Heterocyclic modulators of lipid synthesis

Abstract

The present invention relates to heterocyclic modulators of lipid synthesis. Compounds are provided as modulators of fatty acid synthesis. The compounds are useful in treating disorders characterized by dysregulation of fatty acid synthase function and / or the fatty acid synthase pathway by modulating fatty acid synthase function and / or the fatty acid synthase pathway. Methods for treating such disorders are provided, including viral infections, such as hepatitis C infection, cancer, and metabolic disorders, such as nonalcoholic steatohepatitis (NASH).

Description

[0001] This application is a divisional application of the invention application filed on November 13, 2017, with Chinese application number 201780083446.7 and invention title "Heterocyclic Regulator of Lipid Synthesis".

[0002] Related applications

[0003] This application claims priority and interest in the following cases: U.S. Provisional Application No. 62 / 574,497, filed October 19, 2017; and U.S. Application No. 15 / 349,960, filed November 11, 2016, which is a partial continuation of U.S. Application No. 14 / 874,961, filed October 5, 2015; which is a continuation of U.S. Application No. 14 / 315,133, filed June 25, 2014, which has been abandoned; and which is a continuation of U.S. Application No. 14 / 315,133, filed March 8, 2012. The application filed on [date] is a continuation of U.S. Application No. 13 / 415,660, now U.S. Patent No. 8,871,790. U.S. Application No. 13 / 415,660 and now U.S. Patent No. 8,871,790 claim the interests of previously filed Provisional Applications No. 61 / 450,561 (filed March 8, 2011), No. 61 / 508,611 (filed July 16, 2011), and No. 61 / 585,642 (filed January 11, 2012), and is a partial continuation of U.S. Application No. 15 / 201,824 (filed July 5, 2016). US Patent Application No. 15 / 201,824 is a divisional of U.S. Application No. 14 / 587,908, now U.S. Patent No. 9,428,502, filed on December 31, 2014. U.S. Application No. 14 / 587,908, now U.S. Patent No. 9,428,502, is a continuation of PCT / US2013 / 048950, filed on July 1, 2013. PCT / US2013 / 048950 requests the earlier filed U.S. Provisional Application No. 61 / 667,894, filed on July 3, 2012, and U.S. Provisional Application No. 61 / 698,511, filed on September 7, 2012. The rights to U.S. Provisional Application 61 / 699,819, filed September 11, 2012, and U.S. Provisional Application 61 / 785,933, filed March 14, 2013, and a partial continuation of U.S. Application 15 / 110,154, filed July 7, 2016. U.S. Application 15 / 110,154 is a U.S. national phase application filed under Section 371 of the United States Code, PCT / US2015 / 010459, filed January 7, 2015, which claims the rights to the earlier filed U.S. Provisional Application 61 / 924,520, filed January 7, 2014.

[0004] The entire contents of each of these applications are incorporated hereby by reference for all purposes. Technical Field

[0005] This disclosure generally relates to heterocyclic regulators of lipid synthesis and methods of using them. The heterocyclic regulators of lipid synthesis disclosed herein can be used to treat conditions in subjects characterized by fatty acid synthase dysfunction by modulating the fatty acid synthase pathway and / or fatty acid synthase function. Background Technology

[0006] Viral diseases pose a significant health threat to a large portion of the population. Some characteristics associated with viral infections that are of concern to healthcare professionals include their high transmissibility (e.g., HIV, SARS) and high mutability. Some viruses are also carcinogenic (such as HPV, EBV, and HBV). Although viruses are among the simplest organisms in structure, they are considered the most difficult to control and present a significant challenge to the development of antiviral drugs.

[0007] To date, only a few antiviral drugs have been widely used in patients, such as amantadine and oseltamivir for influenza; acyclovir for HSV-related infections; ganciclovir for CMV infections; and various agents for the treatment of AIDS, including co-blended drugs (efavirenz, emtricitabine, and tonfovir disoproxilfumarate). These drugs have a variety of adverse neurological, metabolic, and immunological side effects. Therefore, the development of new antiviral therapies has become a major focus of medical and pharmaceutical research and development.

[0008] Hepatitis C virus (HCV) infection is a serious health problem. It is estimated that 170 million people worldwide are chronically infected with HCV. HCV infection can lead to chronic hepatitis, cirrhosis, liver failure, and hepatocellular carcinoma. Chronic HCV infection is therefore a leading cause of premature liver-related death worldwide.

[0009] Current standard of care for HCV infection involves a combination therapy of interferon-alpha and ribavirin, often with the addition of a direct-acting protease inhibitor (terapivvir or boprevir). Treatment is cumbersome and sometimes has debilitating and severe side effects. Consequently, many patients do not receive treatment in the early stages of the disease. Furthermore, some patient groups do not respond to treatment sustainably. There is an urgent need for novel and effective treatments for HCV infection.

[0010] Current main treatments for cancer include surgical removal of the primary tumor, tumor irradiation, and non-enteric administration of anti-mitotic cytotoxic agents. Unfortunately, only a relatively small percentage of cancer patients have tumors that are "addicted" to specific pathways and are therefore available for treatment with newer targeted agents. Survival rates for the majority of cancer patients have not improved, reflecting the continued dominance of these long-established therapies. In addition to limited clinical success rates, traditional therapies are accompanied by devastating side effects. Both radiation-based and cytotoxic therapies damage rapidly dividing hematopoietic cells and intestinal epithelial cells, leading to impaired immune function, anemia, and reduced nutrient absorption. Surgical interventions often result in the release of tumor cells into the circulation or lymphatic system, from which metastatic tumors can subsequently form. Improved cancer treatments are needed.

[0011] Nonalcoholic liver disease (NAFLD) is a condition in which the liver contains more than 5% fat by weight and is not caused by alcohol consumption. It currently affects approximately 20-30% of the total population in the United States and the Western world, and is associated with a significantly increased risk of developing cardiovascular disease (i.e., carotid atherosclerotic plaques and endothelial dysfunction), chronic kidney disease, and malignant diseases. Obesity and metabolic syndrome are two key risk factors for NAFLD, characterized by an imbalance between energy utilization and storage. This imbalance leads to metabolic pathway dysregulation and inflammatory responses, resulting in other changes that cause liver damage and comorbidities. As metabolic syndrome progresses, NAFLD leads to more advanced liver disease, starting with nonalcoholic steatohepatitis (NASH) and then progressing to severe liver diseases, including cirrhosis and hepatocellular carcinoma.

[0012] In subjects with metabolic syndrome and NAFLD, fatty acid synthesis in the liver (a pathway known as de novo lipogenesis (DNL)) was increased (Donnelly, KL et al., “Sources of Fatty Acids Stored in Liver and Secreted via Lipoproteins in Patients with Nonalcoholic Fatty Liver Disease,” J. Clin. Invest. 115(5). 2005, 1343-51; Lambert, JE et al., “Increased De Novo Lipogenesis Is a Distinct Characteristic of Individuals with Nonalcoholic Fatty Liver Disease,” Ygast 146(3). 2014, 726-35). The DNL pathway not only produces fatty acids that contribute to increased liver triglyceride reserves, but also produces saturated fatty acids, primarily palmitic acid, which contributes to signaling events that enhance liver inflammation (Wei, Y., “Saturated Fatty Acids Induce Endoplasmic Reticulum Stress and Apoptosis Independently of Ceramide in Liver Cells,” Am. J. Physio. Endocrinol. Metab. 291(2): 2006, E275-81; Kakazu, E. et al., “Hepatocytes Release Ceramide-rich Proinflammatory Extracellular Vesicles in an IRE 1alpha-dependent manner,” Abstract 58. AASLD-The Liver Meeting, San Francisco, CA, USA, 13-17, November 2015). One of the key enzymes in the DNL pathway is fatty acid synthase (FASN), which is solely responsible for synthesizing palmitic acid. Therefore, DNL is an important therapeutic intervention pathway that can reduce the consequences associated with metabolic syndrome and NAFLD.

[0013] Inhibiting FASNs has the potential to be a treatment for a variety of diseases, including cancer, viral diseases, metabolic diseases, NAFLD, NASH, and inflammatory diseases (i.e., rheumatoid arthritis, gout, pulmonary fibrosis, COPD, IBD, and graft rejection). Additionally, FASN inhibition may offer therapeutic benefits in cardiovascular diseases, type 2 diabetes, and metabolic syndrome. Successful treatment of these diseases remains a pressing need. While treatments exist for diabetes and cardiovascular diseases, there are currently no approved drugs for treating metabolic syndrome, NAFLD, or NASH. Therefore, novel and effective small-molecule FASN inhibitors are needed to treat these diseases. Summary of the Invention

[0014] This disclosure addresses the shortcomings of antiviral and anticancer therapies by providing novel heterocyclic regulators of lipid synthesis with improved antiviral and anticancer activities.

