Heteroaryl compounds for the treatment of pain - Patents.com

Abstract

Compounds and pharma- ceutically acceptable salts thereof useful as inhibitors of sodium channels are provided. Pharmaceutical compositions comprising the compounds or pharma- ceutically acceptable salts, as well as methods of using the compounds, pharma- ceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain, are also provided. The present invention relates to methods of treating or reducing the severity of various diseases, disorders, or conditions in a subject, including, but not limited to, chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, post-operative pain (e.g., bunionectomy pain, herniorrhaphy pain, or abdominoplasty pain), visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough, or cardiac arrhythmia, by administering a compound, a pharma- ceutically acceptable salt, or pharmaceutical composition to the subject.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Application No. 63 / 333,873, filed April 22, 2022, which is incorporated herein by reference in its entirety. [Background technology]

[0002] Pain is a protective mechanism that allows healthy animals to avoid tissue damage and prevent further damage to injured tissue. Nevertheless, there are many conditions in which pain persists beyond its usefulness or in which patients would benefit from pain suppression. Neuropathic pain is a form of chronic pain caused by damage to sensory nerves (Dieleman, JP, et al., Incidence rates and treatment of neuropathic pain conditions in the general population. Pain, 2008. 137(3):pp. 681-688). Neuropathic pain can be divided into two categories: pain caused by systemic metabolic damage to nerves and pain caused by discrete nerve injury. Metabolic neuropathies include postherpetic neuropathy, diabetic neuropathy, and drug-induced neuropathy. Indications for discrete nerve injury include nerve entrapment injuries such as post-amputation pain, postoperative nerve injury pain, and neuropathic back pain.

[0003] Voltage-gated sodium channels (Na V ) is involved in pain signaling. V Sodium channel receptors (SCRs) are biological mediators of electrical signaling and mediate the rapid upstroke of action potentials in many excitable cell types (e.g., neurons, skeletal muscle cells, cardiac myocytes). Evidence for a role for these channels in normal physiology, pathological conditions resulting from mutations in sodium channel genes, preclinical studies in animal models, and clinical pharmacology of known sodium channel modulators all support the role of Na in pain sensation. V(Rush, A. M. and T. R. Cummins, Painful Research: Identification of a Small-Molecule Inhibitor that Selectively Targets Na V 1.8 Sodium Channels.Mol.Interv.,2007.7(4):p.192-5), England,S.,Voltage-gated sodium channels:the search for subtype-selective analgesics. Expert Opin. Investig. Drugs 17(12),p. 1849-64(2008), Krafte,DSand Bannon,AW,Sodium and Nociception: recent concepts and therapeutic opportunities. Curr. Opin. Pharmacol. 8(1), p. 50-56 (2008)). Na V Na mediates the rapid upstroke of action potentials in many excitable cell types (e.g., neurons, skeletal muscle cells, cardiac myocytes) and is therefore involved in the initiation of signal transduction in those cells (Hille, Bertil, Ion Channels of Excitable Membranes, Third ed. (Sinauer Associates, Inc., Sunderland, MA, 2001)). Na plays a key role in the initiation and propagation of neuronal signals. V Because of the role played by Na V Antagonists that reduce current can prevent or reduce nerve signaling, VIt has been thought that these channels are likely to reduce pain in conditions where hyperexcitability is observed (Chahine, M., Chatelier, A., Babich, O., and Krupp, JJ, Voltage-gated sodium channels in neurological disorders. CNS Neurol. Disord. Drug Targets 7(2), p. 144-58 (2008)). Several clinically useful analgesics are known to be sodium-gated. V Local anesthetics such as lidocaine have been identified as inhibitors of the Na channel. V Other compounds, such as carbamazepine, lamotrigine, and tricyclic antidepressants, which block pain by inhibiting channels and have been shown to be effective in reducing pain, have also been suggested to act by blocking sodium channels (Soderpalm, B., Anticonvulsants: aspects of their mechanisms of action. Eur. J. Pain 6 Suppl. A, p. 3-9 (2002); Wang, GK, Mitchell, J., and Wang, SY, Block of persistent late Na + currents by antidepressant sertraline and paroxetine.J.Membr.Biol.222(2),p.79-90(2008)).

[0004] Na V form a subfamily of the voltage-gated ion channel superfamily and V 1.1~Na V It contains nine isoforms, designated 1.1 and 1.9. The tissue localization of the nine isoforms varies. V 1.4 is the primary sodium channel in skeletal muscle, and Na V 1.5 is the primary sodium channel in cardiac myocytes. Na V 1.7, 1.8, and 1.9 are primarily localized in the peripheral nervous system, and Na V1.1, 1.2, 1.3, and 1.6 are neuronal channels found in both the central and peripheral nervous systems. The functional behavior of the nine isoforms is similar, but they differ in the details of their voltage dependence and kinetic behavior (Catterall, WA, Goldin, AL, and Waxman, SG, International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol. Rev. 57(4), p. 397 (2005)).

[0005] At the time of their discovery, Na V The 1.8 channel was identified as a likely target for analgesia (Akopian, AN, L. Sivilotti, and JN Wood, A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature, 1996. 379(6562):pp. 257-62). Subsequently, Na V 1.8 has been shown to be a carrier of the sodium current that sustains action potential firing in small dorsal root ganglion (DRG) neurons in nociceptive sensory neurons (Blair, NT and BP Bean, Roles of tetrodotoxin (TTX)-sensitive Na + Current, TTX-resistant Na + current, and Ca 2+ current in the action potentials of nociceptive sensory neurons.J.Neurosci.,2002.22(23):p.10277-90). Na V1.8 is involved in spontaneous firing in injured neurons, such as those that cause neuropathic pain (Roza, C., et al., The tetrodotoxin-resistant Na + Channel Na V 1.8 is essential for the expression of spontaneous activity in damaged sensory axons of mice.J.Physiol.,2003.550(Pt 3):p.921-6, Jarvis,MF,et al.,A-803467,a potent and selective Na V 1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat.Proc.Natl.Acad.Sci.USA,2007.104(20):p.8520-5, Joshi,SK,et al.,Involvement of the TTX-resistant sodium channel Na V 1.8 in inflammatory and neuropathic,but not post-operative,pain states.Pain,2006.123(1-2):pp.75-82, Lai, J., et al.,Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel,Na V 1.8.Pain,2002.95(1-2):p.143-52, Dong,XW,et al.,Small interfering RNA-mediated selective knockdown of Na V1.8 tetrodotoxin-resistant sodium channel reverses mechanical allodynia in neuropathic rats.Neuroscience,2007.146(2):p.812-21, Huang, HL, et al., Proteomic profiling of neuromas reveals alterations in protein composition and local protein synthesis in hyper-excitable nerves.Mol.Pain,2008.4:p.33, Black, JA, et al. al.,Multiple sodium channel isoforms and mitogen-activated protein kinases are present in painful human neuromas.Ann.Neurol.,2008.64(6):p.644-53, Coward,K.,et al.,Immunolocalization of SNS / PN3 and NaN / SNS2 sodium channels in human pain states.Pain,2000.85(1-2):p.41-50, Yiangou,Y.,et al.,SNS / PN3 and SNS2 / NaN sodium channel-like immunoreactivity in human adult and neonate injured sensory nerves.FEBS Lett.,2000.467(2-3):p.249-52, Ruangsri,S.,et al.,Relationship of axonal voltage-gated sodium channel 1.8(Na V 1.8) mRNA accumulation to sciatic nerve injury-induced painful neuropathy in rats.J.Biol.Chem.286(46):p.39836-47). Na V The small DRG neurons in which Na1.8 is expressed contain nociceptors involved in pain signaling.V 1.8 mediates large-amplitude action potentials in small neurons of the dorsal root ganglion (Blair, NT and BP Bean, Roles of tetrodotoxin (TTX)-sensitive Na + Current, TTX-resistant Na + current, and Ca 2+ current in the action potentials of nociceptive sensory neurons.J.Neurosci.,2002.22(23):p.10277-90). Na V 1.8 is required for rapid repetitive action potentials in nociceptors and for spontaneous activity of injured neurons. (Choi, JS and SG Waxman, Physiological interactions between Na V 1.7 and Na V 1.8 sodium channels: a computer simulation study.J.Neurophysiol.106(6):p.3173-84, Renganathan, M., TRCummins, and SGWaxman, Contribution of Na( V )1.8 sodium channels to action potential electrogenesis in DRG neurons.J.Neurophysiol.,2001.86(2):p.629-40, Roza,C.,et al.,The tetrodotoxin-resistant Na + Channel Na V 1.8 is essential for the expression of spontaneous activity in damaged sensory axons of mice. J. Physiol., 2003. 550(Pt 3): pp. 921-926. In depolarized or damaged DRG neurons, Na V1.8 appears to be a driver of hyperexcitability (Rush, AM, et al., A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. Proc. Natl. Acad. Sci. USA, 2006. 103(21):p.8245-50). In some animal pain models, Na V 1.8 mRNA expression level shows an increase in DRG (Sun, W., et al., Reduced conduction failure of the main axon of polymodal nociceptive C-fibers contributes to painful diabetic neuropathy in rats. Brain, 135(Pt 2): pp. 359-75; Strickland, IT, et al., Changes in the expression of Na V 1.7,Na V 1.8 and Na V 1.9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain.Eur.J.Pain,2008.12(5):p.564-72, Qiu,F.,et al.,Increased expression of tetrodotoxin-resistant sodium channels Na V 1.8 and Na V 1.9 within dorsal root ganglia in a rat model of bone cancer pain.Neurosci.Lett.,512(2):p.61-6). The present inventors have found that some voltage-gated sodium channel inhibitors, for example, have a poor therapeutic window (e.g., Na VIt has been discovered that selective Na V There remains a need to develop selective voltage-gated sodium channel inhibitors, such as 1.8 inhibitors. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Dieleman,JP,et al.,Incidence rates and treatment of neuropathic pain conditions in the general population.Pain,2008.137(3):p.681-8 [Non-patent document 2] Rush,AMand TRCummins,Painful Research:Identification of a Small-Molecule Inhibitor that Selectively Targets NaV1.8 Sodium Channels.Mol.Interv.,2007.7(4):p.192-5 [Non-patent document 3] England, S., Voltage-gated sodium channels: the search for subtype-selective analgesics. Expert Opin. Investig. Drugs 17(12), p. 1849-64(2008) [Non-patent document 4] Krafte, DSand Bannon, AW, Sodium channels and nociception: recent concepts and therapeutic opportunities. Curr. Opin. Pharmacol.8(1), p. 50-56(2008) [Non-patent document 5] Hille, Bertil, Ion Channels of Excitable Membranes, Third ed. (Sinauer Associates, Inc., Sunderland, MA, 2001) [Non-patent document 6] Chahine, M., Chatelier, A., Babich, O., and Krupp, JJ, Voltage-gated sodium channels in neurological disorders.CNS Neurol.Disord.Drug Targets 7(2), p.144-58(2008) [Non-Patent Document 7] Soderpalm, B., Anticonvulsants: aspects of their mechanisms of action.Eur.J.Pain 6 Suppl.A, p.3-9(2002) [Non-patent document 8] Catterall, WA, Goldin, AL, and Waxman, SG, International Union of Pharmacology.XLVII.Nomenclature and structure-function relationships of voltage-gated sodium channels.Pharmacol.Rev.57(4), p.397(2005) [Non-Patent Document 9] Akopian, AN, L. Sivilotti, and JNWood, A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.Nature, 1996.379(6562):p.257-62 Summary of the Invention [Means for solving the problem]

[0007] In one aspect, the present invention relates to a compound described herein, or a pharmaceutically acceptable salt thereof.

[0008] In another aspect, the invention relates to pharmaceutical compositions comprising a compound, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or vehicles.

[0009] In yet another aspect, the invention relates to a method of inhibiting voltage-gated sodium channels in a subject by administering to the subject a compound, a pharmaceutically acceptable salt, or a pharmaceutical composition.

[0010] In yet another aspect, the present invention relates to methods of treating or lessening the severity of various diseases, disorders, or conditions in a subject, including, but not limited to, chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, post-operative pain (e.g., bunionectomy pain, herniorrhaphy pain, or abdominoplasty pain), visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough, or cardiac arrhythmia, by administering a compound, pharmaceutically acceptable salt, or pharmaceutical composition to the subject. DETAILED DESCRIPTION OF THE INVENTION

[0011] In one aspect, the present invention provides a compound of formula (I): [ka] During the ceremony, X 5a But, N, N + -O - , or N + -CH3, X 9a But N or CR 9a and R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, R 4a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, R6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ , substituted as necessary with R 9a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, Each R a’ are independently halo, —OH, C1-C6 alkyl, C1-C6 haloalkyl, —C(O)O(C1-C6 alkyl), or -C(O)NH2, Y is, [ka] and X 2b But N or CR 2b and X 3b But N or CR 3b and X 4b But N or CR 4b and X 5b But N or CR 5b and X 6b But N or CR 6b and Z optionally contains 1 to 3 heteroatoms selected from nitrogen and oxygen, and one or more R z is a 5- to 7-membered aromatic or non-aromatic ring optionally substituted with R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo; R 3b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -(C1-C6 haloalkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl), C6-C 10 aryl, C3-C 10 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein the C3-C 10 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ , substituted as necessary with R 5b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 6bis H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or the cycloalkyl in said (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo; R 7b is C1-C6 alkyl, R 9b is C1-C6 alkyl, R 10b is H or halo, Each R b’ is independently C1-C6 alkyl or C1-C6 haloalkyl; R z halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkenyl, -CN, -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), or -C(O)OH, however, (i) Y is [ka] and X 3b is CR 3b and X 6b is CR 6b If R 2b , R 3b, R 4b , R 5b , and R 6b Three or fewer of the characters must be H. (ii) Y is [ka] and X 3b is N and X 6b is CR 6b If R 2b , R 4b , R 5b , and R 6b Three or fewer of the characters must be H. (iii) Y is [ka] and X 3b is CR 3b and X 6b If N, then R 2b , R 3b , R 4b , and R 5b Three or fewer of the characters must be H. (iv) X 9a is N and Y is [ka] and X 3b is CR 3b and X 6b is CR 6b If R 2b , R 3b , R 4b , R 5b , and R 6b Two or fewer of these are halos, (v) X 9a is N and Y is [ka] and X 4b is CR 4b and X 5b is CR 5b and X 6b is CR6b If R 4b , R 5b , and R 6b Not more than two of are H, or R with one or more Zs z or a pharmaceutically acceptable salt thereof, provided that:

[0012] In another aspect, the present invention provides a compound of formula (II): [ka] During the ceremony, R 3c is H, halo, or C1-C6 alkyl; R 4c is H, halo, —CN, or C1-C6 alkoxy; R 5c is H, halo, —CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or —C(O)O(C1-C6 alkyl); R 6c is H, halo, —OH, —CN, C1-C6 alkoxy, C(O)NH2, or a 5-10 membered heteroaryl containing 1-3 heteroatoms selected from nitrogen and oxygen; R 9c is H, C1-C6 alkyl, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-O(C1-C6 alkyl), or -C(O)O(C1-C6 alkyl), Y is, [ka] and X 3d But N or CR 3d and R 2d , R 3d , and R 4d But the following: (i) R 2dis H, halo, -OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or -(C1-C6 alkylene)-OH, R 3d is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C1-C6 haloalkoxy; R 4d is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -Si(C1-C6 alkyl)3, -C(O)O(C1-C6 alkyl), (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogen or -CN; or (ii) R 2d and R 3d together with the carbon atoms to which they are attached, form the formula: [ka] forming a ring of R 4d is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -Si(C1-C6 alkyl)3, -C(O)O(C1-C6 alkyl), (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogen or -CN; or (iii) R 2d is H, halo, -OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or -(C1-C6 alkylene)-OH, R 3d and R 4d together with the carbon atoms to which they are attached, form the formula: [ka] is defined as forming a ring of R 5d is H, halo, C-C alkyl, C-C haloalkyl, C-C alkoxy, or —C(O)(C-C alkyl); R 6d is H, halo, or C1-C6 alkyl; R 7d is C1-C6 alkyl, R 9d is C1-C6 alkyl, however, (i) Y' is [ka] and X 3d is CR 3d If R 2d , R 3d , R 4d , R 5d , and R 6d four or fewer of the (ii) Y' is [ka] and X 3dIf N, then R 2d , R 4d , R 5d , and R 6d and wherein not more than three of are H, or a pharmaceutically acceptable salt thereof.

[0013] In another aspect, the present invention provides a compound of formula (III): [ka] During the ceremony, X 3k is N or CH, X 4k is N or CH, X 5k But N or CR 5k and X 6k But, N, N + -O - , or CR 6k and R 5k is H, C1-C6 alkoxy, —OH, —OCH2CH2N(CH3)2, or —N(CH3)(CH2CH2OCH3), R 6k is H, —OH, C1-C6 alkoxy, or —C(O)NH2; R 2L is C1-C6 alkyl, R 4L is C1-C6 alkyl, C1-C6 haloalkyl, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-; R 5L is H, halo, or C1-C6 alkyl, however, (i) X 3k , X 4k , and X 5k At least one of is N or X 6k is N or N + -O - And, (ii) X 3k , X 4k , X5k , and X 6k Two or fewer of the are N, (iii) X 6k N + -O - If X 3k and X 4k is CH and X 5k is CR 5k And, (iv) X 5k If N, then X 4k is N, or a pharmaceutically acceptable salt thereof.

[0014] For purposes of this invention, chemical elements are identified according to the Periodic Table of the Elements, Handbook of Chemistry and Physics, 75th Edition, CAS Edition. Further, general principles of organic chemistry are described in "Organic Chemistry," Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry," 5 th Ed., Ed.: Smith, MB and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are incorporated herein by reference.

[0015] As used herein, the term "compounds of the invention" refers to compounds of Formula (I), Formula (II), and Formula (III), and all embodiments thereof (e.g., Formula (IA), Formula (IB), Formula (IC), Formula (ID), Formula (IE), Formula (IF), Formula (IG), Formula (II-A), Formula (II-B), Formula (II-C), Formula (III-A), etc.), as described herein, and compounds identified in Tables A and B.

[0016] As described herein, the compounds of the present invention may contain multiple variables (e.g., X 5a , R 4a, Y, Z, etc. As one of ordinary skill in the art will recognize, combinations of groups envisioned by the present invention are those that result in the formation of stable or chemically feasible compounds. The term "stable" in this context refers to compounds that do not substantially change when subjected to conditions that allow for their production, detection, and preferably their recovery, purification, and use for one or more of the purposes disclosed herein. In some embodiments, a stable compound or a chemically viable compound is one that does not substantially change when kept at a temperature of 40° C. or less for at least one week in the absence of moisture or other chemically reactive conditions.

[0017] The chemical structures depicted herein are intended to be understood as they would be understood by one of ordinary skill in the art. For example, with respect to formulas (III) and (III-A), X 6k and X 5k are connected by a double bond, and X 5k and X 4k are connected by a single bond, although the bond between these groups may be hidden by atom labels in the chemical structures. Additionally, a substituent designated in a chemical structure as "CF3" or "F3C" refers to a trifluoromethyl substituent regardless of where that depiction appears in the chemical structure.

[0018] As used herein, the term "halo" means F, Cl, Br, or I.

[0019] As used herein, the term "alkyl" refers to a straight or branched hydrocarbon chain radical group, consisting solely of carbon and hydrogen atoms, containing no unsaturation, and having the specified number of carbon atoms, which is attached to the rest of the molecule by a single bond. For example, a "C1-C6 alkyl" group is an alkyl group having from 1 to 6 carbon atoms.

[0020] As used herein, the term "alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms containing one or more carbon-carbon double bonds and having a specified number of carbon atoms, which is attached to the rest of the molecule by a single bond. For example, a "C2-C6 alkenyl" group is an alkenyl group having from 2 to 6 carbon atoms.

[0021] As used herein, the term "cycloalkyl" refers to a stable non-aromatic monocyclic or bicyclic (fused, bridged, or spiro) saturated hydrocarbon radical, consisting solely of carbon and hydrogen atoms, having the specified number of carbon ring atoms, which is attached to the remainder of the molecule by a single bond. For example, a "C3-C8 cycloalkyl" group is a cycloalkyl group having from 3 to 8 carbon atoms.

[0022] As used herein, the term "alkoxy" refers to a group of the formula -OR a where R a is an alkyl group having the specified number of carbon atoms. For example, a "C1-C6 alkoxy" group is a group of the formula -OR a where R a is an alkyl group having 1 to 6 carbon atoms.

[0023] As used herein, the term "haloalkyl" refers to an alkyl group having a specified number of carbon atoms, in which one or more of the alkyl group's hydrogen atoms are replaced by a halo group. For example, a "C1-C6 haloalkyl" group is an alkyl group having 1 to 6 carbon atoms, in which one or more of the alkyl group's hydrogen atoms are replaced by a halo group.

[0024] As used herein, the term "haloalkenyl" refers to an alkenyl group having a specified number of carbon atoms, in which one or more of the alkenyl group's hydrogen atoms are replaced by a halo group. For example, a "C1-C6 haloalkenyl" group is an alkenyl group having 1 to 6 carbon atoms, in which one or more of the alkenyl group's hydrogen atoms are replaced by a halo group.

[0025] As used herein, the term "haloalkoxy" refers to an alkoxy group having the specified number of carbon atoms, wherein one or more of the alkyl group's hydrogen atoms is replaced by a halo group.

[0026] As used herein, the term "alkylene" refers to a divalent straight or branched hydrocarbon chain radical group, consisting solely of carbon and hydrogen atoms, without unsaturation and having the specified number of carbon atoms, which is attached to the rest of the molecule by two single bonds. For example, a "C1-C6 alkylene" group is an alkylene group having from 1 to 6 carbon atoms.

[0027] As used herein, the term "alkenylene" refers to a divalent straight or branched hydrocarbon chain radical group, consisting solely of carbon and hydrogen atoms, containing one or more carbon-carbon double bonds and having a specified number of carbon atoms, which is attached to the rest of the molecule by two single bonds. For example, "C2-C6 alkenylene" is an alkenylene group having from 1 to 6 carbon atoms.

[0028] As used herein, the term "haloalkylene" refers to an alkylene group having a specified number of carbon atoms, in which one or more of the alkylene group's hydrogen atoms are replaced by a halo group. For example, a "C1-C6 haloalkylene" group is an alkylene group having 1 to 6 carbon atoms, in which one or more of the alkylene group's hydrogen atoms are replaced by a halo group.

[0029] As used herein, the term "heterocyclyl" refers to a stable non-aromatic monocyclic, bicyclic, or tricyclic (fused, bridged, or spiro) radical having a specified number of ring atoms and attached to the remainder of the molecule by a single bond, in which one or more ring atoms are heteroatoms (e.g., heteroatoms independently selected from N, O, P, and S). The heterocyclic ring may be saturated or contain one or more double or triple bonds. In some embodiments, a "heterocyclyl" group has a specified number of ring members, in which one or more ring members are heteroatoms independently selected from oxygen, sulfur, nitrogen, phosphorus, and silicon, and each ring in the system contains 3 to 7 ring members. For example, a 6-membered heterocyclyl contains a total of 6 ring members, at least one of which is a heteroatom (e.g., a heteroatom independently selected from N, O, P, and S).

[0030] As used herein, the term "heteroaryl" refers to a stable monocyclic, bicyclic, or tricyclic ring radical having the specified number of ring atoms, wherein at least one ring in the system is aromatic and at least one aromatic ring in the system contains one or more heteroatoms (e.g., one or more heteroatoms independently selected from N, O, P, and S). In some embodiments, each ring in the system contains 3 to 7 ring members. For example, a 6-membered heteroaryl contains a total of 6 ring members, at least one of which is a heteroatom selected from N, S, O, and P. The term "heteroaryl" may be used interchangeably with the term "heteroaryl ring" or the term "heteroaromatic."

[0031] As used herein, labels such as "*2" and "*3" such as those shown in the structures below refer to the corresponding R group (in this case, R 2d Groups and R 3d Specify the carbon atom to which the (a) group is attached: [ka]

[0032] Similarly, "*3" and "*4" in the following structures represent R 3d Groups and R 4d Specify the carbon atom to which the group is attached: [ka]

[0033] Unless otherwise specified, the compounds of the invention, whether identified by chemical name or chemical structure, include all stereoisomers (e.g., enantiomers and diastereomers), double bond isomers (e.g., (Z) and (E)), conformational isomers, and tautomers of the compounds identified by the chemical names and chemical structures provided herein. Furthermore, single stereoisomers, double bond isomers, conformational isomers, and tautomers, as well as mixtures of stereoisomers, double bond isomers, conformational isomers, and tautomers, are within the scope of the invention.

[0034] As used herein, in any chemical structure or formula, a straight, non-bold bond attached to a stereogenic center of a compound, such as in the formula: [ka] Indicates that the configuration of a stereocenter is unspecified. The compound may have any configuration or a mixture of configurations at the stereocenter.

