Heteroaryl compounds for treatment of pain

Abstract

Compounds and pharmaceutically acceptable salts thereof useful as inhibitors of sodium channels are provided. Also provided are pharmaceutical compositions comprising the compounds or the pharmaceutically acceptable salts, and methods of using the compounds, the pharmaceutically acceptable salts, and the pharmaceutical compositions in the treatment of various conditions, including pain.

Description

[0001] Cross-reference to related applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 333,814, filed April 22, 2022, which is incorporated herein by reference in its entirety. Background Art

[0003] Pain is a protective mechanism that allows healthy animals to avoid tissue damage and prevent further damage to injured tissue. Despite this, in many cases, pain persists beyond its scope of action, or patients benefit from pain suppression. Neuropathic pain is a form of chronic pain caused by sensory nerve damage (Dieleman, JP et al., Incidence rates and treatment of neuropathic pain conditions in the general population. Pain, 2008.137 (3): p. 681-8). Neuropathic pain can be divided into two categories: pain caused by systemic metabolic damage to nerves and pain caused by discrete nerve damage. Metabolic neuropathy includes post-herpetic neuropathy, diabetic neuropathy, and drug-induced neuropathy. Discrete nerve damage indications include post-amputation pain, postoperative nerve damage pain, and nerve entrapment injury, such as neuropathic back pain.

[0004] Voltage-gated sodium channels (Na V ) is involved in pain signal transduction. V Sodium channel is a biological mediator of electrical signaling because it mediates the rapid rise of the action potential in many excitable cell types (e.g., neurons, skeletal muscle cells, and cardiac myocytes). Evidence from the role of these channels in normal physiology, pathological conditions caused by mutations in sodium channel genes, preclinical work in animal models, and clinical pharmacology of known sodium channel modulators all point to the role of sodium channel in normal physiology. V Central role in pain perception (Rush, AM and TR Cummins, Painful Research: Identification of a Small-Molecule Inhibitor that Selectively Targets NaV1.8 Sodium Channels) V1.8 Sodium Channels). Mol. Interv., 2007. 7(4): 192-5; England, S., Voltage-gated sodium channels: the search for subtype-selective analgesics. Expert Opin. Investig. Drugs 17(12), 1849-64 (2008); Krafte, DS and Bannon, AW, Sodium channels and nociception: recent concepts and therapeutic opportunities. Curr. Opin. Pharmacol. 8(1), 50-56 (2008). Na V Mediates the rapid rise of the action potential of 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, 3rd ed. (Sinauer Associates, Inc., Sunderland, MA, 2001)). V The role played in the initiation and propagation of neuronal signals, reducing Na V Antagonists of this current can prevent or reduce nerve signaling, and Na V Channels have been considered as possible targets for alleviating 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), pp. 144-58 (2008)). Several clinically useful analgesics have been identified as Na V Channel inhibitors. VChannel-blocking pain local anesthetics such as lidocaine and other compounds that have been shown to be effective in reducing pain such as carbamazepine, lamotrigine, and tricyclic antidepressants have also been suggested to act through sodium channel inhibition (Soderpalm, B., Anticonvulsants: aspects of their mechanisms of action. Eur. J. Pain 6 Suppl A, pp. 3-9 (2002); Wang, GK, Mitchell, J. and Wang, SY, Block of persistent late Na+ current by the antidepressants sertraline and paroxetine. + currents by antidepressantsertraline and paroxetine). Journal of Membrane Biology (J. Membr. Biol.), 222(2), pp. 79-90 (2008).

[0005] Na V Forms a subfamily of the voltage-gated ion channel superfamily and contains nine isoforms named Na V 1.1-Na V 1.9. These nine isoforms have different tissue localizations. V 1.4 is the major sodium channel in skeletal muscle, and Na V 1.5 is the main sodium channel in myocardial cells. V 1.7, 1.8, and 1.9 are mainly localized to the peripheral nervous system, while Na V 1.1, 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 different 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)).

[0006] Once discovered, Na V 1.8 channel was identified as a possible analgesic target (Akopian, AN, L. Sivilotti and JN Wood, A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature, 1996. 379(6562): p. 257-62). V 1.8 has been shown to be a carrier of the sodium current that sustains action potential discharges in small dorsal root ganglion (DRG) neurons (Blair, NT and BPBean, Role of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na+ current, and Ca2+ current in the action potential of nociceptive sensory neurons (Roles of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na+ current, and Ca2+ current in the action potential of nociceptive sensory neurons) + current, and Ca 2+ current in the action potentials of nociceptive sensory neurons). Journal of Neuroscience (J. Neurosci.), 2002.22(23): p.10277-90). Na V 1.8 has been implicated in spontaneous firing in injured neurons, such as those that drive neuropathic pain (Roza, C. et al., The tetrodotoxin-resistant Na+ channel NaV1.8 is essential for the expression of spontaneous activity in injured sensory axons of mice (The tetrodotoxin-resistant Na + channelNa V 1.8 is essential for the expression of spontaneous activity in damaged sensory axons of mice). Journal of Physiology, 2003.550(Pt 3): p. 921-6; Jarvis, MF et al., A-803467, a potent and selective NaV1.8 sodium channel blocker, reduces neuropathic and inflammatory pain in rats. V1.8 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 NaV1.8 in inflammatory and neuropathic pain states, but not in postoperative pain states. V 1.8 in inflammatory and neuropathic, but not post-operative, pain states. Pain, 2006. 123(1-2): 75-82; Lai, J. et al., Inhibition of neuropathic pain by decreased expression of thetetrodotoxin-resistant sodium channel, NaV1.8. V 1.8). Pain, 2002.95(1-2): p. 143-52; Dong, XW et al., Small interfering RNA-mediated selective knockdown of NaV1.8 anti-tetrodotoxin sodium channel reverses mechanical hyperalgesia in rats with neuropathic pain. V1.8tetrodotoxin-resistant sodium channel reverses mechanical allodynia in neuropathic rats). Neuroscience, 2007.146(2):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, 2008.4:33; Black, JA et al. Multiple sodium channel isoforms and mitogen-activated protein kinases are present in painful human neuromas. Neuromas). Ann. Neurol., 2008. 64(6): 644-53; Coward, K. et al. Immunolocalization of SNS / PN3 and NaN / SNS2 sodium channels in human pain states. Pain, 2000. 85(1-2): 41-50; Yiangou, Y. et al. SNS / PN3 and SNS2 / NaN sodium channel-like immunoreactivity in human adult and neonate injured sensory nerves. FEBS Letters. Lett.), 2000. 467(2-3): p. 249-52; Ruangsri, S. et al., Axonal voltage-gated sodium channel 1.8 (NaV1.8) Relationship of axonal voltage-gated sodium channel 1.8 (Na. V 1.8) mRNA accumulation to sciatic nerve injury-induced painful neuropathy in rats. Journal of Biological Chemistry (J.Biol.Chem.) 286(46): p. 39836-47). Among them, Na V The small DRG neurons of 1.8 include nociceptors involved in pain signaling. V 1.8 mediates large-amplitude action potentials in small neurons of the dorsal root ganglion (Blair, NT and BPBean, tetrodotoxin (TTX)-sensitive Na + Current, TTX resistance Na + Current and Ca 2+ The role of current in the action potential of nociceptive sensory neurons (Journal of Neuroscience, 2002. 22(23): p. 10277-90). V 1.8 is required for rapid repetitive action potentials in nociceptors and spontaneous activity in injured neurons. (Choi, JS and SG Wixman, Physiological interactions between NaV1.7 and NaV1.8 sodium channels: a computer simulation study) V 1.7 and Na V 1.8 sodium channels: a computer simulation study). J. Neurophysiol. 106(6): 3173-84; Renganathan, M., T. R. Cummins and S. G. Wixman. Contribution of Na(V)1.8 sodium channels to action potential generation in DRG neurons. V )1.8sodium channels to action potential electrogenesis in DRG neurons). Journal of Neurophysiology, 2001.86(2): p.629-40; Roza, C. et al., Anti-tetrodotoxin Na + Channel Na V1.8 is essential for the expression of spontaneous activity in injured sensory axons of mice. Journal of Physiology, 2003. 550(Pt 3): p. 921-6). In depolarized or injured DRG neurons, Na V 1.8 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. Proceedings of the National Academy of Sciences of the United States of America, 2006. 103(21): p. 8245-50). In some animal pain models, Na V NaV1.8 mRNA expression levels have been shown to be increased 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): 359-75; Strickland, IT et al., Changes in the expression of NaV1.7, NaV1.8, and NaV1.9 in different dorsal root ganglion populations innervating the rat knee joint in a model of chronic inflammatory joint pain). V 1.7,Na V 1.8and 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). European Journal of Pain, 2008.12(5): p. 564-72; Qiu, F. et al. Increased expression of tetrodotoxin-resistant sodium channels NaV1.8 and NaV1.9 in dorsal root ganglia in a rat model of bone cancer pain. V1.8 and Na V 1.9 within dorsal root ganglia in an arat model of bone cancer pain. Neurosci. Lett. 512(2): 61-6.

[0007] The present inventors have found that, due to, for example, a poor therapeutic window (e.g., due to lack of Na V Some voltage-gated sodium channel inhibitors have limitations as therapeutic agents due to isotype selectivity, low potency, and / or other reasons. Therefore, there is still a need to develop selective voltage-gated sodium channel inhibitors, such as selective Na V 1.8 Inhibitors. Summary of the Invention

[0008] In one aspect, the present invention relates to a compound described herein or a pharmaceutically acceptable salt thereof.

[0009] In another aspect, the present invention relates to a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or vehicles.

[0010] In still another aspect, the present invention relates to a method of inhibiting a voltage-gated sodium channel in a subject by administering the compound, the pharmaceutically acceptable salt, or the pharmaceutical composition to the subject.

[0011] In another aspect, the present invention relates to a method for treating or lessening the severity of various diseases, disorders or conditions in a subject by administering to the subject the compound, the pharmaceutically acceptable salt or the pharmaceutical composition, including but not limited to chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postoperative pain (e.g., bunionectomy pain, hernia repair pain or abdominoplasty pain), visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough and arrhythmia. DETAILED DESCRIPTION

[0012] In one aspect, the present invention relates to a compound of formula (I):

[0013]

[0014] or a pharmaceutically acceptable salt thereof, wherein:

[0015] X is CR 5b or N;

[0016] R 2a and R 3a The following definitions are given:

[0017] (i)R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl)2, or -N(C1-C6 haloalkyl)2; and

[0018] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2)、-CH2CH2NHC(O)CH(CH3)(NH2)、-NHC(O)CH(CH3)(NH2)、-C(O)NHC(O)(C1-C6 alkyl)、-NHS(O)2CH3、-S(C1-C6 alkyl)、C3-C7 cycloalkyl、C6-C 10 Aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; or

[0019] (ii)R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(N(C1-C6 alkyl))R' or -S(O)2NCH3R'; and

[0020] R 2aand R' together with the atoms to which they are attached join together to form a 4-7 membered heterocyclic group;

[0021] R 5a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -C(O)O(C1-C6 haloalkyl), or a 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'replace;

[0022] Each R a ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl);

[0023] R 2b 、R 3b and R 4b The following definitions are given:

[0024] (i)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -OCH2CH2OH, -OCH2CH2OCH3, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens;

[0025] R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0026] R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or

[0027] (ii)R 2b and R 3b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0028] and

[0029] R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl is optionally substituted with one or more halogens; or

[0030] (iii)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0031] R 3b and R 4b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0032]

[0033] R 5bis H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0034] R 6b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens;

[0035] R n is H or C1-C6 alkyl,

[0036] The conditions are:

[0037] (i) If X is N, then R 3b and R 4b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0038] and

[0039] (ii) If R 2a is H, then R 3a Halogenated, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、-C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and

[0040] (iii) If R 3a is -C(O)O(C1-C2 alkyl), then R 4b is H, fluorine, chlorine, C1-C6 alkyl, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0041] (iv)R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than four of them are H; and

[0042] (v)R 2b 、R 3b 、R 4b 、R 5b and R 6b not more than one of them is fluorine; and

[0043] (vi)R 2b 、R 3b 、R 4b 、R 5b and R 6b not more than one of which is chlorine; and

[0044] (vii) If R 2b 、R 3b 、R 4b 、R 5b and R 6b If any one of R 2b、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0045] (viii) If R 2b or R 6b is -OCH3, and R 3a is H, then R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0046] (ix) If R 3b is fluorine, then R 6b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0047] (x) If R 5b is fluorine, then R 2b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0048] (xi) If R 3b or R 5b is -CH3, then R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0049] (xii) If R 3b or R 5b is a C1 haloalkyl group, then R 2b、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0050] (xiii) If R3 b or R 5b is -OCH3, then R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0051] (xiv) If R 4b is a C1 haloalkyl group, then R 2b 、R 3b 、R 5b and R 6b No more than three of them are H; and

[0052] (xv) If R 4b is -OCH3, then R 2b 、R 3b 、R 5b and R 6b No more than three of them are H; and

[0053] (xvi) If R 4b is a C1 haloalkoxy group, then R 2b 、R 3b 、R 5b and R 6b No more than three of them are H; and

[0054] (xvii) If R 4b is chlorine or bromine, then R 2b and R 6b each independently represents H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0055] (xviii) If R 4b and R 3b Each is -OCH3, then R 2b 、R 5b and R6b No more than two of them are H; and

[0056] (xix) If R 4b and R 5b Each is -OCH3, then R 2b 、R 3b and R 6b No more than two of them are H.

[0057] In another aspect, the present invention relates to a compound of formula (II):

[0058]

[0059] or a pharmaceutically acceptable salt thereof, wherein:

[0060] Y is CR 3d or N;

[0061] R 2c is a C1-C6 alkyl group;

[0062] R 3c is H, halo, C1-C6 alkyl, -S(O)2(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), or 4-10 membered heteroaryl, wherein the heteroaryl is optionally substituted with C1-C6 alkyl;

[0063] R 3d is halo, C1-C6 alkyl or C1-C6 haloalkyl;

[0064] R 4d is H, C1-C6 alkyl or C1-C6 haloalkyl; and

[0065] R 6d is H, C1-C6 alkyl or C1-C6 alkoxy.

[0066] In yet another aspect, the present invention relates to a compound of formula (III):

[0067]

[0068] or a pharmaceutically acceptable salt thereof, wherein:

[0069] R 2e is a C1-C6 alkyl group;

[0070] R 2f is a C1-C6 alkyl group; and

[0071] R 4f It is a C1-C6 alkyl group.

[0072] In another aspect, the present invention relates to a compound of formula (IV):

[0073]

[0074] or a pharmaceutically acceptable salt thereof, wherein:

[0075] R 2g and R 3g The following definitions are given:

[0076] (i)R 2g is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl)2, or -N(C1-C6 haloalkyl)2; and

[0077] R 3g H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2)、-CH2CH2NHC(O)CH(CH3)(NH2)、-NHC(O)CH(CH3)(NH2)、-C(O)NHC(O)(C1-C6 alkyl)、-NHS(O)2CH3、-S(C1-C6 alkyl)、C3-C7 cycloalkyl、C6-C 10 Aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R g 'Replace; or

[0078] (ii)R 3gis -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(N(C1-C6 alkyl))R' or -S(O)2NCH3R'; and

[0079] R 2g and R' together with the atoms to which they are attached join together to form a 4-7 membered heterocyclic group;

[0080] R 5g is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -C(O)O(C1-C6 haloalkyl), or a 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R g 'replace;

[0081] Each R g ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl);

[0082] R 2h is H, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens;

[0083] R 4h and R 5h The following definitions are given:

[0084] (i)R 4his H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0085] R 5h is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or

[0086] (ii)R 4h and R 5h Together with the C atoms to which they are attached, they join together to form a C5-C6 cycloalkyl group, wherein the cycloalkyl group is optionally substituted by 1-2 C1-C6 alkyl groups.

[0087] For purposes of the present invention, chemical elements are identified according to the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th ed. In addition, general principles of organic chemistry are described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999 and "March's Advanced Organic Chemistry", 5th ed., eds.: Smith, MB and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are incorporated herein by reference.

[0088] As used herein, the term "compound of the present invention" refers to compounds of Formula (I), (II), (III), (IV) and all embodiments thereof as described herein (e.g., Formula (IA-1), (IA-2), (IB-1), (IB-2), (IC-1), (IC-2), (ID-1), (ID-2), (IE-1), (IE-2), (IF), (II-A), etc.), as well as compounds identified in Table A, Table B, Table C, and Table D.

[0089] As described herein, the compounds of the present invention contain a number of variable groups (e.g., X, R 2a , Y, etc.). As will be appreciated by one of ordinary skill in the art, the combinations of groups contemplated by the present invention are those that result in the formation of stable or chemically feasible compounds. In this context, the term "stable" refers to compounds that remain substantially unchanged when subjected to conditions that allow them to be produced, detected, and preferably recovered, purified, and used for one or more of the purposes disclosed herein. In some embodiments, a stable compound or chemically feasible compound is one that does not undergo substantial change when stored at 40°C or less in the absence of moisture or other chemically reactive conditions for at least one week.

[0090] The chemical structures depicted herein are intended to be understood as chemical structures that would be understood by one of ordinary skill in the art. For example, a substituent described as "CF3" or "F3C" in a chemical structure refers to a trifluoromethyl substituent, regardless of which description appears in the chemical structure.

[0091] As used herein, the term "halo" means F, Cl, Br, or I.

[0092] As used herein, the term "alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation and having the specified number of carbon atoms, which is attached to the remainder of the molecule by a single bond. For example, a "C1-C6 alkyl" is an alkyl group having from one to six carbon atoms.

[0093] As used herein, the term "cycloalkyl" refers to a stable, non-aromatic, monocyclic or bicyclic (fused, bridged, or spirocyclic) saturated hydrocarbon radical consisting solely of carbon and hydrogen atoms, having the specified number of carbon ring atoms and attached to the remainder of the molecule by a single bond. For example, a "C3-C8 cycloalkyl" is a cycloalkyl radical having three to eight carbon atoms.

[0094] As used herein, the term "alkoxy" refers to a group of the formula -OR a A group in which R ais an alkyl group having the specified number of carbon atoms. For example, "C1-C6 alkoxy" is of the formula -OR a A group in which R a is an alkyl group having one to six carbon atoms.

[0095] As used herein, the term "haloalkyl" refers to an alkyl group having a specified number of carbon atoms, wherein one or more of the alkyl group's hydrogen atoms are replaced by a halo group. For example, a "C1-C6 haloalkyl" is an alkyl group having from one to six carbon atoms, wherein one or more of the alkyl group's hydrogen atoms are replaced by a halo group.

[0096] As used herein, the term "haloalkoxy" refers to an alkoxy group having the specified number of carbon atoms in which one or more of the hydrogen atoms of the alkyl group are replaced by a halo group.

[0097] As used herein, the term "alkylene" refers to a divalent straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation and having a specified number of carbon atoms, the alkylene being attached to the remainder of the molecule by two single bonds. For example, "C1-C6 alkylene" is an alkylene having from one to six carbon atoms.

[0098] As used herein, the term "haloalkylene" refers to an alkylene group having a specified number of carbon atoms, wherein one or more of the hydrogen atoms of the alkylene group are replaced by a halo group. For example, a "C1-C6 haloalkylene group" is an alkylene group having one to six carbon atoms, wherein one or more of the hydrogen atoms of the alkylene group are replaced by a halo group.

[0099] As used herein, the term "heterocyclic radical" refers to a stable, non-aromatic, monocyclic, bicyclic or tricyclic (fused, bridged or spirocyclic) radical, wherein one or more ring atoms are heteroatoms (e.g., heteroatoms independently selected from N, O, P and S), the heterocyclic radical has a specified number of ring atoms, and the heterocyclic radical is connected to the rest of the molecule by a single bond. Heterocycle can be saturated or can include one or more double or triple bonds. In certain embodiments, "heterocyclic radical" has an indicated number of ring members, wherein one or more ring members are heteroatoms independently selected from oxygen, sulphur, nitrogen and phosphorus, and each ring in the ring system includes 3 to 7 ring members. For example, a 6-membered heterocyclic radical includes 6 ring members in total, and at least one of the ring members is a heteroatom (e.g., heteroatoms independently selected from N, O, P and S).

[0100] As used herein, the term "heteroaryl" refers to a stable monocyclic, bicyclic or tricyclic radical having a 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 comprises 3 to 7 ring members. For example, a 6-membered heteroaryl group comprises a total of 6 ring members, at least one of the ring members being a heteroatom selected from N, S, O and P. The term "heteroaryl" can be used interchangeably with the term "heteroaryl ring" or the term "heteroaromatic".

[0101] As used herein, labels such as "*2" and "*3", as in the following structures, denote the corresponding R groups (in this case, R 2b and R 3b The carbon atom to which the group is attached:

[0102]

[0103] Similarly, the “*3” and “*4” in the following structures represent R 3b and R 4b The carbon atom to which the group is attached:

[0104]

[0105] Unless otherwise indicated, the compounds of the present 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)), conformers, and tautomers of the compounds identified by the chemical names and chemical structures provided herein. In addition, individual stereoisomers, double bond isomers, conformers, and tautomers, as well as mixtures of stereoisomers, double bond isomers, conformers, and tautomers, are within the scope of the present invention.

[0106] As used herein, in any chemical structure or formula, a non-bold direct bond to a stereogenic center of a compound, such as in

[0107]

[0108] The configuration of a stereocenter is unspecified. The compound may have any configuration or mixture of configurations at the stereocenter.

[0109] As used herein, the prefix "rac-" when used in conjunction with a chiral compound refers to a racemic mixture of the compound.

[0110] As used herein, the prefix "rel-" when used in conjunction with 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 not necessarily the absolute stereochemistry of the compound. In cases where the relative stereochemistry of a given stereocenter is unknown, no stereochemical designator is provided.

[0111] 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 there may be isotopic variations between the constituent atoms of the molecules. The term "compound" includes such a collection of molecules without regard to the purity of a given sample containing the collection of molecules. Thus, the term "compound" includes 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.

[0112] In the specification and claims, unless otherwise indicated, any atom in any compound of the present invention that is not specifically designated as a particular isotope is intended to represent any stable isotope of the specified element. In examples, where an atom in any compound of the present invention is not specifically designated as a particular isotope, no effort has been made to enrich that atom in that particular isotope, and thus, one of ordinary skill in the art will understand that such atom is likely to be present at approximately the natural abundance isotopic composition of the specified element.

[0113] As used herein, the term "stable" when referring to an isotope means that the isotope is not currently known to undergo spontaneous radioactive decay. Stable isotopes include, but are not limited to, isotopes for which no decay mode is determined in V.S. Shirley and C.M. Lederer, Isotopes Project, Nuclear Science Division, Lawrence Berkeley Laboratory, Table of Nuclides (January 1980).

[0114] As used herein in the specification and claims, "H" means hydrogen and includes any stable isotope of hydrogen, i.e. 1 H and D. In instances where atoms are designated as "H," no effort has been made to enrich the atom in a particular isotope of hydrogen, and thus one of ordinary skill in the art will understand that such hydrogen atoms are likely to be present at approximately the natural abundance isotopic composition of hydrogen.

[0115] As used herein, “1 H" refers to protium. Where an atom in a compound of the invention or a pharmaceutically acceptable salt thereof is designated as protium, the protium is present at the designated position at a concentration of at least the natural abundance of protium.

[0116] As used herein, "D", "d" and " 2 H" refers to deuterium.

[0117] In some embodiments, the compounds of the present invention and pharmaceutically acceptable salts thereof include approximately the natural abundance isotopic composition of a designated element for each constituent atom.

[0118] In some embodiments, the compounds of the present invention and pharmaceutically acceptable salts thereof include 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 a designated element ("isotopically labeled" compounds and salts). Examples of commercially available stable isotopes suitable for the present invention include, but are not limited to, isotopes of hydrogen, carbon, nitrogen, oxygen, and phosphorus, such as, respectively. 2 H. 13 C. 15 N. 18 O. 17 O and 31 P.