[0015] In several respects, this disclosure provides compounds of structure (I) or pharmaceutically acceptable salts thereof:

[0016]

[0017] in:

[0018] X, Y, and Z are each independently CR or NR′, where R is hydrogen or C. 1-6 Alkyl group and R′ is hydrogen, C 1-6 Alkyl groups may not be present;

[0019] A is CH or N;

[0020] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[0021] q can be 0, 1, 2, 3, or 4;

[0022] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[0023] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[0024] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[0025] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[0026] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[0027] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[0028] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, alkylamino, -N(R) 15 R 16 ) or -S(=O)2R 20 ;

[0029] R 15 and R 16Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino;

[0030] R 17 and R 18 Each is independently hydrogen or alkyl, or optionally bonded together to form a bond;

[0031] n is 1 or 2; and

[0032] m is 0 or 1.

[0033] In several respects, this disclosure provides compounds of structure (II) or pharmaceutically acceptable salts thereof:

[0034]

[0035] in:

[0036] X, Y, and Z are each independently CR or NR′, where R is hydrogen or C. 1-6 Alkyl group and R′ is hydrogen, C 1-6 Alkyl groups may not be present;

[0037] L and D are each independently C or N;

[0038] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[0039] q can be 0, 1, 2, 3, or 4;

[0040] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[0041] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[0042] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[0043] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[0044] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[0045] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[0046] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, alkylamino, -N(R) 15 R 16 ) or -S(=O)2R 20 ;

[0047] R 15 and R 16 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino;

[0048] R 17 and R 18 Each is independently hydrogen or alkyl, or optionally bonded together to form a bond;

[0049] n is 1 or 2; and

[0050] m is 0 or 1.

[0051] In several respects, this disclosure provides compounds of structure (III) or pharmaceutically acceptable salts thereof:

[0052]

[0053] in:

[0054] X, Y, and Z are each independently CR or NR′, where R is hydrogen or C. 1-6 Alkyl group and R1 is hydrogen, C 1-6 Alkyl groups may not be present;

[0055] Q is either C or N;

[0056] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, or if Q is N, then R3 does not exist;

[0057] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[0058] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[0059] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[0060] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[0061] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, alkylamino, -N(R) 15 R 16 ) or -S(=O)2R 20 ;

[0062] R 15 and R 16 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino;

[0063] R 17 and R 18 Each is independently hydrogen or alkyl, or optionally bonded together to form a bond;

[0064] R 19 It is aryl, heteroaryl, cycloalkyl, or heterocyclic;

[0065] n is 0, 1, or 2; and

[0066] m is 0 or 1.

[0067] In several respects, this disclosure provides compounds of the (IV-A), (IV-B), or (IV-C) structure or pharmaceutically acceptable salts thereof:

[0068]

[0069]

[0070] in:

[0071] L1, L2, L3, L4 and A are each independently CH or N;

[0072] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) qC(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[0073] q can be 0, 1, 2, 3, or 4;

[0074] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[0075] R2 is hydrogen, halogen, or C. 1-6 Alkoxy or C 1-6 alkyl;

[0076] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl or C 1-6 Alkoxy;

[0077] R 21 and R 22 Each is independently hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkyl, CF3, -OCF3 or -S(O)2R 20 ;

[0078] R 23 For hydrogen, -N(R) 13 (R) 14 C 1-6 Alkyl, C 1-6 Alkoxy group, if L1 is N, then R 23 Does not exist, or R 23 and R 24 Together with the atoms they are attached to, they bond together to form heterocyclic, heteroaryl, or cycloalkyl groups;

[0079] R 24 For hydrogen, -N(R) 13 (R) 14 C 1-6 Alkyl, C 1-6 Alkoxy, -(C 1-6 alkoxy (heterocyclic group), heterocyclic group, or R 23 and R 24 Together with the atoms they are attached to, they bond together to form heterocyclic, heteroaryl, or cycloalkyl groups;

[0080] R 26 It is hydrogen, heteroaryl, heterocyclic, -N(R) 13 (R) 14 ) or -S(=O)2R20 ;

[0081] R 13 and R 14 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, alkylamino, -N(R) 15 R 16 ) or -S(=O)2R 20 ;

[0082] R 25 For hydrogen, C 1-6 Alkyl or C 1-6 alkoxy groups; and

[0083] R 15 and R 16 Each independently is hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, or alkylamino.

[0084] In several respects, this disclosure provides compounds of structure (V) or pharmaceutically acceptable salts thereof:

[0085]

[0086] in:

[0087] L7 is either N or O, where if L7 is O, then R 30 It does not exist;

[0088] A is CH or N;

[0089] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[0090] q can be 0, 1, 2, 3, or 4;

[0091] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[0092] R2 is hydrogen, halogen, or C. 1-6 Alkoxy or C1-6 alkyl;

[0093] R3 is a halogen, C 1-6 Alkyl or C 1-6 Alkoxy;

[0094] R 21 and R 22 Each is independently hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkyl group, CF3, -OCF3 or -S(=O)2R 20 ;

[0095] R 29 and R 30 Each independently is hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, hydroxyalkyl, heteroaryl, heterocyclic, -N(R) 15 R 16 -C(=O)R 46 -R 48 C(=O)R 47 , or R 29 and R 30 Together with the atoms they are attached to, they bond together to form heteroaryl or heterocyclic groups, where if L7 is O, then R 30 It does not exist;

[0096] R 46 and R 47 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, -N(R) 15 R 16 ) or -S(=O)2R 20 ;

[0097] R 48 It is an alkyl group or does not exist;

[0098] R 31 For hydrogen, C 1-6 Alkyl or C 1-6 Alkoxy;

[0099] R 13 and R 14 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, alkylamino, -N(R) 15 R 16 ) or -S(=O)2R 20 ;

[0100] R 15 and R 16Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, or alkylamino; and

[0101] v is 0 or 1.

[0102] In several respects, this disclosure provides compounds of structure (VI-A) or (VI-B) or pharmaceutically acceptable salts thereof:

[0103]

[0104] in:

[0105] L 13 L 14 L 15 And A can be independently CH or N;

[0106] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[0107] q can be 0, 1, 2, 3, or 4;

[0108] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[0109] R2 is hydrogen, halogen, or C. 1-6 Alkoxy or C 1-6 alkyl;

[0110] R3 is a halogen, C 1-6 Alkyl or C 1-6 Alkoxy;

[0111] R 21 and R 22 Each is independently hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkyl group, CF3, -OCF3 or -S(=O)2R 20 ;

[0112] R 34 For hydrogen, C 1-6 Alkyl, C 1-6Alkoxy, cycloalkyl, hydroxy, hydroxyalkyl, aryl, heterocyclic, heteroaryl, alkylamino, CF3, -OCF3, -S(=O)2R 20 or -N(R) 15 R 16 );

[0113] R 35 For hydrogen, C 1-6 Alkyl or C 1-6 Alkoxy;

[0114] R 36 For hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 15 R 16 ), heterocyclic group or heteroaryl group;

[0115] R 13 and R 14 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, alkylamino, -N(R) 15 R 16 ) or -S(=O)2R 20 ;and

[0116] R 15 and R 16 Each independently is hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, or alkylamino.

[0117] In several respects, this disclosure provides compounds of structure (VI-J) or pharmaceutically acceptable salts thereof:

[0118]

[0119] in:

[0120] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0121] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms; and

[0122] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0123] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[0124] R 3 It can be H, -OH or halogen;

[0125] R 21 It is cyclobutyl, azircyclobutane-1-yl or cyclopropyl;

[0126] R 22 It is H, halogen, or C1-C2 alkyl;

[0127] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[0128] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group.

[0129] In some aspects of the structure (VI-J), R 3 It is H or halogen.

[0130] In some aspects of the structure (VI-J), R 1 It is a halogen, -CN, or C1-C2 haloalkyl.

[0131] In some aspects of the structure (VI-J), R 22 It is a C1-C2 alkyl group.

[0132] In some aspects of the structure (VI-J), R 21 It is cyclobutyl and R 22 It is a C1-C2 alkyl group.

[0133] In some aspects of the structure (VI-J), R 21 It is cyclobutyl.

[0134] In some aspects of the structure (VI-J), R 3 It can be H or F.

[0135] In some aspects of the structure (VI-J), R 1 For -CN.

[0136] In some aspects of the structure (VI-J), R 1 It is -CF3.

[0137] In some aspects of the structure (VI-J), R 22 It can be H, methyl, or ethyl.

[0138] In some aspects of the structure (VI-J), R 22 For H.