[0035] As used herein, the prefix "rac-" when used in reference to a chiral compound refers to a racemic mixture of the compound.

[0036] As used herein, the prefix "rel-," when used in reference to a chiral compound, refers to a single enantiomer of unknown absolute configuration. In compounds bearing the "rel-" prefix, the (R)- and (S)- designators in the chemical name reflect the relative stereochemistry of the compound, but do not necessarily reflect the absolute stereochemistry of the compound. If the relative stereochemistry of a given stereocenter is unknown, no stereochemical designator is provided.

[0037] As used herein, the term "compound," when referring to a compound of the present invention, refers to a collection of molecules having the same chemical structure except that isotopic variations may exist among the constituent atoms of the molecule. The term "compound" includes a collection of molecules regardless of the purity of a given sample containing the collection of molecules. Thus, the term "compound" includes such a collection of molecules in pure form, in a mixture with one or more other substances (e.g., a solution, suspension, colloid, or pharmaceutical composition or dosage form), or in the form of a hydrate, solvate, or co-crystal.

[0038] In this specification and claims, unless otherwise specified, any atom not specifically designated as a particular isotope of any compound of the invention is intended to represent any stable isotope of the specified element. In the examples, when an atom is not specifically designated as a particular isotope of any compound of the invention, no effort was made to enrich that atom in a particular isotope, and therefore, one of ordinary skill in the art would understand that such atom was likely present in about the natural abundance isotopic composition of the specified element.

[0039] As used herein, the term "stable," when referring to an isotope, means that the isotope is not known to undergo spontaneous radioactive decay. Stable isotopes include, but are not limited to, isotopes whose decay mode is not identified in V.S. Shirley & C.M. Lederer, Isotopes Project, Nuclear Science Division, Lawrence Berkeley Laboratory, Table of Nuclides (January 1980).

[0040] As used herein in the specification and claims, "H" refers to hydrogen and includes any stable isotope of hydrogen, i.e. 1Includes H and D. In the examples, when an atom is designated as "H," no attempt has been made to enrich that atom in a particular isotope of hydrogen, and thus, one of skill in the art will understand that such hydrogen atom was likely present in about the natural abundance isotopic composition of hydrogen.

[0041] As used herein, " 1 "H" refers to protium. When an atom in a compound of the invention or a pharmaceutically acceptable salt thereof is designated as protium, protium is present at the designated position at least at the natural abundance concentration of protium.

[0042] As used herein, "D", "d", and " 2 "H" refers to deuterium.

[0043] In some embodiments, the compounds of the invention and pharmaceutically acceptable salts thereof comprise each constituent atom at about the natural abundance isotopic composition of the specified element.

[0044] In some embodiments, the compounds of the present invention and pharmaceutically acceptable salts thereof contain one or more atoms having an atomic mass or mass number different from the atomic mass or mass number of the most abundant isotope of the specified element ("isotopically labeled" compounds and salts). Examples of stable isotopes that are commercially available and suitable for the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, and phosphorus, e.g., 2 H, 13 C. 15 N, 18 O. 17 O, and 31 Examples include, but are not limited to, P.

[0045] Isotopically labeled compounds and salts can be used in several beneficial ways, including as pharmaceuticals. In some embodiments, isotopically labeled compounds and salts contain deuterium ( 2 H) labeled. For example, deuterium ( 2 H) The labeled compounds and salts are therapeutically useful and non- 23H-labeled compounds have potential therapeutic advantages over H-labeled compounds. 2 H) Labeled compounds and salts may have higher metabolic stability compared to non-isotopically labeled counterparts due to kinetic isotope effects, as described below. Higher metabolic stability translates directly into increased in vivo half-life or lower dosages, which under most circumstances represent preferred embodiments of the present invention. Isotopically labeled compounds and salts can generally be prepared by following the procedures disclosed in the synthetic schemes, examples, and related description, substituting readily available isotopically labeled reactants for non-isotopically labeled reactants.

[0046] deuterium( 2 H) labeled compounds and salts can manipulate the rate of oxidative metabolism of a compound through the primary kinetic isotope effect. The primary kinetic isotope effect is a change in the rate of a chemical reaction resulting from the exchange of an isotope nucleus, which in turn is caused by a change in the ground state energy of the covalent bond involved in the reaction. The exchange of a heavier isotope usually results in a lowering of the ground state energy of the chemical bond and therefore a decrease in rate-limiting bond scission. If bond scission occurs within or near a saddle point region along the configuration of a multi-product reaction, the product distribution ratio can change significantly. For example, if deuterium is attached to a carbon atom at a non-exchangeable position, k H / k D A rate difference of 2 to 7 is typical. For further discussion, see S.L. Harbeson and R.D. Tung, Deuterium In Drug Discovery and Development, Ann. Rep. Med. Chem. 2011, 46, 403-417, which is incorporated herein by reference in its entirety.

[0047] The concentration of an isotope (e.g., deuterium) incorporated at a given position in an isotopically labeled compound of the present invention or a pharmaceutically acceptable salt thereof can be defined by the isotopic enrichment factor. As used herein, the term "isotopic enrichment factor" refers to the ratio between the abundance of an isotope at a given position in an isotopically labeled compound (or salt) and the natural abundance of the isotope.

[0048] When an atom in a compound of the invention or a pharmaceutically acceptable salt thereof is designated as deuterium, such compound (or salt) has an isotopic enrichment factor for such atom of at least 3000 (about 45% deuterium incorporation). In some embodiments, the isotopic enrichment factor is at least 3500 (about 52.5% deuterium incorporation), at least 4000 (about 60% deuterium incorporation), at least 4500 (about 67.5% deuterium incorporation), at least 5000 (about 75% deuterium incorporation), at least 5500 (about 82.5% deuterium incorporation), at least 6000 (about 90% deuterium incorporation), at least 6333.3 (about 95% deuterium incorporation), at least 6466.7 (about 97% deuterium incorporation), at least 6600 (about 99% deuterium incorporation), or at least 6633.3 (about 99.5% deuterium incorporation).

[0049] In some embodiments, the present invention relates to compounds of formula (I), wherein: R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), or -C(S)NH2; Y is, [ka] and R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo.

[0050] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 5a In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein X 5a N + -O - In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 5a N + -CH3.

[0051] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 9a is CR 9a In some embodiments, the present invention relates to compounds of formula (I), wherein X 9a is CR 9a and R 9a is H, halo, C1-C6 alkyl, C1-C6 alkoxy, In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is —C(O)OH, or —C(O)O(C1-C6 alkyl). 9a is CR 9a and R 9a But, H, halo, C1-C6 alkyl, or C1-C6 alkoxy. In other embodiments, R 9a is halo. In other embodiments, R 9a teeth, In another embodiment, R9a is C1-C6 alkoxy. In other embodiments, R 9a is —C(O)OH. In other embodiments, R 9a is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to compounds of formula (I), wherein R 9a is H, Cl, Br, -CH3, -OCH3, -OCH2CH3, -C(O)OH, or -C(O)OCH3. In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein: X 9a is CR 9a and R 9a is H, Cl, Br, —CH, —OCH, or —OCHCH. In other embodiments, R 9a is H. In other embodiments, R 9a is Cl. In other embodiments, R 9a is Br. In other embodiments, R 9a is -CH3. In other embodiments, R 9a is —OCH3. In other embodiments, R 9a teeth, In another embodiment, R 9a is -C(O)OCH3.

[0052] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 3a is H or C1-C6 alkyl. In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein R 3a is H or -CH3. In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein R 3a is H. In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein R 3a is -CH3.

[0053] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R4a is H.

[0054] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, C1-C6 alkoxy, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5-10 membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1-2 R a’ where each R is substituted as needed. a’ are independently Cl, -OH, -CH3, -CH2CH3, -CF3, In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, C1-C6 alkoxy, -NH(C1-C6 alkyl), -OH, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or In another embodiment, R 6a is C1-C6 alkoxy. In other embodiments, R 6a is —NH(C1-C6 alkyl). In other embodiments, R 6ais —O(C1-C6 alkylene)-(C1-C6 alkoxy). In other embodiments, R 6a teeth, -O(C1-C6 alkylene)-N(C1-C6 alkyl). In other embodiments, R 6a is —C(O)NH(C1-C6 alkyl). In other embodiments, R 6a is —C(O)N(C1-C6 alkyl). In other embodiments, R 6a is —C(O)O(C1-C6 alkyl). In other embodiments, R 6a is —N(C1-C6 alkyl). In other embodiments, R 6a is —NHC(O)NH. In other embodiments, R 6a is —NHC(O)NH(C1-C6 alkyl). In other embodiments, R 6a is —C(NH)NH. In other embodiments, R 6a is -SO2NH2. In other embodiments, R 6a is a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ where each R is substituted as needed. a’ are independently Cl, -OH, -CH3, -CH2CH3, -CF3, -C(O)OCH2CH3, or In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein R 6a is H, -CN, -OCH3, -OCH2CH2CH(CH3)2, -NH(CH3), -N(CH3)2, -NHC(O)NH2, -NHC(O)NHCH3, -OH, -OCH2CH2OCH3, -OCH2CH2N(CH3)2, -C(O)NH2, -C(O)NH(CH3), -C(O)N(CH3)2, -C(O)OH, -C(O)OCH3, -C(NH)NH2, -C(S)NH2, -SO2NH2, [ka] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, -OCH3, -OCH2CH2CH(CH3)2, -NH(CH3), -OH, -OCH2CH2OCH3, -OCH2CH2N(CH3)2, -C(O)NH2, -C(O)NH(CH3), -C(O)N(CH3)2, In other embodiments, R 6a is H. In other embodiments, R 6a teeth,- In another embodiment, R 6a is —OCH3. In other embodiments, R 6a is —OCH2CH2CH(CH3)2. In other embodiments, R 6a is —NH(CH). In other embodiments, R 6a is —OH. In other embodiments, R 6a teeth, In another embodiment, R 6a is —OCH2CH2N(CH3)2. In other embodiments, R 6a teeth, In another embodiment, R 6a is —C(O)NH(CH). In other embodiments, R 6a is —C(O)N(CH) . In other embodiments, R 6a is —C(O)OH. In other embodiments, R 6a is —C(O)OCH. In other embodiments, R 6a is —C(S)NH. In other embodiments, R 6a is —N(CH). In other embodiments, R 6a teeth, In another embodiment, R 6a is —NHC(O)NHCH. In other embodiments, R 6a teeth, In another embodiment, R 6ais -SO2NH2. In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] is.

[0055] In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein Y is: [ka] In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein Y is: [ka] In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein Y is: [ka] In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein Y is: [ka] In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein Y is: [ka] is.

[0056] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 3b In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein X 3b is CR 3b In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3b is H, halo, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3b is H, C1-C6 alkyl, or C1-C6 haloalkyl. 3b is C1-C6 alkyl. In other embodiments, R 3b is C1-C6 haloalkyl. In other embodiments, R 3b In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein R 3b is H, F, —CH 3 , or —CF 3 . In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein X 3b is CR 3b and R 3b is H, —CH, or —CF. In other embodiments, R 3b is H. In other embodiments, R 3bis -CH3. In other embodiments, R 3b is -CF3. In other embodiments, R 3b is D. In other embodiments, R 3b is -C(CD3)3. In other embodiments, R 3b is F.

[0057] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 6b In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein X 6b is CR 6b In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, halo, or C1-C6 alkyl. In other embodiments, R 6b is halo. In other embodiments, R 6b In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is C1-C6 alkyl. 6b is CR 6b and R 6b is H, F, or —CH. In other embodiments, R 6b is H. In other embodiments, R 6b is F. In other embodiments, R 6b is -CH3. In other embodiments, R 6b is D. In other embodiments, R 6b is -C(CD3)3.

[0058] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 2b But, H, halo, C1-C6 alkyl, C1-C6 alkoxy, or -(C1-C6 alkylene)-OH. In other embodiments, R 2b is halo. In other embodiments, R 2b is C1-C6 alkyl. In other embodiments, R 2b is C1-C6 alkoxy. In other embodiments, R 2b is -(C1-C6 alkylene)-OH. In other embodiments, R 2b is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, F, Cl, -CH3, -CH2CH3, -OCH3, -CH2OH, -CH2CH2CH2OH, or -C(O)OCH3. In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, F, Cl, —CH, —CHCH, —OCH, or —CHCHCHOH. 2b is H. In other embodiments, R 2b is F. In other embodiments, R 2b is Cl. In other embodiments, R 2b is -CH3. In other embodiments, R 2b is -CH2CH3. In other embodiments, R 2b is —OCH3. In other embodiments, R 2b is -CH2CH2CH2OH. In other embodiments, R 2b is D. In other embodiments, R 2b teeth, In another embodiment, R 2b is —CHOH. In other embodiments, R 2b is -C(O)OCH3.

[0059] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 haloalkoxy, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -(C1-C6 haloalkylene)-C(O)OH, -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C6-C 10 Aryl, C3-C 10 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein the C3-C 10 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ where each R is substituted as needed. b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, -(C1-C6 alkylene)-OH, -(C-C alkylene)-C(O)OH, -Si(C-C alkyl), or (C-C haloalkyl)-(C-C cycloalkyl). In other embodiments, R 4b is halo. In other embodiments, R 4b is C1-C6 alkyl. In other embodiments, R 4b teeth, In another embodiment, R 4bis C1-C6 haloalkenyl. In other embodiments, R 4b teeth,- (C1-C6 alkylene)-OH. In other embodiments, R 4b is -(C1-C6 alkylene)-C(O)OH. In other embodiments, R 4b is —Si(C1-C6 alkyl). In other embodiments, R 4b is (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4b is C1-C6 alkenyl. In other embodiments, R 4b is C1-C6 haloalkoxy. In other embodiments, R 4b is -(C1-C6 haloalkylene)-OH. In other embodiments, R 4b teeth,- (C1-C6 haloalkylene)-C(O)OH. In other embodiments, R 4b is —C(O)O(C1-C6 alkyl). In other embodiments, R 4b is C6-C 10 In another embodiment, R 4b is C3-C 10 In another embodiment, R 4b is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-. In other embodiments, R 4b is a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen. 10 The cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with one to two R b’ where each R is substituted as needed. b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 4b But H, Cl, -CH3, -CH(CH3)2, -C(CH3)3,-C(CH3)2(CH2CH3),-CF3,-C(CH3)2(CHF2),-C(CH3)2(CF3),-CH2C(CH3)2F,-C(=CH2)(CF3), -CH=C(CH3)2,-OCF3,-C(CH3)2(CH2OH),-C(CH3)(CF3)(CH2OH),-C(CH3)2(C(O)OH), -C(CH3)(CF3)(C(O)OH), -C(O)OCH3, -Si(CH3)3, phenyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, cyclobutyl, 1-methylcyclobutyl, 3,3-difluoro-1-methylcyclobutyl, cyclopentyl, 1-methylcyclopentyl, 1-trifluoromethylcyclopentyl, 3,3-difluoro-1-methylcyclopentyl, 4,4-difluoro-1-methylcyclohexyl, [ka] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CF3), -C(=CH2)(CF3), -C(CH3)2(CH2OH), -C(CH3)2(C(O)OH), -Si(CH3)3, or In another embodiment, R 4b is H. In other embodiments, R 4b is Cl. In other embodiments, R 4b is -CH3. In other embodiments, R 4b is —CH(CH). In other embodiments, R 4b teeth, In another embodiment, R 4b is —C(CH)(CHCH). In other embodiments, R 4b is -CF3. In other embodiments, R4b is —C(CH)(CF). In other embodiments, R 4b is —C(═CH)(CF). In other embodiments, R 4b is —C(CH)(CHOH). In other embodiments, R 4b is —C(CH)(C(O)OH). In other embodiments, R 4b is —Si(CH3)3. In other embodiments, R 4b is 1-trifluoromethylcyclopropyl. In other embodiments, R 4b is D. In other embodiments, R 4b is -C(CD3)3. In other embodiments, R 4b teeth, 1-(methyl-d3)cyclopropyl. In another embodiment, R 4b is —C(CD3)(CH3)(CF3). In other embodiments, R 4b is -C( 13 In another embodiment, R 4b is —C(CD3)2(CD2OH). In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 5b is H, halo, C-C alkyl, C-C haloalkyl, C-C alkoxy, or C-C cycloalkyl. 5b is halo. In other embodiments, R 5b is C1-C6 alkyl. In other embodiments, R 5b is C1-C6 haloalkyl. In other embodiments, R 5b is C1-C6 alkoxy. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 5b is H, F, Cl, —CH, —CHCH, —CH(CH), —C(CH), —CF, —OCH, or cyclopropyl. 5b is H. In other embodiments, R5b is F. In other embodiments, R 5b is Cl. In other embodiments, R 5b is -CH3. In other embodiments, R 5b is -CH2CH3. In other embodiments, R 5b teeth, In another embodiment, R 5b is —C(CH3)3. In other embodiments, R 5b is -CF3. In other embodiments, R 5b is —OCH3. In other embodiments, R 5b is cyclopropyl. In other embodiments, R 5b is D. In other embodiments, R 5b is -C(CD3)3. In other embodiments, R 5b is —C(CH)(CHF). In other embodiments, R 5b is —CHC(CH)F. In other embodiments, R 5b is -CH=C(CH3)2. In other embodiments, R 5b is -OCF3. In other embodiments, R 5b is —C(CH)(CF)(CHOH). In other embodiments, R 5b is —C(CH)(CF)(C(O)OH). In other embodiments, R 5b is —C(O)OCH. In other embodiments, R 5b is phenyl. In another embodiment, R 5b is 1-methylcyclopropyl. In another embodiment, R 5b is cyclobutyl. In another embodiment, R 5b is 1-methylcyclobutyl. In another embodiment, R 5b teeth, In another embodiment, R 5b is cyclopentyl. In another embodiment, R 5b is 1-methylcyclopentyl. In another embodiment, R 5bis 1-trifluoromethylcyclopentyl. In another embodiment, R 5b is 3,3-difluoro-1-methylcyclopentyl. In another embodiment, R 5b is 4,4-difluoro-1-methylcyclohexyl. In another embodiment, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] In other embodiments, R 5b teeth, [ka] is.

[0060] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b and R 2b is H or C1-C6 alkyl. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is C1-C6 alkyl. 2b is CR 2b and R 2b is H or -CH3. In other embodiments, R 2bis H. In other embodiments, R 2b is -CH3.

[0061] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 5b In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein X 5b is CR 5b In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b and R 5b is H or C1-C6 alkyl. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X is C1-C6 alkyl. 5b is CR 5b and R 5b is H or -CH3. In other embodiments, R 5b is H. In other embodiments, R 5b is -CH3.

[0062] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, C1-C6 alkyl, —OH, or —N(C1-C6 alkyl). In other embodiments, R 6b is C1-C6 alkyl. In other embodiments, R 6b In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b H, -CH3, -OH, -N(CH3)2, -N(CH2CH2CH2)3, -N(CH3)(CH2CH2CH2CH3), -N(CH2CH3)(CH2CH2CH2CH3), or In another embodiment, R 6b is H. In other embodiments, R 6b is -CH3. In other embodiments, R 6b is —OH. In other embodiments, R 6b is —N(CH). In other embodiments, R 6b teeth, In another embodiment, R 6b is —N(CH)(CHCHCHCH). In other embodiments, R 6b is —N(CH2CH3)(CH2CH2CH2CH3). In other embodiments, R 6b is -N(CHCH(CH)).

[0063] In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein Z is one to four R z In some embodiments, the present invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, wherein Z is: [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] is.

[0064] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R z is C1-C6 alkyl or C1-C6 haloalkyl. In other embodiments, R z is C1-C6 alkyl. In other embodiments, R z In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R z is —CH or —CF. In other embodiments, R z is -CH3. In other embodiments, R z is -CF3.

[0065] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 7b is —CH or —CH(CH). In other embodiments, R 7b is -CH3. In other embodiments, R 7b is -CH(CH3)2.

[0066] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 9b is -C(CH3)3.

[0067] In some embodiments, the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein R 10b is H or Cl. In other embodiments, R 10b is H. In other embodiments, R 10b is Cl.

[0068] In some embodiments, the present invention provides a compound of formula (IA): [ka] During the ceremony, X 5a But N or N + -O - and X 9a But N or CR 9a and R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C4 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ , substituted as necessary with R 9a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, Each R a’ are independently halo, —OH, C1-C6 alkyl, C1-C6 haloalkyl, —C(O)O(C1-C6 alkyl), or -C(O)NH2, Y is, [ka] and X2b But N or CR 2b and X 3b But N or CR 3b and X 4b But N or CR 4b and X 5b But N or CR 5b and X 6b But N or CR 6b and Z optionally contains 1 to 3 heteroatoms selected from nitrogen and oxygen, and one or more R z is a 5- to 7-membered aromatic or non-aromatic ring optionally substituted with R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo; R 3b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 haloalkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C6-C 10 Aryl, C3-C 10 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein the C3-C 10 cycloalkyl, The cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ , substituted as necessary with R 5b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 6b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)(C2-C6 alkyl), -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 7b is C1-C6 alkyl, R 9b is C1-C6 alkyl, R 10b is H or halo, Each R b’ is independently C1-C6 alkyl or C1-C6 haloalkyl; R z halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkenyl, -CN, -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl), or -C(O)OH, however, (i) Y is [ka] and X 3b is CR 3b and X 6b is CR 6b If R 2b , R 3b , R 4b , R 5b , and R 6b Three or fewer of the characters must be H. (ii) Y is [ka] and X 3b is N and X 6b is CR 6b If R 2b , R 4b , R 5b , and R 6b Three or fewer of the characters must be H. (iii) Y is [ka] and X 3b is CR 3b and X 6b If N, then R 2b , R 3b , R 4b , and R 5bThree or fewer of the characters must be H. (iv) X 9a is N and Y is [ka] and X 3b is CR 3b and X 6b is CR 6b If R 2b , R 3b , R 4b , R 5b , and R 6b Two or fewer of these are halos, (v) X 9a is N and Y is [ka] and X 4b is CR 4b and X 5b is CR 5b and X 6b is CR 6b If R 4b , R 5b , and R 6b Not more than two of are H, or R with one or more Zs z or a pharmaceutically acceptable salt thereof, provided that:

[0069] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein: R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C4 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, Y is, [ka] and R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein The cycloalkyl in C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo.

[0070] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 5a is N. In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 5a N + -O - is.

[0071] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 9a is CR 9a In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 9a is CR 9a and R 9a is H, halo, C1-C6 alkyl, C1-C6 alkoxy, or —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 9a is CR9a and R 9a is H, halo, C1-C6 alkyl, or C1-C6 alkoxy. 9a is halo. In other embodiments, R 9a is C1-C6 alkyl. In other embodiments, R 9a is C1-C6 alkoxy. In other embodiments, R 9a is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, Cl, Br, -CH3, -OCH3, -OCH2CH3, or In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X is —C(O)OCH 3 . 9a is CR 9a and R 9a is H, Cl, Br, -CH3, -OCH3, or In another embodiment, R 9a is H. In other embodiments, R 9a is Cl. In other embodiments, R 9a is Br. In other embodiments, R 9a is -CH3. In other embodiments, R 9a is —OCH3. In other embodiments, R 9a is —OCH2CH3. In other embodiments, R 9a is -C(O)OCH3.

[0072] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, C1-C4 alkoxy, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5-10 membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1-2 R a’ where each R is substituted as needed. a’ are independently Cl, -OH, -CH3, -CH2CH3, -CF3, In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, C1-C4 alkoxy, -NH(C1-C6 alkyl), -OH, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or In another embodiment, R 6a is H. In other embodiments, R 6a is C1-C4 alkoxy. In other embodiments, R 6a is —NH(C1-C6 alkyl). In other embodiments, R 6a is —O(C1-C6 alkylene)-(C1-C6 alkoxy). In other embodiments, R 6a is —O(C-C alkylene)-N(C-C alkyl). In other embodiments, R 6a teeth, In another embodiment, R 6a is —C(O)N(C1-C6 alkyl). In other embodiments, R 6a is —C(O)O(C1-C6 alkyl). In other embodiments, R6a is —N(C1-C6 alkyl). In other embodiments, R 6a teeth, In another embodiment, R 6a is —NHC(O)NH(C1-C6 alkyl). In other embodiments, R 6a teeth, In another embodiment, R 6a is -SO2NH2. In other embodiments, R 6a is a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ where each R is substituted as needed. a’ is independently Cl, —OH, —CH, —CHCH, —CF, —C(O)OCHCH, or —C(O)NH. In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 6a is H,-CN,-OCH3,-NH(CH3),-N(CH3)2,-NHC(O)NH2,-NHC(O)NHCH3,-OH,-OCH2CH2OCH3,-OCH2CH2N(CH3)2,-C(O)NH2, -C(O)NH(CH3),-C(O)N(CH3)2,-C(O)OH,-C(O)OCH3,-C(NH)NH2,-C(S)NH2,-SO2NH2, [ka] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, -OCH3, -NH(CH3), -OH, -OCH2CH2OCH3, -OCH2CH2N(CH3)2, -C(O)NH2, -C(O)NH(CH3), -C(O)N(CH3)2, -C(O)OH, In other embodiments, R 6a is H. In other embodiments, R 6ais -CN. In other embodiments, R 6a is —OCH3. In other embodiments, R 6a is —NH(CH). In other embodiments, R 6a is —OH. In other embodiments, R 6a is —OCH2CH2OCH3. In other embodiments, R 6a is —OCH2CH2N(CH3)2. In other embodiments, R 6a is —C(O)NH. In other embodiments, R 6a is —C(O)NH(CH). In other embodiments, R 6a is —C(O)N(CH) . In other embodiments, R 6a is —C(O)OH. In other embodiments, R 6a is —C(O)OCH. In other embodiments, R 6a is —C(S)NH. In other embodiments, R 6a is —N(CH). In other embodiments, R 6a is —NHC(O)NH. In other embodiments, R 6a is —NHC(O)NHCH. In other embodiments, R 6a is —C(NH)NH. In other embodiments, R 6a is -SO2NH2. In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] is.

