# US 11,306,079 B2 · 3-(5-amino-pyrazin-2-yl)-benzenesulfonamide derivatives and related compounds as PI3K-gamma kinase inhibitors

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- Number: US 11,306,079 B2
- Document ID: US11306079B2
- Status: Granted
- Kind: B2
- Application number: 16/955,240
- Filed: 2018-12-20
- Published: 2020-10-22
- Granted: 2022-04-19
- Earliest claimed: 2017-12-21
- Assignees: Incyte Corporation
- Applicants: Incyte Corporation
- Inventors: Artem Shvartsbart; Andrew P. Combs; Nikoo Falahatpisheh; Padmaja Polam; Lixin Shao; Stacey Shepard
- Web page: https://patentgrep.com/patent/US11306079B2

## CPC

- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/14: containing three or more hetero rings
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 403/14: containing three or more hetero rings
- C07D 407/14: containing three or more hetero rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- C07D 487/08: Bridged systems
- C07D 493/08: Bridged systems
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## 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 compound of Formula (I):
or a pharmaceutically acceptable salt thereof; wherein:
X1 is N or CR1;
X6 is N or CR6;
Ring A is a C5-10 bridged bicycloalkyl which is optionally substituted by 1, 2, 3, or 4 independently selected R2 groups;
Y1 is a C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl and 4-14 membered heterocycloalkyl of Y1 are each optionally substituted with 1, 2, 3, or 4 independently selected Rb substituents;
R1, R5, R6, and R7 are each independently selected from H, D, halo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, 4-14 membered heterocycloalkyl-C1-6 alkyl-, CN, NO2, ORa, SRa, NHORa, C(O)Ra, C(O)NRaRa, C(O)ORa, OC(O)Ra, OC(O)NRaRa, NRaRa, NRaC(O)Ra, NRaC(O)ORa, NRaC(O)NRaRa, C(═NRk)Ra, C(═NRk)NRaRa, NRaC(═NRk)NRaRa NRaC(═NOH)NRaRa, NRaC(═NCN)NRaRa, NRaS(O)Ra, NRaS(O)2Ra, NRaS(O)2NRaRa, S(O)Ra, S(O)NRaRa, S(O)2Ra, S(O)(═NRk)Ra, SF5, —P(O)RaRa, —P(O)(ORa)(ORa), B(ORa)2 and S(O)2NRaRa, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 5-14 membered heterocycloalkyl-C1-4 alkyl- of R1, R5, R6 and R7 are each optionally substituted with 1, 2, 3, or 4 independently selected Rb substituents;
each R2 is independently selected from D, OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, cyano-C1-6 alkyl, HO—C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C3-10 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, —O-carbamyl, —O—C1-6 alkylcarbamyl, —O-di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino;
R8 is selected from H, D, CN, OH, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
R9 is selected from H, D, halo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, 4-14 membered heterocycloalkyl-C1-6 alkyl-, CN, NO2, ORn, SRn, NHORn, C(O)Rn, C(O)NRnRn, C(O)ORn, OC(O)Rn, OC(O)NRnRn, NRnRn, NRnC(O)Rn, NRnC(O)ORn, NRnC(O)NRnRn, C(═NRk)Rn, C(═NRk)NRnRn, NRnC(═NRk)NRnRn, NRnC(═NOH)NRnRn, NRnC(═NCN)NRnRn, NRnS(O)Rn, NRnS(O)2Rn, NRnS(O)2NRnRn, S(O)Rn, S(O)NRnRn, S(O)2Rn, S(O)(═NRk)Rn, SF5, —P(O)RnRn, —P(O)(ORn)(ORn), B(ORn)2 and S(O)2NRnRn, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-4 alkyl- of R9 are each optionally substituted with 1, 2, 3, or 4 independently selected Rm substituents;
each Ra is independently selected from H, D, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl- and 4-14 membered heterocycloalkyl-C1-6 alkyl- of Ra is each optionally substituted with 1, 2, 3, or 4 independently selected Rb substituents;
each Rb is independently selected from D, halo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, 4-14 membered heterocycloalkyl-C1-6 alkyl-, CN, NO2, ORc, SRc, NHORc, C(O)Rc, C(O)NRcRc, C(O)ORc, OC(O)Rc, OC(O)NRcRc, NRcRc, NRcC(O)Rc, NRc(O)ORc, NRc(O)NRcRc, C(═NRk)Rc, C(═NRk)NRcRc, NRc(═NRk)NRcRc, NRc(═NOH)NRcRc, NRc(═NCN)NRcRc, NRcS(O)Rc, NRcS(O)2Rc, NRcS(O)2NRcRc, S(O)Rc, S(O)NRcRc, S(O)2Rc, S(O)(═NRk)Rc, SF5, —P(O)RcRc, —P(O)(ORc)(ORc), B(ORc)2 and S(O)2NRcRc, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-4 alkyl- of Rb is each optionally substituted with 1, 2, 3, or 4 independently selected Rd substituents;