[0139] In some aspects of the structure (VI-J), R 22 It is a methyl group.

[0140] In some aspects of the structure (VI-J), R 35 -C(O)-NHR 351 .

[0141] In some aspects of the structure (VI-J), R 351 It is isopropyl, isobutyl, (R)-3-tetrahydrofuranyl, (S)-3-tetrahydrofuranyl, (R)-(tetrahydrofuran-2-yl)methyl, (S)-(tetrahydrofuran-2-yl)methyl, (R)-tetrahydro-2H-pyran-3-yl or (S)-tetrahydro-2H-pyran-3-yl.

[0142] In some aspects of the structure (VI-J), R 351 It is (R)-(tetrahydrofuran-2-yl)methyl or (S)-(tetrahydrofuran-2-yl)methyl.

[0143] In some aspects of the structure (VI-J), R 1 For -CN, each R 2 For hydrogen, R 3 For H or F, R 21 It is a C3-C4 cycloalkyl group, R 22 For H, R 35 -C(O)-NHR 351 , where R 351 It is isopropyl, isobutyl, (R)-3-tetrahydrofuranyl, (S)-3-tetrahydrofuranyl, (R)-(tetrahydrofuran-2-yl)methyl, (S)-(tetrahydrofuran-2-yl)methyl, (R)-tetrahydro-2H-pyran-3-yl or (S)-tetrahydro-2H-pyran-3-yl.

[0144] In some aspects of the structure (VI-J), R 35 -C(O)-OR 351 .

[0145] In some aspects of the structure (VI-J), R 351 It is isopropyl, isobutyl, (R)-3-tetrahydrofuranyl, (S)-3-tetrahydrofuranyl, (R)-(tetrahydrofuran-2-yl)methyl, (S)-(tetrahydrofuran-2-yl)methyl, (R)-tetrahydro-2H-pyran-3-yl or (S)-tetrahydro-2H-pyran-3-yl.

[0146] In some aspects of the structure (VI-J), R 1 For -CN, each R 2 For H, R3 For H or F, R 21 It is a C3-C4 cycloalkyl group, R 22 For H, R 35 -C(O)-OR 351 , where R 351 It is isopropyl, isobutyl, (R)-3-tetrahydrofuranyl, (S)-3-tetrahydrofuranyl, (R)-(tetrahydrofuran-2-yl)methyl, (S)-(tetrahydrofuran-2-yl)methyl, (R)-tetrahydro-2H-pyran-3-yl or (S)-tetrahydro-2H-pyran-3-yl.

[0147] In some aspects of the structure (VI-J), R 351 It is (R)-3-tetrahydrofuranyl or (S)-3-tetrahydrofuranyl.

[0148] In some aspects of the structure (VI-J), the compound has a structure selected from the following:

[0149]

[0150] In several respects, this disclosure provides compounds of structure (VII-A) or (VII-B) or pharmaceutically acceptable salts thereof:

[0151]

[0152] in:

[0153] L 16 Let L be C or N, where L is... 16 If N, then R 41 It does not exist;

[0154] L 17 L 18 And A can be independently CH or N;

[0155] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[0156] q can be 0, 1, 2, 3, or 4;

[0157] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 Alkyl or -N(R)13 (R) 14 );

[0158] R2 is hydrogen, halogen, or C. 1-6 Alkoxy or C 1-6 alkyl;

[0159] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl or C 1-6 Alkoxy;

[0160] R 21 and R 22 Each is independently hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkyl group, CF3, -OCF3 or -S(=O)2R 20 ;

[0161] R 40 R 42 and R 43 Each independently is hydrogen, C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 -C(=O)R, hydroxyalkyl, hydroxyl, -N(R) 13 R 14 ), or R 41 and R 42 Together with the atoms they are attached to, they bond together to form heteroaryl or heterocyclic groups;

[0162] R 41 For hydrogen, C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 -C(=O)R, hydroxyalkyl, hydroxyl, -N(R) 13 R 14 If L 16 If N, then R 41 Does not exist, or R 41 and R 42 Together with the atoms they are attached to, they bond together to form heteroaryl or heterocyclic groups;

[0163] R represents hydrogen, C represents... 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, -N(R) 15 R 16 ) or -S(=O)2R 20 ;

[0164] R 39 For hydrogen, C 1-6 Alkyl or C 1-6 Alkoxy;

[0165] R 13 and R 14 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, alkylamino, -N(R) 15 R 16 ) or -S(=O)2R 20 ;and

[0166] R 15 and R 16 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, or alkylamino.

[0167] In several respects, this disclosure provides compounds of structure (VIII-A), (VIII-B) or (VIII-C) or pharmaceutically acceptable salts thereof:

[0168]

[0169] in:

[0170] L 19 And A can be independently CH or N;

[0171] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[0172] q can be 0, 1, 2, 3, or 4;

[0173] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 Alkyl or -N(R) 13 (R) 14 );

[0174] R2 is hydrogen, halogen, or C. 1-6 Alkoxy or C 1-6 alkyl;

[0175] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl or C 1-6 Alkoxy;

[0176] R 21 and R 22Each is independently hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkyl group, CF3, -OCF3 or -S(=O)2R 20 ;

[0177] R 39 For hydrogen, C 1-6 Alkyl or C 1-6 Alkoxy;

[0178] R 44 and R 45 Each independently is hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, cycloalkyl, hydroxyalkyl, aryl, heterocyclic, heteroaryl, alkylamino, -S(=O)2R 20 -C(=O)R or -N(R) 13 R 14 );and

[0179] R 13 and R 14 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, alkylamino, -N(R) 15 R 16 ) or -S(=O)2R 20 ;and

[0180] R 15 and R 16 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, or alkylamino.

[0181] In several respects, compounds of structure (IX) or pharmaceutically acceptable salts thereof are provided:

[0182]

[0183] in:

[0184] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0185] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0186] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0187] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0188] R 3 It can be H, -OH or halogen;

[0189] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[0190] R 22 It is H, halogen, or C1-C2 alkyl;

[0191] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t (C3-C5 cycloalkyl) or (C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[0192] t is 0 or 1;

[0193] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0194] L 1 For CR 23 Or N;

[0195] L 2 For CH or N;

[0196] L 1 or L 2 At least one of them is N; and

[0197] R 23 It is an H or C1-C4 straight-chain or branched alkyl group.

[0198] In some aspects of the structure (IX), R 24 It is a C1-C4 straight-chain or branched alkyl group or -(C1-C4 alkyl group). t O-(C1-C4 straight-chain or branched alkyl), where t is 0 or 1.

[0199] In some aspects of the structure (IX), R 21 It is a halogen; a C1-C4 straight-chain or branched alkyl group; a C3-C5 cycloalkyl group, wherein the C3-C5 cycloalkyl group optionally includes an oxygen or nitrogen heteroatom; -S(O) u -(C1-C4 straight-chain or branched alkyl), where u is 0 or 2; or -S(O) u-(C3-C5 cycloalkyl), where u is 0 or 2.

[0200] In some aspects of the structure (IX), R 3 It is H or halogen.

[0201] In some aspects of the structure (IX), R 1 It is a halogen, -CN, or C1-C2 haloalkyl.

[0202] In some aspects of the structure (IX), L 1 With L 2 All are N.

[0203] In some aspects of the structure (IX), R 21 It is a C1-C2 alkyl or C3-C5 cycloalkyl and R 22 It is a C1-C2 alkyl group.

[0204] In some aspects of the structure (IX), R 21 It is a C3-C5 cycloalkyl group and R 22 It is a C1-C2 alkyl group.

[0205] In some aspects of the structure (IX), R 24 -(C1-C2 alkyl) t -O-(C1-C2 alkyl), where t is 0 or 1.

[0206] In some aspects of the structure (IX), R 21 It is a C3-C5 cycloalkyl group, R 22 It is a C1-C2 alkyl group and R 24 It is a C1-C2 alkyl group.

[0207] In some aspects of the structure (IX), R 21 It is cyclobutyl, R 22 It is a C1-C2 alkyl group and R 24 It is a C1-C2 alkyl group.

[0208] In some aspects of the structure (IX), R 21 It is cyclobutyl.

[0209] In some aspects of the structure (IX), R 3 It can be H or F.

[0210] In some aspects of the structure (IX), R 1 For -CN.

[0211] In some aspects of the structure (IX), R 1 It is -CF3.

[0212] In some aspects of the structure (IX), R 22It can be H, methyl, or ethyl.

[0213] In some aspects of the structure (IX), R 22 For H.

[0214] In some aspects of the structure (IX), R 22 It is a methyl group.

