# US 12,180,215 B2 · Substituted pyrrolo[3,4-d]imidazoles as JAK inhibitors

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- Number: US 12,180,215 B2
- Document ID: US12180215B2
- Status: Granted
- Kind: B2
- Application number: 18/169,580
- Filed: 2023-02-15
- Published: 2023-06-22
- Granted: 2024-12-31
- Earliest claimed: 2019-02-25
- Assignees: Henan Medinno Pharmaceutical Technology Co., Ltd.
- Applicants: Henan Medinno Pharmaceutical Technology Co., Ltd.
- Inventors: Liang Lu; Hai Huang; Longzheng Zhang; Saisai Zhao; Jixuan Zhang
- Web page: https://patentgrep.com/patent/US12180215B2

## CPC

- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- C07D 487/04: Ortho-condensed systems
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/16: for decreasing, blocking or antagonising the activity of the thyroid hormones
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 7/06: Antianaemics
- 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 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/04: Antipruritics
- A61P 17/06: Antipsoriatics
- A61P 17/14: for baldness or alopecia
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- 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 27/02: Ophthalmic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- 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
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present disclosure relates to a class of JAK inhibitor compounds and uses thereof. Specifically, the present disclosure discloses a compound represented by formula (G), isotopically labeled compound thereof, or optical isomer thereof, geometric isomer thereof, a tautomer thereof or a mixture of various isomers, or a pharmaceutically acceptable salt thereof, or a prodrug thereof, or a metabolite thereof. The present disclosure also relates to the application of the compounds in medicine.

## Claims

### Claim 1

A compound of formula (G),
or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
each R2 is independently H, halogen, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, or a bicyclic 7-11 membered heteroaryl;
wherein each C1-6 alkyl, C2-6 alkenyl, OC1-6 alkyl, OC1-6 haloalkyl, and SC1-4 alkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl, 4-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, and 7-11 membered heteroaryl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-7 cycloalkyl;
L is a bond, —CH2—, —C(O)—, or —S(O)2—;
R13 is H, halogen, CN, NO2, C1-6 alkyl, NR17R18, OH, OC1-6 alkyl, OC1-4 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, C5-11 bicycloalkyl, a 3-7 membered heterocycloalkyl, a bicyclic 5-11 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, a bicyclic 7-11 membered heteroaryl, or an 11-15 membered tricyclyl, wherein R13 is optionally substituted with 1, 2, 3, or 4 independently selected R1 substituents;
each R1 is independently halogen, CN, NO2, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-8 alkyl, OC1-4 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, C5-11 bicycloalkyl, a 3-10 membered heterocycloalkyl, a bicyclic 5-11 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, a bicyclic 7-11 membered heteroaryl, or an 11-15 membered tricyclyl;
wherein each C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, OC1-8 alkyl, and SC1-4 alkyl is optionally and independently substituted with 1, 2, 3, or 4 independently selected R3 substituents; and
wherein each C3-7 cycloalkyl, 3-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, and 7-11 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 independently selected R4 substituents; and
each R3 is independently halogen, CN, NO2, C(O)R12, C(O)NR7R8, C(O)OR12, NR5R6, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 3-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, or a bicyclic 7-11 membered heteroaryl;
wherein each C3-7 cycloalkyl, 3-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, or 7-11 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
each R4 is independently halogen, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)R12, C(O)NR7R8, C(O)OR12, NR5R6, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 3-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, or a bicyclic 7-11 membered heteroaryl;
wherein each C1-6 alkyl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-4 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
wherein each C3-7 cycloalkyl, 3-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, and 7-11 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substitutes substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-4haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
each R5 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substitutes substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NH(CH3), N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substitutes substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NH(CH3), N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
each R6 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
each R7 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
each R8 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
X1 is CR14 or N;
X2 is CR15 or N;
X3 is CR16 or N;
R14 is H, halogen, CN, NO2, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-4haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl, wherein the C1-6 alkyl, OC1-6 alkyl, or SC1-4 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)(C(O) C1-4 alkyl), OH, OC1-4 alkyl, OC1-4 haloalkyl, SC1-4 alkyl, and C3-7 cycloalkyl; and
wherein the C3-7 cycloalkyl, or 3-7 membered heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)-C(O)C1-4 alkyl, OH, OC1-4 alkyl, OC1-4 haloalkyl, SC1-4 alkyl, and C3-7 cycloalkyl;
R15 is H, halogen, CN, NO2, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl,
wherein the C1-6 alkyl, OC1-6 alkyl, or SC1-4 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)(C(O) C1-4 alkyl), OH, OC1-4 alkyl, OC1-4 haloalkyl, SC1-4 alkyl, and C3-7 cycloalkyl; and
wherein the C3-7 cycloalkyl, or 3-7 membered heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)-C(O)C1-4 alkyl, OH, OC1-4 alkyl, OC1-4 haloalkyl, SC1-4 alkyl, and C3-7 cycloalkyl;
R16 is H, halogen, CN, NO2, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-4haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl,
wherein the C1-6 alkyl, OC1-6 alkyl, or SC1-4 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)(C(O) C1-4 alkyl), OH, OC1-4 alkyl, OC1-4 haloalkyl, SC1-4 alkyl, C3-7 cycloalkyl; and
wherein the C3-7 cycloalkyl, or 3-7 membered heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, N(C1-4 alkyl)-C(O)C1-4 alkyl, OH, OC1-4 alkyl, OC1-4 haloalkyl, SC114 alkyl, and C3-7 cycloalkyl;
R17 is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, OC1-6 haloalkyl, C3-7 cycloalkyl, C5-11 bicycloalkyl, a 3-7 membered heterocycloalkyl, a bicyclic 5-11 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, a bicyclic 7-11 membered heteroaryl, or an 11-15 membered tricycyl;
wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, or OC1-6 haloalkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, and a bicyclic 7-11 membered heteroaryl;
wherein the C3-7 cycloalkyl, C5-11 bicycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, 7-11 membered heteroaryl, or 11-15 membered tricyclyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, and a bicyclic 7-11 membered heteroaryl;
wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, OC1-6 haloalkyl and SC1-4 haloalkyl substituent is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl; and
wherein each C3-7 cycloalkyl, 4-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, and 7-11 membered heteroaryl substituent is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
R18 is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, OC1-6 haloalkyl, C3-7 cycloalkyl, C5-11 bicycloalkyl, a 3-7 membered heterocycloalkyl, a bicyclic 5-11 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, a bicyclic 7-11 membered heteroaryl, or an 11-15 membered tricycyl;
wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, or OC1-6 haloalkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, and a bicyclic 7-11 membered heteroaryl;
wherein the C3-7 cycloalkyl, C5-11 bicycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heteroaryl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, 7-11 membered heteroaryl, or 11-15 membered tricyclyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, and a bicyclic 7-11 membered heteroaryl;
wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OC1-6 alkyl, OC1-6 haloalkyl, and SC1-4 haloalkyl substituent is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl; and
wherein each C3-7 cycloalkyl, 4-10 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, and 7-11 membered heteroaryl substituent is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl; or
R17 and R18 together with the nitrogen atom to which they are attached, form a 3-14 membered heterocyclyl;
each R9 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
each R10 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl;
each R11 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl; and
each R12 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, SC3-7 cycloalkyl.