each Rc is independently selected from H, D, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl- and 4-14 membered heterocycloalkyl-C1-6 alkyl- of Rc is each optionally substituted with 1, 2, 3, or 4 independently selected Rd substituents;
each Rd is independently selected from D, halo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, 4-14 membered heterocycloalkyl-C1-6 alkyl-, CN, NO2, ORe, SRe, NHORe, C(O)Re, C(O)NReRe, C(O)ORe, OC(O)Re, OC(O)NReRe, NReRe, NReC(O)Re, NReC(O)ORe, NReC(O)NReRe, C(═NRk)Re, C(═NRk)NReRe, NReC(═NRk)NReRe, NReC(═NOH)NReRe, NReC(═NCN)NReRe, NReS(O)Re, NReS(O)2Re, NReS(O)2NReRe, S(O)Re, S(O)NReRe, S(O)2Re, S(O)(═NRk)Re, SF5, —P(O)ReRe, —P(O)(ORe)(ORe), B(ORe)2 and S(O)2NReRe, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-4 alkyl- of Rd is each optionally substituted with 1, 2, 3, or 4 independently selected Rf substituents;
each Re is independently selected from H, D, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl- and 4-14 membered heterocycloalkyl-C1-6 alkyl- of Re is each optionally substituted with 1, 2, 3, or 4 independently selected Rf substituents;
each Rf is independently selected from D, halo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, 4-14 membered heterocycloalkyl-C1-6 alkyl-, CN, NO2, ORg, SRg, NHORg, C(O)Rg, C(O)NRgRg, C(O)ORg, OC(O)Rg, OC(O)NRgRg, NRgRg, NRgC(O)Rg, NRgC(O)ORg, NRgC(O)NRgRg, C(═NRk)Rg, C(═NRk)NRgRg, NRgC(═NRk)NRgRg, NRgC(═NOH)NRgRg, NRgC(═NCN)NRgRg, NRgS(O)Rg, NRgS(O)2Rg, NRgS(O)2NRgRg, S(O)Rg, S(O)NRgRg, S(O)2Rg, S(O)(═NRk)Rg, SF5, —P(O)RgRg, —P(O)(ORg)(ORg), B(ORg)2 and S(O)2NRgRg, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-4 alkyl- of Rf is each optionally substituted with 1, 2, 3, or 4 independently selected Rh substituents;
each Rg is independently selected from H, D, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5+-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl- and 4-14 membered heterocycloalkyl-C1-6 alkyl- of Rg is each optionally substituted with 1, 2, 3m or 4 independently selected Rh substituents;
each Rh is independently selected from H, D, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl- and 4-14 membered heterocycloalkyl-C1-6 alkyl- of Rh is each optionally substituted with 1 or 2 independently selected Ri substituents;
each Ri is independently selected from H, D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-6 alkyl-;
each Rk is independently selected from H, CN, OH, C1-4 alkyl, and C1-4 alkoxy;
each Rm is independently selected from D, OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, cyano-C1-6 alkyl, HO—C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C3-10 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, —O-carbamyl, —O—C1-6 alkylcarbamyl, —O-di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino; and
each Rn is independently selected from H, D, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-6 membered heterocycloalkyl;
or any two Rn substituents, together with the atom to which they attached form a 4-, 5-, 6, or 7-membered heterocycloalkyl group, wherein said heterocycloalkyl group is optionally substituted by 1, 2, 3, or 4 independently selected Rm groups.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is a C5-10 bridged bicycloalkyl.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from bicyclo[1.1.1]pentanylene, bicyclo[2.1.1]hexanylene, bicyclo[2.2.1]heptanylene, and bicyclo[2.2.2]octanylene, each of which is optionally substituted by 1, 2, or 3 independently selected R2 groups.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from

### Claim 5 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X1 is N or CH.

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X1 is N.