[0215] In some aspects of the structure (IX), R 1 For -CN, each R 2 For H, R 3 For H or F, R 21 It is a C3-C4 cycloalkyl group, R 22 Methyl, L 1 and L 2 Let N be the number of elements and R be the number of elements. 24 It can be methyl, ethyl, hydroxymethyl, methoxymethyl, or 2-methoxyethyl.

[0216] In some aspects of the structure (IX), R 1 For -CN, each R 2 For H, R 3 For H or F, R 21 It is a C3-C4 cycloalkyl group, R 22 Methyl, L 1 and L 2 Let N be the number of elements and R be the number of elements. 24 It is methoxy or ethoxy.

[0217] In some aspects of the structure (IX), R 1 For -CN, each R 2 For H, R 3 For H or F, R 21 It is a C3-C4 cycloalkyl group, R 22 Methyl, L 1 For CH, L 2 Let N be the number of elements and R be the number of elements. 24 It can be methyl, ethyl, hydroxymethyl, methoxymethyl or 2-methoxyethyl.

[0218] In some aspects of the structure (IX), R 1 For -CN, each R 2 For H, R 3 For H or F, R 21 It is a C3-C4 cycloalkyl group, R 22 Methyl, L 1 For N, L 2 It is CH, and R 24 It can be methyl, ethyl, hydroxymethyl, methoxymethyl or 2-methoxyethyl.

[0219] In some aspects of structure (IX), the compound has a structure selected from the following:

[0220]

[0221] In several respects, a compound of structure (X) or a pharmaceutically acceptable salt thereof is provided:

[0222]

[0223] in:

[0224] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0225] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms; and

[0226] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0227] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0228] R 3 It can be H, -OH, or a halogen;

[0229] L 3 For C(R) 60 2. O or NR 50 ;

[0230] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl) or -C(O)-N(R) 601 )2, of which:

[0231] t is 0 or 1, and

[0232] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms;

[0233] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally including oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[0234] t is 0 or 1, and

[0235] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms;

[0236] n is 1, 2, or 3;

[0237] m is 1 or 2;

[0238] R 21 It can be H, halogen, C1-C4 straight-chain or branched alkyl, or C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[0239] R 22 It can be H, halogen, or C1-C2 alkyl;

[0240] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[0241] t is 0 or 1, and

[0242] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms;

[0243] s is 0, 1, or 2;

[0244] Each R 601 and R 501 Independently, it is an H or a C1-C4 straight-chain or branched alkyl group; and wherein R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 .

[0245] In some aspects of the structure (X), R 21It is a halogen, a C1-C4 straight-chain or branched alkyl group, or a C3-C5 cycloalkyl group.

[0246] In some aspects of the structure (X), R 3 It is H or halogen.

[0247] In some aspects of the structure (X), R 1 It is a -CN or C1-C2 haloalkyl group.

[0248] In some aspects of the structure (X), R 3 It can be H or F.

[0249] In some aspects of the structure (X), R 1 For -CN.

[0250] In some aspects of the structure (X), R 1 It is -CF3.

[0251] In some aspects of the structure (X), n is 1.

[0252] In some aspects of the structure (X), n is 2.

[0253] In some aspects of the structure (X), m is 1.

[0254] In some aspects of the structure (X), m is 2.

[0255] In some aspects of the structure (X), R 21 It is a C1-C2 alkyl or C3-C5 cycloalkyl and R 22 It is a C1-C2 alkyl group.

[0256] In some aspects of structure (X), R 21 It is a C3-C5 cycloalkyl group and R 22 It is a C1-C2 alkyl group.

[0257] In some aspects of the structure (X), n is 2, m is 1, and L 3 It is -NC(O)-O-(C1-C2 alkyl).

[0258] In some aspects of structure (X), L 3 For NR 50 ;R 50 It is a C1-C2 alkyl group; R 21 It is cyclobutyl; R 22 H or methyl; R 3 For H; R 1 It is -CN; m is 2 and n is 1 or 2.

[0259] In some aspects of the structure (X), n is 2, m is 1, and L 3 It is O and s is 0.

[0260] In some aspects of the structure (X), R 22 It can be H, methyl, or ethyl.

[0261] In some aspects of the structure (X), R 22 It is a methyl group.

[0262] In some aspects of the structure (X), R 22 For H.

[0263] In some aspects of the structure (X), R 1 For -CN, each R 2 For H, R 3 For H or F, R 21 It is a C3-C4 cycloalkyl group, R 22 It is a methyl group, n is 2 and L 3 For NR 50 , where R 50 It can be methyl or ethyl.

[0264] In some aspects of the structure (X), R 1 For -CN, each R 2 For H, R 3 For H or F, R 21 It is a C3-C4 cycloalkyl group, R 22 It is a methyl group, n is 2 and L 3 It is O.

[0265] In some aspects of structure (X), the compound has a structure selected from the following:

[0266]

[0267] In several respects, compounds of structure (XI) or pharmaceutically acceptable salts thereof are provided:

[0268]

[0269] in:

[0270] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0271] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0272] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0273] Each R 2Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[0274] R 3 It can be H, -OH or halogen;

[0275] R 21 It is cyclobutyl, azircyclobutane-1-yl or cyclopropyl;

[0276] R 22 It is H, halogen, C1-C2 alkyl; and

[0277] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[0278] In some aspects of the structure (XI), R 3 It is H or halogen.

[0279] In some aspects of the structure (XI), R 1 It is a halogen, -CN, or C1-C2 haloalkyl.

[0280] In some aspects of the structure (XI), R 21 It is a C3-C4 cycloalkyl group and R 22 It is a C1-C2 alkyl group.

[0281] In some aspects of the structure (XI), R 21 It is cyclobutyl and R 22 It is a C1-C2 alkyl group.

[0282] In some aspects of the structure (XI), R 21 It is cyclobutyl.

[0283] In some aspects of the structure (XI), R 3 It can be H or F.

[0284] In some aspects of the structure (XI), R 1 For -CN.

[0285] In some aspects of the structure (XI), R 1 It is -CF3.

[0286] In some aspects of the structure (XI), R 22 It can be H, methyl, or ethyl.

[0287] In some aspects of the structure (XI), R 22 For H.

[0288] In some aspects of the structure (XI), R 22 It is a methyl group.

[0289] In some aspects of the structure (XI), R1 For -CN, each R 2 For H, R 3 For H or F, R 21 It is cyclobutyl, R 22 It is methyl and R 351 It can be methyl or ethyl.

[0290] In some aspects of structure (XI), the compound has a structure selected from the following:

[0291]

[0292] In several aspects, this disclosure provides pharmaceutical compositions comprising any one of compounds of structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), or (XI) and a pharmaceutically acceptable carrier, excipient, or diluent.

[0293] In several aspects, this disclosure provides a method for treating a condition characterized by fatty acid synthase dysfunction in a subject, the method comprising administering to the subject requiring the treatment an effective amount of a compound of any one of structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), or (XI). In several aspects, the condition characterized by fatty acid synthase dysfunction is a viral infection or cancer. In several aspects, a viral infection is treated by combining a compound of any one of structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), or (XI) with one or more additional antiviral treatments. In several aspects, cancer is treated by combining a compound of any one of structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), or (XI) with one or more additional cancer treatments. In several aspects, the viral infection is hepatitis C.

[0294] In various respects, this disclosure relates to a method for treating fatty liver disease in a subject of need, the method comprising administering a fatty acid synthase inhibitor having the following formula to the subject of need:

[0295] (a) Equation (IX)

[0296]

[0297] Or its pharmaceutically acceptable salt, wherein:

[0298] R 1The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0299] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0300] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0301] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0302] R 3 It can be H, -OH or halogen;

[0303] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[0304] R 22 It is H, halogen, or C1-C2 alkyl;

[0305] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[0306] t is 0 or 1;

[0307] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0308] L 1 For CR 23 Or N;

[0309] L 2 For CH or N;

[0310] L 1 or L 2 At least one of them is N; and

[0311] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[0312] (b) Equation (X):

[0313]

[0314] Or its pharmaceutically acceptable salt, wherein:

[0315] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0316] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0317] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0318] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0319] R 3 It can be H, -OH or halogen;

[0320] L 3 For C(R) 60 2. O or NR 50 ;

[0321] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl), or -C(O)-N(R) 601 )2, of which:

[0322] t is 0 or 1; and

[0323] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0324] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[0325] t is 0 or 1; and

[0326] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0327] n is 1, 2, or 3;

[0328] m is 1 or 2;

[0329] R 21H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[0330] R 22 It can be H, halogen, or C1-C2 alkyl;

[0331] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[0332] t is 0 or 1; and

[0333] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0334] s is 0, 1, or 2;

[0335] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[0336] Where R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[0337] (c) Equation (VI-J)

