WO2019168847A1 - Imidazopyrimidines and triazolopyrimidines as a2a / a2b inhibitors - Google Patents

Imidazopyrimidines and triazolopyrimidines as a2a / a2b inhibitors Download PDF

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Publication number
WO2019168847A1
WO2019168847A1 PCT/US2019/019582 US2019019582W WO2019168847A1 WO 2019168847 A1 WO2019168847 A1 WO 2019168847A1 US 2019019582 W US2019019582 W US 2019019582W WO 2019168847 A1 WO2019168847 A1 WO 2019168847A1
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alkyl
membered
independently selected
aryl
cycloalkyl
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French (fr)
Inventor
Xiaozhao Wang
Pei Gan
Heeoon HAN
Taisheng Huang
Matthew S. MCCAMMANT
Chao QI
Ding-Quan Qian
Liangxing Wu
Wenqing Yao
Zhiyong Yu
Fenglei Zhang
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Incyte Corp
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Incyte Corp
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Priority to CR20230030A priority patent/CR20230030A/es
Priority to CR20200441A priority patent/CR20200441A/es
Priority to IL276873A priority patent/IL276873B2/en
Priority to BR112020017421-1A priority patent/BR112020017421A2/pt
Priority to MX2020008949A priority patent/MX2020008949A/es
Priority to EA202092016A priority patent/EA202092016A1/ru
Priority to PE2020001285A priority patent/PE20211001A1/es
Priority to JP2020567459A priority patent/JP7474709B2/ja
Priority to CN201980027624.3A priority patent/CN112384515B/zh
Priority to EP19713602.1A priority patent/EP3759112A1/en
Priority to BR122023024273-4A priority patent/BR122023024273A2/pt
Priority to AU2019227607A priority patent/AU2019227607C1/en
Priority to PE2024003132A priority patent/PE20251291A1/es
Application filed by Incyte Corp filed Critical Incyte Corp
Priority to CN202311603774.9A priority patent/CN117903140A/zh
Priority to IL303087A priority patent/IL303087B2/en
Priority to KR1020207027865A priority patent/KR20200139153A/ko
Publication of WO2019168847A1 publication Critical patent/WO2019168847A1/en
Priority to PH12020551332A priority patent/PH12020551332A1/en
Anticipated expiration legal-status Critical
Priority to CONC2020/0011908A priority patent/CO2020011908A2/es
Priority to AU2022283611A priority patent/AU2022283611B2/en
Priority to JP2023096889A priority patent/JP7624476B2/ja
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—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

Definitions

  • the present invention provides imidazopyrimidine and triazolopyrimidine compounds that modulate the activity of adenosine receptors, such as subtypes A2A and A2B, and are useful in the treatment of diseases related to the activity of adenosine receptors including, for example, cancer, inflammatory' diseases, cardiovascular diseases, and neurode generative diseases.
  • Adenosine is an extracellular signaling molecule that can modulate immune responses through many immune cell types.
  • Adenosine was first recognized as a physiologic regulator of coronary vascular tone by Drury and Szent-Gyorgyu (Sachdeva, S. and Gupta, M. Saudi Pharmaceutical Journal, 2013, 21, 245-253), however it was not until 1970 that Sattin and Rail showed that adenosine regulates cell function via occupancy of specific receptors on the cell surface (Sattin, A., and Rail, T.W., 1970. Mol. Pharmacol. 6, 13-23; Hasko', G., at al, 2007, Pharmacol. Ther. 113, 264-275).
  • Adenosine pla s a vital role in various other ph siological functions. It is involved in the synthesis of nucleic acids, when linked to three phosphate groups; it forms ATP, the integral component of the cellular energy system. Adenosine can be generated by the enzy matic breakdown of extracellular ATP, or can be also released from injured neurons and glial cells by passing the damaged plasma membrane (Tautenhahn, M. et al.
  • Adenosine produces various pharmacological effects, both in periphery and in the central nervous system, through an action on specific receptors localized on cell membranes (Matsumoto, T. et al. Pharmacol. Res., 2012, 65, 81- 90).
  • Alternative pathways for extracellular adenosine generation have been described. These pathways include the production of adenosine from nicotinamide dinucleotide (NAD) instead of ATP by the concerted action of CD38, CD203a and CD73.
  • NAD nicotinamide dinucleotide
  • CD73 -independent produc tion of adenosine can also occur by other phosphates such as alkaline phosphatase or prostate- specific phosphatase.
  • adenosine receptor There are four known subtypes of adenosine receptor in humans including Al, A2A, A2B, and A3 receptors. Al and A2A are high affinity receptors, whereas A2B and A3 are low affinity receptors. Adenosine and its agonists can act via one or more of these receptors and can modulate the activity of adenylate cyclase, the enzyme responsible for increasing cyclic AMP (cAMP). The different receptors have differential stimulatory and inhibitory effects on this enzyme. Increased intracellular concentrations of cAMP can suppress the activity' of immune and inflammatory cells (Livingston, M. et al., In fiamm. Res., 2004, 53, 171-178).
  • the A2A adenosine receptor can signal in the periphery and the CNS, with agonists explored as anti-inflammatory' drugs and antagonists explored for neurodegenerative diseases (Carlsson, I. et al., J. Med. Chem., 2010, 53, 3748-3755). In most cell types the A2A subtype inhibits intracellular calcium levels whereas the A2B potentiates them. The A2A receptor generally appears to inhibit inflammatory response from immune cells (Borrmann, T. et al., J. Med. Chem., 2009, 52(13), 3994-4006).
  • A2B receptors are highly expressed in the gastrointestinal tract, bladder, lung and on mast cells (Antonioli, L et ah, Nature Reviews Cancer, 2013, 13, 842-857).
  • the A2B receptor although structurally closely related to the A2A receptor and able to activate aden late cyclase is functionally different. It has been postulated that this subtype may utilize signal transduction systems other than adenylate cyclase (Livingston, M. et ah, Inflamm. Res., 2004, 53, 171-178).
  • the A2B adenosine receptor is a low affinity receptor that is thought to remain silent under physiological conditions and to be activated in consequence of increased extracellular adenosine levels (Ryzhov, S. et al.
  • Neoplasia 2008, 10, 987-995.
  • Activation of A2B adenosine receptor can stimulate adenylate cyclase and phospholipase C through activation of Gs and Gq proteins, respectively.
  • Coupling to mitogen activated protein kinases has also been described (Borrmann, T. et al., J. Med. Chem., 2009, 52(13), 3994-4006).
  • Adenosine signalin can be a critical regulatory mechanism that protects tissues against excessive immune reactions.
  • Adenosine can negatively modulate immune responses through many immune cell types, including T -cells, natural-killer cells, macrophages, dendritic ceils, mast cells and myeloid-derived suppressor cells (Allard, B. et al. Current Opinion m Pharmacology, 2016, 29, 7-16).
  • adenosine was mainly generated from extracellular ATP by CD39 and CD73. Multiple cell types can generate adenosine by expressing CD39 and CD73. This is the case for tumor cells, T-effector cells, T-regulatory cells, tumor associated macrophages, myeloid derived suppressive cells (MDSCs), endothelial cells, cancer- associated fibroblast (CAFs) and mesenchymal stromal/stem cells (MSCs).
  • adenosine level in solid tumors is unusually high compared to normal physiological conditions.
  • A2A are mostly expressed on l mphoid -derived cells, including T-effecior cells, T regulatory cells and nature killing cells. Blocking A2A receptor can prevent downstream immunosuppressive signals that temporarily inactivate T ceils.
  • A2B receptors are mainly expressed on monocyte-derived cells including dendritic cells, tumor-associated
  • Blocking A2B receptor in preclinical models can suppress tumor growth, block metastasis, and increase the presentation of tumor antigens.
  • A2A/A2B In terms of safety profile of ADORA2A/ADORA2B (A2A/A2B) blockage, the A2A and A2B receptor knockout mice are all viable, showing no growth abnormalities and are fertile (Allard, B. et ai. Current Opinion in Pharmacology, 2016, 29, 7-16).
  • A2A KQ mice displayed increased levels of pro-inflammatory cytokines only upon challenge with LPS and no evidence of inflammation at baseline (Antonioli, L. et al.. Nature Reviews Cancer, 2013, 13, 842-857).
  • A2B KG mice exhibited normal platelet, red blood, and white cell counts but increased inflammation at baseline (TNF-alpha, IL-6) in naive A2B KO mice (Antonioli, L.
  • mice also exhibited increased vascular adhesion molecules that mediate inflammation as well leukocyte adhesion/rolling; enhanced mast-cell activation; increased sensitivity to IgE -mediated anaphylaxis and increased vascular leakage and neutrophil influx under hypoxia (Antonioli, L. et al., Nature Reviews Cancer, 2013, 13, 842-857).
  • the present invention relates to, inter alia, compounds of Formula (I):
  • the present invention further provides pharmaceutical compositions comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and a
  • the present invention further provides methods of inhibiting an activity of an adenosine receptor, comprising contacting the receptor with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.
  • the present invention further provides methods of treating a disease or a disorder associated with abnormal expression of adenosine receptors, comprising administering to said patient a therapeutically effective amount of a compound of Formula (I), or a
  • the present invention further provides a compound of Formula (I), or a
  • the present invention further provides use of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for use in any of the methods described herein.
  • the present invention relates to, inter alia, compounds of Formula (i):
  • X is N or CR :
  • Ci -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C&-34 aryl, C3- M cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CS- M ar l-Cw alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ⁇ alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R 1 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R d substituents;
  • R 2 is selected from H, D, halo, C - 6 alkyl, C - 6 haloalkyl, C 2-6 alkenyl, C2-6 alkynyl, CV 14 aryl, Cs-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C S-M aryl-Ci- 6 alkyl-, Cs-u cycloalky l-Ci- 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, CN, N0 2 , OR a2 , SR a2 , NHOR ai , C(0)R b2 ,
  • NR c2 S(0)R b2 N R SiOi R K' .
  • heterocycloalkyl, Ce-w aryl-Ci-6 alkyl-, C3..14 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl- of R ⁇ are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected substituents;
  • R 3 is selected from H, D, halo, Ci-s alkyl, Ci-s haloalkyl, C 2-6 alkenyl, alkynyl, de ⁇ n ary!, C3-34 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heierocycloalkyl, C * aryl-Ci- 6 alkyl-, CVw cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl) ⁇ Ci- 6 alkyl-, (4-14 member
  • heterocycloalkyl C M * aryl-C -6 alkyl-, C 3-14 cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl) ⁇ C 1-6 alkyl- of R 3 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R ⁇ substituents;
  • Cy 1 is Cfs-M aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the C S-M aryl, Cs-ncycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 11 substituents;
  • Cy 1 is not pyridin-4-yl optionally substituted with i, 2, 3, or 4 independently selected R ⁇ substituents;
  • Cy 1 is not pyrimidin-4-yl optionally substituted with 1, 2, or 3, independently selected R substituents;
  • Cy 1 is not quinolin-4-yl optionally substituted with 1 , 2, 3, 4, 5, or 6 independently selected R b substituents;
  • Cy is C &-34 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heierocycloalkyl, wherein the Ce-u aryl, C 3-H cycloalky 1, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with l, 2, 3, 4, 5, 6, 7, or 8 independently selected R b substituents;
  • each R a! , R c l , R ds , R a2 , R c2 , R d2 , R a3 , R c3 , and R d3 is independently selected from H, Ci. 6 alkyl, C - 6 haloalkyl, alkenyl, C 2-6 alkynyl, CX- H aryl, C 3U4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heierocycloalkyl, Ce-n aryl-C 3-5 alkyl-, Cs-i + cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4- 14 membered heterocycloalkyl)-Ci- 6 alkyl-, wherein the Cj-e alkyl, C2-6 alkenyl, C2-6 alkynyi, Ce-u aryl, €3-5+
  • any R ci and R al attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroary l or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R° substituents;
  • R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R° substituents;
  • R c3 and R d3 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R & substituents;
  • each R bl , R h3 , and R b3 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyi, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 aryl-Cs- 6 alkyl-, Cs-w cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyi, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci- 6 alkyl-
  • each R ei , R 5 , and R e3 is independently selected from H, OH, CN, Ci- 6 alkyl, Ci- 6 alkoxy, Cj- 6 haloalkyl, Ci-ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyi, C 6 -i4 aryl, C3- M cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w aiyl-Cj-6 alkyl-, G3- H cycloalkyl-Ci- 6 alkyl-, (5-14 membered heteroaryl)-C ]-6 alkyl-, and (4-14 membered heterocy cloalky 1)-C 1.5 alky 1-;
  • each R g , R g2 , R iJ , and R g3 is independently selected from H, Cj- 6 alkyl, C]- 6 aikoxj r , Ci- 6 haloalkyl, Cj-e haloalkoxy, C2-6 alkenyl, C2-6 alkynyi, €5-54 aryl, 63-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CM* aryl-Ci-6 alkyl-, C3-14 cycloalkyl- Ci-6 alkyl-, (5-14 membered heteroai l)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R 112 , R l2 , R !l3 , and R 1J is independently selected from H, C - & alkyl, C - & haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C3-1 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, e- aryl-C *- 6 alkyl-, C3- K cycioalkyl-C -6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl) ⁇ C 1-6 alkyl-;
  • each R j , R ki , R J C and R k3 is independently selected from OH, C -e alkoxy, and Ci- 6 haloaikoxy;
  • R j2 and R k2 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- 6 alkyl and C 1-6 haloalkyl;
  • R JJ and R kJ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalky 1 group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alkyl and Ci- 6 haloalkyl;
  • each R b , R c , R d , R e , R f , and R° is independently selected from D, halo, oxo, Cj- & alkyl, Ci-6 haloalkyl, C 2- e alkenyl, C2-6 alkynyl, C&-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u ary l-C -6 alkyl-, C3-14 cycloalk l-Cw alkyl- (5-14 membered heteroaryi)-Ci-6 alkyl-, (4-14 membered heterocycloalkyi)-Ci-6 alkyl-, CN, NO2, OR a4 , SR a4 , NHOR 84 , C(0)R M , C(0)NR c4 R d4 , C(0)NR c4 (0R a4 ), C(0)0R 34 .
  • NR c4 S(0)NR c4 R d4 , NR c4 S(0) 2 R b4 , NR c4 S(0)(-NR e4 )R b4 , NR c4 S(0) 2 NR c4 R d4 , S(0)R b4 , S(0)NR c+ R d+ , S(0) 2 R b+ , S(0) 2 NR c4 R d4 , 0S(0)( NR e4 )R b4 , 0S(0) 2 R b4 , SF s , P(0)R f4 R g4 , 0P(0)(0R h4 )(0R 14 ), P(0)(0R h4 )(0R 4 ), and BR.
  • heterocycloalkyl Ce-u aryl-C 1.5 alkyl-, C3-14 cycloalk I-C1-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C ue alkyl- of R B , R c , R D , R E , R F , and R° are each optionally substituted with 1 , 2, 3, 4, 5, 6, 7, or 8 independently selected
  • each R a4 , R c+ , and R d4 is independently selected from H, C i-s alkyl, C i-s haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryd, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocy cloalkyl, Ce-u aryl-C i-e alkyl-, C 3 -i cycloalkyl-C - 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-, wherein the Ci-s alkyl, C2-6 alkenyl, C2-6 alkynyl, C f .- aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u
  • each R fc4 is independently selected from H, Cne alkyl, Cne haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce- aryd, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl CM* aryl-C [-6 alkyl-, C3-14 cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl) ⁇ C 1-6 alkyl-, wherein the Ci-s alkyl €2-5 alkenyl, C2-S alkynyl, C&-14 aryd, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, M * aryl-C i-b alkyl-, C3- K cycloalkyl-Cj-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl- of R° 4 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R H substituents; each R 84
  • each R f4 and R g4 is independently selected from H, C -- 6 alkyl, Ci-e alkoxy, Ci- 6 haloalkyl, Ci-ghaloalkoxy, C2-6 alkenyl, €2-5 alkynyl, aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C i-b alkyl-, C3-14 cycloalkyl- Ci- d alkyl-, (5-14 membered heteroaiyl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R M and R 14 is independently selected from H, Ci-s alkyl, Ci ⁇ haloalkyl, C2-6 alkenyl, €2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 aryl-Cj-e alkyd-, Cs-w cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaiyl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R j4 and R K4 is independently selected from OH, Cj-saikoxy, and Ci-ehaloalkoxy; or, any R j4 and R k+ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Cne alkyl and Cj- 6 haloalkyl; each R H is independently selected from D, halo, oxo, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-& alkynyl, Ce-u aryl, C B-H cycloalkyl, 5-14 tnembered heteroaryd, 4-14 membered heterocycloalkyl, Ce-n aiyl-Ci-6 alkyl-, Cs- H cycloalkyi-Ci-e alkyl-, (5-14 membered hetero
  • heterocycloalkyl Ce-u aryl-C i-e alkyl-, C B -i4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl- of R 1 ! are each optionally substituted with 1, 2, 3, or 4 independently selected R 1 substituents;
  • each R a ⁇ R c5 , and R d> is independently selected from H, Cj-b alkyl, Cj-b haloalkyl, C2-6 alkenyl, C 2- e alkynyl, €5-14 aryl, CB-H cycloalkyl, 5-14 membered heteroaryd, 4-14 membered heterocycloalkyl, Ce-n aryl-C 1 -5 alkyd-, CB-H cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-, wherein the Ci-e alkyl, C 2-& alkenyl, C 2-& alkynyl, Ce-w aryl, C B-M cycloalkyl, 5-14 membered heteroaryd, 4-14 membered heterocycloalkyl, Ce-u aryl-Cj-e alky
  • each R b5 is independently selected from H, Cue alkyd, Cue haloalkyl, C 2-6 alkenyl, C 2-& alkynyl, C&-14 aryl, C B-H cycloalk l, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce-u aryd-C i-e alkyl-, C3-i4 cycloalkyd-Ci-6 alkyl-, (5-14 membered heteroaryi)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyi) ⁇ C 1-6 alkyl-, wherein the Ci- 6 alkyl, C 2 -e alkenyl, C 2-6 alkynyl, C &-J 4 aryl, CB-H cycloalkyl, 5-14 membered heteroaryd, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-e alkyl-, Ci-u cycloalkyl-C -6 alky' 1-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloa3kyl)-Ci-6 alkyl- of R 03 are each optionally substituted with 1, 2, 3, or 4 independently selected R 1 substituents;
  • each R e5 is independently selected from H, OH, CN, C M alkyl, Ci-e alkoxy, Ci- 6 haloalkyl, Ci-ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ca-u aryl, C;-w cycloalkyi, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aiyl-Ci- 6 alkyl-, Cs-u cycloalkyi- C M alkyl-, (5-14 membered heteroaryl) -C - 6 alkyl-, and (4-14 membered heterocycioalkyl)-C - 6 alkyl-;
  • each R 6 and R p is independently selected from H, Cm, alkyl, Ci « alkoxy, Ci- 6 haloalkyl, Ci- 6 haloalkoxy, C>;-s alkenyl, C2-6 alkynyl, C K aryl, C3- S 4 cycloalkyl, 5-14 membered heteroary l, 4-14 membered heterocycloalkyl, C M 4 ary l-Ci- 6 alkyl-, C3-14 cycloalky 1- C [- 6 alkyl-, (5-14 membered heteroaiyl)-Ci- 6 alkyl-, and (4-14 membered heteroeycloalkyli-Ci- 6 alkyl-;
  • each R tD and R 15 is independently selected from H, C alkyl, C M haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, Cj-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce- aryl-C 1.5 alkyl-, C3-14 cycloalky 1-C M alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C alkyl-;
  • each R j5 and R k5 is independently selected from OH, Ci-e alkoxy, and C -ehaloalkoxy; or, any R
  • each R ! is independently selected from D, halo, oxo, C , alkyl, C , haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, Ce-u aryl, Cs-u cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary 1-C M alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ]-6 alkyl-, and (4-14 membered heterocycioalkyl)-Ci- 6 alkyl-, CN, N(3 ⁇ 4, OR ab , SR ®6 , NHGR a5 , C(0)R b6 , C(0)NR c6 R d6 , C(0)NR c6 (0R a6 ). C(0)GR af> , GC(G)R b6 ,
  • heterocycloalkyl, Ce-i aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl- of R l are each optionally substituted with 1 , 2, 3, or 4 independently selected R J substituents;
  • each R a5 , R c6 , and R d6 is independently selected from H, C i-s alkyl, C i-s haloalkyl, C M alkenyl, CM alkynyl, C&-14 aryl, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryd-C M alkyl-, C3-i4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-, wherein the C M alkyl, C 2-6 alkenyl, C2-6 alkynyl, Ci.-u aryl, C J-M cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-e alkyl
  • R 06 and R dR attached to the same N atom, together with the N atom to winch they are attached, form a 5- or 6-membered heteroary l or a 4-14 membered heterocycloalkyl group, wiierein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R b6 is independently selected from H, CM alkyl, CM haloalkyl, C 2 -s alkenyl, C 2 -6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered
  • heterocycloalkyl Ce-w ary I-C1-& alkyl-, C3-1 4 cycloalkyl-Cw alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyi)-Ci-6 alkyl-, wiierein the C alkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Cs-w aryi-C M alkyl-, CVw cycloalkyl-C M alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1 ⁇ 2 alkyl- of R b6 are each optionally substituted with 1 , 2, 3, or 4 independently selected R:' substituents;
  • each R ®6 is independently selected from H, OH, CN, Ci-e alkyl, Cue lkoxy, Ci-e haloalkyl, Ci-ghaloalkoxy, C2-6 alkenyl, C 2 « alkynyl, Ce-n aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce-u axyl-Ci-e alkyl-, C3-14 cycloalkyl- Ci- d alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alky 1-;
  • each R ® and R s ° is independently selected from H, Ci-e alkyl, Ci-e alkoxy, Ci-e haloalkyl, Cwehaloalkoxy, C2-6 alkenyl, C 2-f, alkynyl, Ce-w aryl, C3-W cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce-i4 aryl-Cj- 6 alkyl-, Cs-w cycloalkyi- Ci-, (5-14 membered heteroaryi) -Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-Ci. & alkyi-;
  • each R h6 and R 16 is independently selected from H, Cj-e alkyl, Cj-b haloalkyl, C M alkenyl, C 2-6 alkynyl, C &-J 4 aryl, C3-1 4 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce-w ary l-Ci- 6 alkyl-, C -i+ cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-;
  • each R j6 and R k6 is independently selected from OH, C -s alkoxy, and C i-ehaloalkoxy; or, any R j6 and R k6 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alkyl and Ci- 6 haloalkyl; each R: 1 is independently selected from D, halo, oxo, C - 6 alkyl, C - 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, Caur cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce- aryl-C 1.5 alkyl-, C 3-14 cycloalky I-C 1-6 alkyl-, (5-14 membered heteroarv'l)-C
  • Ci- 5 alkyl C 2.s alkenyl, C 2.s alkynyl, Ct,-u aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4- 14 membered
  • heterocycloalkyl Ce-w ary' l-Ci- 6 alkyl-, C -i+ cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl- of R J are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R a/ , R c ', and R d ' is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, €2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6 -i4 aiyl-Ci- 6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaiyl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1 ⁇ 2 alkyl- wherein the Ci- 6 alkyl, C 2-6 alkenyl, C2-6 alkymyl, Ce-i+ aryl, Ci-n cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u ary l-C
  • each R b? is independently selected from H, Ci-b alkyl, Cue haloalkyl, C2-6 alkenyl, C 2 -e alkynyl, C &-J 4 aryl, Cs-u cycloalkyl, 5-14 membered heteroaryl, 4- 14 membered heterocycloalkyl, Ce-w aryl-Ci-e alkyl-, Cj-i + cycloalkyl-Cj-e alkyl-, (5-14 memhered heteroaryl)-Cj- 6 alkyl-, and (4-14 membered heterocycloa3kyl)-Ci- 6 alkyl-, wherein the Cj- 6 alkyl, C2-6 alkenyl, C2-6 alkyny!, C &-K aryl, Cs- M cyeloalkyi, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CS- M ar l-Cw alkyl
  • each R c/ is independently selected from H, OH, CN, Ci-e alkyl, C2-6 alkenyl, C3-6 alkoxy, Ci- 6 haloalkyl, Ci-ehaloalkoxy, C2-6 alkynyl, Ce-ir aryl, C3-34 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl;
  • each R 17 and R s? is independently selected from H, Ci- 6 alkyl, Cj-5 alkoxy, C M;
  • haloalkyl Ci-ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 aiyl-Ci-e alkyl-, C3-14 cycloalkyl- Ci- 6 alkyl-, (5-14 membered heteroaiyll-Ci-g alkyl-, and (4-14 membered heterocycloalkyl)-Ci- s alkyl-;
  • each R h/ and R" is independently selected from H, Ci-s alkyl, C M haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&.34 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C M ar I-C1- & alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R J / and R*' is independently selected from OH, C 3-6 alkoxy, and Ci-ehaloalkoxy ; or, any R J ' and R k/ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C3-6 alkyl and C [- 6 haloalkyl;
  • each R K is independently selected from H, D, OH, halo, oxo, CN, C(Q)OH, NH 2 ,
  • any heteroaryl group of any of the above-recited substituents optionally comprises an N-oxide on any ring-forming nitrogen
  • X is N or CR ;
  • R 1 is selected from H, Cj- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C M haloalkyl;
  • R 2 is selected from H, D, halo, C 3 -6 alkyl, C3 -6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce- 1 aryl, C3-34 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 aryi-C -6 alkyl-, C3- M cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaiyl)-C -6 alky 1-, (4-14 membered heterocycloalkyl)-C M alkyl-, CN, NO?, OR 32 , SR 32 , NHQR 32 , C(0)R b2 ,
  • CiOiNR ⁇ R : . C(0)NR c2 (0R a2 ), C(G)OR a2 , 0C(0)R b2 , 0C(0)NR c2 R d2 , X R R 12 .