[0119] Isotopically labeled compounds and salts can be used in a variety of beneficial ways, including as pharmaceuticals. In some embodiments, isotopically labeled compounds and salts are deuterated ( 2 H) labeled. 2 H) The labeled compounds and salts are therapeutically useful and are comparable to those without 2 H-labeled compounds have potential therapeutic advantages. In general, compared to non-isotope-labeled compounds and salts, deuterium ( 2 H) labeled compounds and salts may have higher metabolic stability due to the kinetic isotope effect described below. Higher metabolic stability directly translates into increased in vivo half-life or lower dosage, which in most cases will represent a preferred embodiment 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 descriptions, substituting readily available isotopically labeled reactants for non-isotopically labeled reactants.

[0120] Deuterium ( 2H) labeled compounds and salts can manipulate the oxidative metabolic rate of a compound through the primary kinetic isotope effect. The primary kinetic isotope effect is a change in the rate of a chemical reaction caused by the exchange of isotopic nuclei, which in turn is caused by a change in the ground state energy of the covalent bonds involved in the reaction. The exchange of heavier isotopes generally lowers the ground state energy of the chemical bond and therefore reduces the rate-limiting bond breakage. If bond breakage occurs in or near the saddle point region along the coordinates of a multi-product reaction, the product distribution ratio may change significantly. For example, if deuterium is bonded to a carbon atom at a non-exchangeable position, then k H / k D Rate differences of 2-7 are typical. For further discussion, see SL Harbeson and RD Tung, Deuterium In Drug Discovery and Development, Ann. Rep. Med. Chem. 2011, 46, 403-417, which is incorporated herein by reference in its entirety.

[0121] The concentration of an isotope (e.g., deuterium) incorporated at a given position of an isotopically labeled compound of the invention, or a pharmaceutically acceptable salt thereof, can be defined by an isotopic enrichment factor. As used herein, the term "isotopic enrichment factor" means 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.

[0122] Where an atom in a compound of the invention or a pharmaceutically acceptable salt thereof is designated as deuterium, the isotopic enrichment factor of such compound (or salt) for such atom is at least 3000 (approximately 45% deuterium incorporation). In some embodiments, the isotopic enrichment factor is at least 3500 (approximately 52.5% deuterium incorporation), at least 4000 (approximately 60% deuterium incorporation), at least 4500 (approximately 67.5% deuterium incorporation), at least 5000 (approximately 75% deuterium incorporation), at least 5500 (approximately 82.5% deuterium incorporation), at least 6000 (approximately 90% deuterium incorporation), at least 6333.3 (approximately 95% deuterium incorporation), at least 6466.7 (approximately 97% deuterium incorporation), at least 6600 (approximately 99% deuterium incorporation), or at least 6633.3 (approximately 99.5% deuterium incorporation).

[0123] In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein:

[0124] R 2ais H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2;

[0125] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and

[0126] R 5a It is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl).

[0127] In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein X is N. In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b , and R 5bis H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or -C(O)(C1-C6 alkyl). 5b In other embodiments, R 5b is a C1-C6 alkyl group. In other embodiments, R 5b is a C1-C6 haloalkyl group. 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 X is CR 5b , and R 5b is H, F, Cl, -CH3, -C(CH3)3, -CF3, -OCH3 or -C(O)CH3. In other embodiments, R 5b is H. In other embodiments, R 5b is F. In other embodiments, R 5b In other embodiments, R 5b In other embodiments, R 5b is -C(CH3)3. In other embodiments, R 5b In other embodiments, R 5b In other embodiments, R 5b It is -C(O)CH3.

[0128] In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or -N(C1-C6 alkyl)2. In other embodiments, R 2a is a C1-C6 alkyl group. In other embodiments, R 2a is a C1-C6 haloalkyl group. In other embodiments, R 2a is C1-C6 alkoxy. In other embodiments, R 2a In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 2a is H, -CH3, -CF3, -OCH3 or -N(CH3)2. In other embodiments, R 2a is H. In other embodiments, R 2a In other embodiments, R 2a In other embodiments, R 2a In other embodiments, R2a It is -N(CH3)2.

[0129] In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2), -C(O)NHC(O)CH3, -NHS(O)2CH3, -S(C1-C6 alkyl), C3-C7 cycloalkyl, C6-C 10 Aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; and each R a ' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)NH 2、-C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2. In other embodiments, R 3a In other embodiments, R 3a is a C1-C6 alkyl group. In other embodiments, R 3a is C1-C6 alkoxy. In other embodiments, R 3a is -N(C1-C6 alkyl)2. In other embodiments, R 3a is -(C1-C6 alkylene)-OH. In other embodiments, R 3a is -(C1-C6 alkylene)-NH2. In other embodiments, R 3a is -C(O)(C1-C6 alkyl). In other embodiments, R 3a is -C(O)NH2. In other embodiments, R 3a is -C(O)O(C1-C6 alkyl). In other embodiments, R 3a is -S(O)2-(C1-C6 alkyl). In other embodiments, R 3a is -S(O)(NH)(C1-C6 alkyl). In other embodiments, R 3a is -CH2C(O)NH(C1-C6 alkyl). In other embodiments, R 3a is -NHC(O)(C1-C6 alkyl). In other embodiments, R 3a is -C(O)NHC(O)CH3. In other embodiments, R 3a is -NHS(O)2CH3. In other embodiments, R 3a is -S(C1-C6 alkyl). In other embodiments, R 3a is a C3-C7 cycloalkyl group. In other embodiments, R 3a C6-C 10 In other embodiments, R 3a is a 4-10 membered heterocyclic group, wherein the heterocyclic group is optionally substituted by 1-2 R a 'Replace; and each R a' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In other embodiments, R 3a is a 4-10 membered heteroaryl group, wherein the heteroaryl group is optionally substituted by 1-2 R a 'Replace; and each R a ' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 3a is H, Cl, Br, -CN, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH), -C(CH3)2(OH), -CH2NH 2. -C(O)CH3, -C(O)NH2, -C(O)OCH2CH3, -S(O)2-(CH3), -S(O)2CH(CH3)2, -S(O)(NH)(CH3), -S(O)(NH)CH( CH3)2, -CH2C(O)NH2, -CH2C(O)NH(CH3), -NHC(O)CH3, -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3 )(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2), -C(O)NHC(O)CH3, -NHS(O)2CH3, -SCH 3、 Cyclopropyl, phenyl, In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 3ais H, Cl, -CN, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH), -C(CH3)2(OH), -CH2NH2, -C(O)C H3, -C(O)NH2, -C(O)OCH2CH3, -S(O)2-(CH3), -S(O)(NH)(CH3), -CH2C(O)NH2, -CH2C(O)NH(CH3), -NHC(O)CH3,

[0130] -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2) or -NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is H. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)2. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -N(CH3)2. In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)(OH). In other embodiments, R 3a is -C(CH3)2(OH). In other embodiments, R 3a In other embodiments, R 3a is -C(O)CH3. In other embodiments, R 3a is -C(O)NH2. In other embodiments, R 3a In other embodiments, R 3a is -S(O)2-(CH3). In other embodiments, R 3a is -S(O)(NH)(CH3). In other embodiments, R 3a is -CH2C(O)NH2. In other embodiments, R 3a is -CH2C(O)NH(CH3). In other embodiments, R 3a is -NHC(O)CH3. In other embodiments, R 3ais -CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a for

[0131] -CH2N(CH3)C(O)CH(CH3)(N(CH3)2). In other embodiments, R 3a is -CH2CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is -NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is Br. In other embodiments, R 3a is -S(O)2CH(CH3)2. In other embodiments, R 3a is -S(O)(NH)CH(CH3)2. In other embodiments, R 3a is -C(O)NHC(O)CH3. In other embodiments, R 3a is -NHS(O)2CH3. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for

[0132] In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(NCH3)R' or -S(O)2NCH3R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a is -S(O)R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a -S(O)2R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a -S(O)(NH)R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a -S(O)(NCH3)R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a -S(O)2NCH3R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group.

[0133] In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 5ais H, halo, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -C(O)O(C1-C6 alkyl), or a 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'Replace; and R a ' is -CH3, -CHF2 or -CH2OCH3. In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 5a is H, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl) or -C(O)O(C1-C6 alkyl). In other embodiments, R 5a is a C1-C6 alkyl group. In other embodiments, R 5a is C1-C6 alkoxy. In other embodiments, R 5a is -CH2O(C1-C6 alkyl). In other embodiments, R 5a is -C(O)O(C1-C6 alkyl). In other embodiments, R 5a In other embodiments, R 5a is a 4-10 membered heteroaryl group, wherein the heteroaryl group is optionally replaced by R a 'Replace; and R a ' is -CH3, -CHF2 or -CH2OCH3. In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 5a It is H, Br, -CH3, -OCH3, -OCH2CH3, -CH2OH, -CH2OCH3, -C(O)OCH2CH3, In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 5a In other embodiments, R 5a is H. In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a is Br. In other embodiments, R 5a for In other embodiments, R 5a for In other embodiments, R 5a for In other embodiments, R 5a for

[0134] 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, -OH, -CH2OH, -OCH2CH2OH or -OCH2CH2OCH3. In other embodiments, R 2b In other embodiments, R 2b is a C1-C6 alkyl group. 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 R 2b In other embodiments, R 2b is H. In other embodiments, R 2b is F. In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2b is -CH(CH3)2. In other embodiments, R 2b is -C(CH3)3. In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2b It is -OCH2CH2OCH3.

[0135] In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy. 3b In other embodiments, R 3bis a C1-C6 alkyl group. In other embodiments, R 3b is a C1-C6 haloalkyl group. In other embodiments, R 3b In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 3b is H, F, Cl, -CH3, -C(CH3)3, -CF3, -OCH3, -OCH2CH3 or -OC(CH3)3. In other embodiments, R 3b is H. In other embodiments, R 3b is F. In other embodiments, R 3b In other embodiments, R 3b In other embodiments, R 3b is -C(CH3)3. In other embodiments, R 3b In other embodiments, R 3b In other embodiments, R 3b In other embodiments, R 3b It is -OC(CH3)3.

[0136] 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 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. 4b In other embodiments, R 4b is a C1-C6 alkyl group. In other embodiments, R 4b is a C1-C6 haloalkyl group. In other embodiments, R 4b is C1-C6 alkoxy. In other embodiments, R 4b is C1-C6 haloalkoxy. In other embodiments, R 4b is a C3-C6 cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more halogens. 4bis (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 alkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In other embodiments, R 4b is (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 4b is H, F, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CF3), -OCH3, -OCH(CH3)2, -OC(CH3)3, -OCF3, cyclopropyl, 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl, 3,3-difluoro-1-methylcyclobutyl or In other embodiments, R 4b is H. In other embodiments, R 4b is F. In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b is -CH(CH3)2. In other embodiments, R 4b is -C(CH3)3. In other embodiments, R 4b is -C(CH3)2(CH2CH3). In other embodiments, R 4b In other embodiments, R 4b is -C(CH3)2(CF3). In other embodiments, R 4b In other embodiments, R 4b is -OCH(CH3)2. In other embodiments, R 4b is -OC(CH3)3. In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b is 3,3-difluoro-1-methylcyclobutyl. In other embodiments, R 4b for In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 4bIn some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 4b It is -C(CD3)(CH3)(CF3).

[0137] In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 2b and R 3b Together with the carbon atom to which they are attached, they form a In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 2b and R 3b Together with the carbon atom to which they are attached, they form a The ring, and R 4b is H. In other embodiments, R 2b and R 3b Together with the carbon atom to which they are attached, they form a In other embodiments, R 2b and R 3b Together with the carbon atom to which they are attached, they form a Ring.

[0138] In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 3b and R 4b Together with the carbon atom to which they are attached, they form a In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 3b and R 4b Together with the carbon atom to which they are attached, they form a The ring, and R 2b is H. In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a Ring.

[0139] In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R n In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R n is -CH3.

[0140] In some embodiments, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 6b is H, halo, C1-C6 alkyl or C1-C6 alkoxy. 6b In other embodiments, R 6b is a C1-C6 alkyl group. 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 R 6b is H, Cl, -CH3 or -OCH3. In other embodiments, R 6b is H. In other embodiments, R 6b In other embodiments, R 6b In other embodiments, R 6b It is -OCH3.

[0141] In some embodiments, the present invention relates to a compound of formula (IA-1):

[0142]

[0143] or a pharmaceutically acceptable salt thereof, wherein:

[0144] X is CR 5b or N;

[0145] R 2a and R 3a The following definitions are given:

[0146] (i)R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl)2, or -N(C1-C6 haloalkyl)2; and

[0147] R 3aH, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2)、-CH2CH2NHC(O)CH(CH3)(NH2) or -NHC(O)CH(CH3)(NH2)、-C(O)NHC(O)(C1-C6 alkyl)、-NHS(O)2CH3、-S(C1-C6 alkyl)、C3-C7 cycloalkyl、C6-C 10 aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl and S, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; or

[0148] (ii)R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(N(C1-C6 alkyl))R' or -S(O)2NCH3R'; and

[0149] R 2a and R' together with the atoms to which they are attached join together to form a 4-7 membered heterocyclic group;

[0150] R 5a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -C(O)O(C1-C6 haloalkyl) or 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'replace;

[0151] Each R a ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl);

[0152] R 2b 、R 3b and R 4b The following definitions are given:

[0153] (i)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens;

[0154] R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0155] R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or

[0156] (ii)R 2b and R 3b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0157] and

[0158] R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or

[0159] (iii)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0160] R 3b and R 4b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0161]

[0162] R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0163] R 6b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens;

[0164] R n is H or C1-C6 alkyl,

[0165] The conditions are:

[0166] (i) If X is N, then R 3b and R 4b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0167] and

[0168] (ii) If R 2a is H, then R 3a Halogenated, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and

[0169] (iii) If R 3ais -C(O)O(C1-C2 alkyl), then R 4b is H, fluorine, chlorine, C1-C6 alkyl, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0170] (iv)R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than four of them are H; and

[0171] (v)R 2b 、R 3b 、R 4b 、R 5b and R 6b not more than one of them is fluorine; and

[0172] (vi)R 2b 、R 3b 、R 4b 、R 5b and R 6b not more than one of which is chlorine; and

[0173] (vii) If R 2b 、R 3b 、R 4b 、R 5b and R 6b If any one of R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0174] (viii) If R 2b or R 6b is -OCH3, and R 3a is H, then R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0175] (ix) If R3b is fluorine, then R 6b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0176] (x) If R 5b is fluorine, then R 2b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0177] (xi) If R 3b or R 5b is -CH3, then R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0178] (xii) If R 3b or R 5b is a C1 haloalkyl group, then R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0179] (xiii) If R3 b or R 5b is -OCH3, then R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0180] (xiv) If R 4bis a C1 haloalkyl group, then R 2b 、R 3b 、R 5b and R 6b No more than three of them are H; and

[0181] (xv) If R 4b is -OCH3, then R 2b 、R 3b 、R 5b and R 6b No more than three of them are H; and

[0182] (xvi) If R 4b is a C1 haloalkoxy group, then R 2b 、R 3b 、R 5b and R 6b No more than three of them are H; and

[0183] (xvii) If R 4b is chlorine or bromine, then R 2b and R 6b each independently represents H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and

[0184] (xviii) If R 4b and R 3b Each is -OCH3, then R 2b 、R 5b and R 6b No more than two of them are H; and

[0185] (xix) If R 4b and R 5b Each is -OCH3, then R 2b 、R 3b and R 6b No more than two of them are H.

[0186] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein:

[0187] R 2ais H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2;

[0188] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and

[0189] R 5a It is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl).

[0190] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein X is N. In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b , and R 5bis H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or -C(O)(C1-C6 alkyl). 5b In other embodiments, R 5b is a C1-C6 alkyl group. In other embodiments, R 5b is a C1-C6 haloalkyl group. 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-1) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b , and R 5b is H, F, Cl, -CH3, -C(CH3)3, -CF3, -OCH3 or -C(O)CH3. In other embodiments, R 5b is H. In other embodiments, R 5b is F. In other embodiments, R 5b In other embodiments, R 5b In other embodiments, R 5b is -C(CH3)3. In other embodiments, R 5b In other embodiments, R 5b In other embodiments, R 5b It is -C(O)CH3.

[0191] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or -N(C1-C6 alkyl)2. In other embodiments, R 2a is a C1-C6 alkyl group. In other embodiments, R 2a is a C1-C6 haloalkyl group. In other embodiments, R 2a is C1-C6 alkoxy. In other embodiments, R 2a In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 2a is H, -CH3, -CF3, -OCH3 or -N(CH3)2. In other embodiments, R 2a is H. In other embodiments, R 2a In other embodiments, R 2a In other embodiments, R 2a In other embodiments, R2a It is -N(CH3)2.

[0192] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2)-C(O)NHC(O)CH3, -NHS(O)2CH3, -S(C1-C6 alkyl), C3-C7 cycloalkyl, C6-C 10 Aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; and each R a ' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)NH 2、-C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2. In other embodiments, R 3a In other embodiments, R 3a is a C1-C6 alkyl group. In other embodiments, R 3a is C1-C6 alkoxy. In other embodiments, R 3a is -N(C1-C6 alkyl)2. In other embodiments, R 3a is -(C1-C6 alkylene)-OH. In other embodiments, R 3a is -(C1-C6 alkylene)-NH2. In other embodiments, R 3a is -C(O)(C1-C6 alkyl). In other embodiments, R 3a is -C(O)O(C1-C6 alkyl). In other embodiments, R 3a is -S(O)2-(C1-C6 alkyl). In other embodiments, R 3a is -S(O)(NH)(C1-C6 alkyl). In other embodiments, R 3a is -CH2C(O)NH(C1-C6 alkyl). In other embodiments, R 3a is -NHC(O)(C1-C6 alkyl). In other embodiments, R 3a is -C(O)NHC(O)CH3. In other embodiments, R 3a is -NHS(O)2CH3. In other embodiments, R 3a is -S(C1-C6 alkyl). In other embodiments, R 3a is a C3-C7 cycloalkyl group. In other embodiments, R 3a C6-C 10 In other embodiments, R 3a is a 4-10 membered heterocyclic group, wherein the heterocyclic group is optionally substituted by 1-2 R a 'Replace; and each R a' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In other embodiments, R 3a is a 4-10 membered heteroaryl group, wherein the heteroaryl group is optionally substituted by 1-2 R a 'Replace; and each R a ' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 3a is H, Cl, Br, -CN, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH)-C(CH3)2(OH), -CH2NH2, -C(O)CH3, -C(O)NH 2、 -C(O)OCH2CH3, -S(O)2-(CH3), -S(O)2CH(CH3)2, -S(O)(NH)(CH3), -S(O)(NH)CH(CH3)2, -CH2C(O)NH2, -CH2C(O)NH(CH3), -NHC(O)(CH3), -CH2NHC( O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2), -C(O)NHC(O)CH3, -NHS(O)2CH3, -SCH 3、 Cyclopropyl, phenyl, In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 3a is H, Cl, -CN, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH)-C(CH3)2(OH), -CH2NH2, -C(O)CH3, -C(O)NH 2、-C(O)OCH2CH3, -S(O)2-(CH3), -S(O)(NH)(CH3), -CH2C(O)NH2, -CH2C(O)NH(CH3), -NHC(O)(CH3), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is H. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)2. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -N(CH3)2. In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)(OH). In other embodiments, R 3a is -C(CH3)2(OH). In other embodiments, R 3a In other embodiments, R 3a is -C(O)CH3. In other embodiments, R 3a is -C(O)NH2. In other embodiments, R 3a In other embodiments, R 3a is -S(O)2-(CH3). In other embodiments, R 3a is -S(O)(NH)(CH3). In other embodiments, R 3a is -CH2C(O)NH2. In other embodiments, R 3a is -CH2C(O)NH(CH3). In other embodiments, R 3a is -NHC(O)(CH3). In other embodiments, R 3a is -CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is -CH2N(CH3)C(O)CH(CH3)(N(CH3)2). In other embodiments, R 3a is -CH2CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3ais -NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is Br. In other embodiments, R 3a is -S(O)2CH(CH3)2. In other embodiments, R 3a is -S(O)(NH)CH(CH3)2. In other embodiments, R 3a is -C(O)NHC(O)CH3. In other embodiments, R 3a is -NHS(O)2CH3. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for

[0193] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(NCH3)R' or -S(O)2NCH3R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a is -S(O)R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a is -S(O)2R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a is -S(O)(NH)R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a is -S(O)(NCH3)R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a is -S(O)2NCH3R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group.

[0194] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 5a is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -C(O)O(C1-C6 alkyl), 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'Replace; and R a ' is -CH3, -CHF2 or -CH2OCH3. In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 5ais H, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl) or -C(O)O(C1-C6 alkyl). In other embodiments, R 5a is a C1-C6 alkyl group. In other embodiments, R 5a is C1-C6 alkoxy. In other embodiments, R 5a is -CH2O(C1-C6 alkyl). In other embodiments, R 5a is -C(O)O(C1-C6 alkyl). In other embodiments, R 5a In other embodiments, R 5a is a 4-10 membered heteroaryl group, wherein the heteroaryl group is optionally replaced by R a 'Replace; and R a ' is -CH3, -CHF2 or -CH2OCH3. In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 5a It is H, Br, -CH3, -OCH3, -OCH2CH3, -CH2OH, -CH2OCH3, -C(O)OCH2CH3, In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 5a In other embodiments, R 5a is H. In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a is Br. In other embodiments, R 5a for In other embodiments, R 5a for In other embodiments, R 5a for In other embodiments, R 5a for

[0195] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH or -CH2OH. In other embodiments, R 2b In other embodiments, R 2b is a C1-C6 alkyl group. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 2b is H, F, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -OCH3, -OCH2CH3, -OH or -CH2OH. In other embodiments, R 2b is H. In other embodiments, R 2b is F. In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2b is -CH(CH3)2. In other embodiments, R 2b is -C(CH3)3. In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2b It is -CH2OH.

[0196] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy. 3b In other embodiments, R 3b is a C1-C6 alkyl group. In other embodiments, R 3b is a C1-C6 haloalkyl group. In other embodiments, R 3b In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 3b is H, F, Cl, -CH3, -C(CH3)3, -CF3, -OCH3, -OCH2CH3 or -OC(CH3)3. In other embodiments, R 3b is H. In other embodiments, R 3b is F. In other embodiments, R 3b In other embodiments, R 3b In other embodiments, R 3bis -C(CH3)3. In other embodiments, R 3b In other embodiments, R 3b In other embodiments, R 3b In other embodiments, R 3b It is -OC(CH3)3.

[0197] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 4b R is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In other embodiments, R 4b In other embodiments, R 4b is a C1-C6 alkyl group. In other embodiments, R 4b is a C1-C6 haloalkyl group. In other embodiments, R 4b is C1-C6 alkoxy. In other embodiments, R 4b is C1-C6 haloalkoxy. In other embodiments, R 4b is a C3-C6 cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more halogens. 4b is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 alkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In other embodiments, R 4b is (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 4b is H, F, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CF3), -OCH3, -OC(CH3)3, -OC(CH3)3, -OCF3, cyclopropyl, 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl or 3,3-difluoro-1-methylcyclobutyl. In other embodiments, R 4bis H. In other embodiments, R 4b is F. In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b is -CH(CH3)2. In other embodiments, R 4b is -C(CH3)3. In other embodiments, R 4b is -C(CH3)2(CH2CH3). In other embodiments, R 4b In other embodiments, R 4b is -C(CH3)2(CF3). In other embodiments, R 4b In other embodiments, R 4b is -OC(CH3)3. In other embodiments, R 4b is -OC(CH3)3. In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b It is 3,3-difluoro-1-methylcyclobutyl.

[0198] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 2b and R 3b Together with the carbon atom to which they are attached, they form a In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 2b and R 3b Together with the carbon atom to which they are attached, they form a The ring, and R 4b is H. In other embodiments, R 2b and R 3b Together with the carbon atom to which they are attached, they form a In other embodiments, R 2b and R 3b Together with the carbon atom to which they are attached, they form a Ring.

[0199] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 3b and R4b Together with the carbon atom to which they are attached, they form a In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 3b and R 4b Together with the carbon atom to which they are attached, they form a The ring, and R 2b is H. In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a Ring.

[0200] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R n In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R n is -CH3.