[0338]

[0339] Or its pharmaceutically acceptable salt, wherein:

[0340] R 1The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0341] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0342] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0343] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0344] R 3 It can be H, -OH or halogen;

[0345] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[0346] R 22 It is H, halogen, or C1-C2 alkyl;

[0347] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[0348] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[0349] (d) Formula (XII):

[0350]

[0351] Or its pharmaceutically acceptable salt, wherein:

[0352] L-Ar is

[0353] Ar for

[0354] Het is a 5- to 6-membered heteroaryl group;

[0355] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0356] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0357] R 3 For H or F;

[0358] R 11 It is H or -CH3;

[0359] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[0360] R 22 It is H, halogen, or C1-C2 alkyl;

[0361] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[0362] t is 0 or 1;

[0363] u is 0 or 1;

[0364] The constraint is that when u is 1, t is 1; and

[0365] Each R 241 Independently H or C1-C2 alkyl; and

[0366] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[0367] (e) Equation (XIII):

[0368]

[0369] Or its pharmaceutically acceptable salt, wherein:

[0370] L-Ar is

[0371] Ar for

[0372] Het is a 5- to 6-membered heteroaryl group;

[0373] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0374] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0375] R 3 For H or F;

[0376] R 11 It is H or -CH3;

[0377] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[0378] R 22 It is H, halogen, or C1-C2 alkyl; and

[0379] Each R 24 and R 25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[0380] Each t is independently 0 or 1;

[0381] Each u is independently 0 or 1; and

[0382] Each R 241 Independently H or C1-C2 alkyl; or

[0383] (f) Equation (XIV):

[0384]

[0385] Or its pharmaceutically acceptable salt, wherein:

[0386] L-Ar is

[0387] Ar for The constraint is that when L-Ar is Ar not for

[0388] Het is a 5- to 6-membered heteroaryl group;

[0389] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0390] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0391] R 3 For H or F;

[0392] R 11 It is H or -CH3;

[0393] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[0394] R 22 It is H, halogen, or C1-C2 alkyl; and

[0395] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[0396] Each t is independently 0 or 1; and

[0397] Each R 241 Independently H or C1-C2 alkyl; or

[0398] (g) Equation (XV):

[0399]

[0400] Or its pharmaceutically acceptable salt, wherein:

[0401] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[0402] n is 1, 2, or 3;

[0403] m can be 1 or 2, and the constraint is that n+m≥3;

[0404] L x Ar for

[0405] Ar for The constraint is that when L-Ar is Ar not for

[0406] Het is a 5- to 6-membered heteroaryl group;

[0407] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0408] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0409] R 3 For H or F;

[0410] R 11 It is H or -CH3;

[0411] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[0412] R 22 It is H, halogen, or C1-C2 alkyl; or

[0413] (h) formula (XVI):

[0414]

[0415] Or its pharmaceutically acceptable salt, wherein:

[0416] L - Ar for

[0417] Ar for

[0418] Het is a 5- to 6-membered heteroaryl group;

[0419] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0420] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0421] R 3 For H or F;

[0422] R 11 It is H or -CH3;

[0423] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[0424] R 22 It is H, halogen, or C1-C2 alkyl; and

[0425] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[0426] (i) Equation (XVII):

[0427]

[0428] Or its pharmaceutically acceptable salt, wherein:

[0429] L - Ar for

[0430] Ar for The constraint is that when L-Ar is Ar not for

[0431] Het is a 5- to 6-membered heteroaryl group;

[0432] R 1It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0433] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0434] R 3 For H or F;

[0435] R 11 It is H or -CH3;

[0436] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[0437] R 22 It is H, halogen, or C1-C2 alkyl; and

[0438] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[0439] t is 0 or 1;

[0440] u is 0 or 1;

[0441] The constraint is that when u is 1, t is 1; and

[0442] R 241 It is H or C1-C2 alkyl; or

[0443] (j) Equation (XVIII):

[0444]

[0445] Or its pharmaceutically acceptable salt, wherein:

[0446] L-Ar is

[0447] Ar for The constraint is that when L-Ar is Ar not for

[0448] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[0449] Het is a 5- to 6-membered heteroaryl group;

[0450] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0451] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0452] R 3 For H or F;

[0453] R 11 It is H or -CH3;

[0454] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0455] R 22 It is H, halogen, or C1-C2 alkyl; and

[0456] R 35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[0457] (k) Equation (XIX):

[0458]

[0459] Or its pharmaceutically acceptable salt, wherein:

[0460] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[0461] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[0462] Each R 27 Independently H or C1-C4 alkyl, or two R 27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[0463] Ar for

[0464] Het is a 5- to 6-membered heteroaryl group;

[0465] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0466] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0467] R 3 For H or F;

[0468] R 11 It is H or -CH3;

[0469] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[0470] R 22 It is H, halogen, or C1-C2 alkyl; or

[0471] (l) Equation (XX):

[0472]

[0473] Or its pharmaceutically acceptable salt, wherein:

[0474] L - Ar for

[0475] Ar for

[0476] R1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0477] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0478] R 3 For H or F;

[0479] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0480] R 22 It is H, halogen, or C1-C2 alkyl;

[0481] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[0482] R 25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[0483] (m) Equation (XI):

[0484]

[0485] Or its pharmaceutically acceptable salt, wherein:

[0486] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0487] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0488] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0489] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0490] R 3It can be H, -OH or halogen;

[0491] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[0492] R 22 It is H, halogen, C1-C2 alkyl; and

[0493] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[0494] In various respects, this disclosure relates to a method for treating non-alcoholic steatohepatitis (NASH) in a subject of need, the method comprising administering a fatty acid synthase inhibitor having the following formula to the subject of need:

[0495] (a) Equation (IX)

[0496]

[0497] Or its pharmaceutically acceptable salt, wherein:

[0498] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0499] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0500] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0501] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0502] R 3 It can be H, -OH or halogen;

[0503] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[0504] R 22 It is H, halogen, or C1-C2 alkyl;

[0505] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t-(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[0506] t is 0 or 1;

[0507] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0508] L 1 For CR 23 Or N;

[0509] L 2 For CH or N;

[0510] L 1 or L 2 At least one of them is N; and

[0511] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[0512] (b) Equation (X):

[0513]

[0514] Or its pharmaceutically acceptable salt, wherein:

[0515] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0516] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0517] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0518] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0519] R 3 It can be H, -OH or halogen;

[0520] L 3 For C(R) 60 2. O or NR 50 ;

[0521] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl), or -C(O)-N(R) 601 )2, of which:

[0522] t is 0 or 1; and

[0523] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0524] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[0525] t is 0 or 1; and

[0526] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0527] n is 1, 2, or 3;

[0528] m is 1 or 2;

[0529] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[0530] R 22 It can be H, halogen, or C1-C2 alkyl;

[0531] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[0532] t is 0 or 1; and

[0533] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0534] s is 0, 1, or 2;

[0535] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[0536] Where R26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[0537] (c) Equation (VI-J)

[0538]

[0539] Or its pharmaceutically acceptable salt, wherein:

[0540] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0541] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0542] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0543] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0544] R 3 It can be H, -OH or halogen;

[0545] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[0546] R 22 It is H, halogen, or C1-C2 alkyl;

[0547] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[0548] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[0549] (d) Formula (XII):

[0550]

[0551] Or its pharmaceutically acceptable salt, wherein:

[0552] L-Ar is

[0553] Ar for

[0554] Het is a 5- to 6-membered heteroaryl group;

[0555] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0556] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0557] R 3 For H or F;

[0558] R 11 It is H or -CH3;

[0559] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0560] R 22 It is H, halogen, or C1-C2 alkyl;

[0561] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[0562] t is 0 or 1;

[0563] u is 0 or 1;

[0564] The constraint is that when u is 1, t is 1; and

[0565] Each R 241 Independently H or C1-C2 alkyl; and

[0566] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[0567] (e) Equation (XIII):

[0568]

[0569] Or its pharmaceutically acceptable salt, wherein:

[0570] L-Ar is

[0571] Ar for

[0572] Het is a 5- to 6-membered heteroaryl group;

[0573] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0574] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0575] R 3 For H or F;

[0576] R 11 It is H or -CH3;

[0577] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0578] R 22 It is H, halogen, or C1-C2 alkyl; and

[0579] Each R 24 and R 25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u-(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[0580] Each t is independently 0 or 1;

[0581] Each u is independently 0 or 1; and

[0582] Each R 241 Independently H or C1-C2 alkyl; or

[0583] (f) Equation (XIV):

[0584]

[0585] Or its pharmaceutically acceptable salt, wherein:

[0586] L-Ar is

[0587] Ar for The constraint is that when L-Ar is Ar not for

[0588] Het is a 5- to 6-membered heteroaryl group;

[0589] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0590] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0591] R 3 For H or F;

[0592] R 11 It is H or -CH3;

[0593] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0594] R 22 It is H, halogen, or C1-C2 alkyl; and

[0595] R 24It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[0596] Each t is independently 0 or 1; and

[0597] Each R 241 Independently H or C1-C2 alkyl; or

[0598] (g) Equation (XV):

[0599]

[0600] Or its pharmaceutically acceptable salt, wherein:

[0601] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[0602] n is 1, 2, or 3;

[0603] m can be 1 or 2, and the constraint is that n+m≥3;

[0604] L-Ar is

[0605] Ar for The constraint is that when L-Ar is Ar not for

[0606] Het is a 5- to 6-membered heteroaryl group;

[0607] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0608] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0609] R 3 For H or F;

[0610] R 11 It is H or -CH3;

[0611] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[0612] R 22 It is H, halogen, or C1-C2 alkyl; or

[0613] (h) formula (XVI):

[0614]

[0615] Or its pharmaceutically acceptable salt, wherein:

[0616] L-Ar is

[0617] Ar for

[0618] Het is a 5- to 6-membered heteroaryl group;

[0619] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0620] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0621] R 3 For H or F;

[0622] R 11 It is H or -CH3;

[0623] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0624] R 22 It is H, halogen, or C1-C2 alkyl; and

[0625] R 24 and R 25Each is independently H, -C1-C4 alkyl, or halogen; or

[0626] (i) Equation (XVII):

[0627]

[0628] Or its pharmaceutically acceptable salt, wherein:

[0629] L-Ar is

[0630] Ar for The constraint is that when L-Ar is Ar not for

[0631] Het is a 5- to 6-membered heteroaryl group;

[0632] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0633] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0634] R 3 For H or F;

[0635] R 11 It is H or -CH3;

[0636] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0637] R 22 It is H, halogen, or C1-C2 alkyl; and

[0638] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[0639] t is 0 or 1;

[0640] u is 0 or 1;

[0641] The constraint is that when u is 1, t is 1; and

[0642] R 241 It is H or C1-C2 alkyl; or

[0643] (j) Equation (XVIII):

[0644]

[0645] Or its pharmaceutically acceptable salt, wherein:

[0646] L x Ar for

[0647] Ar for The constraint is that when L-Ar is Ar not for

[0648] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[0649] Het is a 5- to 6-membered heteroaryl group;

[0650] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0651] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0652] R 3 For H or F;

[0653] R 11 It is H or -CH3;

[0654] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0655] R 22 It is H, halogen, or C1-C2 alkyl; and

[0656] R35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[0657] (k) Equation (XIX):

[0658]

[0659] Or its pharmaceutically acceptable salt, wherein:

[0660] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[0661] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[0662] Each R 27 Independently H or C1-C4 alkyl, or two R 27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[0663] Ar for

[0664] Het is a 5- to 6-membered heteroaryl group;

[0665] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0666] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0667] R 3 For H or F;

[0668] R 11 It is H or -CH3;

[0669] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[0670] R 22 It is H, halogen, or C1-C2 alkyl; or

[0671] (l) Equation (XX):

[0672]

[0673] Or its pharmaceutically acceptable salt, wherein:

[0674] L - Ar for

[0675] Ar for

[0676] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0677] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0678] R 3 For H or F;

[0679] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0680] R 22 It is H, halogen, or C1-C2 alkyl;

[0681] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[0682] R 25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[0683] (m) Equation (XI):

[0684]

[0685] Or its pharmaceutically acceptable salt, wherein:

[0686] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0687] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0688] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0689] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[0690] R 3 It can be H, -OH or halogen;

[0691] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[0692] R 22 It is H, halogen, C1-C2 alkyl; and

[0693] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[0694] In various respects, this disclosure relates to a method for treating non-alcoholic fatty liver disease (NAFLD) in a subject of need, the method comprising administering to the subject of need a fatty acid synthase inhibitor having the following formula:

[0695] (a) Equation (IX)

[0696]

[0697] Or its pharmaceutically acceptable salt, wherein:

[0698] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0699] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0700] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0701] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0702] R 3 It can be H, -OH, or a halogen;

[0703] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[0704] R 22 It is H, halogen, or C1-C2 alkyl;

[0705] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[0706] t is 0 or 1;

[0707] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0708] L 1 For CR 23 Or N;

[0709] L 2 For CH or N;

[0710] L 1 or L 2 At least one of them is N; and

[0711] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[0712] (b) Equation (X):

[0713]

[0714] Or its pharmaceutically acceptable salt, wherein:

[0715] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0716] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0717] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0718] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0719] R 3 It can be H, -OH or halogen;

[0720] L 3 For C(R) 60 2. O or NR 50 ;

[0721] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl) or -C(O)-N(R) 601 )2, of which:

[0722] t is 0 or 1; and

[0723] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0724] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[0725] t is 0 or 1; and

[0726] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0727] n is 1, 2, or 3;

[0728] m is 1 or 2;

[0729] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[0730] R 22 It can be H, halogen, or C1-C2 alkyl;

[0731] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -Ot -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[0732] t is 0 or 1; and

[0733] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0734] s is 0, 1, or 2;

[0735] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[0736] Where R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[0737] (c) Equation (VI-J)

[0738]

[0739] Or its pharmaceutically acceptable salt, wherein:

[0740] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0741] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0742] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0743] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[0744] R 3 It can be H, -OH or halogen;

[0745] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[0746] R 22 It is H, halogen, or C1-C2 alkyl;

[0747] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[0748] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[0749] (d) Formula (XII):

[0750]

[0751] Or its pharmaceutically acceptable salt, wherein:

[0752] L-Ar is

[0753] Ar for

[0754] Het is a 5- to 6-membered heteroaryl group;

[0755] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0756] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0757] R 3 For H or F;

[0758] R 11 It is H or -CH3;

[0759] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0760] R 22 It is H, halogen, or C1-C2 alkyl;

[0761] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[0762] t is 0 or 1;

[0763] u is 0 or 1;

[0764] The constraint is that when u is 1, t is 1; and

[0765] Each R 241 Independently H or C1-C2 alkyl; and

[0766] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[0767] (e) Equation (XIII):

[0768]

[0769] Or its pharmaceutically acceptable salt, wherein:

[0770] L-Ar is

[0771] Ar for

[0772] Het is a 5- to 6-membered heteroaryl group;

[0773] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0774] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0775] R3 For H or F;

[0776] R 11 It is H or -CH3;

[0777] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0778] R 22 It is H, halogen, or C1-C2 alkyl; and

[0779] Each R 24 and R 25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[0780] Each t is independently 0 or 1;

[0781] Each u is independently 0 or 1; and

[0782] Each R 241 Independently H or C1-C2 alkyl; or

[0783] (f) Equation (XIV):

[0784]

[0785] Or its pharmaceutically acceptable salt, wherein:

[0786] L-Ar is

[0787] Ar for The constraint is that when L-Ar is Ar not for

[0788] Het is a 5- to 6-membered heteroaryl group;

[0789] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0790] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0791] R 3 For H or F;

[0792] R 11 It is H or -CH3;

[0793] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0794] R 22 It is H, halogen, or C1-C2 alkyl; and

[0795] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[0796] Each t is independently 0 or 1; and

[0797] Each R 241 Independently H or C1-C2 alkyl; or

[0798] (g) Equation (XV):

[0799]

[0800] Or its pharmaceutically acceptable salt, wherein:

[0801] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[0802] n is 1, 2, or 3;

[0803] m can be 1 or 2, and the constraint is that n+m≥3;

[0804] L-Ar is

[0805] Ar for The constraint is that when L-Ar is Ar not for

[0806] Het is a 5- to 6-membered heteroaryl group;

[0807] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0808] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0809] R 3 For H or F;

[0810] R 11 It is H or -CH3;

[0811] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[0812] R 22 It is H, halogen, or C1-C2 alkyl; or

[0813] (h) formula (XVI):

[0814]

[0815] Or its pharmaceutically acceptable salt, wherein:

[0816] L-Ar is

[0817] Ar for

[0818] Het is a 5- to 6-membered heteroaryl group;

[0819] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0820] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0821] R 3 For H or F;

[0822] R 11 It is H or -CH3;

[0823] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0824] R 22 It is H, halogen, or C1-C2 alkyl; and

[0825] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[0826] (i) Equation (XVII):

[0827]

[0828] Or its pharmaceutically acceptable salt, wherein:

[0829] L-Ar is

[0830] Ar for The constraint is that when L-Ar is Ar not for

[0831] Het is a 5- to 6-membered heteroaryl group;