  • heterocycloalkyl CX-w aryl-Cs-6 alkyl-, C3-i 4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R 2 are each optionally substituted with 1 , 2, 3, 4, 5, 6, 7, or 8 independently selected R c substituents;
  • R 3 is selected from H, D, halo, C M alkyl, C M haloalkyi, C M alkenyl, C M alkynyl, Ce- 14 and, C3.14 cycloalkyl 5-14 membered heteroaryl, 4-14 membered heterocycloalk l, Ce-14 aryd-C -6 alkyl-, C3-14 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, (4-14 membered heterocycloalkyl)-Ci.. 6 alkyl-, CN, NG 2 , OR a3 , SR 33 , NHGR a3 , C(0)R w ,
  • CiOiNR ⁇ R CiOiNR ⁇ R ; . C(0)NR c3 (QR a3 ), C(0)0R a3 , 0C(0)R b3 , 0C(0)NR c3 R d3 , N RdC.
  • heterocycloalkyl Ce-w ary 1-CM alkyl-, C3-14 cycloalkyl-C alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C M alkyl- of R 3 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R ! substituents;
  • Cy 1 is C M 4 aryl, C J-M cycloalky 3, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the Ce-u aryl C3-i 4 cycloalkyl, 5-14 membered heteroaiyl, or 4-14 membered heterocycloalkyl is optionally substituted with l, 2, 3, 4, 5, 6, 7, or 8 independently selected R E substituents;
  • Cy 2 is Ce- H aryl, C 3- i4 cycloalkyl, 5-14 membered heteroaiyl, or 4-14 membered heterocycloalkyl, wherein the Ce-i 4 aryl, C3-14 cycloalky 1, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R b substituents;
  • each R a 6 R° 2 , R d2 , R a3 , R c3 , and R d3 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, C3 -14 cycloalkyl, 5-14 membered heteroaryl, 4- 14 membered heterocycloalkyl, C &-K aryl -Ci-s alkyl-, C 3-i 4cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci ⁇ alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, wherein the Cj-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, CM* aryl, C3-W cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalky
  • R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1 , 2, 3, or 4 independently selected R 11 substituents;
  • R cJ and R d3 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R° substituents;
  • each R b2 , and R bJ is independently selected from H, Cs- 6 alkyl, Cs- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&-14 aryl, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CM* aiyl-C i-b alkyl-, C3-14 cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryi)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyi) ⁇ C 1-6 alkyl-, wherein the Ci-s alkyl, €2-5 alkenyl, C2- S alkynyl, C&-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, M * aryl-Ci-e alkyl-, C 3-
  • each R f2 , R s3 , R f3 , and R s3 is independently selected from H, Ci- 6 alkyl, Ci-e alkoxyy Ci haloalkyl, Cj-ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyi, C &-J 4 aryl, C 3- u cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C M 4 ary l-Ci-6 alkyl-, C3-14 cycloalky 1- C [-6 alkyl-, (5-14 membered heteroaiyl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R h , R , R a3 , and R' 3 is independently selected from H, Ci. & alkyl, Ci. & haloalkyl, C2-6 alkenyl, C2-6 alkynyi, Ce-u aryl, C3-14 eycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-e alkyl-, Cs-u cycloalky l-Ci-6 alkyl-, (5-14 membered heteroaryd)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C i-e alkyl-;
  • each R j2 , R k2 , R 3 , and R* 3 is independently selected from OH, Cwalkoxy, and Ci-e haloalkoxy;
  • R j2 and R K attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- 6 alkyl and C 1-6 haloalkyl;
  • R j3 and R ⁇ 3 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1 , 2, 3, or 4 substituents independently selected from Ci-e alkyl and C ue haloalkyl;
  • each R c , R D , R b , R f , and R° is independently selected from D, halo, oxo, Ci « alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyi, Ce-u aryl, C3-14 eycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u ary l-Ci- 6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, (4-14 membered heterocycloalky l)-Ci- 6 alkyl-, CN, N0 2 , OR 34 , SR a4 , N ⁇ iOR n C(0)R m , C(0)NR c4 R d4 , C(0)NR c4 (0R a4 ), C(0)0R a4
  • R c , R D , R 11 , R b , and R' J are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R h substituents;
  • each R 34 , R c4 , and R d4 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C - & alkenyl, C 2-& alkynyi, CVu aryl, Cj-u eycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci- 6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci ⁇ alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-, wherein the Ci-6 alkyl, C2-6 alkenyl, C2-6 a!kynyl, Ce-i + aiyl, C3-14 cycloalkyl, 5-14 membered heteroaiyl, 4-14 membered heterocycloalkyl, C -u aryl-Ci
  • each R w is independently selected from H, Ci- 6 alky l, Ci-e haloalkyi, C2-6 alkenyl, C2-0 alkynyl, Ce-w aryl, C3-H cycloalkyl, 5-14 membered heteroaiyl, 4-14 membered
  • heterocycloalkyl Cg-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C M aryl, Ci- K cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cs-w aryi-Cj-g alkyl-, C3-14 cycloalky l-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C i-e alkyl- ofR 04 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R H substituents;
  • each R f4 and R 84 is independently selected from H, Ci-e alkyl, Ci- 6 alkoxy, Ci ⁇ haloalkyi, Ci-ehaloalkoxj , C2-6 alkenyl, C2-6 alkynyl, Ca-u aryl, C3-i4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C & -u aryd-Ci-e alkyl-, C3-1 cycloalky 1- Ci- f, alkyl-, (5-14 membered heteroaryl) -Cj- 6 alkyl-, and (4-14 membered heterocyc!oalkyl)-Cj- 6 alkyl-;
  • each R h4 and R 14 is independently selected from H, Ci- 6 alkyl, C1-6 haloalkyi, C2-6 alkenyl, C 2-6 alkynyl, C&-14 aryl, C-t-u cycloalkyl, 5-14 membered heteroaiyl, 4-14 membered heterocycloalkyl, Ce-w ary l-Ci-6 alkyl-, C3-14 cycloalkyl-Cw alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycioalkyi)-Cs- 6 alkyl-;
  • each R ⁇ ' 4 and R k4 is independently selected from OH, Cj-g alkoxy, and Ci-ghaloalkoxy; or, any R j4 and R k+ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Cj- 6 alkyl and Cj- 6 haloalkyl; each R H is independently selected from D, halo, oxo, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ce-w aryl, Cj-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroary
  • heterocycloalkyl Ce-u aryl-C i-e alkyl-, C3-i4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl- of R 1 ! are each optionally substituted with 1, 2, 3, or 4 independently selected R 1 substituents;
  • each R 85 , R c5 , and R d> is independently selected from H, Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C 2- e alkynyl, C ⁇ 5-i4 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 aryl-Cj-e alkyd-, Cs-w cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Ci-e alkyl, C 2-6 alkenyl, C 2-& alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Cj-e alky
  • each R b5 is independently selected from H, Cue alkyl. Cue haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C&-14 aryl, €3-14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered
  • each R e5 is independently selected from H, OH, CN, CM alkyl, Ci-e alkoxy, Ci- 6 haloalkyl, Ci-ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ca-u aryl, C;-w cycloalkyi, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aiyl-Ci- 6 alkyl-, Cs-u cycloalkyi- CM, alkyl-, (5-14 membered heteroaryl) -C - 6 alkyl-, and (4-14 membered heterocycioalkyl)-C - 6 alkyl-;
  • each R 6 and R p is independently selected from H, Cm, alkyl, Ci «alkoxy, Ci- 6 haloalkyl, Ci- 6 haloalkoxy, C>;-s alkenyl, C2-6 alkynyl, C K aryl, C3- H cycloalkyl, 5-14 membered heteroary l, 4-14 membered heterocycloalkyl, C M 4 ary l-Ci- 6 alkyl-, C 3 -1 4 cycloalky 1- C [- 6 alkyl-, (5-14 membered he teroaryli-Ci- f , alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R tD and R 15 is independently selected from H, C alkyl, C M haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, Cj-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce- aryi-C 1.5 alkyl-, C3-1 cycloalky l-Ci-6 alkyl-, (5-14 membered
  • heteroaryl Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-;
  • each R j5 and R k5 is independently selected from OH, Ci-salkoxy, and C -ehaloalkoxy; or, any R
  • each R ! is independently selected from D, halo, oxo, C , alkyl, C , haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, Ce-u aryl, Cs-ucycloalkyi, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary 1-C M alkyl-, C3-14 eyeloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C ]-6 alkyl-, CN, N(3 ⁇ 4, OR ab , SR ®6 , NHOR a5 , C(0)R b6 , C(0)NR c6 R d6 , C(G)NR c6 (OR a6 ). C(0)OR af> , OC(0)R b6 ,
  • heterocycloalkyl, Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl- of R l are each optionally substituted with 1 , 2, 3, or 4 independently selected R J substituents;
  • each R a5 , R c6 , and R d6 is independently selected from H, C i-s alkyl, C i-s haloalkyl, C 2-6 alkenyl, C 2 -s alkynyl, C&-14 aryl, C 3 ..
  • R 06 and R dR attached to the same N atom, together with the N atom to winch they are attached, form a 5- or 6-membered heteroary l or a 4-14 membered heterocycloalkyl group, wiierein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R b6 is independently selected from H, Cj- 6 alkyl, Cj- 6 haloalkyl, C 2 -s alkenyl, C 2 -6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered
  • heterocycloalkyl Ce-w ary I-C1-& alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wiierein the Cj-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Cs-w aryi-Cj- 6 alkyl-, CVw cycloalkyl-C i-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1 ⁇ 2 alkyl- of R b6 are each optionally substituted with 1 , 2, 3, or 4 independently selected R:' substituent
  • each R ®6 is independently selected from H, OH, CN, Ci-e alkyl, Cue lkoxy, Ci-e haloalkyl, Ci-ghaloalkoxy, C2-6 alkenyl, C 2 « alkynyl, Ce-n aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce-u axyl-Ci-e alkyl-, C3-14 cycloalkyl- Ci- d alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alky 1-;
  • each R ® and R s ° is independently selected from H, Ci-e alkyl, Ci-e alkoxy, Ci-e haloalkyl, Cwehaloalkoxy, C2-6 alkenyl, C 2-f, alkynyl, Ce-w aryl, C3-W cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce- 14 aryl-Cj- 6 alkyl-, Cs-w cycloalkyi- Ci-, (5-14 membered heteroaryi) -Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-Ci. & alkyi-;
  • each R h6 and R 16 is independently selected from H, Cj-e alkyl, Cj-e haloalkyl, C 2 _6 alkenyl, C 2 -e alkynyl, C &-J 4 aryl, C3-14 cycloalkyl, 5-14 membered heteroary i, 4-14 membered heterocycloalkyl, Ce-w ary l-Ci ⁇ alkyl-, Cs-i+ cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-;
  • each R j6 and R k6 is independently selected from OH, C -s alkoxy, and C i-ehaloalkoxy; or, any R j6 and R k6 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C -e alkyl and Ci- 6 haloalkyl; each R: 1 is independently selected from D, halo, oxo, C - 6 alkyl, C - 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce- aryl-C 1.5 alkyl-, C3-1 cycloalky I-C1-6 alkyl-, (5-14 membered heteroaryl)-C
  • heterocycloalkyl Ce-w ary 1-C 1-6 alkyl-, C -ir cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl- of R J are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R a/ , R c ', and R d ' is independently selected from H, Ci- 6 alkyl, Ci-e haloalkyl, C2-6 alkenyl, €2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aryl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroatyl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- wherein the Ci- 6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-i4 aryl, Ci- H cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u ary l-Ci-e
  • each R b? is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ci.-n aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4- 14 membered heterocycloalkyl, Ce-u ary l-Ci-6 alkyl-, C -i + cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloa3kyl)-Ci- 6 alkyl-, wherein the Cj-6 alkyl, C ?
  • R fc7 are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R c/ is independently selected from H, OH, CN, C3-6 alkyl, C2-6 alkenyl, C3-6 alkoxy, Ci ⁇ haloalkyi, Ci-ehaloalkoxy, C 2-6 aikynyl, C 6 -i 4 aryl, C3-34 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl;
  • each R 17 and R s? is independently selected from H, Ci- 6 alkyl, Cs- 6 alkoxy, C M> haloalkyl, Ci-ehaloalkoxy, C2-6 alkenyl, C2-6 aikynyl, Ce- aryl, C 3-i 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C M 4 aiyl-Ci-e alkyl-, C 3-34 cycloalkyl- Ci- 6 alkyl-, (5-14 membered heteroaiyll-Ci-g alkyl-, and (4-14 membered heterocycloalkyl)-C ].
  • each R h/ and R 1 ' is independently selected from H, Ci-s alkyl, Ci-b haloalkyl, C2-6 alkenyl, C2-6 aikynyl, C &.24 aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ar I-C1-& alkyl-, C3- 14 cycloalkyl-Cr-e alkyl-, (5-14 membered
  • heteroaryl C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R J / and R*' is independently selected from OH, C 3-6 alkoxy, and Ci-ehaloalkoxy ; or, any R J ' and R k/ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C -6 alkyl and C - 6 haloalkyl;
  • each R K is independently selected from H, D, OH, halo, oxo, CN, C(0)0H, NH 2 ,
  • any heteroaryl group of any of the above-recited substituents optionally comprises an N-oxide on any ring-forming nitrogen.
  • X is CR :
  • Ci -6 aikyi, C‘ alkenyl, C2-6 alkynyl, C&- K axyl, C B-M cycloalkyl, 5-14 mem bered heteroaryl, 4-14 membered heterocycloalkyl, CS- M ar l-Cw alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 aikyl-, and (4-14 membered heterocycloalkyl)-C ]-6 aikyi- of R 1 are each optionally substituted with i, 2, 3, 4, 5, 6, 7, or 8 independently selected R d substituents;
  • R 2 is selected from H, D, halo, C - 6 alkyl, C - 6 haloalkyl, C 2-6 alkenyl, C2-6 alkynyl, C i4 aryl, Cs- cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C S-M aryl-Ci4s alkyl-, Cs-u cycloalky l-Ci- 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, (4-14 membered heterocycloalkyl)-C ! -e alkyl-, CN, N ⁇ 3 ⁇ 4, OR 82 , SR 32 , NHOR 32 , C(0)R b2 ,
  • NR c2 S(0)R b2 N R S;()i R K' .
  • heterocycloalkyl Ce-w ary i-C 1-6 alkyl-, Ca-i + cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-C 1.6 alkyl- of R ⁇ are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R substituents;
  • R ;i is selected from H, D, halo, Ci. & alkyl, Ci. & haloalkyl, C 2.. e alkenyl, C2-6 alkynyl, Ce- i4 aryl, C 3-34 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C M * aryl-C - 6 alkyl-, Cs- H cycloaikyl-C 1-6 alkyl-, (5-14 membered heteroaryi) ⁇ Ci- 6 alkyl-, (4-14 membered heterocycloalky l)-Ci- 5 alkyl-, CN, NO ... OR a3 , SR fr M )OR :: . C(0)R b3 ,
  • heterocycloalkyl Ce-u aryl-C i-b alkyl-, C3-i 4 cycloalkyl-C - 6 alkyl-, (5-14 membered heteroaryi)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyi) ⁇ C 1-6 alkyl- of R J are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 17 substituents;
  • Cy ! is Ce-w aiyl, Ca-u cycloalkyl, 5-14 membered heteroaryi, or 4-14 membered heterocycloalkyl, wherein the C 5-14 aryl, C3-! 4 cycloalkyl, 5- 14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1 2, 3, 4, 5, 6 7, or 8 independently selected R substituents;
  • Cy 1 is not pyridin-4-yl optionally substituted with 1, 2, 3, or 4 independently selected R' substituents;
  • Cy ! is not pyrimidm-4-yl optionally substituted with 1, 2, or 3, independently selected R K substituents;
  • Cy 1 is not quinolin-4-yl optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R E substituents;
  • Cy 2 is C b -14 aryl, C -w cycloalkyl, 5-14 membered heteroaryi, or 4-14 membered heterocycloalkyl, wherein the C 5-14 aryl, C3- M cycloalkyl, 5- 14 membered heteroaryi, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R " substituents;
  • each R 31 , R ci , R d! , R 82 , R c2 , R d2 , R 33 , R 03 , and R ® is independently selected from H, Gi ⁇ ft alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, C3-i 4 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce-w ary l-C -6 alkyl-, C 3-14 cycloalky I-C 1-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkylj-Ci-e alkyl-, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, Gs- 14 aryl, C 3-14 cycloalkyl, 5-14 membered
  • R cl , R ® , R 3 , R c2 , R d2 , R 83 , R", and R d ’ are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R° substituents;
  • R c2 and R d2 attached to the same N atom, together with the N atom to winch they are attached, form a 5- or 6-membered heteroaryi or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryi or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R° substituents;
  • R c3 and R d3 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryi or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroary l or 4-14 membered heterocycloalkyl group is optionally substituted with 1 , 2, 3, or 4 independently selected R° substituents;
  • each R bl , R b2 , and R b3 is independently selected from H, C alkyl, C M haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&-14 aryl, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C M alkyl-, Ci- H cycloalkyl-C M alkyl-, (5-14 membered heteroaryi)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyi) ⁇ C 1-6 alkyl-, wherein the C alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci.-u aryd, C3-14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cs-ir aryl-Ci-e alkyl-, Ch- M cyc
  • each R el , R e2 , and R e is independently selected from H, OH, CN, C1-6 alkyl.
  • each R g , R g , R fi , and R g3 is independently selected from H, CM alkyl.
  • each R llZ , R l2 , R 03 , and R 1 is independently selected from H, C M alkyl.
  • each R ⁇ ' 3 , R k2 , R jJ , and R k is independently selected front OH, C M alkoxy, and C M haloalkoxy;
  • R j2 and R K attached to the same B atom, together wdth the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted wdth 1, 2, 3, or 4 substituents independently selected from C M alkyl and C M haloalkyl;
  • each R b , R c , R d , R b , R f , and R° is independently selected from D, halo, oxo, Ci-e alkyl, Ci- & haloalkyl, C 2-6 alkenyl, C2-6 alkysiyl, C H aryl, C3- H cyeloalkyl, 5-14 membered heteroatyl, 4-14 membered heteroeyeloaikyl, Ce-w aiyl-Ci-6 alkyl-, C3- H cycloalkyl-Ci-e alkyl-, (5-14 membered hetero
  • heteroeyeloaikyl CM* aiy r l-C i-b alkyl-, C3-14 cycloalkyl-Cj-e alkyl-, (5- 14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl) ⁇ C 1-6 alkyl- of R B , R c , R D , R ⁇
  • R ⁇ and R° are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R H substituents;
  • each R a4 , R c+ , and R d4 is independently selected from H, Ci- & alkyl, Ci- & haloalkyl, C 2.. e alkenyl, C 2-6 alkynyl, Ci.-u aryl, C -u cyeloalkyl, 5-14 membered heteroaryl, 4-14 membered heteroeyeloaikyl, Ce-w ary 1-C 1-6 alkyl-, C 3-i 4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl-, wherein the Ci.
  • each R b4 is independently selected from H, Cue alkyl. Cue haloalkyl, C 2-6 alkenyl, C 2-& alkynyl, C&-14 aryl, €3-14 cyeloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • each R f4 and R 8 * is independently selected from H, Cm, alkyl, Cwalkoxy, Ci- 6 haloalkyl, Cwhaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C K aryl, C 3-i 4 cycloalkyl, 5-14 membered heteroary l, 4-14 membered heterocycloalkyl, C M 4 ary' i-C 1-6 alkyl-, C 3-i 4 cycloalky 1- C - 6 alkyl-, (5-14 membered heteroaryli-Ci- f , alkyl-, and (4-14 membered heterocycloaikyli-Ci- 6 alkyl-;
  • each R h4 and R l4 is independently selected from H, Ci. & alkyl, Ci. & haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, Cj-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce- aryl-C 1.5 alkyl-, Cs-u cycloa kyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-;
  • each R j4 and R“ 4 is independently selected from OH, Cwalkoxy, and Cwhaloalkoxy; or, any R
  • each R H is independently selected from D, halo, oxo, Cw alkyl, Cw haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, C 3- u cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary l-Cw alkyl-, C 3-14 cycloalkyl-Cw alkyl-, (5-14 membered heteroaryl)-Cw alkyl-, (4-14 membered heterocy oalky -Cw alkyl-, CN, NO2, OR 35 , SR a5 , NHOR a5 , C(0)R b5 , C(0)NR c5 R d5 , C(0)NR c5 (0R a5 ), C(0)0R 35 , 0C(0)R bs , 0C(0)NR c5 R d5 .