[0073] In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] is.

[0074] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 3b is N. In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3bIn some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3b is H, halo, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3b is H, C1-C6 alkyl, or C1-C6 haloalkyl. 3b is C 1-C6 alkyl. In other embodiments, R 3b is C1-C6 haloalkyl. In other embodiments, R 3b In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 3b is H, F, —CH 3 , or —CF 3 . In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 3b is H, —CH, or —CF. In other embodiments, R 3b is H. In other embodiments, R 3b is -CH3. In other embodiments, R 3b is -CF3. In other embodiments, R 3b is D. In other embodiments, R 3b is -C(CD3)3. In other embodiments, R 3b is F.

[0075] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 6b is N. In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR6b and R 6b is H, halo, or C1-C6 alkyl. In other embodiments, R 6b is halo. In other embodiments, R 6b In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, F, or —CH. In other embodiments, R 6b is H. In other embodiments, R 6b is F. In other embodiments, R 6b is -CH3. In other embodiments, R 6b is D. In other embodiments, R 6b is -C(CD3)3.

[0076] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 2b But, H, halo, C1-C6 alkyl, C1-C6 alkoxy, or -(C1-C6 alkylene)-OH. In other embodiments, R 2b is halo. In other embodiments, R 2b is C1-C6 alkyl. In other embodiments, R 2b is C1-C6 alkoxy. In other embodiments, R 2b is -(C1-C6 alkylene)-OH. In other embodiments, R 2b is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 2bis H, F, Cl, -CH3, -CH2CH3, -OCH3, -CH2OH, -CH2CH2CH2OH, or -C(O)OCH3. In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, F, Cl, —CH, —CHCH, —OCH, or —CHCHCHOH. 2b is H. In other embodiments, R 2b is F. In other embodiments, R 2b is Cl. In other embodiments, R 2b is -CH3. In other embodiments, R 2b is -CH2CH3. In other embodiments, R 2b is —OCH3. In other embodiments, R 2b is -CH2CH2CH2OH. In other embodiments, R 2b is D. In other embodiments, R 2b teeth, In another embodiment, R 2b is —CHOH. In other embodiments, R 2b is -C(O)OCH3.

[0077] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 haloalkoxy, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -(C1-C6 haloalkylene)-C(O)OH, -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C6-C 10 Aryl, C3-C 10 cycloalkyl, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein: The C3-C in question 10 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ where each R is substituted as needed. b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 4b H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, -(C1-C6 alkylene)-OH, -Si(C1-C6 alkyl)3, or (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4b is halo. In other embodiments, R 4b is C1-C6 alkyl. In other embodiments, R 4b is C1-C6 haloalkyl. In other embodiments, R 4b is C 1-C6 haloalkenyl. In other embodiments, R 4b is -(C1-C6 alkylene)-OH. In other embodiments, R 4b teeth,- Si(C1-C6 alkyl)3. In other embodiments, R 4b is (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4b is C1-C6 alkenyl. In other embodiments, R 4b is C1-C6 haloalkoxy. In other embodiments, R 4b is -(C1-C6 haloalkylene)-OH. In other embodiments, R 4b teeth, -(C1-C6 alkylene)-C(O)OH. In other embodiments, R 4b is -(C1-C6 haloalkylene)-C(O)OH. In other embodiments, R 4bis —C(O)O(C1-C6 alkyl). In other embodiments, R 4b is C6-C 10 In another embodiment, R 4b is C3-C 10 In another embodiment, R 4b is a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen. 10 The cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with one to two R b’ where each R is substituted as needed. b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 4b But H, Cl, -CH3, -CH(CH3)2, -C(CH3)3,-C(CH3)2(CH2CH3),-CF3,-C(CH3)2(CHF2),-C(CH3)2(CF3),-CH2C(CH3)2F,-CH=C(CH3)2, -C(=CH2)(CF3),-OCF3,-C(CH3)2(CH2OH),-C(CH3)(CF3)(CH2OH),-C(CH3)2(C(O)OH), -C(CH3)(CF3)(C(O)OH), -C(O)OCH3, -Si(CH3)3, phenyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, cyclobutyl, 1-methylcyclobutyl, 3,3-difluoro-1-methylcyclobutyl, cyclopentyl, 1-methylcyclopentyl, 1-trifluoromethylcyclopentyl, 3,3-difluoro-1-methylcyclopentyl, 4,4-difluoro-1-methylcyclohexyl, [ka] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CF3), -C(=CH2)(CF3), -C(CH3)2(CH2OH), -Si(CH3)3, or In another embodiment, R 4b is H. In other embodiments, R 4b is Cl. In other embodiments, R 4b is -CH3. In other embodiments, R 4b is —CH(CH). In other embodiments, R 4b teeth, In another embodiment, R 4b is —C(CH)(CHCH). In other embodiments, R 4b is -CF3. In other embodiments, R 4b is —C(CH)(CF). In other embodiments, R 4b is —C(═CH)(CF). In other embodiments, R 4b is —C(CH)(CHOH). In other embodiments, R 4b is —Si(CH3)3. In other embodiments, R 4b is 1-trifluoromethylcyclopropyl. In other embodiments, R 4b is D. In other embodiments, R 4b teeth, In another embodiment, R 4b is —C(CH)(CHF). In other embodiments, R 4b is —CHC(CH)F. In other embodiments, R 4b is -CH=C(CH3)2. In other embodiments, R 4b is -OCF3. In other embodiments, R 4b is —C(CH)(CF)(CHOH). In other embodiments, R4b is —C(CH)(C(O)OH). In other embodiments, R 4b is —C(CH)(CF)(C(O)OH). In other embodiments, R 4b is —C(O)OCH. In other embodiments, R 4b is phenyl. In another embodiment, R 4b is 1-methylcyclopropyl. In another embodiment, R 4b is cyclobutyl. In another embodiment, R 4b is 1-methylcyclobutyl. In another embodiment, R 4b teeth, In another embodiment, R 4b is cyclopentyl. In another embodiment, R 4b teeth, In another embodiment, R 4b is 1-trifluoromethylcyclopentyl. In another embodiment, R 4b is 3,3-difluoro-1-methylcyclopentyl. In another embodiment, R 4b is 4,4-difluoro-1-methylcyclohexyl. In another embodiment, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] is.

[0078] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C3-C6 cycloalkyl. In other embodiments, R 5b is halo. In other embodiments, R 5b is C 1-C6 alkyl. In other embodiments, R 5b is C1-C6 haloalkyl. In other embodiments, R 5b is C1-C6 alkoxy. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 5b But H, F, Cl, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CF3, -OCH3, or cyclopropyl. In other embodiments, R 5b is H. In other embodiments, R 5b is F. In other embodiments, R 5b is Cl. In other embodiments, R 5b is -CH3. In other embodiments, R 5b is -CH2CH3. In other embodiments, R 5b is —CH(CH). In other embodiments, R 5b is —C(CH3)3. In other embodiments, R 5b is -CF3. In other embodiments, R 5b is —OCH3. In other embodiments, R 5b is cyclopropyl. In other embodiments, R 5b is D. In other embodiments, R 5b teeth, -C(CD3)3.

[0079] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b and R 2b is H or C1-C6 alkyl. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b and R 2b is H or -CH3. In other embodiments, R 2b is H. In other embodiments, R 2b is -CH3.

[0080] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 5b is N. In some embodiments, the present invention relates to compounds of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b and R 5b is H or C1-C6 alkyl. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b and R 5b is H or -CH3. In other embodiments, R 5b is H. In other embodiments, R 5b is -CH3.

[0081] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, C-C alkyl, or —N(C-C alkyl)(C-C alkyl). In other embodiments, R 6b is C1-C6 alkyl. In other embodiments, R 6b is —N(C1-C6 alkyl)(C2-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, -CH3, -N(CH3)(CH2CH2CH2CH3), -N(CH2CH3)(CH2CH2CH3), -N(CH2CH2CH3)2, or In another embodiment, R 6b is H. In other embodiments, R 6b is -CH3. In other embodiments, R 6b is —N(CH)(CHCHCHCH). In other embodiments, R 6b teeth, In another embodiment, R 6b is —N(CH2CH2CH3)2. In other embodiments, R 6b is -N(CHCH(CH)).

[0082] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein Z is one to four R z In some embodiments, the present invention relates to compounds of formula (IA), or pharmaceutically acceptable salts thereof, wherein Z is: [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] is.

[0083] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R z In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R z is -CH3.

[0084] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R7b is —CH or —CH(CH). In other embodiments, R 7b is -CH3. In other embodiments, R 7b is -CH(CH3)2.

[0085] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 9b is -C(CH3)3.

[0086] In some embodiments, the present invention relates to a compound of formula (IA), or a pharmaceutically acceptable salt thereof, wherein R 10b is H or Cl. In other embodiments, R 10b is H. In other embodiments, R 10b is Cl.

[0087] In some embodiments, the present invention provides a compound of formula (IB): [ka] During the ceremony, X 5a But N or N + -O - and R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, R 4a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C4 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ , substituted as necessary with R 9a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, Each Ra’ are independently halo, —OH, C1-C6 alkyl, C1-C6 haloalkyl, —C(O)O(C1-C6 alkyl), or -C(O)NH2, Y is, [ka] and X 2b But N or CR 2b and X 3b But N or CR 3b and X 4b But N or CR 4b and X 5b But N or CR 5b and X 6b But N or CR 6b and Z optionally contains 1 to 3 heteroatoms selected from nitrogen and oxygen, and one or more R z is a 5- to 7-membered aromatic or non-aromatic ring optionally substituted with R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo; R 3b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 haloalkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C6-C 10 Aryl, C3-C 10cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein the C3-C 10 cycloalkyl, The cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ , substituted as necessary with R 5b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 6b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)(C2-C6 alkyl), -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 7b is C1-C6 alkyl, R 9b is C1-C6 alkyl, R 10b is H or halo, Each R b’ is independently C1-C6 alkyl or C1-C6 haloalkyl; R z halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkenyl, -CN, -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl), or -C(O)OH, however, (i) Y is [ka] and X 3b is CR 3b and X 6b is CR 6b If R 2b , R 3b , R 4b , R 5b , and R 6b and n is 0 or 1. The present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, provided that no more than three of

[0088] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein: R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C4 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, Y is, [ka] and R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo.

[0089] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 5a is N. In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 5a N + -O - is.

[0090] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 3ais H or C1-C6 alkyl. In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 3a is H or —CH 3 . In some embodiments, the present invention relates to compounds of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 3a is H. In other embodiments, R 3a is C1-C6 alkyl. In other embodiments, R 3a is -CH3.

[0091] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 4a is H.

[0092] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, C1-C4 alkoxy, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5-10 membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1-2 R a’ where each R is substituted as needed. a’ is Cl, —OH, —CH, —CHCH, —CF, —C(O)OCHCH, or —C(O)NH. In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, C1-C4 alkoxy, -NH(C1-C6 alkyl), -OH, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-N(C1-C6 alkyl), -C(O)NH , —C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl), —C(O)OH, —C(O)O(C1-C6 alkyl), or —C(S)NH. In other embodiments, R 6a is C1-C4 alkoxy. In other embodiments, R 6a is —NH(C1-C6 alkyl). In other embodiments, R 6a is —O(C1-C6 alkylene)-(C1-C6 alkoxy). In other embodiments, R 6a teeth, -O(C1-C6 alkylene)-N(C1-C6 alkyl). In other embodiments, R 6a is —C(O)NH(C1-C6 alkyl). In other embodiments, R 6a is —C(O)N(C1-C6 alkyl). In other embodiments, R 6a is —C(O)O(C1-C6 alkyl). In other embodiments, R 6a is —N(C1-C6 alkyl). In other embodiments, R 6a is —NHC(O)NH. In other embodiments, R 6a is —NHC(O)NH(C1-C6 alkyl). In other embodiments, R 6a is —C(NH)NH. In other embodiments, R 6a is -SO2NH2. In other embodiments, R 6a teeth, a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ where each R is substituted as needed. a’ is Cl, —OH, —CH, —CHCH, —CF, —C(O)OCHCH, or —C(O)NH. In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 6ais H, -CN, -OCH3, -NH(CH3), -N(CH3)2, -NHC(O)NH2, -NHC(O)NHCH3, -OH, -OCH2CH2OCH3, -OCH2CH2N(CH3)2, -C(O)NH2, -C(O)NH(CH3), -C(O)N(CH3)2, -C(O)OH, -C(O)OCH3, -C(NH)NH2, -C(S)NH2, -SO2NH2, [ka] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 6a But, H, -CN, -OCH3, -NH(CH3), -OH, -OCH2CH2OCH3, -OCH2CH2N(CH3)2, -C(O)NH2, -C(O)NH(CH3), In other embodiments, R 6a is H. In other embodiments, R 6a is -CN. In other embodiments, R 6a is —OCH3. In other embodiments, R 6a teeth, In another embodiment, R 6a is —OH. In other embodiments, R 6a is —OCH2CH2OCH3. In other embodiments, R 6a is —OCH2CH2N(CH3)2. In other embodiments, R 6a is —C(O)NH. In other embodiments, R 6a is —C(O)NH(CH). In other embodiments, R 6a is —C(O)N(CH) . In other embodiments, R 6a is —C(O)OH. In other embodiments, R 6a is —C(O)OCH. In other embodiments, R 6a is —C(S)NH. In other embodiments, R 6ais —N(CH). In other embodiments, R 6a is —NHC(O)NH. In other embodiments, R 6a is —NHC(O)NHCH. In other embodiments, R 6a is —C(NH)NH. In other embodiments, R 6a is -SO2NH2. In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] is.

[0093] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, halo, C1-C6 alkyl, C1-C6 alkoxy, —C(O)OH, or —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, halo, C1-C6 alkyl, or C1-C6 alkoxy. 9a is halo. In other embodiments, R9a is C1-C6 alkyl. In other embodiments, R 9a teeth, In another embodiment, R 9a is —C(O)OH. In other embodiments, R 9a teeth, In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, Cl, Br, —CH, —OCH, —OCHCH, —C(O)OH, or —C(O)OCH. In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, Cl, Br, —CH, —OCH, or —OCHCH. In other embodiments, R 9a is H. In other embodiments, R 9a is Cl. In other embodiments, R 9a is Br. In other embodiments, R 9a is -CH3. In other embodiments, R 9a is —OCH3. In other embodiments, R 9a teeth, In another embodiment, R 9a is —C(O)OH. In other embodiments, R 9a is -C(O)OCH3.

[0094] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] is.

[0095] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 3b is N. In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3b is H, halo, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3b is H, C1-C6 alkyl, or C1-C6 haloalkyl. 3b is C 1-C6 alkyl. In other embodiments, R 3b is C1-C6 haloalkyl. In other embodiments, R 3b In some embodiments, the present invention relates to compounds of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R3b is H, F, —CH 3 , or —CF 3 . In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein: X 3b is CR 3b and R 3b But R 3b But, H, In other embodiments, R 3b is H. In other embodiments, R 3b is -CH3. In other embodiments, R 3b is -CF3. In other embodiments, R 3b is D. In other embodiments, R 3b is -C(CD3)3. In other embodiments, R 3b is F.

[0096] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 6b is N. In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, halo, or C1-C6 alkyl. In other embodiments, R 6b is halo. In other embodiments, R 6b In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, F, or —CH. In other embodiments, R 6b is H. In other embodiments, R 6b is F. In other embodiments, R 6b is -CH3. In other embodiments, R 6b is D. In other embodiments, R6b is -C(CD3)3.

[0097] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, The cycloalkyl in the (C-C alkyl)-(C-C cycloalkyl)- or (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo. In other embodiments, R 2b is D. In other embodiments, R 2b is -C(CD3)3.

[0098] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 2b But, H, halo, C1-C6 alkyl, C1-C6 alkoxy, or -(C1-C6 alkylene)-OH. In other embodiments, R 2b is H. In other embodiments, R2b is halo. In other embodiments, R 2b is C1-C6 alkyl. In other embodiments, R 2b teeth, In another embodiment, R 2b is -(C1-C6 alkylene)-OH. In other embodiments, R 2b teeth, In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, F, Cl, -CH3, -CH2CH3, -OCH3, -CH2OH, In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, F, Cl, -CH3, -CH2CH3, -OCH3, or In another embodiment, R 2b is H. In other embodiments, R 2b is F. In other embodiments, R 2b is Cl. In other embodiments, R 2b is -CH3. In other embodiments, R 2b is -CH2CH3. In other embodiments, R 2b is —OCH3. In other embodiments, R 2b is -CH2CH2CH2OH. In other embodiments, R 2b is —CHOH. In other embodiments, R 2b is -C(O)OCH3.

[0099] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 haloalkoxy, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -(C1-C6 haloalkylene)-C(O)OH, -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C6-C 10 Aryl, C3-C 10 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein the C3-C 10 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ where each R is substituted as needed. b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, -(C1-C6 alkylene)-OH, -Si(C1-C6 alkyl)3, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-. In other embodiments, R 4b is halo. In other embodiments, R 4b is C1-C6 alkyl. In other embodiments, R 4b is C1-C6 haloalkyl. In other embodiments, R 4b is C1-C6 haloalkenyl. In other embodiments, R 4b is -(C1-C6 alkylene)-OH. In other embodiments, R 4b is —Si(C1-C6 alkyl). In other embodiments, R 4bis (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4b is C1-C6 alkenyl. In other embodiments, R 4b is C1-C6 haloalkoxy. In other embodiments, R 4b is -(C1-C6 haloalkylene)-OH. In other embodiments, R 4b teeth, -(C1-C6 alkylene)-C(O)OH. In other embodiments, R 4b is -(C1-C6 haloalkylene)-C(O)OH. In other embodiments, R 4b is —C(O)O(C1-C6 alkyl). In other embodiments, R 4b is C6-C 10 In another embodiment, R 4b is C3-C 10 In another embodiment, R 4b is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-. In other embodiments, R 4b is a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen. 10 cycloalkyl, The cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ where each R is substituted as needed. b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CHF2), -C(CH3)2(CF3), -CH2C(CH3)2F, -CH=C(CH3)2, -C(=CH2)(CF3), -OCF3, -C(CH3)2(CH2OH), -C(CH3)(CF3)(CH2OH), -C(CH3)2(C(O)OH), -C(CH3)(CF3)(C(O)OH), -C(O)OCH3, -Si(CH3)3, phenyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, cyclobutyl, 1-methylcyclobutyl, 3,3-difluoro-1-methylcyclobutyl, cyclopentyl, 1-methylcyclopentyl, 1-trifluoromethylcyclopentyl, 3,3-difluoro-1-methylcyclopentyl, 4,4-difluoro-1-methylcyclohexyl, [ka] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CF3), -C(=CH2)(CF3), -C(CH3)2(CH2OH), -Si(CH3)3, or In another embodiment, R 4b is H. In other embodiments, R 4b is Cl. In other embodiments, R 4b is -CH3. In other embodiments, R 4b is —CH(CH). In other embodiments, R 4b teeth, In another embodiment, R 4b is —C(CH)(CHCH). In other embodiments, R 4b is -CF3. In other embodiments, R 4b is —C(CH)(CF). In other embodiments, R 4b is —C(═CH)(CF). In other embodiments, R 4bis —C(CH)(CHOH). In other embodiments, R 4b is —Si(CH3)3. In other embodiments, R 4b is 1-trifluoromethylcyclopropyl. In other embodiments, R 4b is D. In other embodiments, R 4b teeth, In another embodiment, R 4b is —C(CH)(CHF). In other embodiments, R 4b is —CHC(CH)F. In other embodiments, R 4b is -CH=C(CH3)2. In other embodiments, R 4b is -OCF3. In other embodiments, R 4b is —C(CH)(CF)(CHOH). In other embodiments, R 4b is —C(CH)(C(O)OH). In other embodiments, R 4b is —C(CH)(CF)(C(O)OH). In other embodiments, R 4b is —C(O)OCH. In other embodiments, R 4b is phenyl. In another embodiment, R 4b is 1-methylcyclopropyl. In another embodiment, R 4b is cyclobutyl. In another embodiment, R 4b is 1-methylcyclobutyl. In another embodiment, R 4b teeth, In another embodiment, R 4b is cyclopentyl. In another embodiment, R 4b is 1-methylcyclopentyl. In another embodiment, R 4b is 1-trifluoromethylcyclopentyl. In another embodiment, R 4b is 3,3-difluoro-1-methylcyclopentyl. In another embodiment, R 4b is 4,4-difluoro-1-methylcyclohexyl. In another embodiment, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] is.

[0100] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C3-C6 cycloalkyl. In other embodiments, R 5b is halo. In other embodiments, R 5b is C 1-C6 alkyl. In other embodiments, R 5b is C1-C6 haloalkyl. In other embodiments, R 5b is C1-C6 alkoxy. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 5b But H, F, Cl, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CF3, -OCH3, or cyclopropyl. In other embodiments, R 5b is H. In other embodiments, R 5bis F. In other embodiments, R 5b is Cl. In other embodiments, R 5b is -CH3. In other embodiments, R 5b is -CH2CH3. In other embodiments, R 5b is —CH(CH). In other embodiments, R 5b is —C(CH3)3. In other embodiments, R 5b is -CF3. In other embodiments, R 5b is —OCH3. In other embodiments, R 5b is cyclopropyl. In other embodiments, R 5b is D. In other embodiments, R 5b teeth, -C(CD3)3.

[0101] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b and R 2b is H or C1-C6 alkyl. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b and R 2b is H or -CH3. In other embodiments, R 2b is H. In other embodiments, R 2b is -CH3.

[0102] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 5b is N. In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5bIn some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b and R 5b is H or C1-C6 alkyl. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b and R 5b is H or -CH3. In other embodiments, R 5b is H. In other embodiments, R 5b is -CH3.

[0103] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, C-C alkyl, or —N(C-C alkyl)(C-C alkyl). In other embodiments, R 6b is C1-C6 alkyl. In other embodiments, R 6b is —N(C1-C6 alkyl)(C2-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b But R 6b is H, -CH3, -N(CH3)(CH2CH2CH2CH3), -N(CH2CH3)(CH2CH2CH3), -N(CH2CH2CH3)2, or In another embodiment, R 6b is H. In other embodiments, R 6b is -CH3. In other embodiments, R 6bis —N(CH)(CHCHCHCH). In other embodiments, R 6b teeth, In another embodiment, R 6b is —N(CH2CH2CH3)2. In other embodiments, R 6b is -N(CHCH(CH)).

[0104] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein Z is one to four R z In some embodiments, the present invention relates to compounds of formula (IB), or pharmaceutically acceptable salts thereof, wherein Z is: [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] is.

[0105] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R z In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R z but -CH3.

[0106] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 7b is —CH or —CH(CH). In other embodiments, R 7b is -CH3. In other embodiments, R 7b is -CH(CH3)2.

[0107] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 9b is -C(CH3)3.

[0108] In some embodiments, the present invention relates to a compound of formula (IB), or a pharmaceutically acceptable salt thereof, wherein R 10b is H or Cl. In other embodiments, R 10b is H. In other embodiments, R 10b is Cl.

