# US 12,006,320 B2 · Heterocyclic derivatives as PI3K inhibitors

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- Number: US 12,006,320 B2
- Document ID: US12006320B2
- Status: Granted
- Kind: B2
- Application number: 17/356,986
- Filed: 2021-06-24
- Published: 2021-12-23
- Granted: 2024-06-11
- Earliest claimed: 2018-11-13
- Assignees: Incyte Corporation
- Applicants: Incyte Corporation
- Inventors: Stacey Shepard; Yanran Ai; Andrew P. Combs; Nikoo Falahatpisheh; Lixin Shao; Artem Shvartsbart
- Web page: https://patentgrep.com/patent/US12006320B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This application relates to compounds of Formula (I): or pharmaceutically acceptable salts thereof, which are inhibitors of PI3K-γ which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.

## Claims

### Claim 1

A method of treating a disease or disorder in a patient, wherein said disease or disorder is associated with abnormal expression or activity of PI3Kγ kinase, wherein the disease or disorder is lung cancer, melanoma, pancreatic cancer, breast cancer, prostate cancer, liver cancer, colon cancer, endometrial cancer, bladder cancer, skin cancer, cancer of the uterus, renal cancer, gastric cancer, seminoma, teratocarcinoma, astrocytoma, neuroblastoma, glioma, sarcoma, acute myeloid leukemia, acute monocytic leukemia, small lymphocytic lymphoma, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), multiple myeloma, T-cell acute lymphoblastic leukemia (T-ALL), cutaneous T-cell lymphoma, large granular lymphocytic leukemia, mature (peripheral) t-cell neoplasm (PTCL), anaplastic large cell lymphoma (ALCL), lymphoblastic lymphoma, Burkitt's lymphoma, acute myeloblastic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, hairy cell leukemia, Mantle cell lymphoma, small lymphocytic lymphoma, follicular lymphoma, xeroderma pigmentosum, keratoacanthoma, lymphoplasmacytic lymphoma, extranodal marginal zone lymphoma, Waldenstrom's macroglobulinemia, prolymphocytic leukemia, acute lymphoblastic leukemia, myelofibrosis, mucosa-associated lymphatic tissue (MALT) lymphoma, mediastinal (thymic) large B-cell lymphoma, lymphomatoid granulomatosis, splenic marginal zone lymphoma, primary effusion lymphoma, intravascular large B-cell lymphoma, plasma cell leukemia, extramedullary plasmacytoma, smoldering myeloma (aka asymptomatic myeloma), monoclonal gammopathy of undetermined significance (MGUS), diffuse large B cell lymphoma, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematous, asthma, allergy, allergic rhinitis, pancreatitis, psoriasis, anaphylaxis, glomerulonephritis, inflammatory bowel disease, thrombosis, meningitis, encephalitis, diabetic retinopathy, benign prostatic hypertrophy, myasthenia gravis, Sjögren's syndrome, osteoarthritis, restenosis, atherosclerosis, autoimmune hemolytic anemia, systemic lupus erythematosus, lupus nephritis, or pemphigus, the method comprising administering to said patient a therapeutically effective amount of a compound of Formula (IIu):
or a pharmaceutically acceptable salt thereof; wherein:
X2 is N or CR2;
R2 is selected from H, D, halo, CN, OH, NH2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and C3-7 cycloalkyl;
provided that:
(a) when X2 is N, then R1 is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa1, SRa1, NHORa1, C(O)Rb1, C(O)NRc1Rd1, C(O)NRc1(ORa1), C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, and NRc1C(O)NRc1Rd1, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R1 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R1A substituents; or
(b) when X2 is CR2, then R1 is selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa1, SRa1, NHORa1, C(O)Rb1, C(O)NRc1Rd1, C(O)NRc1(ORa1), C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, and NRc1C(O)NRc1Rd1 wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C16 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R1 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R1A substituents;
each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra1, Rb1, Rc1 and Rd1 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R1A substituents;
or, any Rc1 and Rd1, attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl group or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl group or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R1A substituents;
each R1A is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa11, SRa11, NHORa11, C(O)Rb11, C(O)NRc11Rd11, C(O)NRc11(ORa11), C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)ORa11, and NRc11C(O)NRc11Rd11, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R1A are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RM substituents;
each Ra11, Rb11, Rc11, and Rd11 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra11, Rb11, Rc11 and Rd11 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RM substituents;
or, any Rc11 and Rd11, attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl group or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl group or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RM substituents;
each RM is independently selected from D, OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-C1-3 alkyl, HO—C1-3 alkyl, C1-3 alkoxy-C1-3 alkyl, C3-6 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(C1-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-4 alkoxycarbonyl, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3 alkylcarbonyloxy, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(C1-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(C1-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(C1-3 alkyl)aminocarbonylamino;
R3 is selected from H, D, halo, CN, OH, NH2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, cyano-C1-6 alkyl, HO—C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkylamino, di(C1-6 alkyl)amino, and C(O)NRa3Rb3;
each Ra3 and Rb3 is 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-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Ra3 and Rb3 are each optionally substituted with 1, 2, 3 or 4 independently selected RM substituents;
or, any Ra3 and Rb3, attached to the same N atom, together with the N atom to which they are attached, form a 5-6 membered heteroaryl group or a 4-7 membered heterocycloalkyl group, wherein the 5-6 membered heteroaryl group or 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