  • heterocycloalkyl, Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-C]-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R fl are each optionally substituted with 1 , 2, 3, or 4 independently selected R* substituents;
  • each R a5 , R c5 , and R d5 is independently selected from H, C i-s alkyl, Ci-s haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&-14 aryl, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryd-C i-e alkyl-, C3-i4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-, wherein the Ci-s alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ci.-u aryl, C J-M cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-
  • R 05 and R da attached to the same N atom, together with the N atom to winch they are attached, form a 5- or 6-membered heteroary l or a 4-14 membered heterocycloalkyl group, wirerein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R ! substituents;
  • each R to is independently selected from H, Cj- 6 alkyl, Cj- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl C w ary I-C1- & alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wirerein the Cj-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cs-w aryl-Ci-e alkyl-, CVw cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1 ⁇ 2 alkyl- of R b5 are each optionally substituted with 1 , 2, 3, or 4 independently selected R 1 substituent
  • each R e5 is independently selected from H, OH, CN, Ci-e alkyl, Ci-e alkoxy, Ci-e haloalkyl, Ci-ehaioalkoxy, C2-6 alkenyl, €2-5 alkynyl, C G-M aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u axyl-Ci-e alkyl-, Cj-w cycloalkyl- Ci- d alkyl-, (5-14 membered heteroaryi)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alky 1-;
  • each R f5 and R 85 is independently selected from H, Ci-e alkyl Ci-ealkoxy, Ci-e haloalkyl, Ci-ehaloalkoxy, C2-6 alkeny l, Ci-t, alkynyl, Ce-w aiyl, C3- W cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ob- aryl-Cj- 6 alkyl-, Cs-w cycloalkyi- Ci-, (5-14 membered heteroaryl) -Ci- 6 alkyl-, and (4-14 membered heterocycloaikyl)-Ci- & alkyi-;
  • each R 115 and R 15 is independently selected from H, Cj-e alkyl, Cj-b haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, C &-J 4 aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary i-Ci-6 alkyl-, C -i + cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloa3kyl)-Ci-6 alkyl-;
  • each R Ji and R ’ ° is independently selected from OH, C -salkoxy, and Ci-ehaloalkoxy; or, any R jd and R k5 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alky l and Ci- 6 haloalkyl;
  • each R l is independently selected from D, halo, oxo, Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C2-6 a!kynyl, Ce-u aryl, Caur cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce- aryl-C 1-5 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered
  • heteroaryl C 1-6 alkyl-, and (4-14 membered heteroeyeloalkyi)-Ci-s alkyl-, CN, N0 2 , OK a5 , SR 36 , NHOR a6 , C(0)R b6 , C(0)NR c6 R d6 , C(0)NR c6 (0R a6 ), C(0)OR a6 , OC(0)R b6 ,
  • heteroaryi)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky i)-C 1.6 alkyl- of R 1 are each optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R a6 , R cf> , and R d6 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2.6 alkenyl, C 2-& alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aryl-Ci-6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered
  • each R b6 is independently selected from H, Ci- 6 alkyl, Cue haloalkyl, C 2-6 alkenyl, C2-6 alkynyl, C &-J 4 aryl, C B-M cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, 65- 14 ary 1-6 i-e alkyl-, C -i + cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloa3kyl)-Ci- 6 alkyl-, wherein the C - 6 aikyi, alkenyl, C 2-6 alkyny!, 5-14 aryl, € 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, 65- 14 ar l-Cw alkyl-, C 3-14 cycloalkyl
  • each R e6 is independently selected from H, OH, CN, Ci-e alkyl, Ci-e alkoxy, Ci- & haloalkyl, Ci-ehaioalkoxy', 6 2-5 alkenyl, C 2-6 alkynyl, 6 5-14 aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, 6 5-14 aryl-6 1-5 aikyi-, C 3-14 cycloalky 1- 6 1 -5 alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-C ] - 6 alkyl-;
  • each R f6 and R g6 is independently selected from H, Ci-e alkyl, Ci-e alkoxy, Ci- & haloalkyl, C -ehaloalkoxy, C 2-6 alkenyl, 6 2-5 alkynyl, 6 5-14 aryi, 6 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, 6 5-14 ary l-Ci- 6 alkyl-, C 3..14 cycloalky 1- C i-6 alkyl-, (5-14 membered heteroaryl)-6i-s alkyl-, and (4-14 membered heterocycloalkyl)-C i- 6 alkyl-;
  • each R h6 and R l6 is independently selected from H, C - 6 alkyl, 6 1-5 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, 6 5-14 aryl, 6 3 -1 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, 5- 1 aryl-6 1.5 alkyl-, C 3-14 cycloalky l-Ci-6 alkyl-, (5-14 membered heteroarvd)-C 1-6 alkyl-, and (4-14 membered heteroeyeloalkyl)-Ci-s alkyl-;
  • each R Jf> and R* 6 is independently selected from OH, Ci-ealkoxy, and Ci-ehaloalkoxy; or, any R j6 and R kb attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalky 1 group optionally substituted with 1, 2, 3, or 4 substituents independently selected from 61- 5 alkyl and Ci- 6 haloalky l;
  • each R J is independently selected from D, halo, oxo, Ci- 6 alkyl, 6 1-5 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, 6 5.14 aryd, 6 3-1 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, 5-14 ar l-Cw alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered
  • heterocycloalkyl C M * aiyl-Ci-e alkyl-, C3-14 cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl-, and (4-14 membered heteroeycloalkyl)-Ci-s alkyl- of R J are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R a7 , R c7 , and R d is independently selected from H, Cj- 6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C M * ar I-C1-& alkyl-, C3-14 cycloalkyl-Cw alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl- wherein the C1-6 alkyl, C 2-& alkenyl, C 2 « alkynyl, Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C w ary l-Ch-s alkyl-, C 3-i 4 cycl
  • R substituents are each optionally substituted with 1, 2, 3, or 4 independently selected R substituents; or any R c/ and R d7 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R b7 is independently selected from H, Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, Ce- aryd, C 3-i 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce- aryl-C 1.5 alkyl-, C3-14 cycloalky l-Ci-6 alkyl-, (5-14 membered heteroaryd)-C 1-6 alkyl-, and (4-14 membered heterocycloalkylVC i-s alkyl-, wherein the Ci-s alkyl, C 2 - s alkenyl, C 2 -s alkynyl, C&-14 aryd, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cg-w aryl-Ci-e alkyl-, C 3 -u cycloalk l-Ci-d alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl- of R 0/ are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R s ' is independently selected from H, OH, CN, Ci-e alkyl, C2-6 alkenyl, C 1-6 alkoxy, Ci. & haloalkyl, Cj-shaloalkoxy, C 2 -e alkynyl, Ce-ir aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl;
  • each R f? and R g/ is independently selected from H, Ci-e alkyl, Cue alkoxy, Ci-e haloalkyl, C;i- f! haloalkoxy, C 2-6 alkeny l, C 2-& alkynyl, Ce-w aiyl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, €b- aryl-Cj- 6 alkyl-, Cs-w cycloalkji- Ci- 6 alkyl-, (5-14 membered heteroaryl) -C1-6 alkyl-, and (4-14 membered heterocycloalky 1)-Ci. & alkyd-;
  • each R h? and R 1 ' is independently selected from H, Ci-g alkyl, Cj ⁇ haloalkyl, C 2-6 alkenyl, C 2 -e alkynyl, C &-J 4 aryd, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • J2 heterocycloalkyl Ce-w ary 1-C 1-6 alkyl-, Cj-i + cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalky 1)-Cw alkyl-;
  • each R j7 and R k ' is independently selected from OH, Cj-salkoxy, and Ci-shaloalkoxy; or, any R j ' and R k/ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alkyl and Ci-e haloalkyl;
  • each R is independently selected from H, D, OH, halo, oxo, CN, C(0)0H, NH 2 , NO2, SFs, Cj- 6 alkyl, Cj-e alkoxy, Ci-ehaloalkoxy, Cj-e haloalkyl, C2-6 alkenyl, C 2 -e alkynyl, Ce ⁇ l aryl, C B-M cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalky 1, Ce-u aryl-Ci- 6 alkyl-, CVw cyctoalkyl-Ci-e alkyl-, (5-14 membered heteroaryi)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-; and
  • any heteroaryl group of any of the above-recited substituents optionally comprises an N-oxide on any ring-forming nitrogen.
  • X is CR 3 ;
  • R ! is selected from H, Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci-b haloalkyl;
  • R 2 is selected from H, D, halo, Cj- 6 alkyl, Cj- 6 haloalkyl, C2.-6 alkenyl, C2-6 alkynyl, CV i4 aryl, Cs-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CX- M aryl-Ci- 6 alkyl-, Cs-u cycloalky l-Ci- 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, (4-14 membered heterocycloalkyl)-C !-e alkyl-, CN, N ⁇ 3 ⁇ 4, OR 82 , SR 32 , NHOR 32 , C(0)R b2 ,
  • NR c2 S(0)R b2 N R S;()i R K' .
  • heterocycloalkyl Ce-w aryl-Ci-6 alkyl-, Cj-i + cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalky 1)-Cw alkyl- of R ⁇ are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R substituents;
  • R 3 is selected from H, D, halo, Ci. & alkyl, Ci. & haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce- i 4 aiyl, €3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CV14 aryl-Ci- 6 alkyl-, C S-H cycloalky l-C 1-6 alkyl-, (5-14 membered heteroaryl) ⁇ Ci- 6 alkyl-, (4-14 membered heterocy cloalkyl)-C 1-6 alkyl-, CN, N0 2, OR a3 , SR a3 , NHOR a3 , C(0)R b3 ,
  • Ci-e alkyl C 2-6 alkenyl, C 2-6 alkynyl, Ci.-n aryl, C B-U cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce-w ary l-Ci- 6 alkyl-, C -i + cycloalkyl-C -e alkyl-, (5-14 membered heteroaryi)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky i)-Ci- 6 alkyl- of R 3 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 13 substituents;
  • Cy ! is Ce-w aryl, C -u cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the C 5-14 aryl, C 3-! 4 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R or R M substituents;
  • Cy 2 is Ce-w aryl, C B-M cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the Ce-w aryl, C 3 -i 4 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R r substituents;
  • each R 3i , R c ⁇ R d2 , R aJ , R c3 , and R d3 is independently selected from H, C . 6 alkyl, C . 6 haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, Cs-n aryl, Cs-wcycloalkyl, 5-14 membered heteroaryl, 4- 14 membered heterocycloalkyl, C ⁇ 5 -i 4 ary l-Ci-6 alkyl-, C 3-14 cycloalky 1-Cw alkyl-, (5-14 membered he ternary l)-Ci- & alkyl-, and (4-14 membered heterocycloalkyl)-Cw alkyl-, wherein the C - 6 alkyl, C 2 -g alkenyl, C 2-6 alkynyl, Ce-u aryl, C 3 -i 4 cycloalkyl, 5-14 membered heteroaryl
  • R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroary l or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R° substituents;
  • R c3 and R d3 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroary l or 4-14 membered heterocycloalkyl group is optionally substituted with 1 , 2, 3, or 4 independently selected R° substituents;
  • each R fc2 and R b3 is independently selected from H, Ci-e alkyl, Ci-e haloalkyl, C 2-6 alkenyl, C2-6 alkynyl, C&-14 aryl, C3..14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce-u aryl-C i-e alkyl-, C3-i 4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryi)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyi) ⁇ C 1-6 alkyl-, wherein the Ci-s alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci.-u aryd, C3-14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-e alkyl-, Cs-u
  • each R f2 , R g3 , R f3 , and R g3 is independently selected from H, Ci-b alkyl, Ci-e alkoxy, Ci- f .haloalkyl, Cj-ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C &-J 4 aryl, Cs-u cycloalkyl, 5-14 membered heteroary l, 4-14 membered heterocycloalkyl, C M 4 ary l-Ci- 6 alkyl-, C3-14 cycloalky 1- Ci- d alkyl-, (5-14 membered heteroaiyi)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R h2 , R 12 , R“ 3 , and R l3 is independently selected from H, Ci. & alkyl, Ci-ehaloalkyl, C2-6 alkenyl, C2-6 alkynyl, C &-J 4 aryd, C3-14 cycloalkyl, 5-14 membered heteroary l, 4-14 membered heterocycloalkyl, Ce-u aryl-Cj-e alkyl-, C3-14 cycloalky 1-Cw alkyl-, (5-14 membered heteroaryl)-Ci.6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-;
  • each R j2 , R k2 , R , and R K3 is independently selected from OH, Ci-e alkoxy, and Ci- 6 haloalkoxy;
  • R j3 and R ⁇ 3 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1 , 2, 3, or 4 substituents independently selected from C -.-e alkyd and Ci-shaloalkyl;
  • each R c , R D , R b , R M , R f' , and R° is independently selected from D, halo, oxo, C1-6 alkyl, Ci-e haloalkyl, C3-6 alkenyl, C2-6 alkynyl, C M * aryl, C3-14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C &.J4 ary l-Ci-6 alkyl-, Cs-ir cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl) -Ci .. 6 alkyl-, (4-14 membered heterocycloalkyl)-Ci ⁇ , alkyl-, CN,
  • R c , R D , R”, R M , R r , and R° are each optionally substituted with 1 , 2, 3, 4, 5, 6, 7, or 8 independently selected R ri substituents;
  • each R a4 , R c4 , and R d4 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2.6 alkenyl, C 2-6 alkynyl, Ce-u aryl, Cj-w cycloalkyl 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C 1.5 alkyl-, C3-14 cycloalky l-Ci-6 alkyl-, (5-14 membered heteroaryd)-Ci-6 alky!-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-, wherein the Ci-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ce-u aiyi, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci- 6 alkyl-, C3-14
  • each R w is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C 2 -6 alkenyl, C2-6 alkynyl, Ce-u aryl, C3- W cycloalkyl, 5-14 membered heteroaryl 4-14 membered
  • heterocycloalkyl C 6 -i4 aryl-C - 6 alkyl-, Cs-w cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, -wherein the Ci- 6 alkyl, C 2-& alkenyl, C 2-& alkynyl, C u aryl, Ci-u cycloalkyl, 5-14 membered heteroaryl 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-e alkyl-, Cs-u cycloalky l-Ci-6 alkyl-, (5-14 membered heteroaryl)-C]-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl- of R b4 are each optionally substituted with 1 , 2, 3, 4, 5, 6, 7, or 8 independently selected R
  • each R f4 and R g4 is independently selected from H, Ci-e alkyl Ci-e alkoxy, Ci-e haloalkyl, Ci-ehaloalkoxy, C2-6 alkenyl, C 2-6 alkynyl, Cl-ir aiyl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 aryl-Cj- 6 alkyl-, Cs-sr cyeloalkyi- C 1-6 alkyl-, (5-14 membered heteroaiy l)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R h4 and R l4 is independently selected from H, Cj-e alkyl, Cs-g haloalkyl, C2-6 alkenyl, Cz-s alkynyl, C&-14 aryl, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C i-e alkyl-, Cl- H cyeloalkyl-Cs-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-C 1.6 alkyl-;
  • each R J4 and R“ 4 is independently selected from OH, Cj-ealkoxy, and Ci-ehaloalkoxy; or, any R j4 and R k+ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalky 1 group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Cs- 6 alkyl and Cs- 6 haloalkyl;
  • each R H is independently selected from D, halo, oxo, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, €2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aryl-Ci-g alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaiyl)-Ci-6 alkyl-, (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR 85 , SR 3' , NHOR 35 .
  • heterocycloalkyl Ce-u aryl-C i-e alkyl-, €3-14 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl- of R 1 ! are each optionally substituted with 1, 2, 3, or 4 independently selected R !
  • each R a ⁇ R c5 , and R d> is independently selected from H, Ci-e alkyl, Ci-e haloalkyi, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce-i4 aryt-C -6 alkyl-, Cs- M cyeloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.
  • R 3> R c5 , and R d5 are each optionally substituted with 1, 2, 3, or 4 independently selected R 1 substituents;
  • R cS and R d5 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryi or 4-14 membered heterocycloalkyl group is optionally substituted with 1 , 2, 3, or 4 independently selected R 1 substituents;
  • each R b5 is independently selected from H, Ci-e alkyl, Cue haloalkyi, C2-6 alkenyl, C2-6 alkynyl, C&-14 aryl, C3-14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce-u aryl-Ci-e alkyl-, C 3 -i 4 eyeloalkyl-C - 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-C 1.6 alkyl-, wherein the Ci.
  • each R s5 is independently selected from H, OH, CN, C.-s alkyl, C.-s alkoxy, Ci- 6 haloalkyi, Ci-ehaloalkoxy, C2-6 alkeny l, C2-6 alkynyl, Ce-w aiyl, C3- H cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aiyl-Ci- 6 alkyl-, C3-14 cycloalkyl- Ci- 6 alkyl-, (5-14 membered heteroaryl) -C1-6 alkyl-, and (4-14 membered heterocycloalky 1)-Ci. & alkyd-;
  • each R b and R g5 is independently selected from H, Cm, alkyl, Ci «alkoxy, Ci-e haloalkyi, C -ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ci.-n aryl, C3-14 cycloalky 1, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, C M 4 ary l-Ci- 6 alkyl-, C3-14 cycloalky 1- C [- 6 alkyl-, (5-14 membered heteroaryi) -Ci-g alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R tD and R 15 is independently selected from H, Ci. & alkyl, Ci. & haloalkyi, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, €3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce-i aiyi-Ci-6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C ue alkyl-; each R Jd and R k5 is independently selected from OH, Ci-e alkoxy, and Cj-ehaloalkoxy; or, any R' 5 and R to attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-mem bered heterocycloalkyl group optionally substituted with 1, 2, 3,
  • heterocycloalkyl Ce- aryl-C 1 -5 alkyl-, C3-14 cycloalky l-Ci-6 alkyl-, (5-14 membered heteroarvd)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C [- 6 alkyl- of R 1 are each optionally substituted with 1 , 2, 3, or 4 independently selected R J substituents;
  • each R a6 , R c6 , and R d5 is independently selected from H, Ci- & alkyl, Ci- & haloalkyl, C 2.. e alkenyl, C 2- e alkynyl, C&-14 aryl, €3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 ar l-Ci-6 alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloalky 1)-Cw alkyl-, wherein the Cj- 6 alkyl, C 2-& alkenyl, C 2-6 alkynyl, Ce-u aryl, C3-14 cycloalky l, 5-14 membered heteroaryd, 4-14 membered heterocycloalkyl, CS- M ary l-Ci
  • each R b6 is independently selected from H, Cj- 6 alkyl, Cj- 6 haloalk l, C 2.& alken l, C 2-& alkynyl, Ca-u aryl, C 3-i4 cycloalkyl, 5-14 membered heteroaryd, 4-14 membered
  • heterocycloalkyl Ce-i aryd-Ci-e alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C i-6 alkyl-, wherein the Ci-g alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ce-u arvd, C 3-i 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CM* aryl-Ci-e alkyl-, C3- M cycloalky 1-Ci-e alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl-, and (4-14 membered heteroeycloalkyl)-C i-s alkyl- of R Db are each optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R ab is independently selected from H, OH, CN, Cj- 6 alkyl, Ci-e alkoxy, C M haloalkyl, Cj-ehaloalkoxy, C2-6 alkenyl, C 2-6 alkynyl, Ce-u aryl, 63-14 cycloalkyl, 5-14 membered heteroaiyl, 4-14 membered heterocycloalkyl, C&-14 ary l-Ci-6 alkyl-, C3-14 cycloalkyl- C 1-6 alkyl-, (5-14 membered heteroaiy l)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R fb and R g5 is independently selected from H, Ci- 6 alkyl, Cj-e alkoxy, C i- 6 haloalkyl, Ci-ehaioalkoxy, C 2 -s alkenyl, C 2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, aryl-C w, alkyl-, C3-14 cycloalkyl- Ci- 6 alkyl-, (5-14 membered heteroaiyll-Ci-g alkyl-, and (4-14 membered heterocycloalkyll-C]- s alkyl-;
  • each R hb and R lb is independently selected from H, C ue alkyl, C i-b haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, €5-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C w ary l-Cw alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaiy l)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-;
  • each R Jb and R*° is independently selected from OH, Ci ⁇ alkoxy, and Ci-ehaloalkoxy ; or, any R Jb and R kb attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C i-e alkyl and Chr, haloalkyl;
  • each R J is independently selected from D, halo, oxo, Che alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C2-6 alkynyl, C&-14 aryl, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C i-e alkyl-, C3-i 4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl-, CN, NO2, OR a? ,
  • NR c7 S(0)NR c7 R d7 , NR c7 S(0) 2 R b7 , NR c7 S(0)( NR e7 )R b7 , NR c7 S(0) 2 NR c7 R d7 , S(0)R b7 , S(0)NR c7 R d7 , ScOi -R 1' . S(0) 2 NR c7 R d7 .
  • heterocycloalkyl C w ary l-Cw alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R J are each optionally substituted with 1 , 2, 3, or 4 independently selected R substituents;
  • each R a/ , R c ', and R d7 is independently selected from H, C i-s alkyl, Ci-s haloalkyl, C 2-6 alkenyl, C 2 -s alkynyl, C&-14 aryl, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryd-C i-e alkyl-, C3-i4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl- wherein the Ci-e alkyl, C 2-6 alkenyl, C 2-f, alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Cj-
  • each R b/ is independently selected from H, Ci- 6 alkyl, Cj- 6 haloalkyl, C 2 -s alkenyl, C 2 -6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce-w ary I-C1- & alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Cj-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cs-w aryl-Ci-e alkyl-, CVw cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1 ⁇ 2 alkyl- of R b? are each optionally substituted with 1 , 2, 3, or 4 independently selected R substituents;
  • each R e ' is independently selected from H, OH, CN, Ci-e alkyl, C2-6 alkenyl, C 5 -6 alkoxy, Ci-b haloalkyl, Cwhaloalkoxy, C2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl;
  • each R f/ and R g? is independently selected from H, C .-s alkyl, Ci « alkoxy, Ci-e haloalkyl, Ci-ehaloalkoxy, C2-6 alkenyl, C 2- e alkynyl, C&-J4 aryl, cycloalkyl, 5-14 membered heteroary l, 4-14 membered heterocycloalkyl, Ce-u ary l-Ci- 6 alkyl-, C3-14 cycloalky 1- C [- 6 alkyl-, (5-14 membered he teroarydi-Ci- f , alkyl-, and (4-14 membered heteroeycioalkyli-Ci- 6 alkyl-;
  • each R h/ and R 1 ' is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C 2 .6 alkenyl, C alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryd)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C i- 6 alkyl-; each R J ' and R K/ is independently selected from OH, Ci-ealkoxy, and C -ehaloalkoxy; or, any R J / and R k ' attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-mem bered heterocycloalkyl group optionally substituted
  • each R K is independently selected from H, D, OH, halo, oxo, CN, C(0)QH, NH 2 ,
  • any heteroaryl group of any of the above-recited substituents optionally comprises an N -oxide on any ring-forming nitrogen.
  • X is N
  • R 2 is selected from H, D, halo, C -6 alkyl, C -6 haloalky l, C 2 - 6 alkenyl, C 2 -e alkynyl, Ce- 14 aryl, C3-14 cycloalky l, 5-14 membered heteroaryl, 4-14 membered heierocycloalkyl, €5-1 aryd-C -6 alkyl-, Cn-i Cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, (4-14 membered heterocycloalkyl)-Cw alkyl-, CN, N0 2 , OR a3 , SR a2 , NHGR ai , C(0)R b2 ,
  • heterocycloalkyl C w aryl-Ci-6 alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R 3 are each optionally substituted with 1 , 2, 3, 4, 5, 6, 7, or 8 independently selected R c substituents;
  • Cy ! is C&-14 aryl, €3-14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the Ce-u aryl, C3 -14 cycloalky 1, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R & substituents;
  • Cy z is Ce-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the aryl, C3-14 cycloalky 1, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R" substituents;
  • each R al , R ci , R dl , R a2 , R° 2 , and R d2 is independently selected from H, C -e alkyl, Cue haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3.14 cycloalkyl, 5-14 membered heteroaryl, 4- 14 membered heterocycloalkyl, C K aryl -Ci-s alkyl-, C;-i4eyeloalkyi-C 1-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci..6 alkyl-, wherein the C -6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aiyl, C3- M cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloal
  • R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroary l or 4-14 membered heterocycloalkyl group is optionally substituted with 1 , 2, 3, or 4 independently selected R° substituents;
  • each R bl and R b2 is independently selected from H, Ci-s alkyl, Ci-e haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&-14 aryl, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C i-b alkyl-, C3-i4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1) ⁇ C R> alkyl-, wherein the C M alkyl, C2-6 alkenyl, C2-6 alkynyl, C &-J 4 aryl, C J-M cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C -e alkyl-, Ci-u
  • each R Bl and R e2 is independently selected from H, OH, CN, C i-s aikyl, C i-s alkoxy, Ci- 6 haloalkyl, C -e haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryi, Cs-u cycloalkyi, 5-14 membered heteroaryl, 4-14 membered heierocycloalkyl, CM* ary l-Ci-6 alkyl-, C3-14 cycloalkyl- C 1.6 alkyl-, (5-14 membered heteroaryi) ⁇ Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each G and R g2 is independently selected from H, Ci- 6 alkyl, C -e alkoxy, C M> haloalkyl, Ci-ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce- aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C i-e alkyl-, C3-14 cycloallcyl- Ci- 6 alkyl-, (5-14 membered heteroaiyll-Ci-g alkyl-, and (4-14 membered heterocycloalkyl)-C ] - s alkyl-;
  • each R M and R l2 is independently selected from H, C i-s alkyl C i-b haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C M ary I-C1-& alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-;
  • each R j2 and R*“ is independently selected from OH, Ci-ealkoxy, and Ci-ehaloalkoxy ; or any R j2 and R K attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C i- 6 alkyl and C - 6 haloalkyl;
  • each R b , R c , R , R b , and R G is independently selected from D, halo, oxo, Ci- 6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C 2- e alkynyl, aryl, C3.14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-14 aryl-C i-s alky!-, Ci-w cyeloalkyl-C 1.5 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO ?.
  • heterocycloalkyl CVM aryl-Ci ⁇ , alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R b , R c , R b , R 1' , and R' J are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R h substituents;
  • each R a4 , R c4 , and R d4 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, Cj-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C i-e alkyl-, wherein the Ci- 6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-i + aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cs-w aryl-C -
  • each R w is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce-i4 ar t-C -6 alkyl-, Cs-w cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, wherein the Ci- 6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C -6 alkyl-, Cs-u cycloalky l-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.