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X1 is CH.

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R5 is C1-6 alkyl or CD3.

### Claim 9 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R5 is methyl or —CD3.

### Claim 10 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X6 is CR6.

### Claim 11 (depends on 10)

The compound of claim 10, or a pharmaceutically acceptable salt thereof, wherein R6 is H or halo.

### Claim 12 (depends on 10)

The compound of claim 10, or a pharmaceutically acceptable salt thereof, wherein R6 is H or fluoro.

### Claim 13 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X6 is N.

### Claim 14 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R7 is H.

### Claim 15 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R8 is H.

### Claim 16 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R7 and R8 are each H.

### Claim 17 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y1 is phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, or 4-7 membered heterocycloalkyl, wherein the phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, or 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected Rb substituents.

### Claim 18 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y1 is a 5-6 membered heteroaryl group which is optionally substituted by 1, 2, 3, or 4 independently selected Rb substituents.

### Claim 19 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y1 is selected from thiazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, pyridyl, and pyrimidinyl, wherein the thiazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, pyridyl, and pyrimidinyl are each optionally substituted by 1 or 2 independently selected Rb substituents.

### Claim 20 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y1 is selected from thiazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, pyridyl, and pyrimidinyl, wherein the thiazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, pyridyl, and pyrimidinyl are each optionally substituted by 1 or 2 independently selected Rb substituents.

### Claim 21 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the Rb substituents on Y1 are each independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, CN, NRcRc, and SRc.

### Claim 22 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the Rb substituents on Y1 are each independently selected from fluoro, methyl, trifluoromethyl, cyclopropyl, CN, dimethylamino, and methylthio.

### Claim 23 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Y1 is selected from 2-methylthiazol-5-yl, 2-cyclopropylthiazol-5-yl, oxazol-2-yl, oxazol-5-yl, 2-methyloxazol-5-yl, 1H-pyrazol-1-yl, 1-methyl-1H-pyrazol-3-yl, 1,3-dimethyl-1H-pyrazol-4-yl, 1H-1,2,4-triazol-1-yl, 1H-1,2,3-triazol-1-yl, 2H-1,2,3-triazol-2-yl, 1-methyl-1H-1,2,4-triazol-3-yl, 2H-tetrazol-5-yl, pyridin-3-yl, pyridin-4-yl, 2-methylpyridin-4-yl, 2-cyanopyridin-4-yl, 3-fluoropyridin-4-yl, 2-(trifluoromethyl)pyridin-4-yl, 3-cyanopyridin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, 2-(methylthio)pyrimidin-4-yl, and 2-(dimethyl amino)pyrimidin-5-yl.

### Claim 24 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R9 is selected from H, D, halo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, CN, ORn, C(O)Rn, C(O)NRnRn, C(O)ORn, OC(O)Rn, OC(O)NRnRn, NRnRn, NRnC(O)Rn, NRnC(O)ORn, and NRnC(O)NRnRn, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy of R9 are each optionally substituted with 1, 2, 3 or 4 independently selected Rm substituents.

### Claim 25 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R9 is selected from H, C1-6 alkyl, C1-6 alkoxy, CN, ORn, C(O)Rn, C(O)NRnRn, NRnC(O)Rn, and NRnC(O)ORn, wherein the C1-6 alkyl and C1-6 alkoxy are each optionally substituted with 1 or 2 independently selected Rm substituents.