[0832] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0833] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0834] R 3 For H or F;

[0835] R 11 It is H or -CH3;

[0836] R21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0837] R 22 It is H, halogen, or C1-C2 alkyl; and

[0838] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[0839] t is 0 or 1;

[0840] u is 0 or 1;

[0841] The constraint is that when u is 1, t is 1; and

[0842] R 241 It is H or C1-C2 alkyl; or

[0843] (j) Equation (XVIII):

[0844]

[0845] Or its pharmaceutically acceptable salt, wherein:

[0846] L-Ar is

[0847] Ar for The constraint is that when L-Ar is Ar not for

[0848] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[0849] Het is a 5- to 6-membered heteroaryl group;

[0850] R 1The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0851] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0852] R 3 For H or F;

[0853] R 11 It is H or -CH3;

[0854] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0855] R 22 It is H, halogen, or C1-C2 alkyl; and

[0856] R 35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[0857] (k) Equation (XIX):

[0858]

[0859] Or its pharmaceutically acceptable salt, wherein:

[0860] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[0861] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[0862] Each R 27 Independently H or C1-C4 alkyl, or two R 27All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[0863] Ar for

[0864] Het is a 5- to 6-membered heteroaryl group;

[0865] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0866] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0867] R 3 For H or F;

[0868] R 11 It is H or -CH3;

[0869] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[0870] R 22 It is H, halogen, or C1-C2 alkyl; or

[0871] (l) Equation (XX):

[0872]

[0873] Or its pharmaceutically acceptable salt, wherein:

[0874] L-Ar is

[0875] Ar for

[0876] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0877] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0878] R 3 For H or F;

[0879] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0880] R 22 It is H, halogen, or C1-C2 alkyl;

[0881] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[0882] R 25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[0883] (m) Equation (XI):

[0884]

[0885] Or its pharmaceutically acceptable salt, wherein:

[0886] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0887] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0888] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0889] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0890] R 3 It can be H, -OH or halogen;

[0891] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[0892] R 22 It is H, halogen, C1-C2 alkyl; and

[0893] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[0894] In various respects, this disclosure relates to a method for treating metabolic syndrome in a subject of need, the method comprising administering a fatty acid synthase inhibitor having the following formula to the subject of need:

[0895] (a) Equation (IX)

[0896]

[0897] Or its pharmaceutically acceptable salt, wherein:

[0898] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0899] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0900] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0901] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0902] R 3 It can be H, -OH or halogen;

[0903] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[0904] R 22 It is H, halogen, or C1-C2 alkyl;

[0905] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[0906] t is 0 or 1;

[0907] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0908] L 1 For CR 23 Or N;

[0909] L 2For CH or N;

[0910] L 1 or L 2 At least one of them is N; and

[0911] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[0912] (b) Equation (X):

[0913]

[0914] Or its pharmaceutically acceptable salt, wherein:

[0915] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0916] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0917] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0918] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[0919] R 3 It can be H, -OH or halogen;

[0920] L 3 For C(R) 60 2. O or NR 50 ;

[0921] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl), or -C(O)-N(R) 601 )2, of which:

[0922] t is 0 or 1; and

[0923] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0924] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R)501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[0925] t is 0 or 1; and

[0926] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0927] n is 1, 2, or 3;

[0928] m is 1 or 2;

[0929] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[0930] R 22 It can be H, halogen, or C1-C2 alkyl;

[0931] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[0932] t is 0 or 1; and

[0933] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[0934] s is 0, 1, or 2;

[0935] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[0936] Where R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501Or two Rs 601 ;or

[0937] (c) Equation (VI-J)

[0938]

[0939] Or its pharmaceutically acceptable salt, wherein:

[0940] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[0941] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[0942] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[0943] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[0944] R 3 It can be H, -OH or halogen;

[0945] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[0946] R 22 It is H, halogen, or C1-C2 alkyl;

[0947] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[0948] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[0949] (d) Formula (XII):

[0950]

[0951] Or its pharmaceutically acceptable salt, wherein:

[0952] L-Ar is

[0953] Ar for

[0954] Het is a 5- to 6-membered heteroaryl group;

[0955] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0956] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0957] R 3 For H or F;

[0958] R 11 It is H or -CH3;

[0959] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0960] R 22 It is H, halogen, or C1-C2 alkyl;

[0961] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[0962] t is 0 or 1;

[0963] u is 0 or 1;

[0964] The constraint is that when u is 1, t is 1; and

[0965] Each R 241 Independently H or C1-C2 alkyl; and

[0966] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[0967] (e) Equation (XIII):

[0968]

[0969] Or its pharmaceutically acceptable salt, wherein:

[0970] L-Ar is

[0971] Ar for

[0972] Het is a 5- to 6-membered heteroaryl group;

[0973] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0974] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0975] R 3 For H or F;

[0976] R 11 It is H or -CH3;

[0977] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0978] R 22 It is H, halogen, or C1-C2 alkyl; and

[0979] Each R 24 and R 25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[0980] Each t is independently 0 or 1;

[0981] Each u is independently 0 or 1; and

[0982] Each R 241Independently H or C1-C2 alkyl; or

[0983] (f) Equation (XIV):

[0984]

[0985] Or its pharmaceutically acceptable salt, wherein:

[0986] L-Ar is

[0987] Ar for The constraint is that when L-Ar is Ar not for

[0988] Het is a 5- to 6-membered heteroaryl group;

[0989] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[0990] Each R2 is independently H, halogen, or C1-C4 alkyl;

[0991] R 3 For H or F;

[0992] R 11 It is H or -CH3;

[0993] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[0994] R 22 It is H, halogen, or C1-C2 alkyl; and

[0995] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[0996] Each t is independently 0 or 1; and

[0997] Each R 241 Independently H or C1-C2 alkyl; or

[0998] (g) Equation (XV):

[0999]

[1000] Or its pharmaceutically acceptable salt, wherein:

[1001] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[1002] n is 1, 2, or 3;

[1003] m can be 1 or 2, and the constraint is that n+m≥3;

[1004] L-Ar is

[1005] Ar for The constraint is that when L-Ar is Ar not for

[1006] Het is a 5- to 6-membered heteroaryl group;

[1007] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1008] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1009] R 3 For H or F;

[1010] R 11 It is H or -CH3;

[1011] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[1012] R 22 It is H, halogen, or C1-C2 alkyl; or

[1013] (h) formula (XVI):

[1014]

[1015] Or its pharmaceutically acceptable salt, wherein:

[1016] L-Ar is

[1017] Ar for

[1018] Het is a 5- to 6-membered heteroaryl group;

[1019] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1020] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1021] R 3 For H or F;

[1022] R 11 It is H or -CH3;

[1023] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1024] R 22 It is H, halogen, or C1-C2 alkyl; and

[1025] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[1026] (i) Equation (XVII):

[1027]

[1028] Or its pharmaceutically acceptable salt, wherein:

[1029] L - Ar for

[1030] Ar for The constraint is that when L-Ar is Ar not for

[1031] Het is a 5- to 6-membered heteroaryl group;

[1032] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1033] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1034] R 3 For H or F;

[1035] R 11 It is H or -CH3;

[1036] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1037] R 22 It is H, halogen, or C1-C2 alkyl; and

[1038] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[1039] t is 0 or 1;

[1040] u is 0 or 1;

[1041] The constraint is that when u is 1, t is 1; and

[1042] R 241 It is H or C1-C2 alkyl; or

[1043] (j) Equation (XVIII):

[1044]

[1045] Or its pharmaceutically acceptable salt, wherein:

[1046] L-Ar is

[1047] Ar for The constraint is that when L-Ar is Ar not for

[1048] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[1049] Het is a 5- to 6-membered heteroaryl group;

[1050] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1051] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1052] R 3 For H or F;

[1053] R 11 It is H or -CH3;

[1054] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1055] R 22 It is H, halogen, or C1-C2 alkyl; and

[1056] R 35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[1057] (k) Equation (XIX):

[1058]

[1059] Or its pharmaceutically acceptable salt, wherein:

[1060] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[1061] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[1062] Each R 27 Independently H or C1-C4 alkyl, or two R 27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[1063] Ar for

[1064] Het is a 5- to 6-membered heteroaryl group;

[1065] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1066] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1067] R 3 For H or F;

[1068] R 11 It is H or -CH3;

[1069] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[1070] R 22 It is H, halogen, or C1-C2 alkyl; or

[1071] (l) Equation (XX):

[1072]

[1073] Or its pharmaceutically acceptable salt, wherein:

[1074] L-Ar is

[1075] Ar for

[1076] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1077] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1078] R 3 For H or F;