[0201] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 6b is H, halo, C1-C6 alkyl or C1-C6 alkoxy. 6b In other embodiments, R 6b is a C1-C6 alkyl group. In other embodiments, R 6b In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein R 6b is H, Cl, -CH3 or -OCH3. In other embodiments, R 6b is H. In other embodiments, R 6b In other embodiments, R 6b In other embodiments, R 6b It is -OCH3.

[0202] In some embodiments, the present invention relates to a compound of formula (IA-1) or a pharmaceutically acceptable salt thereof, wherein:

[0203] X is CR 5b , and R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or -C(O)(C1-C6 alkyl);

[0204] R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH or -CH2OH; and

[0205] R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

[0206] In some embodiments, the present invention relates to a compound of formula (IA-2):

[0207]

[0208] or a pharmaceutically acceptable salt thereof, wherein:

[0209] X is CR 5b or N;

[0210] R 2a is H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2;

[0211] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2;

[0212] R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl);

[0213] R 2b 、R 3b and R 4b The following definitions are given:

[0214] (i)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens;

[0215] R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0216] R4b is C2-C6 alkyl, C2-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or

[0217] (ii)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0218] R 3b and R 4b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0219]

[0220] R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0221] R 6bis H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens,

[0222] The conditions are:

[0223] (i) If X is N, then R 3b and R 4b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0224] and

[0225] (ii) If R 2a is H, then R 3a Halogenated, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and

[0226] (iii)R 2b 、R 3b 、R 5b and R 6b Not more than one of them is chlorine.

[0227] In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein X is N. In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b , and R 5b is H, halo, C1-C6 alkyl or C1-C6 haloalkyl. In other embodiments, R 5b In other embodiments, R 5b is a C1-C6 alkyl group. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b , and R 5b is H, F, Cl, -CH3 or -CF3. In other embodiments, R 5b is H. In other embodiments, R 5b is F. In other embodiments, R 5b In other embodiments, R 5b In other embodiments, R 5b It is -CF3.

[0228] In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 2a is H, C1-C6 alkyl, C1-C6 alkoxy or -N(C1-C6 alkyl)2. In other embodiments, R 2a is a C1-C6 alkyl group. In other embodiments, R 2a is C1-C6 alkoxy. In other embodiments, R 2a In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 2a is H, -CH3, -OCH3 or -N(CH3)2. In other embodiments, R 2a is H. In other embodiments, R 2a In other embodiments, R 2a In other embodiments, R 2a It is -N(CH3)2.

[0229] In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 3ais H, halo, -CN, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2. In other embodiments, R 3a In other embodiments, R 3a is a C1-C6 alkyl group. In other embodiments, R 3a is C1-C6 alkoxy. In other embodiments, R 3a is -N(C1-C6 alkyl)2. In other embodiments, R 3a is -(C1-C6 alkylene)-OH. In other embodiments, R 3a is -(C1-C6 alkylene)-NH2. In other embodiments, R 3a is -C(O)(C1-C6 alkyl). In other embodiments, R 3a is -C(O)O(C1-C6 alkyl). In other embodiments, R 3a is -S(O)2-(C1-C6 alkyl). In other embodiments, R 3a is -S(O)(NH)(C1-C6 alkyl). In other embodiments, R 3a is -CH2C(O)NH(C1-C6 alkyl). In other embodiments, R 3a In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 3aR is H, Cl, -CN, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH), -C(CH3)2(OH), -CH2NH2, -C(O)CH3, -C(O)NH2, -C(O)OCH2CH3, -S(O)2-CH3, -S(O)(NH)(CH3), -CH2C(O)NH2, -CH2C(O)NH(CH3), -NHC(O)(CH3), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2. In other embodiments, R 3a is H. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)2. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -N(CH3)2. In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)(OH). In other embodiments, R 3a is -C(CH3)2(OH). In other embodiments, R 3a In other embodiments, R 3a is -C(O)CH3. In other embodiments, R 3a is -C(O)NH2. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -S(O)(NH)(CH3). In other embodiments, R 3a is -CH2C(O)NH2. In other embodiments, R 3a is -CH2C(O)NH(CH3). In other embodiments, R 3a is -NHC(O)(CH3). In other embodiments, R 3a is -CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3ais -CH2N(CH3)C(O)CH(CH3)(N(CH3)2). In other embodiments, R 3a is -CH2CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a It is -NHC(O)CH(CH3)(NH2).

[0230] In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 5a is H, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl) or -C(O)O(C1-C6 alkyl). In other embodiments, R 5a is a C1-C6 alkyl group. In other embodiments, R 5a is C1-C6 alkoxy. In other embodiments, R 5a is -CH2O(C1-C6 alkyl). In other embodiments, R 5a In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 5a In other embodiments, R 5a is H. In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a It is -C(O)OCH2CH3.

[0231] In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl or C1-C6 alkoxy. 2b In other embodiments, R 2b is a C1-C6 alkyl group. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 2b is H, F, -CH3, -CH(CH3)2 or -OCH3. In other embodiments, R2b is H. In other embodiments, R 2b is F. In other embodiments, R 2b In other embodiments, R 2b is -CH(CH3)2. In other embodiments, R 2b It is -OCH3.

[0232] In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 3b is H or C1-C6 alkyl. In other embodiments, R 3b In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 3b is H or -CH3. In other embodiments, R 3b is H. In other embodiments, R 3b is -CH3.

[0233] In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 4b is C2-C6 alkyl, C2-C6 haloalkyl, C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In other embodiments, R 4b is a C2-C6 alkyl group. In other embodiments, R 4b is a C2-C6 haloalkyl group. In other embodiments, R 4b is a C4-C6 cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more halogens. 4b is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 alkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In other embodiments, R 4b is (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 4bis -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -C(CH3)2(CF3), 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl or 3,3-difluoro-1-methylcyclobutyl. In other embodiments, R 4b is -CH(CH3)2. In other embodiments, R 4b is -C(CH3)3. In other embodiments, R 4b is -C(CH3)2(CH2CH3). In other embodiments, R 4b is -C(CH3)2(CF3). In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b It is 3,3-difluoro-1-methylcyclobutyl.

[0234] In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 3b and R 4b Together with the carbon atom to which they are attached, they form a In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 3b and R 4b Together with the carbon atom to which they are attached, they form a The ring, and R 2b For H.

[0235] In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 6b is H, C1-C6 alkyl or C1-C6 alkoxy. In other embodiments, R 6b is a C1-C6 alkyl group. In other embodiments, R 6b In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein R 6b is H, -CH3 or -OCH3. In other embodiments, R 6b is H. In other embodiments, R 6b In other embodiments, R 6b It is -OCH3.

[0236] In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein:

[0237] X is CR5b , and R 5b is H, halo, C1-C6 alkyl or C1-C6 haloalkyl;

[0238] R 2b is H, halo, C1-C6 alkyl or C1-C6 alkoxy; and

[0239] R 4b It is C2-C6 alkyl, C2-C6 haloalkyl, C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

[0240] In some embodiments, the present invention relates to a compound of formula (IA-2) or a pharmaceutically acceptable salt thereof, wherein:

[0241] R 5b is H, F, Cl, -CH3 or -CF3;

[0242] R 2b is H, F, -CH3, -CH(CH3)2 or -OCH3;

[0243] R 4b It is -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -C(CH3)2(CF3), 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl or 3,3-difluoro-1-methylcyclobutyl.

[0244] In some embodiments, the present invention relates to a compound of formula (IB-1):

[0245]

[0246] or a pharmaceutically acceptable salt thereof, wherein:

[0247] X is CR 5b or N;

[0248] R 3aH, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2)、-CH2CH2NHC(O)CH(CH3)(NH2)、-NHC(O)CH(CH3)(NH2)、-C(O)NHC(O)(C1-C6 alkyl)、-NHS(O)2CH3、-S(C1-C6 alkyl)、C3-C7 cycloalkyl、C6-C 10 Aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'replace;

[0249] R 5a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -C(O)O(C1-C6 haloalkyl) or 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'replace;

[0250] Each R a ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl);

[0251] R 2b 、R 3b and R 4b The following definitions are given:

[0252] (i)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens;

[0253] R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0254] R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; or

[0255] (ii)R 2b and R 3b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0256] and

[0257] R 4bis H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; or

[0258] (iii)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0259] R 3b and R 4b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0260]

[0261] R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0262] R 6bis H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens;

[0263] R n is H or C1-C6 alkyl,

[0264] The conditions are:

[0265] (i) If X is N, then R 3b and R 4b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0266] and

[0267] (ii) If R 3a is -C(O)O(C1-C2 alkyl), then R 4b is H, fluorine, chlorine, C1-C6 alkyl, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0268] (iii)R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than four of them are H; and

[0269] (iv)R 2b 、R 3b 、R 4b 、R 5b and R 6b not more than one of them is fluorine; and

[0270] (v)R 2b 、R 3b 、R 4b、R 5b and R 6b not more than one of which is chlorine; and

[0271] (vi) If R 2b 、R 3b 、R 4b 、R 5b and R 6b If any one of R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0272] (vii) If R 2b or R 6b is -OCH3, and R 3a is H, then R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0273] (viii) If R 3b is fluorine, then R 6b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0274] (ix) If R 5b is fluorine, then R 2b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0275] (x) If R 3b or R 5bis -CH3, then R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0276] (xi) If R 3b or R 5b is a C1 haloalkyl group, then R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0277] (xii) If R3 b or R 5b is -OCH3, then R 2b 、R 3b 、R 4b 、R 5b and R 6b No more than three of them are H; and

[0278] (xiii) If R 4b is a C1 haloalkyl group, then R 2b 、R 3b 、R 5b and R 6b No more than three of them are H; and

[0279] (xiv) If R 4b is -OCH3, then R 2b 、R 3b 、R 5b and R 6b No more than three of them are H; and

[0280] (xv) If R 4b is a C1 haloalkoxy group, then R 2b 、R 3b 、R 5b and R 6b No more than three of them are H; and

[0281] (xvi) If R 4b is chlorine or bromine, then R 2b and R 6beach independently represents H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0282] (xvii) If R 4b and R 3b Each is -OCH3, then R 2b 、R 5b and R 6b No more than two of them are H; and

[0283] (xviii) If R 4b and R 5b Each is -OCH3, then R 2b 、R 3b and R 6b No more than two of them are H.

[0284] In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein:

[0285] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、-C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and

[0286] R 5a It is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl).

[0287] In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein X is N. In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b , and R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or -C(O)(C1-C6 alkyl). 5b In other embodiments, R 5b is a C1-C6 alkyl group. In other embodiments, R 5b is a C1-C6 haloalkyl group. 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-1) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b , and R 5b is H, F, Cl, -CH3, -C(CH3)3, -CF3, -OCH3 or -C(O)CH3. In other embodiments, R 5b is H. In other embodiments, R 5b is F. In other embodiments, R5b In other embodiments, R 5b In other embodiments, R 5b is -C(CH3)3. In other embodiments, R 5b In other embodiments, R 5b In other embodiments, R 5b It is -C(O)CH3.

[0288] In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 3a For H, halo, -CN, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl) alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2), -C(O)NHC(O)CH3, -NHS(O)2CH3, -S(C1-C6 alkyl), C3-C7 cycloalkyl, C6-C 10 Aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; and each R a ' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 3aR is H, halo, -CN, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2. In other embodiments, R 3a In other embodiments, R 3a is a C1-C6 alkyl group. In other embodiments, R 3a is C1-C6 alkoxy. In other embodiments, R 3a is -N(C1-C6 alkyl)2. In other embodiments, R 3a is -(C1-C6 alkylene)-OH. In other embodiments, R 3a is -(C1-C6 alkylene)-NH2. In other embodiments, R 3a is -C(O)(C1-C6 alkyl). In other embodiments, R 3a is -C(O)O(C1-C6 alkyl). In other embodiments, R 3a is -S(O)2-(C1-C6 alkyl). In other embodiments, R 3a is -S(O)(NH)(C1-C6 alkyl). In other embodiments, R 3a is -CH2C(O)NH(C1-C6 alkyl). In other embodiments, R 3a is -NHC(O)(C1-C6 alkyl). In other embodiments, R 3a is -C(O)NHC(O)CH3. In other embodiments, R 3a is -NHS(O)2CH3. In other embodiments, R 3a is -S(C1-C6 alkyl). In other embodiments, R 3a is a C3-C7 cycloalkyl group. In other embodiments, R 3a C6-C 10 In other embodiments, R 3a is a 4-10 membered heterocyclic group, wherein the heterocyclic group is optionally substituted by 1-2 R a 'Replace; and each R a' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In other embodiments, R 3a is a 4-10 membered heteroaryl group, wherein the heteroaryl group is optionally substituted by 1-2 R a 'Replace; and each R a ' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 3a is H, Cl, Br, -CN, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH), -C(CH3)2(OH), -CH2 NH2, -C(O)CH3, -C(O)OCH2CH3, -S(O)2-(CH3), -S(O)2CH(CH3)2, -S(O)(NH)(CH3), -S(O)(NH)CH(CH3) 2. -CH2C(O)NH2, -CH2C(O)NH(CH3), -NHC(O)CH3, -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3) (N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2) -C(O)NHC(O)CH3, -NHS(O)2CH3, -SCH 3、 Cyclopropyl, phenyl, In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 3aR is H, Cl, -CN, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH), -C(CH3)2(OH), -CH2NH2, -C(O)CH3, -C(O)OCH2CH3, -S(O)2-(CH3), -S(O)(NH)(CH3), -CH2C(O)NH2, -CH2C(O)NH(CH3), -NHC(O)CH3, -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2. In other embodiments, R 3a is H. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)2. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -N(CH3)2. In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)(OH). In other embodiments, R 3a is -C(CH3)2(OH). In other embodiments, R 3a In other embodiments, R 3a is -C(O)CH3. In other embodiments, R 3a In other embodiments, R 3a is -S(O)2-(CH3). In other embodiments, R 3a is -S(O)(NH)(CH3). In other embodiments, R 3a is -CH2C(O)NH2. In other embodiments, R 3a is -CH2C(O)NH(CH3). In other embodiments, R 3a is -NHC(O)CH3. In other embodiments, R 3a is -CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is -CH2N(CH3)C(O)CH(CH3)(N(CH3)2). In other embodiments, R3a is -CH2CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is -NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is Br. In other embodiments, R 3a is -S(O)2CH(CH3)2. In other embodiments, R 3a is -S(O)(NH)CH(CH3)2. In other embodiments, R 3a is -C(O)NHC(O)CH3. In other embodiments, R 3a is -NHS(O)2CH3. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for

[0289] In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 5a is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl) or -C(O)O(C1-C6 alkyl), 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'Replace; and R a ' is -CH3, -CHF2 or -CH2OCH3. In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 5a is H, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl) or -C(O)O(C1-C6 alkyl). In other embodiments, R 5a is a C1-C6 alkyl group. In other embodiments, R 5a is C1-C6 alkoxy. In other embodiments, R 5a is -CH2O(C1-C6 alkyl). In other embodiments, R 5a is -C(O)O(C1-C6 alkyl). In other embodiments, R 5a In other embodiments, R 5a is a 4-10 membered heteroaryl group, wherein the heteroaryl group is optionally replaced by R a 'Replace; and R a ' is -CH3, -CHF2 or -CH2OCH3. In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 5a It is H, Br, -CH3, -OCH3, -OCH2CH3, -CH2OH, -CH2OCH3, -C(O)OCH2CH3, In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 5aIn other embodiments, R 5a is H. In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a is Br. In other embodiments, R 5a for In other embodiments, R 5a for In other embodiments, R 5a for In other embodiments, R 5a for

[0290] In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH or -CH2OH. In other embodiments, R 2b In other embodiments, R 2b is a C1-C6 alkyl group. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 2b is H, F, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -OCH3, -OCH2CH3, -OH or -CH2OH. In other embodiments, R 2b is H. In other embodiments, R 2b is F. In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2b is -CH(CH3)2. In other embodiments, R 2b is -C(CH3)3. In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2bIn other embodiments, R 2b It is -CH2OH.

[0291] In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy. 3b In other embodiments, R 3b is a C1-C6 alkyl group. In other embodiments, R 3b is a C1-C6 haloalkyl group. In other embodiments, R 3b In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 3b is H, F, Cl, -CH3, -C(CH3)3, -CF3, -OCH3, -OCH2CH3 or -OC(CH3)3. In other embodiments, R 3b is H. In other embodiments, R 3b is F. In other embodiments, R 3b In other embodiments, R 3b In other embodiments, R 3b is -C(CH3)3. In other embodiments, R 3b In other embodiments, R 3b In other embodiments, R 3b In other embodiments, R 3b It is -OC(CH3)3.

[0292] In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 4b R is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, 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 halogens. In other embodiments, R 4b In other embodiments, R 4b is a C1-C6 alkyl group. In other embodiments, R 4b is a C1-C6 haloalkyl group. In other embodiments, R4b is C1-C6 alkoxy. In other embodiments, R 4b is C1-C6 haloalkoxy. In other embodiments, R 4b is a C3-C6 cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more halogens. 4b is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 alkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In other embodiments, R 4b is (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 4b is H, F, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CF3)-OCH3, -OCH(CH3)2, -OC(CH3)3, -OCF3, cyclopropyl, 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl or 3,3-difluoro-1-methylcyclobutyl. In other embodiments, R 4b is H. In other embodiments, R 4b is F. In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b is -CH(CH3)2. In other embodiments, R 4b is -C(CH3)3. In other embodiments, R 4b is -C(CH3)2(CH2CH3). In other embodiments, R 4b In other embodiments, R 4b is -C(CH3)2(CF3). In other embodiments, R 4b In other embodiments, R 4b is -OCH(CH3)2. In other embodiments, R 4b is -OC(CH3)3. In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4bIt is 3,3-difluoro-1-methylcyclobutyl.

[0293] In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 2b and R 3b Together with the carbon atom to which they are attached, they form a In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 2b and R 3b Together with the carbon atom to which they are attached, they form a The ring, and R 4b is H. In other embodiments, R 2b and R 3b Together with the carbon atom to which they are attached, they form a In other embodiments, R 2b and R 3b Together with the carbon atom to which they are attached, they form a Ring.

[0294] In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 3b and R 4b Together with the carbon atom to which they are attached, they form a In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 3b and R 4b Together with the carbon atom to which they are attached, they form a The ring, and R 2b is H. In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a In other embodiments, R 3b and R 4b Together with the carbon atom to which they are attached, they form a Ring.

[0295] In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R n In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R n is -CH3.

[0296] In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 6b is H, halo, C1-C6 alkyl or C1-C6 alkoxy. 6b In other embodiments, R 6b is a C1-C6 alkyl group. In other embodiments, R 6b In some embodiments, the present invention relates to a compound of formula (IB-1) or a pharmaceutically acceptable salt thereof, wherein R 6b is H, Cl, -CH3 or -OCH3. In other embodiments, R 6b is H. In other embodiments, R 6b In other embodiments, R 6b In other embodiments, R 6b It is -OCH3.

[0297] In some embodiments, the present invention relates to a compound of formula (IB-2):

[0298]

[0299] or a pharmaceutically acceptable salt thereof, wherein:

[0300] X is CR 5b or N;

[0301] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、-C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2;

[0302] R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl);

[0303] R 2b 、R 3b and R 4b The following definitions are given:

[0304] (i)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens;

[0305] R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0306] R 4bis C2-C6 alkyl, C2-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or

[0307] (ii)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0308] R 3b and R 4b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0309]

[0310] R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0311] R 6bis H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens,

[0312] The conditions are:

[0313] (i) If X is N, then R 3b and R 4b Together with the carbon atoms to which they are attached, they form a ring having the formula:

[0314] and

[0315] (ii)R 2b 、R 3b 、R 5b and R 6b Not more than one of them is chlorine.

[0316] In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein X is N. In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein X is CR 5b , and R 5b is H, halo, C1-C6 alkyl or C1-C6 haloalkyl. In other embodiments, R 5b In other embodiments, R 5b is a C1-C6 alkyl group. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 5b is H, F, Cl, -CH3 or -CF3. In other embodiments, R 5b is H. In other embodiments, R 5b is F. In other embodiments, R 5b In other embodiments, R 5b In other embodiments, R 5b It is -CF3.

[0317] In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 3a R is H, halo, -CN, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2. In other embodiments, R 3a In other embodiments, R 3a is a C1-C6 alkyl group. In other embodiments, R 3a is C1-C6 alkoxy. In other embodiments, R 3a is -N(C1-C6 alkyl)2. In other embodiments, R 3a is -(C1-C6 alkylene)-OH. In other embodiments, R 3a is -(C1-C6 alkylene)-NH2. In other embodiments, R 3a is -C(O)(C1-C6 alkyl). In other embodiments, R 3a is -C(O)O(C1-C6 alkyl). In other embodiments, R 3a is -S(O)2-(C1-C6 alkyl). In other embodiments, R 3a is -S(O)(NH)(C1-C6 alkyl). In other embodiments, R 3a is -CH2C(O)NH(C1-C6 alkyl). In other embodiments, R 3a In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 3aR is H, Cl, -CN, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH), -C(CH3)2(OH), -CH2NH2, -C(O)CH3, -C(O)OCH2CH3, -S(O)2-(CH3), -S(O)(NH)(CH3), -CH2C(O)NH2, -CH2C(O)NH(CH3), -NHC(O)CH3, -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2. In other embodiments, R 3a is H. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)2. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -N(CH3)2. In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)(OH). In other embodiments, R 3a is -C(CH3)2(OH). In other embodiments, R 3a In other embodiments, R 3a is -C(O)CH3. In other embodiments, R 3a In other embodiments, R 3a is -S(O)2-(CH3). In other embodiments, R 3a is -S(O)(NH)(CH3). In other embodiments, R 3a is -CH2C(O)NH2. In other embodiments, R 3a is -CH2C(O)NH(CH3). In other embodiments, R 3a is -NHC(O)CH3. In other embodiments, R 3a is -CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is -CH2N(CH3)C(O)CH(CH3)(N(CH3)2). In other embodiments, R3a is -CH2CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a It is -NHC(O)CH(CH3)(NH2).

[0318] In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 5a is H, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl) or -C(O)O(C1-C6 alkyl). In other embodiments, R 5a is a C1-C6 alkyl group. In other embodiments, R 5a is C1-C6 alkoxy. In other embodiments, R 5a is -CH2O(C1-C6 alkyl). In other embodiments, R 5a In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 5a In other embodiments, R 5a is H. In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a It is -C(O)OCH2CH3.

[0319] In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 2b is H, halo, C1-C6 alkyl or C1-C6 alkoxy. 2b In other embodiments, R 2b is a C1-C6 alkyl group. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 2b is H, F, -CH3, -CH(CH3)2 or -OCH3. In other embodiments, R 2b is H. In other embodiments, R 2bis F. In other embodiments, R 2b In other embodiments, R 2b is -CH(CH3)2. In other embodiments, R 2b It is -OCH3.

[0320] In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 3b is H or C1-C6 alkyl. In other embodiments, R 3b In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 3b is H or -CH3. In other embodiments, R 3b is H. In other embodiments, R 3b is -CH3.

[0321] In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 4b is C2-C6 alkyl, C2-C6 haloalkyl, C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In other embodiments, R 4b is a C2-C6 alkyl group. In other embodiments, R 4b is a C2-C6 haloalkyl group. In other embodiments, R 4b is a C4-C6 cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more halogens. 4b is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 alkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In other embodiments, R 4b is (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 4bis -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -C(CH3)2(CF3), 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl, 3,3-difluoro-1-methylcyclobutyl. In other embodiments, R 4b is -CH(CH3)2. In other embodiments, R 4b is -C(CH3)3. In other embodiments, R 4b is -C(CH3)2(CH2CH3). In other embodiments, R 4b is -C(CH3)2(CF3). In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b It is 3,3-difluoro-1-methylcyclobutyl.

[0322] In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 3b and R 4b Together with the carbon atom to which they are attached, they form a In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 3b and R 4b Together with the carbon atom to which they are attached, they form a The ring, and R 2b For H.