### Claim 26 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R9 is selected from H, C1-6 alkyl, C1-6 alkoxy, CN, ORn, C(O)Rn, C(O)NRnRn, NRnC(O)Rn, and NRnC(O)ORn, wherein the C1-6 alkyl are each optionally substituted with 1 or 2 Rm groups selected from OH and —O—C1-6 alkylcarbamyl, and each Rn is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; or two Rn substituents, together with the nitrogen atom to which they attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group.

### Claim 27 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R9 is selected from H, CN, OH, methyl, 2-isopropyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxypropan-2-yl, —CH2OC(O)NHCH3, C(O)NHCH3, C(O)N(CH3)2, C(O)-azetidin-1-yl, C(O)NHCH2CF3, NHC(O)OCH2CH3, and NHC(O)CH3.

### Claim 28 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
X1 is N or CH;
X6 is N or CR6;
Ring A is a C5-10 bridged bicycloalkyl which is optionally substituted by 1, 2, 3, or 4 independently selected R2 groups;
R2 is selected from D, OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, cyano-C1-6 alkyl, HO—C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C3-10 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, —O— carbamyl, —O—C1-6 alkylcarbamyl, —O-di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino;
R5 is C1-6 alkyl;
R6 is H or halo;
R7 is H;
R8 is H;
Y1 is phenyl, C3-7 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein the phenyl, C3-7 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected Rb substituents;
R9 is selected from H, D, halo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, CN, ORn, C(O)Rn, C(O)NRnRn, C(O)ORn, OC(O)Rn, OC(O)NRnRn, NRnRn NRnC(O)Rn, NR1C(O)ORn, and NRnC(O)NRnRn, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy of R9 are each optionally substituted with 1, 2, 3 or 4 independently selected Rm substituents;
each Rb is independently selected from D, halo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, 4-14 membered heterocycloalkyl-C1-6 alkyl-, CN, NO2, ORc, SRc, NHORc, C(O)Rc, C(O)NRcRc, C(O)ORc, OC(O)Rc, OC(O)NRcRc, NRcRc, NRc(O)Rc, NRc(O)ORc, NRc(O)NRcRc, C(═NRk)Rc, C(═NRk)NRcRc, NRc(═NRk)NRcRc, NRc(═NOH)NRcRc, NRc(═NCN)NRcRc, NRcS(O)Rc, NRcS(O)2Rc, NRcS(O)2NRcRc, S(O)Rc, S(O)NRcRc, S(O)2Rc, S(O)(═NRk)Rc, SF5, —P(O)RcRc, —P(O)(ORc)(ORc), B(ORc)2 and S(O)2NRcRc, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-4 alkyl- of Rb is each optionally substituted with 1, 2, 3, or 4 independently selected Rd substituents;
each Rc is independently selected from H, D, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-6 alkyl-, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl- and 4-14 membered heterocycloalkyl-C1-6 alkyl- of Rc is each optionally substituted with 1, 2, 3, or 4 independently selected Rd substituents;
each Rd is independently selected from D, halo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, 4-14 membered heterocycloalkyl-C1-6 alkyl-, CN, NO2, ORe, SRe, NHORe, C(O)Re, C(O)NReRe, C(O)ORe, OC(O)Re, OC(O)NReRe, NReRe, NReC(O)Re, NReC(O)ORe, NReC(O)NReRe, C(═NRk)Re, C(═NRk)NReRe, NReC(═NRk)NReRe, NReC(═NOH)NReRe, NReC(═NCN)NReRe, NReS(O)Re, NReS(O)2Re, NReS(O)2NReRe, S(O)Re, S(O)NReRe, S(O)2Re, S(O)(═NRk)Re, SF5, —P(O)ReRe, —P(O)(ORe)(ORe), B(ORe)2 and S(O)2NReRe;
each Re is independently selected from H, D, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-6 alkyl-, C3-10 cycloalkyl-C1-6 alkyl-, 5-14 membered heteroaryl-C1-6 alkyl-, and 4-14 membered heterocycloalkyl-C1-6 alkyl-;
each Rk is independently selected from H, CN, OH, C1-4 alkyl, and C1-4 alkoxy;
each Rm is independently selected from D, OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, cyano-C1-6 alkyl, HO—C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C3-10 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, —O-carbamyl, —O—C1-6 alkylcarbamyl, —O-di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino; and
each Rn is independently selected from H, D, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-6 membered heterocycloalkyl;
or any two Rn substituents, together with the atom to which they attached form a 4-, 5-, 6, or 7-membered heterocycloalkyl group.