R6 is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa6, SRa6, NHORa6, C(O)Rb6, C(O)NRc6Rd6, C(O)NRc6(ORa6), C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6NRd6Rd6, NRc6C(O)Rb6, NRc6C(O)ORa6, NRc6C(O)NRc6Rd6, C(═NRe6)Rb6, C(═NOH)Rb6, C(═NCN)Rb6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, NRc6C(═NOH)NRc6Rd6, NRc6C(═NCN)NRc6Rd6, NRc6C(═NRe6)Rb6, NRc6S(O)NRc6Rd6, NRc6S(O)Rb6, NRc6S(O)2Rb6, NRc6S(O)(═NRe6)Rb6, NRc6S(O)2NRc6Rd6 S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, S(O)2NRc6Rd6, S(O)(═NRe6)Rb6, OS(O)(═NRe6)Rb6, OS(O)2Rb6, and SF5, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R6 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R6A substituents;
each Ra6, Rb6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra6, Rb6, Rc6 and Rd6 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R6A substituents;
or, any Rc6 and Rd6, attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl group or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl group or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R6A substituents;
each Re6 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;
each R6A is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa61, SRa61, NHORa61, C(O)Rb61, C(O)NRc61Rd61, C(O)NRc61(ORa61), C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NRc61NRc61Rd61, NRc61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, C(═NRe61)Rb61, C(═NOH)Rb61, C(═NCN)Rb61, C(═NRe61)NRc61Rd61, NRc61C(═NRe61)NRc61Rd61, NRc61C(═NOH)NRc61Rd61, NRc61C(═NCN)NRc61Rd61, NRc61C(═NRe61)Rb61, NRc61S(O)NRc61Rd61, NRc61S(O)Rb61, NRc61S(O)2Rb61, NR61S(O)(═NRe61)Rb61, NRc61S(O)2NRc61Rd61, S(O)Rb61, S(O)NRc61Rd61, S(O)2Rb61, S(O)2NRc61Rd61, S(O)(═NRe61)Rb61, OS(O)(═NRe61)Rb61, OS(O)2Rb61, and SF5, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R6A are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RM substituents;
each Ra61 Rb61, Rc61, and Rd61 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra61, Rb6, Rc61 and Rd61 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RM substituents;
or, any Rc61 and Rd61, attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl group or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl group or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RM substituents;
each Re61 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;
X9 is NR9N, or C(R9)2;
X11 is NR11N, or C(R11)2;
R9N is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb9N, C(O)NRc9NRd9N, C(O)ORa9N, C(═NRe9N)Rb9NC(═NRe9N)NRc9NRd9N, C(═NCN)NRc9NRd9N, C(═NORa9N)NRc9N, S(O)2Rb9N, S(O)(═NR9N)Rd9N, and S(O)2NRe9NRd9N, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl- and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R9N are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R9NA substituents;
each Ra9N, Rb9N, Rc9N, and Rd9N is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra9N, Rb9N, Rc9N, and Rd9N are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R9NA substituents;
or, any Re9N and Rd9N, attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl group or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl group or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R9NA substituents;
each Re9N is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;
each R9NA is selected from H, D, halo, 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-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, (4-7 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa9N2, SRa9N2, NHORa9N2, C(O)Rb9N2, C(O)NR9N2Rd9N2, C(O)NRc9N2(ORa9N2), C(O)ORa9N2, OC(O)Rb9N2, OC(O)NR9N2Rd9N2, NRc9N2Rd9N2, NRc9N2NRc9N2Rd9N2, NRc9N2C(O)Rb9N2, NRe9N2C(O)ORa9N2 and NRc9N2C(O)NR9N2Rd9N2 wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of R9NA are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
each Ra9N2, Rb9N2, Rc9N2, and Rd9N2 is 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-C1-6 alkyl-, C3.7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3.7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Ra9N2, Rb9N2 Rc9N2 and Rd9N2 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
or, any Rc9N2 and Rd9N2, attached to the same N atom, together with the N atom to which they are attached, form a 5-6 membered heteroaryl group or a 4-7 membered heterocycloalkyl group, wherein the 5-6 membered heteroaryl group or 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
each R9 is independently selected from H, D, halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa91, SRa91, NHORa91, C(O)Rb91, C(O)NRc91Rd91, C(O)NRc91(ORa91), C(O)ORa91, OC(O)Rb91, OC(O)NRc91Rd91, NRc91Rd91, NRc91NRc691Rd91, NRc91C(O)Rb91, NRc91C(O)ORa91 and NRc91C(O)NRc91Rd91, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R9 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R9A substituents;
or, alternatively, two R9 groups together form an oxo group;
each Ra91, Rb91, Rc91, and Rd91 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra91, Rb91, Rc91 and Rd91 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R9A substituents;
or, any Rc91 and Rd91, attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl group or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl group or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R9A substituents;
each R9A is selected from H, D, halo, 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-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, (4-7 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa92, SRa92, NHORa92, C(O)Rb92, C(O)NRc92Rd92, C(O)NRc92(ORa92), C(O)ORa92, OC(O)Rb92, OC(O)NRc92Rd92, NRc92Rd92, NRc92NRc92Rd92, NRc92C(O)Rb92, NRc92C(O)ORa92, and NRc92C(O)NRc92Rd92, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of R9A are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
each Ra92, Rb92, Rc92, and Rd92 is 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-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Ra92, Rb92, Rc92 and Rd92 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
or, any Rc92 and Rd92, attached to the same N atom, together with the N atom to which they are attached, form a 5-6 membered heteroaryl group or a 4-7 membered heterocycloalkyl group, wherein the 5-6 membered heteroaryl group or 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