[0109] In some embodiments, the present invention provides a compound of formula (IC): [ka] During the ceremony, R 6ais H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C4 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ , substituted as necessary with R 9a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, Each R a’ are independently halo, —OH, C1-C6 alkyl, C1-C6 haloalkyl, —C(O)O(C1-C6 alkyl), or -C(O)NH2, Y is, [ka] and X 2b But N or CR 2b and X 3b But N or CR 3b and X 4b But N or CR 4b and X 5b But N or CR 5b and X 6b But N or CR 6b and Z optionally contains 1 to 3 heteroatoms selected from nitrogen and oxygen, and one or more R z is a 5- to 7-membered aromatic or non-aromatic ring optionally substituted with R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo; R 3b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 haloalkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C6-C 10 Aryl, C3-C 10 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein the C3-C 10 cycloalkyl, The cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ , substituted as necessary with R 5b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 6b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)(C2-C6 alkyl), -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 7b is C1-C6 alkyl, R 9b is C1-C6 alkyl, R 10b is H or halo, Each R b’ is independently C1-C6 alkyl or C1-C6 haloalkyl; R z halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkenyl, -CN, -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl), or -C(O)OH, however, (i) Y is [ka] and X 3b is CR 3b and X 6b is CR 6b If R 2b , R 3b , R 4b , R 5b , and R 6band n is 0 or 1. The present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, provided that no more than three of

[0110] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein: R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C4 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, Y is, [ka] and R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo.

[0111] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, C1-C4 alkoxy, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5-10 membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1-2 R a’ where each R is substituted as needed. a’ is Cl, —OH, —CH, —CHCH, —CF, —C(O)OCHCH, or —C(O)NH. In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, C1-C4 alkoxy, -NH(C1-C6 alkyl), -OH, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-N(C1-C6 alkyl), -C(O)NH , —C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl), —C(O)OH, —C(O)O(C1-C6 alkyl), or —C(S)NH. In other embodiments, R 6a is C1-C4 alkoxy. In other embodiments, R 6a is —NH(C1-C6 alkyl). In other embodiments, R 6a is —O(C1-C6 alkylene)-(C1-C6 alkoxy). In other embodiments, R 6a teeth, -O(C1-C6 alkylene)-N(C1-C6 alkyl). In other embodiments, R 6a is —C(O)NH(C1-C6 alkyl). In other embodiments, R 6a is —C(O)N(C1-C6 alkyl). In other embodiments, R 6a is —C(O)O(C1-C6 alkyl). In other embodiments, R 6a is —N(C1-C6 alkyl). In other embodiments, R 6ais —NHC(O)NH. In other embodiments, R 6a is —NHC(O)NH(C1-C6 alkyl). In other embodiments, R 6a is —C(NH)NH. In other embodiments, R 6a is -SO2NH2. In other embodiments, R 6a is a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ where each R is substituted as needed. a’ is Cl, —OH, —CH, —CHCH, —CF, —C(O)OCHCH, or —C(O)NH. In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, -OCH3, -NH(CH3), -N(CH3)2, -NHC(O)NH2, -NHC(O)NHCH3, -OH, -OCH2CH2OCH3, -OCH2CH2N(CH3)2, -C(O)NH2, -C(O)NH(CH3), -C(O)N(CH3)2, -C(O)OH, -C(O)OCH3, -C(NH)NH2, -C(S)NH2, -SO2NH2, [ka] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, -OCH3, -NH(CH3), -OH, -OCH2CH2OCH3, -OCH2CH2N(CH3)2, -C(O)NH2, -C(O)NH(CH3), -C(O)N(CH3)2, In other embodiments, R 6a is H. In other embodiments, R 6a teeth,- In another embodiment, R 6a is —OCH3. In other embodiments, R 6ais —NH(CH). In other embodiments, R 6a is —OH. In other embodiments, R 6a is —OCH2CH2OCH3. In other embodiments, R 6a is —OCH2CH2N(CH3)2. In other embodiments, R 6a is —C(O)NH. In other embodiments, R 6a teeth, In another embodiment, R 6a is —C(O)N(CH) . In other embodiments, R 6a is —C(O)OH. In other embodiments, R 6a is —C(O)OCH. In other embodiments, R 6a is —C(S)NH. In other embodiments, R 6a is —N(CH). In other embodiments, R 6a is —NHC(O)NH. In other embodiments, R 6a is —NHC(O)NHCH. In other embodiments, R 6a is —C(NH)NH. In other embodiments, R 6a is -SO2NH2. In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] is.

[0112] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, halo, C1-C6 alkyl, C1-C6 alkoxy, or In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, halo, C1-C6 alkyl, or C1-C6 alkoxy. 9a is halo. In other embodiments, R 9a is C1-C6 alkyl. In other embodiments, R 9a teeth, In another embodiment, R 9a is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, Cl, Br, —CH 3 , —OCH 3 , —OCH 2 CH 3 , or —C(O)OCH 3 . In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, Cl, Br, —CH, —OCH, or —OCHCH. In other embodiments, R 9a is H. In other embodiments, R 9a is Cl. In other embodiments, R 9a is Br. In other embodiments, R 9a is -CH3. In other embodiments, R 9a is —OCH3. In other embodiments, R 9a is —OCH2CH3. In other embodiments, R 9a is -C(O)OCH3.

[0113] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein: [ka] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein: [ka] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] is.

[0114] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 3b is N. In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3b In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3bis H, halo, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3b is H, C1-C6 alkyl, or C1-C6 haloalkyl. 3b is C1-C6 alkyl. In other embodiments, R 3b is C1-C6 haloalkyl. In other embodiments, R 3b In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 3b is H, F, —CH 3 , or —CF 3 . In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein: X 3b is CR 3b and R 3b is H, —CH, or —CF. In other embodiments, R 3b is H. In other embodiments, R 3b is -CH3. In other embodiments, R 3b is -CF3. In other embodiments, R 3b is D. In other embodiments, R 3b is -C(CD3)3. In other embodiments, R 3b is F.

[0115] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 6b is N. In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, halo, or C1-C6 alkyl. In other embodiments, R 6bis halo. In other embodiments, R 6b In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, F, or —CH. In other embodiments, R 6b is H. In other embodiments, R 6b is F. In other embodiments, R 6b is -CH3. In other embodiments, R 6b is D. In other embodiments, R 6b is -C(CD3)3.

[0116] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, The cycloalkyl in the (C-C alkyl)-(C-C cycloalkyl)- or (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo. In other embodiments, R 2b is D. In other embodiments, R 2b is -C(CD3)3.

[0117] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 2b halo, C1-C6 alkyl, C1-C6 alkoxy, In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 2b But, halo, C1-C6 alkyl, C1-C6 alkoxy, or -(C1-C6 alkylene)-OH. In other embodiments, R 2b is halo. In other embodiments, R 2b is C1-C6 alkyl. In other embodiments, R 2b is C1-C6 alkoxy. In other embodiments, R 2b is -(C1-C6 alkylene)-OH. In other embodiments, R 2b is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 2b is F, Cl, -CH3, -CH2CH3, -OCH3, -CH2OH, -CH2CH2CH2OH, or -C(O)OCH3. In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 2b is F, Cl, —CH, —CHCH, —OCH, or —CHCHCHOH. 2b is F. In other embodiments, R 2b is Cl. In other embodiments, R 2b is -CH3. In other embodiments, R 2b teeth, In another embodiment, R 2b is —OCH3. In other embodiments, R 2b is -CH2CH2CH2OH. In other embodiments, R 2b is —CHOH. In other embodiments, R 2b is -C(O)OCH3.

[0118] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 haloalkoxy, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -(C1-C6 haloalkylene)-C(O)OH, -C(O)(O)(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C6-C 10 Aryl, C3-C 10 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein the C3-C 10 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ where each R is substituted as needed. b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, -(C1-C6 alkylene)-OH, -Si(C1-C6 alkyl)3, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-. In other embodiments, R 4b is halo. In other embodiments, R 4b is C1-C6 alkyl. In other embodiments, R 4b is C1-C6 haloalkyl. In other embodiments, R 4b is C1-C6 haloalkenyl. In other embodiments, R 4bis -(C1-C6 alkylene)-OH. In other embodiments, R 4b is —Si(C1-C6 alkyl). In other embodiments, R 4b is (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4b is C1-C6 alkenyl. In other embodiments, R 4b is C1-C6 haloalkoxy. In other embodiments, R 4b is -(C1-C6 haloalkylene)-OH. In other embodiments, R 4b teeth, -(C1-C6 alkylene)-C(O)OH. In other embodiments, R 4b is -(C1-C6 haloalkylene)-C(O)OH. In other embodiments, R 4b is —C(O)(O)(C1-C6 alkyl). In other embodiments, R 4b is C6-C 10 In another embodiment, R 4b is C3-C 10 In another embodiment, R 4b is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-. In other embodiments, R 4b is a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen. 10 cycloalkyl, The cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ where each R is substituted as needed. b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CHF2), -C(CH3)2(CF3), -CH2C(CH3)2F, -CH=C(CH3)2, -C(=CH2)(CF3), -OCF3, -C(CH3)2(CH2OH), -C(CH3)(CF3)(CH2OH), -C(CH3)2(C(O)OH), -C(CH3)(CF3)(C(O)OH), -C(O)OCH3, -Si(CH3)3, phenyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, cyclobutyl, 1-methylcyclobutyl, 3,3-difluoro-1-methylcyclobutyl, cyclopentyl, 1-methylcyclopentyl, 1-trifluoromethylcyclopentyl, 3,3-difluoro-1-methylcyclopentyl, 4,4-difluoro-1-methylcyclohexyl, [ka] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CF3), -C(=CH2)(CF3), -C(CH3)2(CH2OH), -Si(CH3)3, or In another embodiment, R 4b is H. In other embodiments, R 4b is Cl. In other embodiments, R 4b is -CH3. In other embodiments, R 4b is —CH(CH). In other embodiments, R 4b teeth, In another embodiment, R 4b is —C(CH)(CHCH). In other embodiments, R 4b is -CF3. In other embodiments, R 4bis —C(CH)(CF). In other embodiments, R 4b is —C(═CH)(CF). In other embodiments, R 4b is —C(CH)(CHOH). In other embodiments, R 4b is —Si(CH3)3. In other embodiments, R 4b is 1-trifluoromethylcyclopropyl. In other embodiments, R 4b is D. In other embodiments, R 4b teeth, In another embodiment, R 4b is —C(CH)(CHF). In other embodiments, R 4b is —CHC(CH)F. In other embodiments, R 4b is -CH=C(CH3)2. In other embodiments, R 4b is -OCF3. In other embodiments, R 4b is —C(CH)(CF)(CHOH). In other embodiments, R 4b is —C(CH)(C(O)OH). In other embodiments, R 4b is —C(CH)(CF)(C(O)OH). In other embodiments, R 4b is —C(O)OCH. In other embodiments, R 4b is phenyl. In another embodiment, R 4b is 1-methylcyclopropyl. In another embodiment, R 4b is cyclobutyl. In another embodiment, R 4b is 1-methylcyclobutyl. In another embodiment, R 4b teeth, In another embodiment, R 4b is cyclopentyl. In another embodiment, R 4b is 1-methylcyclopentyl. In another embodiment, R 4b is 1-trifluoromethylcyclopentyl. In another embodiment, R 4bis 3,3-difluoro-1-methylcyclopentyl. In another embodiment, R 4b is 4,4-difluoro-1-methylcyclohexyl. In another embodiment, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] is.

[0119] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C3-C6 cycloalkyl. In other embodiments, R 5b is halo. In other embodiments, R 5b is C 1-C6 alkyl. In other embodiments, R 5b is C1-C6 haloalkyl. In other embodiments, R 5b is C1-C6 alkoxy. In other embodiments, R 5b or C3-C6 cycloalkyl. In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 5b But H, F, Cl, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CF3, -OCH3, or cyclopropyl. In other embodiments, R 5b is H. In other embodiments, R 5b is F. In other embodiments, R 5b is Cl. In other embodiments, R 5b is -CH3. In other embodiments, R 5b is -CH2CH3. In other embodiments, R 5b is —CH(CH). In other embodiments, R 5b is —C(CH3)3. In other embodiments, R 5b is -CF3. In other embodiments, R 5b is —OCH3. In other embodiments, R 5b is cyclopropyl. In other embodiments, R 5b is D. In other embodiments, R 5b teeth, -C(CD3)3.

[0120] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b and R 2b is H or C1-C6 alkyl. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b and R 2b is H or -CH3. In other embodiments, R 2b is H. In other embodiments, R 2b is -CH3.

[0121] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 5b is N. In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b and R 5b is H or C1-C6 alkyl. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b and R 5b is H or -CH3. In other embodiments, R 5b is H. In other embodiments, R 5b is -CH3.

[0122] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, C-C alkyl, or —N(C-C alkyl)(C-C alkyl). In other embodiments, R 6b is C1-C6 alkyl. In other embodiments, R 6b is —N(C1-C6 alkyl)(C2-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, -CH3, -N(CH3)(CH2CH2CH2CH3), -N(CH2CH3)(CH2CH2CH3), -N(CH2CH2CH3)2, or In another embodiment, R 6b is H. In other embodiments, R 6b is -CH3. In other embodiments, R 6b is —N(CH)(CHCHCHCH). In other embodiments, R 6b teeth, In another embodiment, R 6b is —N(CH2CH2CH3)2. In other embodiments, R 6b is -N(CHCH(CH)).

[0123] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein Z is one to four R z In some embodiments, the present invention relates to compounds of formula (IC), or pharmaceutically acceptable salts thereof, wherein Z is: [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] is.

[0124] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R z In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R z is -CH3.

[0125] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 7b is —CH or —CH(CH). In other embodiments, R 7b is -CH3. In other embodiments, R 7b is -CH(CH3)2.

[0126] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 9b is -C(CH3)3.

[0127] In some embodiments, the present invention relates to a compound of formula (IC), or a pharmaceutically acceptable salt thereof, wherein R 10b is H or Cl. In other embodiments, R 10b is H. In other embodiments, R 10b is Cl.

[0128] In some embodiments, the present invention provides a compound of formula (ID): [ka] During the ceremony, R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ , substituted as necessary with R 9a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, Each R a’ are independently halo, —OH, C1-C6 alkyl, C1-C6 haloalkyl, —C(O)O(C1-C6 alkyl), or -C(O)NH2, X 2b But N or CR 2b and X 5b But N or CR 5b and X 6b But N or CR 6b and Z optionally contains 1 to 3 heteroatoms selected from nitrogen and oxygen, and one or more R z is a 5- to 7-membered aromatic or non-aromatic ring optionally substituted with R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo; R 5b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 6b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)(C2-C6 alkyl), -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R z halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkoxy, C1-C6 haloalkenyl, -CN, -C(O)NH2, The present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein the compound is —C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl)2, or —C(O)OH.

[0129] In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein: R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo.

[0130] In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein R 6a is —OH or —C(O)NH. In other embodiments, R 6a is —OH. In other embodiments, R 6a is -C(O)NH2.

[0131] In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein R 9a is H.

[0132] In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b and R 2bis H or C1-C6 alkyl. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein X 2b is CR 2b and R 2b is H or -CH3. In other embodiments, R 2b is H. In other embodiments, R 2b is -CH3.

[0133] In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, The cycloalkyl in the (C-C alkyl)-(C-C cycloalkyl)- or (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo. In other embodiments, R 2b is D. In other embodiments, R 2b is -C(CD3)3.

[0134] In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein X 5bis N. In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b and R 5b is H or C1-C6 alkyl. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein X 5b is CR 5b and R 5b is H or -CH3. In other embodiments, R 5b is H. In other embodiments, R 5b is -CH3.

[0135] In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, C-C alkyl, or —N(C-C alkyl)(C-C alkyl). In other embodiments, R 6b is C1-C6 alkyl. In other embodiments, R 6b is —N(C1-C6 alkyl)(C2-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, -CH3, -N(CH3)(CH2CH2CH2CH3), -N(CH2CH3)(CH2CH2CH3), -N(CH2CH2CH3)2, or In another embodiment, R 6bis H. In other embodiments, R 6b is -CH3. In other embodiments, R 6b is —N(CH)(CHCHCHCH). In other embodiments, R 6b teeth, In another embodiment, R 6b is —N(CH2CH2CH3)2. In other embodiments, R 6b is -N(CHCH(CH)).

[0136] In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein Z is one to four R z In some embodiments, the present invention relates to compounds of formula (ID), or pharmaceutically acceptable salts thereof, wherein Z is: [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] In other embodiments, Z is [ka] is.

[0137] In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein R z In some embodiments, the present invention relates to a compound of formula (ID), or a pharmaceutically acceptable salt thereof, wherein R z is -CH3.

[0138] In some embodiments, the present invention provides a compound of formula (IE): [ka] During the ceremony, X 5a But N or N + -O - and R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C4 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ , substituted as necessary with R 9a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, Each R a’ are independently halo, —OH, C1-C6 alkyl, C1-C6 haloalkyl, —C(O)O(C1-C6 alkyl), or -C(O)NH2, X 3b But N or CR 3b and X 6b But N or CR 6b and R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo; R 3b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 haloalkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)(O)(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C6-C 10 Aryl, C3-C 10 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein the C3-C 10 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ , substituted as necessary with R 5b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 6b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; Each R b’ is independently C1-C6 alkyl or C1-C6 haloalkyl, However, X 3b is CR 3b and X 6b is CR 6b If R 2b , R 3b , R 4b , R 5b , and R 6bwherein no more than three of are H, or a pharmaceutically acceptable salt thereof.

[0139] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein: R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C4 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), or -C(S)NH2; R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo.

[0140] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein X 5a is N. In some embodiments, the present invention relates to compounds of formula (IE), or a pharmaceutically acceptable salt thereof, wherein X 5a N + -O - is.

[0141] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, C1-C4 alkoxy, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5-10 membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1-2 R a’ where each R is substituted as needed. a’ is Cl, —OH, —CH, —CHCH, —CF, —C(O)OCHCH, or —C(O)NH. In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, C1-C4 alkoxy, -NH(C1-C6 alkyl), -OH, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-N(C1-C6 alkyl), -C(O)NH , —C(O)NH(C1-C6 alkyl), —C(O)N(C1-C6 alkyl), —C(O)OH, —C(O)O(C1-C6 alkyl), or —C(S)NH. In other embodiments, R 6a is C1-C4 alkoxy. In other embodiments, R 6a is —NH(C1-C6 alkyl). In other embodiments, R 6a is —O(C1-C6 alkylene)-(C1-C6 alkoxy). In other embodiments, R 6a teeth, -O(C1-C6 alkylene)-N(C1-C6 alkyl). In other embodiments, R 6a is —C(O)NH(C1-C6 alkyl). In other embodiments, R 6a is —C(O)N(C1-C6 alkyl). In other embodiments, R 6ais —C(O)O(C1-C6 alkyl). In other embodiments, R 6a is —N(C1-C6 alkyl). In other embodiments, R 6a is —NHC(O)NH. In other embodiments, R 6a is —NHC(O)NH(C1-C6 alkyl). In other embodiments, R 6a is —C(NH)NH. In other embodiments, R 6a is -SO2NH2. In other embodiments, R 6a teeth, a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ where each R is substituted as needed. a’ is Cl, —OH, —CH, —CHCH, —CF, —C(O)OCHCH, or —C(O)NH. In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, -OCH3, -NH(CH3), -N(CH3)2, -NHC(O)NH2, -NHC(O)NHCH3, -OH, -OCH2CH2OCH3, -OCH2CH2N(CH3)2, -C(O)NH2, -C(O)NH(CH3), -C(O)N(CH3)2, -C(O)OH, -C(O)OCH3, -C(NH)NH2, -C(S)NH2, -SO2NH2, [ka] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 6a But, H, -CN, -OCH3, -NH(CH3), -OH, -OCH2CH2OCH3, -OCH2CH2N(CH3)2, -C(O)NH2, -C(O)NH(CH3), In other embodiments, R 6ais H. In other embodiments, R 6a is -CN. In other embodiments, R 6a is —OCH3. In other embodiments, R 6a teeth, In another embodiment, R 6a is —OH. In other embodiments, R 6a is —OCH2CH2OCH3. In other embodiments, R 6a is —OCH2CH2N(CH3)2. In other embodiments, R 6a is —C(O)NH. In other embodiments, R 6a is —C(O)NH(CH). In other embodiments, R 6a is —C(O)N(CH) . In other embodiments, R 6a is —C(O)OH. In other embodiments, R 6a is —C(O)OCH. In other embodiments, R 6a is —C(S)NH. In other embodiments, R 6a is —N(CH). In other embodiments, R 6a is —NHC(O)NH. In other embodiments, R 6a is —NHC(O)NHCH. In other embodiments, R 6a is —C(NH)NH. In other embodiments, R 6a is -SO2NH2. In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R6a teeth, [ka] In other embodiments, R 6a or [ka] is.

[0142] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, halo, C1-C6 alkyl, C1-C6 alkoxy, or In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, halo, C1-C6 alkyl, or C1-C6 alkoxy. 9a is halo. In other embodiments, R 9a is C1-C6 alkyl. In other embodiments, R 9a teeth, In another embodiment, R 9a is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein H, Cl, Br, In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, Cl, Br, —CH, —OCH, or —OCHCH. In other embodiments, R 9a is H. In other embodiments, R 9a is Cl. In other embodiments, R 9a is Br. In other embodiments, R 9a is -CH3. In other embodiments, R 9a is —OCH3. In other embodiments, R 9ais —OCH2CH3. In other embodiments, R 9a is -C(O)OCH3.

[0143] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein X 3b is N. In some embodiments, the present invention relates to compounds of formula (IE), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3b is H, halo, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3b is H, C1-C6 alkyl, or C1-C6 haloalkyl. 3b is C 1-C6 alkyl. In other embodiments, R 3b is C1-C6 haloalkyl. In other embodiments, R 3b In some embodiments, the present invention relates to compounds of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 3b is H, F, —CH 3 , or —CF 3 . In some embodiments, the present invention relates to compounds of formula (IE), or a pharmaceutically acceptable salt thereof, wherein X 3b is CR 3b and R 3b is H, —CH, or —CF. In other embodiments, R 3b is H. In other embodiments, R 3b is -CH3. In other embodiments, R 3b is -CF3. In other embodiments, R 3b is F.

[0144] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein X 6b is N. In some embodiments, the present invention relates to compounds of formula (IE), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, halo, or C1-C6 alkyl. In other embodiments, R 6b is halo. In other embodiments, R 6b In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein X 6b is CR 6b and R 6b is H, F, or —CH. In other embodiments, R 6b is H. In other embodiments, R 6b is F. In other embodiments, R 6b is -CH3.

[0145] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, The cycloalkyl in the (C-C alkyl)-(C-C cycloalkyl)- or (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo. In other embodiments, R 2b is D. In other embodiments, R 2b is -C(CD3)3.

[0146] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 2b halo, C1-C6 alkyl, C1-C6 alkoxy, In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 2b But, halo, C1-C6 alkyl, C1-C6 alkoxy, or -(C1-C6 alkylene)-OH. In other embodiments, R 2b is halo. In other embodiments, R 2b is C1-C6 alkyl. In other embodiments, R 2b is C1-C6 alkoxy. In other embodiments, R 2b is -(C1-C6 alkylene)-OH. In other embodiments, R 2b is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 2b is F, Cl, -CH3, -CH2CH3, -OCH3, -CH2OH, -CH2CH2CH2OH, or -C(O)OCH3. In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 2b is F, Cl, —CH, —CHCH, —OCH, or —CHCHCHOH. 2b is F. In other embodiments, R 2b is Cl. In other embodiments, R 2bis -CH3. In other embodiments, R 2b teeth, In another embodiment, R 2b is —OCH3. In other embodiments, R 2b is -CH2CH2CH2OH. In other embodiments, R 2b is —CHOH. In other embodiments, R 2b is -C(O)OCH3.