### Claim 29 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
X1 is N or CH;
X6 is N or CR6;
Ring A is bicyclo[1.1.1]pentanylene, bicyclo[2.1.1]hexanylene, bicyclo[2.2.1]heptanylene, or bicyclo[2.2.2]octanylene;
R5 is C1-6 alkyl;
R6 is H or halo;
R7 is H;
R8 is H;
Y1 is a 5-6 membered heteroaryl group which is optionally substituted by 1, 2, 3, or 4 independently selected Rb substituents;
R9 is selected from H, D, halo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, CN, ORn, C(O)Rn, C(O)NRnRn, C(O)ORn, OC(O)Rn, OC(O)NRnRn, NRnRn NRnC(O)Rn, NRnC(O)ORn, and NRnC(O)NRnRn, wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy of R9 are each optionally substituted with 1, 2, 3 or 4 independently selected Rm substituents;
each Rb is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, CN, NRcRc, and SRc;
each Rc is independently selected from H, D, and C1-6 alkyl;
each Rm is independently selected from D, OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, cyano-C1-6 alkyl, HO—C1-6 alkyl, C1-6 alkoxy-C1-6 alkyl, C3-10 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, —O-carbamyl, —O—C1-6 alkylcarbamyl, —O-di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino; and
each Rn is independently selected from H, D, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, and 4-6 membered heterocycloalkyl;
or any two Rn substituents, together with the atom to which they attached form a 4-, 5-, 6, or 7-membered heterocycloalkyl group.

### Claim 30 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
X1 is N or CH;
X6 is N or CR6;
Ring A is
R5 is C1-6 alkyl;
R6 is H or halo;
R7 is H;
R8 is H;
Y1 is selected from thiazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, pyridyl, and pyrimidinyl, wherein the thiazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, pyridyl, and pyrimidinyl are each optionally substituted by 1 or 2 independently selected Rb substituents;
R9 is selected from H, C1-6 alkyl, C1-6 alkoxy, CN, ORn, C(O)Rn, C(O)NRnRn, NRnC(O)Rn, and NRnC(O)ORn, wherein the C1-6 alkyl and C1-6 alkoxy are each optionally substituted with 1 or 2 Rm substituents;
each Rb is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, CN, NRcRc, and SRc;
each Rc is independently selected from H, D, and C1-6 alkyl;
each Rm is independently selected from OH and —O—C1-6 alkylcarbamyl; and
each Rn is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;
or any two Rn substituents, together with the atom to which they attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group.

### Claim 31 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is a compound of Formula (II):
or a pharmaceutically acceptable salt thereof.

### Claim 32 (depends on 1)

The compound of claim 1, wherein the compound of Formula (I) is a compound of Formula (III):
or a pharmaceutically acceptable salt thereof.

### Claim 33 (depends on 1)

The compound of claim 1, wherein the compound of Formula (I) is a compound of Formula (IV):
or a pharmaceutically acceptable salt thereof.

### Claim 34 (depends on 1)

The compound of claim 1, wherein the compound of Formula (I) is a compound of Formula (V):
or a pharmaceutically acceptable salt thereof.

### Claim 35 (depends on 1)

The compound of claim 1, wherein the compound of Formula (I) is a compound of Formula (VI):
or a pharmaceutically acceptable salt thereof.

### Claim 36 (depends on 1)

The compound of claim 1, wherein the compound of Formula (I) is a compound of Formula (VII):
or a pharmaceutically acceptable salt thereof.

### Claim 37 (depends on 1)

The compound of claim 1, wherein the compound of Formula (I) is a compound of Formula (VIII):
or a pharmaceutically acceptable salt thereof.

### Claim 38 (depends on 1)

The compound of claim 1, wherein the compound of Formula (I) is a compound of Formula (IX):
or a pharmaceutically acceptable salt thereof.