R10N is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C16 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb10N, C(O)NR10NRd10N, C(O)ORa10N, C(═NRe10N)Rb10N, C(═NRe10N)NRc10NRd10N, C(═NCN)NRc10NRd10N, C(═NORa10N)NRc10N, S(O)2Rb10N, S(O)(═NRc10N)Rd10N, and S(O)2NRc10NRd10N, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl- and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R10N are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R10NA substituents;
each Ra10N, Rb10N, Rc10N, and Rd10N is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra10N, Rb10N, Rc10N, and Rd10N are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R10NA substituents;
or, any Rc10N and Rd10N, attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl group or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl group or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R10NA substituents;
each Re10N is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;
each R10NA is selected from H, D, halo, 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-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, (4-7 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa10N2, SRa10N2, NHORa10N2, C(O)Rb10N2, C(O)NRc10N2Rd10N2, C(O)NRc10N2(ORa10N2) C(O)ORa10N2, OC(O)Rb10N2 OC(O)NRc10N2Rd10N2, NRc10N2Rd10N2, NRc10N2Rc10N2Rc10N2Rd10N2, NRc10N2C(O)Rb10N2, NRe10N2C(O)ORa10N2, NRc10N2C(O)NRc10N2Rd10N2, and NRc10N2S(O)2Rb10N2 wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of R10NA are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
each Ra10N2, Rb10N2, Rc10N2, and Rd10N2 is 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-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Ra10N2, Rb10N2, Rc10N2 and Rd10N2 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
or, any Rc10N2 and Rd10N2, attached to the same N atom, together with the N atom to which they are attached, form a 5-6 membered heteroaryl group or a 4-7 membered heterocycloalkyl group, wherein the 5-6 membered heteroaryl group or 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
R11N is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb11N, C(O)NRc11NRd11N, C(O)ORa11N, C(═NRe11N)Rb11N, C(═NRe11N)NRc11NRd11N, C(═NCN)NRc11NRd11N, C(═NORa11N)NRc11N S(O)2Rb11N, S(O)(═NRc11N)Rd11N and S(O)2NRc11NRd11N wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl- and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R11N are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R11NA substituents;
each Ra11N, Rb11N, Rc11N, and Rd11N is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra11N, Rb11N, Rc11N, and Rd11N are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R11NA substituents;
or, any Rc11N and Rd11N attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl group or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl group or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R11NA substituents;
each Re11N is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, and C2-6 alkynyl;
each R11NA is independently selected from H, D, halo, 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-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, (4-7 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa11N2, SRa11N2, NHORa11N2, C(O)Rb11N2, C(O)NRc11N2Rd11N2, C(O)NRc11N2(ORa11N2), C(O)ORa11N2, OC(O)Rb11N2, OC(O)NRc11N2Rd11N2, NRc11N2Rd11N2, NRc11N2NRc11N2Rd11N2, NRc11N2C(O)Rb11N2, NRc11N2C(O)ORa11N2 and NRc11N2C(O)NRc11N2Rd11N2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of R11NA are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
each Ra11N2, Rb11N2, Rc11N2, and Rd11N2 is 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-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Ra11N2, Rb11N2, Rc11N2 and Rd11N2 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
or, any Rc11N2 and Rd11N2, attached to the same N atom, together with the N atom to which they are attached, form a 5-6 membered heteroaryl group or a 4-7 membered heterocycloalkyl group, wherein the 5-6 membered heteroaryl group or 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
each R11 is independently selected from H, D, halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, (4-10 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa111, SRa111, NHORa111, C(O)Rb111, C(O)NRc111Rd111, C(O)NRc111(ORa111), C(O)ORa111, OC(O)Rb111, OC(O)NRc111Rd111, NRc111Rd111, NRc111NRc111Rd111, NRc111C(O)Rb111, NRc111C(O)ORa111, and NRc111C(O)NRc111Rd111, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of R11 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R11A substituents;
each Ra111, Rb111, Rc111, and Rd111 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, (5-10 membered heteroaryl)-C1-6 alkyl-, and (4-10 membered heterocycloalkyl)-C1-6 alkyl- of Ra111, Rb111, Rc111 and Rd111 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R11A substituents;
or, any Rc111 and Rd111, attached to the same N atom, together with the N atom to which they are attached, form a 5-10 membered heteroaryl group or a 4-10 membered heterocycloalkyl group, wherein the 5-10 membered heteroaryl group or 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R11A substituents; and
each R11A is independently selected from H, D, halo, 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-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, (4-7 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa112, SRa112, NHORa112, C(O)Rb112, C(O)NRc112Rd112, C(O)NRc112(ORa112), C(O)ORa112, OC(O)Rb112, OC(O)NRc112Rd112, NRc112Rd112, NRc112NRc112Rd112, NRc112C(O)Rb112, NRc112C(O)ORa112, and NRc112C(O)NRc112Rd112, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of R11A are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents; and
each Ra112, Rb112, Rc112, and Rd112 is 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-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-7 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-7 membered heterocycloalkyl)-C1-6 alkyl- of Ra112, Rb112, Rc112 and Rd112 are each optionally substituted with 1, 2, 3, or 4 independently selected RM substituents;
or, any Rc112 and Rd112, attached to the same N atom, together with the N atom to which they are attached, form a 5-6 membered heteroaryl group or a 4-7 membered heterocycloalkyl group, wherein the 5-6 membered heteroaryl group or 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RM substituents.