[0147] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 haloalkoxy, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -(C1-C6 haloalkylene)-C(O)OH, -Si(C1-C6 alkyl)3, C6-C 10 aryl, C3-C 10 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein the C3-C 10 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ where each R is substituted as needed. b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, -(C1-C6 alkylene)-OH, -Si(C1-C6 alkyl)3, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-. In other embodiments, R 4b is halo. In other embodiments, R 4b is C1-C6 alkyl. In other embodiments, R 4b is C1-C6 haloalkyl. In other embodiments, R 4b is C1-C6 haloalkenyl. In other embodiments, R 4b is -(C1-C6 alkylene)-OH. In other embodiments, R 4b is —Si(C1-C6 alkyl). In other embodiments, R 4b is (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4b is C1-C6 alkenyl. In other embodiments, R 4b is C1-C6 haloalkoxy. In other embodiments, R 4b is -(C1-C6 haloalkylene)-OH. In other embodiments, R 4b teeth, -(C1-C6 alkylene)-C(O)OH. In other embodiments, R 4b is -(C1-C6 haloalkylene)-C(O)OH. In other embodiments, R 4b is C6-C 10 In another embodiment, R 4b is C3-C 10 In another embodiment, R 4b is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-. In other embodiments, R 4b is a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen. 10 The cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with one to two R b’ where each R is substituted as needed.b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CH=C(CH3)2, -CF3, -C(CH3)2(CHF2), -C(CH3)2(CF3), -CH2C(CH3)2F, -C(=CH2)(CF3), -OCF3, -C(CH3)2(CH2OH), -C(CH3)(CF3)(CH2OH), -C(CH3)2(C(O)OH), -C(CH3)(CF3)(C(O)OH), -C(O)OCH3, -Si(CH3)3, phenyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, cyclobutyl, 1-methylcyclobutyl, 3,3-difluoro-1-methylcyclobutyl, cyclopentyl, 1-methylcyclopentyl, 1-trifluoromethylcyclopentyl, 3,3-difluoro-1-methylcyclopentyl, 4,4-difluoro-1-methylcyclohexyl, [ka] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 4b is H, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CF3), -C(=CH2)(CF3), -C(CH3)2(CH2OH), -Si(CH3)3, or In another embodiment, R 4b is H. In other embodiments, R 4b is Cl. In other embodiments, R 4b is -CH3. In other embodiments, R 4b is —CH(CH). In other embodiments, R 4b teeth, In another embodiment, R 4b is —C(CH)(CHCH). In other embodiments, R 4b is -CF3. In other embodiments, R 4b is —C(CH)(CF). In other embodiments, R 4b is —C(═CH)(CF). In other embodiments, R 4b is —C(CH)(CHOH). In other embodiments, R 4b is —Si(CH3)3. In other embodiments, R 4b is 1-trifluoromethylcyclopropyl. In other embodiments, R 4b is D. In other embodiments, R 4b teeth, In another embodiment, R 4b is -CH=C(CH3)2. In other embodiments, R 4b is —C(CH)(CHF). In other embodiments, R 4b is —CHC(CH)F. In other embodiments, R 4b is -OCF3. In other embodiments, R 4b is —C(CH)(CF)(CHOH). In other embodiments, R 4b is —C(CH)(C(O)OH). In other embodiments, R 4b is —C(CH)(CF)(C(O)OH). In other embodiments, R 4b is —C(O)OCH. In other embodiments, R 4b is phenyl. In another embodiment, R 4b is 1-methylcyclopropyl. In another embodiment, R 4b is cyclobutyl. In another embodiment, R 4b is 1-methylcyclobutyl. In another embodiment, R 4b teeth, In another embodiment, R 4b is cyclopentyl. In another embodiment, R 4bis 1-methylcyclopentyl. In another embodiment, R 4b is 1-trifluoromethylcyclopentyl. In another embodiment, R 4b is 3,3-difluoro-1-methylcyclopentyl. In another embodiment, R 4b is 4,4-difluoro-1-methylcyclohexyl. In another embodiment, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] is.

[0148] In some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or C3-C6 cycloalkyl. In other embodiments, R 5b is halo. In other embodiments, R 5b is C 1-C6 alkyl. In other embodiments, R 5b is C1-C6 haloalkyl. In other embodiments, R 5b is C1-C6 alkoxy. In other embodiments, R 5bIn some embodiments, the present invention relates to a compound of formula (IE), or a pharmaceutically acceptable salt thereof, wherein R 5b But H, F, Cl, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CF3, -OCH3, or cyclopropyl. In other embodiments, R 5b is H. In other embodiments, R 5b is F. In other embodiments, R 5b is Cl. In other embodiments, R 5b is -CH3. In other embodiments, R 5b is -CH2CH3. In other embodiments, R 5b is —CH(CH). In other embodiments, R 5b is —C(CH3)3. In other embodiments, R 5b is -CF3. In other embodiments, R 5b is —OCH3. In other embodiments, R 5b is cyclopropyl. In other embodiments, R 5b is D. In other embodiments, R 5b teeth, -C(CD3)3.

[0149] In some embodiments, the present invention provides a compound of formula (IF): [ka] During the ceremony, X 5a But, N, N + -O - , or N + -CH3, R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ , substituted as necessary with R 9a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, Each R a’ are independently halo, —OH, C1-C6 alkyl, C1-C6 haloalkyl, —C(O)O(C1-C6 alkyl), or -C(O)NH2, X 3b is N or CH, R 2b halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo; R 4b halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 haloalkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)(O)(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C6-C 10 Aryl, C3-C 10 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein C3-C6 cycloalkyl, the cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ , substituted as necessary with R 5b halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; Each R b’ is independently C1-C6 alkyl or C1-C6 haloalkyl, or a pharmaceutically acceptable salt thereof.

[0150] In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein: R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, R 2b halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo.

[0151] In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein X 5a is N. In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein X 5a N + -O - is.

[0152] In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, C1-C6 alkoxy, -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(NH)NH2, -SO2NH2, or a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ where each R is substituted as needed. a’ is Cl, —OH, —CH, —CHCH, —CF, —C(O)OCHCH, or —C(O)NH. In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, -OH, -C(O)NH2, -C(O)NH(C1-C6 alkyl), In other embodiments, R 6a is —C(O)NH(C1-C6 alkyl). In other embodiments, R 6a is —C(O)N(C1-C6 alkyl). In other embodiments, R 6a is —N(C1-C6 alkyl). In other embodiments, R 6a is —NHC(O)NH. In other embodiments, R 6a is —NHC(O)NH(C1-C6 alkyl). In other embodiments, R 6a is C1-C6 alkoxy. In other embodiments, R 6a is —C(NH)NH. In other embodiments, R 6a is -SO2NH2. In other embodiments, R 6a is a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ where each R is substituted as needed. a’is Cl, —OH, —CH, —CHCH, —CF, —C(O)OCHCH, or —C(O)NH. In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, -N(CH3)2, -NHC(O)NH2, -NHC(O)NHCH3, -OH, -OCH3, -C(O)NH2, -C(O)NH(CH3), -C(O)N(CH3)2, -C(O)OH, -C(NH)NH2, -SO2NH2, [ka] In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 6a But, H, -CN, -OH, -C(O)NH, -C(O)NH(CH), -C(O)NH(CH), or -C(O)OH. In other embodiments, R 6a is H. In other embodiments, R 6a is -CN. In other embodiments, R 6a is —OH. In other embodiments, R 6a teeth, In another embodiment, R 6a is —C(O)NH(CH). In other embodiments, R 6a teeth, In another embodiment, R 6a is —C(O)OH. In other embodiments, R 6a is —N(CH). In other embodiments, R 6a is —NHC(O)NH. In other embodiments, R 6a is —NHC(O)NHCH. In other embodiments, R 6a is —OCH3. In other embodiments, R 6a is —C(NH)NH. In other embodiments, R 6a teeth, In another embodiment, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] In other embodiments, R 6a teeth, [ka] is.

[0153] In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 9a is H or C1-C6 alkyl. In other embodiments, R 9a In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 9a is H or -CH3. In other embodiments, R 9a is H. In other embodiments, R 9a is -CH3.

[0154] In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein X 3b is N. In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein X 3b is CH.

[0155] In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, The cycloalkyl in the (C-C alkyl)-(C-C cycloalkyl)- or (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo. In other embodiments, R 2b is D. In other embodiments, R 2b is -C(CD3)3.

[0156] In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 2b is C1-C6 alkyl, In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 2b is C1-C6 alkyl. In other embodiments, R 2b is -(C1-C6 alkylene)-OH. In other embodiments, R 2b is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 2bis —CH 3 , —CH 2 OH, or —C(O)OCH 3 . In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 2b is —CH3. In another embodiment, R 2b is —CH3. In another embodiment, R 2b is —CHOH. In another embodiment, R 2b is -C(O)OCH3.

[0157] In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 4b is halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 haloalkoxy, or -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -(C1-C6 haloalkylene)-C(O)OH, C6-C 10 Aryl, C3-C 10 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein C3-C 10 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ where each R is substituted as needed. b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 4b halo, C1-C6 alkyl, C-C haloalkyl, C-C haloalkenyl, or -(C-C alkylene)-OH. In other embodiments, R 4bis halo. In other embodiments, R 4b is C1-C6 alkyl. In other embodiments, R 4b is C1-C6 haloalkyl. In other embodiments, R 4b is C1-C6 haloalkenyl. In other embodiments, R 4b is -(C1-C6 alkylene)-OH. In other embodiments, R 4b is C1-C6 alkenyl. In other embodiments, R 4b is C1-C6 haloalkoxy. In other embodiments, R 4b is -(C1-C6 haloalkylene)-OH. In other embodiments, R 4b teeth, -(C1-C6 alkylene)-C(O)OH. In other embodiments, R 4b is -(C1-C6 haloalkylene)-C(O)OH. In other embodiments, R 4b is C6-C 10 In another embodiment, R 4b is C3-C 10 In another embodiment, R 4b is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-. In other embodiments, R 4b teeth, (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4b is a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen. 10 The cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with one to two R b’ where each R is substituted as needed. b’ is independently -CH3 or -CF3. In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 4b is Cl, -CH3, -CH(CH3)2, -C(CH3)3, -CH=C(CH3)2, -CF3, -C(CH3)2(CHF2), -C(CH3)2(CF3), -CH2C(CH3)2F, -C(=CH2)(CF3), -OCF3, -C(CH3)2(CH2OH), -C(CH3)(CF3)(CH2OH), -C(CH3)2(C(O)OH), -C(CH3)(CF3)(C(O)OH), phenyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, cyclobutyl, 1-methylcyclobutyl, 3,3-difluoro-1-methylcyclobutyl, cyclopentyl, 1-methylcyclopentyl, 1-trifluoromethylcyclopentyl, 3,3-difluoro-1-methylcyclopentyl, 4,4-difluoro-1-methylcyclohexyl, [ka] In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 4b But Cl, -CH3, -CH(CH), -C(CH), -CF, -C(CH)(CF), -C(=CH)(CF), or -C(CH)(CHOH). 4b is Cl. In other embodiments, R 4b is -CH3. In other embodiments, R 4b is —CH(CH). In other embodiments, R 4b is —C(CH3)3. In other embodiments, R 4b is -CF3. In other embodiments, R 4b is —C(CH)(CF). In other embodiments, R 4b is —C(═CH)(CF). In other embodiments, R 4b teeth,- C(CH)(CHOH). In other embodiments, R 4b is D. In other embodiments, R 4b is -C(CD3)3. In other embodiments, R4b is -CH=C(CH3)2. In other embodiments, R 4b is —C(CH)(CHF). In other embodiments, R 4b is —CHC(CH)F. In other embodiments, R 4b is -OCF3. In other embodiments, R 4b is —C(CH)(CF)(CHOH). In other embodiments, R 4b is —C(CH)(C(O)OH). In other embodiments, R 4b is —C(CH)(CF)(C(O)OH). In other embodiments, R 4b is phenyl. In another embodiment, R 4b teeth, In another embodiment, R 4b is 1-trifluoromethylcyclopropyl. In other embodiments, R 4b is cyclobutyl. In another embodiment, R 4b is 1-methylcyclobutyl. In another embodiment, R 4b teeth, In another embodiment, R 4b is cyclopentyl. In another embodiment, R 4b is 1-methylcyclopentyl. In another embodiment, R 4b is 1-trifluoromethylcyclopentyl. In another embodiment, R 4b is 3,3-difluoro-1-methylcyclopentyl. In another embodiment, R 4b is 4,4-difluoro-1-methylcyclohexyl. In another embodiment, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4bteeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] In other embodiments, R 4b teeth, [ka] is.

[0158] In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 5b is halo, C-C alkyl, C-C haloalkyl, C-C alkoxy, or C-C cycloalkyl. 5b is halo. In other embodiments, R 5b is C1-C6 alkyl. In other embodiments, R 5b is C1-C6 haloalkyl. In other embodiments, R 5b is C1-C6 alkoxy. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (IF), or a pharmaceutically acceptable salt thereof, wherein R 5b F, Cl, -CH3, -CH2CH3, In other embodiments, R 5b is F. In other embodiments, R 5b is Cl. In other embodiments, R 5b is -CH3. In other embodiments, R 5b is -CH2CH3. In other embodiments, R 5b is —CH(CH). In other embodiments, R 5b is -CF3. In other embodiments, R 5b is —OCH3. In other embodiments, R 5b is cyclopropyl. In other embodiments, R5b is D. In other embodiments, R 5b teeth, -C(CD3)3.

[0159] In some embodiments, the present invention provides a compound of formula (IG): [ka] During the ceremony, X 5a But N or N + -O - and R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C4 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NHC(O)NH2, -NHC(O)NH(C1-C6 alkyl), -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)OH, -C(O)O(C1-C6 alkyl), -C(NH)NH2, -C(S)NH2, -SO2NH2, or a 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is selected from 1 to 2 R a’ , substituted as necessary with R 9ais H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, Each R a’ are independently halo, —OH, C1-C6 alkyl, C1-C6 haloalkyl, —C(O)O(C1-C6 alkyl), or -C(O)NH2, X 3b is N or CH, R 2b halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo; R 4b halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 haloalkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -(C1-C6 haloalkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -C(O)(O)(C1-C6 alkyl), -Si(C1-C6 alkyl)3, C6-C 10 aryl, C3-C 10 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or a 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms selected from nitrogen and oxygen, wherein the C3-C 10 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo, and the heterocyclyl is optionally substituted with 1 to 2 R b’ , substituted as necessary with Each R b’ is independently C1-C6 alkyl or C1-C6 haloalkyl, or a pharmaceutically acceptable salt thereof.

[0160] In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein: R 6a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C4 alkoxy, C1-C6 haloalkoxy, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -OH, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene)-N(C1-C6 alkyl)2, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-NH2, -O(C1-C6 alkylene)-NH(C1-C6 alkyl), -O(C1-C6 alkylene)-N(C1-C6 alkyl)2, -C(O)(C1-C6 alkyl), -C(O)NH, -C(O)NH(C-C alkyl), -C(O)N(C-C alkyl), -C(O)OH, -C(O)O(C-C alkyl), or -C(S)NH2, R 2b halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halo; R 4b halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl) C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo.

[0161] In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein X 5a is N. In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein X 5a N + -O - is.

[0162] In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, C1-C4 alkoxy, -NH(C1-C6 alkyl), -OH, -O(C1-C6 alkylene)-(C1-C6 alkoxy), -O(C1-C6 alkylene)-N(C1-C6 alkyl), -C(O)NH, -C(O)OH, -C(O)O(C1-C6 alkyl), or -C(S)NH2. In other embodiments, R 6a is C1-C4 alkoxy. In other embodiments, R 6a is —NH(C1-C6 alkyl). In other embodiments, R 6a is —O(C1-C6 alkylene)-(C1-C6 alkoxy). In other embodiments, R 6a is —O(C-C alkylene)-N(C-C alkyl). In other embodiments, R 6a teeth,- C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein R 6a is H, -CN, -OCH3, -NH(CH3), -OH, -OCH2CH2OCH3, -OCH2CH2N(CH3)2, C(O)NH2, -C(O)OH, -C(O)OCH3, or -C(S)NH2. In other embodiments, R 6a is H. In other embodiments, R 6a is -CN. In other embodiments, R 6a is —OCH3. In other embodiments, R 6a is —NH(CH). In other embodiments, R 6a is —OH. In other embodiments, R 6a teeth, In another embodiment, R 6a is —OCH2CH2N(CH3)2. In other embodiments, R 6a is C(O)NH. In other embodiments, R 6a is —C(O)OH. In other embodiments, R 6a is —C(O)OCH. In other embodiments, R 6a is -C(S)NH2.

[0163] In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein R 9ais H, halo, C1-C6 alkoxy, or —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, halo, or C1-C6 alkoxy. In other embodiments, R 9a is halo. In other embodiments, R 9a is C1-C6 alkoxy. In other embodiments, R 9a is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, Cl, Br, —OCH3, —OCH2CH3, or —C(O)OCH3. In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein R 9a is H, Cl, Br, —OCH, or —OCHCH. In other embodiments, R 9a is H. In other embodiments, R 9a is Cl. In other embodiments, R 9a is Br. In other embodiments, R 9a is —OCH3. In other embodiments, R 9a is —OCH2CH3. In other embodiments, R 9a is -C(O)OCH3.

[0164] In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein X 3b is N. In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein X 3b is CH.

[0165] In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-C(O)OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), -Si(C1-C6 alkyl)3, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the C3-C6 cycloalkyl, The cycloalkyl in the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halo.

[0166] In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein R 2b is halo, C1-C6 alkyl, C1-C6 alkoxy, or In another embodiment, R 2b is halo. In other embodiments, R 2b is C1-C6 alkyl. In other embodiments, R 2b is C1-C6 alkoxy. In other embodiments, R 2b is —(C1-C6 alkylene)-OH. In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein R 2b is F, Cl, —CH, —CHCH, —OCH, or —OCHCHCHOH. 2b is F. In other embodiments, R 2b is Cl. In other embodiments, R 2b is -CH3. In other embodiments, R 2b teeth, In another embodiment, R 2bis —OCH3. In other embodiments, R 2b is —OCH2CH2CH2OH. In other embodiments, R 2b is D. In other embodiments, R 2b is -C(CD3)3.

[0167] In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein R 4b is C-C alkyl, C-C haloalkyl, -Si(C-C alkyl), or (C-C haloalkyl)-(C-C cycloalkyl)-. In another embodiment, R 4b is C1-C6 alkyl. In another embodiment, R 4b is C1-C6 haloalkyl. In another embodiment, R 4b is —Si(C1-C6 alkyl). In another embodiment, R 4b teeth, In some embodiments, the present invention relates to a compound of formula (IG), or a pharmaceutically acceptable salt thereof, wherein R 4b But -C(CH3)3, In other embodiments, R is —C(CH)(CH)(CH), —C(CH)(CF), —Si(CH), or 1-trifluoromethylcyclopropyl. 4b is —C(CH3)3. In other embodiments, R 4b is —C(CH)(CH)(CH). In other embodiments, R 4b is —C(CH)(CF). In other embodiments, R 4b is —Si(CH3)3. In other embodiments, R 4b is 1-trifluoromethylcyclopropyl. In other embodiments, R 4b is D. In other embodiments, R 4b teeth, -C(CD3)3.

[0168] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein: R 6c is H, halo, —OH, —CN, C1-C6 alkoxy, or C(O)NH2; Y is, [ka] is.

[0169] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 3c is H, halo, or C1-C6 alkyl. In other embodiments, R 3c is halo. In other embodiments, R 3c In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 3c is H, F, or —CH. In other embodiments, R 3c is H. In other embodiments, R 3c is F. In other embodiments, R 3c is -CH3.

[0170] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 4c is H, halo, —CN, or C1-C6 alkoxy. 4c is halo. In other embodiments, R 4c In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 4c is H, F, —CN, or —OCH. In other embodiments, R 4c is H. In other embodiments, R 4c is F. In other embodiments, R 4c is -CN. In other embodiments, R 4c is -OCH3.

[0171] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 5c is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or —C(O)O(C1-C6 alkyl). In other embodiments, R 5c is halo. In other embodiments, R 5c is C1-C6 alkyl. In other embodiments, R 5c is C1-C6 haloalkyl. In other embodiments, R 5c is C1-C6 alkoxy. In other embodiments, R 5c is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 5c is H, F, —CN, —CH, —CF, —OCH, or —C(O)OCH. In other embodiments, R 5c is H. In other embodiments, R 5c is F. In other embodiments, R 5c is -CN. In other embodiments, R 5c is -CH3. In other embodiments, R 5c is -CF3. In other embodiments, R 5c is —OCH3. In other embodiments, R 5c is -C(O)OCH3.

[0172] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, F, Cl, -OH, -CN, -OCH3, C(O)NH2, or [ka] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, halo, —OH, —CN, C-C alkoxy, or C(O)NH. In other embodiments, R6c is halo. In other embodiments, R 6c In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, F, Cl, —OH, —CN, —OCH, or C(O)NH. In other embodiments, R 6c is H. In other embodiments, R 6c is F. In other embodiments, R 6c is Cl. In other embodiments, R 6c is —OH. In other embodiments, R 6c teeth, In another embodiment, R 6c is —OCH3. In other embodiments, R 6c is C(O)NH. In other embodiments, R 6c teeth, [ka] is.

[0173] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 9c is H, C1-C6 alkyl, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-O(C1-C6 alkyl), or -C(O)O(C1-C6 alkyl). In other embodiments, R 9c is C1-C6 alkyl. In other embodiments, R 9c is -(C1-C6 alkylene)-OH. In other embodiments, R 9c teeth, -(C1-C6 alkylene)-O(C1-C6 alkyl). In other embodiments, R 9c is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 9c is H, —CH, —CHOH, —CHOCH, or —C(O)OCHCH. In other embodiments, R9c is H. In other embodiments, R 9c is -CH3. In other embodiments, R 9c is —CHOH. In other embodiments, R 9c is —CH2OCH3. In other embodiments, R 9c is -C(O)OCH2CH3.

[0174] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] In some embodiments, the present invention relates to compounds of formula (II), or a pharmaceutically acceptable salt thereof, wherein Y is: [ka] is.

[0175] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein X 3d In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein X 3d is CR 3d In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein X 3d is CR 3d and R 3d is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or In another embodiment, R 3d is halo. In other embodiments, R 3d is C1-C6 alkyl. In other embodiments, R 3d is C1-C6 haloalkyl. In other embodiments, R 3d is C1-C6 alkoxy. In other embodiments, R 3dIn some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein X 3d is CR 3d and R 3d is H, F, Cl, —CH, —CHCH, —CF, —OCH, —OCHCH, or —OCF. In other embodiments, R 3d is H. In other embodiments, R 3d is F. In other embodiments, R 3d is Cl. In other embodiments, R 3d is -CH3. In other embodiments, R 3d teeth, In another embodiment, R 3d is -CF3. In other embodiments, R 3d is —OCH3. In other embodiments, R 3d is —OCH2CH3. In other embodiments, R 3d is -OCF3.

[0176] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein X 3d is CR 3d and R 2d and R 3d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 2d and R 3d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 2d and R 3d together with the carbon atoms to which they are attached, have the formula [ka] It forms a ring.

[0177] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein X 3d is CR 3d and R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] It forms a ring.

[0178] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 2d is H, halo, -OH, C1-C6 alkyl, C1-C6 alkoxy, C-C haloalkoxy, or -(C-C alkylene)-OH. In other embodiments, R 2d is halo. In other embodiments, R 2d is C1-C6 alkyl. In other embodiments, R 2d is C1-C6 alkoxy. In other embodiments, R 2d is C In another embodiment, R 2d is —(C1-C6 alkylene)-OH. In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 2d is H, F, Cl, —OH, —CH, —CHCH, —CH(CH), —C(CH), —OCH, —OCHCH, —OCH(CH), —OCF, or —CHOH. 2d is H. In other embodiments, R 2d is F. In other embodiments, R 2d is Cl. In other embodiments, R 2d is —OH. In other embodiments, R 2d is -CH3. In other embodiments, R 2d is -CH2CH3. In other embodiments, R 2d is —CH(CH). In other embodiments, R 2dis —C(CH3)3. In other embodiments, R 2d is —OCH3. In other embodiments, R 2d is —OCH2CH3. In other embodiments, R 2d teeth, In another embodiment, R 2d is -OCF3. In other embodiments, R 2d is -CHOH.

[0179] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 4d is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -Si(C1-C6 alkyl)3, -C(O)O(C1-C6 alkyl), (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halogen or -CN. In other embodiments, R 4d is halo. In other embodiments, R 4d is C1-C6 alkyl. In other embodiments, R 4d is C1-C6 haloalkyl. In other embodiments, R 4d is C1-C6 haloalkenyl. In other embodiments, R 4d is C1-C6 alkoxy. In other embodiments, R 4d is C1-C6 haloalkoxy. In other embodiments, R 4d teeth, In another embodiment, R4d is -(C1-C6 alkylene)-(C1-C6 alkoxy). In other embodiments, R 4d is —Si(C1-C6 alkyl). In other embodiments, R 4d is —C(O)O(C1-C6 alkyl). In other embodiments, R 4d is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-. In other embodiments, R 4d teeth, (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4d is a C3-C6 cycloalkyl, wherein the cycloalkyl is optionally substituted with one or more halogen or -CN. In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 4d is H, F, Cl, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CH2C(CH3)3, -CF3, -CH(CH3)(CF3), -C(CH3)2(CF3), -C(=CH2)(CF3), -OCH3, -OCH(CH3)2, -OC(CH3)3, -OCF3, -C(CH3)2OH, -C(CH3)2(OCH3), -Si(CH3)3, -C(O)OCH2CH3, cyclopropyl, 1-cyanocyclopropyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, 1-methylcyclobutyl, or 3,3-difluorocyclobutyl. In other embodiments, R 4d is H. In other embodiments, R 4d is F. In other embodiments, R 4d is Cl. In other embodiments, R 4d teeth, In another embodiment, R 4d is -CH2CH3. In other embodiments, R 4d is —CH(CH). In other embodiments, R 4d is —C(CH3)3. In other embodiments, R 4d is —CHC(CH). In other embodiments, R4d is -CF3. In other embodiments, R 4d is —CH(CH)(CF). In other embodiments, R 4d is —C(CH)(CF). In other embodiments, R 4d is —C(═CH)(CF). In other embodiments, R 4d is —OCH3. In other embodiments, R 4d is —OCH(CH). In other embodiments, R 4d is —OC(CH). In other embodiments, R 4d is -OCF3. In other embodiments, R 4d is —C(CH)OH. In other embodiments, R 4d is —C(CH)(OCH). In other embodiments, R 4d is —Si(CH3)3. In other embodiments, R 4d is —C(O)OCH2CH3. In other embodiments, R 4d is cyclopropyl. In other embodiments, R 4d is 1-cyanocyclopropyl. In other embodiments, R 4d teeth, In another embodiment, R 4d is 1-trifluoromethylcyclopropyl. In other embodiments, R 4d is 1-methylcyclobutyl. In another embodiment, R 4d is 3,3-difluorocyclobutyl.