  • each R e4 is independently selected from H, OH, CN, Ci-e alkyl, Ci-e alkoxy , Ci- 6 haloalkyl, C -ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C &-J 4 aryl, Cs-u cycloalky 1, 5-14 membered heteroary l, 4-14 membered heterocycloalkyl, Ce-u ary l-Ci- 6 alkyl-, C3-14 cycloalky 1- C [-6 alkyl-, (5-14 membered he teroarydi-Ci- f , alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-
  • each R f4 and R 84 is independently selected from H, Ci- 6 alkyl, Ci- 6 alkoxy, Ci ⁇ haloalkyl, Ci-ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, Ch-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aiyd-Ci- 6 alkyl-, Cs-u cycloalkyi- C 1-6 alkyl-, (5-14 membered heteroaryl) ⁇ Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R h+ and R l4 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2 -s alkynyl, C aryl, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CM* aryl-C i-e alkyl-, C3-i4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-;
  • each R j4 and R k4 is independently selected from OH, Cj-ealkoxy, and Ci-ehaloalkoxy; or, any R j and R k+ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalky 1 group optionally substituted -with 1, 2, 3, or 4 substituents independently selected from Cj- 6 alkyl and Cs- 6 haloalkyl;
  • each R H is independently selected from D, halo, oxo, Cue alkyl, C R> haloalkyl, C 2- 6 alkenyl, C 2-f, alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6 -i4 aiyl-Ci-6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaiyl)-Ci-6 alkyl-, (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, CN, N0 2 , OR 85 , SR 3" , NHOR a5 , C(0)R b5 , C(0)NR c5 R d5 , C(0)NR c5 (0R a5 ), C(0)0R a5 , 0C(0)R bs , 0C(0)NR
  • heterocycloalkyl CM* aiyl-C [-6 alkyl-, C3-14 cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-C R> alkyl- of R H are each optionally substituted with 1, 2, 3, or 4 independently selected R ! substituents;
  • each R 35 , R c5 , and R d " is independently selected from H, Ci-e alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, €5-14 aryl, C3-1 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CM* ar I-C - & alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered
  • R c5 , and R d5 are each optionally substituted with 1 , 2, 3, or 4 independently selected R 1 substituents;
  • R c and R d5 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroary l or 4-14 membered heterocycloalkyl group is optionally substituted with 1 , 2, 3, or 4 independently selected R 1 substituents;
  • each R b5 is independently selected from H, Cue alkyl. Cue haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&-1 aryl, C3-14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce-u aryl-C M alkyl-, ifr-n eyeloalkyl-C alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-C R > alkyl-, wherein the CM alkyl, C ?
  • each R s?' is independently selected from H, OH, CN, C M alky l, Ci-e alkoxy, C haloalkyl, C;i- f! haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-w aiyl, C3- M cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6 -i4 aiyl-Ci- 6 alkyl-, C 3-14 cycloalky!- Ci- 6 alkyl-, (5-14 membered heteroaryl) -C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- & alkyl-;
  • each R b and R g5 is independently selected from H, C M alkyl, Ci « alkoxy, Ci- 6 haloalkyl, Cj-ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, ( M-M aryl, C 3-14 cycloalky 1, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce-u ary' i-C 1-6 alkyl-, C 3-i 4 cyc!oalky 1- CM alk l-, (5-14 membered heteroaiyl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R to and R 15 is independently selected from H, CM alkyl, C haloalkyl, C2-6 alkenyl, €2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce-w aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-;
  • each R p and R* 5 is independently selected from OH, Cj-s aikoxy, and Ci-shaloalkoxy; or, any R j5 and R* 5 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C alkyl and C 1-6 haloalkyl;
  • each R 1 is independently selected from D, halo, oxo, C , alkyl, C , haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce-w ary 1-C M alkyl-, C3-14 eyeloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 aikyl-, and (4-14 membered heterocycioalkyi)-Ci- 6 alkyl-, CN, N(3 ⁇ 4, OR a6 ,
  • heterocycloalkyl Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl- of R ! are each optionally substituted with 1 , 2, 3, or 4 independently selected R J substituents;
  • each R 36 , R c6 , and R d5 is independently selected from H, Ci- & alkyl, Ci- & haloalkyl, C 2.. e alkenyl, C 2- e alkymyl, C &-K aryl, C-t-u cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary l-Ci-6 alkyl-, Ca-i + cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, wherein the C - 6 alkyl, C 2-& alkenyl, C 2-6 alkynyl, Ce-u aryl, Cs-u cycloalkyi, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C S-M ary
  • R c6 and R* attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R bo is independently selected from H, CM alkyl, CM haloalk l, C 2.6 alkenyl, C 2-& alkynyl, Ce-w aryl, C3- H cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the C M alkyl, C 2-& alkenyl, C 2-& alkynyl, CV aryl, Ci- K cycloalkyl, 5-14 membered heteroaryd, 4-14 membered heterocycloalkyl, Cs-w aryl-Ci- 6 alkyl-, C3-14 cycloalky l-Ci- 6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C ue alkyl- of R b6 are each optionally substituted with 1 , 2, 3, or 4 independently selected R J substituents;
  • each R e6 is independently selected from H, OH, CN, C , alkyl, Ci- 6 alkoxy, Ci-6 haloalkyl, C ] -6haloalkoxy, C 2 -s alkenyl, C 2- e alkynyl, C K aryl, €3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i ary l-Ci-6 alkyl-, C3..14 cycloalky 1- C i-6 alkyl-, (5-14 membered heteroaryi)-Ci-s alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-; each R ® and R s ° is independently selected from H, Ci-e alkyl Ci-e alkoxy, Ci-e haloalkyl, C;i- f!
  • haloa3koxy C2-6 alkenyl, C2-6 alkynyl, Ce-w aiyl, C3- H cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Gs-w aryl-C - 6 alkyl-, Cs- M cycloalkyl- Ci- 6 alkyl-, (5-14 membered heteroaryl) -C1-6 alkyl-, and (4-14 membered heterocycloalky 1)-Ci. & alkyl-;
  • each R h6 and R' 6 is independently selected from H, C -6 alkyl, C -e haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ci.-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CN- M aryl-Ci-e alkyl-, C -i+ cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl-;
  • each R' 6 and R k6 is independently selected from OH, C -s alkoxy, and C i-ehaloalkoxy; or, any R jf> and R kb attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alky l and Ci-e haloalkyl;
  • each R 1 is independently selected from D, halo, oxo, Ci-b alkyl, Ci-b haloalkyl, C2.6 alkenyl, C2-6 alkynyl, C M aryl, C 3-i 4 cycloalkyl, 5-14 membered heteroaryd, 4-14 membered heterocycloalkyl, Ce- aryi-C 1.5 alkyl-, C3-1 cycloalky I-C1-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C [-6 alkyl-, CN, NO2, OR a7 ,
  • Ci-e alkyl C 2-6 alkenyl, C 2-6 alkynyl, Ce-u aryl, €3-14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce-u aryl-C i-e alkyl-, C 3 -i 4 cycloalkyl-C - 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl- of R ! are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R a/ , R c , and R d ' is independently selected from H, Cj-b alkyl, Ci-e haloalkyl, C2-6 alkenyl, €2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 aryl-C -6 alkyl-, Cs-w cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl- wherein the Ci-6 alkyl, C2-6 alkenyl, C2-6 alkymyl, C6-i4 aryl, Ci- H cycloalkyl, 5-14 membered heteroaryd, 4-14 membered heterocycloalkyl, C 6-i4 aryl-Ci-e alkyl-
  • R K substituents are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents; or any R c/ and R d7 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R b is independently selected from H, Ci-e alkyl, Ci-e haloalkyl, C 2-6 alkenyl, C2-6 alkynyl, Ce- aryd, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Cg-w aryl-C 1.5 alkyl-, C3-14 cycloalky 1-Ci- alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl-, and (4-14 membered heterocycloaikyi)-Ci-6 alkyl-, wherein the Ci-s alkyl, C2-6 alkenyl, C2-6 alkynyl, C -u aryd, C 3-i 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cg-u aryl-Ci-e alkyl-, C3-34 cycloalk l-Ci ⁇ alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloaikyi) ⁇ Ci-g alkyl- of R B? are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R 57 is independently selected from H, OH, CN, Ci-g alkyl, C2-6 alkenyl, Ci-g alkoxy, Ci-g haloalkyl, Ci-ghaloalkoxy, C2-6 alkynyl, Cg-ir aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, and 4- 14 membered heterocycloalkyl;
  • each R f? and R g/ is independently selected from H, Ci-e alkyl, C 1-6 alkoxy, Ci-e haloalkyl, Ci-ghaloalkoxy, C2-6 alkenyl, C2.6 alkynyl, Cgur aryd, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w aryt-Cj-g alkyl-, Cs-ir eyeloalkyi- Ci- 6 alkyl-, (5-14 membered heteroaryl) -Ci-g alkyl-, and (4-14 membered heterocycloalky 1)-Ci. 6 alkyl-;
  • each R h? and R 1 ' is independently selected from H, Ci- 6 alkyl, Cj-g haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Cg.u aryd, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cg-u aryl-Ci-g alkyl-, Ch-n cycloalkyl-Cj-g alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-C 1.6 alkyl-;
  • each R J ' and R K is independently selected from OH, Cj-g alkoxy, and Ci-ghaloalkoxy; or, any R" and R k/ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Cj-g alkyl and Cs-g haloalkyl;
  • each R K is independently selected from H, D, OH, halo, oxo, CN, C(0)OH, NH 2 ,
  • any heteroaryl group of any of the above-recited substituents optionally comprises an N-oxide on any ring-forming nitrogen.
  • X is N
  • R 1 is selected from H, C M alkyl, C2-6 alkenyl, C M alkynyl, and C M haloalkyl;
  • R 2 is selected from H, D, halo, C M alkyl, C M haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce- 14 and, C3.14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-6 alkyl-, CVw cyctoalkyl-C M alkyl-, (5-14 membered heteroaryl) ⁇ Ci-6 alkyl-, (4-14 membered heterocycloalky 1)-C M alkyl-, CN, N(3 ⁇ 4, GR 32 , SR 32 , NHOR a2 , C(0)R b3 ,
  • heterocycloalkyl Ce- aryl-C alkyl-, C3-1 cycloalky l-Ci-6 alkyl-, (5-14 membered heteroaryl)-C alkyl-, and (4-14 membered heteroeyeloaikyi)-C[-s alkyl- of R 2 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R c substituents;
  • Cy 1 is Ce aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the Cs-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R7 or R M substituents;
  • Cy 2 is Ce-14 aryl, C3.14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the C -u and, C3-14 cyeloalkyl, 5-14 membered heteroaryl, or 4-14 membered heteroc cloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R b substituents;
  • each R 32 , R c2 , and R d2 is independently selected from H, C alkyl, C haloalkyl, C M alkenyl, C 2 -s alkynyl, C&-14 aryl, €3-1 + cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C M alkyl-, Ci- H cycloalkyl-C M alkyl-, (5-14 membered heteroaryi)-Ci- 6 alky 1-, and (4-14 membered heterocycloalky 1) ⁇ C alkyl-, wherein the C M alkyl.
  • C M alkenyl, C M alkyny l, C &-J 4 aryl, C 3 -i4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-e alkyl-, Ci-u cycloalkyl-C -6 alky' 1-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl- of R a2 , R c , and R di are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R G substituents;
  • R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1 , 2, 3, or 4 independently selected R u substituents;
  • each R b2 is independently selected from H, C.-s alkyl, C.-s haloalkyl, C2-6 alkenyl, C2.6 alkynyl, C M * aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce-w aryl-Ci-e alkyl-, C -i + cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the C -6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, Cs-u cycloalkyi, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, aryl-Cw alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalky l)-C]- 6 alkyl- of R fc2 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R ⁇ J substituents;
  • each R G and R g2 is independently selected from H, Ci-e alkyl, Ci-b haloalkyl, C - 6 alkoxy, C 1-6 haloalkyl, Ci-ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Cs-u aryl, C 3-i4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cs-u aryl-Ci-e alkyl-, C3 -14 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-;
  • each R h2 and R l2 is independently selected from H, C - 6 alkyl, C - 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryd, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C M * aryd-C [-6 alkyl-, C 3-H cycloalkyl-C] ⁇ alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl-, and (4-14 membered heterocyeloalkyd)-Ci-6 alkyl-;
  • each R J and R k2 is independently selected from OH, Ci- & alkoxy, and Ci-ehaloalkoxy; or any R 2 and R k2 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalky 1 group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C M alkyl and C 1-5 haloalkyl; each R c , R E , R M , R f , and R° is independently selected from D, halo, oxo, Ci-e alkyl, C [- 6 haloalkyl, C 2.g alkenyl, C2-6 alkynyl, Cg-u and, C 3-14 cycloalkyl, 5- 14 membered heteroatyl, 4-14 membered heterocycloalky 1, Ce-u aryl-Ci alkyl-, C3- H cycloalkyl-Ci-e alkyl-, (5
  • heterocycloalkyl CM* aiyl-C i-g alkyl-, C 3-14 cycloalkyl-Cj-e alkyl-, (5- 14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyi) ⁇ Ci-g alkyl- of R c , R E , R M , R F , and R G are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R H substituents;
  • each R a4 , R c+ , and R d4 is independently selected from H, Ci-g alkyl, Ci-g haloalkyl, C 2..g alkenyl, C 2-g alkynyl, Cg-u aryl, C -u cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cg-i 4 ary 1-Ci-g alkyl-, C -i+ cycloalkyl-C -g alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl-, wherein the Ci-g alkyl, C 2-g alkenyl, C 2-g alkynyl, Cg-n aryl, C 3-i 4 cycloalkyl, 5-14 membered heteroaryd, 4-14 membered heterocycloalkyl, C -n ar l
  • each R b4 is independently selected from H, Ci-e alkyl, Ci- haloalkyl, C 2-g alkenyl, C 2-g alkynyl, Cg-u aryl, €3-14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Cg-u aryl-C i-g alkyl-, €3-14 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci-g alkyl-, and (4-14 membered heterocycloalky 1)-C R > alkyl-, wherein the CM alkyl, C 2 -g alkenyl, C 2 -g alkynyl, Cg-u aryl, C J-M cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-e alkyl-, Ci-u cycloalkyl-C -6 alky' 1-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl- of R B4 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R ri substitu
  • each R f4 and R 8 * is independently selected from H, C.-s alkyl, Ci «alkoxy, Ci- 6 haloalkyl, Ci- 6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C K aryl, C3 U 4 cycloalkyl, 5-14 membered heteroary l, 4-14 membered heterocycloalkyl, Ce-u ary l-Ci- 6 alkyl-, C3-14 cycloalky 1- C [-6 alkyl-, (5-14 membered he teroaryl)-Ci- 6 alkyl-, and (4-14 membered heierocyeloalkyli-Ci- 6 alkyl-;
  • each R h4 and R l4 is independently selected from H, Ci. & alkyl, Ci. & haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, Cj-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce- aryl-C 1.5 alkyl-, C3-14 cycloalky l-Ci-b alkyl-, (5-14 membered heteroaiyd)-Ci- 6 alkyl-, and (4-14 membered keterocycloalkyl)-C i-e alkyl-;
  • each R j4 and R“ 4 is independently selected from OH, Ci-ealkoxy, and C -ehaloalkoxy; or, any R
  • each R H is independently selected from D, halo, oxo, C [- 6 alkyl, C [- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, Cs-ucycloalkyi, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary l-Ci-6 alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR 35 , SR a5 , NI-IOR 35 , C(0)R b5 , C(0)NR c5 R d5 , C(0)NR c5 (0R a5 ), C(0)0R 35 , 0C(0)R bs , 0C(0)NR c5 R d5 .
  • heterocycloalkyl C 6 -i4 aiyl-Ci- 6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R fl are each optionally substituted with 1 , 2, 3, or 4 independently selected R 1 substituents;
  • each R a5 , R° 5 , and R di is independently selected from H, C i-s alkyl, Ci-s haloalkyl, C 2-6 alkenyl, C 2-G alkynyl, C G-M aryl, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CG- M aryl-C i-e alkyl-, C3-i4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-C R> alkyl-, wherein the C M alkyl, C 2 -e alkenyl, C 2-6 alkynyl, CG-M aryd, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CG-M aryl-C -6 al
  • R 05 and R da attached to the same N atom, together with the N atom to winch they are attached, form a 5- or 6-membered heteroary l or a 4-14 membered heterocycloalkyl group, wirerein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R ! substituents;
  • each R to is independently selected from H, C J-G alkyl, C2-6 alkenyl, C2-0 alky nyl, C 6 -i4 aryl, C3 -14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CG- M aryl- Ci- f, alkyl-, C3-14 cycloalkyl-Ci- G alkyl-, (5-14 membered heteroary!)-Ci-e, alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl-, wirerein the Ci-e alkyl, C 2-6 alkenyl, C2-6 alkynyl, CG- 1 aryi, C3-1 + cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloaikyi, C G-M aryi-Ci-e alkyl-, Cs-w cycloaikyl-
  • each R e5 is independently selected from H, OH, CN, C I -G alkyl, Ci-e alkoxy, Ci-e haloalkyl, Ci-ehaloalkoxy, C 2-G alkenyl, C 2 « alkynyl, C G-M aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloaikyi, Cs- 14 aryi-Ci-e alkyl-, C3-14 cycloalkyl- Ci-5 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alky 1-;
  • each R f5 and R 85 is independently selected from H, Ci-e alkyl Ci-e alkoxy, C1-6 haloalkyl, Cwehaloalkoxy, C 2-G alkeny l, C 2-G alkynyl, C G-M aryl, C3- M cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloaikyi, C G- M ar l-C -6 alkyl-, Cs- M cycloalkyi- Ci-6 alkyl-, (5-14 membered heteroaryl) -C I-G alkyl-, and (4-14 membered heterocycloalky 1)-Ci. 6 alkyi-;
  • each R 115 and R 15 is independently selected from H, Ci-s alkyl, Ci-s haloalkyl, C 2 -e alkenyl, C 2-6 alkynyl, C &-J 4 aryi, C 3- cycloalkyl, 5-14 membered heteroary l, 4-14 membered heterocycloalkyl, Ce-u ary i-Ci-6 alkyl-, C -i+ cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-;
  • each R Ji and R ’ ° is independently selected from OH, C -s alkoxy, and C i-ehaloalkoxy; or, any R jd and R k5 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alky l and Ci- 6 haloalkyl; each R l is independently selected from D, halo, oxo, Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C2-6 a!kynyl, Ce-u aryl, C -ir cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce- aryl-C i- d alkyl-, C3-1 cycloalky I-C1-6 alkyl-, (5-14 membered heteroar
  • heterocycloalkyl Ce-14 ary i-Ci- 6 alkyl-, Ca-i+ cycloalkyl-C -e alkyl-, (5-14 membered heteroaryi)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyi)-C 1.6 alkyl- of R 1 are each optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R a6 , R cf> , and R d6 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2.6 alkenyl, C 2-& alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.
  • R ao , R c6 , and R d6 are each optionally substituted with 1, 2, 3, or 4 independently selected R J substituents; or any R CR and R d6 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered
  • each R b6 is independently selected from H, Ci- 6 alkyl, Cue haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ci.-n aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4- 14 membered heterocycloalkyl, 65-14 ary 1-6 i-e alkyl-, C -i+ cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the C -6 aikyi, C‘ alkenyl, C2-6 alkyny!, 65-14 aryl, €3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, 65-14 ar l-Cw alkyl-, C3-14 cycloalkyl-Ci-e al
  • each R e6 is independently selected from H, OH, CN, Ci-e alkyl, Ci-e alkoxy, Ci- & haloalkyl, Ci-ehaloalkoxj', 6 2-5 alkenyl, C 2-6 alkynyl, 6 5-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, 6 5-1 aryl-6 i-s alkyl-, C 3-14 cycloalky 1- Ci- 6 alkyl-, (5-14 membered heteroaryl)-C ]-6 alkyl-, and (4-14 membered heterocycioalkyi)-Oi- 6 alkyl-;
  • each R f6 and R g6 is independently selected from H, Ci-e alkyl, Ci-e alkoxy, Ci- & haloalkyl, Oi-ehaloalkoxy, C2-6 alkenyl, 62-5 alkynyl, 65-14 aryl, 63-14 cycloalkyl, 5-14 membered heteroaiyl, 4-14 membered heterocycloalkyl, 65-14 ary l-Ci- 6 alkyl-, C3..14 cycloalky 1- C i-6 alkyl-, (5-14 membered heteroaryi)-C i-s alkyl-, and (4-14 membered heterocycloalkyl)-6 i- 6 alkyl-;
  • each R h6 and R l6 is independently selected from H, C - 6 alkyl, haloalkyl, C2-6 alkenyl, C2-6 alkynyl, 65-14 aryl, 63-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, 65-1 aryl-61.5 alkyl-, C3-14 cycloalky l-Ci-6 alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl-, and (4-14 membered heteroeyeloalkyi)-O i-s alkyl-;
  • each R Jf> and R* 6 is independently selected from OH, Ci-ealkoxy, and Ci-ehaloalkoxy; or, any R j6 and R kb attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalky 1 group optionally substituted with 1, 2, 3, or 4 substituents independently selected from 61-5 alkyl and Ci-6 haloalkyl;
  • each R J is independently selected from 13, halo, oxo, Ci-6 alkyl, 61-5 haloalkyl, C 2 -6 alkenyl, C2-6 alkynyl, 65.14 aryl, 63-1 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, 65-14 ar I-C1-& alkyl-, 63-14 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-6 ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-6i-6 alkyl-, 6N, NO2, OR a/ , SR a? , NHOR 87 , 6(0)R b7 , 6(0)NR c7 R d7 , 6(0)NR c7 (QR a7 ), C(0)0R* 7 , 06(0)R b7 ,
  • heterocycloalkyl C M * aiyl-C [-6 alkyl-, C3-14 cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryd)-C 1-6 alkyl-, and (4-14 membered heteroeyeloaikyi)-C[-s alkyl- of R J are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R a7 , R c7 , and R d is independently selected from H, Cj- 6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, Ce-u aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C M * ar I-C1- & alkyl-, C3- 14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- wherein the C1-6 alkyl, C 2-6 alkenyl, C 2 « alkynyl, Ce-u aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, €5-14 atyl-Ci-s alkyl-,
  • R substituents are each optionally substituted with 1, 2, 3, or 4 independently selected R substituents; or any R c/ and R d7 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R b7 is independently selected from H, Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, Ce- aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce- aryl-C 1.5 alkyl-, C 3-14 cycloalky I-C 1 -6 alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl-, and (4-14 membered heterocy cloaikyi)-Ci-6 alkyl-, wherein the Ci-s alkyl, €2-5 alkenyl, C 2 -s alkynyl, C&-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C * aryl-Ci-e alkyl-, C3-34 cycloalkyl-Ci-s alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloaikyi) ⁇ C [-6 alkyl- of R 0/ are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R s ' is independently selected from H, OH, CN, Ci-e alkyl, C 2-6 alkenyl, C 1-6 alkoxy, Ci. & haloalkyl, Cj-shaloalkoxy, C2-6 alkynyl, Ce-i aryl, C 3-1 cycloalkyl, 5-14 membered heteroaryl, and 4- 14 membered heterocycloalkyl;
  • each R f? and R g/ is independently selected from H, Ci-e alkyl, Cue alkoxy, Ci-e haloalkyl, C;i- f! haloalkoxy, C2-6 alkenyl, C 2-6 alkynyl, Ce-w aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w aryl-Cj- 6 alkyl-, Cs-w cycloalkji- Ci- 6 alkyl-, (5-14 membered heteroaryl) -C 1-6 alkyl-, and (4-14 membered heterocycloalky 1)-Ci. & alkyd-;
  • each R h? and R 1 ' is independently selected from H, Ci- 6 alkyl, Cj ⁇ haloalkyl, C2-6 alkenyl, C 2-f , alkynyl, G M 4 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u ary l-Ci-6 alkyl-, C -i + cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-;
  • each R j7 and R k ' is independently selected from OH, C -salkoxy, and Ci-ehaloalkoxy; or, any R j ' and R k/ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alky l and Ci-b haloalkyl;
  • each R is independently selected from H, D, OH, halo, oxo, CN, C(0)0H, NH2, NO2, SFs, C - 6 alkyl, C -e alkoxy, Ci-ehaloalkoxy, C-- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce ⁇ l and, C3.14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloaikyi, Ce-ir aryl-Ci- 6 alkyl-, CVw cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl-; and
  • any heteroaryl group of any of the above-recited substituents optionally comprises an N-oxide on any ring-forming nitrogen.