### Claim 39 (depends on 1)

The compound of claim 1, selected from:
3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(4-(hydroxymethyl)bicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(4-(hydroxymethyl)bicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
3-(5-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(pyridin-3-yl)pyrazin-2-yl)-N-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(pyri din-4-yl)pyrazin-2-yl)-N-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(4-(hydroxymethyl)bicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-(2-hydroxypropan-2-yl)bicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(4-hydroxybicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
(3-(3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methylphenylsulfonamido)bicyclo[1.1.1]pentan-1-yl)methyl methylcarbamate;
3-(3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methylphenyl sulfonamido)-N-methylbicyclo[1.1.1]pentane-1-carboxamide;
3-(3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methylphenyl sulfonamido)-N,N-dimethylbicyclo[1.1.1]pentane-1-carboxamide;
3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-(azetidine-1-carbonyl)bicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methylphenylsulfonamido)-N-(2,2,2-trifluoroethyl)bicyclo[1.1.1]pentane-1-carboxamide;
3-(5-Amino-6-(2H-tetrazol-5-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(2H-tetrazol-5-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
Ethyl 3-(3-(5-amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methylphenyl sulfonamido)bicyclo[1.1.1]pentan-1-ylcarbamate;
N-(3-(3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-4-methylphenyl sulfonamido)bicyclo[1.1.1]pentan-1-yl)acetamide;
3-(5-Amino-6-(2H-1,2,3-triazol-2-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(2H-1,2,3-triazol-2-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1H-1,2,3-triazol-1-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1H-1,2,3-triazol-1-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1-methyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1-methyl-1H-1,2,4-triazol-3-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(1H-1,2,4-triazol-1-yl)pyrazin-2-yl)-N-(3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(2H-1,2,3-triazol-2-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(2H-1,2,3-triazol-2-yl)pyrazin-2-yl)-N-(3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(1H-pyrazol-1-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
3-(5-Amino-6-(1-methyl-1H-pyrazol-3-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(pyrimidin-5-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(2-methylthiazol-5-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(2-methyloxazol-5-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(2-(dimethylamino)pyrimidin-5-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(oxazol-5-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(pyrimidin-2-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(oxazol-2-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(pyrimidin-4-yl)pyrazin-2-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(oxazol-5-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(oxazol-5-yl)pyrazin-2-yl)-N-(4-hydroxybicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(oxazol-5-yl)pyrazin-2-yl)-N-(3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(2-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(2-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)-N-(4-hydroxybicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(2-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)-N-(3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(pyrimidin-4-yl)pyrazin-2-yl)-N-(3-cyanobicyclo[1.1.1]pentan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(pyrimidin-4-yl)pyrazin-2-yl)-N-(4-hydroxybicyclo[2.1.1]hexan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(5-Amino-6-(pyrimidin-4-yl)pyrazin-2-yl)-N-(3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)-4-(methyl-d3)benzenesulfonamide;
3-(6-Amino-5-(1,3-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide;
3-(6-amino-5-(2-methylthiazol-5-yl)pyridin-3-yl)-N-(4-cyanobicyclo[2.1.1]hexan-1-yl)-4-methylbenzenesulfonamide; and
3-(6-amino-5-(2-methylthiazol-5-yl)pyridin-3-yl)-N-(3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)-4-methylbenzenesulfonamide;
or a pharmaceutically acceptable salt thereof.

### Claim 40 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt or a tautomer thereof, and a pharmaceutically acceptable excipient or carrier.

### Claim 41 (depends on 1)

A method of inhibiting an activity of PI3Kγ kinase, comprising contacting the kinase with a compound of claim 1, or a pharmaceutically acceptable salt or a tautomer thereof.

### Claim 42 (depends on 41)

The method of claim 41, wherein said compound, or a pharmaceutically acceptable salt thereof, is a selective inhibitor for PI3Kγ over one or more of PI3Kα, PI3Kβ, and PI3Kδ.

### Claim 43 (depends on 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, comprising administering to said patient a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 44 (depends on 43)

The method of claim 43, wherein the disease or disorder is an autoimmune disease or disorder, cancer, cardiovascular disease, or neurodegenerative disease.