### Claim 2 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
one R2 is H; and
the other R2(s) are independently H, halogen, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, OH, OC1-6 alkyl, OC1-6haloalkyl, SH, SC1-4 alkyl, SF5, C3-7 cycloalkyl, or a 4-10 membered heterocycloalkyl;
wherein each C1-6 alkyl, and SC1-4 alkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, and OC1-4haloalkyl; and
wherein each C3-7 cycloalkyl and a 4-10 membered heterocycloalkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, and OC1-4 haloalkyl.

### Claim 3 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
one R2 is H; and
the other R2(s) are independently H, halogen, C1-6 alkyl, or C3-6 cycloalkyl;
wherein each C1-6 alkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, and OC1-4 haloalkyl; and
wherein each C3-6 cycloalkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, and OC1-4 haloalkyl.

### Claim 4 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
one R2 is H; and
the other R2(s) are independently H, halogen, or C1-6 alkyl wherein each C1-6 alkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-4haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, 0-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-7 cycloalkyl.

### Claim 5 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein L is —CH2—, —C(O)—, or —S(O)2—.

### Claim 6 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
R13 is H, halogen, CN, NO2, C1-6 alkyl, NR17R18, OH, OC1-6 alkyl, SH, SC1-4 alkyl, SF5, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, a bicyclic 7-11 membered heteroaryl, or an 11-15 membered tricyclyl, wherein the C1-6 alkyl, OC1-6 alkyl, SC1-4 alkyl, C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, 7-11 membered heteroaryl, or 11-15 membered tricyclyl is optionally substituted with 1, 2, 3, or 4 independently selected R1 substituents.

### Claim 7 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
R13 is H, C1-6 alkyl, NR17R18, OC1-6 alkyl, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl, wherein the C1-6 alkyl, OC1-6 alkyl, C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, C5-7 aryl, or 5-7 membered heteroaryl is optionally substituted with 1, 2, 3, or 4 independently selected R1 substituents.