  • each R J is independently selected from 13, halo, oxo, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C 3-1 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloaikyi, C M ar I-C1- & alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered
  • each R a ', R c ', and R d ' is independently selected from H, €1-5 alkyl, C - 6 haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, C &.14 aryl, C 3-1 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloaikyi, C M aryl-Ci ⁇ , alkyl-, C 3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered
  • heteroaryl C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-;
  • each R b/ is independently selected from H, Cj-6 alkyl, Cj-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ce-u aryl, 6(3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary i-Ci-6 alkyl-, C -i+ cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloa3kyl)-Ci-6 alkyl-.
  • each R 1 is independently selected from D, halo, oxo, C .-s alkyl, C .-s haloaikyl, C 2.6 alkenyl, C2-6 alkynyl, Ce-w aryl, Cj-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyi, Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C [- 6 alkyl-, CN, NO2, OR a6 , SR a6 , NHOR a6 , C(0)R b6 , C(0)NR c6 R d6 , C(0)NR c6 (0R a6 ), C(0)OR a6 , OC(0)R b6 ,
  • each R a6 , R c6 , and R' fo is independently selected from H, Ci-e alkyl, Ci-e haloaikyl, C 2-6 alkenyl, C 2-6 alkynyl, Ce-w aryl, Cj-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyi, Ce- aryl-C 1.5 alkyl-, C 3-14 cycloalky I-C 1-6 alkyl-, (5-14 membered heteroaryl)-Ci ⁇ alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-;
  • R 06 and R do attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14-membered heterocycloalkyi group;
  • each R bo is independently selected from H, C - 6 alkyl, C - 6 haloaikyl, C 2.& alkenyl, C 2-& alkynyl, Ce-w aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyi Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-.
  • each R h is independently selected from D, halo, oxo, C - 6 alkyl, Ci-6 haloaikyl, C 2- e alkenyl, C2-6 alkynyl, CN, Ci.& alkoxy, Ci-b haloalkoxy, amino, Ci-6 alkylamino, di-Ci -s alkylamino, Cw, alkylsulfonyl, aminosulfonyl, C - 6 aikyiaminosulfonyi, di-Ci- 6 alkylaminosulfonyl, and C - 6 alkylsulfonylamino; wherein said Cl -6 alkyl is optionally substituted by 1, 2, 3, 4, 5, 6, 7, or 8 independently selected halogens.
  • each R 35 , R°, and R d: ’ is independently selected from H, Ci- 6 alkyl, Ci « haloaikyl, C2-6 alkenyl, C « alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyi, phenyl-Ci-e alkyl-, Crw- cyeloalkyi-Ci-e alkyl-, (5-6 membered heteroaryi)-C i- 6 alkyl-, and (4-7 membered heterocycloalkyl)-C ]-6 alkyl-, wherein the Ci- 6 alkyl, C 2-6 alkenyl, C 2-& alkynyl, phenyl, C3- ?
  • each R to is independently selected from H, C alkyl, C haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C i- 6 alkyl-, C 3-7 cycloalkyl-Ci-e alkyl-, (5-6 membered heteroaryl)-Ci- 6 alkyl-, and (4-7 membered heterocycloalky 1)-C M alkyl-, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryi, 4-7 membered heterocycloalkyl, phenyl-Ci- 6 alkyl-, Cfr cycloalkyl-C M alkyl-, (5-6 membered heteroaryl)-Ci
  • each R 5 is independently selected from H, OH, CN, C , alkyl, C M , alkoxy, C M , haloalkyl, and C M haioalkoxy;
  • each R ft and R 83 is independently selected from H, C M alkyl, C M haloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-Ci-6 alkyl-, C3-7 cycloalky I-C M alkyl-, (5-6 membered heteroaryl)-Ci- 6 alkyl-, and (4-7 membered heterocycloalkyi)-C M alkyl-;
  • each R to and R 15 is independently selected from H, C M haloalkyl, C alkyl, C 2-6 alkenyl, C2-6 alkynyl, phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C -6 alkyl-, C3-7 cycloalky 1-C alkyl-, (5-6 membered heteroaryl)-Cj- 6 alkyl-, and (4-7 membered heterocycloalky 1)-O M alkyl-;
  • each R j5 and R* 5 is independently selected from OH, C M alkoxy, and Ci ⁇ haloalkoxy;
  • each R 1 is D, halo, oxo, C M alkyl.
  • each R ! and R 3 is independently selected from D, halo, oxo, C M alkyl, C M haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, C M alkoxy.
  • C haioalkoxy, amino, Ci-6 alkylamino, di-C M alkylamino, C M alkylsulfonyl, aminosulfonyl.
  • alkylaminosulfonyl di-C M alkylaminosulfonyl, and C M alkylsulfonylamino;
  • each R K is independently selected from H, D, OH, halo, oxo, CN, C(0)GH, NH 2 ,
  • X is N
  • R 2 is selected from H, D, halo, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce- 14 a d, €3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aryi-Ci-6 alkyl-, C3 -14 cycloalkyl-C 1-6 alkyl-, (5-14 membered heieroaryl)-Ci- 6 alkyl-, (4-14 membered heterocycloalkyl) ⁇ Ci-6 alkyl-, CN, N0 2 , OR 32 , SR 32 , NHOR 32 , C(0)R b2 ,
  • heterocycloalkyl, Ce-i aiyl-Ci-6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycioalkyl)-C 1 ⁇ 2 alkyl- of R 2 are each optionally substituted with 1 , 2, 3, 4, 5, 6, 7, or 8 independently selected R c substituents;
  • Cy 1 is C-6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the Cg-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R h substituents;
  • Cy 1 is not pyridin-4-yl optionally substituted with 1, 2, 3, or 4 independently selected R' substituents; provided that Cy 1 is not pyrimidin-4-yl optionally substituted with 1, 2, or 3, independently selected R fc substituents;
  • Cy 1 is not quinolin-4-yl optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R substituents;
  • Cy 2 is Ce- M aryl, C B-M cycloalkyl, 5-14 mem bered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the Ce-u aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 1' substituents;
  • each R al , R cl , R d! , R a2 , R c2 , and R d2 is independently selected from H, Cw alkyl, Cw haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C M 4 aryl, Cs-wcycloalkyl, 5-14 membered heteroaryl, 4- 14 membered heterocycloalkyl, C 4 aryl-Ci-6 alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered he ternary l)-Ci- & alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, wherein the C]- 6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalky
  • R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1 , 2, 3, or 4 independently selected R ' substituents;
  • each R bi and R b2 is independently selected from H, C.-s alkyl, C.-s haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C M 4 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary i-C 1-6 alkyl-, Cj- H cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloa3kyl)-Ci-6 alkyl-, wherein the Cj-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C&-34 aryl, €3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 4 aryl-Cw alkyl-, C3-14 cycloalky
  • each R c and R g2 is independently selected from H, C -- 6 alkyl, Ci-e alkoxy, Ci- 6 haloalkyl, Ci-ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ci.-n aryl, C3-14 cycloalky 1, 5-14 membered heteroary l, 4-14 membered heterocycloalkyl, C M 4 ary l-Ci- 6 alkyl-, C3-14 cycloalky 1- Ci- d alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R h2 and R l3 is independently selected from H, Ci-s alkyl, Ci ⁇ haloalkyl, C2-6 alkenyl, €2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaiyl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R j2 and R* 2 is independently selected from OH, Cj-s alkoxy, and Ci-ehaloalkoxy; or any R j2 and R k2 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alkyl and C 1-6 haloalkyl;
  • R F , and R G is independently selected from D, halo, oxo, Ci-b alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, € 6 - ⁇ 4 aryl, C3-1 cycloalkyd, 5-14 membered heteroaryl, 4-14 membered heterocycloalky 1, C&.14 ary l-Ci-6 alkyl-, C3-14 cycloalky 1-Cw alkyl-, (5-14 membered heteroaryl)-Ci -f, alkyl-, (4-14 membered heterocycloalkyi)-Ci -f, alkyl-, CN,
  • R B , R c , R E , R F , and R & are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R H substituents; each R a+ , R c4 , and R d4 is independently selected from H, Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heieroaryl, 4-14 membered heterocycloalkyl, Ce-w aryl-C -6 alkyl-, Cs-w eyeloalkyl,
  • each R M is independently selected from H, Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&-14 aryl, C3-14 cycloalkyl, 5-14 membered heieroaryl, 4-14 membered
  • heterocycloalkyl Ce-n ary I-C1- & alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the C -e alkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heieroaryl, 4-14 membered heterocycloalkyl, Cs-w aryl-Ci-e alkyl-, CVw cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.
  • each R e4 is independently selected from H, OH, CN, Ci-e alkyl, Ci ⁇ alkoxy, Ci-e haloalkyl, Ci-ghaloalkoxy, C2-6 alkenyl, €2-5 alkynyl, C G-M aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u axyl-Ci-e alkyl-, C3-14 cycloalkyl- Ci- d alkyl-, (5-14 membered heteroary r l)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alky 1-;
  • each R f4 and R s‘! is independently selected from H, Ci-e alkyl, Ci-ealkoxy, Ci-e haloalkyl, Ci-ehaloalkoxy, C2-6 alkeny l, C2-6 alkynyl, Ce-w aiyl, C3- W cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary!-Cs-e alkyl-, Cs-w cycloalkyi- Ci- 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-Ci. & alkyd-;
  • each R h4 and R' 4 is independently selected from H, C -b alkyl, C -b haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C f .-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w aryi-Ci-e alkyl-, C -i+ cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloaikyl)-Ci-6 alkyl-;
  • each R Jd and R k4 is independently selected from OH, C -s alkoxy, and C i-ehaloalkoxy; or, any R j4 and R k4 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alkyl and Ci- 6 haloalkyl; each R H is independently selected from D, halo, oxo, Ci- 6 alkyl, Cw haloalkyl, C 2-6 alkenyl, C2-6 alkynyi, Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-e alkyl-, C3- 1 cycloalky l-Ci-b alkyl-, (5-14 membered heteroaryl)-C
  • heterocycloalkyl Ce-w aryl-Ci- 6 alkyl-, C3-i4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-C 1.6 alkyl- of R H are each optionally substituted with 1, 2, 3, or 4 independently selected R : substituents;
  • each R a ⁇ R c5 , and R db is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C 2-f, alkynyi, Ce-w aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i aiyl-Ci-6 alkyl-, Cs- H cycloalkyi-Ci-e alkyl-, (5-14 membered heteroatyl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, wherein the C1.6 alkyl, C 2-6 alkenyl, C2-6 alkynyi, Ce-w aryl, Ci- K cycloalkyl, 5-14 membered heteroaryd, 4-14 membered heterocycloalkyl, Cs-w aryl-Ci ⁇ alkyl
  • R cS and R d5 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1 , 2, 3, or 4 independently selected R 1 substituents;
  • each R b5 is independently selected from H, C - 6 alkyl, Cue haloalkyl, C 2-6 alkenyl, C2-6 alkynyi, C &-J 4 aryl, C B-U cycloalkyl, 5-14 membered heteroaryl, 4- 14 membered heterocycloalkyl, Ce-u aryl-Ci ⁇ alkyl-, Cs-ir cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the CM alkyl, C2-6 alkenyl, C 2-6 alkymyl, C &-14 aryl, €3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Cw alkyl-, C 3-14 cycloalkyl-C
  • each R e5 is independently selected from H, OH, CN, CM alkyl, Ci-s alkoxy, Ci- & haloalkyl, Ci-ehaioalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce- aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-e alkyl-, C3-1 cycloalky 1- C -e alkyl-, (5-14 membered heteroaryl)-C ]-6 alkyl-, and (4-14 membered heterocycloalkyi)-C - 6 alkyl-;
  • each R e and R is independently selected from H, Cue alkyl, Ci-e alkoxy, Ci- & haloalkyl, C -ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryi, C3- M cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u ary l-Ci- 6 alkyl-, C3..14 cycloalky 1- C i-6 alkyl-, (5-14 membered heteroaryl)-C i-s alkyl-, and (4-14 membered heterocycloalkyl)-C i- 6 alkyl-;
  • each R h5 and R l5 is independently selected from H, C - 6 alkyl, haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryd, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C 1.5 alkyl-, C3-1 cycloalky l-Ci-b alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl-, and (4-14 membered heterocyeloaikyi)-C i-6 alkyl-;
  • each R Jd and R k5 is independently selected from OH, Ci-e alkoxy, and Ci-ehaloalkoxy; or, any R j5 and R ⁇ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalky 1 group optionally substituted with 1, 2, 3, or 4 substituents independently selected from CM alkyl and Ci- 6 haloalkyl;
  • each R 1 is independently selected from 13, halo, oxo, CM alkyl, CM haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C &.14 aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u ary I-C 1 -& alkyl-, C 3-14 cycloalkyl-Cw alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, CN, NO2, OR ao , SR a6 , NHOR 85 , C(0)R b6 , C(0)NR c6 R d6 , C(0)NR c6 (QR afr ), C(0)0R 36 , OC(Q)R b6 ,
  • heterocycloalkyl C M * aiyl-C -6 alkyl-, C3-14 cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryd)-C 1-6 alkyl-, and (4-14 membered heteroeyeloaikyl)-C -s alkyl- of R 1 are each optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R 3b , R c6 , and R d6 is independently selected from H, C - 6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C M * ar I-C1- & alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, wherein the C -e alkyl, C2-6 alkenyl, C2-6 alkynyl, C&.34 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cs-w aryi-C -e al
  • R c6 and R df> attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with i, 2, 3, or 4 independently selected R J substituents;
  • each R b6 is independently selected from H, Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce- aryd, C 3-i 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce- aryl-C 1.5 alkyl-, C3-14 cycloalky I-C1-6 alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl-, and (4-14 membered heterocyeloalkyl)-Ci-s alkyl-, wherein the Ci-s alkyl, €2-5 alkenyl, C 2 « alkynyl, C&-14 aryd, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C * aryl-Ci-e alkyl-, C 3 -u cycioalkyl-Ci-s alkyl-, (5-14 membered heteroaryi)-Ci- 6 alkyl-, and (4-14 membered heterocycloaikyi) ⁇ C [-6 alkyl- of R 00 are each optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R 86 is independently selected from H, OH, CN, Cj- 6 alkyl, Ci-e alkoxy, Cw haloalkyl, Ci-ehaloalkoxy, C 2.6 alkenyl, C 2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroasyl, 4-14 membered heterocycloalkyl, CM* ary l-Ci-6 alkyl-, C 3-i 4 cycloalky 1- Ci- 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloaiky ⁇ ) ⁇ Ci- 6 alkyl-;
  • each R fb and R g5 is independently selected from H, Ci- 6 alkyl, C -e alkoxy, Ci-e haloalkyl, Ci-ghaloalkoxy, C 2-6 alkenyl, C 2 « alkynyl, Ce-n aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-e alkyl-, C3-14 cycloalkyl- Ci- 6 alkyl-, (5-14 membered heteroaiyli-Ci-g alkyl-, and (4-14 membered heterocycloalkyil-C - 6 alkyl-; each R ho and R l5 is independently selected from H, C aikyi, C haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl,
  • each R j6 and R K6 is independently selected from OH, C -salkoxy, and Ci-shaloalkoxy; or, any R j6 and R kf> attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C alkyl and C M haloalkyl;
  • each R J is independently selected from D, halo, oxo, C M alkyl, C M haloalkyl, C M alkenyl, C M alkynyl, C &-K aryl, C-t-u cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w aryl-C M alkyl-, C - cycloalkyl-C -e alkyl-, (5-14 membered
  • heteroaiyl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R J are each optionally substituted with 1 , 2, 3, or 4 independently selected R substituents;
  • each R a ', R c/ , and R d/ is independently selected from H, C M alkyl, C M haloalkyl, C M alkenyl, C 2 -s alkynyl, C&-14 aryd, C 3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C M alkyl-, €3-14 cycloalkyl-C M alkyl-, (5-14 membered
  • R a/ , R c ', and R d ' are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents; or any R c/ and R d ' attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a
  • heterocycloalkyl CX-w aryl-Cs- 6 alkyl-, Cs-w eyeloalkyi-Ci-e alkyl-, (5-14 membered heteroaiyl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, wherein the C1.6 alkyl, C2-6 alkenyl, C2-6 alkynyl, CV 14 aryl, Ci- K cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C -e alkyl-, CS- M cycloalky l-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heierocycloalkyl)-C ue alkyl- of R s? are each optionally substituted with 1 , 2, 3, or 4 independently selected R substituent
  • each R e ' is independently selected from H, OH, CN, Cue alkyl, C2-6 alkenyl, Ci-e alkoxy, Ci ⁇ haloalkyl, Cwhaloalkoxy, C2-6 alkynyl, C M * aryl, Cs-wcycloalkyl, 5-14 membered heteroaryi, and 4-14 membered heterocycloalkyl;
  • each R ⁇ and R s ' is independently selected from H, Ci-e alkyl, C [-6 alkoxy, Ci- & haloalkyl, C -ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryi, C3- H cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 ar l-Ci-6 alkyl-, C3..14 cycloalky 1- C i-6 alkyl-, (5-14 membered heteroaryl)-Ci-s alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R h7 and R 1 ' is independently selected from H, C - 6 alkyl, haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryd, C3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Ce- aryl-C 1 -5 alkyl-, C3-14 cycloalky l-Ci-6 alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl-, and (4-14 membered heterocycloalkyi)-Ci-s alkyl-;
  • each R J ' and R K/ is independently selected from OH, Ci- & alkoxy, and Ci-ehaloalkoxy; or, any R j7 and R k ' attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalky 1 group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alkyl and C 1.6 haloalkyl;
  • each R K is independently selected from H, D, OH, halo, oxo, CN, C(0)OH, NH 2,
  • any heteroaryi group of any of the above-recited substituents optionally comprises an N-oxide on any ring-forming nitrogen
  • X is N
  • R 1 is selected from H, CVe alkyl, C2-6 alkenyl, C2-6 alkynyl, and Cw haloalkyl
  • R 2 is selected from H, D, halo, Ci-s alkyl, Ci-s haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce- i4 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C C-M aryl-Ci-6 alkyl-, CVw cyctoalkyl-Ci-e alkyl-, (5-14 membered heteroaryi) ⁇ Ci-6 alkyl-, (4-14 membered heterocycloalky 1)-Ci. 5 alkyl-, CN, N0 2 , OK" ' . SR w M IOR" . C(0)R b2 ,
  • heterocycloalky 1 C M * aiy r i-C i-b alkyl-, C3-14 cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl- of R 2 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R c substituents;
  • Cy 1 is C W 4 aryl, C J-M cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the C S-M aryl, C 3-i4 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R 11 or R M substituents;
  • Cy 2 is C&-14 aryl, C 3-i4 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalky 1, wherein the C5-14 aryl, C 3-] 4 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R r substituents;
  • each R 32 , R c2 , and R d2 is independently selected from H, Ci-b alkyl, Ci-b haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C M * ary I-C1- & alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, wherein the C -e alkyl, C2-6 alkenyl, C2- & alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CX-w aryl-Ci-e
  • R 3 , R c2 , and R d2 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R & substituents; or any R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R° substituents;
  • each R b2 is independently selected from H, Cue alkyl. Cue haloalky!, C2-6 alkenyl, C2-6 aikynyl, Ce-u aryl, C3- H cycioalkyi, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl C w ar I-C1- & alkyl-, C3-14 cycloalkyl-Cw alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Cj-e alkyl, C2-6 alkenyl, C2-6 aikynyl, C&.34 aryl, C3-1 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-H aryl-Ci-e alkyl-, CVw cyctoalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C]- 6 alkyl-, and (4-14 membered heterocy cloalkyl)-Ci- 6 alkyl- of R b2 are each optionally substituted with 1 , 2, 3, 4, 5, 6, 7, or 8 independently
  • each R 12 and R g2 is independently selected from H, Ci-e alkyl, Cue haloalkyl, Ci-e alkoxy, Ci. & haloalkyl, Cj-shaloalkoxy, C2-6 alkenyl, C2-6 aikynyl, Cs-ir aryl, Csur cycloalkyl, 5-14 membered heteroaiyl, 4-14 membered heterocycloalkyl, C S-H aryl-C 1-6 alkyl-, C3- 14 cycloalkyl-C 1-6 alk l-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl-;
  • each R 12 and R i is independently selected from H, Cj-e alkyl, Cj-e haloalkyl, C2-6 alkenyl, C2-6 aikynyl, C&-14 aryd, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C i-e alkyl-, C 3 -i 4 cycloalkyl-Cj- 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl-;
  • each R J and R K is independently selected from OH, C3-6 alkoxy, and Ci-ghaloalkoxy; or any R' 2 and R K attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Cj- 6 alkyl and Cj- 6 haloalkyl;
  • each R c , R E , R M , R ⁇ and R° is independently selected from D, halo, oxo, C-- 6 alkyl, Ci-e haloalkyl, C2-6 alkenyl, C2-6 aikynyl, CS- M aryd, C3- 14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-n ar l-C] - 6 alkyl-, Cs-ircycioalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C i- 6 alkyl-, (4-14 membered heterocy cloalkyl)-C [- 6 alkyl-, CN,
  • R c , R E , R M , R " , and R° are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R h substituents;
  • each R a+ , R c4 , and R d4 is independently selected from H, Cj- 6 alkyl, Cj- 6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C&-14 aryl, C3-u cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ar l-Ci-6 alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyi)-Cs- 6 alkyl-, wherein the Cj- 6 alkyl, C2-6 alkenyl, C2-6 alkynyl, €5-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C -r ary 1-Cw alkyl-
  • each R b4 is independently selected from H, Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C 2 « alkynyl, C&-J4 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4- 14 membered
  • heierocycloalkyi Ce-14 ary' 1-C 1-6 alkyl-, Ca-i+ cycloalkyl-Cj-e alkyl-, (5-14 membered heteroary l)-Cj- 6 alkyl-, and (4-14 membered heterocycloalky l)-Ci- 6 alkyl-, w'herein the Cj- 6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C&-14 aryl, Cs-i+ cyeloalkyi, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CS- M ar l-Cw alkyl-, C3-14 cycloalky 1-C 1-6 alkyl-, (5-14 membered heteroaryl)-Cj-6 alkyl-, and (4-14 membered heterocycloalkyl)-Cj-6 alkyl- of R b4 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently
  • haloa3koxy C2-6 alkenyl, C2-6 alkynyl, Ce-w aiyl, C3- W cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, € 6 - aryl-C - 6 alkyl-, Cs-u eyeloalkyi- Ci- 6 alkyl-, (5-14 membered heteroaryl) -C1-6 alkyl-, and (4-14 membered heterocycloalky 1)-Ci. & alkyl-;
  • each R f4 and R g4 is independently selected from H, CM alkyl, Ci-e alkoxy, C haloalkyl, C -ehaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, (M-M aryl, C 3-14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CM 4 ary l-Ci- 6 alkyl-, C 3 -1 4 cycloalky 1- CM alkyl-, (5-14 membered heteroaryl)-C alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R M and R 14 is independently selected from H, CM alkyl, CM haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci.6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-;
  • each R j4 and R K4 is independently selected from OH, C -s alkoxy, and Ci-shaloalkoxy; or, any R J+ and R k4 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alkyl and C M haloalkyl;
  • each R H is independently selected from D, halo, oxo, CM alkyl, CM haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C & -K aryl, C-t-u cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary l-Ci-6 alkyl-, C3-14 eyeloalkyl-Cw alkyl-, (5-14 membered heteroaryl)-C ] .s alkyl-, (4-14 membered heterocycloalky l)-Ci-6 alky!-, CN, NO2, OR 3 , SR ®5 ,
  • CM alkyl CM alkenyl, C2-6 alkynyl, Ce-w aryl, C3- H cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl C 6 -i4 aryl-C M alkyl-, C3-i4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaiyl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1 ⁇ 2 alkyl- of R h are each optionally substituted with 1 , 2, 3, or 4 independently selected R 1 substituents;
  • each R 35 , R° 5 , and R d5 is independently selected from H, CM alkyl, CM haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ci.-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary i-Ci-e alkyl-, Cj-i + cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Cj-6 aikyi, C‘ alkenyl, C2-6 alkyny!, C &-K aryl, €3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cg-n ar l-Cw alkyl-
  • R c5 and R ds attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R : substituents;
  • each R to is independently selected from H, Cj-g alky l, C2-6 alkenyl, C2-6 alkynyl, Cg- 14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cg-w aryl- Ci- 6 alkyl-, Cs-u cycloalkyl-Ci-g alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, wherein the Ci-g alkyl, €2-5 alkenyl, C2-6 alkynyl, Cg.