[0323] In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 6b is H, C1-C6 alkyl or C1-C6 alkoxy. In other embodiments, R 6b is a C1-C6 alkyl group. In other embodiments, R 6b In some embodiments, the present invention relates to a compound of formula (IB-2) or a pharmaceutically acceptable salt thereof, wherein R 6b is H, -CH3 or -OCH3. In other embodiments, R 6b is H. In other embodiments, R 6b In other embodiments, R 6b It is -OCH3.

[0324] In some embodiments, the present invention relates to a compound of formula (IC-1):

[0325]

[0326] or a pharmaceutically acceptable salt thereof, wherein:

[0327] R 2a and R 3a The following definitions are given:

[0328] (i)R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl)2, or -N(C1-C6 haloalkyl)2; and

[0329] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2)、-CH2CH2NHC(O)CH(CH3)(NH2)、-NHC(O)CH(CH3)(NH2)、-C(O)NHC(O)(C1-C6 alkyl)、-NHS(O)2CH3、-S(C1-C6 alkyl)、C3-C7 cycloalkyl、C6-C 10 Aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; or

[0330] (ii)R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(N(C1-C6 alkyl))R' or -S(O)2NCH3R'; and

[0331] R 2a and R' together with the atoms to which they are attached join together to form a 4-7 membered heterocyclic group;

[0332] R 5a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -C(O)O(C1-C6 haloalkyl) or 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'replace;

[0333] Each R a ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl);

[0334] R 2b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens;

[0335] R 4b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0336] R 5bis halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens,

[0337] The conditions are:

[0338] (i) If R 2a is H, then R 3a Halogenated, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and

[0339] (ii)R 2b 、R 4b and R 5b Not more than one of them is chlorine.

[0340] In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein:

[0341] R 2ais H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2;

[0342] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and

[0343] R 5a It is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl).

[0344] In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 5bIt is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0345] In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 2a is H or C1-C6 alkyl. In other embodiments, R 2a In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 2a is H or -CH3. In other embodiments, R 2a is H. In other embodiments, R 2a is -CH3.

[0346] In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 3a H, halo, -CN, C1-C6 alkyl, -C(O)NH 2、 -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(CH3), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -C(O)NHC(O)CH3, -NHS(O)2CH3, -S(C1-C6 alkyl), C3-C7 cycloalkyl, C6-C 10 Aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; and each R a ' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 3aH, halo, -CN, C1-C6 alkyl, -C(O)NH 2、 -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(CH3) or -CH2N(CH3)C(O)CH(CH3)(N(CH3)2). In other embodiments, R 3a In other embodiments, R 3a is a C1-C6 alkyl group. In other embodiments, R 3a is -C(O)O(C1-C6 alkyl). In other embodiments, R 3a is -S(O)2-(C1-C6 alkyl). In other embodiments, R 3a is -S(O)(NH)(C1-C6 alkyl). In other embodiments, R 3a is -C(O)NHC(O)CH3. In other embodiments, R 3a is -NHS(O)2CH3. In other embodiments, R 3a is -S(C1-C6 alkyl). In other embodiments, R 3a is a C3-C7 cycloalkyl group. In other embodiments, R 3a C6-C 10 In other embodiments, R 3a is a 4-10 membered heterocyclic group, wherein the heterocyclic group is optionally substituted by 1-2 R a 'Replace; and each R a ' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In other embodiments, R 3a is a 4-10 membered heteroaryl group, wherein the heteroaryl group is optionally substituted by 1-2 R a 'Replace; and each R a ' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl. In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 3a H, Cl, Br, -CN, -CH3, -C(O)NH2、 -C(O)OCH2CH3, -S(O)2-(CH3), -S(O)2CH(CH3)2, -S(O)(NH)(CH3), -S(O)(NH)CH(CH3)2, -CH2C(O) NH2, -CH2C(O)NH(CH3), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -C(O)NHC(O)CH3, -NHS(O)2CH3, -SCH 3、 Cyclopropyl, phenyl, In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 3a H, Cl, -CN, -CH3, -C(O)NH 2、 -C(O)OCH2CH3, -S(O)2-(CH3), -S(O)(NH)(CH3), -CH2C(O)NH2, -CH2C(O)NH(CH3), or -CH2N(CH3)C(O)CH(CH3)(N(CH3)2). In other embodiments, R 3a is H. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -C(O)NH2. In other embodiments, R 3a In other embodiments, R 3a is -S(O)2-(CH3). In other embodiments, R 3a is -S(O)(NH)(CH3). In other embodiments, R 3a is -CH2C(O)NH2. In other embodiments, R 3a is -CH2C(O)NH(CH3). In other embodiments, R 3a is -CH2N(CH3)C(O)CH(CH3)(N(CH3)2). In other embodiments, R 3a is Br. In other embodiments, R 3a is -S(O)2CH(CH3)2. In other embodiments, R 3a is -S(O)(NH)CH(CH3)2. In other embodiments, R 3a is -C(O)NHC(O)CH3. In other embodiments, R 3a is -NHS(O)2CH3. In other embodiments, R3a In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for

[0347] In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(NCH3)R' or -S(O)2NCH3R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a is -S(O)R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R3a is -S(O)2R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a is -S(O)(NH)R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group. In other embodiments, R 3a is -S(O)(NCH3)R'. In other embodiments, R 3a is -S(O)2NCH3R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group.

[0348] In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 5a is H, halo, C1-C6 alkyl, -C(O)O(C1-C6 alkyl), or 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'Replace; and R a ' is -CH3, -CHF2 or -CH2OCH3. In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 5a is H or -C(O)O(C1-C6 alkyl). In other embodiments, R 5a is -C(O)O(C1-C6 alkyl). In other embodiments, R 5a In other embodiments, R 5a is a C1-C6 alkyl group. In other embodiments, R 5a is a 4-10 membered heteroaryl group, wherein the heteroaryl group is optionally replaced by R a 'Replace; and R a ' is -CH3, -CHF2 or -CH2OCH3. In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein H, Br, -CH3, -C(O)OCH2CH3, In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 5a is H or -C(O)OCH2CH3. In other embodiments, R 5a is H. In other embodiments, R 5a In other embodiments, R 5a is Br. In other embodiments, R 5a In other embodiments, R 5a for In other embodiments, R 5a for In other embodiments, R 5a for In other embodiments, R 5a for

[0349] In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 2b is halo, C1-C6 alkyl or C1-C6 alkoxy. 2b In other embodiments, R 2b is a C1-C6 alkyl group. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 2b is F, Cl, -CH3 or -OCH3. In other embodiments, R 2b is F. In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2b It is -OCH3.

[0350] In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 4b is C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy. 4b is a C1-C6 alkyl group. In other embodiments, R 4b is a C1-C6 haloalkyl group. In other embodiments, R 4b In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 4b is -CH3, -C(CH3)3, -C(CH3)2(CF3) or -OCH3. In other embodiments, R 4b In other embodiments, R 4b is -C(CH3)3. In other embodiments, R 4b is -C(CH3)2(CF3). In other embodiments, R 4b It is -OCH3.

[0351] In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 5bis halo, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy. 5b In other embodiments, R 5b is a C1-C6 alkyl group. In other embodiments, R 5b is a C1-C6 haloalkyl group. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein R 5b is F, Cl, -CH3, -CF3 or -OCH3. In other embodiments, R 5b is F. In other embodiments, R 5b In other embodiments, R 5b In other embodiments, R 5b In other embodiments, R 5b It is -OCH3.

[0352] In some embodiments, the present invention relates to a compound of formula (IC-1) or a pharmaceutically acceptable salt thereof, wherein:

[0353] R 2b is halogenated, C1-C6 alkyl or C1-C6 alkoxy;

[0354] R 4b is C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy; and

[0355] R 5b is halo, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy.

[0356] In some embodiments, the present invention relates to a compound of formula (IC-2):

[0357]

[0358] or a pharmaceutically acceptable salt thereof, wherein:

[0359] R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2;

[0360] R 3aH, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2;

[0361] R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl);

[0362] R 2b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens;

[0363] R 4bis halo, C2-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0364] R 5b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens,

[0365] The conditions are:

[0366] (i) If R 2a is H, then R 3a Halogenated, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、-C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and

[0367] (ii)R 2b 、R 4b and R 5b Not more than one of them is chlorine.

[0368] In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 2b It is halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0369] In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 5b It is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0370] In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 2a is H or C1-C6 alkyl. In other embodiments, R2a In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 2a is H or -CH3. In other embodiments, R 2a is H. In other embodiments, R 2a is -CH3.

[0371] In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 3a H, halo, -CN, C1-C6 alkyl, -C(O)NH 2、 -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), or -CH2N(CH3)C(O)CH(CH3)(N(CH3)2). In other embodiments, R 3a In other embodiments, R 3a is a C1-C6 alkyl group. In other embodiments, R 3a is -C(O)O(C1-C6 alkyl). In other embodiments, R 3a is -S(O)2-(C1-C6 alkyl). In other embodiments, R 3a is -S(O)(NH)(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 3a H, Cl, -CN, -CH3, -C(O)NH 2、 -C(O)OCH2CH3, -S(O)2-(CH3), -S(O)(NH)(CH3), -CH2C(O)NH2, -CH2C(O)NH(CH3), or -CH2N(CH3)C(O)CH(CH3)(N(CH3)2). In other embodiments, R 3a is H. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -C(O)NH2. In other embodiments, R 3a In other embodiments, R 3a is -S(O)2-(CH3). In other embodiments, R 3a is -S(O)(NH)(CH3). In other embodiments, R3a is -CH2C(O)NH2. In other embodiments, R 3a is -CH2C(O)NH(CH3). In other embodiments, R 3a is -CH2N(CH3)C(O)CH(CH3)(N(CH3)2).

[0372] In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 5a is H or -C(O)O(C1-C6 alkyl). In other embodiments, R 5a In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 5a is H or -C(O)OCH2CH3. In other embodiments, R 5a is H. In other embodiments, R 5a It is -C(O)OCH2CH3.

[0373] In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 2b In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 2b is -CH3.

[0374] In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 4b is C2-C6 alkyl or C1-C6 haloalkyl. 4b is a C2-C6 alkyl group. In other embodiments, R 4b In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 4b is -C(CH3)3 or -C(CH3)2(CF3). In other embodiments, R 4b is -C(CH3)3. In other embodiments, R 4b It is -C(CH3)2(CF3).

[0375] In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 5b is halo, C1-C6 alkyl or C1-C6 haloalkyl. 5b In other embodiments, R 5bis a C1-C6 alkyl group. In other embodiments, R 5b In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein R 5b is F, Cl, -CH3 or -CF3. In other embodiments, R 5b is F. In other embodiments, R 5b In other embodiments, R 5b In other embodiments, R 5b It is -CF3.

[0376] In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein:

[0377] R 2b is a C1-C6 alkyl group;

[0378] R 4b is a C2-C6 alkyl group or a C1-C6 haloalkyl group; and

[0379] R 5b is halogenated, C1-C6 alkyl or C1-C6 haloalkyl.

[0380] In some embodiments, the present invention relates to a compound of formula (IC-2) or a pharmaceutically acceptable salt thereof, wherein:

[0381] R 2b is -CH3;

[0382] R 4b is -C(CH3)3 or -C(CH3)2(CF3); and

[0383] R 5b It is F, Cl, -CH3 or -CF3.

[0384] In some embodiments, the present invention relates to a compound of formula (ID-1):

[0385]

[0386] or a pharmaceutically acceptable salt thereof, wherein:

[0387] R 2a and R 3a The following definitions are given:

[0388] (i)R 2ais C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl)2, or -N(C1-C6 haloalkyl)2; and

[0389] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2、-CH2CH2NHC(O)CH(CH3)(NH2) or -NHC(O)CH(CH3)(NH2)-C(O)NHC(O)(C1-C6 alkyl), -NHS(O)2CH3、-S(C1-C6 alkyl), C3-C7 cycloalkyl, C6-C 10 Aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; or

[0390] (ii)R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(N(C1-C6 alkyl))R' or -S(O)2NCH3R'; and

[0391] R 2a and R' together with the atoms to which they are attached join together to form a 4-7 membered heterocyclic group;

[0392] R 5ais H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl), or a 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'replace;

[0393] Each R a ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl);

[0394] R 2b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0395] R 4b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens,

[0396] The conditions are:

[0397] (i)R 2b and R 4b not more than one of which is chlorine; and

[0398] (ii) If R4b is chlorine or bromine, then R 2b It is halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0399] In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein:

[0400] R 2a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2;

[0401] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2,

[0402] -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2); and

[0403] R 5aIt is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl).

[0404] In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 2b It is halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0405] In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 2a is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or -N(C1-C6 alkyl)2. 2a is a C1-C6 alkyl group. In other embodiments, R 2a is a C1-C6 haloalkyl group. In other embodiments, R 2a is C1-C6 alkoxy. In other embodiments, R 2a In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 2a is -CH3, -CF3, -OCH3 or -N(CH3)2. In other embodiments, R 2a In other embodiments, R 2a In other embodiments, R 2a In other embodiments, R 2a It is -N(CH3)2.

[0406] In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 3ais H, halo, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2), -NHS(O)2CH3, 4-10 membered heterocyclyl or 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally replaced by R a 'Replace; and R a ' is -CN or -CH3. In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 3a R is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2CH2NHC(O)CH(CH3)(NH2) or -NHC(O)CH(CH3)(NH2. In other embodiments, R 3a In other embodiments, R 3a is a C1-C6 alkyl group. In other embodiments, R 3a is C1-C6 alkoxy. In other embodiments, R 3a is -N(C1-C6 alkyl)2. In other embodiments, R 3a is -(C1-C6 alkylene)-OH. In other embodiments, R 3a is -(C1-C6 alkylene)-NH2. In other embodiments, R 3a is -C(O)(C1-C6 alkyl). In other embodiments, R 3a is -C(O)O(C1-C6 alkyl). In other embodiments, R 3a is -S(O)2-(C1-C6 alkyl). In other embodiments, R 3a is -NHC(O)(C1-C6 alkyl). In other embodiments, R 3a is -NHS(O)2CH3. In other embodiments, R 3a is a 4-10 membered heterocyclic group, wherein the heterocyclic group is optionally replaced by Ra 'Replace; and R a ' is -CN or -CH3. In other embodiments, R 3a is a 4-10 membered heteroaryl group, wherein the heteroaryl group is optionally replaced by R a 'Replace; and R a ' is -CN or -CH3. In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 3a is H, Cl, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH), -C(CH3)2(OH), -CH2NH2, -C(O)CH3, -C(O)OCH2CH3, -S(O)2-(C H3), -S(O)2CH(CH3)2, -NHC(O)(CH3), -CH2NHC(O)CH(CH3)(NH2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2), -NHS(O)2CH3, In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 3a is H, Cl, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH), -C(CH3)2(OH), -CH2NH2, -C(O)CH3, -C(O)OCH2CH3, -S(O)2-(CH3), -NHC(O)(CH3), -CH2NHC(O)CH(CH3)(NH2), -CH2CH2NHC(O)CH(CH3)(NH2) or -NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is H. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)2. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -N(CH3)2. In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)(OH). In other embodiments, R 3a is -C(CH3)2(OH). In other embodiments, R3a In other embodiments, R 3a is -C(O)CH3. In other embodiments, R 3a In other embodiments, R 3a is -S(O)2-(CH3). In other embodiments, R 3a is -NHC(O)(CH3). In other embodiments, R 3a is -CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is -CH2CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is -NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is -S(O)2CH(CH3)2. In other embodiments, R 3a is -NHS(O)2CH3. In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for In other embodiments, R 3a for

[0407] In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 5a is H, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl) or -C(O)O(C1-C6 alkyl). In other embodiments, R 5a is a C1-C6 alkyl group. In other embodiments, R 5a is C1-C6 alkoxy. In other embodiments, R 5a is -CH2O(C1-C6 alkyl). In other embodiments, R 5a is -C(O)O(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 5a In other embodiments, R 5a is H. In other embodiments, R 5a In other embodiments, R5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a It is -C(O)OCH2CH3.

[0408] In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 2b is halo, C1-C6 alkyl, C1-C6 alkoxy or -OH. In other embodiments, R 2b In other embodiments, R 2b is a C1-C6 alkyl group. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 2b is F, -CH3, -CH(CH3)2, -OCH3, -OCH2CH3 or -OH. In other embodiments, R 2b is F. In other embodiments, R 2b In other embodiments, R 2b is -CH(CH3)2. In other embodiments, R 2b In other embodiments, R 2b In other embodiments, R 2b It is -OH.

[0409] In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 4b R is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, 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 halogens. In other embodiments, R 4b In other embodiments, R 4b is a C1-C6 alkyl group. In other embodiments, R 4b is a C1-C6 haloalkyl group. In other embodiments, R 4b is C1-C6 alkoxy. In other embodiments, R4b is C1-C6 haloalkoxy. In other embodiments, R 4b is a C3-C6 cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more halogens. 4b is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 alkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In other embodiments, R 4b is (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein R 4b is Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CF3), -OCH3, -OCF3, cyclopropyl, 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl or 3,3-difluoro-1-methylcyclobutyl. In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b is -CH(CH3)2. In other embodiments, R 4b is -C(CH3)3. In other embodiments, R 4b is -C(CH3)2(CH2CH3). In other embodiments, R 4b In other embodiments, R 4b is -C(CH3)2(CF3). In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b It is 3,3-difluoro-1-methylcyclobutyl.

[0410] In some embodiments, the present invention relates to a compound of formula (ID-1) or a pharmaceutically acceptable salt thereof, wherein:

[0411] R 2b is halo, C1-C6 alkyl, C1-C6 alkoxy or -OH; and

[0412] R4b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, 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 by one or more halogens.

[0413] In some embodiments, the present invention relates to a compound of formula (ID-2):

[0414]

[0415] or a pharmaceutically acceptable salt thereof, wherein:

[0416] R 2a C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2;

[0417] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2;

[0418] R 5ais H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl);

[0419] R 2b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0420] R 4b It is C2-C6 alkyl, C2-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

[0421] In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein R 2b It is halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0422] In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein R 2ais C1-C6 alkyl, C1-C6 alkoxy or -N(C1-C6 alkyl)2. In other embodiments, R 2a is a C1-C6 alkyl group. In other embodiments, R 2a is C1-C6 alkoxy. In other embodiments, R 2a In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein R 2a is -CH3, -OCH3 or -N(CH3)2. In other embodiments, R 2a In other embodiments, R 2a In other embodiments, R 2a It is -N(CH3)2.

[0423] In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein R 3a R is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2CH2NHC(O)CH(CH3)(NH2) or -NHC(O)CH(CH3)(NH2. In other embodiments, R 3a In other embodiments, R 3a is a C1-C6 alkyl group. In other embodiments, R 3a is C1-C6 alkoxy. In other embodiments, R 3a is -N(C1-C6 alkyl)2. In other embodiments, R 3a is -(C1-C6 alkylene)-OH. In other embodiments, R 3a is -(C1-C6 alkylene)-NH2. In other embodiments, R 3a is -C(O)(C1-C6 alkyl). In other embodiments, R 3a is -C(O)O(C1-C6 alkyl). In other embodiments, R 3a is -S(O)2-(C1-C6 alkyl). In other embodiments, R 3a is -NHC(O)(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein R 3ais H, Cl, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH), -C(CH3)2(OH), -CH2NH2, -C(O)CH3, -C(O)OCH2CH3, -S(O)2-(CH3), -NHC(O)(CH3), -CH2NHC(O)CH(CH3)(NH2), -CH2CH2NHC(O)CH(CH3)(NH2) or -NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is H. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)2. In other embodiments, R 3a In other embodiments, R 3a In other embodiments, R 3a is -N(CH3)2. In other embodiments, R 3a In other embodiments, R 3a is -CH(CH3)(OH). In other embodiments, R 3a is -C(CH3)2(OH). In other embodiments, R 3a In other embodiments, R 3a is -C(O)CH3. In other embodiments, R 3a In other embodiments, R 3a is -S(O)2-(CH3). In other embodiments, R 3a is -NHC(O)(CH3). In other embodiments, R 3a is -CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a is -CH2CH2NHC(O)CH(CH3)(NH2). In other embodiments, R 3a It is -NHC(O)CH(CH3)(NH2).

[0424] In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein R 5a is H, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl) or -C(O)O(C1-C6 alkyl). In other embodiments, R 5a is a C1-C6 alkyl group. In other embodiments, R 5ais C1-C6 alkoxy. In other embodiments, R 5a is -CH2O(C1-C6 alkyl). In other embodiments, R 5a In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein R 5a In other embodiments, R 5a is H. In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a In other embodiments, R 5a It is -C(O)OCH2CH3.

[0425] In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein R 2b is C1-C6 alkyl or C1-C6 alkoxy. 2b is a C1-C6 alkyl group. In other embodiments, R 2b In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein R 2b is -CH3, -CH(CH3)2 or -OCH3. In other embodiments, R 2b In other embodiments, R 2b is -CH(CH3)2. In other embodiments, R 2b It is -OCH3.

[0426] In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein R 4b is C2-C6 alkyl, C2-C6 haloalkyl, C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In other embodiments, R 4bis a C2-C6 alkyl group. In other embodiments, R 4b is a C2-C6 haloalkyl group. In other embodiments, R 4b is a C4-C6 cycloalkyl group, wherein the cycloalkyl group is optionally substituted with one or more halogens. 4b is (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 alkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In other embodiments, R 4b is (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in said (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens. In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein R 4b is -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -C(CH3)2(CF3), 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl or 3,3-difluoro-1-methylcyclobutyl. In other embodiments, R 4b is -CH(CH3)2. In other embodiments, R 4b is -C(CH3)3. In other embodiments, R 4b is -C(CH3)2(CH2CH3). In other embodiments, R 4b is -C(CH3)2(CF3). In other embodiments, R 4b In other embodiments, R 4b In other embodiments, R 4b It is 3,3-difluoro-1-methylcyclobutyl.

[0427] In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein:

[0428] R 2b is a C1-C6 alkyl group or a C1-C6 alkoxy group; and

[0429] R 4b It is C2-C6 alkyl, C2-C6 haloalkyl, C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, the (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or the (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

[0430] In some embodiments, the present invention relates to a compound of formula (ID-2) or a pharmaceutically acceptable salt thereof, wherein:

[0431] R 2b is -CH3, -CH(CH3)2 or -OCH3; and

[0432] R 4b It is -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -C(CH3)2(CF3), 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl or 3,3-difluoro-1-methylcyclobutyl.

[0433] In some embodiments, the present invention relates to a compound of formula (IE-1):

[0434]

[0435] or a pharmaceutically acceptable salt thereof, wherein:

[0436] R 2a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2;

[0437] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、-C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2;

[0438] R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), or -C(O)O(C1-C6 haloalkyl); and

[0439] R 4b It is C1-C6 alkyl, C2-C6 haloalkyl, C2-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0440] In some embodiments, the present invention relates to a compound of formula (IE-1) or a pharmaceutically acceptable salt thereof, wherein R 2a In some embodiments, the present invention relates to a compound of formula (IE-1) or a pharmaceutically acceptable salt thereof, wherein R 2a is -CH3.

[0441] In some embodiments, the present invention relates to a compound of formula (IE-1) or a pharmaceutically acceptable salt thereof, wherein R 3a is H or C1-C6 alkyl. In other embodiments, R 3a In some embodiments, the present invention relates to a compound of formula (IE-1) or a pharmaceutically acceptable salt thereof, wherein R 3a is H or -CH3. In other embodiments, R 3ais H. In other embodiments, R 3a is -CH3.

[0442] In some embodiments, the present invention relates to a compound of formula (IE-1) or a pharmaceutically acceptable salt thereof, wherein R 5a is H or C1-C6 alkyl. In other embodiments, R 5a In some embodiments, the present invention relates to a compound of formula (IE-1) or a pharmaceutically acceptable salt thereof, wherein R 5a is H or -CH3. In other embodiments, R 5a is H. In other embodiments, R 5a is -CH3.