### Claim 2 (depends on 1)

The method of claim 1, wherein X2 is N.

### Claim 3 (depends on 2)

The method of claim 2, wherein R1 is H.

### Claim 4 (depends on 1)

The method of claim 1, wherein X2 is CR2.

### Claim 5 (depends on 4)

The method of claim 4, wherein R2 is selected from H, D, and C1-6 alkyl.

### Claim 6 (depends on 4)

The method of claim 4, wherein R1 is selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)Rb1, C(O)NRc1Rd1, C(O)NRc1(ORa1), C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1 and 5-6 membered heteroaryl, wherein the C1-6 alkyl and 5-6 membered heteroaryl are optionally substituted with 1 or 2 independently selected R1A substituents.

### Claim 7 (depends on 4)

The method of claim 4, wherein each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl wherein the C1-6 alkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl of Rc1 and Rd1 are each optionally substituted with 1 or 2 independently selected R1A substituents.

### Claim 8 (depends on 4)

The method of claim 4, wherein R1 is selected from CF3, isopropylcarbamoyl, (tetrahydro-2H-pyran-4-yl)carbamoyl, azetidine-1-carbonyl, bicyclo[1.1.1]pentan-1-ylcarbamoyl, 3,3-dimethylazetidine-1-carbonyl, 3,3-difluoroazetidine-1-carbonyl, 3-hydroxyazetidine-1-carbonyl, (3-hydroxycyclobutyl)carbamoyl, (3-hydroxytetrahydro-2H-pyran-4-yl)carbamoyl, 2-methylthiazol-5-yl, 1-methyl-1H-pyrazol-4-yl, 1-methyl-1H-pyrazol-5-yl, 5-methyl-1H-pyrazol-4-yl, and 1H-pyrazol-4-yl.

### Claim 9 (depends on 1)

The method of claim 1, wherein R3 is H.

### Claim 10 (depends on 1)

The method of claim 1, wherein R6 is selected from H, D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, SRa6, C(O)Rb6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, and S(O)2NRc6Rd6, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2 or 3 independently selected R6A substituents.

### Claim 11 (depends on 1)

The method of claim 1 wherein R6 is selected from H, halo, C1-6 alkyl, SRa6, C(O)Rb6, S(O)Rb6, and S(O)2Rb6, wherein the C1-6 alkyl is optionally substituted by 1, 2 or 3 independently selected R6A substituents;
Ra6 and Rb6 are each independently selected from H and C1-6 alkyl; and
each R6A is selected from halo, OH, and C1-6 haloalkyl.

### Claim 12 (depends on 1)

The method of claim 1, wherein R6 is selected from H, chloro, methyl, SCH3, S(O)2CH3, C(O)CH3, CH(CH3)OH, C(CH3)2OH, and 1,1,1-trifluoro-2,3-dihydroxypropan-2-yl.

### Claim 13 (depends on 1)

The method of claim 1, wherein X9 is C(R9)2.

### Claim 14 (depends on 1)

The method of claim 1, wherein two R9 groups together form an oxo group.

### Claim 15 (depends on 1)

The method of claim 1, wherein R10N is selected from H, C1-6 alkyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-6 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl-, and (4-6 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, 4-6 membered heterocycloalkyl, phenyl-C1-6 alkyl-, C3-6 cycloalkyl-C1-6 alkyl-, (5-6 membered heteroaryl)-C1-6 alkyl- and (4-6 membered heterocycloalkyl)-C1-6 alkyl- of R10N are each optionally substituted with 1 or 2 independently selected R10NA substituents.

### Claim 16 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein R10N is selected from H, C1-6 alkyl, phenyl-C1-6 alkyl-, and C3-6 cycloalkyl-C1-6 alkyl-, wherein the C1-6 alkyl, phenyl-C1-6 alkyl-, and C3-6 cycloalkyl-C1-6 alkyl- of R10N are each optionally substituted with 1 or 2 independently selected R10NA substituents independently selected from phenyl, C3-7 cycloalkyl, ORa10N2, NRc10N2Rd10N2, C(O)NRc10N2Rd10N2, C(O)ORa10N2, NRc10N2C(O)Rb10N2, NRc10N2C(O)ORa10N2, and NRc10N2S(O)2Rb10N2, wherein each Ra10N2, Rb10N2, Rc10N2, and Rd10N2 is independently selected from H and C1-6 alkyl.