[0180] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 5d is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, or —C(O)(C1-C6 alkyl). In other embodiments, R 5d is halo. In other embodiments, R 5d is C1-C6 alkyl. In other embodiments, R 5dis C1-C6 haloalkyl. In other embodiments, R 5d is C1-C6 alkoxy. In other embodiments, R 5d is —C(O)(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 5d But H, F, Cl, Br, In other embodiments, R 5d is H. In other embodiments, R 5d is F. In other embodiments, R 5d is Cl. In other embodiments, R 5d is Br. In other embodiments, R 5d is -CH3. In other embodiments, R 5d is —C(CH3)3. In other embodiments, R 5d is -CF3. In other embodiments, R 5d is —OCH3. In other embodiments, R 5d is -C(O)CH3.

[0181] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 6d is H, halo, or C1-C6 alkyl. In other embodiments, R 6d is halo. In other embodiments, R 6d In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 6d is H, Cl, or —CH. In other embodiments, R 6d is H. In other embodiments, R 6d is Cl. In other embodiments, R 6d is -CH3.

[0182] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 7d is -CH3.

[0183] In some embodiments, the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt thereof, wherein R 9d is -C(CH3)3.

[0184] In some embodiments, the present invention provides a compound of formula (II-A): [ka] During the ceremony, R 3c is H, halo, or C1-C6 alkyl; R 4c is H, halo, —CN, or C1-C6 alkoxy; R 5c is H, halo, —CN, C1-C6 alkyl, or C1-C6 alkoxy; R 6c is H, halo, —OH, —CN, C1-C6 alkoxy, C(O)NH2, or a 5-10 membered heteroaryl containing 1-3 heteroatoms selected from nitrogen and oxygen; R 9c is H, C1-C6 alkyl, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-O(C1-C6 alkyl), or -C(O)O(C1-C6 alkyl), X 3d But N or CR 3d and R 2d , R 3d , and R 4d But the following: (i) R 2d is H, halo, —OH, C1-C6 alkyl, or C1-C6 alkoxy; R 3d is H or halo, R 4d is H, chloro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -Si(C1-C6 alkyl)3, -C(O)O(C1-C6 alkyl), (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in said (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogen or -CN; or (ii) R 2d is H, halo, -OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or -(C1-C6 alkylene)-OH, R 3d and R 4d together with the carbon atoms to which they are attached, form the formula: [ka] is defined as forming a ring of R 5d is H, halo, C1-C6 alkyl, or C1-C6 haloalkyl; R 6d is H, halo, or C1-C6 alkyl, however, (i) X 3d If N, then R 2d , R 4d , R 5d , and R 6d Two or fewer of the following are H, (ii) R 3d and R 4d together with the carbon atoms to which they are attached, form the formula: [ka] , When forming a ring of R 2d , R5d , and R 6d Two or fewer of the following are H, (iii) R 4d If is H, then R 2d is C1-C6 alkyl, and R 5d is C1-C6 alkyl or C1-C6 haloalkyl; (iv) R 4d If is chloro, R 2d is —OH or C1-C6 alkyl; (v) R 4d is -CH3, R 2d is —OH, C1-C6 alkyl, or C1-C2 alkoxy; (vi) R 4d is -C(CH3)3, R 2d is H, chloro, —OH, C1-C6 alkyl, or C1-C6 alkoxy; (vii) R 4d If is -CF3, R 2d is C1-C6 alkyl or C1-C6 alkoxy; (viii) R 4d If is -OCH3, R 2d is halo, —OH, C1-C6 alkyl, or C1-C6 alkoxy, and R 5d But, halo, C1-C6 alkyl or C1-C6 haloalkyl; (ix) R 4d If is -OC(CH3)3, R 2d , R 3d , R 5d , and R 6d Three or fewer of the characters must be H. (x) R 4d If is -OCF3, R 2d is halo, —OH, C1-C6 alkyl, or C1-C6 alkoxy; (xi) R 4d When R is cyclopropyl, 2d is H, chloro, —OH, C1-C6 alkyl, or C1-C6 alkoxy, and R6d is H or C1-C6 alkyl; (xii) R 2d is -OCH3 and R 4d is -CH3, R 5d is halo, C1-C6 alkyl, or C1-C6 haloalkyl, or a pharmaceutically acceptable salt thereof.

[0185] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, halo, —OH, —CN, C1-C6 alkoxy, or C(O)NH2.

[0186] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 3c is H, halo, or C1-C6 alkyl. In other embodiments, R 3c is halo. In other embodiments, R 3c In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 3c is H, F, or —CH. In other embodiments, R 3c is H. In other embodiments, R 3c is F. In other embodiments, R 3c is -CH3.

[0187] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 4c is H, halo, —CN, or C1-C6 alkoxy. 4c is halo. In other embodiments, R 4c In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 4c is H, F, —CN, or —OCH. In other embodiments, R4c is H. In other embodiments, R 4c is F. In other embodiments, R 4c is -CN. In other embodiments, R 4c is -OCH3.

[0188] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 5c is H, halo, —CN, C1-C6 alkyl, or C1-C6 alkoxy. 5c is halo. In other embodiments, R 5c is C1-C6 alkyl. In other embodiments, R 5c In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 5c is H, F, —CN, —CH, or —OCH. In other embodiments, R 5c is H. In other embodiments, R 5c is F. In other embodiments, R 5c is -CN. In other embodiments, R 5c is -CH3. In other embodiments, R 5c is -OCH3.

[0189] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 6c H, F, Cl, -OH, -CN, -OCH3, -C(O)NH2, or [ka] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, halo, —OH, —CN, C-C alkoxy, or C(O)NH. In other embodiments, R 6c is halo. In other embodiments, R 6cIn some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, F, Cl, —OH, —CN, —OCH, or —C(O)NH. In other embodiments, R 6c is H. In other embodiments, R 6c is F. In other embodiments, R 6c is Cl. In other embodiments, R 6c is —OH. In other embodiments, R 6c is -CN. In other embodiments, R 6c is —OCH3. In other embodiments, R 6c teeth, In another embodiment, R 6c teeth, [ka] is.

[0190] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 9c is H, C1-C6 alkyl, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-O(C1-C6 alkyl), or -C(O)O(C1-C6 alkyl). In other embodiments, R 9c is C1-C6 alkyl. In other embodiments, R 9c is -(C1-C6 alkylene)-OH. In other embodiments, R 9c teeth, -(C1-C6 alkylene)-O(C1-C6 alkyl). In other embodiments, R 9c is —C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 9c is H, —CH, —CHOH, —CHOCH, or —C(O)OCHCH. In other embodiments, R 9c is H. In other embodiments, R9c is -CH3. In other embodiments, R 9c is —CHOH. In other embodiments, R 9c is —CH2OCH3. In other embodiments, R 9c is -C(O)OCH2CH3.

[0191] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein X 3d In some embodiments, the present invention relates to compounds of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein X 3d is CR 3d In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein X 3d is CR 3d and R 3d is H or halo. In other embodiments, R 3d In some embodiments, the present invention relates to compounds of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein X is halo. 3d is CR 3d and R 3d is H or Cl. In other embodiments, R 3d is H. In other embodiments, R 3d is Cl.

[0192] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein X 3d is CR 3d and R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] In another embodiment, R 3d and R 4d together with the carbon atoms to which they are attached, have the formula [ka] It forms a ring.

[0193] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 2d is H, halo, —OH, C1-C6 alkyl, or C1-C6 alkoxy. 2d is halo. In other embodiments, R 2d is C1-C6 alkyl. In other embodiments, R 2d In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 2d is H, F, Cl, -OH, -CH3, -CH2CH3, -CH(CH3)2, In another embodiment, R 2d is H. In other embodiments, R 2d is F. In other embodiments, R 2d is Cl. In other embodiments, R 2d is —OH. In other embodiments, R 2d is -CH3. In other embodiments, R 2dis -CH2CH3. In other embodiments, R 2d is —CH(CH). In other embodiments, R 2d teeth, In another embodiment, R 2d is -OCH2CH3.

[0194] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 4d is H, chloro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -Si(C1-C6 alkyl)3, -C(O)O(C1-C6 alkyl), (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halogen or -CN. In other embodiments, R 4d is C1-C6 alkyl. In other embodiments, R 4d is C1-C6 haloalkyl. In other embodiments, R 4d is C1-C6 haloalkenyl. In other embodiments, R 4d is C1-C6 alkoxy. In other embodiments, R 4d is C1-C6 haloalkoxy. In other embodiments, R 4d is -(C1-C6 alkylene)-(C1-C6 alkoxy). In other embodiments, R 4d is —Si(C1-C6 alkyl). In other embodiments, R 4d is —C(O)O(C1-C6 alkyl). In other embodiments, R 4dis (C1-C6 alkyl)-(C3-C6 cycloalkyl)-. In other embodiments, R 4d teeth, (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4d or C3-C6 cycloalkyl, where the cycloalkyl is optionally substituted with one or more halogen or -CN. In some embodiments, the present invention relates to compounds of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 4d is H, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -CH2C(CH3)3, -CF3, -CH(CH3)(CF3), -C(CH3)2(CF3), -C(=CH2)(CF3), -OCH3, -OCF3, -C(CH3)2(CH2OCH3), -Si(CH3)3, -C(O)OCH2CH3, cyclopropyl, 1-cyanocyclopropyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, 1-methylcyclobutyl, or In another embodiment, R 4d is H. In other embodiments, R 4d is Cl. In other embodiments, R 4d is -CH3. In other embodiments, R 4d is —CH(CH). In other embodiments, R 4d teeth, In another embodiment, R 4d is —CHC(CH). In other embodiments, R 4d is -CF3. In other embodiments, R 4d is —CH(CH)(CF). In other embodiments, R 4d is —C(CH)(CF). In other embodiments, R 4d is —C(═CH)(CF). In other embodiments, R 4d is —OCH3. In other embodiments, R 4d is -OCF3. In other embodiments, R 4dis —C(CH)(CHOCH). In other embodiments, R 4d is —Si(CH3)3. In other embodiments, R 4d is —C(O)OCH2CH3. In other embodiments, R 4d is cyclopropyl. In other embodiments, R 4d is 1-cyanocyclopropyl. In other embodiments, R 4d is 1-methylcyclopropyl. In another embodiment, R 4d is 1-trifluoromethylcyclopropyl. In other embodiments, R 4d is 1-methylcyclobutyl. In another embodiment, R 4d is 3,3-difluorocyclobutyl.

[0195] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 5d is H, halo, C-C alkyl, or C-C haloalkyl. 5d is halo. In other embodiments, R 5d is C1-C6 alkyl. In other embodiments, R 5d is C In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 5d is H, F, Cl, Br, —CH, —C(CH), or —CF. In other embodiments, R 5d is H. In other embodiments, R 5d is F. In other embodiments, R 5d is Cl. In other embodiments, R 5d is Br. In other embodiments, R 5d is -CH3. In other embodiments, R 5d is —C(CH3)3. In other embodiments, R 5d is -CF3.

[0196] In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 6d is H, halo, or C1-C6 alkyl. In other embodiments, R 6d is halo. In other embodiments, R 6d In some embodiments, the present invention relates to a compound of formula (II-A), or a pharmaceutically acceptable salt thereof, wherein R 6d is H, Cl, or —CH. In other embodiments, R 6d is H. In other embodiments, R 6d is Cl. In other embodiments, R 6d is -CH3.

[0197] In some embodiments, the present invention provides a compound of formula (II-B): [ka] During the ceremony, R 3c is H, halo, or C1-C6 alkyl; R 4c is H, halo, —CN, or C1-C6 alkoxy; R 5c is H, halo, —CN, C1-C6 alkyl, or C1-C6 alkoxy; R 6c is H, halo, —OH, —CN, C1-C6 alkoxy, C(O)NH2, or a 5-10 membered heteroaryl containing 1-3 heteroatoms selected from nitrogen and oxygen; R 9c is H, C1-C6 alkyl, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-O(C1-C6 alkyl), or -C(O)O(C1-C6 alkyl), X 3d is N or CH, R 2d is halo, —OH, C1-C6 alkyl, or C1-C6 alkoxy; R 4dhalo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -Si(C1-C6 alkyl)3, -C(O)O(C1-C6 alkyl), (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogen or —CN; R 5d is halo, C1-C6 alkyl, or C1-C6 haloalkyl; however, (i) R 2d If is chloro, X 3d is N, and (ii) R 4d is -CH3 and R 5d is -CH3, R 2d is —OH, C1-C6 alkyl, or C1-C2 alkoxy, or a pharmaceutically acceptable salt thereof.

[0198] In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, halo, —OH, —CN, C1-C6 alkoxy, or C(O)NH2.

[0199] In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 3c is H or halo. In other embodiments, R 3c In some embodiments, the present invention relates to compounds of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 3cis H or F. In other embodiments, R 3c is H. In other embodiments, R 3c is F.

[0200] In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 4c is H, halo, —CN, or C1-C6 alkoxy. 4c is halo. In other embodiments, R 4c In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 4c is H, F, —CN, or —OCH. In other embodiments, R 4c is H. In other embodiments, R 4c is F. In other embodiments, R 4c is -CN. In other embodiments, R 4c is -OCH3.

[0201] In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 5c is H, halo, or C1-C6 alkoxy. In other embodiments, R 5c is halo. In other embodiments, R 5c In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 5c But H, F, or In another embodiment, R 5c is H. In other embodiments, R 5c is F. In other embodiments, R 5c teeth,- It is OCH3.

[0202] In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 6cis H, F, Cl, -OH, -CN, -OCH3, -C(O)NH2, or [ka] In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, halo, —OH, —CN, C-C alkoxy, or C(O)NH. In other embodiments, R 6c is halo. In other embodiments, R 6c In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, F, Cl, —OH, —CN, —OCH, or —C(O)NH. In other embodiments, R 6c is H. In other embodiments, R 6c is F. In other embodiments, R 6c is Cl. In other embodiments, R 6c is —OH. In other embodiments, R 6c is -CN. In other embodiments, R 6c is —OCH3. In other embodiments, R 6c teeth, In another embodiment, R 6c teeth, [ka] is.

[0203] In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 9c is H.

[0204] In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein X 3d In some embodiments, the present invention relates to compounds of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein X 3dis CH.

[0205] In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 2d is halo, C1-C6 alkyl, or C1-C6 alkoxy. 2d is halo. In other embodiments, R 2d is C1-C6 alkyl. In other embodiments, R 2d is C In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 2d is F, Cl, —CH, or —OCH. In other embodiments, R 2d is F. In other embodiments, R 2d is Cl. In other embodiments, R 2d is -CH3. In other embodiments, R 2d is -OCH3.

[0206] In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 4d halo, C1-C6 alkyl, C1-C6 haloalkyl, In other embodiments, R 4d is halo. In other embodiments, R 4d is C 1-C6 alkyl. In other embodiments, R 4d is C1-C6 haloalkyl. In other embodiments, R 4d is C 1-C6 haloalkenyl. In other embodiments, R 4d In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 4dis Cl, —CH, —CH(CH), —C(CH), —CF, —CH(CH)(CF), —C(CH)(CF), —C(═CH)(CF), or —OCH. 4d is Cl. In other embodiments, R 4d is -CH3. In other embodiments, R 4d teeth, In another embodiment, R 4d is —C(CH3)3. In other embodiments, R 4d is -CF3. In other embodiments, R 4d is —CH(CH)(CF). In other embodiments, R 4d is —C(CH)(CF). In other embodiments, R 4d is —C(═CH)(CF). In other embodiments, R 4d is -OCH3.

[0207] In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 5d is halo or C1-C6 alkyl. In other embodiments, R 5d is halo. In other embodiments, R 5d In some embodiments, the present invention relates to a compound of formula (II-B), or a pharmaceutically acceptable salt thereof, wherein R 5d is F, Cl, Br, or In another embodiment, R 5d is F. In other embodiments, R 5d is Cl. In other embodiments, R 5d is Br. In other embodiments, R 5d is -CH3.

[0208] In some embodiments, the present invention provides a compound of formula (II-C): [ka] During the ceremony, R3c is H, halo, or C1-C6 alkyl; R 4c is H, halo, —CN, or C1-C6 alkoxy; R 5c is H, halo, —CN, C1-C6 alkyl, or C1-C6 alkoxy; R 6c is H, halo, —OH, —CN, C1-C6 alkoxy, C(O)NH2, or a 5-10 membered heteroaryl containing 1-3 heteroatoms selected from nitrogen and oxygen; R 9c is H, C1-C6 alkyl, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-O(C1-C6 alkyl), or -C(O)O(C1-C6 alkyl), X 3d is N or CH, R 2d is —OH, C1-C6 alkyl, or C1-C6 alkoxy; R 4d halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -Si(C1-C6 alkyl)3, -C(O)O(C1-C6 alkyl), (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens or -CN, however, (i) R 2d is -OH, R 4d halo, C1-C6 alkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -Si(C1-C6 alkyl)3, -C(O)O(C1-C6 alkyl), (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or wherein the cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens or -CN; (ii) R 2d is -CH3, R 4d halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 haloalkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -Si(C1-C6 alkyl)3, -C(O)O(C1-C6 alkyl), (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or wherein the cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens or -CN; (iii) R 2d If is -OCH3, R 4d is C2-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkenyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -Si(C1-C6 alkyl)3, -C(O)O(C1-C6 alkyl), (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, provided that the cycloalkyl in the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogen or —CN.

[0209] In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, halo, —OH, —CN, C1-C6 alkoxy, or C(O)NH2.

[0210] In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 3c is H, halo, or C1-C6 alkyl. In other embodiments, R 3c is halo. In other embodiments, R 3c or C1-C6 alkyl. In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 3c is H, F, or —CH. In other embodiments, R 3c is H. In other embodiments, R 3c is F. In other embodiments, R 3c is -CH3.

[0211] In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 4c is H, halo, —CN, or C1-C6 alkoxy. 4c is halo. In other embodiments, R 4c In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 4c is H, F, —CN, or —OCH. In other embodiments, R4c is H. In other embodiments, R 4c is F. In other embodiments, R 4c is -CN. In other embodiments, R 4c is -OCH3.

[0212] In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 5c is H, halo, —CN, C1-C6 alkyl, or C1-C6 alkoxy. 5c is halo. In other embodiments, R 5c is C1-C6 alkyl. In other embodiments, R 5c In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 5c is H, F, —CN, —CH, or —OCH. In other embodiments, R 5c is H. In other embodiments, R 5c is F. In other embodiments, R 5c is -CN. In other embodiments, R 5c is -CH3. In other embodiments, R 5c is -OCH3.

[0213] In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, halo, —OH, —CN, C-C alkoxy, or C(O)NH. In other embodiments, R 6c is halo. In other embodiments, R 6c In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 6c is H, F, —OH, —CN, —OCH, or —C(O)NH. In other embodiments, R 6c is H. In other embodiments, R 6c is F. In other embodiments, R6c is —OH. In other embodiments, R 6c is -CN. In other embodiments, R 6c is —OCH3. In other embodiments, R 6c is -C(O)NH2.

[0214] In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 9c is H, C1-C6 alkyl, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-O(C1-C6 alkyl), or -C(O)O(C1-C6 alkyl). In other embodiments, R 9c is H. In other embodiments, R 9c is C1-C6 alkyl. In other embodiments, R 9c is -(C1-C6 alkylene)-OH. In other embodiments, R 9c is -(C1-C6 alkylene)-O(C1-C6 alkyl). In other embodiments, R 9c teeth, In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 9c is H, -CH3, -CH2OH, -CH2OCH3, or In another embodiment, R 9c is H. In other embodiments, R 9c is -CH3. In other embodiments, R 9c is —CHOH. In other embodiments, R 9c is —CH2OCH3. In other embodiments, R 9c teeth, -C(O)OCH2CH3.

[0215] In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein X 3dis N. In some embodiments, the present invention relates to compounds of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein X 3d is CH.

[0216] In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 2d is —OH, C1-C6 alkyl, or C1-C6 alkoxy. 2d is C1-C6 alkyl. In other embodiments, R 2d In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 2d is —OH, —CH, —CHCH, —CH(CH), —OCH, or —OCHCH. In other embodiments, R 2d is —OH. In other embodiments, R 2d is -CH3. In other embodiments, R 2d is -CH2CH3. In other embodiments, R 2d teeth, In another embodiment, R 2d is —OCH3. In other embodiments, R 2d is -OCH2CH3.

[0217] In some embodiments, the present invention relates to a compound of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 4d halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -Si(C1-C6 alkyl)3, -C(O)O(C1-C6 alkyl), (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or C3-C6 cycloalkyl, wherein the C3-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the (C-C haloalkyl)-(C-C cycloalkyl)- is optionally substituted with one or more halogen or -CN. In other embodiments, R 4d is halo. In other embodiments, R 4d is C1-C6 alkyl. In other embodiments, R 4d is C1-C6 haloalkyl. In other embodiments, R 4d is C1-C6 haloalkoxy. In other embodiments, R 4d teeth, -(C1-C6 alkylene)-(C1-C6 alkoxy). In other embodiments, R 4d is —Si(C1-C6 alkyl). In other embodiments, R 4d is —C(O)O(C1-C6 alkyl). In other embodiments, R 4d is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-. In other embodiments, R 4d is (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4d is C In some embodiments, the present invention relates to compounds of formula (II-C), or a pharmaceutically acceptable salt thereof, wherein R 4d is Cl, -CH3, -CH(CH3)2, -C(CH3)3, -CH2C(CH3)3, -CF3, -C(CH3)2(CF3), -OCF3, -CH(CH2)(OCH3), -Si(CH3)3, -C(O)OCH2CH3, cyclopropyl, 1-cyanocyclopropyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, 1-methylcyclobutyl, or In another embodiment, R 4d is Cl. In other embodiments, R 4d is -CH3. In other embodiments, R 4d is —CH(CH). In other embodiments, R 4dis —C(CH3)3. In other embodiments, R 4d teeth, In another embodiment, R 4d is -CF3. In other embodiments, R 4d is —C(CH)(CF). In other embodiments, R 4d is -OCF3. In other embodiments, R 4d is —CH(CH)(OCH). In other embodiments, R 4d is —Si(CH3)3. In other embodiments, R 4d is —C(O)OCH2CH3. In other embodiments, R 4d is cyclopropyl. In other embodiments, R 4d is 1-cyanocyclopropyl. In other embodiments, R 4d teeth, In another embodiment, R 4d is 1-trifluoromethylcyclopropyl. In other embodiments, R 4d is 1-methylcyclobutyl. In another embodiment, R 4d is 3,3-difluorocyclobutyl.

[0218] In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein R 6k is H, —OH, or C1-C6 alkoxy.

[0219] In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X 3k In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X 3k is CH.

[0220] In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X 4kIn some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X 4k is CH.

[0221] In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X 5k In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X 5k is CR 5k In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X 5k is CR 5k and R 5k is H, C1-C6 alkoxy, -OH, -OCH2CH2N(CH3)2, or In another embodiment, R 5k In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X is C1-C6 alkoxy. 5k is CR 5k and R 5k is H, —OH, —OCH, —OCHCHN(CH), or —N(CH)(CHCHOCH). 5k is H. In other embodiments, R 5k is —OH. In other embodiments, R 5k is —OCH3. In other embodiments, R 5k is —OCH2CH2N(CH3)2. In other embodiments, R 5k is -N(CH3)(CH2CH2OCH3).

[0222] In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X 6k In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X 6k N +-O - In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X 6k is CR 6k and R 6k is H, —OH, —OCH 3 , or —C(O)NH 2 . In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein: X 6k is CR 6k and R 6k is H, —OH, or C1-C6 alkoxy. 6k is C In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein X is 1-C6 alkoxy. 6k is CR 6k and R 6k is H, —OH, or —OCH. In other embodiments, R 6k is H. In other embodiments, R 6k is —OH. In other embodiments, R 6k is —OCH3. In other embodiments, R 6k is -C(O)NH2.

[0223] In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein R 2L is -CH3.

[0224] In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein R 4L is C1-C6 alkyl, C1-C6 haloalkyl, or (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4L is C1-C6 alkyl. In other embodiments, R 4L is C1-C6 haloalkyl. In other embodiments, R 4Lis (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-. In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein R 4L is —C(CH3)3, —C(CH3)2(CF3), or 1-trifluoromethylcyclopropyl. 4L is —C(CH3)3. In other embodiments, R 4L teeth, In another embodiment, R 4L is 1-trifluoromethylcyclopropyl.