[0443] In some embodiments, the present invention relates to a compound of formula (IE-1) or a pharmaceutically acceptable salt thereof, wherein R 4b is C1-C6 alkyl, C2-C6 haloalkyl, C2-C6 alkoxy or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl is optionally substituted with one or more halogens. 4b is a C1-C6 alkyl group. In other embodiments, R 4b is a C2-C6 haloalkyl group. In other embodiments, R 4b is a C2-C6 alkoxy group. In other embodiments, R 4b -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl is optionally substituted with one or more halogens. In some embodiments, the present invention relates to a compound of formula (IE-1) or a pharmaceutically acceptable salt thereof, wherein R 4b is -C(CH3)3, -C(CH3)2(CF3), -OC(CH3)3 or 1-trifluoromethylcyclopropyl. In other embodiments, R 4b is -C(CH3)3. In other embodiments, R 4b is -C(CH3)2(CF3). In other embodiments, R 4b is -OC(CH3)3. In other embodiments, R 4b It is 1-trifluoromethylcyclopropyl.

[0444] In some embodiments, the present invention relates to a compound of formula (IE-2):

[0445]

[0446] or a pharmaceutically acceptable salt thereof, wherein:

[0447] R 2aC1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2;

[0448] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2;

[0449] R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), or -C(O)O(C1-C6 haloalkyl); and

[0450] R 4b It is C1-C6 alkyl, C2-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0451] In some embodiments, the present invention relates to a compound of formula (IE-2) or a pharmaceutically acceptable salt thereof, wherein R 2a In some embodiments, the present invention relates to a compound of formula (IE-2) or a pharmaceutically acceptable salt thereof, wherein R 2a is -CH3.

[0452] In some embodiments, the present invention relates to a compound of formula (IE-2) or a pharmaceutically acceptable salt thereof, wherein R 3a is H or C1-C6 alkyl. In other embodiments, R 3a In some embodiments, the present invention relates to a compound of formula (IE-2) or a pharmaceutically acceptable salt thereof, wherein R 3a is H or -CH3. In other embodiments, R 3a is H. In other embodiments, R 3a is -CH3.

[0453] In some embodiments, the present invention relates to a compound of formula (IE-2) or a pharmaceutically acceptable salt thereof, wherein R 5a is H or C1-C6 alkyl. In other embodiments, R 5a In some embodiments, the present invention relates to a compound of formula (IE-2) or a pharmaceutically acceptable salt thereof, wherein R 5a is H or -CH3. In other embodiments, R 5a is H. In other embodiments, R 5a is -CH3.

[0454] In some embodiments, the present invention relates to a compound of formula (IE-2) or a pharmaceutically acceptable salt thereof, wherein R 4b is C1-C6 alkyl, C2-C6 haloalkyl or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl is optionally substituted with one or more halogens. 4b is a C1-C6 alkyl group. In other embodiments, R 4b is a C2-C6 haloalkyl group. In other embodiments, R 4b -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl is optionally substituted with one or more halogens. In some embodiments, the present invention relates to a compound of formula (IE-2) or a pharmaceutically acceptable salt thereof, wherein R 4b is -C(CH3)3, -C(CH3)2(CF3) or 1-trifluoromethylcyclopropyl. In other embodiments, R 4bis -C(CH3)3. In other embodiments, R 4b is -C(CH3)2(CF3). In other embodiments, R 4b It is 1-trifluoromethylcyclopropyl.

[0455] In some embodiments, the present invention relates to a compound of formula (IF):

[0456]

[0457] or a pharmaceutically acceptable salt thereof, wherein:

[0458] R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2;

[0459] R 3a H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2;

[0460] R 5ais H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl);

[0461] R 2b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens;

[0462] R 3b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens;

[0463] R 4b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 halogens; and

[0464] R 6bis halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0465] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 2b It is halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0466] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 3b It is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0467] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 6bIt is halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), 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 by one or more halogens.

[0468] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 2a In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 2a is -CH3.

[0469] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 3a is -S(O)(NH)(C1-C6 alkyl). In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 3a It is -S(O)(NH)(CH3).

[0470] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 5a For H.

[0471] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 2b In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 2b For F.

[0472] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 3b In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 3b is -CH3.

[0473] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 4b In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R4b It is -C(CH3)3.

[0474] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 6b In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein R 6b is -CH3.

[0475] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein:

[0476] R 2b is halogenated;

[0477] R 3b is a C1-C6 alkyl group;

[0478] R 4b is a C1-C6 alkyl group; and

[0479] R 6b It is a C1-C6 alkyl group.

[0480] In some embodiments, the present invention relates to a compound of formula (IF) or a pharmaceutically acceptable salt thereof, wherein:

[0481] R 2b is F;

[0482] R 3b is -CH3;

[0483] R 4b is -C(CH3)3; and

[0484] R 6b is -CH3.

[0485] 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, C1-C6 alkyl or -S(O)(NH)(C1-C6 alkyl).

[0486] In some embodiments, the present invention relates to a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein Y is N. In some embodiments, the present invention relates to a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein Y is CR 3d In some embodiments, the present invention relates to a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein Y is CR 3d , and R 3dis halo, C1-C6 alkyl or C1-C6 haloalkyl. 3d In other embodiments, R 3d is a C1-C6 alkyl group. In other embodiments, R 3d In some embodiments, the present invention relates to a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein Y is CR 3d , and R 3d is Cl, -CH3 or -CF3. In other embodiments, R 3d In other embodiments, R 3d -CH3. In other embodiments, R 3d -CF3.

[0487] In some embodiments, the present invention relates to a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein R 2c is -CH3.

[0488] 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, C1-C6 alkyl, -S(O)2(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl) or 4-10 membered heteroaryl, wherein the heteroaryl is optionally substituted with C1-C6 alkyl. 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, C1-C6 alkyl or -S(O)(NH)(C1-C6 alkyl). In other embodiments, R 3c In other embodiments, R 3c is a C1-C6 alkyl group. In other embodiments, R 3c is -S(O)(NH)(C1-C6 alkyl). In other embodiments, R 3c is -S(O)2(C1-C6 alkyl). In other embodiments, R 3c is a 4-10 membered heteroaryl group, wherein the heteroaryl group is optionally substituted by a C1-C6 alkyl group. In some embodiments, the present invention relates to a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein R 3c is H, Cl, -CH3, -S(O)2CH3, -S(O)(NH)(CH3) or In some embodiments, the present invention relates to a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein R 3c is H, Cl, -CH3 or -S(O)(NH)(CH3). In other embodiments, R 3cis H. In other embodiments, R 3c In other embodiments, R 3c In other embodiments, R 3c is -S(O)(NH)(CH3). In other embodiments, R 3c In other embodiments, R 3c for

[0489] In some embodiments, the present invention relates to a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein R 4d is H, C1-C6 alkyl or C1-C6 haloalkyl. 4d is a C1-C6 alkyl group. In other embodiments, R 4d In some embodiments, the present invention relates to a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein R 4d is H, -CH3, -C(CH3)3 or -CF3. In other embodiments, R 4d is H. In other embodiments, R 4d In other embodiments, R 4d is -C(CH3)3. In other embodiments, R 4d or -CF3.

[0490] In some embodiments, the present invention relates to a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein R 6d is H, C1-C6 alkyl or C1-C6 alkoxy. In other embodiments, R 6d is a C1-C6 alkyl group. 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, -CH3, -OCH3, -OCH2CH3 or -OCH(CH3)2. In other embodiments, R 6d is H. In other embodiments, R 6d In other embodiments, R 6d In other embodiments, R 6d In other embodiments, R 6d It is -OCH(CH3)2.

[0491] In some embodiments, the present invention relates to a compound of formula (II-A):

[0492]

[0493] or a pharmaceutically acceptable salt thereof, wherein:

[0494] R 2c is a C1-C6 alkyl group;

[0495] R 3c is halo, C1-C6 alkyl or -S(O)(NH)(C1-C6 alkyl);

[0496] R 3d is halo, C1-C6 alkyl or C1-C6 haloalkyl;

[0497] R 4d is H, C1-C6 alkyl or C1-C6 haloalkyl; and

[0498] R 6d is H, C1-C6 alkyl or C1-C6 alkoxy.

[0499] In some embodiments, the present invention relates to a compound of formula (II-A) or a pharmaceutically acceptable salt thereof, wherein R 2c is -CH3.

[0500] In some embodiments, the present invention relates to a compound of formula (II-A) or a pharmaceutically acceptable salt thereof, wherein R 3c is halo, C1-C6 alkyl or -S(O)(NH)(C1-C6 alkyl). In other embodiments, R 3c In other embodiments, R 3c is a C1-C6 alkyl group. 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 Cl, -CH3 or -S(O)(NH)(CH3). In other embodiments, R 3c In other embodiments, R 3c In other embodiments, R 3c It is -S(O)(NH)(CH3).

[0501] In some embodiments, the present invention relates to a compound of formula (II-A) or a pharmaceutically acceptable salt thereof, wherein R 3d is halogenated or C1-C6 alkyl. In other embodiments, R 3d In other embodiments, R 3d In some embodiments, the present invention relates to a compound of formula (II-A) or a pharmaceutically acceptable salt thereof, wherein R3d is Cl or -CH3. In other embodiments, R 3d In other embodiments, R 3d is -CH3.

[0502] In some embodiments, the present invention relates to a compound of formula (II-A) or a pharmaceutically acceptable salt thereof, wherein R 4d In some embodiments, the present invention relates to a compound of formula (II-A) or a pharmaceutically acceptable salt thereof, wherein R 4d It is -C(CH3)3.

[0503] In some embodiments, the present invention relates to a compound of formula (II-A) or a pharmaceutically acceptable salt thereof, wherein 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 -CH3.

[0504] In some embodiments, the present invention relates to a compound of formula (III) or a pharmaceutically acceptable salt thereof, wherein R 2e is -CH3.

[0505] In some embodiments, the present invention relates to a compound of formula (III) or a pharmaceutically acceptable salt thereof, wherein R 2f is -CH3.

[0506] In some embodiments, the present invention relates to a compound of formula (III) or a pharmaceutically acceptable salt thereof, wherein R 4f It is -C(CH3)3.

[0507] In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 2g In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 2g is -CH3.

[0508] In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 3g is C1-C6 alkyl or 4-10 membered heteroaryl, wherein the heteroaryl is optionally substituted by 1 R g 'Replace; and R g ' is -CH3. In other embodiments, R 3g is a C1-C6 alkyl group. In other embodiments, R 3g is a 4-10 membered heteroaryl group, wherein the heteroaryl group is optionally substituted by 1 Rg 'Replace; and R g ' is -CH3. In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 3g -CH3 or In other embodiments, R 3g In other embodiments, R 3g for

[0509] In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 5g For H.

[0510] In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 2h In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 2h is -CH3.

[0511] In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 4h In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 4h It is -C(CH3)3.

[0512] In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 5h is halogenated or C1-C6 alkyl. In other embodiments, R 5h In other embodiments, R 5h In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 5h is Cl or -CH3. In other embodiments, R 5h In other embodiments, R 5h is -CH3.

[0513] In some embodiments, the present invention relates to a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein R 4h and R 5h Together with the C atoms to which they are attached, they are joined to form a C5-C6 cycloalkyl group, wherein the cycloalkyl group is optionally substituted with 1-2 C1-C6 alkyl groups. 4h and R 5hTogether with the C atoms to which they are attached, they are joined together to form a C6 cycloalkyl group, wherein the cycloalkyl group is substituted by 2 methyl groups.

[0514] 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, ie, a compound in non-salt form.

[0515] Table A: Compound structures and names.

[0516]

[0517]

[0518]

[0519]

[0520]

[0521]

[0522]

[0523]

[0524]

[0525]

[0526]

[0527]

[0528]

[0529]

[0530]

[0531]

[0532] 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, ie, a compound in non-salt form.

[0533] Table B: Compound structures and names.

[0534]

[0535] In some embodiments, the present invention relates to a compound selected from Table C or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to a compound selected from Table C, ie, a compound in non-salt form.

[0536] Table C: Compound structures and names.

[0537]

[0538] In some embodiments, the present invention relates to a compound selected from Table D or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to a compound selected from Table C, ie, a compound in non-salt form.

[0539] Table D: Compound structures and names.

[0540]

[0541]

[0542]

[0543]

[0544]

[0545]

[0546]

[0547]

[0548]

[0549]

[0550]

[0551]

[0552] In some embodiments, the present invention relates to a compound selected from the group consisting of:

[0553]

[0554] 6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-methylsulfonyl-1H-pyridin-4-one;

[0555]

[0556] 6-[4-tert-Butyl-2-methyl-5-(trifluoromethyl)phenyl]-2-methyl-3-methylsulfonyl-1H-pyridin-4-one;

[0557]

[0558] 6-(4-tert-Butyl-2-fluoro-3,6-dimethyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0559]

[0560] (S)-6-(4-tert-Butyl-2-fluoro-3,6-dimethyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0561]

[0562] (R)-6-(4-tert-Butyl-2-fluoro-3,6-dimethyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0563]

[0564] 6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0565]

[0566] (S)-6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0567]

[0568] (R)-6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0569]

[0570] 6-(6-tert-Butyl-5-chloro-2-methyl-3-pyridyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0571]

[0572] (S)-6-(6-tert-Butyl-5-chloro-2-methyl-3-pyridinyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0573]

[0574] (R)-6-(6-tert-butyl-5-chloro-2-methyl-3-pyridinyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0575]

[0576] 6-(4-tert-Butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0577]

[0578] (S)-6-(4-tert-Butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0579]

[0580] (R)-6-(4-tert-Butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one;

[0581]

[0582] (2S)-2-amino-N-[[6-(4-tert-butyl-2-methyl-phenyl)-2-methyl-4-oxo-1H-pyridin-3-yl]methyl]propionamide;

[0583]

[0584] 6-(4-tert-Butyl-2,5-dimethyl-phenyl)-2,3-dimethyl-1H-pyridin-4-one;

[0585]

[0586] 3-Chloro-2-methyl-6-[2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-1H-pyridin-4-one;

[0587]

[0588] 6-(4-tert-Butyl-2,5-dimethyl-phenyl)-2-methyl-4-oxo-1H-pyridine-3-carboxylic acid ethyl ester;

[0589]

[0590] 6-[6-(4-tert-Butyl-5-chloro-2-methyl-phenyl)-2-methyl-4-oxo-1H-pyridin-3-yl]pyridine-2-carboxamide;

[0591]

[0592] 6-(4-tert-Butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(1H-pyrazol-4-yl)-1H-pyridin-4-one;

[0593]

[0594] 6-(4-tert-Butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-methylsulfonyl-1H-pyridin-4-one;

[0595]

[0596] 6-(4-(tert-butyl)-5-chloro-2-methylphenyl)-2-methyl-3-(1-methyl-1H-imidazol-5-yl)pyridin-4(1H)-one;

[0597]

[0598] 6-(5-chloro-2-methyl-4-(1,1,1-trifluoro-2-methylprop-2-yl)phenyl)-2-methyl-3-(1-methyl-1H-pyrazol-4-yl)pyridin-4(1H)-one; and

[0599]

[0600] 6-(4-(tert-butyl)-5-chloro-2-methylphenyl)-2-methyl-3-(1H-1,2,4-triazol-1-yl)pyridin-4(1H)-one,

[0601] or a pharmaceutically acceptable salt thereof.

[0602] In some embodiments, the present invention relates to compounds having the formula

[0603]

[0604] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0605] In some embodiments, the present invention relates to the compound 6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-methylsulfonyl-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0606] In some embodiments, the present invention relates to compounds having the formula

[0607]

[0608] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0609] In some embodiments, the present invention relates to the compound 6-[4-tert-butyl-2-methyl-5-(trifluoromethyl)phenyl]-2-methyl-3-methylsulfonyl-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0610] In some embodiments, the present invention relates to compounds having the formula

[0611]

[0612] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0613] In some embodiments, the present invention relates to the compound 6-(4-tert-butyl-2-fluoro-3,6-dimethyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0614] In some embodiments, the present invention relates to the first eluting isomer of the compound 6-(4-tert-butyl-2-fluoro-3,6-dimethyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one, or a pharmaceutically acceptable salt thereof, when the stereoisomers are resolved using appropriate separation techniques. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0615] In some embodiments, the present invention relates to the second eluting isomer of compound 6-(4-tert-butyl-2-fluoro-3,6-dimethyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one, or a pharmaceutically acceptable salt thereof, when the stereoisomers are resolved using appropriate separation techniques. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as this term is used herein.

[0616] In some embodiments, the present invention relates to compounds having the formula

[0617]

[0618] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0619] In some embodiments, the present invention relates to compound (S)-6-(4-tert-butyl-2-fluoro-3,6-dimethyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0620] In some embodiments, the present invention relates to compounds having the formula

[0621]

[0622] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0623] In some embodiments, the present invention relates to the compound (R)-6-(4-tert-butyl-2-fluoro-3,6-dimethyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0624] In some embodiments, the present invention relates to compounds having the formula

[0625]

[0626] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0627] In some embodiments, the present invention relates to the compound 6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0628] In some embodiments, the present invention relates to the first eluting isomer of the compound 6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one, or a pharmaceutically acceptable salt thereof, when the stereoisomers are resolved using appropriate separation techniques. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0629] In some embodiments, the present invention relates to the second eluting isomer of the compound 6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one, or a pharmaceutically acceptable salt thereof, when the stereoisomers are resolved using appropriate separation techniques. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0630] In some embodiments, the present invention relates to compounds having the formula

[0631]

[0632] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0633] In some embodiments, the present invention relates to the compound (S)-6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0634] In some embodiments, the present invention relates to compounds having the formula

[0635]

[0636] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0637] In some embodiments, the present invention relates to the compound (R)-6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0638] In some embodiments, the present invention relates to compounds having the formula

[0639]

[0640] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0641] In some embodiments, the present invention relates to the compound 6-(6-tert-butyl-5-chloro-2-methyl-3-pyridinyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0642] In some embodiments, the present invention relates to the first eluting isomer of the compound 6-(6-tert-butyl-5-chloro-2-methyl-3-pyridinyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one, or a pharmaceutically acceptable salt thereof, when the stereoisomers are resolved using appropriate separation techniques. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0643] In some embodiments, the present invention relates to the second eluting isomer of the compound 6-(6-tert-butyl-5-chloro-2-methyl-3-pyridinyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one, or a pharmaceutically acceptable salt thereof, when the stereoisomers are resolved using appropriate separation techniques. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0644] In some embodiments, the present invention relates to compounds having the formula

[0645]

[0646] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0647] In some embodiments, the present invention relates to compound (S)-6-(6-tert-butyl-5-chloro-2-methyl-3-pyridyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0648] In some embodiments, the present invention relates to compounds having the formula

[0649]

[0650] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0651] In some embodiments, the present invention relates to the compound (R)-6-(6-tert-butyl-5-chloro-2-methyl-3-pyridyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0652] In some embodiments, the present invention relates to compounds having the formula

[0653]

[0654] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0655] In some embodiments, the present invention relates to the compound 6-(4-tert-butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0656] In some embodiments, the present invention relates to the first eluting isomer of the compound 6-(4-tert-butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one, or a pharmaceutically acceptable salt thereof, when the stereoisomers are resolved using appropriate separation techniques. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0657] In some embodiments, the present invention relates to the second eluting isomer of the compound 6-(4-tert-butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one, or a pharmaceutically acceptable salt thereof, when the stereoisomers are resolved using appropriate separation techniques. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention," as that term is used herein.

[0658] In some embodiments, the present invention relates to compounds having the formula

[0659]

[0660] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0661] In some embodiments, the present invention relates to the compound (S)-6-(4-tert-butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0662] In some embodiments, the present invention relates to compounds having the formula

[0663]

[0664] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0665] In some embodiments, the present invention relates to the compound (R)-6-(4-tert-butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0666] In some embodiments, the present invention relates to compounds having the formula

[0667]

[0668] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0669] In some embodiments, the present invention relates to the compound (2S)-2-amino-N-[[6-(4-tert-butyl-2-methyl-phenyl)-2-methyl-4-oxo-1H-pyridin-3-yl]methyl]propionamide 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 "compounds of the present invention," as that term is used herein.

[0670] In some embodiments, the present invention relates to compounds having the formula

[0671]

[0672] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0673] In some embodiments, the present invention relates to the compound 6-(4-tert-butyl-2,5-dimethyl-phenyl)-2,3-dimethyl-1H-pyridin-4-one 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 "compounds of the present invention" as this term is used herein.

[0674] In some embodiments, the present invention relates to compounds having the formula

[0675]

[0676] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0677] In some embodiments, the present invention relates to the compound 3-chloro-2-methyl-6-[2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0678] In some embodiments, the present invention relates to compounds having the formula

[0679]

[0680] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0681] In some embodiments, the present invention relates to the compound 6-(4-tert-butyl-2,5-dimethyl-phenyl)-2-methyl-4-oxo-1H-pyridine-3-carboxylic acid ethyl ester or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as this term is used herein.

[0682] In some embodiments, the present invention relates to compounds having the formula

[0683]

[0684] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0685] In some embodiments, the present invention relates to the compound 6-[6-(4-tert-butyl-5-chloro-2-methyl-phenyl)-2-methyl-4-oxo-1H-pyridin-3-yl]pyridine-2-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 "compounds of the present invention," as that term is used herein.

[0686] In some embodiments, the present invention relates to compounds having the formula

[0687]

[0688] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0689] In some embodiments, the present invention relates to the compound 6-(4-tert-butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(1H-pyrazol-4-yl)-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0690] In some embodiments, the present invention relates to compounds having the formula

[0691]

[0692] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0693] In some embodiments, the present invention relates to the compound 6-(4-tert-butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-methylsulfonyl-1H-pyridin-4-one 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 "compounds of the present invention," as that term is used herein.

[0694] In some embodiments, the present invention relates to compounds having the formula

[0695]

[0696] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0697] In some embodiments, the present invention relates to the compound 6-(4-(tert-butyl)-5-chloro-2-methylphenyl)-2-methyl-3-(1-methyl-1H-imidazol-5-yl)pyridin-4(1H)-one 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 "compounds of the present invention," as that term is used herein.

[0698] In some embodiments, the present invention relates to compounds having the formula

[0699]

[0700] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0701] In some embodiments, the present invention relates to the compound 6-(5-chloro-2-methyl-4-(1,1,1-trifluoro-2-methylprop-2-yl)phenyl)-2-methyl-3-(1-methyl-1H-pyrazol-4-yl)pyridin-4(1H)-one 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 "compounds of the present invention," as that term is used herein.

[0702] In some embodiments, the present invention relates to compounds having the formula

[0703]

[0704] or a pharmaceutically acceptable salt thereof. In other embodiments, the present invention relates to the aforementioned compounds in non-salt form. Such compounds are considered "compounds of the present invention" as that term is used herein.

[0705] In some embodiments, the present invention relates to the compound 6-(4-(tert-butyl)-5-chloro-2-methylphenyl)-2-methyl-3-(1H-1,2,4-triazol-1-yl)pyridin-4(1H)-one 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 "compounds of the present invention," as that term is used herein.

[0706] Salts, compositions, uses, formulations, administration and additional agents

[0707] Pharmaceutically acceptable salts and compositions

[0708] As discussed herein, the present invention provides compounds and pharmaceutically acceptable salts thereof as voltage-gated sodium channel inhibitors, and thus the compounds of the present invention and pharmaceutically acceptable salts thereof can be used to treat 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, postoperative pain (e.g., bunionectomy pain, hernia repair pain or abdominoplasty pain), visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough or arrhythmia. Therefore, in another aspect of the present invention, pharmaceutical compositions are provided, wherein these compositions comprise compounds as described herein or pharmaceutically acceptable salts thereof, and optionally comprise a pharmaceutically acceptable carrier, adjuvant or vehicle. In certain embodiments, these compositions optionally further comprise one or more additional therapeutic agents. In some embodiments, the additional therapeutic agent is a sodium channel inhibitor.