### Claim 17 (depends on 1)

The method claim 1, wherein R10N is selected from H, ethyl, isopropyl, 1-phenylethyl, 1-cyclopropylethyl, 2-((tert-butoxycarbonyl)amino)-1-cyclopropylethyl, 2-amino-1-cyclopropylethyl, 1-cyclopropyl-2-(methylsulfonamido)ethyl, 2-acetamido-1-cyclopropylethyl, 1-cyclopropyl-2-(methylamino)-2-oxoethyl, 1-cyclopropyl-2-hydroxyethyl, and carboxy(cyclopropyl)methyl.

### Claim 18 (depends on 1)

The method claim 1, wherein X11 is C(R11)2.

### Claim 19 (depends on 1)

The method of claim 1, wherein each R11 is independently selected from H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl with 1 or 2 independently selected R11A substituents.

### Claim 20 (depends on 1)

The method of claim 1, wherein X11 is CH2.

### Claim 21 (depends on 1)

The method of claim 1, wherein:
R1 is selected from H, C1-6 alkyl, C1-6 haloalkyl, C(O)Rb1, C(O)NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1 and 5-6 membered heteroaryl, wherein the C1-6 alkyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 independently selected R1A substituents;
each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl wherein the C1-6 alkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl of Rc1 and Rd1 are each optionally substituted with 1 or 2 independently selected R1A substituents;
or any Rc1 and Rd1, attached to the same N atom, together with the N atom to which they are attached, form a 4-6 membered heterocycloalkyl group, wherein the 4-6 membered heterocycloalkyl group is optionally substituted with 1 or 2 independently selected R1A substituents;
each R1A is independently selected from halo, C1-6 alkyl, and OH;
X2 is N;
R3 is selected from H, D, and C1-6 alkyl;
R6 is selected from H, halo, C1-6 alkyl, SRa6, C(O)Rb6, S(O)Rb6, and S(O)2Rb6, wherein the C1-6 alkyl is optionally substituted by 1, 2 or 3 R6A substituents independently selected from halo, OH, and C1-6 haloalkyl;
Ra6 and Rb6 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;
X9 is C(O);
X11 is C(R11)2;
R10N is H, C1-6 alkyl, phenyl-C1-6 alkyl-, and C3-6 cycloalkyl-C1-6 alkyl-, wherein the C1-6 alkyl, phenyl-C1-6 alkyl-, and C3-6 cycloalkyl-C1-6 alkyl- are each optionally substituted with 1 or 2 R10NA substituents independently selected from phenyl, C3-7 cycloalkyl, ORa10N2, NRc10N2Rd10N2, C(O)NRc10N2Rd10N2, C(O)ORa10N2, NRc10N2C(O)Rb10N2, NRc10N2C(O)ORa10N2, and NRc10N2S(O)2Rb10N2, wherein each Ra10N2, Rb10N2, Rc10N2, and Rd10N2 is independently selected from H and C1-6 alkyl; and
each R11 is independently selected from H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

### Claim 22 (depends on 1)

The method of claim 1, wherein:
R1 is selected from C1-6 alkyl, C1-6 haloalkyl, C(O)Rb1, C(O)NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1 and 5-6 membered heteroaryl, wherein the C1-6 alkyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 independently selected R1A substituents;
each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl wherein the C1-6 alkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl of Rc1 and Rd1 are each optionally substituted with 1 or 2 independently selected R1A substituents;
or any Rc1 and Rd1, attached to the same N atom, together with the N atom to which they are attached, form a 4-6 membered heterocycloalkyl group, wherein the 4-6 membered heterocycloalkyl group is optionally substituted with 1 or 2 independently selected R1A substituents;
each R1A is independently selected from halo, C1-6 alkyl, and OH;
X2 is CR2;
R2 is selected from H, D, and C1-6 alkyl;
R3 is selected from H, D, and C1-6 alkyl;
R6 is selected from H, halo, C1-6 alkyl, SRa6, C(O)Rb6, S(O)Rb6, and S(O)2Rb6, wherein the C1-6 alkyl is optionally substituted by 1, 2 or 3 R6A substituents independently selected from halo, OH, and C1-6 haloalkyl;
Ra6 and Rb6 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;
X9 is C(O);
X11 is C(R11)2;
R10N is H, C1-6 alkyl, phenyl-C1-6 alkyl-, and C3-6 cycloalkyl-C1-6 alkyl-, wherein the C1-6 alkyl, phenyl-C1-6 alkyl-, and C3-6 cycloalkyl-C1-6 alkyl- are each optionally substituted with 1 or 2 R10NA substituents independently selected from phenyl, C3-7 cycloalkyl, ORa10N2, NRc10N2Rd10N2, C(O)NRc10N2Rd10N2, C(O)ORa10N2, NRc10N2C(O)Rb10N2, NRc10N2C(O)ORa10N2, and NRc10N2S(O)2Rb10N2, wherein each Ra10N2, Rb10N2, Rc10N2, and Rd10N2 is independently selected from H and C1-6 alkyl; and
each R11 is independently selected from H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