### Claim 8 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
R13 is optionally substituted with 1 R1 substituent;
R1 is halogen, C1-6 alkyl, OH, C3-7 cycloalkyl, or a 5-7 membered heteroalkyl;
wherein the C1-6 alkyl is optionally and independently substituted with 1, 2, or 3 independently selected R3 substituents; and
wherein the C3-7 cycloalkyl or 5-7 membered heterocycloalkyl is optionally and independently substituted with 1, 2, 3, or 4 independently selected R4 substituents; and
each R4 is independently C1-3 alkyl.

### Claim 9 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
R17 is H, C1-6 alkyl, C3-7 cycloalkyl, or a 3-7 membered heterocycloalkyl;
wherein the C1-6 alkyl, or OC1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5; and
wherein the C3-7 cycloalkyl, or 3-7 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5; and
R18 is H, C1-6 alkyl, C3-7 cycloalkyl, or a 3-7 membered heterocycloalkyl;
wherein the C1-6 alkyl, or OC1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5; and
wherein the C3-7 cycloalkyl, or 3-7 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5.

### Claim 10 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
R13 is H, halogen, CN, NO2, C1-6 alkyl, NR17R18, OH, OC1-6 alkyl, SH, SC1-4 alkyl, SF5, C3-7 cycloalkyl, C5-11 bicycloalkyl, a 3-7 membered heterocycloalkyl, a bicyclic 5-11 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, a bicyclic 7-11 membered heteroaryl, or an 11-15 membered tricyclyl, wherein the C1-6 alkyl, OC1-6 alkyl, SC1-4 alkyl, C3-7 cycloalkyl, C5-11 bicycloalkyl, 3-7 membered heterocycloalkyl, 5-11 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, 7-11 membered heteroaryl, or 11-15 membered tricyclyl is optionally substituted with 1, 2, 3, or 4 independently selected R1 substituents;
R17 is H, C1-6 alkyl, OC1-6 alkyl, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl;
wherein the C1-6 alkyl, or OC1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5; and
wherein the C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, C5-7 aryl, or 5-7 membered heteroaryl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5; and
R18 is H, C1-6 alkyl, OC1-6 alkyl, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl;
wherein the C1-6 alkyl, or OC1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5; and
wherein the C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, C5-7 aryl, or 5-7 membered heteroaryl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5.

### Claim 11 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
L is —C(O)—
R13 is H, halogen, CN, NO2, NR17R18, OH, OC1-6 alkyl, SH, SC1-4 alkyl, or SF5, wherein the OC1-6 alkyl or SC1-4 alkyl is optionally substituted with 1, 2, 3, or 4 independently selected R1 substituents;
R17 is H, C1-6 alkyl, OC1-6 alkyl, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl;
wherein the C1-6 alkyl, or OC1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5; and
wherein the C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, C5-7 aryl, or 5-7 membered heteroaryl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5; and
R18 is H, C1-6 alkyl, OC1-6 alkyl, C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl;
wherein the C1-6 alkyl, or OC1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5; and
wherein the C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, C5-7 aryl, or 5-7 membered heteroaryl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, NO2, OH, SH, and SF5; or
R17 and R18 together with the nitrogen atom to which they are attached, form a 3-14 membered heterocyclyl.

### Claim 12 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
X1 is CR14; and
X2 is CR16.

### Claim 13 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
X1 is CR14;
X2 is CR15;
X3 is CR16;
R14 is H;
R15 is H; and
R16 is H.