[0709] As used herein, the term "pharmaceutically acceptable salt" refers to a salt that is suitable for use in contact with the tissues of humans and lower animals without excessive toxicity, irritation, allergic reaction, etc., and is commensurate with a reasonable benefit / risk ratio, within the scope of sound medical judgment. A "pharmaceutically acceptable salt" of a compound of the present invention includes any non-toxic salt that, when administered to a recipient, is capable of directly or indirectly providing a compound of the present invention or its inhibitory active metabolite or residue. The salt may be in pure form, in a mixture (e.g., solution, suspension, or colloid) containing one or more other substances, or in the form of a hydrate, solvate, or cocrystal. As used herein, the term "its inhibitory active metabolite or residue" means that its metabolite or residue is also a voltage-gated sodium channel inhibitor.

[0710] Pharmaceutically acceptable salts are well known in the art. For example, SM Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, which are incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of the present invention include salts derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are salts formed of amino groups with inorganic acids (such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid) or with organic acids (such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid), or by using salts formed by 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, dodecylsulfate, ethanesulfonate, formate, fumarate, gluconate heptanoate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, 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, and the like. Salts derived from appropriate bases include alkali metal salts, alkaline earth metal salts, ammonium salts and N + (C 1-4 Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Other pharmaceutically acceptable salts include non-toxic ammonium, quaternary ammonium, and amine cations formed when appropriate using counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates.

[0711] As described herein, the pharmaceutically acceptable compositions of the present invention additionally include pharmaceutically acceptable carriers, adjuvants or vehicles as used herein, including any and all solvents, diluents or other liquid vehicles, dispersion or suspension aids, surfactants, isotonic agents, thickeners or emulsifiers, preservatives, solid binders, lubricants, etc., such as those suitable for desired specific dosage forms. Remington's Pharmaceutical Sciences, 16th edition, EW Martin (Mack Publishing Co., Easton, Pa., 1980) discloses various carriers for the preparation of pharmaceutically acceptable compositions and known techniques for their preparation. Unless any conventional carrier medium is incompatible with the compound of the present invention, such as by producing any undesirable biological effect or interacting with any other component of the pharmaceutically acceptable composition in other harmful ways, it is envisioned that it will be used within the scope of the present invention. Some examples of materials that can serve as pharmaceutically acceptable carriers include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins (such as human serum albumin), buffer substances (such as phosphates, glycine, sorbic acid or potassium sorbate), partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes (such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts), colloidal silicon dioxide, magnesium trisilicate, polyvinyl pyrrolidone, polyacrylates, waxes, polyethylene-polyoxypropylene block polymers, lanolin, sugars (such as lactose, glucose and sucrose); starches (such as corn starch and potato starch); cellulose and its derivatives (such as sodium carboxymethylcellulose, ethylcellulose and cellulose acetate); powdered tragacanth; malt; gelatin; talc; excipients (such as cocoa butter and suppository waxes); oils (such as peanut oil, cottonseed oil, safflower oil, sesame oil; olive oil, corn oil and soybean oil); glycols (such as propylene glycol or polyethylene glycol); esters (such as ethyl oleate and ethyl laurate); agar; buffers (such as magnesium hydroxide and aluminum hydroxide); alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethanol and phosphate buffer solutions and other nontoxic compatible lubricants (such as sodium lauryl sulfate and magnesium stearate), and coloring agents, release 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.

[0712] In another aspect, the invention features a pharmaceutical composition comprising a compound of the invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

[0713] In another aspect, the invention features a pharmaceutical composition comprising a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or vehicles.

[0714] Uses of compounds, pharmaceutically acceptable salts, and compositions

[0715] 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 acceptable salt thereof, or a pharmaceutical composition thereof. In another aspect, the voltage-gated sodium channel is Na V 1.8.

[0716] In yet another aspect, the invention features a method of treating or lessening the severity of chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postoperative pain (e.g., bunionectomy pain, hernia repair pain, or abdominoplasty pain), visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough, or cardiac arrhythmia in a subject, comprising administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0717] In yet another aspect, the invention features a method of treating or lessening the severity of chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postoperative pain, hernia repair pain, bunionectomy pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, or cardiac arrhythmia in a subject, the method comprising administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0718] In yet another aspect, the invention features a method of treating or lessening the severity of intestinal pain in a subject, wherein the intestinal pain comprises inflammatory bowel disease pain, Crohn's disease pain, irritable bowel syndrome, endometriosis, erythro-ovarian disease, salpingitis, cervicitis, or interstitial cystitis pain, wherein the method comprises administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0719] On the other hand, the present invention is characterized in that a kind of neuropathic pain for treating subject or the method for alleviating its severity, methods described include applying effective dose of compound of the present invention, its pharmaceutically acceptable salt or its pharmaceutical composition.In some respects, neuropathic pain includes postherpetic neuralgia, small fiber neuropathy, diabetic neuropathy or idiopathic small fiber neuropathy.In some respects, neuropathic pain includes diabetic neuropathy (for example, diabetic peripheral neuropathy).As used herein, phrase " idiopathic small fiber neuropathy " should be understood as including any small fiber neuropathy.

[0720] In yet another aspect, the invention features a method of treating or lessening the severity of neuropathic pain in a subject, wherein the neuropathic pain includes post-herpetic neuralgia, diabetic neuralgia, painful HIV-associated sensory neuropathy, trigeminal neuralgia, burning mouth syndrome, post-amputation pain, phantom limb pain, painful neuroma; traumatic neuroma; Morton's neuroma; nerve entrapment injury, spinal stenosis, carpal tunnel syndrome, radicular pain, sciatica; nerve avulsion injury, brachial plexus avulsion injury; complex regional pain syndrome, drug therapy-induced neuralgia, cancer chemotherapy-induced neuralgia, antiretroviral therapy-induced neuralgia, HIV-induced neuralgia; pain after spinal cord injury, spinal stenosis pain, small fiber neuropathy, idiopathic small fiber neuropathy, idiopathic sensory neuropathy, or trigeminal autonomic cephagia, wherein the method comprises administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0721] In yet another aspect, the invention features a method of treating or lessening the severity of musculoskeletal pain in a subject, the method comprising administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some aspects, musculoskeletal pain includes osteoarthritis pain.

[0722] In yet another aspect, the invention features a method of treating or lessening the severity of musculoskeletal pain in a subject, wherein the musculoskeletal pain includes osteoarthritis pain, back pain, cold pain, burn pain, or dental pain, wherein the method comprises administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0723] In yet another aspect, the invention features a method of treating or lessening the severity of inflammatory pain in a subject, wherein the inflammatory pain comprises rheumatoid arthritis pain, ankylosing spondylitis, or vulvodynia, wherein the method comprises administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0724] In yet another aspect, the invention features a method of treating or lessening the severity of inflammatory pain in a subject, wherein the inflammatory pain includes rheumatoid arthritis pain, wherein the method comprises administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0725] In yet another aspect, the invention features a method of treating or lessening the severity of idiopathic pain in a subject, wherein the idiopathic pain includes fibromyalgia, wherein the method comprises administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0726] In yet another aspect, the invention features a method of treating or lessening the severity of idiopathic pain in a subject, wherein the idiopathic pain includes reflex sympathetic dystrophy pain, wherein the method comprises administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0727] In yet another aspect, the invention features a method of treating or reducing the severity of pathological cough in a subject, wherein the method comprises administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0728] In another aspect, the invention features a method of treating acute pain in a subject or reducing its severity, the method comprising administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some aspects, acute pain includes acute postoperative pain.

[0729] In yet another aspect, the invention features a method of treating or lessening the severity of postoperative pain (e.g., joint replacement pain, soft tissue surgery pain, post-thoracotomy pain, post-mastectomy pain, hemorrhoidectomy pain, hernia repair pain, bunionectomy pain, or abdominoplasty pain) in a subject, the method comprising administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0730] In yet another aspect, the invention features a method of treating or lessening the severity of bunionectomy pain in a subject, the method comprising administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0731] In yet another aspect, the invention features a method of treating or lessening the severity of shoulder replacement pain or shoulder arthroscopic pain in a subject, the method comprising administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0732] In yet another aspect, the invention features a method of treating or lessening the severity of herniorrhaphy pain in a subject, the method comprising administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0733] In yet another aspect, the invention features a method of treating or lessening the severity of abdominoplasty pain in a subject, the method comprising administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0734] In another aspect, the invention features a method of treating or reducing the severity of visceral pain in a subject, the method comprising administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some aspects, the visceral pain comprises visceral pain caused by abdominoplasty.

[0735] In another aspect, the present invention is characterized by a method for treating a neurodegenerative disease in a subject or reducing its severity, the method comprising administering an effective amount of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In some aspects, the neurodegenerative disease comprises multiple sclerosis. In some aspects, the neurodegenerative disease comprises Pitt Hopkins Syndrome (PTHS).

[0736] In yet another aspect, the invention features methods in which a subject is treated with one or more additional therapeutic agents that are administered concurrently with, prior to, or after treatment with an effective amount of the compound, the pharmaceutically acceptable salt, or the pharmaceutical composition. In some embodiments, the additional therapeutic agent is a sodium channel inhibitor.

[0737] In another aspect, the invention features a method of inhibiting a voltage-gated sodium channel in a biological sample, the method comprising contacting the biological sample with an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. In another aspect, the voltage-gated sodium channel is Na V 1.8.

[0738] In another aspect, the invention features a method for treating acute pain, subacute and chronic pain, nociceptive pain, neuropathic pain, inflammatory pain, nociceptive plastic pain, arthritis, migraine, cluster headache, tension headache and all other forms of headache, trigeminal neuralgia, herpetic neuralgia, general neuralgia, epilepsy, epileptic conditions, neurodegenerative disorders, psychiatric disorders, anxiety, depression, bipolar disorder, myotonia, arrhythmias, movement disorders, neuroendocrine disorders, ataxia, central neuropathic pain of multiple sclerosis and irritable bowel syndrome, incontinence, pathological cough, visceral pain, osteoarthritis pain, post-herpetic Neuralgia, diabetic neuropathy, radicular pain, sciatica, back pain, nonspecific chronic back pain, headache, neck pain, moderate pain, severe pain, intractable pain, nociceptive pain, breakthrough pain, postoperative pain (e.g., joint replacement pain, soft tissue surgery pain, post-thoracotomy pain, post-mastectomy pain, hernia repair pain, bunionectomy pain, or abdominoplasty pain), cancer pain (including chronic cancer pain and breakthrough cancer pain), stroke (e.g., central neuropathic pain after stroke), whiplash-related disorders, fragility fractures, vertebral fractures, ankylosing spondylitis, pemphigus, Raynaud's disease Disease), scleroderma, systemic lupus erythematosus, epidermolysis bullosa, gout, juvenile idiopathic arthritis, oleaginous bone disease, polymyalgia rheumatica, pyoderma gangrenosum, chronic widespread pain, diffuse idiopathic skeletal hyperostosis, disc degeneration / herniation pain, radiculopathy, facet joint syndrome, failed back surgery syndrome, burns, carpal tunnel syndrome, Paget's disease pain, spinal stenosis, spondylitis, transverse myelitis, Ehlers-Danlossyndrome, Fabry's disease, mastocytosis, neurofibromatosis, ocular neuropathic pain, sarcoidosis, spondylolisthesis, spondylolisthesis, chemotherapy-induced oral mucositis, Charcot neuropathic osteoarthritis A method for treating or alleviating the severity of angina pectoris, osteoarthropathy, temporomandibular joint disorder, painful arthroplasty, non-cardiac chest pain, pudendal neuralgia, renal colic, biliary tract disease, vascular leg ulcers, Parkinson's disease pain, Alzheimer's disease pain, cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, stress-induced angina pectoris, exercise-induced angina pectoris, palpitations, hypertension or gastrointestinal motility disorders, which comprises administering an effective amount of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0739] In another aspect, the invention features a method for treating femoral cancer pain in a subject; non-malignant chronic bone pain; rheumatoid arthritis; osteoarthritis; spinal stenosis; neuropathic low back pain; myofascial pain syndrome; fibromyalgia; temporomandibular joint pain; chronic visceral pain; abdominal pain; pancreatic pain; IBS pain; chronic and acute headaches; migraines; tension headaches; cluster headaches; chronic and acute neuropathic pain; postherpetic neuralgia; diabetic neuropathy; HIV-associated neuropathy; trigeminal neuralgia; Charcot-Marie-Tooth neuropathy; hereditary sensory neuropathies; peripheral nerve injury; painful neuromas; ectopic proximal and distal discharges; radiculopathy; chemotherapy-induced neuropathic pain; radiation therapy-induced neuropathic pain; persistent / chronic postoperative pain (e.g., post-amputation, post-thoracotomy, post-cardiac surgery); breast Post-atrial resection pain; central pain; spinal cord injury pain; post-stroke pain; thalamic pain; phantom limb pain (e.g., after lower limb, upper limb, or breast resection); refractory pain; acute pain, acute postoperative pain; acute musculoskeletal pain; joint pain; mechanical low back pain; neck pain; tendinitis; injury pain; movement pain; acute visceral pain; pyelonephritis; appendicitis; cholecystitis; intestinal obstruction; hernia; chest pain, cardiac pain; pelvic pain, renal colic, acute labor pain, labor pain; cesarean section pain; acute inflammatory pain, burn pain, trauma pain; acute intermittent pain, endometriosis; acute herpes zoster pain; sickle cell anemia; acute pancreatitis; breakthrough pain; oral and facial pain; sinusitis pain; toothache; multiple sclerosis (MS) pain; depression pain; leprosy pain; Behçet's disease pain disease pain); dolorosa; phlebitis pain; Guillain-Barre syndrome pain; leg and toe pain; Haglund syndrome; erythromelalgia; Fabry's disease pain; bladder and genitourinary system diseases; urinary incontinence; pathological cough; overactive bladder; painful bladder syndrome; interstitial cystitis (IC); prostatitis, complex regional pain syndrome (CRPS) type I, complex regional pain syndrome (CRPS) type II; widespread pain, paroxysmal severe pain, itching, tinnitus or angina-induced pain or a method of reducing the severity thereof, the method comprising administering an effective amount of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0740] In another aspect, the invention features a method of treating or lessening the severity of trigeminal neuralgia, botulinum toxin-treated migraine, cervical radiculopathy, occipital neuralgia, axillary neuropathy, radial neuropathy, ulnar neuropathy, brachial plexopathy, thoracic radiculopathy, intercostal neuralgia, lumbosacral radiculopathy, ilioglossal neuralgia, pudendal neuralgia, femoral neuropathy, meralgia paresthesia, saphenous neuropathy, sciatica, peroneal neuropathy, tibial neuropathy, lumbosacral plexopathy, traumatic neuroma stump pain, or post-amputation pain in a subject, the method comprising administering an effective amount of a compound of the invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0741] Compounds, pharmaceutically acceptable salts, and compositions for use

[0742] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use as a medicament.

[0743] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of inhibiting a voltage-gated sodium channel in a subject. In another aspect, the voltage-gated sodium channel is Na V 1.8.

[0744] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postoperative pain (e.g., hernia repair pain, bunionectomy pain, or abdominoplasty pain), visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough, or cardiac arrhythmia in a subject.

[0745] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postoperative pain, hernia repair pain, bunionectomy pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, or cardiac arrhythmia in a subject.

[0746] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of intestinal pain in a subject, wherein the intestinal pain comprises pain from inflammatory bowel disease, Crohn's disease, irritable bowel syndrome, endometriosis, erythro-ovarian disease, salpingitis, cervicitis, or interstitial cystitis.

[0747] On the other hand, the present invention is characterized in that the compound of the present invention or its pharmaceutically acceptable salt or pharmaceutical composition, it is used to treat the neuropathic pain of experimenter or the method for alleviating its severity.In some aspects, neuropathic pain includes postherpetic neuralgia, small fiber neuropathy, diabetic neuropathy or idiopathic small fiber neuropathy.In some aspects, neuropathic pain includes diabetic neuropathy (for example, diabetic peripheral neuropathy).As used herein, phrase " idiopathic small fiber neuropathy " should be understood as including any small fiber neuropathy.

[0748] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of neuropathic pain in a subject, wherein the neuropathic pain comprises post-herpetic neuralgia, diabetic neuropathy, painful HIV-associated sensory neuropathy, trigeminal neuralgia, burning mouth syndrome, post-amputation pain, phantom limb pain, painful neuroma; traumatic neuroma; Morton's neuroma; nerve entrapment injury, spinal stenosis, carpal tunnel syndrome, radicular pain, sciatica; nerve avulsion injury, brachial plexus avulsion injury; complex regional pain syndrome, drug therapy-induced neuralgia, cancer chemotherapy-induced neuralgia, antiretroviral therapy-induced neuralgia, HIV-induced neuralgia; pain after spinal cord injury, spinal stenosis pain, small fiber neuropathy, idiopathic small fiber neuropathy, idiopathic sensory neuropathy, or trigeminal autonomic cephalus.

[0749] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of musculoskeletal pain in a subject. In some aspects, musculoskeletal pain includes osteoarthritis pain.

[0750] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of musculoskeletal pain in a subject, wherein the musculoskeletal pain includes osteoarthritis pain, back pain, cold pain, burn pain, or toothache.

[0751] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of inflammatory pain in a subject, wherein the inflammatory pain comprises rheumatoid arthritis pain, ankylosing spondylitis, or vulvodynia.

[0752] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of inflammatory pain in a subject, wherein the inflammatory pain includes rheumatoid arthritis pain.

[0753] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of idiopathic pain in a subject, wherein the idiopathic pain includes fibromyalgia.

[0754] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of idiopathic pain in a subject, wherein the idiopathic pain includes reflex sympathetic dystrophy pain.

[0755] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of pathological cough in a subject.

[0756] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or reducing the severity of acute pain in a subject. In some aspects, acute pain includes acute postoperative pain.

[0757] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of postoperative pain (e.g., joint replacement pain, soft tissue surgery pain, post-thoracotomy pain, post-mastectomy pain, hemorrhoidectomy pain, hernia repair pain, bunionectomy pain, or abdominoplasty pain) in a subject.

[0758] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of bunionectomy pain in a subject.

[0759] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of shoulder replacement pain or shoulder arthroscopic pain in a subject.

[0760] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of herniorrhaphy pain in a subject.

[0761] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or lessening the severity of abdominoplasty pain in a subject.

[0762] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or reducing the severity of visceral pain in a subject. In some aspects, the visceral pain includes visceral pain caused by abdominoplasty.

[0763] In another aspect, the present invention features a compound of the present invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in treating a neurodegenerative disease in a subject or a method of alleviating its severity. In some aspects, the neurodegenerative disease comprises multiple sclerosis. In some aspects, the neurodegenerative disease comprises Pitt-Hopkins syndrome (PTHS).

[0764] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method wherein a subject is treated with one or more additional therapeutic agents that are administered concurrently with, prior to, or after treatment with an effective amount of the compound, pharmaceutically acceptable salt, or pharmaceutical composition. In some embodiments, the additional therapeutic agent is a sodium channel inhibitor.

[0765] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of inhibiting a voltage-gated sodium channel in a biological sample, the method comprising contacting the biological sample with an effective amount of a compound of the invention, a pharmaceutically acceptable salt or pharmaceutical composition thereof. In another aspect, the voltage-gated sodium channel is Na V 1.8.

[0766] In another aspect, the invention features a compound of the invention or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof for use in treating acute pain, subacute and chronic pain, nociceptive pain, neuropathic pain, inflammatory pain, nociceptive plasticity pain, arthritis, migraine, cluster headache, tension headache and all other forms of headache, trigeminal neuralgia, herpetic neuralgia, general neuralgia, epilepsy, epileptic conditions, neurodegenerative disorders, psychiatric disorders, anxiety, depression, bipolar disorder, myotonia, arrhythmia, movement disorders, neuroendocrine disorders, ataxia, polymyalgia, dyskinesia ... Central neuropathic pain in sclerosis and irritable bowel syndrome, incontinence, pathological cough, visceral pain, osteoarthritis pain, postherpetic neuralgia, diabetic neuropathy, radicular pain, sciatica, back pain, nonspecific chronic back pain, headache, neck pain, moderate pain, severe pain, intractable pain, nociceptive pain, breakthrough pain, postoperative pain (e.g., joint replacement pain, soft tissue surgery pain, post-thoracotomy pain, post-mastectomy pain, hernia repair pain, bunionectomy pain, or abdominoplasty pain), cancer pain (including chronic cancer pain and breakthrough cancer pain) ), stroke (e.g., post-stroke central neuropathic pain), whiplash-related disorders, fragility fractures, vertebral fractures, ankylosing spondylitis, pemphigus, Raynaud's disease, scleroderma, systemic lupus erythematosus, epidermolysis bullosa, gout, juvenile idiopathic arthritis, ceroid bone disease, polymyalgia rheumatica, pyoderma gangrenosum, chronic widespread pain, diffuse idiopathic skeletal hyperostosis, disc degeneration / herniation pain, radiculopathy, facet joint syndrome, failed back surgery syndrome, burns, carpal tunnel syndrome, Paget's disease pain, spinal stenosis, spondylitis, transverse myelitis, Ehlers- Danlos syndrome, Fabry disease, mastocytosis, neurofibromatosis, ocular neuropathic pain, sarcoidosis, spondylolisthesis, spondylolisthesis, chemotherapy-induced oral mucositis, Charcot neuropathic osteoarthropathy, temporomandibular joint disorder, painful arthroplasty, non-cardiac chest pain, pudendal neuralgia, renal colic, biliary tract disease, vascular leg ulcers, Parkinson's disease pain, Alzheimer's disease pain, cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, stress-induced angina, exercise-induced angina, palpitations, hypertension, or gastrointestinal dysmotility, or methods of reducing the severity thereof.

[0767] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for use in treating femoral cancer pain; non-malignant chronic bone pain; rheumatoid arthritis; osteoarthritis; spinal stenosis; neuropathic low back pain; myofascial pain syndrome; fibromyalgia; temporomandibular joint pain; chronic visceral pain; abdominal pain; pancreatic pain; IBS pain; chronic and acute headaches; migraines; tension headaches; cluster headaches; chronic and acute neuropathic pain; postherpetic neuralgia; diabetic neuropathy; HIV-associated neuropathy; trigeminal pain; and Geminid neuralgia; Charcot-Marie-Tooth neuropathy; hereditary sensory neuropathy; peripheral nerve injury; painful neuroma; ectopic proximal and distal discharges; radiculopathy; chemotherapy-induced neuropathic pain; radiation therapy-induced neuropathic pain; persistent / chronic postoperative pain (e.g., post-amputation, post-thoracotomy, post-cardiac surgery); post-mastectomy pain; central pain; spinal cord injury pain; post-stroke pain; thalamic pain; phantom limb pain (e.g., post-leg, upper limb, breast amputation); refractory pain; acute pain, acute postoperative pain; acute musculoskeletal pain Pain; joint pain; mechanical low back pain; neck pain; tendonitis; injury pain; exercise pain; acute visceral pain; pyelonephritis; appendicitis; cholecystitis; intestinal obstruction; hernia; chest pain, heart pain; pelvic pain, renal colic, acute labor pain, labor pain; cesarean section pain; acute inflammatory pain, burn pain, trauma pain; acute intermittent pain, endometriosis; acute herpes zoster pain; sickle cell anemia; acute pancreatitis; breakthrough pain; oral and facial pain; sinusitis pain; toothache; multiple sclerosis (MS) pain; depression pain; leprosy pain; Pain in Hecht's disease; adiposity dolorosa; pain in phlebitis; pain in Guillain-Barré syndrome; pain in the legs and moving toes; Hägglund's syndrome; erythromelalgia; pain in Fabry's disease; bladder and genitourinary disorders; urinary incontinence; pathological cough; overactive bladder; painful bladder syndrome; interstitial cystitis (IC); prostatitis, complex regional pain syndrome (CRPS) type I, complex regional pain syndrome (CRPS) type II; widespread pain, paroxysmal severe pain, pruritus, tinnitus, or angina-induced pain or a method of reducing its severity.

[0768] In another aspect, the invention features a compound of the invention, or a pharmaceutically acceptable salt or pharmaceutical composition thereof, for use in a method of treating or reducing the severity of trigeminal neuralgia, botulinum toxin-treated migraine, cervical radiculopathy, occipital neuralgia, axillary neuropathy, radial neuropathy, ulnar neuropathy, brachial plexopathy, thoracic radiculopathy, intercostal neuralgia, lumbosacral radiculopathy, ilioglossal neuralgia, pudendal neuralgia, femoral neuropathy, meralgia paresthesia, saphenous neuropathy, sciatica, peroneal neuropathy, tibial neuropathy, lumbosacral plexopathy, traumatic neuroma stump pain, or post-amputation pain in a subject.