### Claim 23 (depends on 1)

The method of claim 1, wherein:
R1 is selected from H, C1-6 alkyl, C1-6 haloalkyl, C(O)Rb1, C(O)NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1 and 5-6 membered heteroaryl, wherein the C1-6 alkyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 independently selected R1A substituents;
each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl wherein the C1-6 alkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl of Rc1 and Rd1 are each optionally substituted with 1 or 2 independently selected R1A substituents;
or any Rc1 and Rd1, attached to the same N atom, together with the N atom to which they are attached, form a 4-6 membered heterocycloalkyl group, wherein the 4-6 membered heterocycloalkyl group is optionally substituted with 1 or 2 independently selected R1A substituents;
each R1A is independently selected from halo, C1-6 alkyl, and OH;
X2 is N or CH;
R3 is selected from H, D, and C1-6 alkyl;
R6 is selected from H, halo, C1-6 alkyl, SRa6, C(O)Rb6, S(O)Rb6, and S(O)2Rb6, wherein the C1-6 alkyl is optionally substituted by 1, 2 or 3 R6A substituents independently selected from halo, OH, and C1-6 haloalkyl;
Ra6 and Rb6 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;
X9 is C(O);
X11 is C(R11)2;
R10N is H, C1-6 alkyl, phenyl-C1-6 alkyl-, and C3-6 cycloalkyl-C1-6 alkyl-, wherein the C1-6 alkyl, phenyl-C1-6 alkyl-, and C3-6 cycloalkyl-C1-6 alkyl- are each optionally substituted with 1 or 2 R10NA substituents independently selected from phenyl, C3-7 cycloalkyl, ORa10N2, NRc10N2Rd10N2, C(O)NRc10N2Rd10N2, C(O)ORa10N2, NRc10N2C(O)Rb10N2, NRc10N2C(O)ORa10N2, and NRc10N2S(O)2Rb10N2, wherein each Ra10N2, Rb10N2, Rc10N2, and Rd10N2 is independently selected from H and C1-6 alkyl; and
each R11 is independently selected from H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

### Claim 24 (depends on 1)

The method of claim 1, wherein:
R1 is selected from H, C1-6 alkyl, C1-6 haloalkyl, C(O)Rb1, C(O)NRc1Rd1, and 5-6 membered heteroaryl, wherein the C1-6 alkyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 independently selected R1A substituents;
each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl wherein the C1-6 alkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl of Rc1 and Rd1 are each optionally substituted with 1 or 2 independently selected R1A substituents;
or any Rc1 and Rd1, attached to the same N atom, together with the N atom to which they are attached, form a 4-6 membered heterocycloalkyl group, wherein the 4-6 membered heterocycloalkyl group is optionally substituted with 1 or 2 independently selected R1A substituents;
each R1A is independently selected from halo, C1-6 alkyl, and OH;
X2 is N or CH;
R3 is H;
R6 is selected from H, halo, C1-6 alkyl, SRa6, C(O)Rb6, S(O)Rb6, and S(O)2Rb6, wherein the C1-6 alkyl is optionally substituted by 1, 2 or 3 R6A substituents independently selected from halo, OH, and C1-6 haloalkyl;
Ra6 and Rb6 are selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;
X9 is C(O);
X11 is CH2;
R10N is H, C1-6 alkyl, phenyl-C1-6 alkyl-, and C3-6 cycloalkyl-C1-6 alkyl-, wherein the C1-6 alkyl, phenyl-C1-6 alkyl-, and C3-6 cycloalkyl-C1-6 alkyl- are each optionally substituted with 1 or 2 R10NA substituents independently selected from phenyl, C3-7 cycloalkyl, ORa10N2, NRc10N2Rd10N2, C(O)NRc10N2Rd10N2, C(O)ORa10N2, NRc10N2C(O)Rb10N2, NRc10N2C(O)ORa10N2, and NRc10N2S(O)2Rb10N2, wherein each Ra10N2, Rb10N2, Rc10N2, and Rd10N2 is independently selected from H and C1-6 alkyl.

### Claim 25 (depends on 1)

The method of claim 1, wherein the compound of Formula (IIu) is selected from:
(S)-5-(8-amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-7-chloro-2-(1-cyclopropylethyl)isoindolin-1-one;
(S)-5-(8-amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)-7-(methylthio)isoindolin-1-one;
(S)-5-(8-amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)-7-(methylsulfonyl)isoindolin-1-one;
5-(8-amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)isoindolin-1-one;
(S)-5-(8-amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)isoindolin-1-one;
(S)-5-(4-aminoimidazo[2,1-f][1,2,4]triazin-7-yl)-2-(1-cyclopropylethyl)isoindolin-1-one;
(S)-5-(4-aminoimidazo[2,1-f][1,2,4]triazin-7-yl)-7-chloro-2-(1-cyclopropylethyl)isoindolin-1-one;
(S)-5-(4-aminoimidazo[2,1-f][1,2,4]triazin-7-yl)-2-(1-cyclopropylethyl)-7-(methylsulfonyl)isoindolin-1-one;
5-(8-amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-2-ethylisoindolin-1-one;
5-(4-aminoimidazo[2,1-f][1,2,4]triazin-7-yl)-2-ethylisoindolin-1-one;
5-(8-amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-phenylethyl)isoindolin-1-one;
5-(4-aminoimidazo[2,1-f][1,2,4]triazin-7-yl)-2-(1-phenylethyl)isoindolin-1-one;
5-(8-amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-2-isopropylisoindolin-1-one;
5-(4-aminoimidazo[2,1-f][1,2,4]triazin-7-yl)-2-isopropylisoindolin-1-one;
(S)-7-acetyl-5-(4-aminoimidazo[2,1-f][1,2,4]triazin-7-yl)-2-(1-cyclopropylethyl)isoindolin-1-one;
5-(4-aminoimidazo[2,1-f][1,2,4]triazin-7-yl)-2-((S)-1-cyclopropylethyl)-7-(1-hydroxyethyl)isoindolin-1-one;
(S)-5-(4-aminoimidazo[2,1-f][1,2,4]triazin-7-yl)-2-(1-cyclopropylethyl)-7-(2-hydroxypropan-2-yl)isoindolin-1-one;
(S)-8-Amino-3-(2-(1-cyclopropylethyl)-7-(methylsulfonyl)-1-oxoisoindolin-5-yl)-N-isopropylimidazo[1,2-a]pyrazine-6-carboxamide; and
(S)-8-Amino-3-(2-(1-cyclopropylethyl)-7-(methylsulfonyl)-1-oxoisoindolin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)imidazo[1,2-a]pyrazine-6-carboxamide;
or a pharmaceutically acceptable salt thereof.