### Claim 14 (depends on 1)

The compound according to claim 1, wherein the compound is of the following Formula:
or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
each R2 is independently H, halogen, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-6 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, C3-7 cycloalkyl, or a 4-10 membered heterocycloalkyl;
wherein each C1-6 alkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-4 alkyl, OC1-4 haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl and 4-10 membered heterocycloalkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-4 alkyl, OC1-4haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-7 cycloalkyl;
L is a bond;
ring A is C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, a bicyclic 7-11 membered heteroaryl, or an 11-15 membered tricyclyl, wherein the C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, 7-11 membered heteroaryl, and 11-15 membered tricyclyl is optionally substituted with 1, 2, 3, or 4 independently selected R1 substituents;
each R1 is independently halogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, OC1-8 alkyl, C3-7 cycloalkyl, a 3-10 membered heterocycloalkyl, a monocyclic C5-7 aryl, a bicyclic C7-11 aryl, a monocyclic 5-7 membered heteroaryl, or a bicyclic 7-11 membered heteroaryl;
wherein each C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, and OC1-8 alkyl is optionally and independently substituted with 1, 2, 3, or 4 independently selected R3 substituents; and
wherein each C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, C5-7 aryl, C7-11 aryl, 5-7 membered heteroaryl, and 7-11 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 independently selected R4 substituents; and
each R3 is independently halogen, CN, C(O)NR7R8, NR5R6, OH, OC1-6 alkyl, or a 3-7 membered heterocycloalkyl;
wherein each 3-7 membered heterocycloalkyl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C(O)R12, C(O)NR9R10, C(O)OR12, NR9R10, NR11C(O)R12, NR11S(O)2R12, OH, OC1-6 alkyl, OC1-4haloalkyl, OC1-4 alkylene-C3-7 cycloalkyl, OC1-4 alkylene-4-10 membered heterocycloalkyl, OC1-4 alkylene-C6-10 aryl, OC1-4 alkylene-5-10 membered heteroaryl, OC(O)R12, OC3-7 cycloalkyl, O-4-14 membered heterocycloalkyl, OC6-10 aryl, O-5-10 membered heteroaryl, SH, SC1-4 alkyl, SC1-4 haloalkyl, SC1-4 alkylene-C3-7 cycloalkyl, SC1-4 alkylene-4-10 membered heterocycloalkyl, SC1-4 alkylene-C6-10 aryl, SC1-4 alkylene-5-10 membered heteroaryl, SF5, S(O)2NR9R10, SC3-7 cycloalkyl, S-4-14 membered heterocycloalkyl, SC6-10 aryl, S-5-10 membered heteroaryl, and C3-6 cycloalkyl;
each R4 is independently halogen, C1-3 alkyl, NH2, NH(CH3), N(CH3)2, OH, or OC1-4 alkyl;
each R5 is independently halogen or C1-4 alkyl;
each R6 is independently halogen or C1-4 alkyl;
each R7 is independently halogen or C1-4 alkyl;
each R8 is independently halogen or C1-4 alkyl;
X1 is CR14 or N;
X2 is CR15 or N;
X3 is CR16 or N;
R14 is H;
R15 is H;
R16 is H;
each R9 is independently H, C1-4 alkyl, C1-4 haloalkyl, or C3-7 cycloalkyl;
each R10 is independently H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-10 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
wherein each C1-6 alkyl, C1-4 haloalkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, CN, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, SC1-4 alkyl, and C3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C(O)H, C(O)C1-4 alkyl, C(O)NH2, C(O)N(C1-4 alkyl)2, C(O)OC1-4 alkyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4haloalkyl, SC1-4 alkyl, and C3-7 cycloalkyl;
each R11 is independently H, C1-4 alkyl, or C3-7 cycloalkyl; and
each R12 is independently H, C1-6 alkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, a 4-14 membered heterocycloalkyl, C6-10 aryl, or 5-10 membered heteroaryl;
wherein each C1-6 alkyl, C1-4 alkylene of C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene of C1-4 alkylene-4-10 membered heterocycloalkyl, C1-4 alkylene of C1-4 alkylene-C6-10 aryl, and C1-4 alkylene of C1-4 alkylene-5-10 membered heteroaryl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, and C3-7 cycloalkyl; and
wherein each C3-7 cycloalkyl of C1-4 alkylene-C3-7 cycloalkyl, 4-10 membered heterocycloalkyl of C1-4 alkylene-4-10 membered heterocycloalkyl, C6-10 aryl of C1-4 alkylene-C6-10 aryl, 5-10 membered heteroaryl of C1-4 alkylene-5-10 membered heteroaryl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, NH2, NHCH3, N(CH3)2, OH, OC1-4 alkyl, OC1-4 haloalkyl, ═O, SC1-4 alkyl, and C3-7 cycloalkyl.

### Claim 15 (depends on 14)

The compound according to claim 14, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
X1 is CR14;
X2 is CR15; and
X3 is CR16.

### Claim 16 (depends on 14)

The compound according to claim 14, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
ring A is C3-7 cycloalkyl, a 3-7 membered heterocycloalkyl, a monocyclic C5-7 aryl, or a monocyclic 5-7 membered heteroaryl, wherein the C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, C5-7 aryl, or 5-7 membered heteroaryl, is optionally substituted with 1, 2, 3, or 4 independently selected R1 substituents.

### Claim 17 (depends on 14)

The compound according to claim 14, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof, wherein
ring A is phenyl or a monocyclic 5-6 membered heteroaryl, wherein the phenyl or 5-6 membered heteroaryl is optionally substituted with 1, 2, 3, or 4 independently selected R1 substituents.

### Claim 18 (depends on 1)

The compound according to claim 1, or an optical isomer thereof, wherein the compound, or optical isomer thereof, is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 1)

A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers, adjuvants or excipients and the compound according to claim 1, or a pharmaceutically acceptable salt, optical isomer, geometric isomer, or tautomer thereof.