  • each R e is independently selected from H, OH, CN, Ci-e alkyl, Ci-e alkoxy , Ci-g haloalkyl, Cj-ghaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Cg-u aryl, Ca-s cycloalkyl, 5-14 membered heteroaiyl, 4-14 membered heterocycloalkyl, Cg-14 aryl-Ci- 6 alkyl-, C3..14 cycloalky 1- C [-6 alkyl-, (5-14 membered he teroaiyl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R ft and R 83 is independently selected from H, Ci-g alkyl, Ci- 6 alkoxy, Ci-g haloalkyl, Ci-ghaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ca-u aryd, C3-i4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalky 1, Cg.44 aryl-Ci-g alkyl-, C3-14 cycloalky 1- Ci- f, alkyl-, (5-14 membered heteroaryl) -Ci-g alkyl-, and (4-14 membered heterocycloalkyl)-Cj- 6 alkyl-;
  • each R to and R' 5 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalky l, C2-6 alkenyl, C 2-6 alkynyl, Cg-k aryl, C-t-u cycloalkyl, 5-14 membered heteroaiyl, 4-14 membered heterocycloalkyl, Ce-w ary l-Ci-6 alkyl-, C3-14 cycloalkyl-Cw alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-C ] - 6 alkyl-;
  • each R ⁇ ' 5 and R ki is independently selected from OH, Cj-g alkoxy, and Ci-ghaloalkoxy; or, any R j5 and R k? ' attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C - 6 alkyl and C - 6 haloalkyl; each R 1 is independently selected from D, halo, oxo, C .-s alkyl, C .-s haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C B-H cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalkyi-Ci-e alkyl-, (5-14
  • heterocycloalkyl Ce-u aryl-C i-e alkyl-, C B -i 4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-C 1.6 alkyl- of R 1 are each optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R 86 , R cf> , and R d6 is independently selected from H, C -b alkyl, C -b haloalkyl, C2-6 alkenyl, C 2- e alkynyl, C ⁇ 5-i 4 aryl, C3-1 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 aryl-C -e alkyd-, Cs-w cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, wherein the Ci-e alkyl, C 2-& alkenyl, C 2-& alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C
  • each R fc5 is independently selected from H, Cue alkyl. Cue haloalkyl, C 2-6 alkenyl, C 2-& alkynyl, C &-14 aryl, € 3-14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce-u aryl-Ci-e alkyl-, € 3-14 cycloalkyl-Ci- 6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalky 1)-C R, alkyl-, wherein the CM alkyl, C 2 -e alkenyl, C 2 -e alkynyl, C &-J 4 aryl, C J-M cycloalky 3, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C -e alkyl-, C 3-i 4 cycloalkyl-C M alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R b6 are each optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R e6 is independently selected from H, OH, CN, C M alkyl, C .-s alkoxy, Ci- 6 haloalkyl, C M haloalkoxy, C2-6 alkenyl, C 2-& alkynyl, Ce-u aryl, C 3-i 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 aiyl-Ci- 6 alkyl-, C 3-i 4 cycloalkyl- Ci- f, alkyl-, (5-14 membered heteroaryl)-C ]-6 alkyl-, and (4-14 membered heterocycloalkyl)-C - 6 alkyl-;
  • each R ® and R g6 is independently selected from H, Cm, alkyl, Ci-ealkoxy, Ci- 6 haloalkyl, Ci- 6 haloalkoxy, C2-6 alkenyl, C 2-6 alkynyl, C K aryl, C 3-i 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C M 4 aryl-C alkyl-, C 3-i 4 cycloalky 1- C -6 alkyl-, (5-14 membered heteroaryl)-C alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R h6 and R 5 is independently selected from H, C alkyl, C M haloalkyl, C 2.6 alkenyl, C M alkynyl, Ce-w aryl, Cj-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C 1 -5 alkyl-, C 3-14 cycloalky l-Ci-6 alkyl-, (5-14 membered heteroar l)-Ci-6 alkyl-, and (4-14 membered keterocycloalkyl)-C M alkyl-;
  • each R Jf> and R k5 is independently selected from OH, Ci-e alkoxy, and C -ehaloalkoxy; or, any R
  • each R J is independently selected from D, halo, oxo.
  • heterocycloalkyl, Ce-ir aryl-Ci- 6 alkyl-, CN-u cycloalkyi-Ci-e alkyl-, (5-14 membered heteroaryl)-C]-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R J are each optionally substituted with 1 , 2, 3, or 4 independently selected R substituents;
  • each R a/ , R 0 ', and R d7 is independently selected from H, C i-s alkyl, C i-s haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C&-14 aryl, C 3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C i-e alkyl-, C3-i 4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocy cloalky 1)-C R> alkyl- wherein the Ci-e alkyl, C 2-6 alkenyl, C 2-f, alkynyl, Ce-w aryl, C 3-i 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C
  • each R b/ is independently selected from H, Cj- 6 alkyl, Cj- 6 haloalkyl, C 2 -s alkenyl, C 2 -6 alkynyl, C &.14 aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl C M ary I-C1- & alkyl-, C 3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocy cloalkyl)-Ci-6 alkyl-, wherein the Cj-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C &.14 aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cs-w aryi-Cj- 6 alkyl-, CVw cy cloalky 1-C i-s alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1.6 alkyl- of R b? are each optionally substituted with 1 , 2, 3, or 4 independently selected R substitu
  • each R e ' is independently selected from H, OH, CN, Ci-e alkyl, C 2 _6 alkenyl, C 5 -6 alkoxy, Ci-b haloalkyl, Cwhaloalkoxy, C2-6 alkynyl, Ce-w aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl;
  • each R f/ and R g? is independently selected from H, C .-s alkyl, Ci « alkoxy, Ci-e haloalkyl, Cj-ehaloalkoxy, C2-6 alkenyl, C 2- e alkynyl, C &-J 4 aryl, Cji-u cy cloalkyi, 5-14 membered heteroary l, 4-14 membered heterocycloalkyl, C M 4 ary' i-C 1-6 alkyl-, C 3-i 4 cyc!oalky 1- C i- 6 alkyl-, (5-14 membered he teroarydi-Ci- f , alky!-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-;
  • each R h/ and R 1 ' is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C 2 .6 alkenyl, C 2- 6 alkynyl, Ce-w aryl, €3-14 ey cloalkyi, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-ir aiyl-Ci-6 alkyl-, Cs-u cycloalky!-Ci-e alkyl-, (5-14 membered heteroaryd)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C i-6 alkyl-; each R J ' and R K/ is independently selected from OH, Ci-ealkoxy, and Ci ⁇ haloalkoxy; or, any R J / and R k ' attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-mem bered heterocycloalkyl group optionally substitute
  • each R K is independently selected from H, D, OH, halo, oxo, CN, C(0)QH, NH 2 ,
  • any heteroaryl group of any of the above-recited substituents optionally comprises an N -oxide on any ring-forming nitrogen.
  • X is N
  • R 1 is selected from H, Ci-b alkyl, C2-6 alkenyl, €2-6 alkynyl, and Ci- 6 haloalkyl;
  • R 2 is selected from H, 13, halo, Ci-s alkyl, Ci-s haloalkyl, C 2- e alkenyl, C2-6 alkynyl, Cs- 14 and, C3.14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-r aryl-Ci- 6 alkyl-, C3-14 cycloalkyl-C ue alkyl-, (5-14 membered heteroaiyl)-Ci-6 alkyl-, (4-14 membered heterocycloalky l)-C -6 alkyl-, CN, N0 2 , OR az , SR 32 , NHOR a2 , C(0)R b3 ,
  • heterocycloalkyl, Ce- aryd-C 1.5 alkyl-, C3-14 cycloalky l-Ci-e alkyl-, (5-14 membered heteroaryd)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C ue alkyl- of R 2 are each optionally substituted with 1 , 2, 3, 4, 5, 6, 7, or 8 independently selected R c substituents;
  • Cy 1 is Ce- 14 aryl, C3-14 cycloalkyl, or 5-14 membered heteroaryl, wherein the C C-M aryl, C3-14 cycloalkyl, or 5-14 membered heteroaryd is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R or R M substituents;
  • Cy 2 is C M * aryl, C3-14 cycloalkyl, 5-14 membered heteroaryd, or 4-14 membered heterocycloalkyl, wherein the Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryd, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R b substituents;
  • each R”, R° 2 , and R tl2 is independently selected from H, C i-s alkyl, C i-s haloalkyl, C 2-6 alkenyl, C 2 -s alkynyl, C&-14 aryd, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-C i-e alkyl-, C3-i 4 cycloalkyl-Cj- 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-C R , alkyl-, wherein the C M alkyl, C2-6 alkenyl, C 2-6 alkynyl, Ci.-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyi, Cs-u aryl-Ci-
  • R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyi group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyi group is optionally substituted with 1 , 2, 3, or 4 independently selected R ⁇ 1 substituents;
  • each R b2 is independently selected from H, Cj- 6 alkyl, Cj- 6 haloalkyl, C 2.& alkenyl, C 2-& alkynyl, Ci.-n aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • each R is independently selected from H, OH, CN, C.-s alkyl, C.-s alkoxy, Ci- 6 haloalkyl, Cj-ehaloalkoxy, C2-6 alkenyl, C 2-& alkynyl, Ca-u aryd, Ch-w eye
  • each R c and R g2 is independently selected from H, Ci-e alkyl, Cw, haloalkyl, Cj- 6 alkoxy, Ci ⁇ aloalkyl, Cj-ehaloalkoxy, C2-6 alkenyl, C 2-6 alkynyl, CS- M aryd, Cs-wcycloalkyl, 5-14 membered heteroary l, 4-14 membered heterocycloalkyi, C M * aryl-C 1-6 alkyl-, C3 -14 eycloalkyd-C]- 6 alkyl-, (5-14 membered heteroaryd)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-: each R h2 and R l3 is independently selected from H, Ci-s aikyi, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-14
  • each R j2 and R* 2 is independently selected from OH, C -s alkoxy, and Ci-shaloalkoxy; or any R j2 and R k2 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci- 6 alkyl and C 1-6 haloalkyl; each R c , R E , R M , R r , and R° is independently selected from D, halo, oxo, Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C 6- H aryl, C3-14 cyctoalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C&04 ary l-Ci-s alkyl-, Cs-ir cycloalkyi-C
  • R c , R b , R M , R r , and R u are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R H substituents;
  • each R a4 , R c4 , and R d4 is independently selected from H, Ci-e alkyl, Ci- 6 haloalkyl, C 2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce- aryl-C 1.5 alkyl-, C3-14 cycloalky I-C1-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1-6 alkyl-, wherein the Ci-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ce-u aryi, Cs-u cycloalkyi, 5-14 membered heteroaiyd, 4-14 membered heterocycloalkyl, C -u aryl-Ci-e alkyl-, C3-
  • heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R H substituents;
  • each R b4 is independently selected from H, C alkyl, C M haloaikyl, C2-6 alken l, C2.6 alkynyl, Ca-u aryl, C 3-i 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Ce-ir aryd-Ci-e alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryd)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-C alkyl-, wherein the C M alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, C 3-i 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cs-w ary 1-C M alkyl-, C3-14 cycloalky l-Ci-6 alkyl-, (5-14 membered heteroaryl)-C 1-6 alkyl-, and (4-14 membered heterocycloaikyi)-Ci-6 alkyl- of R D4 are each optionally substituted with 1 , 2, 3, 4, 5, 6, 7, or 8 independently selected R H substituents; each R ®
  • each R f4 and R* 4 is independently selected from H, C M , alkyl, C M alkoxy, Ci-6 haloaikyl, Ci-ehaloalkoxj', C2-6 alkenyl, C2-6 alkynyl, Ce- aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalky 1, Ce-i4 aryd-C M alkyl-, C3-14 cycloalky 1- Cs-6 alkyl-, (5-14 membered heteroaiyl) -C 1-5 alkyl-, and (4-14 membered heterocycloalkyl)-C ] - 6 alkyl-;
  • each R 1 * 4 and R l4 is independently selected from H, Ci-g alkyl.
  • C haloaikyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaiyi, 4-14 membered heterocycloalkyl, Ce-w ary l-Ci-6 alkyl-, C3-14 cycloalkyl-Cw alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyi-, and (4-14 membered heterocycioalkyi)-Cs-6 alkyl-;
  • each R ⁇ ' 4 and R k4 is independently selected from OH, Ci-ealkoxy, and Ci-ehaloalkoxy ; or, any R j+ and R k4 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C M alkyl and C M haloaikyl;
  • each R H is independently selected from D, halo, oxo, C M alkyl, C M haloaikyl, C2-6 alkenyl, C2-6 alkynyl, C&-14 aryl, C3..1+ cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryd-C 1-6 alkyl-, C 3-i 4 cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, (4-14 membered heterocycloalky 1)-C M alkyl-, CN, NO2, OR 85 , SR 85 , NHQR a5 , C(0)R b5 , C(0)NR c5 R d5 , C(0)NR c5 (0R a5 ), C(0)0R a5 , 0C(0)R b5 , 0C(0)NR c5 R d5 , NR
  • heterocycloalkyl C MA ary 1-Ci-e, alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R h are each optionally substituted with 1, 2, 3, or 4 independently selected R 1 substituents;
  • each R a5 , R° 5 , and R di is independently selected from H, C i-s alkyl, 61- 5 haloalkyl, C2-6 alkenyl, 62-5 alkynyl, 65-11 a d, 63-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C * aryl-6 -6 alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-6i-6 alkyl-, and (4-14 membered heterocycloalky 1) ⁇ 6 R> alkyl-, wherein the 61-6 alkyl 6 2 -s alkenyl, 62 « alkynyl, 6 5-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, 65-114 aryl-61-6 alkyl-, 63-1 cycioal
  • R 05 and R da attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R ! substituents;
  • each R to is independently selected from H, 61-5 alkyl, 6 2-6 alkenyl, 6 2-f! alkynyl, Ce-w ary l, 63-14 cycloalkyl, 5-14 membered heteroaiyl, 4-14 membered heterocycloalkyl, 65-14 aryl- Ci-6 alkyl-, C3-14 eyeloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-6i-5 alkyl-, and (4-14 membered heterocycloalkyl)-6i-6 alkyl- wherein the 1-5 alkyl, C 2-& alkenyl, C2-6 alkynyl, Ce ⁇ lt and, 63.14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloaikyl, 5-1 aryl-61-6 alkyl-, C3-14 cycloalkyl-6 ue alkyl-, (5-14 membered heteroar d)-Ci
  • each R e5 is independently selected from H, OH, 6N, 64-5 alkyl, Ci-ealkoxy, 61 -5 haloalkyl, 6i-6haioalkoxy, 62-5 alkenyl, 62-5 alkynyl, 65-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloaikyl, 65-14 aryl-6 i-e alkyl-, 63-14 cycloalkyl- 61-5 alkyl-, (5-14 membered heteroaiyll-Oi-g alkyl-, and (4-14 membered heterocycloalkyl)-6i- 5 alkyl-; each R f5 and R S3 is independently selected from H, Ci-e alkyl Ci-e alkoxy, Ci-e haloalkyl, C;i- f!
  • haloa3koxy C2-6 alkenyl, C2-6 alkynyl, Ce-w aiyl, C3- H cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, €b- aryl-C - 6 alkyl-, Cs-i cydoalkyi- Ci- 6 alkyl-, (5-14 membered heteroaryl) -C1-6 alkyl-, and (4-14 membered heterocycloalky 1)-Ci. & alkyl-;
  • each R 115 and R 1' is independently selected from H, C -g alkyl, C -g haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Cg-u aryl, C -u cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w aryl-Ci-g alkyl-, C -i+ cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-C 1.6 alkyl-;
  • each R Ji and R ’ ° is independently selected from OH, C .g alkoxy, and C i-ghaloalkoxy; or, any R j5 and R k? ' attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-e alky l and C -g haloalkyl;
  • each R 1 is independently selected from D, halo, oxo, C .-g alkyl, C .-g haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, Cj-w cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cg-u aryl-C 1.5 alkyl-, C3-1 cycloalky I-C1-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C [-6 alkyl-, CN, NO2, OR a6 ,
  • heterocycloalkyl Cg-u aryl-C i-g alkyl-, C 3 -i 4 cycloalkyl-C - 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky l)-C 1.6 alkyl- of R 1 are each optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R 86 , R cf> , and R d6 is independently selected from H, Cj-b alkyl, Ci-e haloalkyl, C2-6 alkenyl, €2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6 -i4 aryl-C -g alkyl-, C3- M cycloalky l-C -6 alkyl-, (5-14 membered heteroaryl)-Ci.
  • R a6 , R c5 , and R d6 are each optionally substituted with 1, 2, 3, or 4 independently selected R' substituents;
  • R c6 and R d6 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R b6 is independently selected from H, Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce- aryd, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl Cg-w aryl-C 1.5 alkyl-, C 3-14 cycloalky l-Ci-g alkyl-, (5-14 membered heteroaryiVC i-g alky 1-, and (4-14 membered heterocyeloaikyi)-C[-s alkyl-, wherein the Ci-s alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-u aryd, C 3-i4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cg-u aryl-Ci-g alkyl-, C3- M cycloalk l-C -g alkyl-, (5-14 membered heteroaryl)-Ci- 6 alky 1-, and (4-14 membered heterocycloaikyi) ⁇ Ci-g alkyl- of R Bb are each optionally substituted with 1, 2, 3, or 4 independently selected R J substituents;
  • each R 66 is independently selected from H, OH, CN, Cj-g alkyl, Cfr-g alkoxy, Cw haloalkyl, Ci-ghaloalkoxy, C2-6 alkenyl, C2.6 alkynyl, Cg-ir aryl, C3- 14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C &-14 ar l-Ci- 6 alkyl-, C 3-14 cycloalkyl- Ci- 6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloaikyl) ⁇ Ci- 6 alkyl-;
  • each R fb and R g5 is independently selected from H, Cfr-g alkyl, Cs-g alkoxy, Ci-g haloalkyl, Ci-ghaloalkoxy, C2-6 alkenyl, €2-5 alkynyl, Cg-n aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalky 1, Cg-u and -Ci-g alkyl-, C 3-14 cycloallcyl- Ci-g alkyl-, (5-14 membered heteroaiyll-Ci- alkyl-, and (4-14 membered heterocycloalkyl)-C ].
  • each R hb and R 16 is independently selected from H, Ci-g aikyd, Ci-g haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Cg-j 4 aryd, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary I-C 1 -& alkyl-, C 3-14 cycloalkyl-Cw alkyl-, (5-14 membered heteroaryl)-C ] - 6 alkyl-, and (4-14 membered heterocycioalkyl)-Ci-g alkyl-;
  • each R j5 and R te is independently selected from OH, Ci-galkoxy, and C -ghaloalkoxy ; or, any R j6 and R k5 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1 , 2, 3, or 4 substituents independently selected from Cb-g aikyd and Ci-g haloalkyl;
  • each R 3 is independently selected from D, halo, oxo, C _g alkyl, C _g haloalkyl, Cb-g alkenyl, C ? _-g alkynyl, Cg-u aryd, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w ary l-Ci-6 alkyl-, Cj-i+ cycloalkyl-Cj-e alkyl-, (5-14 membered heteroaryl)-C ] ⁇ alkyl-, and (4-14 membered heterocycloa3kyl)-Ci-6 alkyl-, CN, NO2, OR a?
  • heterocycloalkyl, Ce-i4 aryl-Cj-6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocy cloalkyi)-Ci-6 alkyl- of R J are each optionally substituted with 1 , 2, 3, or 4 independently selected R substituents;
  • each R a/ , R c7 , and R d7 is independently selected from H, Ci- 6 alkyl Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&-1 aryl, C3..14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryd-C i-e alkyl-, C3-i cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-C 1.6 alkyl- wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl Ce-w aryl, C3-14 cycloalky 1, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-u aryl-Ci-e alkyl-, C3-14 cycl
  • each R b7 is independently selected from H, Cj- 6 alkyl, Cj- 6 haloalkyl C2-6 alkenyl, C2-6 alkynyl, C&-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl 4-14 membered
  • heterocycloalkyl Ce-w ary I-C1-& alkyl-, C3-14 cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, wherein the Cj-e alkyl, C 2-& alkenyl, C 2-& alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6 -H aryl-Ci-e alkyl-, CVw cycloalkyl-C i-e alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-C 1 ⁇ 2 alkyl- of R b7 are each optionally substituted with 1 , 2, 3, or 4 independently selected R substituents; each R
  • each R n and R g/ is independently selected from H, Ci-e alkyl, C M alkoxy, C haloalkyl, C -ghaloalkoxy, C2-6 alkenyl, C2-6 alkynyl, Ca-u aryl, C;-w eyeloalkyi, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cg-i 4 aryl-Ci-g alkyl-, C3-14 cycloalkyl- C M alkyl-, (5-14 membered heteroaryl) -C M alkyl-, and (4-14 membered heterocycloalkyI)-C - 6 alkyl-;
  • each R h? and R" is independently selected from H, C M alkyl, C haloalkyl, C2-6 alkenyl, C 2-6 alkynyl, Cg-k aryl, C-t-u cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cg-w ary 1-C M alkyl-, C -i + cycloalkyl-C -e alkyl-, (5-14 membered heteroaryl)-C ⁇ alkyl-, and (4-14 membered heterocycloalkyi)-Ci-6 alkyl-;
  • each R j7 and R k ' is independently selected from OH, C M alkoxy, and Ci-ghaloalkoxy; or, any R j ' and R k/ attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C M alkyl and Ci-g haloalkyl;
  • each R K is independently selected from H, D, OH, halo, oxo, CN, C(0)0H, NH 2 ,
  • SFs C -g alkyl, C alkoxy, Ci-ghaloaikoxy, CM haloalkyl, Ch-g alkenyl, CC-g alkynyl, Cg. 1 and, C3.14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cg-i 4 aryl-Ci- 6 alkyl-, CVw cycloalkyl-Ci-e alkyl-, (5-14 membered heteroard)-Ci-g alkyl-, and (4-14 membered heterocycloalky 1)-C M alkyl-; and
  • any heteroaryl group of any of the above-recited substituents optionally comprises an N-oxide on any ring-forming nitrogen.
  • the compound of Formula (I) is a compound of Formula (II):
  • the compound of Formula (I) is a compound of Formula (III):
  • Cy 1 is CS-M aryl, wherein the C M 4 aryl is optionally substituted with 1, 2, 3, or 4 independently selected R E substituents.
  • Cy 1 is C3-14 cycloalkyl, wherein the C3-14 cycloalkyl is optionally substituted with I, 2, 3, or 4 independently selected R E substituents.
  • Cy J is 5-14 membered heteroaryl, wherein the 5-14 membered heteroaryl is optionally substituted with 1 , 2, 3, or 4 independently selected R E substituents.
  • C ! is 4-14 membered heterocycloalkyl, wherein the 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R E substituents.
  • Cy 1 is C -10 aryl, wherein the Ce-io aryl is optionally substituted with 1, 2, 3, or 4 independently selected R E substituents.
  • Cy 1 is C3..7 cycloalkyl, wherein the C3-7 cycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R E substituents.
  • C ! is 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with 1, 2, 3, or 4 independently selected R : substituents.
  • Cy 1 is 4-10 membered heterocycloalkyl, wherein the 4-10 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R E substituents.
  • Cy 1 is phenyl or 5-10 membered heteroaryl, wherein the phenyl or 5-10 membered heteroaryl is optionally substituted with l, 2, 3, or 4 independently selected R E substituents.
  • Cy J is phenyl, optionally substituted with 1, 2, 3, or 4 independently selected R M substituents, or C7-14 aryl or 5-14 membered heteroaryl wherein the Cj-uaryl and 5-14 membered heteroaryl are optionally substituted with I, 2, 3, or 4 independently selected R r substituents, and
  • each R M is independently selected from D, halo, oxo, C - 6 alkyl, C - 6 haloalkyl, Ci-e alkoxy, C2-6 alkenyl, C2-6 alkynyl, C 4 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyi, 2-CN, 3-CN, N0 2 , OR 84 , SR a4 , NHOR a4 ,
  • Cy 1 is selected from phenyl, pyridinyl, furanyl, benzofuranyl, and pyrazolyl, each of which is optionally substituted with 1, 2, or 3 substituents selected from C - 3 alkyl, halo, CN, and C 1-3 alkoxy.