### Claim 26 (depends on 1)

The method of claim 1, wherein the compound of Formula (IIu) is selected from:
(S)-5-(8-Amino-6-(azetidine-1-carbonyl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)-7-(methylsulfonyl)isoindolin-1-one;
(S)-8-Amino-N-(bicyclo[1.1.1]pentan-1-yl)-3-(2-(1-cyclopropylethyl)-7-(methylsulfonyl)-1-oxoisoindolin-5-yl)imidazo[1,2-a]pyrazine-6-carboxamide;
(S)-5-(8-Amino-6-(3,3-dimethylazetidine-1-carbonyl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)-7-(methylsulfonyl)isoindolin-1-one;
(S)-5-(8-Amino-6-(3,3-difluoroazetidine-1-carbonyl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)-7-(methylsulfonyl)isoindolin-1-one;
(S)-5-(8-Amino-6-(3-hydroxyazetidine-1-carbonyl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)isoindolin-1-one;
(S)-8-Amino-3-(2-(1-cyclopropylethyl)-1-oxoisoindolin-5-yl)-N-(3-hydroxycyclobutyl)imidazo[1,2-a]pyrazine-6-carboxamide;
8-Amino-3-(2-((S)-1-cyclopropylethyl)-1-oxoisoindolin-5-yl)-N-(3-hydroxytetrahydro-2H-pyran-4-yl)imidazo[1,2-a]pyrazine-6-carboxamide;
(S)-5-(8-Amino-6-(2-methyloxazol-5-yl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)-7-(methylsulfonyl)isoindolin-1-one;
(S)-5-(8-Amino-6-(2-methylthiazol-5-yl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)-7-(methylsulfonyl)isoindolin-1-one;
(S)-5-(8-Amino-6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)-7-(methylsulfonyl)isoindolin-1-one;
(S)-5-(8-Amino-6-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)-7-(methylsulfonyl)isoindolin-1-one;
(S)-5-(8-Amino-6-(5-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)-7-(methylsulfonyl)isoindolin-1-one;
(S)-5-(8-Amino-6-(1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropylethyl)-7-(methylsulfonyl)isoindolin-1-one;
5-(4-Aminoimidazo[2,1-f][1,2,4]triazin-7-yl)-2-((S)-1-cyclopropylethyl)-7-(1,1,1-trifluoro-2,3-dihydroxypropan-2-yl)isoindolin-1-one;
5-(8-Amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-2-((S)-1-cyclopropylethyl)-7-(1,1,1-trifluoro-2,3-dihydroxypropan-2-yl)isoindolin-1-one;
tert-Butyl (2-(5-(8-amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-1-oxoisoindolin-2-yl)-2-cyclopropylethyl)carbamate;
2-(2-Amino-1-cyclopropylethyl)-5-(8-amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)isoindolin-1-one;
N-(2-(5-(8-Amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-1-oxoisoindolin-2-yl)-2-cyclopropylethyl)methanesulfonamide;
N-(2-(5-(8-Amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-1-oxoisoindolin-2-yl)-2-cyclopropylethyl)acetamide;
2-(5-(8-Amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-1-oxoisoindolin-2-yl)-2-cyclopropyl-N-methylacetamide;
5-(8-Amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-2-(1-cyclopropyl-2-hydroxyethyl)isoindolin-1-one; and
2-(5-(8-Amino-6-(trifluoromethyl)imidazo[1,2-a]pyrazin-3-yl)-1-oxoisoindolin-2-yl)-2-cyclopropylacetic acid;
or a pharmaceutically acceptable salt thereof.