[0225] In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein R 5L is H, halo, or C1-C6 alkyl. In other embodiments, R 5L is halo. In other embodiments, R 5L In some embodiments, the present invention relates to a compound of formula (III), or a pharmaceutically acceptable salt thereof, wherein R 5L is H, F, Cl, or In another embodiment, R 5L is H. In other embodiments, R 5L is F. In other embodiments, R 5L is Cl. In other embodiments, R 5L is -CH3.

[0226] In some embodiments, the present invention provides a compound of formula (III-A): [ka] During the ceremony, X 3k is N or CH, X 4k is N or CH, X 5k But N or CR 5k and X 6k But, N, N+ -O - , or CR 6k and R 5k is H, C1-C6 alkoxy, —OH, or —OCH2CH2N(CH3)2; R 6k is H, —OH, C1-C6 alkoxy, or —C(O)NH2; R 2L is C1-C6 alkyl, R 4L is C1-C6 alkyl, C1-C6 haloalkyl, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-; R 5L is H, halo, or C1-C6 alkyl, however, (i) X 3k , X 4k , X 5k , and X 6k Two or fewer of the are N, (ii) X 6k N + -O - If X 3k and X 4k is CH and X 5k is CR 5k And, (iii) X 5k If N, then X 4k is N, or a pharmaceutically acceptable salt thereof.

[0227] In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein R 6k is H, —OH, or C1-C6 alkoxy.

[0228] In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X 3k is N. In some embodiments, the present invention relates to compounds of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X3k is CH.

[0229] In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X 4k is N. In some embodiments, the present invention relates to compounds of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X 4k is CH.

[0230] In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X 5k is N. In some embodiments, the present invention relates to compounds of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X 5k is CR 5k In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X 5k is CR 5k and R 5k is H, C1-C6 alkoxy, —OH, or —OCH2CH2N(CH3)2. In other embodiments, R 5k In some embodiments, the present invention relates to compounds of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X is C1-C6 alkoxy. 5k is CR 5k and R 5k But H, -OCH3, In another embodiment, R 5k is H. In other embodiments, R 5k is —OCH3. In other embodiments, R 5k is —OH. In other embodiments, R 5k is -OCH2CH2N(CH3)2.

[0231] In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X 6kis N. In some embodiments, the present invention relates to compounds of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X 6k N + -O - In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X 6k is CR 6k In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X 6k is CR 6k and R 6k But, H, In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein: X 6k is CR 6k and R 6k is H, —OH, or C1-C6 alkoxy. In another embodiment, C1-C6 alkoxy. In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein X 6k is CR 6k and R 6k is H, —OH, or —OCH. In other embodiments, R 6k is H. In other embodiments, R 6k is —OH. In other embodiments, R 6k is —OCH3. In other embodiments, R 6k is -C(O)NH2.

[0232] In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein R 2L is -CH3.

[0233] In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein R 4L is C1-C6 alkyl, C1-C6 haloalkyl, or (C-C haloalkyl)-(C-C cycloalkyl)-. In other embodiments, R 4L is C1-C6 alkyl. In other embodiments, R 4L is C1-C6 haloalkyl. In other embodiments, R 4L is (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-. In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein R 4L is —C(CH3)3, —C(CH3)2(CF3), or 1-trifluoromethylcyclopropyl. 4L is —C(CH3)3. In other embodiments, R 4L teeth, In another embodiment, R 4L is 1-trifluoromethylcyclopropyl.

[0234] In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein R 5L is H, halo, or C1-C6 alkyl. In other embodiments, R 5L is halo. In other embodiments, R 5L In some embodiments, the present invention relates to a compound of formula (III-A), or a pharmaceutically acceptable salt thereof, wherein R 5L is H, F, Cl, or In another embodiment, R 5L is H. In other embodiments, R 5L is F. In other embodiments, R 5L is Cl. In other embodiments, R 5L is -CH3.

[0235] In some embodiments, the present invention relates to a compound selected from Table A, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to a compound selected from Table A, i.e., a compound in non-salt form.

[0236]

Table A-1

Table A-2

Table A-3

Table A-4

Table A-5

Table A-6

Table A-7

Table A-8

Table A-9

Table A-10

Table A-11

Table A-12

Table A-13

Table A-14

Table A-15

Table A-16

Table A-17

[0237] In some embodiments, the present invention relates to a compound selected from Table B, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to a compound selected from Table B, i.e., a compound in non-salt form.

[0238]

Table B-1

Table B-2

Table B-3

Table B-4

Table B-5

Table B-6

Table B-7

Table B-8

Table B-9

Table B-10

Table B-11

Table B-12

Table B-13

Table B-14

Table B-15

Table B-16

Table B-17

[0239] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0240] In some embodiments, the present invention relates to the compound 2-(4-tert-butyl-5-chloro-2-methyl-phenyl)-4-oxo-1H-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0241] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0242] In some embodiments, the present invention relates to the compound 2-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-4-oxo-1H-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the non-salt form of the aforementioned compound. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0243] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0244] In some embodiments, the present invention relates to the compound 2-(6-tert-butyl-5-chloro-2-methyl-3-pyridyl)-4-oxo-1H-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0245] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0246] In some embodiments, the present invention relates to the compound 2-[4-tert-butyl-2-methyl-5-(trifluoromethyl)phenyl]-4-oxo-1H-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0247] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0248] In some embodiments, the present invention relates to the compound 2-(4-tert-butyl-2-fluoro-3,6-dimethyl-phenyl)-4-oxo-1H-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0249] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0250] In some embodiments, the present invention relates to the compound 2-(4-tert-butyl-2,5-dimethyl-phenyl)-4-oxo-1H-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0251] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0252] In some embodiments, the present invention relates to the compound 2-[2,5-dimethyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-4-oxo-1H-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the non-salt form of the aforementioned compound. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0253] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0254] In some embodiments, the present invention relates to the compound 4-oxo-2-(1,1,7-trimethyltetralin-6-yl)-1H-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the non-salt form of the aforementioned compound. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0255] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0256] In some embodiments, the present invention relates to the compound 2-[4-isopropyl-2-methyl-5-(trifluoromethyl)phenyl]-4-oxo-1H-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0257] In some embodiments, the present invention provides [ka] [ka] [ka] a compound selected from or a pharmaceutically acceptable salt thereof.

[0258] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0259] In some embodiments, the present invention relates to the compound 2-(4-(tert-butyl)-3-chloro-2-fluoro-6-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0260] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0261] In some embodiments, the present invention relates to the compound 2-(5-chloro-4-cyclobutyl-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0262] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0263] In some embodiments, the present invention relates to the compound 2-(5-chloro-2-methyl-4-(1-methylcyclopropyl)phenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0264] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0265] In some embodiments, the present invention relates to the compound 2-(4-(bicyclo[1.1.1]pentan-1-yl)-5-chloro-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0266] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0267] In some embodiments, the present invention relates to the compound 2-(4-(tert-butyl)-3,5-difluoro-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0268] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0269] In some embodiments, the present invention relates to the compound 2-(5-chloro-6-(3,3-difluoro-1-methylcyclopentyl)-2-methylpyridin-3-yl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0270] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0271] In some embodiments, the present invention relates to the compound (R)-2-(5-chloro-6-(3,3-difluoro-1-methylcyclopentyl)-2-methylpyridin-3-yl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0272] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0273] In some embodiments, the present invention relates to the compound (S)-2-(5-chloro-6-(3,3-difluoro-1-methylcyclopentyl)-2-methylpyridin-3-yl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0274] In some embodiments, the present invention relates to the compound rel-(R)-2-(5-chloro-6-(3,3-difluoro-1-methylcyclopentyl)-2-methylpyridin-3-yl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide. In some embodiments, the present invention relates to the compound rel-(R)-2-(5-chloro-6-(3,3-difluoro-1-methylcyclopentyl)-2-methylpyridin-3-yl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, which has the stereochemistry corresponding to the first-eluting isomer when the two diastereomers rel-(R)-4-benzyloxy-2-[5-chloro-6-(3,3-difluoro-1-methylcyclopentyl)-2-methyl-3-pyridyl]-1,6-naphthyridine-5-carbonitrile and rel-(S)-4-benzyloxy-2-[5-chloro-6-(3,3-difluoro-1-methylcyclopentyl)-2-methyl-3-pyridyl]-1,6-naphthyridine-5-carbonitrile are separated by SFC as described in Example 85. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0275] In some embodiments, the present invention relates to the compound rel-(S)-2-(5-chloro-6-(3,3-difluoro-1-methylcyclopentyl)-2-methylpyridin-3-yl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide. In some embodiments, the present invention relates to the compound rel-(S)-2-(5-chloro-6-(3,3-difluoro-1-methylcyclopentyl)-2-methylpyridin-3-yl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, which has the stereochemistry corresponding to the first-eluting isomer when the two diastereomers rel-(R)-4-benzyloxy-2-[5-chloro-6-(3,3-difluoro-1-methylcyclopentyl)-2-methyl-3-pyridyl]-1,6-naphthyridine-5-carbonitrile and rel-(S)-4-benzyloxy-2-[5-chloro-6-(3,3-difluoro-1-methylcyclopentyl)-2-methyl-3-pyridyl]-1,6-naphthyridine-5-carbonitrile are separated by SFC as described in Example 85. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0276] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0277] In some embodiments, the present invention relates to the compound 2-(3-chloro-2-fluoro-6-methyl-4-(1,1,1-trifluoro-2-methylpropan-2-yl)phenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0278] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0279] In some embodiments, the present invention relates to the compound 2-(5-chloro-2-methyl-6-(3-methylbicyclo[1.1.1]pentan-1-yl)pyridin-3-yl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0280] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0281] In some embodiments, the present invention relates to the compound 2-(4-(tert-butyl)-5-chloro-3-fluoro-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0282] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0283] In some embodiments, the present invention relates to the compound 2-(4-(bicyclo[3.1.0]hexan-3-yl)-5-chloro-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0284] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0285] In some embodiments, the present invention relates to the compound 2-(5-chloro-4-(3,3-difluoro-1-methylcyclopentyl)-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0286] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0287] In some embodiments, the present invention relates to the compound (S)-2-(5-chloro-4-(3,3-difluoro-1-methylcyclopentyl)-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0288] In some embodiments, the present invention provides a compound of the following formula: [ka] , or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0289] In some embodiments, the present invention relates to the compound (R)-2-(5-chloro-4-(3,3-difluoro-1-methylcyclopentyl)-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compound in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0290] In some embodiments, the present invention relates to the compound rel-(S)-2-(5-chloro-4-(3,3-difluoro-1-methylcyclopentyl)-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide. In some embodiments, the present invention relates to the compound rel-(S)-2-(5-chloro-4-(3,3-difluoro-1-methylcyclopentyl)-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, which has the stereochemistry corresponding to the first-eluting isomer when the two diastereomers rel-(S)-2-[5-chloro-4-(3,3-difluoro-1-methylcyclopentyl)-2-methylphenyl]-4-oxo-1H-1,6-naphthyridine-5-carboxamide and rel-(R)-2-[5-chloro-4-(3,3-difluoro-1-methylcyclopentyl)-2-methylphenyl]-4-oxo-1H-1,6-naphthyridine-5-carboxamide are separated by SFC as described in Example 84. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0291] In some embodiments, the present invention relates to the compound rel-(R)-2-(5-chloro-4-(3,3-difluoro-1-methylcyclopentyl)-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide. In some embodiments, the present invention relates to the compound rel-(R)-2-(5-chloro-4-(3,3-difluoro-1-methylcyclopentyl)-2-methylphenyl)-4-oxo-1,4-dihydro-1,6-naphthyridine-5-carboxamide, which has the stereochemistry corresponding to the first-eluting isomer when the two diastereomers rel-(S)-2-[5-chloro-4-(3,3-difluoro-1-methylcyclopentyl)-2-methylphenyl]-4-oxo-1H-1,6-naphthyridine-5-carboxamide and rel-(R)-2-[5-chloro-4-(3,3-difluoro-1-methylcyclopentyl)-2-methylphenyl]-4-oxo-1H-1,6-naphthyridine-5-carboxamide are separated by SFC as described in Example 84. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered to be "compounds of the invention" as that term is used herein.

[0292] Salts, Compositions, Uses, Formulations, Administration, and Additional Agents Pharmaceutically Acceptable Salts and Compositions As discussed herein, the present invention provides compounds and pharmaceutically acceptable salts thereof that are inhibitors of voltage-gated sodium channels. Accordingly, the present compounds and pharmaceutically acceptable salts thereof are useful for treating diseases, disorders, and conditions, including, but not limited to, chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, post-operative pain (e.g., bunionectomy pain, herniorrhaphy pain, or abdominoplasty pain), visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough, or cardiac arrhythmia. Accordingly, in another aspect of the present invention, pharmaceutical compositions are provided, which comprise a compound described herein, or a pharmaceutically acceptable salt thereof, and optionally, a pharmaceutically acceptable carrier, adjuvant, or vehicle. In certain embodiments, the compositions optionally further comprise one or more additional therapeutic agents. In some embodiments, the additional therapeutic agent is a sodium channel inhibitor.

[0293] As used herein, the term "pharmaceutically acceptable" refers to a salt that is, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, and that is commensurate with a reasonable benefit / risk ratio. A "pharmaceutically acceptable salt" of a compound of the invention includes any non-toxic salt that, upon administration to a recipient, is capable of providing, either directly or indirectly, a compound of the present disclosure or an inhibitory active metabolite or residue thereof. The salt may be in pure form, a mixture with one or more other substances (e.g., a solution, suspension, or colloid), or in the form of a hydrate, solvate, or co-crystal. As used herein, the term "inhibitorily active metabolite or residue thereof" means that the metabolite or residue thereof is also an inhibitor of voltage-gated sodium channels.

[0294] Pharmaceutically acceptable salts are well known in the art. For example, S.M. Berge et al. describes pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, which is incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of the present invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are salts of amino groups formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or by using other methods used in the art, such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, methylpropional ... Salts derived from appropriate bases include sulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium, and N + (C 1-4Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, etc. Further pharmaceutically acceptable salts include non-toxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates, where appropriate.

[0295] As used herein, a pharmaceutically acceptable composition of the present invention additionally includes pharmaceutically acceptable carriers, adjuvants, or vehicles, including any and all solvents, diluents, or other liquid vehicles, dispersing or suspending aids, surfactants, isotonicity agents, thickening or emulsifying agents, preservatives, solid binders, lubricants, and the like, as used herein, appropriate for the particular dosage form desired. Remington's Pharmaceutical Sciences, Sixteenth Edition, E.W. Martin (Mack Publishing Co., Easton, Pa., 1980) discloses various carriers used in formulating pharmaceutically acceptable compositions and known techniques for their preparation. Except insofar as any conventional carrier medium is incompatible with the compounds of the present invention, for example, by producing any undesirable biological effect or otherwise interacting in a deleterious manner with any other component of the pharmaceutically acceptable composition, its use is contemplated within the scope of the present disclosure.Some examples of materials that can serve as pharmaceutically acceptable carriers include ion exchangers, alumina, aluminum stearate, lecithin, serum proteins (e.g., human serum albumin), buffer substances (e.g., phosphates, glycine, sorbic acid, and potassium sorbate), partial glyceride mixtures of saturated vegetable fatty acids, water, salts, or electrolytes (e.g., protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts), colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, wool fat, sugars (e.g., lactose, glucose, and sucrose), starches (e.g., corn starch and potato starch), cellulose and its derivatives (e.g., sodium carboxymethylcellulose, ethyl cellulose, etc.), and the like. and cellulose acetate), powdered tragacanth, malt, gelatin, talc, excipients (e.g., cocoa butter and suppository wax), oils (e.g., peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil), glycols (e.g., propylene glycol and polyethylene glycol), esters (e.g., ethyl oleate and ethyl laurate), agar, buffers (e.g., magnesium hydroxide and aluminum hydroxide), alginic acid, pyrogen-free water, isotonic saline, Ringer's solution, ethyl alcohol, phosphate buffer solution, and other non-toxic compatible lubricants (e.g., sodium lauryl sulfate and magnesium stearate), as well as coloring agents, releasing agents, coating agents, sweetening, flavoring, and perfuming agents; preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator.

[0296] In another aspect, the invention features a pharmaceutical composition including a compound of the invention, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0297] In another aspect, the invention features a pharmaceutical composition including a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or vehicles. Uses of the Compounds and Pharmaceutically Acceptable Salts and Compositions

[0298] In another aspect, the invention features a method of inhibiting a voltage-gated sodium channel in a subject, the method comprising administering to the subject a compound of the invention, or a pharmaceutically acce...

Claims

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof, 【Chemical 931】 During the ceremony, X ５ａ However, N, N ＋ -O － , or N ＋ -CH ３ And, X ９ａ However, N or CR ９ａ And, R ３ａ is H, halo, -CN, C １ -C ６ alkyl, C １ -C ６ alkenyl, C １ -C ６ haloalkyl, C １ -C ６ haloalkenyl, C １ -C ６ alkoxy, C １ -C ６ haloalkoxy, -NH ２ , -NH(C １ -C ６ alkyl), -N(C １ -C ６ ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​-C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), or -C(S)NH ２ And, R ４ａ is H, halo, -CN, C １ -C ６ alkyl, C １ -C ６ alkenyl, C １ -C ６ haloalkyl, C １ -C ６ haloalkenyl, C １ -C ６ alkoxy, C １ -C ６ haloalkoxy, -NH ２ , -NH(C １ -C ６ alkyl), -N(C １ -C ６ alkyl) ２ , -OH, -(C １ -C ６ alkylene)-OH, -(C １ -C ６ alkylene)-(C １ -C ６ alkoxy), -(C １ -C ６ alkylene)-NH ２ , -(C １ -C ６ alkylene)-NH(C １ -C ６ alkyl), -(C １ -C ６ alkylene)-N(C １ -C ６ alkyl) ２ , -O(C １ -C ６ alkylene)-(C １ -C ６ alkoxy), -O(C １ -C ６ alkylene)-NH ２ , -O(C １ -C ６ alkylene)-NH(C １ -C ６ alkyl), -O(C １ -C ６ alkylene)-N(C １ -C ６ alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), or -C(S)NH ２ And, R ６ａ However, halo, -CN, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , -NHC(O)NH ２ , -NHC(O)NH(C １ -C ６ Alkyl), -OH, -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -(C １ -C ６ Alkilen)-NH ２ , - (C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -(C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -O(C １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -O(C １ -C ６ Alkilen)-NH ２ , -O(C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -O (C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), -C(NH)NH ２ , -C(S)NH ２ , -SO ２ NH ２ , or a 5-10 membered heteroaryl comprising 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur, where the heteroaryl is 1-2 R ａ’ Replaced as needed, R ９ａ However, H, Halo, -CN, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , -OH, -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -(C １ -C ６ Alkilen)-NH ２ , - (C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -(C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -O(C １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -O(C １ -C ６ Alkilen)-NH ２ , -O(C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -O (C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), or -C(S)NH ２ And, Each R ａ’ These become independent: Halo, -OH, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, -C(O)O(C) １ -C ６ Alkyl), or -C(O)NH ２ And, Y, 【Chemical 932】 And, X ２ｂ However, N or CR ２ｂ And, X ３ｂ However, N or CR ３ｂ And, X ４ｂ However, N or CR ４ｂ And, X ５ｂ However, N or CR ５ｂ And, X ６ｂ However, N or CR ６ｂ And, Z optionally contains 1 to 3 heteroatoms selected from nitrogen and oxygen, and 1 or more R ｚ A 5-7 member aromatic or non-aromatic ring, which is substituted as needed. R ２ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH(C) １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -C(O)O(C １ -C ６ Alkyl), -Si (C １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ３ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -Si(C) １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ４ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ (Haloalkylene) -OH, -(C １ -C ６ Alkylene)-C(O)OH,-(C １ -C ６ Haloalkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -C(O)O(C １ -C ６ Alkyl), -Si (C １ -C ６ Alkyl) ３ , C ６ -C １０ Ariel, C ３ -C １０ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ A 4- to 10-membered heterocycline comprising a cycloalkyl)- or 1 to 3 heteroatoms selected from nitrogen and oxygen, where the C ３ -C １０ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos, and the heterocyclyl group has 1 to 2 R groups. ｂ’ Replaced as needed, R ５ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -Si(C) １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ６ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -Si(C) １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ７ｂ However, C １ -C ６ It is alkyl, R ９ｂ However, C １ -C ６ It is alkyl, R １０ｂ However, it is H or halo, Each R ｂ’ C １ -C ６ Alkyl or C １ -C ６ It is a haloalkyl, R ｚ But, hello, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenyl, -CN, -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , or -C(O)OH, however, (i) Y is 【Chemical 933】 X ３ｂ CR ３ｂ and X ６ｂ CR ６ｂ If R ２ｂ , R ３ｂ , R ４ｂ , R ５ｂ , and R ６ｂ Three or fewer of them are H, (ii) Y is 【Chemical 934】 X ３ｂ If N and X ６ｂ CR ６ｂ If R ２ｂ , R ４ｂ , R ５ｂ , and R ６ｂ Three or fewer of them are H, (iii) Y is 【Chemical 935】 X ３ｂ CR ３ｂ and X ６ｂ If R is N, ２ｂ , R ３ｂ , R ４ｂ , and R ５ｂ Three or fewer of them are H, (iv) X ９ａ N is and Y is 【Chemical 936】 X ３ｂ CR ３ｂ and X ６ｂ CR ６ｂ If R ２ｂ , R ３ｂ , R ４ｂ , R ５ｂ , and R ６ｂ Two or fewer of them are Haro, (v) X ９ａ N is and Y is 【Chemical 937】 X ４ｂ CR ４ｂ X ５ｂ CR ５ｂ and X ６ｂ CR ６ｂ If that is the case, R ４ｂ , R ５ｂ , and R ６ｂ Two or fewer of them are H, or Z has one or more R ｚ A compound of formula (I), or a pharmaceutically acceptable salt thereof, provided that it is substituted with and .

2. R ６ａ However, halo, -CN, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , -OH, -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -(C １ -C ６ Alkilen)-NH ２ , - (C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -(C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -O(C １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -O(C １ -C ６ Alkilen)-NH ２ , -O(C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -O (C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), or -C(S)NH ２ And, Y, 【Chemical Formula 938】 And, R ２ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH(C) １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -Si(C) １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ４ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -Si(C) １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The compound according to claim 1, wherein the cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos.

3. The compound is a compound of formula (I-D), 【Chemical 955】 During the ceremony, R ６ａ However, halo, -CN, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , -NHC(O)NH ２ , -NHC(O)NH(C １ -C ６ Alkyl), -OH, -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -(C １ -C ６ Alkilen)-NH ２ , - (C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -(C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -O(C １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -O(C １ -C ６ Alkilen)-NH ２ , -O(C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -O (C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), -C(NH)NH ２ , -C(S)NH ２ , -SO ２ NH ２ , or a 5-10 membered heteroaryl comprising 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur, where the heteroaryl is 1-2 R ａ’ Replaced as needed, R ９ａ is H, halo, -CN, C １ -C ６ alkyl, C １ -C ６ alkenyl, C １ -C ６ haloalkyl, C １ -C ６ haloalkenyl, C １ -C ６ alkoxy, C １ -C ６ haloalkoxy, -NH ２ , -NH(C １ -C ６ alkyl), -N(C １ -C ６ alkyl) ２ , -OH, -(C １ -C ６ alkylene)-OH, -(C １ -C ６ alkylene)-(C<00,00880-C ６ alkoxy), -(C １ -C ６ alkylene)-NH ２ , -(C １ -C ６ alkylene)-NH(C １ -C ６ alkyl), -(C １ -C ６ alkylene)-N(C １ -C ６ alkyl) ２ , -O(C １ -C ６ alkylene)-(C １ -C ６ alkoxy), -O(C １ -C ６ alkylene)-NH ２ , -O(C １ -C ６ alkylene)-NH(C １ -C ６ alkyl), -O(C １ -C ６ alkylene)-N(C １ -C ６ alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), or -C(S)NH ２ And, Each R ａ’ These become independent: Halo, -OH, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, -C(O)O(C) １ -C ６ Alkyl), or -C(O)NH ２ And, X ２ｂ However, N or CR ２ｂ And, X ５ｂ However, N or CR ５ｂ And, X ６ｂ However, N or CR ６ｂ And, Z optionally contains 1 to 3 heteroatoms selected from nitrogen and oxygen, and 1 or more R ｚ A 5-7 member aromatic or non-aromatic ring, which is substituted as needed. R ２ｂ is H, halo, C １ -C ６ alkyl, C １ -C ６ alkenyl, C １ -C ６ haloalkyl, C １ -C ６ haloalkenyl, C １ -C ６ alkoxy, C １ -C ６ haloalkoxy, -OH, -NH(C １ -C ６ alkyl), -N(C １ -C ６ alkyl) ２ , -(C １ -C ６ alkylene)-OH, -(C １ -C ６ alkylene)-C(O)OH, -C(O)(C １ -C ６ alkyl), -C(O)(C １ -C ６ haloalkyl), -C(O)O(C １ -C ６ alkyl), -Si(C １ -C ６ alkyl) ３ , C ３ -C ６ cycloalkyl, (C １ -C ６ alkyl)-(C ３ -C ６ cycloalkyl)-, or (C １ -C ６ haloalkyl)-(C ３ -C ６ cycloalkyl)-, where the C ３ -C ６ cycloalkyl, the (C １ -C<**********>alkyl)-(C ３ -C ６ cycloalkyl)-, or the (C １ -C ６ haloalkyl)-(C ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ５ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -Si(C) １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ６ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ (Alkyl) (C ２ -C ６ Alkyl), -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -Si(C) １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ｚ But, hello, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkenyl, -CN, -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ The compound according to claim 1, or -C(O)OH, or a pharmaceutically acceptable salt thereof.