  • the optionally substituted Cy 1 is selected from cyanophenyl, cyanofluorophenyl, 2, 3-dihydro- l f-pyrrolo[2, 3, -6]pyridine, phenyl, methoxyphenyl, fluorophenyl, pyridinyl, methylfuranyi, benzofuranyl, and methyl-l/Z-pyrazolyl.
  • the optionally substituted Cy ! is selected from cyanophenyl, 2,3-dihydro-l//-pyrrolo[2,3,-h]pyridine, phenyl, methoxyphenyl, fluorophenyl, pyridinyl, methylfuranyi, benzofuranyl, and methyl- l//-pyrazolyl.
  • Cy 1 is selected from 2-cyanophenyl, 3 -cyanophenyl, 3-cyano-
  • the optionally substituted Cy 1 is selected from 2-cyanophenyl
  • the optionally substituted Cy ! is selected from 3-cyanophenyl and phenyl.
  • Cy 1 is 3-cyanophenyl.
  • Cy 2 is Cg-ir aryl, Cs- M cycloalkyi, 5-14 membered heteroaryl or 4-14 membered heterocycloalkyi wherein the CV-r arcl, C 4-14 cycloalkyl, 5-14 membered heteroaryl and 4-14 membered heterocycloalkyi are optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R b substituents.
  • Cy 2 is C S-H aryl, wherein the Ce-n aryl is optionally substituted with 1, 2, 3, or 4 independently selected R h substituents. In some embodiments, Cy 2 is C -u cycloalkyl, wherein the C3-14 cycloalkyl is optionally substituted with 1 , 2, 3, or 4 independently selected R " substituents.
  • Cy 2 is 5-14 membered heteroaryl, wherein the 5-14 membered heteroaiyl is optionally substituted with 1, 2, 3, or 4 independently selected R r substituents.
  • Cy 2 is 4-14 membered heterocycloalkyl, wherein the 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R F substituents.
  • Cy 2 is Cg-io aryl, wherein the Ce-io aryl is optionally substituted with I, 2, 3, or 4 independently selected R F substituents.
  • Cy 2 is C3-7 cycloaikyi, wherein the C3-7 cycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R f substituents.
  • Cy 2 is 5-10 membered heteroaryl, wherein the 5-10 membered heteroaryl is optionally substituted with 1, 2, 3, or 4 independently selected R F substituents.
  • Cy 2 is 4-10 membered heterocycloalkyl, wherein the 4-10 membered heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 independently selected R r substituents.
  • Cy 2 is selected from C cycloalkyl, phenyl, 5-10 membered heteroaryl, and 5-10 membered heterocycloalkyl;
  • the 5-10 membered heteroaiyl and 5-10 membered heterocycloalkyl each comprise one, two, or three nitrogen atoms as ring-forming heteroatoms, wherein one of the one or two nitrogen atoms is optionally an N-oxide, and wherein a ring-forming carbon atom is optionally substituted by oxo;
  • C3-6 cycloaikyi, phenyl, 5-10 membered heteroaryl, and 5-10 membered heterocycloalkyl are each optionally substituted with I, 2, or 3 substituents selected from C 1..3 alkyl, Ci alkyi-OH, halo, CM, C K; alkoxy, and C(0)NH 2
  • Cy 2 is selected from C cycloaikyi, phenyl, 5-10 membered heteroaiyl, and 5-10 membered heterocycloalkyl;
  • the 5-10 membered heteroaryl and 5-10 membered heterocycloalkyl each comprise one or two nitrogen atoms as ring-forming heteroatoms, where in one of the one or two nitrogen atoms is optionally an N-oxide, and wirerein a ring-forming carbon atom is optionally substituted by oxo;
  • C cycloaikyi, Ce-aryi, 5-10 membered heteroaiyl, and 5-10 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents selected from C 1-3 alkyl, halo, CN, C 1-3 alkoxy, and C(0)NH>; .
  • Cy 2 is selected from pyridinyl, tetrahydropyridinyl, piperidinyl, pvridine-N-oxide, oxo-dihydropyridinyl, phenyl, pyrazolo[l,5-a]pyridin-3-yl, pyrazolo[l,5-b]pyridazinyl, pyrazolyl, pyrimidinyl, quinolinyl, oxazolyl, 2,3-dihydro- [l,4]dioxino[2,3-b]pyridin-8-yl, and triazolyl each of which is optionally substituted with I,
  • Cy 2 is selected from pyridinyl, tetrah dropyridinyl, piperidinyl, pyridine-N-oxide, oxo-dihydropyridinyl, phenyl, pyrazolo[l,5-a]pyridin-3-yl, pyrazolo[l,5-b]pyridazinyl, pyrazolyl, pyrimidinyl, quinolinyl, oxazolyl, and 2,3-dihydro- [l,4]dioxino[2,3-b]pyridin-8-yl, each of which is optionally substituted with 1, 2, or 3 substituents selected from Ci- 3 alkyl, halo, CN, Ci- 3 alkoxy, and C(0)NH 2 .
  • Cy 2 is selected from pyridinyl, tetrahydropyridinyl, piperidinyl, pyridine-N-oxide, oxo-dihydropyridinyl, phenyl, pyrazolo
  • Cy 2 is cyclopropyl optionally substituted with 1, 2, or 3 substituents selected from Cu alkyl, halo, CN, C1-3 alkoxy, and C(0)NH 2 .
  • the optionally substituted Cy 2 is selected from 2,6- dimethy!pyridin-4-yl, pyridin-4-yl, 2-methylpyridin-4-yl, 1 -carbamoy 1-1, 2,3,6- tetrahydropyridin-4-yl, 1 -carbamoy lpiperidin-4-yl, 2-methoxypyridin-4-yl, 2-methoxy-6- methylpyridin-4-yl, 2,6-dimethylpyridin-4-yl-oxide, l-ethyl-6-oxo- l,6-dihydropyridin-3-yl, 3-methyipyridin-4 ⁇ yi, 3-fluoropyridin ⁇ 4-yl, 3-chloropyridin-4-yl, 3-methoxypyridin-4-yl, 3- cyanopyridin-4-yl, 4-carbamoylphenyl, pyrazolo[l,
  • the optionally substituted Cy 2 is selected from 2,6- dimethylpyridin-4-yl, pyridin-4-yl, 2-methylpyridin-4-yl, 1 -carbamoy 1-1 , 2,3,6- tetrahydropyridin-4-yl, 1 -carbamoy lpiperidin-4-yl, 2-methoxypyridin-4-yl, 2-methoxy -6- methylpyridin-4-yl, 2,6-dimethylpyridin-4-yl-l -oxide, l-ethyl-6-oxo-l,6-dihydropyridin-3-yl, 3-methylpyridin-4-yl, 3-f]uoropyridin-4-yl, 3-chloropyridin-4-yl, 3-methoxypyridin-4-yl, 3- cyanopyridin-4-yl, 4-carbamoylphenyl, pyrazolo[ l,5-
  • the optionally substituted Cy 2 is selected from 2,6- dimethy lpyridin-4-y 1, p ridin-4-y 1, 2-methylpyridin-4-y 1, 1 -carbamoyl- 1, 2,3,6- tetrahydropyridin-4-yl, l-carbamoylpiperidin-4-yl, 2-methoxypyridin-4-yl, 2,6- dimethy lpyridin-4-y 1- 1 -oxide, 1 -ethy 1-6-oxo- 1 ,6-dihydropyridin-3 -y 1, 3 -methy lpyridin-4-y 1, 3-fluoropyriditi-4-yl, 3-chloropyriditi-4-yl, 3-methoxypyridin-4-yl, 3-cyanopyridin-4-yl, 4- carbamoy lpheny 1, pyrazolo [ 1 ,5 -a jpy ridin-3 -
  • R ! is selected from H, D, Ci-b alkyl, Ci- 6 haloalkyl, C 2.6 alkenyl, C 2-6 alkynyl, C f .- r aryl, C 3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-w aryl-Ci-e alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, (4-14 membered heterocycloalky l)-Ci-6 alkyl-, OR ai , C(0)R b!
  • d alkyl- of R 1 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R B substituents.
  • R ! is selected from H, D, Ci-b alkyl, Cue haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C f .- + aryl, C 3-14 cycloalkyl, 5-8 membered heteroaryl, 4- 14 membered heterocycloalkyl, Ce-w aiyd-Ci-e alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-8 membered heteroaryl)- C -6 alkyl-, (4-14 membered heterocycioalkyl)-Ci-6 lkyl-, OR ai , C(0)R b l , C(0)NR c!
  • R 1 is selected from H, Ch-s alkyl, and 5-8 membered heteroaryl, wherein the 5-8 membered heteroaryl is optionally subsituted by 1 or 2 independently selected K B substituents.
  • R ! is H, Cj-e alkyl, or a 5-8 membered heteroaryl
  • 1 is H or Ci-e alkyl.
  • R ! is H or C 1-3 alkyl.
  • R ! is H, ethyl, or nicotinonitrile.
  • R 1 is H or ethyl.
  • R 1 is H.
  • R ! is 5-8 membered heteroary l which is optionally subsituted by 1 or 2 independently selected R B substituents.
  • R 1 is 5-8 membered heteroaryl.
  • R 1 is pyridyl which is optionally substituted by 1 or 2 R B substituents.
  • R 1 is pyridyl which is optionally substituted by cyano.
  • R 1 is nicotinonitrile
  • R ! is 3-cyanopyridyl
  • R 2 is selected from halo, Cs- 6 alkyl, Cj-5 haloalkyl, C2-0 alkenyl, C2-6 alkynyl, C&-14 aryl, C3..14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalky 1, CM* aiyl-C w, alkyl-, C3-14 cycloalkyl-Cj-e alkyl-, (5- 14 membered heteroaryl)-Ci-6 alkyl-, (4-14 membered heterocycloalk l)-Ci-6 alkyl-, CN, NO2, OR 32 , SR 82 ,
  • heterocycloalkyl Ce-w ary l-Ci-6 alkyl-, C3-14 cycloalkyl-Cw alkyl-, (5-14 membered heteroaryl)-C ] -6 alkyl-, and (4-14 membered heterocycIoalkyl)-C ] -6 alkyl- are each optionally substituted with I, 2, 3, 4, 5, 6, 7, or 8 independently selected R c substituents; and wherein the C -e alkyl is substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R c substituents.
  • R 2 is selected from Cs- 6 alkyl, C M 4 aryl, C ? ,-u cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Ce-i4 ary l-Ci-6 alkyl-, C3..14 cycloalky 1- C i-6 alkyl-, (5-14 membered heteroary l)-Ci-s alkyl-, (4-14 membered heterocycloalkyl)-Ci-6 alkyl-, C(0)R b2 , C(0)NR e2 R d2 , C(0)0R a2 , and NR c2 R d2 , wherein the C M4 aryl, C 3 -i 4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cw4 aryl-Ci- 6 alkyl-, C3-14 cycloalky 1-C alkyl-, (5-14
  • R 2 is selected from C S-M aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 4 aryl-Ci-6 alkyl-, C3-14 cycloalky 1-Cw alkyl-, (5-14 membered heteroaryl) -Cs- 6 alkyl-, (4-14 membered heterocycloalkyl)-C]- 6 alkyl-, C(0)R b3 , C(0)NR c2 R d2 , C(0)QR a2 , and ⁇ R- R ! .
  • R 2 is selected from Ce-u and, C 3-i4 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloaikyl, C 6-M aryl-Ci- 6 alkyl-, C3- W cycloalky 1-C 1-6 alkyl-, (5-14 membered heteroary 1)-C 1-6 alkyl-, and (4-14 membered heterocycloalkyll-Ci-e alkyl-, wherein the Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaiyl, 4-14 membered heterocycloaikyl, Ce-u aryl-C 1-6 alkyl-, C 3 -i 4 cycloalkyl-C - 6 alkyl-, (5-14 membered heteroary l)-Ci- 6 alkyl-, and (4-14 membered heterocycloalky 1)-C 1.6 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5
  • R 2 is selected from H, Ci-e alky l, C3-14 cycloalkyl, C 4aryl, 5- 14 membered heteroary!, 4-14 membered heterocycloalky 1, C H aryl-Ci- 6 alkyl-, C3-14 cycloalky 1-C 1-6 alkyl-, (5-14 membered heteroary l)-C]- 6 alkyl-, (4-14 membered
  • heterocycloalkyl -Ci- 6 alkyi-, NR c2 R d2 , C(0)R B2 , C(0)NR c2 R d2 , and C(0)0R a2 , wherein the Cj. 6 alkyl, C 3-i 4 cycloalkyl, C6-i4 aryl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloaikyl C 6 -i4 aiyd-Ci- 6 alkyl-, Cs-u cycloalkyl-Ci-e alkyl-, (5-14 membered heteroaryl)-C]-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl- are each optionally substituted with 1 , 2, or 3 independently selected R c substituents.
  • R 2 is selected from H, Ci-e alkyl, Ce- M aryi, C3-1 4 cycloalkyl, 5- 14 membered heteroaryl, 4-14 membered heterocycloalkyl, C G-M aiyl-Ci-e alkyl-, C S-M cycloalkyl-Ci-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, (4-14 membered
  • R 2 is selected from H, C -- 6 alky l, Ce- M aryl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C 6-M aryl-Ci- 6 alky!-, (5-14 membered heteroary l)-Ci- 6 alkyl-, (4-14 membered heterocycloalky l)-Ci- 6 alkyl-, NR c2 R d2 , C(0)R b2 , C(0)NR c2 R a2 , and C(G)OR a2 , wherein the Ci-e alkyl, Ce-n aryl, 5-14 membered heieroaryd, 4- 14 membered heterocycloalkyl, C G-M aryl -C I-G alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- are each optionally substituted
  • R 2 is selected from H, C - -6 alky l, Ce- M aryl, €3-54 cycloalkyl, 5- 14 membered heteroaryl, 4-14 membered heterocycloalkyl, aryl-C 1-6 alkyl-, C3.14 cycloalkyl-Ci- G alkyl-, (5-14 membered heteroary l)-C ]-6 alkyl-, (4-14 membered
  • R 2 is selected from H, C J .. G alkyl, C G-M aryl, C3-14 cycloalkyl, 5- 14 membered heteroaryl, 4-14 membered heterocycloalkyl, C G-M aryl-C - 6 alkyl-, C3-M cycloalkyl-Ci- 6 alkyl-, (5-14 membered heteroary l)-Ci- 6 alkyl-, (4-14 membered
  • heterocycloalkyl Ce- ary 1-C I -G alkyl-, C3- cycloalkyl-Cw alkyl-, (5-14 membered heteroary l)-C ]-6 alkyl-, and (4-14 membered heterocycioalkyi)-Cs- 6 alkyl- are each substituted with 1, 2, or 3 independently selected R '- substituents.
  • R' is selected from H, Ce-uaryl, 5-14 membered heteroaryl, C(0)R b2 , C(0)NR c2 R ® , and C(0)0R a2 , wherein the C o -u aryl and 5-14 membered heteroaryl are each optionally substituted wdth 1, 2, or 3 independently selected R c substituents.
  • R is selected from H, C.-s alkyl, phenyl, 5-6 membered heteroaryl, 4-10 membered heterocydoalkyi, Ce-io aryl-Ci-s alkyl-, (5-10 membered heteroaryl)-Ci- 6 alkyl-, (4-10 membered heterocycloalk I)-Cw alkyl-, NR c2 R d2 , C(0)R b2 , C(0)NR c2 R a2 , and C(0)OR a2 , wherein the C - 6 alkyl, phenyl, 5-6 membered heteroaryl, 4-10 membered heterocydoalkyi, Ce-io aryl-C -e alkyl-, (5-10 membered heteroaryl)-Ci- 6 alkyl-, and (4-10 membered heterocycloalkyl)-Ci..
  • R 6 alkyl- are each optionally substituted with 1 or 2 independently selected R c substituents.
  • R 2 is selected from H, phenyl, 5-6 membered heteroaryl, C(0)R b/ , C(0)NR c2 R a2 , and C(Q)OR a2 , wherein the phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 independently selected R c substituents.
  • R is selected from H, C(0)OEt, CONH 2 , and C(0)NHEt.
  • R 2 selected from phenyl and 5-6 membered heteroaryl, each of which is optionally substituted with C(0)OMe.
  • the optionally substituted R is selected from pyridinyhnethyl, hydroxy(phenyl)meth I, hydroxyethylamino(phenyl)ethyi, cyclohexyhnethyl, fluorobenzyl, hydroxy (fluoropheny I j methy 1, (me thy lpy ridiny I j methy L (fluoropy ridiny l)methy 1,
  • benzoisoxazolylmethyl (methylindazolyl)methyl, (hydro xyazetidinyl)methyl, benzoyl, phenylcyclopropyi, (cyano(phenyl)meihyl)amino, tetxahydrofiuanyl,
  • the optionally substituted R z is selected from pyridinyhnethyl, hydroxy (pheny l)methyl, hydroxy ethylamino(phenyl)ethyl, cyclohexyhnethyl, fluorobenzyl, hydroxy (fluoropheny l)m ethyl, (methylpyridinyi)methyl, (fluoropyridinyl)methyi,
  • R 2 is selected from pyridinyimethyl, hydroxy(phenyi)methyl, hydroxy ethylami:no(phe:nyl)ethyl, eyclohexyimethyl, fluorobenzyl,
  • R 2 is selected from pyridin-2-ylmethyl
  • R 2 is selected from pyridin-2-ylmethyl
  • R 2 is selected from pyridin-2-ylmethyl
  • R 32 is selected from H and Ci-s alkyl, wherein the C -5 alkyl is optionally substituted 1, 2, or 3 independently selected R 11 substituents.
  • R b2 is selected from H, Ci- 6 alkyl, Ce-w asyl, and 4- 14 membered heterocycloalkyl, wherein the C -e alkyl, Ce-u ary l, and 4-14 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 independently selected R° substituents.
  • R c2 and R d2 are each independently selected from H, Ci-b alkyl, 5-14 membered heteroaryl, and Ce-u ary l-C - 6 alkyl-, wherein the C -e alkyl, 5- 14 membered heteroaryl, and Ce-u ary l-Ci- 6 alkyl- are each optionally substituted with 1, 2, or 3 independently selected R° substituents.
  • each R° is indepedently selected from CN, OR a4 , and Ci-s alkyl, wherein the Ci- 6 alkyl is optionally substituted I, 2, or 3 independently selected R fl substituents.
  • each R c is independently selected from halo, Ci-b alkyl, Ce-u aryl, 5-14 membered heteroaryd, (4-14 membered keterocycloalkyl)-Ci- 6 alkyl-, OR 34 , C(0)0R a+ , and NR c4 R d4 , wherein the Ci- 6 alkyl, 5-14 membered heteroaryl, and (4-14 membered heterocycloalkyl)-Ci-6 alkyl- are optionally substituted with I, 2, or 3
  • each R '- is independently selected from halo, Ci-e alkyl, C 6 -i4 aryl, 5-14 membered heteroaryl, (4-14 membered heterocycloalkyl)-Ci- 6 alkyl-, OR 34 , C(0)0R a4 , and NR c4 R d4 , wherein the C M alkyl, 5-14 membered heteroaryl, and (4-14 membered heterocycloalky3)-Ci- 6 alkyl- are substituted with 1, 2, or 3 independently selected R ri substituents.
  • R* 4 is selected from H, C M alkyl, Ce-w aryl, and 5-14 membered heteroaryi.
  • each R c4 and R d4 are independently selected from H and C M alkyl, wherein the C M , alkyl is optionally substituted by I , 2, or 3 independently selected R' 1 substituents.
  • each R' 1 is independently selected from halo, oxo, C M alkyl, Cs-6 haloalkyi, OR 85 , C(0)GR a5 , and NR c5 S(0) 2 R b5 .
  • each R a' , and R c5 is selected from H and C M alkyl.
  • R to is selected from H and C M alkyl.
  • R 3 is selected from H, D, halo, oxo, C M alkyl, C M haloalkyi, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, Cs-w ar i-C alkyl-, CVw cycloalkyl-C M alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, (4-14 membered heterocycloalky l)-Ci-6 alkyl-, CN, NO2, GR aJ , SR 83 ,
  • heterocycloalkyl Ce-i4 aryd-C M alkyl-, C3-1 cycloalky 1-C alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalky 1)-C M alkyl- of R 3 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected R ! substituents.
  • R is selected from H, halo, C M alkyl, C M haloalkyi, C &-J 4 aryl, 5-14 membered heteroaryi, CN, and GR a;i , wherein the C M alkyl, Ce-uaryl, and 5-14 membered heteroaryi are each optionally substituted with 1, 2, or 3 independently selected substituents.
  • R’ is selected from H, C M alkyl, halo, CN, morpholinomethyl, 4-ethoxyphenyi, 2-hydroxyethoxy, and pyridinyl.
  • R J is selected from H, methyl, bromo, CN, morpholinomethyl, 4- ethoxyphenyl, 2 -hydroxy ethoxy, and pyridinyl.
  • X is CR 3 ; and R ! is H or Cj-e alkyl.
  • X is CR 3 ; and R ! is H or Ci- 3 alkyl.
  • X is CR 3 ;
  • R 1 is selected from H and Ci-e alkyl
  • R 2 is selected from H, D, Ce-u aiyl, 5-14 membered heteroaryi, C(0)R b2 ,
  • R 3 is selected from H, D, halo, Ci-b alkyl, Ci-b haloalkyl, Ce-u aryl, 5-14 membered heteroaryl, CN, and OR a3 , wherein the Ci- 6 alkyl, Ce-n aryl, and 5-14 membered heteroaryl of R 5 are each optionally substituted with 1, 2, 3, or 4 independently selected R° substituents;
  • Cy 1 is phenyl optionally substituted with 1 , 2, 3, or 4 independently selected R M substituents, or Cio-i4 aryl or 5-14 membered heteroaryi, wherein the Cio-u aryl and 5-14 membered heteroaryi of Cy 1 is optionally substituted with I, 2, 3, or 4 independently selected R E substituents;
  • Cy 2 is C&.14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi or 4-14 membered heterocycloalkyl, wherein the Cg-w aryl, Cso 4 cycloalkyl, 5- 14 membered heteroaryi and 4-14 membered heterocycloalkyl of Cy 2 are each optionally substituted with 1, 2, 3, or 4 independently selected R" substituents;
  • each R 32 , R c2 , R d2 , and R a3 is independently selected from H, Ci- 6 alkyl, C1 -6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C & .i 4 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, and 4-14 membered heterocycloalkyl, wherein the Cj- 6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cg-w aryl, C3-14 cycloalky l, 5-14 membered heteroaryi, and 4-14 membered heterocycloalkyl of R a2 , R c2 , R d2 , and R a3 are each optionally substituted with 1, 2, 3, or 4 independently selected R° substituents;
  • each R b2 is independently selected from Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ci.-n aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, and 4-14 membered heterocycloalkyl, wherein the Cj-e alkyl, C2-6 alkenyl, C2-6 alkynyl, Gs-rr aryl, Cs-n cycloaikyd, 5-14 membered heteroaryi, and 4-14 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R° substituents;
  • each R c , R [) , R E , R “ , and R G is independently selected from D, halo, oxo, Ci- 6 alk l, C i-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C3-i 4 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloaikyi, CN, NO2, OR 34 , SR ®4 , NHOR a4 , C(0)R b4 , C(0)NR c4 R d4 , C(0)OR a4 , OC(0)R b4 , 0C(0)NR c4 R d4 , ⁇ R !