### Claim 27

A method of treating a disease or disorder in a patient, wherein said disease or disorder is associated with abnormal expression or activity of PI3Kγ kinase, wherein the disease or disorder is lung cancer, melanoma, pancreatic cancer, breast cancer, prostate cancer, liver cancer, colon cancer, endometrial cancer, bladder cancer, skin cancer, cancer of the uterus, renal cancer, gastric cancer, seminoma, teratocarcinoma, astrocytoma, neuroblastoma, glioma, sarcoma, acute myeloid leukemia, acute monocytic leukemia, small lymphocytic lymphoma, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), multiple myeloma, T-cell acute lymphoblastic leukemia (T-ALL), cutaneous T-cell lymphoma, large granular lymphocytic leukemia, mature (peripheral) t-cell neoplasm (PTCL), anaplastic large cell lymphoma (ALCL), lymphoblastic lymphoma, Burkitt's lymphoma, acute myeloblastic leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, hairy cell leukemia, Mantle cell lymphoma, small lymphocytic lymphoma, follicular lymphoma, xeroderma pigmentosum, keratoacanthoma, lymphoplasmacytic lymphoma, extranodal marginal zone lymphoma, Waldenstrom's macroglobulinemia, prolymphocytic leukemia, acute lymphoblastic leukemia, myelofibrosis, mucosa-associated lymphatic tissue (MALT) lymphoma, mediastinal (thymic) large B-cell lymphoma, lymphomatoid granulomatosis, splenic marginal zone lymphoma, primary effusion lymphoma, intravascular large B-cell lymphoma, plasma cell leukemia, extramedullary plasmacytoma, smoldering myeloma (aka asymptomatic myeloma), monoclonal gammopathy of undetermined significance (MGUS), diffuse large B cell lymphoma, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematous, asthma, allergy, allergic rhinitis, pancreatitis, psoriasis, anaphylaxis, glomerulonephritis, inflammatory bowel disease, thrombosis, meningitis, encephalitis, diabetic retinopathy, benign prostatic hypertrophy, myasthenia gravis, Sjögren's syndrome, osteoarthritis, restenosis, atherosclerosis, autoimmune hemolytic anemia, systemic lupus erythematosus, lupus nephritis, or pemphigus, the method comprising administering to said patient a therapeutically effective amount of a compound selected from:
7-(2-(1-Cyclopropylethyl)-7-methyl-2H-indazol-5-yl)imidazo[2,1-f][1,2,4]triazin-4-amine;
7-(1-(1-Cyclopropylethyl)-7-methyl-1H-indazol-5-yl)imidazo[2,1-f][1,2,4]triazin-4-amine;
7-(2-(1-cyclopropylethyl)-2H-benzo[d][1,2,3]triazol-5-yl)imidazo[2,1-f][1,2,4]triazin-4-amine;
7-(2-Isopropyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazo[2,1-f][1,2,4]triazin-4-amine;
7-(2-isopropylimidazo[1,2-a]pyridin-6-yl)imidazo[2,1-f][1,2,4]triazin-4-amine;
7-(2-Isopropylpyrazolo[1,5-a]pyridin-5-yl)imidazo[2,1-f][1,2,4]triazin-4-amine;
7-(2-Isopropylpyrazolo[1,5-a]pyrimidin-5-yl)imidazo[2,1-f][1,2,4]triazin-4-amine;
7-(2-(1-Cyclopropylethyl)-2H-pyrazolo[3,4-b]pyridin-5-yl)imidazo[2,1-f][1,2,4]triazin-4-amine;
7-(2-(1-Cyclopropylethyl)-2H-pyrazolo[3,4-c]pyridin-5-yl)imidazo[2,1-f][1,2,4]triazin-4-amine; and
7-(2-(1-Cyclopropylethyl)imidazo[1,2-a]pyridin-6-yl)imidazo[2,1-f][1,2,4]triazin-4-amine;
or a pharmaceutically acceptable salt thereof.

### Claim 28 (depends on 1)

The method of claim 1, wherein the sarcoma is Askin's tumor, sarcoma botryoides, chondrosarcoma, Ewing's sarcoma, malignant hemangioendothelioma, malignant schwannoma, osteosarcoma, alveolar soft part sarcoma, angiosarcoma, cystosarcoma phyllodes, dermatofibrosarcoma protuberans, desmoid tumor, desmoplastic small round cell tumor, epithelioid sarcoma, extraskeletal chondrosarcoma, extraskeletal osteosarcoma, fibrosarcoma, gastrointestinal stromal tumor (GIST), hemangiopericytoma, hemangiosarcoma, Kaposi's sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, lymphosarcoma, malignant peripheral nerve sheath tumor (MPNST), neurofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, or undifferentiated pleomorphic sarcoma.

### Claim 29 (depends on 1)

The method of claim 1, wherein the mature (peripheral) t-cell neoplasm (PTCL) is T-cell prolymphocytic leukemia, T-cell granular lymphocytic leukemia, aggressive NK-cell leukemia, mycosis fungoides/Sezary syndrome, anaplastic large cell lymphoma (T-cell type), enteropathy type T-cell lymphoma, adult T-cell leukemia/lymphoma, or angioimmunoblastic T-cell lymphoma.

### Claim 30 (depends on 1)

The method of claim 1, wherein the anaplastic large cell lymphoma (ALCL) is systemic ALCL or primary cutaneous ALCL.

### Claim 31 (depends on 1)

The method of claim 1, wherein the non-Hodgkin's lymphoma (NHL) is relapsed NHL, refractory NHL, recurrent follicular NHL, indolent NHL (iNHL), or aggressive NHL (aNHL).

### Claim 32 (depends on 1)

The method of claim 1, wherein the diffuse large B cell lymphoma is activated B-cell like (ABC) diffuse large B cell lymphoma, or germinal center B cell (GCB) diffuse large B cell lymphoma.

### Claim 33 (depends on 1)

The method of claim 1, wherein the Burkitt's lymphoma is endemic Burkitt's lymphoma, sporadic Burkitt's lymphoma, or Burkitt's-like lymphoma.