### Claim 45 (depends on 43)

The method of claim 43, wherein disease or disorder is lung cancer, melanoma, pancreatic cancer, breast cancer, prostate cancer, liver cancer, color cancer, endometrial cancer, bladder cancer, skin cancer, cancer of the uterus, renal cancer, gastric cancer, seminoma, teratocarcinoma, astrocytoma, neuroblastoma, glioma, or sarcoma.

### Claim 46 (depends on 45)

The method of claim 45, 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 47 (depends on 43)

The method of claim 43, wherein the disease or disorder is acute myeloid leukemia, acute monocytic leukemia, small lymphocyctic lymphoma, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), multiple myeloma, T-cell actute lymphoblasic leukemia (T-ALL), cutaneous T-cell lymphoma, large granular lymphocytic leukemia, mature (peripheral) t-cell neoplasm (PTCL), anaplastic large cell lymphoma (ALCL), or lymphoblastic lymphoma.

### Claim 48 (depends on 47)

The method of claim 47, 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, naplastic large cell lymphoma (T-cell type), enteropathy type T-cell lymphoma, adult T-cell leukemia/lymphoma, or angioimmunoblastic T-cell lymphoma.

### Claim 49 (depends on 47)

The method of claim 47, wherein the anaplastic large cell lymphoma (ALCL) is systemic ALCL or primary cutaneous ALCL.

### Claim 50 (depends on 43)

The method of claim 43, wherein the disease or disorder is 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, xenoderoma pigmentosum, keratoctanthoma, 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, smouldering myeloma (aka asymptomatic myeloma), monoclonal gammopathy of undetermined significance (MGUS), or diffuse large B cell lymphoma.

### Claim 51 (depends on 50)

The method of claim 50, wherein the non-Hodgkin's lymphoma (NHL) is relapsed NHL, refractory NHL, recucurrent follicular NHL, indolent NHL (iNHL), or aggressive NHL (aNHL).

### Claim 52 (depends on 50)

The method of claim 50, 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 53 (depends on 50)

The method of claim 50, wherein the Burkitt's lymphoma is endemic Burkitt's lymphoma, sporadic Burkitt's lymphoma, or Burkitt's-like lymphoma.

### Claim 54 (depends on 43)

The method of claim 43, wherein the disease or disorder is 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, or atherosclerosis.

### Claim 55 (depends on 43)

The method of claim 43, wherein the disease or disorder is heart hypertropy, cardiac myocyte dysfunction, acute coronary syndrome, chronic obstructive pulmonary disease (COPD), chronic bronchitis, elevated blood pressure, ischemia, ischemia-reperfusion, vasoconstriction, anemia, bacterial infection, viral infection, graft rejection, kidney disease, anaphylactic shock fibrosis, skeletal muscle atrophy, skeletal muscle hypertrophy, angiogenesis, sepsis, graft-versus-host disease, allogeneic or xenogeneic transplantation, glomerulosclerosis, progressive renal fibrosis, idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia, vasculitis, systemic lupus erythematosus, lupus nephritis, pemphigus, or membranous nephropathy.

### Claim 56 (depends on 55)

The method of claim 55, wherein the idiopathic thrombocytopenic purpura (ITP) is relapsed ITP or refractory ITP.

### Claim 57 (depends on 55)

The method of claim 55, wherein the vasculitis is Behcet's disease, Cogan's syndrome, giant cell arteritis, polymyalgia rheumatica (PMR), Takayasu's arteritis, Buerger's disease (thromboangiitis obliterans), central nervous system vasculitis, Kawasaki disease, polyarteritis nodosa, Churg-Strauss syndrome, mixed cryoglobulinemia vasculitis (essential or hepatitis C virus (HCV)-induced), Henoch-Schönlein purpura (HSP), hypersensitivity vasculitis, microscopic polyangiitis, Wegener's granulomatosis, or anti-neutrophil cytoplasm antibody associated (ANCA) systemic vasculitis (AASV).

### Claim 58 (depends on 43)

The method of claim 43, wherein the disease or disorder is Alzheimer's disease, central nervous system trauma, or stroke.