4. The compound is a compound of formula (I-E), 【Chemical 956】 During the ceremony, X ５ａ However, N or N ＋ -O － And, R ６ａ However, halo, -CN, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ４ Alkoxy, C １ -C ６ Haloalkoxy, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , -NHC(O)NH ２ , -NHC(O)NH(C １ -C ６ Alkyl), -OH, -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -(C １ -C ６ Alkilen)-NH ２ , - (C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -(C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -O(C １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -O(C １ -C ６ Alkilen)-NH ２ , -O(C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -O (C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), -C(NH)NH ２ , -C(S)NH ２ , -SO ２ NH ２ , or a 5-10 membered heteroaryl comprising 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur, where the heteroaryl is 1-2 R ａ’ Replaced as needed, R ９ａ However, H, Halo, -CN, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , -OH, -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -(C １ -C ６ Alkilen)-NH ２ , - (C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -(C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -O(C １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -O(C １ -C ６ Alkilen)-NH ２ , -O(C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -O (C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), or -C(S)NH ２ And, Each R ａ’ These become independent: Halo, -OH, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, -C(O)O(C) １ -C ６ Alkyl), or -C(O)NH ２ And, X ３ｂ However, N or CR ３ｂ And, X ６ｂ However, N or CR ６ｂ And, R ２ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH(C) １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -C(O)O(C １ -C ６ Alkyl), -Si (C １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ３ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -Si(C) １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ４ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ (Haloalkylene) -OH, -(C １ -C ６ Haloalkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -C(O)(O)(C １ -C ６ Alkyl), -Si (C １ -C ６ Alkyl) ３ , C ６ -C １０ Ariel, C ３ -C １０ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ A 4- to 10-membered heterocycline comprising a cycloalkyl)- or 1 to 3 heteroatoms selected from nitrogen and oxygen, where the C ３ -C １０ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos, and the heterocyclyl group has 1 to 2 R groups. ｂ’ Replaced as needed, R ５ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -Si(C) １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ６ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -Si(C) １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. Each R ｂ’ C １ -C ６ Alkyl or C １ -C ６ Although it is a haloalkyl, However, X ３ｂ CR ３ｂ and X ６ｂ CR ６ｂ If R ２ｂ , R ３ｂ , R ４ｂ , R ５ｂ , and R ６ｂ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein three or fewer of these atoms are H.

5. The compound is a compound of formula (I-F), 【Chemical 957】 During the ceremony, X ５ａ However, N, N ＋ -O － , or N ＋ -CH ３ And, R ６ａ However, halo, -CN, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , -NHC(O)NH ２ , -NHC(O)NH(C １ -C ６ Alkyl), -OH, -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -(C １ -C ６ Alkilen)-NH ２ , - (C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -(C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -O(C １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -O(C １ -C ６ Alkilen)-NH ２ , -O(C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -O (C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), -C(NH)NH ２ , -C(S)NH ２ , -SO ２ NH ２ , or a 5-10 membered heteroaryl comprising 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur, where the heteroaryl is 1-2 R ａ’ Replaced as needed, R ９ａ However, H, Halo, -CN, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , -OH, -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -(C １ -C ６ Alkilen)-NH ２ , - (C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -(C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -O(C １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -O(C １ -C ６ Alkilen)-NH ２ , -O(C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -O (C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), or -C(S)NH ２ And, Each R ａ’ These become independent: Halo, -OH, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, -C(O)O(C) １ -C ６ Alkyl), or -C(O)NH ２ And, X ３ｂ However, it is N or CH, R ２ｂ But, hello, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH(C) １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -C(O)O(C １ -C ６ Alkyl), -Si (C １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ４ｂ But, hello, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ (Haloalkylene) -OH, -(C １ -C ６ Haloalkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -C(O)(O)(C １ -C ６ Alkyl), -Si (C １ -C ６ Alkyl) ３ , C ６ -C １０ Ariel, C ３ -C １０ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ A 4- to 10-membered heterocycline comprising a cycloalkyl)- or 1 to 3 heteroatoms selected from nitrogen and oxygen, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos, and the heterocyclyl group has 1 to 2 R groups. ｂ’ Replaced as needed, R ５ｂ But, hello, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -Si(C) １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. Each R ｂ’ C １ -C ６ Alkyl or C １ -C ６ A compound according to claim 1, which is a haloalkyl compound, or a pharmaceutically acceptable salt thereof.

6. The compound is a compound of formula (I-G), 【Chemical Formula 958】 During the ceremony, X ５ａ However, N or N ＋ -O － And, R ６ａ However, halo, -CN, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ４ Alkoxy, C １ -C ６ Haloalkoxy, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , -NHC(O)NH ２ , -NHC(O)NH(C １ -C ６ Alkyl), -OH, -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -(C １ -C ６ Alkilen)-NH ２ , - (C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -(C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -O(C １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -O(C １ -C ６ Alkilen)-NH ２ , -O(C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -O (C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), -C(NH)NH ２ , -C(S)NH ２ , -SO ２ NH ２ , or a 5-10 membered heteroaryl comprising 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur, where the heteroaryl is 1-2 R ａ’ Replaced as needed, R ９ａ However, H, Halo, -CN, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , -OH, -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -(C １ -C ６ Alkilen)-NH ２ , - (C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -(C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -O(C １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -O(C １ -C ６ Alkilen)-NH ２ , -O(C １ -C ６ Alkylene)-NH(C) １ -C ６ Alkyl), -O (C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -C(O)(C １ -C ６ Alkyl), -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), or -C(S)NH ２ And, Each R ａ’ These become independent: Halo, -OH, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, -C(O)O(C) １ -C ６ Alkyl), or -C(O)NH ２ And, X ３ｂ However, it is N or CH, R ２ｂ But, hello, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH(C) １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -C(O)O(C １ -C ６ Alkyl), -Si (C １ -C ６ Alkyl) ３ , C ３ -C ６ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl)-, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos. R ４ｂ But, hello, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -OH, -NH ２ ,-NH(C １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , - (C １ -C ６ Alkylene)-OH,-(C) １ -C ６ (Haloalkylene) -OH, -(C １ -C ６ Alkylene)-C(O)OH,-(C １ -C ６ Haloalkylene)-C(O)OH,-C(O)(C １ -C ６ Alkyl), -C(O)(C １ -C ６ Haloalkyl), -C(O)(O)(C １ -C ６ Alkyl), -Si (C １ -C ６ Alkyl) ３ , C ６ -C １０ Ariel, C ３ -C １０ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ A 4- to 10-membered heterocycline comprising a cycloalkyl)- or 1 to 3 heteroatoms selected from nitrogen and oxygen, where the C ３ -C １０ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos, and the heterocyclyl group has 1 to 2 R groups. ｂ’ Replaced as needed, Each R ｂ’ C １ -C ６ Alkyl or C １ -C ６ A compound according to claim 1, which is a haloalkyl compound, or a pharmaceutically acceptable salt thereof.

7. X ５ａ The compound according to claim 1, wherein is N.

8. X ９ａ CR ９ａ And R ９ａ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkoxy, -C(O)OH, or -C(O)O(C １ -C ６ The compound according to claim 1, wherein R 9a is an alkyl group, and optionally R 9a is H, Cl, Br, -CH3, -OCH3, -OCH2CH3, -C(O)OH, or -C(O)OCH3.

9. R ３ａ is H or C １ -C ６ The compound according to claim 1, wherein it is alkyl and optionally R 3a is H or -CH3.

10. R ４ａ The compound according to claim 1, wherein is H.

11. R ６ａ However, H, -CN, C １ -C ６ Alkoxy, -NH(C) １ -C ６ Alkyl), -N(C １ -C ６ Alkyl) ２ , -NHC(O)NH ２ , -NHC(O)NH(C １ -C ６ Alkyl), -OH, -O (C １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -O(C １ -C ６ Alkylene)-N(C) １ -C ６ Alkyl) ２ , -C(O)NH ２ , -C(O)NH(C １ -C ６ Alkyl), -C(O)N(C １ -C ６ Alkyl) ２ , -C(O)OH, -C(O)O(C １ -C ６ Alkyl), -C(NH)NH ２ , -C(S)NH ２ , -SO ２ NH ２ , or a 5-10 membered heteroaryl comprising 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur, where the heteroaryl is 1-2 R ａ’ Replaced as needed, Each R ａ’ These independently form Cl, -OH, and -CH ３ ien-CH ２ CH ３ , -CF ３ , -C(O)OCH ２ CH ３ , or -C(O)NH ２ And, If necessary, R 6a is H, -CN, -OCH 3 , -OCH 2 CH 2 CH (CH 3 ) 2 , -NH(CH 3 ), -N(CH 3 ) 2 , -NHC(O)NH 2 , -NHC(O)NHCH 3 , -OH, -OCH 2 CH 2 OCH 3 , -OCH 2 CH 2 N(CH 3 ) 2 , -C(O)NH 2 , -C(O)NH(CH 3 ), -C(O)N(CH 3 ) 2 , -C(O)OH, -C(O)OCH 3 , -C(NH)NH 2 , -C(S)NH 2 , -SO 2 NH 2 , 【Chemical Formula 959】 The compound according to claim 1.

12. Y, 【Chemical 962】 The compound according to claim 1.

13. X ３ｂ CR ３ｂ And R ３ｂ However, H, Haro, C １ -C ６ Alkyl, or C １ -C ６ The compound according to claim 12, wherein it is a haloalkyl group and R3b is optionally H, F, -CH3, or -CF3.

14. X ６ｂ CR ６ｂ And R ６ｂ However, H, halo, or C １ -C ６ The compound according to claim 12, wherein it is alkyl and R 6b is optionally H, F, or -CH3.

15. R ２ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkoxy, -(C １ -C ６ Alkylene)-OH, or -C(O)O(C) １ -C ６ The compound according to claim 12, wherein R 2b is an alkyl group, and optionally R 2b is H, F, Cl, -CH 3, -CH 2 CH 3, -OCH 3, -CH 2 OH, -CH 2 CH 2 CH 2 OH, or -C(O)OCH 3.

16. R ４ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Alkenil, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Haloalkoxy, -(C) １ -C ６ Alkylene)-OH,-(C) １ -C ６ (Haloalkylene) -OH, -(C １ -C ６ Alkylene)-C(O)OH,-(C １ -C ６ Haloalkylene) -C(O)OH, -C(O)O(C １ -C ６ Alkyl), -Si (C １ -C ６ Alkyl) ３ , C ６ -C １０ Ariel, C ３ -C １０ Cycloalkyl, (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ A 4- to 10-membered heterocycline comprising a cycloalkyl)- or 1 to 3 heteroatoms selected from nitrogen and oxygen, where the C ３ -C １０ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl)-, or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halos, and the heterocyclyl group has 1 to 2 R groups. ｂ’ Replaced as needed, Each R ｂ’ It became independent, -CH ３ or -CF ３ And, If necessary, R 4b is H, Cl, -CH 3 , -CH(CH 3 ) 2 , -C(CH 3 ) 3 , -C(CH 3 ) 2 (CH 2 CH 3 ), -CF 3 , -C(CH 3 ) 2 (CHF 2 ), -C(CH 3 ) 2 (CF 3), -CH2C(CH3)2F, -C(=CH2)(CF3), -CH=C(CH3)2, -OCF3, -C(CH3)2(CH2OH), -C(CH3)(CF3)(CH2OH), -C(CH 3) 2 (C(O)OH), -C(CH3)(CF3 )(C(O)OH), -C(O)OCH3, -Si(CH3)3, phenyl, 1-methylcyclopropyl, 1-trifluoromethylcyclopropyl, cyclobutyl, 1-methylcyclobutyl, 3,3-difluoro-1-methylcyclobutyl, cyclopentyl, 1-methylcyclopentyl, 1-trifluoromethylcyclopentyl, 3,3-difluoro-1-methylcyclopentyl, 4,4-difluoro-1-methylcyclohexyl, 【Chemical 963】 The compound according to claim 1.

17. R ５ｂ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Alkoxy, or C ３ -C ６ The compound according to claim 1, wherein it is cycloalkyl and R 5b is optionally H, F, Cl, -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3, -CF3, -OCH3, or cyclopropyl.

18. Y, 【Chemical 964】 The compound according to claim 1.

19. X ２ｂ CR ２ｂ And R ２ｂ is H or C １ -C ６ The compound according to claim 18, wherein it is alkyl and optionally R2b is H or -CH3.

20. X ５ｂ The compound according to claim 18, wherein is N.

21. X ５ｂ CR ５ｂ And R ５ｂ is H or C １ -C ６ The compound according to claim 18, wherein it is alkyl and optionally R5b is H or -CH3.

22. X ６ｂ CR ６ｂ And R ６ｂ However, H, C １ -C ６ Alkyl, -OH, or -N(C) １ -C ６ Alkyl) ２ The compound according to claim 18, wherein R 6b is, if necessary, H, -CH3, -OH, -N(CH3)2, -N(CH2CH2CH2)3, -N(CH3)(CH2CH2CH2CH2CH3), -N(CH2CH3)(CH2CH2CH2CH2CH3), or -N(CH2CH(CH3)2).

23. Z has 1 to 4 R ｚ A 5-6 member aromatic or non-aromatic carbon ring, optionally substituted, wherein R z is optionally C1-C6 alkyl or C1-C6 haloalkyl, and / or R z is -CH3 or -CF3, and / or Z is 【Chemical 965】 The compound according to claim 18.

24. A compound of formula (II), 【Chemical Formula 969】 During the ceremony, R ３ｃ However, H, halo, or C １ -C ６ It is alkyl, R ４ｃ However, H, halo, -CN, or C １ -C ６ It is an alkoxy, R ５ｃ However, H, Halo, -CN, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Alkoxy, or -C(O)O(C １ -C ６ It is alkyl, R ６ｃ However, halo, -OH, -CN, C １ -C ６ Alkoxy, C(O)NH ２ , or a 5-10 membered heteroaryl compound containing 1-3 heteroatoms selected from nitrogen and oxygen, R ９ｃ However, H, C １ -C ６ Alkyl, -(C １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene)-O(C) １ -C ６ Alkyl), or -C(O)O(C １ -C ６ It is alkyl, Y, 【Chemical 970】 And, X ３ｄ However, N or CR ３ｄ And, R ２ｄ , R ３ｄ , and R ４ｄ However, the following: (i) R ２ｄ However, H, halo, -OH, C １ -C ６ Alkyl, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy or -(C １ -C ６ It is alkylene)-OH R ３ｄ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Alkoxy or C １ -C ６ It is a haloalkoxy, R ４ｄ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -(C) １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -Si (C １ -C ６ Alkyl) ３ , -C(O)O(C １ -C ６ (Alkyl), (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl) - or C ３ -C ６ It is a cycloalkyl, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl) - or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halogens or -CN groups, or (ii) R ２ｄ and R ３ｄ However, together with the carbon atoms to which they are bonded, the formula is: 【Chemical 971】 Forming a ring, R ４ｄ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Haloalkenil, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy, -(C) １ -C ６ Alkylene)-OH,-(C) １ -C ６ Alkylene) - (C １ -C ６ Alkoxy), -Si (C １ -C ６ Alkyl) ３ , -C(O)O(C １ -C ６ (Alkyl), (C １ -C ６ (Alkyl)-(C ３ -C ６ (Cycloalkyl)-, (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ Cycloalkyl) - or C ３ -C ６ It is a cycloalkyl, where the C ３ -C ６ Cycloalkyl, the above (C １ -C ６ (Alkyl)-(C ３ -C ６ Cycloalkyl) - or the above (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ The cycloalkyl group in the cycloalkyl group is optionally substituted with one or more halogens or -CN groups, or (iii) R ２ｄ However, H, halo, -OH, C １ -C ６ Alkyl, C １ -C ６ Alkoxy, C １ -C ６ Haloalkoxy or -(C １ -C ６ It is alkylene)-OH R ３ｄ and R ４ｄ However, together with the carbon atoms to which they are bonded, the formula is: 【Chemical 972】 It is defined as forming a ring, R ５ｄ However, H, Haro, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C １ -C ６ Alkoxy, or -C(O)(C １ -C ６ It is alkyl, R ６ｄ However, H, halo, or C １ -C ６ It is alkyl, R ７ｄ However, C １ -C ６ It is alkyl, R ９ｄ However, C １ -C ６ It is alkyl, however, (i) Y' is 【Chemical 973】 and X ３ｄ CR ３ｄ If R ２ｄ , R ３ｄ , R ４ｄ , R ５ｄ , and R ６ｄ Four or fewer of them are H, (ii) Y' is 【Chemical 974】 and X ３ｄ If R is N, ２ｄ , R ４ｄ , R ５ｄ , and R ６ｄ A compound of formula (II), or a pharmaceutically acceptable salt thereof, provided that three or fewer of these atoms are H.

25. R ６ｃ However, halo, -OH, -CN, C １ -C ６ Alkoxy, or C(O)NH ２ And, Y, 【Chemical 975】 The compound according to claim 24.

26. A compound of formula (III), 【Chemical 981】 During the ceremony, X ３ｋ However, it is N or CH, X ４ｋ However, it is N or CH, X ５ｋ However, N or CR ５ｋ And, X ６ｋ However, N, N ＋ -O － , or CR ６ｋ And, R ５ｋ However, H, C １ -C ６ Alkoxy, -OH, -OCH ２ CH ２ N(CH ３ ) ２ , or -N(CH ３ ) (CH ２ CH ２ OCH ３ ) and R ６ｋ However, H, -OH, C １ -C ６ Alkoxy, or -C(O)NH ２ And, R ２Ｌ However, C １ -C ６ It is alkyl, R ４Ｌ However, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, or (C １ -C ６ (Haloalkyl)-(C) ３ -C ６ It is a cycloalkyl)-, R ５Ｌ However, H, halo, or C １ -C ６ It is alkyl, however, (i) X ３ｋ , X ４ｋ , and X ５ｋ At least one of them is N, or X ６ｋ is N or N ＋ -O － That is, (ii) X ３ｋ , X ４ｋ , X ５ｋ , and X ６ｋ Two or fewer of them are N, (iii)X ６ｋ is N ＋ -O － If X ３ｋ and X ４ｋ CH is, X ５ｋ CR ５ｋ That is, (iv) X ５ｋ If X is N, ４ｋ A compound of formula (III), or a pharmaceutically acceptable salt thereof, provided that is N and .

27. R ６ｋ However, H, -OH, or C １ -C ６ The compound according to claim 26, which is an alkoxy. 【Request Item 28】 【Table A-32】 Table A-33 Table A-34 Table A-35 Table A-36 Table A-37 Table A-38 Table A-39 Table A-40 Table A-41 Table A-42 Table A-43 Table A-44 Table A-45 Table A-46 Table A-47 Table A-48 Table A-49 Table A-50 Table A-51 Table A-52 Table A-53 Table A-54 Table A-55 Table A-56 Table A-57 Table A-58 Table A-59 Table A-60 Table A-61 Table A-62 A compound selected from, or a pharmaceutically acceptable salt thereof. 【Request Item 29】 【Table B-19】 Table B-20 Table B-21 Table B-22 Table B-23 Table B-24 Table B-25 Table B-26 Table B-27 Table B-28 Table B-29 Table B-30 Table B-31 Table B-32 Table B-33 Table B-34 Table B-35 Table B-36 A compound selected from, or a pharmaceutically acceptable salt thereof. 【Request Item 30】 【Chemistry 983-1】 【Chemical Engineering 983-2】 【Chemical Engineering 983-3】 A compound selected from, or a pharmaceutically acceptable salt thereof. 【Request Item 31】 【Chemistry 984】 A compound, or a pharmaceutically acceptable salt thereof. 【Request Item 32】 【Chemistry 985】 A compound, or a pharmaceutically acceptable salt thereof. 【Request Item 33】 【Chemistry 986】 A compound, or a pharmaceutically acceptable salt thereof. 【Request Item 34】 【Chemistry 987】 A compound, or a pharmaceutically acceptable salt thereof. 【Request Item 35】 【Chemistry 988】 A compound, or a pharmaceutically acceptable salt thereof. 【Request Item 36】 【Chemistry 989】 【Chemical Formula 990】 【Chem.991】 A compound selected from the following. 【Request Item 37】 【Chemistry 992】 It is a compound. 【Request Item 38】 【Chemistry 993】 It is a compound. 【Request Item 39】 【Chemistry 994】 It is a compound. 【Request Item 40】 【Chemistry 995】 It is a compound. 【Request Item 41】 【Chemistry 996】 It is a compound.

42. A compound according to any one of claims 1 to 35, which is in a non-salt form.

43. A pharmaceutical composition comprising a compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof, or a compound according to any one of claims 36 to 41, or a compound according to any one of claims 1 to 35 in a non-salt form, and one or more pharmaceutically acceptable carriers or vehicles.

44. A composition for inhibiting voltage-gated sodium channels in a target, wherein the composition comprises a compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof, and optionally the voltage-gated sodium channel is Na V 1.

8.

45. The pharmaceutical composition according to claim 43 for use in inhibiting voltage-gated sodium channels in a target.

46. A composition for treating or reducing the severity of chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postoperative pain, visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough, or cardiac arrhythmia, comprising a compound or a pharmaceutically acceptable salt thereof as described in any one of claims 1 to 35.

47. The composition is (i) Neuropathic pain, and as necessary The aforementioned neuropathic pain includes postherpetic neuralgia; or The neuropathic pain includes small fiber neuropathy; or The neuropathic pain includes idiopathic small-diameter fiber neuropathy; or The neuropathic pain includes diabetic neuropathy, and optionally, the diabetic neuropathy includes diabetic peripheral neuropathy; or (ii) Musculoskeletal pain, wherein the musculoskeletal pain includes, if necessary, osteoarthritis; or (iii) Acute pain, which, if necessary, includes acute postoperative pain; or (iv) Postoperative pain, if necessary, The aforementioned postoperative pain includes pain from aponeurosis excision; or The aforementioned postoperative pain includes pain from abdominal wall reconstruction; or Postoperative pain includes pain from hernia repair surgery; or (v) Visceral pain The composition according to claim 46, for treating or reducing the severity thereof in the subject.

48. The pharmaceutical composition according to claim 43 for use in treating or reducing the severity of chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postoperative pain, visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough, or cardiac arrhythmia.

49. The pharmaceutical composition is (i) Neuropathic pain, and as necessary The aforementioned neuropathic pain includes postherpetic neuralgia; or The neuropathic pain includes small fiber neuropathy; or The neuropathic pain includes idiopathic small-diameter fiber neuropathy; or The neuropathic pain includes diabetic neuropathy, and optionally, the diabetic neuropathy includes diabetic peripheral neuropathy; or (ii) Musculoskeletal pain, wherein the musculoskeletal pain includes, if necessary, osteoarthritis; or (iii) Acute pain, which, if necessary, includes acute postoperative pain; or (iv) Postoperative pain, if necessary, The aforementioned postoperative pain includes pain from aponeurosis excision; or The aforementioned postoperative pain includes pain from abdominal wall reconstruction; or Postoperative pain includes pain from hernia repair surgery; or (v) Visceral pain The pharmaceutical composition according to claim 48, for treating or reducing the severity thereof in the subject.

50. A composition comprising a compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof, or a compound according to any one of claims 36 to 41, or a compound according to any one of claims 1 to 35 in a non-salt form and one or more pharmaceutically acceptable carriers or vehicles, for the purpose of inhibiting voltage-gated sodium channels in a subject, or for the purpose of treating or reducing the severity thereof in a subject, wherein the subject is treated simultaneously with, before or after, treatment with one or more additional therapeutic agents administered with the compound, the pharmaceutically acceptable salt, or the pharmaceutical composition.

51. A composition for use as a pharmaceutical agent, comprising a compound according to any one of claims 1 to 35 or a pharmaceutically acceptable salt thereof.

52. The pharmaceutical composition according to claim 43 for use as a pharmaceutical agent.

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