[0769] Preparation of drugs

[0770] In another aspect, the present invention provides use of the compound of the present invention or a pharmaceutically acceptable salt or pharmaceutical composition thereof for preparing a medicament.

[0771] In another aspect, the present invention provides a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in the preparation of a medicament for inhibiting voltage-gated sodium channels. In another aspect, the voltage-gated sodium channel is Na V 1.8.

[0772] In another aspect, the present invention provides the use of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating chronic pain, intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postoperative pain (e.g., hernia repair pain, bunionectomy pain, or abdominoplasty pain), visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough, or arrhythmia in a subject, or for reducing the severity thereof.

[0773] In another aspect, the present invention provides the use of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament 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, hernia repair pain, bunionectomy pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, or arrhythmia in a subject.

[0774] In another aspect, the present invention provides the use of a compound, pharmaceutically acceptable salt or pharmaceutical composition described herein for preparing a medicament for treating intestinal pain in a subject or reducing its severity, wherein intestinal pain includes pain caused by inflammatory bowel disease, Crohn's disease, irritable bowel syndrome, endometriosis, erythroblastic ovarian disease, salpingitis, cervicitis or interstitial cystitis.

[0775] On the other hand, the present invention provides compound of the present invention, its pharmaceutically acceptable salt or its pharmaceutical composition, it is used for the preparation of the neuropathic pain for treating experimenter or the medicine for alleviating its severity.In some respects, neuropathic pain includes postherpetic neuralgia, small fiber neuropathy, diabetic neuropathy or idiopathic small fiber neuropathy.In some respects, neuropathic pain includes diabetic neuropathy (for example, diabetic peripheral neuropathy).

[0776] In another aspect, the present invention provides a use of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating neuropathic pain in a subject or alleviating its severity, wherein the neuropathic pain includes post-herpetic neuralgia, diabetic neuropathy, painful HIV-associated sensory neuropathy, trigeminal neuralgia, burning mouth syndrome, post-amputation pain, phantom limb pain, painful neuroma; traumatic neuroma; Morton's neuroma; nerve entrapment injury, spinal stenosis, carpal tunnel syndrome, radicular pain, sciatica; nerve avulsion injury, brachial plexus avulsion injury; complex regional pain syndrome, drug therapy-induced neuralgia, cancer chemotherapy-induced neuralgia, antiretroviral therapy-induced neuralgia, HIV-induced neuralgia; pain after spinal cord injury, spinal stenosis pain, small fiber neuropathy, idiopathic small fiber neuropathy, idiopathic sensory neuropathy, or trigeminal autonomic neuropathy.

[0777] In another aspect, the present invention provides a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in the preparation of a medicament for treating musculoskeletal pain in a subject or reducing its severity. In some aspects, musculoskeletal pain includes osteoarthritis pain.

[0778] In another aspect, the present invention provides the use of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating musculoskeletal pain in a subject or alleviating its severity, wherein the musculoskeletal pain includes osteoarthritis pain, back pain, cold pain, burn pain, or toothache.

[0779] In another aspect, the present invention provides the use of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating inflammatory pain in a subject or alleviating its severity, wherein the inflammatory pain includes rheumatoid arthritis pain, ankylosing spondylitis, or vulvodynia.

[0780] In another aspect, the present invention provides use of the compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating inflammatory pain in a subject or alleviating its severity, wherein inflammatory pain includes rheumatoid arthritis pain.

[0781] In another aspect, the present invention provides use of the compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating idiopathic pain in a subject or alleviating its severity, wherein idiopathic pain includes fibromyalgia.

[0782] In another aspect, the present invention provides use of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating idiopathic pain in a subject or alleviating its severity, wherein idiopathic pain includes reflex sympathetic dystrophy pain.

[0783] In another aspect, the present invention provides use of the compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating pathological cough in a subject or alleviating its severity.

[0784] In another aspect, the present invention provides a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in the preparation of a medicament for treating acute pain in a subject or alleviating the severity thereof. In some aspects, acute pain includes acute postoperative pain.

[0785] In another aspect, the present invention provides the use of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating postoperative pain (e.g., joint replacement pain, soft tissue surgery pain, post-thoracotomy pain, post-mastectomy pain, hemorrhoidectomy pain, hernia repair pain, bunionectomy pain, or abdominoplasty pain) in a subject or reducing its severity.

[0786] In another aspect, the present invention provides use of the compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating or alleviating the severity of herniorrhaphy pain in a subject.

[0787] In yet another aspect, the present invention provides use of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating or reducing the severity of bunionectomy pain in a subject.

[0788] In another aspect, the present invention provides use of the compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating shoulder replacement pain or shoulder arthroscopic pain in a subject or reducing its severity.

[0789] In another aspect, the present invention provides use of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating or alleviating the severity of abdominoplasty pain in a subject.

[0790] In another aspect, the present invention provides a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in the preparation of a medicament for treating visceral pain in a subject or alleviating its severity. In some aspects, visceral pain includes visceral pain caused by abdominoplasty.

[0791] In another aspect, the present invention is characterized in that the compound of the present invention or its pharmaceutically acceptable salt or pharmaceutical composition is used to prepare a medicament for treating a neurodegenerative disease in a subject or reducing its severity. In some aspects, the neurodegenerative disease comprises multiple sclerosis. In some aspects, the neurodegenerative disease comprises Pitt-Hopkins syndrome (PTHS).

[0792] In another aspect, the present invention provides the use of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for the preparation of a medicament for use in combination with one or more additional therapeutic agents, the one or more additional therapeutic agents being administered concurrently with, prior to, or after treatment with the compound or pharmaceutical composition. In some embodiments, the additional therapeutic agent is a sodium channel inhibitor.

[0793] In another aspect, the present invention provides a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in the preparation of a preparation for treating acute pain, subacute and chronic pain, nociceptive pain, neuropathic pain, inflammatory pain, nociceptive plasticity pain, arthritis, migraine, cluster headache, tension headache and all other forms of headache, trigeminal neuralgia, herpetic neuralgia, general neuralgia, epilepsy, epileptic conditions, neurodegenerative disorders, psychiatric disorders, anxiety, depression, bipolar disorder, myotonia, arrhythmia, movement disorders, neuroendocrine disorders, ataxia, multiple sclerosis Central neuropathic pain of irritable bowel syndrome, incontinence, pathological cough, visceral pain, osteoarthritis pain, postherpetic neuralgia, diabetic neuropathy, radicular pain, sciatica, back pain, nonspecific chronic back pain, headache, neck pain, moderate pain, severe pain, intractable pain, nociceptive pain, breakthrough pain, postoperative pain (e.g., joint replacement pain, soft tissue surgery pain, post-thoracotomy pain, post-mastectomy pain, hernia repair pain, bunionectomy pain, or abdominoplasty pain), cancer pain (including chronic cancer pain and breakthrough cancer pain), Stroke (e.g., central neuropathic pain after stroke), whiplash-related disorders, fragility fractures, vertebral fractures, ankylosing spondylitis, pemphigus, Raynaud's disease, scleroderma, systemic lupus erythematosus, epidermolysis bullosa, gout, juvenile idiopathic arthritis, oleaginous bone disease, polymyalgia rheumatica, pyoderma gangrenosum, chronic widespread pain, diffuse idiopathic skeletal hyperostosis, disc degeneration / herniation pain, radiculopathy, facet joint syndrome, failed back surgery syndrome, burns, carpal tunnel syndrome, Paget's disease pain, spinal stenosis, spondylitis, transverse myelitis, Ehlers-Danlos syndrome, Fabry disease, mastocytosis, neurofibromatosis, ocular neuropathic pain, sarcoidosis, spondylolisthesis, spondylolisthesis, chemotherapy-induced oral mucositis, Charcot neuropathic osteoarthropathy, temporomandibular joint disorder, painful arthroplasty, non-cardiac chest pain, pudendal neuralgia, renal colic, biliary tract disease, vascular leg ulcers, Parkinson's disease pain, Alzheimer's disease pain, cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, stress-induced angina, exercise-induced angina, palpitations, hypertension, or gastrointestinal dysmotility, or the use of drugs to reduce their severity.

[0794] In another aspect, the present invention provides a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for use in the preparation of a pharmaceutical composition for treating femoral cancer pain; non-malignant chronic bone pain; rheumatoid arthritis; osteoarthritis; spinal stenosis; neuropathic low back pain; myofascial pain syndrome; fibromyalgia; temporomandibular joint pain; chronic visceral pain; abdominal pain; pancreatic pain; IBS pain; chronic and acute headaches; migraines; tension headaches; cluster headaches; chronic and acute neuropathic pain; postherpetic neuralgia; diabetic neuropathy; HIV-associated neuropathy; trigeminal neuralgia; Charcot-Marie-Tooth neuropathy; hereditary sensory neuropathy; peripheral nerve injury; painful neuromas; ectopic proximal and distal discharges; radiculopathy; chemotherapy-induced neuropathic pain; radiation-induced neuropathic pain; persistent / chronic postoperative pain (e.g., post-amputation, post-thoracotomy, post-cardiac surgery), post-mastectomy pain; central pain; spinal cord injury pain; post-stroke pain; thalamic pain; phantom limb pain (e.g., post-leg, upper limb, breast amputation); refractory pain; acute pain; acute postoperative pain; acute musculoskeletal pain; Joint pain; mechanical low back pain; neck pain; tendonitis; pain from injury; pain from exercise; acute visceral pain; pyelonephritis; appendicitis; cholecystitis; intestinal obstruction; hernia; chest pain; cardiac pain; pelvic pain; renal colic; acute labor pain; labor pain; cesarean section pain; acute inflammatory pain; burn pain; trauma pain; acute intermittent pain; endometriosis; acute herpes zoster pain; sickle cell anemia; acute pancreatitis; breakthrough pain; oral and facial pain; sinusitis pain; toothache; multiple sclerosis (MS) pain; depression pain; leprosy pain; Behçet Pain in Guillain-Barré syndrome; adiposity dolorosa; phlebitis pain; Guillain-Barré syndrome pain; pain in the legs and moving toes; Hägglund syndrome; erythromelalgia; Fabry disease pain; bladder and genitourinary disorders; urinary incontinence; pathological cough; overactive bladder; painful bladder syndrome; interstitial cystitis (IC); prostatitis; complex regional pain syndrome (CRPS) type I, complex regional pain syndrome (CRPS) type II; use of drugs for widespread pain, paroxysmal severe pain, itching, tinnitus, or angina-induced pain or to reduce the severity of the same.

[0795] In another aspect, the present invention provides the use of a compound of the present invention, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for preparing a medicament for treating trigeminal neuralgia, migraine treated with botulinum toxin, cervical radiculopathy, occipital neuralgia, axillary neuropathy, radial neuropathy, ulnar neuropathy, brachial plexopathy, thoracic radiculopathy, intercostal neuralgia, lumbosacral radiculopathy, ilioglossal neuralgia, pudendal neuralgia, femoral neuropathy, paresthesia meralgia, saphenous neuropathy, sciatica, peroneal neuropathy, tibial neuropathy, lumbosacral plexopathy, traumatic neuroma stump pain, or post-amputation pain, or for alleviating the severity thereof.

[0796] Administration of compounds, pharmaceutically acceptable salts, and compositions

[0797] In certain embodiments of the present invention, an "effective amount" of the compound of the present invention, its pharmaceutically acceptable salt, or pharmaceutical composition thereof is an amount effective to treat one or more of the above-mentioned conditions or to lessen their severity.

[0798] According to the method of the present invention, the compound, the salt and the composition can be administered using any amount and any route of administration that effectively treats one or more of the pain or non-painful diseases described herein or alleviates the severity thereof. The precise amount required will vary from subject to subject, depending on the species, age and general condition of the subject, the severity of the condition, the specific agent, the mode of administration of the agent, etc. The compound, salt and composition of the present invention are preferably formulated in dosage unit form for ease of administration and dosage uniformity. As used herein, the expression "dosage unit form" refers to a physically discrete dosage unit suitable for the subject to be treated. However, it should be understood that the total daily dose of the compound, salt and composition of the present invention will be determined by the attending physician within the scope of reasonable medical judgment. The specific effective dosage level for any particular subject or organism will depend on a variety of factors, including the condition being treated and the severity of the condition; the activity of the specific compound or salt employed; the specific composition employed; the age, weight, general health, sex, and diet of the subject; the time of administration, route of administration, and excretion rate of the specific compound or salt employed; the duration of treatment; drugs used in combination or concomitantly with the specific compound or salt employed, and similar factors well known in the medical arts. As used herein, the term "subject" or "patient" means an animal, preferably a mammal, and most preferably a human.

[0799] The pharmaceutically acceptable compositions of the present invention can be administered to humans and other animals orally, rectally, parenterally, intracisternal, intravaginal, intraperitoneal, topically (e.g., by powder, ointment, or drops), buccally, in the form of an oral spray or nasal spray, etc., depending on the severity of the condition being treated. In certain embodiments, the compounds, salts, and compositions of the present invention can be administered orally or parenterally once or more a day at a dosage level of about 0.001 mg / kg to about 1000 mg / kg effective to achieve the desired therapeutic effect.

[0800] Liquid dosage forms for oral administration include but are not limited to pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to active compound or salt, liquid dosage forms can contain inert diluents commonly used in the art, such as water or other solvents, solubilizing agents and emulsifiers, such as ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oil (particularly, cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol and fatty acid esters of sorbitan and mixtures thereof. In addition to inert diluents, oral compositions can also include adjuvants, such as wetting agents, emulsifiers and suspending agents, sweeteners, flavorings and fragrances.

[0801] Injectable preparations (e.g., sterile injectable aqueous or oily suspensions) can be formulated according to known techniques using suitable dispersants or wetting agents and suspending agents. Sterile injectable preparations can also be sterile injectable solutions, suspensions or emulsions in parenteral acceptable non-toxic diluents or solvents, such as solutions in 1,3-butanediol. Acceptable vehicles and solvents that can be employed include water, Ringer's solution, USP, and isotonic sodium chloride solution. Additionally, sterile fixed oils are conventionally used as solvents or suspending media. For this purpose, any gentle fixed oil can be employed, including synthetic monoglycerides or diglycerides. Additionally, injectables are prepared using fatty acids such as oleic acid.

[0802] The injectable formulations can be sterilized, for example, by filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium just prior to use.

[0803] In order to prolong the effect of the compound of the present invention, it is generally desired to slow down the absorption of the compound from subcutaneous or intramuscular injection. This can be achieved by using a liquid suspension of a crystalline or amorphous material with poor water solubility. Thus, the absorption rate of the compound depends on its dissolution rate, and the dissolution rate can then depend on the crystal size and crystal form. Alternatively, delayed absorption of the compound form administered parenterally can be achieved by dissolving or suspending the compound in an oily vehicle. Injectable reservoir forms are prepared by forming a microcapsule matrix of the compound in a biodegradable polymer (such as polylactide-polyglycolide). Depending on the ratio of the compound to the polymer and the properties of the specific polymer used, the compound release rate can be controlled. Examples of other biodegradable...

Claims

1. A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein: X is CR 5b or N; R 2a and R 3a The following definition: (i)R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl)2, or -N(C1-C6 haloalkyl)2; and R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2)、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2)、-CH2CH2NHC(O)CH(CH3)(NH2)、-NHC(O)CH(CH3)(NH2)、-C(O)NHC(O)(C1-C6 alkyl)、-NHS(O)2CH3、-S(C1-C6 alkyl)、C3-C7 cycloalkyl、C6-C 10 aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; or (ii) R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(N(C1-C6 alkyl))R' or -S(O)2NCH3R'; and R 2a and R' together with the atoms to which they are attached join together to form a 4-7 membered heterocyclic group; R 5a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -C(O)O(C1-C6 haloalkyl), or 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'replace; Each R a ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl); R 2b , R 3b and R 4b The following definition: (i)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -OCH2CH2OH, -OCH2CH2OCH3, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens; or (ii) R 2b and R 3b Together with the carbon atoms to which they are attached they form a ring having the formula: and R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl is optionally substituted with one or more halogens; or (iii) R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula: R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 6b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R n is H or C1-C6 alkyl, The conditions are: (i) If X is N, then R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula: and (ii) If R 2a is H, then R 3a is halogenated, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and (iii) If R 3a is -C(O)O(C1-C2 alkyl), then R 4b is H, fluorine, chlorine, C1-C6 alkyl, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (iv) R 2b , R 3b , R 4b , R 5b and R 6b No more than four of them are H; and (v)R 2b , R 3b , R 4b , R 5b and R 6b no more than one of them is fluorine; and (vi)R 2b , R 3b , R 4b , R 5b and R 6b not more than one of them is chlorine; and (vii) If R 2b , R 3b , R 4b , R 5b and R 6b If any one of is halogenated, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (viii) If R 2b or R 6b is -OCH3, and R 3a is H, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (ix) If R 3b is fluorine, then R 6b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (x) If R 5b is fluorine, then R 2b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (xi) If R 3b or R 5b is -CH3, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (xii) If R 3b or R 5b is a C1 haloalkyl group, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (xiii) If R3 b or R 5b is -OCH3, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (xiv) If R 4b is a C1 haloalkyl group, then R 2b , R 3b , R 5b and R 6b No more than three of them are H; and (xv) If R 4b is -OCH3, then R 2b , R 3b , R 5b and R 6b No more than three of them are H; and (xvi) If R 4b is a C1 haloalkoxy group, then R 2b , R 3b , R 5b and R 6b No more than three of them are H; and (xvii) If R 4b is chlorine or bromine, then R 2b and R 6b Each is independently H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (xviii) If R 4b and R 3b Each is -OCH3, then R 2b , R 5b and R 6b No more than two of them are H; and (xix) If R 4b and R 5b Each is -OCH3, then R 2b , R 3b and R 6b The number of H is no more than two.

2. The compound according to claim 1, wherein: R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and R 5a It is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl).

3. The compound according to claim 1 or 2, wherein X is N.

4. The compound according to claim 1 or 2, wherein X is CR 5b , and R 5b It is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or -C(O)(C1-C6 alkyl).

5. The compound according to claim 4, wherein R 5b It is H, F, Cl, -CH3, -C(CH3)3, -CF3, -OCH3 or -C(O)CH3.

6. A compound according to any one of claims 1 to 5, wherein R 2a It is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or -N(C1-C6 alkyl)2.

7. The compound according to claim 6, wherein R 2a It is H, -CH3, -CF3, -OCH3 or -N(CH3)2.

8. A compound according to any one of claims 1 to 7, wherein R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl) 1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2), -C(O)NHC(O)CH3, -NHS(O)2CH3, -S(C1-C6 alkyl), C3-C7 cycloalkyl, C6-C 10 aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'replace; and Each R a ' is independently F, Cl, -CN, -OH, oxo, -CH3, -CH2CH3, -CH(CH3)2, -CHF2, -CF3, -OCH3, -CH2OCH3, -C(O)NH2, -C(O)OH, -S(O)2CH3, cyclopropyl, azetidinyl or 1-methylazetidinyl.

9. The compound according to claim 8, wherein R 3a It is H, Cl, Br, -CN, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH), -C(CH3)2(OH), -CH2NH2, - C(O)CH3, -C(O)NH2, -C(O)OCH2CH3, -S(O)2-(CH3), -S(O)2CH(CH3)2, -S(O)(NH)(CH3), -S(O)(NH)CH(CH3)2 、-CH2C(O)NH2、-CH2C(O)NH(CH3)、-NHC(O)CH3、-CH2NHC(O)CH(CH3)(NH2)、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2)、-CH2CH2NHC(O)CH(CH3)(NH2)、-NHC(O)CH(CH3)(NH2)、-NHC(O)CH(CH3)(NH2)、-C(O)NHC(O)CH3、-NHS(O)2CH3、-SCH3、cyclopropyl, phenyl, 10. A compound according to any one of claims 1 to 7, wherein R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 alkoxy, -NH2, -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-NH2, -C(O)(C1-C6 alkyl), -C(O)NH2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2.

11. The compound according to claim 10, wherein R 3a is H, Cl, -CN, -CH3, -CH(CH3)2, -OCH3, -NH2, -N(CH3)2, -CH2OH, -CH(CH3)(OH), -C(CH3 )2(OH), -CH2NH2, -C(O)CH3, -C(O)NH2, -C(O)OCH2CH3, -S(O)2-(CH3), -S(O)(NH)(CH 3), -CH2C(O)NH2, -CH2C(O)NH(CH3), -NHC(O)CH3, -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2) or -NHC(O)CH(CH3)(NH2).

12. A compound according to any one of claims 1 to 11, wherein R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(NCH3)R' or -S(O)2NCH3R'; and R 2a and R' together with the atoms to which they are attached join together to form a 6-membered heterocyclic group.

13. A compound according to any one of claims 1 to 12, wherein R 5a is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -C(O)O(C1-C6 alkyl), 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'replace; and R a ' is -CH3, -CHF2 or -CH2OCH3.

14. The compound according to claim 13, wherein R 5a It is H, Br, -CH3, -OCH3, -OCH2CH3, -CH2OH, -CH2OCH3, -C(O)OCH2CH3, 15. A compound according to any one of claims 1 to 12, wherein R 5a It is H, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -CH2O(C1-C6 alkyl) or -C(O)O(C1-C6 alkyl).

16. The compound according to claim 15, wherein R 5a It is H, -CH3, -OCH3, -OCH2CH3, -CH2OH, -CH2OCH3 or -C(O)OCH2CH3.

17. A compound according to any one of claims 1 to 16, wherein R 2b It is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -OCH2CH2OH or -OCH2CH2OCH3.

18. The compound according to claim 17, wherein R 2b It is H, F, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -OCH3, -OCH2CH3, -OH, -CH2OH, -OCH2CH2OH or -OCH2CH2OCH3.

19. A compound according to any one of claims 1 to 18, wherein R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy.

20. The compound according to claim 19, wherein R 3b It is H, F, Cl, -CH3, -C(CH3)3, -CF3, -OCH3, -OCH2CH3 or -OC(CH3)3.

21. A compound according to any one of claims 1 to 20, wherein R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, or The cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

22. The compound according to claim 21, wherein R 4b is H, F, Cl, -CH3, -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -CF3, -C(CH3)2(CF3), -OCH3, -OCH(CH3)2, -OC(CH3)3, -OCF3, cyclopropyl, 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl, 3,3-difluoro-1-methylcyclobutyl or 23. A compound according to any one of claims 1 to 14, wherein R 2b and R 3b Together with the carbon atoms to which they are attached they form a ring having the formula:

24. The compound according to claim 23, wherein R 4b For H.

25. A compound according to any one of claims 1 to 14, wherein R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula:

26. The compound according to claim 25, wherein R n It is a C1-C6 alkyl group.

27. The compound according to claim 26, wherein R n It is -CH3.

28. A compound according to any one of claims 25 to 27, wherein R 2b For H.

29. A compound according to any one of claims 1 to 28, wherein R 6b is H, halo, C1-C6 alkyl or C1-C6 alkoxy.

30. The compound according to claim 29, wherein R 6b It is H, Cl, -CH3 or -OCH3.

31. A compound of formula (IA-1): or a pharmaceutically acceptable salt thereof, wherein: X is CR 5b or N; R 2a and R 3a The following definition: (i)R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl)2, or -N(C1-C6 haloalkyl)2; and R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2)、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2)、-CH2CH2NHC(O)CH(CH3)(NH2) or -NHC(O)CH(CH3)(NH2)、-C(O)NHC(O)(C1-C6 alkyl)、-NHS(O)2CH3、-S(C1-C6 alkyl)、C3-C7 cycloalkyl、C6-C 10 aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl and S, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; or (ii) R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(N(C1-C6 alkyl))R' or -S(O)2NCH3R'; and R 2a and R' together with the atoms to which they are attached join together to form a 4-7 membered heterocyclic group; R 5a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -C(O)O(C1-C6 haloalkyl) or 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'replace; Each R a ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl); R 2b , R 3b and R 4b The following definition: (i)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or (ii) R 2b and R 3b Together with the carbon atoms to which they are attached they form a ring having the formula: and R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or (iii) R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula: R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 6b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R n is H or C1-C6 alkyl, The conditions are: (i) If X is N, then R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula: and (ii) If R 2a is H, then R 3a is halogenated, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2); and (iii) If R 3a is -C(O)O(C1-C2 alkyl), then R 4b is H, fluorine, chlorine, C1-C6 alkyl, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (iv) R 2b , R 3b , R 4b , R 5b and R 6b No more than four of them are H; and (v)R 2b , R 3b , R 4b , R 5b and R 6b no more than one of them is fluorine; and (vi)R 2b , R 3b , R 4b , R 5b and R 6b not more than one of them is chlorine; and (vii) If R 2b , R 3b , R 4b , R 5b and R 6b If any one of is halogenated, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (viii) If R 2b or R 6b is -OCH3, and R 3a is H, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (ix) If R 3b is fluorine, then R 6b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (x) If R 5b is fluorine, then R 2b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (xi) If R 3b or R 5b is -CH3, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (xii) If R 3b or R 5b is a C1 haloalkyl group, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (xiii) If R3 b or R 5b is -OCH3, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (xiv) If R 4b is a C1 haloalkyl group, then R 2b , R 3b , R 5b and R 6b No more than three of them are H; and (xv) If R 4b is -OCH3, then R 2b , R 3b , R 5b and R 6b No more than three of them are H; and (xvi) If R 4b is a C1 haloalkoxy group, then R 2b , R 3b , R 5b and R 6b No more than three of them are H; and (xvii) If R 4b is chlorine or bromine, then R 2b and R 6b Each is independently H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (xviii) If R 4b and R 3b Each is -OCH3, then R 2b , R 5b and R 6b No more than two of them are H; and (xix) If R 4b and R 5b Each is -OCH3, then R 2b , R 3b and R 6b The number of H is no more than two.

