10c, —SR10c, —N(R10c)2, —C(O)R10c, —C(O)N(R10c)2, —N(R10c)C(O)R10c, —N(R10c)C(O)N(R10c)2, —OC(O)N(R10c)2, —N(R10c)C(O)OR10c, —C(O)OR10c, —OC(O)R10c, —S(O)R10c, —S(O)2R10c, —NO2, ═O, ═S, ═N(R10c), and —CN;
• each R10a is independently selected from:
• hydrogen;
• and
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C3-10 carbocycle, 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, 3- to 10-membered heterocycle, and C1-6 haloalkyl;
• each R10b is independently selected from:
• hydrogen;
• and
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C3-10 carbocycle, 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, 3- to 10-membered heterocycle, and C1-6 haloalkyl;
• each R10c is independently selected from:
• hydrogen;
• and
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C3-10 carbocycle, 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, 3- to 10-membered heterocycle, and C1-6 haloalkyl;
• each R10d is independently selected from:
• hydrogen;
• and
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C3-10 carbocycle, 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, 3- to 10-membered heterocycle, and C1-6 haloalkyl;
• and
• each R10e is independently selected from:
• hydrogen;
• and
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C3-10 carbocycle, 3- to 10-membered heterocycle;
• and
• C3-10 carbocycle, and 3- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —CN, —OH, —SH, —NO2, —NH2, ═O, ═S, —O—C1-6 alkyl, —S—C1-6 alkyl, —N(C1-6 alkyl)2, —NH(C1-6 alkyl), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, 3- to 10-membered heterocycle, and C1-6 haloalkyl;
• wherein when R5 or R6 is isopropyl;
• then R2 is selected from:
• C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —C(O)OR10b, —OC(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, —CN, C3-10 carbocycle and 3- to 10-membered heterocycle, wherein the C3-10 carbocycle and 3- to 10-membered heterocycle are each optionally substituted with one or more substituents independently selected from R9b;
• C3-10 carbocycle, 3- to 4-membered heterocycle, and 6- to 10-membered heterocycle, each of which is optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), —CN, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9b;
• and
• 5-membered heterocycle, optionally substituted with one or more substituents independently selected from halogen, —OR10b, —SR10b, —N(R10b)2, —C(O)R10b, —C(O)N(R10b)2, —N(R10b)C(O)R10b, —N(R10b)C(O)N(R10b)2, —OC(O)N(R10b)2, —N(R10b)C(O)OR10b, —C(O)OR10b, —OC(O)R10b, —S(O)R10b, —S(O)2R10b, —NO2, ═O, ═S, ═N(R10b), —CN, C2-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein C2-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with one or more substituents independently selected from R9b.