  • each R a4 , R c4 , and R d4 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CVw aryl, C-t-u cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the Cm alkyl, C2-6 alkenyl, C2-6 alkynyl, Cs-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl of R a4 , R c4 , and R d4 are each optionally substituted with 1, 2, 3, or 4 independently selected R H substituents; each R b4 is independently selected from Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C&-14 aryl, €3-14
  • each R e4 is independently selected from H, OH, CN, C .-s alkyl, C .-s alkoxy, Ci- 6 haloalkyl, and C i-shaloalkoxyy
  • each R H is independently selected from D, halo, oxo, Ci- 6 alkyl, Ci-b haloalk l, C2-6 alkenyl, C2-6 alkynyl, C &-J 4 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CN, N0 2 ,
  • NR c5 S(G)2NR c5 R d5 wherein the Ci-6 alkyl, C2.6 alkenyl, C2.6 alkynyl, Ce-i4 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryd, 4-14 membered heterocycloalkyl, of R H are each optionally substituted with 1, 2, 3, or 4 independently selected R 1 substituents; each R 3 ' 5 , R c5 , and R d> is independently selected from H, Cj-b alkyl, Ci-e haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C -u cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the C i-s alkyl, C2-6 alkenyl, C2-6 alkynyl, Cs-w ary!, C 3- w cycloalkyl, 5
  • each R b5 is independently selected from Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ci.-w aryl, C 3 -i cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, -wherein the C -e alkyl, C 2-6 alkenyl, C2-6 alkynyl, C b-u aryl, C 3- w cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R 1 substituents;
  • each R 85 is independently selected from H, OH, CN, Ci-e alkyl, Ci-e alkoxy, Ci-e haloalkyl, and Ci-ehaloalkoxy;
  • each R 36 , R cf> , and R d6 is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, €2-6 alkynyl, Ce-w aryl, C J-M cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the CM alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-w aryl, C 3 -w cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl of R a6 , R CR , and R d6 are each optionally substituted with 1, 2, 3, or 4 independently selected R J substituents; each R b6 is independently selected from Ci « alkyl, Ci « haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C &-J 4 aryl, C 3-i
  • each R e6 is independently selected from H, OH, CN, C .-s alkyl, C .-s alkoxy, Ci- 6 haloalkyl, and C i-ehaloalkoxy;
  • each R 3 is independently selected from D, halo, oxo, C -e alkyl, C -e haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C w aryl, C3- cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CN, N0 2 , OR 37 , SR 37 , NHOR a? , C(0)R b7 , C(0)NR c7 R d7 , C(0)OR a7 ,
  • Ci-6 alkyl, C2.6 alkenyl, C2.6 alkynyi, €5-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryd, 4-14 membered heterocycloalkyl, of R H are each optionally substituted with 1, 2, 3, or 4 independently selected R K substituents;
  • each R a/ , R e ', and R d ' is independently selected from H, Ci- 6 alkyl, Ci- 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyi, Ce-i + aiyl, C3-14 cycloalkyl, 5-14 membered heteroaryd, and 4-14 membered heterocycloalkyl, wherein the Ci.
  • each R b ' is independently selected from Ci-e alkyl, Ci-e haloalkyl, C2-6 alkenyl, C2-6 alkynyi, Ce-u aryl, fb-ir cycloalkyl, 5-14 membered heteroaiyi, and 4-14 membered heterocycloalkyl, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyi, Gs-14 aryl, C 3-14 cycloalkyl, 5-14 membered heteroary l, and 4-14 membered heterocycloalkyl,
  • each R e7 is independently selected from H, OH, CN, Ci-e alkyl, Ci-e alkoxy, Ci- & haloalkyl, and Ci-shaloalkoxy;
  • each R K is independently selected from H, D, OH, halo, oxo, CN, C(0)0H, NH 2 , NO 2 , SF 5 , C I-6 alkyl, Ci-e alkoxy, C -ehaloalkoxy, C *- 6 haloalkyl, tb-s alkenyl, C 2-6 alkynyi, C &. 14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaiyi, 4-14 membered heterocycloalkyl; and wherein any heteroaryl group of any of the above-recited substituents optionally comprises an N-oxide on any ring-forming nitrogen.
  • X is CR 3 ;
  • R ! is selected from H and Ci- 6 alkyl
  • R 2 is selected from H, D, C f, -i4 ryl, 5-14 membered heteroaryl, C(0)R bi ,
  • R 3 is selected from H, D, halo, C - & alkyl, Ce-u aryl, 5-14 membered heteroaryd, CN, and OR 33 , wherein the Ci-e alkyl, Ce-w ar l, and 5-14 membered heteroaryd of R 3 are each optionally substituted with 1 , 2, 3, or 4 independently selected R D substituents;
  • Cy 1 is pheny l, optionally substituted with 1, 2, 3, or 4 independently selected R M substituents; or Cy 1 is Cio-u and or 5-14 membered heteroaryd, wherein the C IO-H and and 5- 14 membered heteroaryl of Cy 1 are each optionally substituted with 1, 2, 3, or 4
  • Cy z is Ce-u aryl, C B-M cycloalkyl, 5-14 membered heteroaryl or 4-14 membered heterocycloalkyl, wherein the Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl and 4-14 membered heterocycloalkyl of Cy 2 are each optionally substituted with 1, 2, 3, or 4 independently selected R' substituents;
  • each R 32 , R”, R di , and R a3 is independently selected from H, Ci- 6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-n aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the C M alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-war l, C3-14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl of R 32 , R c2 , R d2 , and R 33 are each optionally substituted with 1, 2, 3, or 4 independently selected R substituents;
  • each R b2 is independently selected from C alkyl, C2-6 alkenyl, C2-6 alkynyl, CM ⁇ » ary l, C3- ! 4 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C&.14 aryd, C3. 14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R° substituents;
  • each R c , R D , R E , R r , and R° is independently selected from D, halo, oxo, C M alkyl, C2-6 alkenyl C M alkynyl, Ce-u aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, CN, N0 2 , OR 3 , SR 34 , NHOR 34 , C(0)R b4 , C(Q)NR c4 R d4 ,
  • each R M is independently selected from D, halo, oxo, Ci- 6 alk l, C2.6 alkenyl, C2-6 alkynyl, Cw4ai l, C3- W cycloalkyl, 5-14 membered heteroaryl, 4-14 membered
  • NR c4 S(0) 2 NR c4 R d4 wherein the Ci- 6 alkyl, C2-6 alkenyl, C2-6 alkynyl, €5-14 aryi, C3..14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl of R M are each optionally substituted with 1, 2, 3, or 4 independently selected R H substituents; each R a+ , R c4 , and R d4 is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-i + aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the Ci-b alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-n aryl, Cs-w cycloalky 1, 5-14 membered heteroaryl, and 4-14 membered
  • each R M is independently selected from C 1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, C3-! 4 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the C -e alky l, C2-6 alkenyl, C2-6 alky nyl, Ce-u aryl, €3-5 + cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalk l are each optionally substituted with 1, 2, 3, or 4 independently selected R H substituents;
  • each R s+ is independently selected from H, OH, CN, C-- 6 alky l, C -e alkoxy, C1-6 haloalkyl, and Ci-ehaloalkoxy;
  • each R H is independently selected from D, halo, oxo, Ci-e alkyl, CN, NO2, OR ®5 , SR 33 ,
  • each R a5 , R ®3 , and R ds is independently selected from H, and Ci-b alkyl;
  • each R b3 is independently selected from Ci-e alkyl, C 2 -e alkeny l, C2-6 alkynyl, Ce-n aryl, C3 -14 cycloalkyl, 5-14 membered heteroaryd, and 4-14 membered heterocycloalkyl; and each R e5 is independently selected from H and C - 6 alkyl.
  • X is CR 3 ;
  • R ! is selected from H and C -e alky l
  • R 2 is selected from H, D, Ce-io aryl, 5-10 membered heteroaryl, C(G)R b2 ,
  • R 3 is selected from H, D, halo, C - 6 alkyl, Cwo aiyl, 5-10 membered heteroaryl, CN, and OR 83 , wherein the Ci-b alkyl, Ce-ic. aryl, and 5-10 membered heteroaryl of R 3 are each optionally substituted with 1 , 2, 3, or 4 independently selected 4 ' substituents;
  • Cy ! is pheny l, optionally substituted with 1 , 2, 3, or 4 independently selected R M substituents; or Cy 1 is C10 aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl, wherein the C10 aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of Cy 3 are each optionally substituted with 1, 2, 3, or 4 independently selected R substituents; Cy 2 is C b -io aiyl, C3-7 cycloalkyl, 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl, wherein the C b -io aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heteroeyeloalkyl of Cy 2 are each optionally substituted with 1, 2, 3, or 4 independently selected R r substituents;
  • each R 32 , R ci , R d2 , and R 33 is independently selected from H, Ci-s alkyl, C 2 -s alkenyl, C2-6 alkynyl, Ce-io ary l, C3-7 cycloalkyl, 5-10 membered heteroaryi, and 4-10 membered heteroeyeloalkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heteroeyeloalkyl of R a2 , R c2 , R d2 , and R 3J are each optionally substituted with 1, 2, 3, or 4 independently selected R G substituents;
  • each R b2 is independently selected from Cw alkyl, C2-6 alkenyl, C2-6 alkynyl, C S-JO aryl, €3-7 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heteroeyeloalkyl, wherein the C , alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-7 cycloalkyl, 5-10 membered heteroaryi, and 4-10 membered heteroeyeloalkyl are each optionally substituted with 1 , 2, 3, or 4 independently selected R° substituents;
  • each R c , R D , R E , R" , and R G is independently selected from D, halo, oxo, Cw alkyl, €2-5 alkenyl, C2- S alkynyl, C b -io aryl, C3-7 cycloalkyl, 5-10 membered heteroaryi, 4-10 membered heteroeyeloalkyl, CN, N0 2 , OR !, i . SR 34 , NHOR a4 , C(0)R b4 , C(0)NR c4 R d4 ,
  • each R M is independently selected from D, halo, oxo, Ci-s alkyl, €2-5 alkenyl, C2- S alkynyl, Ce-io aryl, C3-7 cycloaikyl, 5-10 membered heteroaryi, 4-10 membered
  • each R 34 , R c4 , and R d4 is independently selected from H, C M alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-ioatyi, C 3-7 cycloalkyl, 5-10 membered heteroaiyl, and 4-10 membered heteroeyeloalkyl, wherein the C M alkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ce- aryl, CV C yclQalky!, 5-10 membered heteroaiyl, and 4-10 membered heterocycloalkyl of R a4 , R c4 , and R d+ are each optionally substituted with 1 , 2, 3, or 4 independently selected R M substituents;
  • each R fc+ is independently selected from Cw alkyl, C 2- e alkenyl, C2-6 alkynyl, C S-JO aryl, C3.7 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, wherein the Cj- 6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Cs-io aryl, C3-7 cycloalkyl, 5-10 membered heteroaiyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R ri substituents;
  • each R 84 is independently selected from H, OH, CN, Ci-e alky l, Ci-e alkoxy, Ci-e haloalkyl, and Ci-ehaloalkoxy;
  • each R H is independently selected from D, halo, oxo, C - 6 alkyl, CN, NO2, OR 35 , SR a' , NHOR 35 , C(0)R b5 , C(0)NR c5 R d5 , C(0)OR a5 , OC(0)R b5 , 0C(0)NR c5 R d5 , NR c5 R d5 ,
  • each R a ⁇ R c y and R ds is independently selected from H, and Ci-b alkyl;
  • each R to is independently selected from Cs- 6 alkyl, C 2-& alkenyl, C2-6 alkynyl, C 10 aryl, C3 -10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl; and each R e5 is independently selected from H and C - 6 alkyl.
  • X is N
  • R 1 is selected from H, C - 6 alkyl, and a 5-14 membered heteroaryl, wherein the Ci-e alkyl and a 5-14 membered heteroaryl are each optionally substituted with 1, 2, or 3 independently selected R B substituents;
  • R 2 is selected from H, D, Ci- 6 alkyl, Ce-uaryl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, Cs-ir ary l-Ci-e alkyl-, (5-14 membered heteroaryi)-Ci-6 alkyl-, ( - 14 membered heterocycloalkyl)-C ] ⁇ alkyl-, NR ⁇ R ⁇ .CCOiR 02 , C(0)NR c2 R d2 , and C(0)OR a2 , wherein the Ci-e alkyl, Ce- aryl, 5-14 membered heteroaryl, 4-14 membered
  • heterocycloalkyl C M ar I-C1- & alkyl-, (5-14 membered heteroar l) -C -6 alkyl-, (4-14 membered heterocycloalkyi)-Ci- 6 alkyl- of R 2 are each optionally substituted with 1, 2, 3, or 4 independently selected R c substituents;
  • Cy ! is pheny l, optionally substituted with 1, 2, 3, or 4 independently selected R M substituents, or Cio-u aryl or 5-14 membered heteroaryl, wherein the C IO-M aryl and 5-14 membered heteroaryi of Cy !
  • Cy 2 is Ce-i+ aiyl, C3-14 cycloalkyl, 5-14 membered heteroaryi or 4-14 membered heterocycloalkyl, wherein the CVi aiyi, C3-14 cycloalkyl, 5-14 membered heteroaryl and 4-14 membered heterocycloalkyl of Cy 2 are each optionally substituted with 1, 2, 3, or 4 independently selected R r substituents;
  • each R 32 , R ci , and R d2 is independently selected from H, C 1-5 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-n aryl, Ce-ir aryl-C -.e alkyl-, C S-M cycloalkyl, 5-14 membered heteroaryi, and 4-14 membered heterocy cloalkyl, wherein the Ci- 6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-i+aiyl, C M aryl-Ci-6 alkyl-, C3- M cycloalkyl, 5-14 membered heteroaryi, and 4-14 membered
  • heterocycloalkyl of R 32 , R ci , and R 02 are each optionally substituted with 1, 2, 3, or 4 independently selected R° substituents;
  • each R b2 is independently selected from C1-6 alkyl, C2-6 alkeny l, C2-6 alkynyl, Ce-n aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, and 4-14 membered heterocycloalkyl, wherein the Ci-e alkyl, C2-6 alkenyl, C 2-6 alkynyl, C S-M aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, and 4-14 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R u substituents;
  • each R b , R c , R , R b , and R G is independently selected from D, halo, oxo, C1.6 alkyl, C2-6 alkenyl, C 2-6 alkynyl, Ce-w aryl, C3-14 cycloalkyl, 5-14 membered heteroaryi, 4-14 membered heterocycloalkyl, CN, N0 2 , OR 34 , SR ®4 , NHOR ®4 , C(0)R M , C(0)NR c4 R d4 ,
  • each R M is independently selected from D, halo, oxo, Cs- 6 alkyl, C 2-6 alkenyl, C2-6 alkynyl, Ck-i+ aryl, C3-14 cycloalky 1, 5-14 membered heteroaryi, 4-14 membered
  • NR c S(0) 2 NR c R d4 wherein the Cs- 6 alkyl, C2-6 alkenyl, C 2-6 alkynyl, CVw axyl, C3- M cycloalkyl, 5-14 membered heteroaryi, and 4-14 membered heterocycloalky 1 of R M are each optionally substituted with 1 , 2, 3, or 4 independently selected R H substituents;
  • each R 34 , R c+ , and R d4 is independently selected from H, Ci- 6 alkyl, C 2-6 alkenyl, C2-6 alkynyl, C f, - 4 aiyl, C3-i 4 cycioalkyl, 5-14 membered heteroaryd, and 4-14 membered heterocycloalkyl, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-waxyl, €3-14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl of R 34 , R 64 , and R d4 are each optionally substituted with 1, 2, 3, or 4 independently selected R H substituents;
  • each R M is independently selected from Ci « alkyl, C 2 « alkenyl, C2-6 alkynyl, Ce-14 a d, Cs- 14 cycloalkyl 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, wherein the C -6 alkyl, C2-6 alkenyl, C 2 -6 alkynyl, CS- M aryl, Cs- cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl are each optionally substituted with 1 , 2, 3, or 4 independently selected R ri substituents;
  • each R e4 is independently selected from H, OH, CN, Cue alkyl, Ci-e alkoxy , Ci-e haloalkyl, and Ci-ehaloalkoxy;
  • each R M is independently selected from D, halo, oxo, Cue alkyl, CN, NO2, OR a> , SR 35 , NHOR a5 , C(0)R b5 , C(0)NR c5 R d5 , C(0)OR a5 , OC(0)R b5 , 0C(0)NR c 3 ⁇ 4 d5 , NR c5 R d5 ,
  • each R 3 , R c5 , and R d5 is independently selected from H, and Cs- 6 alkyl;
  • each R b5 is independently selected from Ci- 6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C S-M aryl, C3-! 4 cycloalky 1, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl; and each R e5 is independently selected from H and Ci- 6 alkyl.
  • X is N
  • R 1 is H or a 5-14 membered heteroaryl optionally substituted with 1, 2, or 3 independently selected R B substituents;
  • R 2 is selected Ci- 6 alkyl, 4-14 membered heterocycloalkyl, C f r.34 ary I-C1-6 alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, (4-14 membered heterocycloalkyl)-C 1-5 alkyl-, and NR c2 R d2 , wherein the C - 6 alkyl, 4-14 membered heterocycloalkyl, Ce-ir aryd-C i-b alkyl-, (5-14 membered heteroaryl)-Ci-6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci..6 alkyl- of R 2 are each optionally substituted with 1, 2, or 3 independently selected R c substituents;
  • Cy ! is phenyl optionally substituted with 1, 2, or 3 independently selected R' substituents
  • Cy 2 is 5-14 membered heteroaryl optionally substituted with 1 , 2, or 3 independently selected R r substituents.
  • X is N; R ! IS H or a 5-14 membered heteroaryl optionally substituted with 1, 2, or 3 independently selected R H substituents;
  • each R B is independently selected from D, halo, oxo, C - 6 alkyl, C - 6 haloalkyi, C2-6 alkenyl, CN, NO2 and OH;
  • R 2 is selected C i-s alkyl, 4-14 membered heterocycloalkyl, Ce-u ary l-Ci- 6 alkyl-, (5-14 membered heteroaryl)-Ci ⁇ alkyl-, (4-14 membered heterocycloalky 1)-C i-b alkyl-, and NR“R d/ ⁇ , wherein the Ci-e alkyl, 4-14 membered heterocycloalkyl, Ce-i4 ary 1-Ci-e, alkyl-, (5-14 membered heteroaryl)-Ci- 6 alkyl-, and (4-14 membered heterocycloalkyl)-Ci- 6 alkyl- of R 2 are each optionally substituted with 1, 2, or 3 independently selected R c substituents;
  • each R c2 and R d2 are independently selected from H, C i-s alkyl, Ce-w aiyl-Ci- 6 alkyl-, wherein the C -e alky l and Ce-u ary I-C1-6 alkyl- of R c2 and R d2 are each optionally substituted with 1, 2, or 3 independently selected R u substituents;
  • each R c is independently selected from D, halo, oxo, C - 6 alkyl, C 6 -i4 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heteroc cloalk l, OR 34 , C(0)NR c4 R d4 and NR c4 R d4 , wherein the Ci-e alkyl, C 6 -w aryl, €3-14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl, of R c is optionally substituted with 1, 2, or 3 independently selected R H substituents;
  • each R 84 , R c4 , and R d4 is independently selected from H, Ci-b alkyl, Cj- 6 haloalkyi, C2-6 alkenyl, and 5-14 membered heteroaryl, wherein the Ci-b alkyl, C2-6 alkenyl, and 5-14 membered heteroaryl, of R ®4 , R 0 *, and R d are each optionally substituted with 1 , 2, or 3 independently selected R d substituents;
  • each R G is independently selected from D, halo, oxo, Ci-e alkyl, CN, NO2, and OH;
  • Cy 1 is phenyl optionally substituted with 1, 2, or 3 independently selected R substituents
  • each R E is independently selected from D, halo, oxo, Ci-e alkyl, CN, O2 and OH;
  • Cy 2 is 5-14 membered heteroaryl optionally substituted with 1, 2, or 3 independently selected R r substituents;
  • each R* is independently selected from D, halo, oxo, Ci- 6 alkyl, C2-6 alkenyl, CN,
  • each R 34 is independently selected from H, Ci- 6 alkyl and Ci-b alkoxy; and each R H is independently selected from D, halo, oxo, CVe alkyl, CN, NO and OH.
  • X is N; R ! IS H or a 5-10 membered heteroaryl optionally substituted with 1, 2, or 3 independently selected R H substituents;
  • each R B is independently selected from D, halo, oxo, C - 6 alkyl, C - 6 haloalkyi, C2-6 alkenyl, CN, NO2 and OH;
  • R 2 is selected Ci-s alkyl, 4-10 membered heterocycloalkyl, Cs-io ary l-Ci- 6 alkyl-, (5-10 membered heteroaryl)-Ci ⁇ alkyl-, (4-10 membered heterocycloalkyl)-Ci-6 alkyl-, and NR“R d/ ⁇ , wherein the Ci-e alkyl, 4-10 membered heterocycloalkyl, Ce-io ary 1-Ci-e, alkyl-, (5-10 membered heteroaryl)-Ci- 6 alkyl-, and (4-10 membered heterocycloalkyl)-Ci- 6 alkyl- of R 2 are each optionally substituted with 1, 2, or 3 independently selected R c substituents;
  • each R c2 and R d2 are independently selected from H, Ci-s alkyl, CV10 asyl-Ci- 6 alkyl-, wherein the C -e alkyl and Ce-io ary l-Ci- 6 alkyl- of R c2 and R d2 are each optionally substituted with 1, 2, or 3 independently selected R u substituents;
  • each R c is independently selected from D, halo, oxo, C - 6 alkyl, C 6 -io aryl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heteroc cloalk l, OR 34 , C(0)NR c4 R d4 and NR c4 R d4 , wherein the Ci-e alkyl, C 6 -io aryl, C3- ? cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, of R c is optionally substituted with 1, 2, or 3 independently selected R rf substituents;
  • each R 84 , R c4 , and R d4 is independently selected from H, Cj-b alkyl, Ci-e haloalkyi, C2-6 alkenyl, and 5-10 membered heteroaryl, wherein the Ci-b alkyl, C2-6 alkenyl, and 5-10 membered heteroaryl, of R ®4 , R 0 *, and R d4 are each optionally substituted with 1, 2, or 3 independently selected R d substituents;
  • each R G is independently selected from D, halo, oxo, Ci-e alkyl, CN, NO2, and OH;
  • Cy 1 is phenyl optionally substituted with 1, 2, or 3 independently selected R substituents
  • each R E is independently selected from D, halo, oxo, Ci-e alkyl, CN, O2 and OH;
  • Cy 2 is 5-10 membered heteroaryl optionally substituted with 1, 2, or 3 independently selected R r substituents;
  • each R* is independently selected from D, halo, oxo, Ci- 6 alkyl, C2-6 alkenyl, CN,
  • each R 34 is independently selected from H, Ci- 6 alkyl and Ci-b alkoxy; and each R H is independently selected from D, halo, oxo, CVe alkyl, CN, NO and OH.
  • X is N; R ! is H or nicotinonitriie;
  • R 2 is pyridinylmethyl, hydroxy(phenyl)methyl, hydroxyetiiylamino(phenyl)ethyl, cyelohexyimethyi, fluorobenzyl, hydroxy (fluorophenyl)methyl, methylpyridinylmetliyl, fluoropyridinylmethyl, melhoxypyridinylmethyl, methylpyrazolylbenzyl- benzoisoxazolylmethyl, methylindazoly!methyl, hydroxyazetidinylmethyl, benzoyl, phenyicyclopropyl, cyano(phenyl)methylamino, tetrahydrofuranyl, or phenyl(pyridin-2- yloxy)methy5;
  • Cy ! is cyanophenyl
  • Cy 2 is pyrimidinyl, eth lpyrazolyl propylpyrazol l, quinolinyl, iluoropyrimidinyl, pyridinyl, methylpyridinyl, methoxy-methylpyridinyl, pyrazolopyridazinyl, methyloxazolyl, hydroxymethyl-methyloxazolyl, or methoxymethyl-methyloxazolyl.
  • X is N
  • R* is H
  • R 2 is selected from pyridin-2-ylmethyl, hydroxy(phenyl)methyl, (2 ⁇
  • Cy 1 is cyanophenyl
  • Cy 2 is selected from 2,6-dimethylpyridin-4-yl, pyridin-4-yl, 2-methylpyridin-4-yl, 1- carbamoyl- 1 ,2,3,6-tetrahydrop ridin-4-yl, l-carbamoylpiperidin-4-yl, 2-methoxypyridin-4-yl, 2-meihoxy-6 ⁇ methylpyridin-4-yl, 2,6 ⁇ dimethyipyridin-4 ⁇ yT ⁇ l-oxide, l-ethyl-6-oxo-l,6- dihydropyridin-3-yl, 3-methylpyridin-4-yl, 3-fluoropyridin-4-yl, 3-chloropyridin-4-yl, 3- methoxypyridin-4-y 1, 3 -cyanopyridin -4-yl, 4-carbamoy lpheny 1 , pyrazolo[ 1,5 -a ⁇ pyridin -3 -yl,
  • the compound is the (S) -enantiomer of one of the preceding compounds, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is the (R) -enantiomer of one of the preceding compounds, or a pharmaceutically acceptable salt thereof.

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AU2019227607A AU2019227607C1 (en) 2018-02-27 2019-02-26 Imidazopyrimidines and triazolopyrimidines as A2A / A2B inhibitors
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