32. The compound according to claim 31, wherein: R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and R 5a It is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl).

33. The compound according to claim 31 or 32, wherein: X is CR 5b , and R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or -C(O)(C1-C6 alkyl); R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH or -CH2OH; and R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

34. A compound of formula (IA-2): or a pharmaceutically acceptable salt thereof, wherein: X is CR 5b or N; R 2a is H, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl); R 2b , R 3b and R 4b The following definition: (i)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 4b C2-C6 alkyl, C2-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or (ii) R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula: R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 6b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; The conditions are: (i) If X is N, then R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula: and (ii) If R 2a is H, then R 3a is halogenated, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and (iii) R 2b , R 3b , R 5b and R 6b Not more than one of them is chlorine.

35. The compound according to claim 34, wherein: X is CR 5b , and R 5b is H, halo, C1-C6 alkyl or C1-C6 haloalkyl; R 2b is H, halo, C1-C6 alkyl or C1-C6 alkoxy; and R 4b It is C2-C6 alkyl, C2-C6 haloalkyl, C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

36. The compound according to claim 35, wherein: R 5b is H, F, Cl, -CH3 or -CF3; R 2b is H, F, -CH3, -CH(CH3)2 or -OCH3; R 4b It is -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -C(CH3)2(CF3), 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl or 3,3-difluoro-1-methylcyclobutyl.

37. A compound of formula (IB-1): or a pharmaceutically acceptable salt thereof, wherein: X is CR 5b or N; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2)、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2)、-CH2CH2NHC(O)CH(CH3)(NH2)、-NHC(O)CH(CH3)(NH2)、-C(O)NHC(O)(C1-C6 alkyl)、-NHS(O)2CH3、-S(C1-C6 alkyl)、C3-C7 cycloalkyl、C6-C 10 aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'replace; R 5a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -C(O)O(C1-C6 haloalkyl) or 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'replace; Each R a ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl); R 2b , R 3b and R 4b The following definition: (i)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or (ii) R 2b and R 3b Together with the carbon atoms to which they are attached they form a ring having the formula: and R 4b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or (iii) R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula: R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 6b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R n is H or C1-C6 alkyl, The conditions are: (i) If X is N, then R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula: and (ii) If R 3a is -C(O)O(C1-C2 alkyl), then R 4b is H, fluorine, chlorine, C1-C6 alkyl, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (iii) R 2b , R 3b , R 4b , R 5b and R 6b No more than four of them are H; and (iv) R 2b , R 3b , R 4b , R 5b and R 6b no more than one of them is fluorine; and (v)R 2b , R 3b , R 4b , R 5b and R 6b not more than one of them is chlorine; and (vi) If R 2b , R 3b , R 4b , R 5b and R 6b If any one of is halogenated, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (vii) If R 2b or R 6b is -OCH3, and R 3a is H, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (viii) If R 3b is fluorine, then R 6b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (ix) If R 5b is fluorine, then R 2b is H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (x) If R 3b or R 5b is -CH3, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (xi) If R 3b or R 5b is a C1 haloalkyl group, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (xii) If R3 b or R 5b is -OCH3, then R 2b , R 3b , R 4b , R 5b and R 6b No more than three of them are H; and (xiii) If R 4b is a C1 haloalkyl group, then R 2b , R 3b , R 5b and R 6b No more than three of them are H; and (xiv) If R 4b is -OCH3, then R 2b , R 3b , R 5b and R 6b No more than three of them are H; and (xv) If R 4b is a C1 haloalkoxy group, then R 2b , R 3b , R 5b and R 6b No more than three of them are H; and (xvi) If R 4b is chlorine or bromine, then R 2b and R 6b Each is independently H, halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and (xvii) If R 4b and R 3b Each is -OCH3, then R 2b , R 5b and R 6b No more than two of them are H; and (xviii) If R 4b and R 5b Each is -OCH3, then R 2b , R 3b and R 6b The number of H is no more than two.

38. The compound according to claim 37, wherein: R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and R 5a It is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl).

39. The compound according to claim 37 or 38, wherein R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula:

40. A compound of formula (IB-2): or a pharmaceutically acceptable salt thereof, wherein: X is CR 5b or N; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl); R 2b , R 3b and R 4b The following definition: (i)R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R 3b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 4b C2-C6 alkyl, C2-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or (ii) R 2b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula: R 5b is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 6b is H, halo, C1-C6 alkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens, The conditions are: (i) If X is N, then R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula: and (ii) R 2b , R 3b , R 5b and R 6b Not more than one of them is chlorine.

41. The compound according to claim 40, wherein R 3b and R 4b Together with the carbon atoms to which they are attached they form a ring having the formula:

42. The compound according to claim 40 or 41, wherein R 6b It is H, C1-C6 alkyl or C1-C6 alkoxy.

43. A compound of formula (IC-1): or a pharmaceutically acceptable salt thereof, wherein: R 2a and R 3a The following definition: (i)R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl)2, or -N(C1-C6 haloalkyl)2; and R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2)、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2)、-CH2CH2NHC(O)CH(CH3)(NH2)、-NHC(O)CH(CH3)(NH2)、-C(O)NHC(O)(C1-C6 alkyl)、-NHS(O)2CH3、-S(C1-C6 alkyl)、C3-C7 cycloalkyl、C6-C 10 aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; or (ii) R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(N(C1-C6 alkyl))R' or -S(O)2NCH3R'; and R 2a and R' together with the atoms to which they are attached join together to form a 4-7 membered heterocyclic group; R 5a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -C(O)O(C1-C6 haloalkyl) or 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'replace; Each R a ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl); R 2b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R 4b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 5b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens, The conditions are: (i) If R 2a is H, then R 3a is halogenated, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and (ii) R 2b , R 4b and R 5b Not more than one of them is chlorine.

44. The compound according to claim 43, wherein: R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and R 5a It is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl).

45. The compound according to claim 43 or 44, wherein: R 2b is halogenated, C1-C6 alkyl or C1-C6 alkoxy; R 4b is C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy; and R 5b It is halo, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy.

46. ​​A compound of formula (IC-2): or a pharmaceutically acceptable salt thereof, wherein: R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl); R 2b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R 4b is halo, C2-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 5b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens, The conditions are: (i) If R 2a is H, then R 3a is halogenated, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2; and (ii) R 2b , R 4b and R 5b Not more than one of them is chlorine.

47. The compound according to claim 46, wherein: R 2b is a C1-C6 alkyl group; R 4b is C2-C6 alkyl or C1-C6 haloalkyl; and R 5b It is halogenated, C1-C6 alkyl or C1-C6 halogenated alkyl.

48. The compound according to claim 47, wherein: R 2b is -CH3; R 4b is -C(CH3)3 or -C(CH3)2(CF3); and R 5b It is F, Cl, -CH3 or -CF3.

49. A compound of formula (ID-1): or a pharmaceutically acceptable salt thereof, wherein: R 2a and R 3a The following definition: (i)R 2a is C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl)2, or -N(C1-C6 haloalkyl)2; and R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(C1-C6 alkylene)-OH, -(C1-C6 alkylene)-(C1-C6 alkoxy), -(C1-C6 alkylene)-NH2, -(C1-C6 alkylene)-NH(C1-C6 alkyl), -(C1-C6 alkylene) -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2) or -NHC(O)CH(CH3)(NH2)-C(O)NHC(O)(C1-C6 alkyl), -NHS(O)2CH3, -S(C1-C6 alkyl), C3-C7 cycloalkyl, C6-C 10 aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R a 'Replace; or (ii) R 3a is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(N(C1-C6 alkyl))R' or -S(O)2NCH3R'; and R 2a and R' together with the atoms to which they are attached join together to form a 4-7 membered heterocyclic group; R 5a is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl), or a 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R a 'replace; Each R a ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl); R 2b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 4b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens, The conditions are: (i)R 2b and R 4b not more than one of them is chlorine; and (ii) If R 4b is chlorine or bromine, then R 2b It is halo, C1-C6 alkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

50. The compound according to claim 49, wherein: R 2a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; and R 5a It is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl).

51. The compound according to claim 49 or 50, wherein: R 2b is halo, C1-C6 alkyl, C1-C6 alkoxy or -OH; and R 4b It is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

52. A compound of formula (ID-2): or a pharmaceutically acceptable salt thereof, wherein: R 2a C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), or -NHC(O)CH(CH3)(NH2; R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl); R 2b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 4b It is C2-C6 alkyl, C2-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

53. The compound according to claim 52, wherein: R 2b is C1-C6 alkyl or C1-C6 alkoxy; and R 4b It is C2-C6 alkyl, C2-C6 haloalkyl, C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C4-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

54. The compound according to claim 53, wherein: R 2b is -CH3, -CH(CH3)2 or -OCH3; and R 4b It is -CH(CH3)2, -C(CH3)3, -C(CH3)2(CH2CH3), -C(CH3)2(CF3), 1-trifluoromethylcyclopropyl, 3,3-difluorocyclobutyl or 3,3-difluoro-1-methylcyclobutyl.

55. A compound of formula (IE-1): or a pharmaceutically acceptable salt thereof, wherein: R 2a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2; R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl); and R 4b It is C1-C6 alkyl, C2-C6 haloalkyl, C2-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

56. The compound according to claim 55, wherein R 4b It is C1-C6 alkyl, C2-C6 haloalkyl, C2-C6 alkoxy or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl is optionally substituted by one or more halogens.

57. The compound according to claim 56, wherein R 4b It is -C(CH3)3, -C(CH3)2(CF3), -OC(CH3)3 or 1-trifluoromethylcyclopropyl.

58. A compound of formula (IE-2): or a pharmaceutically acceptable salt thereof, wherein: R 2a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2; R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl); and R 4b It is C1-C6 alkyl, C2-C6 haloalkyl, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

59. The compound according to claim 58, wherein R 4b is C1-C6 alkyl, C2-C6 haloalkyl or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl is optionally substituted with one or more halogens.

60. The compound according to claim 59, wherein R 4b It is -C(CH3)3, -C(CH3)2(CF3) or 1-trifluoromethylcyclopropyl.

61. A compound of formula (IF): or a pharmaceutically acceptable salt thereof, wherein: R 2a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl) or -N(C1-C6 haloalkyl)2; R 3a is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), -CH2NHC(O)CH(CH3)(NH2), -CH2N(CH3)C(O)CH(CH3)(N(CH3)2), -CH2CH2NHC(O)CH(CH3)(NH2), -NHC(O)CH(CH3)(NH2; R 5a is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy; -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl) or -C(O)O(C1-C6 haloalkyl); R 2b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R 3b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R 4b is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 6b It is halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)- or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted by one or more halogens.

62. The compound according to claim 61, wherein: R 2b is halogenated; R 3b is a C1-C6 alkyl group; R 4b is a C1-C6 alkyl group; and R 6b It is a C1-C6 alkyl group.

63. The compound according to claim 62, wherein: R 2b is F; R 3b is -CH3; R 4b is -C(CH3)3; and R 6b It is -CH3.

64. A compound of formula (II): or a pharmaceutically acceptable salt thereof, wherein: Y is CR 3d or N; R 2c is a C1-C6 alkyl group; R 3c is H, halo, C1-C6 alkyl, -S(O)2(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), or 4-10 membered heteroaryl, wherein the heteroaryl is optionally substituted with C1-C6 alkyl; R 3d is halo, C1-C6 alkyl or C1-C6 haloalkyl; R 4d is H, C1-C6 alkyl or C1-C6 haloalkyl; and R 6d It is H, C1-C6 alkyl or C1-C6 alkoxy.

65. The compound according to claim 64, wherein R 3c is H, halo, C1-C6 alkyl or -S(O)(NH)(C1-C6 alkyl).

66. The compound according to claim 64 or 65, wherein Y is CR 3d , and R 3d It is Cl, -CH3 or -CF3.

67. A compound of formula (II-A): or a pharmaceutically acceptable salt thereof, wherein: R 2c is a C1-C6 alkyl group; R 3c is halogenated, C1-C6 alkyl or -S(O)(NH)(C1-C6 alkyl); R 3d is halo, C1-C6 alkyl or C1-C6 haloalkyl; R 4d is H, C1-C6 alkyl or C1-C6 haloalkyl; and R 6d It is H, C1-C6 alkyl or C1-C6 alkoxy.

68. The compound according to claim 67, wherein R 3d It is halogenated or C1-C6 alkyl.

69. The compound according to claim 67 or 68, wherein R 4d It is a C1-C6 alkyl group.

70. A compound of formula (III): or a pharmaceutically acceptable salt thereof, wherein: R 2e is a C1-C6 alkyl group; R 2f is a C1-C6 alkyl group; and R 4f It is a C1-C6 alkyl group.

71. The compound according to claim 70, wherein R 2e It is -CH3.

72. The compound according to claim 70 or 71, wherein R 4f It is -C(CH3)3.

73. A compound of formula (IV): or a pharmaceutically acceptable salt thereof, wherein: R 2g and R 3g The following definition: (i)R 2g is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -N(C1-C6 alkyl)2, -N(C1-C6 alkyl)(C1-C6 haloalkyl)2, or -N(C1-C6 haloalkyl)2; and R 3g is H, halo, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -OH, -NH2, -NH(C1-C6 alkyl), -N(C1-C6 alkyl)2, -(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, -C(O)(C1-C6 alkyl), -C(O)NH 2、 -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2, -C(O)O(C1-C6 alkyl), -S(O)2-(C1-C6 alkyl), -S(O)(NH)(C1-C6 alkyl), -CH2C(O)NH2, -CH2C(O)NH(C1-C6 alkyl), -CH2C(O)N(C1-C6 alkyl)2, -NHC(O)(C1-C6 alkyl), - CH2NHC(O)CH(CH3)(NH2)、-CH2N(CH3)C(O)CH(CH3)(N(CH3)2)、-CH2CH2NHC(O)CH(CH3)(NH2)、-NHC(O)CH(CH3)(NH2)、-C(O)NHC(O)(C1-C6 alkyl)、-NHS(O)2CH3、-S(C1-C6 alkyl)、C3-C7 cycloalkyl、C6-C 10 aryl, 4-10 membered heterocyclyl, 4-10 membered heteroaryl, wherein the heterocyclyl or heteroaryl is optionally substituted by 1-2 R g 'Replace; or (ii) R 3g is -S(O)R', -S(O)2R', -S(O)(NH)R', -S(O)(N(C1-C6 alkyl))R' or -S(O)2NCH3R'; and R 2g and R' together with the atoms to which they are attached join together to form a 4-7 membered heterocyclic group; R 5g is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, -CH2OH, -CH2O(C1-C6 alkyl), -CH2O(C1-C6 haloalkyl), -C(O)O(C1-C6 alkyl), -C(O)O(C1-C6 haloalkyl), or 4-10 membered heteroaryl, wherein the heteroaryl is optionally replaced by R g 'replace; Each R g ' is independently halo, -CN, -OH, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -(C1-C6 alkylene)-(C1-C6 alkoxy), -C(O)NH2, -C(O)OH, -S(O)2(C1-C6 alkyl), C3-C7 cycloalkyl, 4-10 membered heterocyclyl or -(4-10 membered heterocyclyl)-(C1-C6 alkyl); R 2h is H, C1-C6 alkyl, C1-C6 alkoxy, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)-, wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; R 4h and R 5h The following definition: (i)R 4h is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; and R 5h is H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, -OH, -CH2OH, -C(O)(C1-C6 alkyl), -C(O)(C1-C6 haloalkyl), C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or -(C1-C6 haloalkyl)-(C3-C6 cycloalkyl), wherein the cycloalkyl in the C3-C6 cycloalkyl, (C1-C6 alkyl)-(C3-C6 cycloalkyl)-, or (C1-C6 haloalkyl)-(C3-C6 cycloalkyl)- is optionally substituted with one or more halogens; or (ii) R 4h and R 5h Together with the C atoms to which they are attached, they are joined together to form a C5-C6 cycloalkyl group, wherein the cycloalkyl group is optionally substituted by 1-2 C1-C6 alkyl groups.

74. The compound according to claim 73, wherein R 2g It is a C1-C6 alkyl group.

75. The compound according to claim 73 or 74, wherein R 3g is C1-C6 alkyl or 4-10 membered heteroaryl, wherein the heteroaryl is optionally substituted by 1 R g 'replace; and R g ' is -CH3.

76. according to the compound described in any one of claims 73 to 75, wherein R 5g For H.

77. A compound according to any one of claims 73 to 76, wherein R 2h It is a C1-C6 alkyl group.

78. A compound according to any one of claims 73 to 77, wherein R 4h It is a C1-C6 alkyl group.

79. according to the compound described in any one of claims 73 to 78, wherein R 5h It is halogenated or C1-C6 alkyl.

80. A compound selected from Table A or a pharmaceutically acceptable salt thereof.

81. A compound selected from Table D or a pharmaceutically acceptable salt thereof.

82. A compound selected from: 6-[5-Chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-methylsulfonyl-1H-pyridin-4-one; 6-[4-tert-Butyl-2-methyl-5-(trifluoromethyl)phenyl]-2-methyl-3-methylsulfonyl-1H-pyridin-4-one; 6-(4-tert-Butyl-2-fluoro-3,6-dimethyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one; (S)-6-(4-tert-Butyl-2-fluoro-3,6-dimethyl-phenyl)-2-methyl-3-(methylsulfonimide)-1H-pyridin-4-one; (R)-6-(4-tert-Butyl-2-fluoro-3,6-dimethyl-phenyl)-2-methyl-3-(methylsulfonimide)-1H-pyridin-4-one; 6-[5-Chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one; (S)-6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one; (R)-6-[5-chloro-2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one; 6-(6-tert-butyl-5-chloro-2-methyl-3-pyridinyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one; (S)-6-(6-tert-butyl-5-chloro-2-methyl-3-pyridinyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one; (R)-6-(6-tert-butyl-5-chloro-2-methyl-3-pyridinyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one; 6-(4-tert-Butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(methylsulfimidoyl)-1H-pyridin-4-one; (S)-6-(4-tert-Butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(methylsulfonimide)-1H-pyridin-4-one; (R)-6-(4-tert-butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(methylsulfonimide)-1H-pyridin-4-one; (2S)-2-amino-N-[[6-(4-tert-butyl-2-methyl-phenyl)-2-methyl-4-oxo-1H-pyridin-3-yl]methyl]propanamide; 6-(4-tert-Butyl-2,5-dimethyl-phenyl)-2,3-dimethyl-1H-pyridin-4-one; 3-Chloro-2-methyl-6-[2-methyl-4-(2,2,2-trifluoro-1,1-dimethyl-ethyl)phenyl]-1H-pyridin-4-one; 6-(4-tert-Butyl-2,5-dimethyl-phenyl)-2-methyl-4-oxo-1H-pyridine-3-carboxylic acid ethyl ester; 6-[6-(4-tert-Butyl-5-chloro-2-methyl-phenyl)-2-methyl-4-oxo-1H-pyridin-3-yl]pyridine-2-carboxamide; 6-(4-tert-Butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-(1H-pyrazol-4-yl)-1H-pyridin-4-one; 6-(4-tert-Butyl-5-chloro-2-methyl-phenyl)-2-methyl-3-methylsulfonyl-1H-pyridin-4-one; 6-(4-(tert-butyl)-5-chloro-2-methylphenyl)-2-methyl-3-(1-methyl-1H-imidazol-5-yl)pyridin-4(1H)-one; 6-(5-chloro-2-methyl-4-(1,1,1-trifluoro-2-methylpropan-2-yl)phenyl)-2-methyl-3-(1-methyl-1H-pyrazol-4-yl)pyridin-4(1H)-one; and 6-(4-(tert-butyl)-5-chloro-2-methylphenyl)-2-methyl-3-(1H-1,2,4-triazol-1-yl)pyridine -4(1H)-ketone, or a pharmaceutically acceptable salt thereof.

83. A compound according to any one of claims 1 to 82 in non-salt form.

84. A pharmaceutical composition comprising a therapeutically effective amount of: i) a compound according to any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof; or ii) a compound according to claim 83; or iii) a compound selected from Table B or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or vehicles.

85. A pharmaceutical composition comprising: i) a compound according to any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof; or ii) a compound according to claim 83; or iii) a compound selected from Table B or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or vehicles.

86. A method of inhibiting a voltage-gated sodium channel in a subject, the method comprising administering to the subject: i) a compound according to any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof; or ii) a compound according to claim 83; or iii) a compound selected from Table B or a pharmaceutically acceptable salt thereof; or iv) a pharmaceutical composition according to claim 84 or 85; or v) a compound selected from Table C or a pharmaceutically acceptable salt thereof.

87. The method of claim 86, wherein the voltage-gated sodium channel is Na V 1.

8.

88. A method of 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 arrhythmia in a subject, the method comprising administering to the subject an effective amount of: i) a compound according to any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof; or ii) a compound according to claim 83; or iii) a compound selected from Table B or a pharmaceutically acceptable salt thereof; or iv) a pharmaceutical composition according to claim 84 or 85; or v) a compound selected from Table C or a pharmaceutically acceptable salt thereof.

89. The method of claim 88, wherein the method comprises treating or reducing the severity of chronic pain in the subject.

90. The method of claim 88, wherein the method comprises treating or reducing the severity of neuropathic pain in the subject.

91. The method of claim 88, wherein the method comprises treating or reducing the severity of musculoskeletal pain in the subject.

92. The method of claim 88, wherein the method comprises treating or reducing the severity of acute pain in the subject.

93. The method of any one of claims 88 to 92, wherein the subject is treated with one or more additional therapeutic agents that are administered concurrently with, prior to, or after treatment with the compound, pharmaceutically acceptable salt, or pharmaceutical composition.

94. The following are used as medicines: i) a compound according to any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof; or ii) a compound according to claim 83; or iii) a compound selected from Table B or a pharmaceutically acceptable salt thereof; or iv) A pharmaceutical composition according to claim 84 or 85.

95. Use of the following in the preparation of a medicament for treating pain: i) a compound according to any one of claims 1 to 82, or a pharmaceutically acceptable salt thereof; or ii) a compound according to claim 83; or iii) a compound selected from Table B or a pharmaceutically acceptable salt thereof; or iv) A pharmaceutical composition according to claim 84 or 85.

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