[1079] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1080] R 22 It is H, halogen, or C1-C2 alkyl;

[1081] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[1082] R 25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[1083] (m) Equation (XI):

[1084]

[1085] Or its pharmaceutically acceptable salt, wherein:

[1086] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1087] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1088] When R1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1089] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1090] R 3 It can be H, -OH, or a halogen;

[1091] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[1092] R 22 It is H, halogen, C1-C2 alkyl; and

[1093] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[1094] In various respects, this disclosure relates to a method for treating cirrhosis in a subject in need, the method comprising administering a fatty acid synthase inhibitor having the following formula to the subject in need:

[1095] (a) Equation (IX)

[1096]

[1097] Or its pharmaceutically acceptable salt, wherein:

[1098] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1099] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1100] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1101] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1102] R 3 It can be H, -OH, or a halogen;

[1103] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[1104] R 22 It is H, halogen, or C1-C2 alkyl;

[1105] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[1106] t is 0 or 1;

[1107] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1108] L 1 For CR 23 Or N;

[1109] L 2 For CH or N;

[1110] L 1 or L 2 At least one of them is N; and

[1111] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[1112] (b) Equation (X):

[1113]

[1114] Or its pharmaceutically acceptable salt, wherein:

[1115] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1116] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1117] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1118] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1119] R 3 It can be H, -OH, or a halogen;

[1120] L 3 For C(R) 60 2. O or NR 50 ;

[1121] Each R60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl), or -C(O)-N(R) 601 )2, of which:

[1122] t is 0 or 1; and

[1123] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1124] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[1125] t is 0 or 1; and

[1126] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1127] n is 1, 2, or 3;

[1128] m is 1 or 2;

[1129] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[1130] R 22 It can be H, halogen, or C1-C2 alkyl;

[1131] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[1132] t is 0 or 1; and

[1133] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1134] s is 0, 1, or 2;

[1135] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[1136] Where R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[1137] (c) Equation (VI-J)

[1138]

[1139] Or its pharmaceutically acceptable salt, wherein:

[1140] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1141] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1142] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1143] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[1144] R 3 It can be H, -OH, or a halogen;

[1145] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[1146] R 22 It is H, halogen, or C1-C2 alkyl;

[1147] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR351 or S(O)2R 351 ;and

[1148] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[1149] (d) Formula (XII):

[1150]

[1151] Or its pharmaceutically acceptable salt, wherein:

[1152] L-Ar is

[1153] Ar for

[1154] Het is a 5- to 6-membered heteroaryl group;

[1155] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1156] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1157] R 3 For H or F;

[1158] R 11 It is H or -CH3;

[1159] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1160] R 22 It is H, halogen, or C1-C2 alkyl;

[1161] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u-(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[1162] t is 0 or 1;

[1163] u is 0 or 1;

[1164] The constraint is that when u is 1, t is 1; and

[1165] Each R 241 Independently H or C1-C2 alkyl; and

[1166] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[1167] (e) Equation (XIII):

[1168]

[1169] Or its pharmaceutically acceptable salt, wherein:

[1170] L-Ar is

[1171] Ar for

[1172] Het is a 5- to 6-membered heteroaryl group;

[1173] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1174] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1175] R 3 For H or F;

[1176] R 11 It is H or -CH3;

[1177] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1178] R 22 It is H, halogen, or C1-C2 alkyl; and

[1179] Each R 24 and R25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[1180] Each t is independently 0 or 1;

[1181] Each u is independently 0 or 1; and

[1182] Each R 241 Independently H or C1-C2 alkyl; or

[1183] (f) Equation (XIV):

[1184]

[1185] Or its pharmaceutically acceptable salt, wherein:

[1186] L-Ar is

[1187] Ar for The constraint is that when L-Ar is Ar not for

[1188] Het is a 5- to 6-membered heteroaryl group;

[1189] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1190] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1191] R 3 For H or F;

[1192] R 11 It is H or -CH3;

[1193] R 21It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1194] R 22 It is H, halogen, or C1-C2 alkyl; and

[1195] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[1196] Each t is independently 0 or 1; and

[1197] Each R 241 Independently H or C1-C2 alkyl; or

[1198] (g) Equation (XV):

[1199]

[1200] Or its pharmaceutically acceptable salt, wherein:

[1201] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[1202] n is 1, 2, or 3;

[1203] m can be 1 or 2, and the constraint is that n+m≥3;

[1204] L-Ar is

[1205] Ar for The constraint is that when L-Ar is Ar not for

[1206] Het is a 5- to 6-membered heteroaryl group;

[1207] R1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1208] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1209] R 3 For H or F;

[1210] R 11 It is H or -CH3;

[1211] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[1212] R 22 It is H, halogen, or C1-C2 alkyl; or

[1213] (h) formula (XVI):

[1214]

[1215] Or its pharmaceutically acceptable salt, wherein:

[1216] L-Ar is

[1217] Ar for

[1218] Het is a 5- to 6-membered heteroaryl group;

[1219] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1220] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1221] R 3 For H or F;

[1222] R 11 It is H or -CH3;

[1223] R 21It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1224] R 22 It is H, halogen, or C1-C2 alkyl; and

[1225] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[1226] (i) Equation (XVII):

[1227]

[1228] Or its pharmaceutically acceptable salt, wherein:

[1229] L-Ar is

[1230] Ar for The constraint is that when L-Ar is Ar not for

[1231] Het is a 5- to 6-membered heteroaryl group;

[1232] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1233] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1234] R 3 For H or F;

[1235] R 11 It is H or -CH3;

[1236] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1237] R 22 It is H, halogen, or C1-C2 alkyl; and

[1238] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -Ou -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[1239] t is 0 or 1;

[1240] u is 0 or 1;

[1241] The constraint is that when u is 1, t is 1; and

[1242] R 241 It is H or C1-C2 alkyl; or

[1243] (j) Equation (XVIII):

[1244]

[1245] Or its pharmaceutically acceptable salt, wherein:

[1246] L-Ar is

[1247] Ar for The constraint is that when L-Ar is Ar not for

[1248] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[1249] Het is a 5- to 6-membered heteroaryl group;

[1250] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1251] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1252] R 3 For H or F;

[1253] R 11 It is H or -CH3;

[1254] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1255] R 22 It is H, halogen, or C1-C2 alkyl; and

[1256] R 35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[1257] (k) Equation (XIX):

[1258]

[1259] Or its pharmaceutically acceptable salt, wherein:

[1260] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[1261] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[1262] Each R 27 Independently H or C1-C4 alkyl, or two R 27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[1263] Ar for

[1264] Het is a 5- to 6-membered heteroaryl group;

[1265] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1266] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1267] R 3 For H or F;

[1268] R 11 It is H or -CH3;

[1269] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[1270] R 22 It is H, halogen, or C1-C2 alkyl; or

[1271] (l) Equation (XX):

[1272]

[1273] Or its pharmaceutically acceptable salt, wherein:

[1274] L-Ar is

[1275] Ar for

[1276] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1277] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1278] R 3 For H or F;

[1279] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1280] R 22 It is H, halogen, or C1-C2 alkyl;

[1281] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[1282] R 25It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[1283] (m) Equation (XI):

[1284]

[1285] Or its pharmaceutically acceptable salt, wherein:

[1286] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1287] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1288] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1289] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[1290] R 3 It can be H, -OH or halogen;

[1291] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[1292] R 22 It is H, halogen, C1-C2 alkyl; and

[1293] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[1294] In various respects, this disclosure relates to a method for treating liver fibrosis in a subject of need, the method comprising administering a fatty acid synthase inhibitor having the following formula to the subject of need:

[1295] (a) Equation (IX)

[1296]

[1297] Or its pharmaceutically acceptable salt, wherein:

[1298] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1299] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1300] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1301] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1302] R 3 It can be H, -OH or halogen;

[1303] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[1304] R 22 It is H, halogen, or C1-C2 alkyl;

[1305] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[1306] t is 0 or 1;

[1307] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1308] L 1 For CR 23 Or N;

[1309] L 2 For CH or N;

[1310] L 1 or L 2 At least one of them is N; and

[1311] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[1312] (b) Equation (X):

[1313]

[1314] Or its pharmaceutically acceptable salt, wherein:

[1315] R 1The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1316] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1317] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1318] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1319] R 3 It can be H, -OH or halogen;

[1320] L 3 For C(R) 60 2. O or NR 50 ;

[1321] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl) or -C(O)-N(R) 601 )2, of which:

[1322] t is 0 or 1; and

[1323] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1324] Each R 5O Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[1325] t is 0 or 1; and

[1326] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1327] n is 1, 2, or 3;

[1328] m is 1 or 2;

[1329] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[1330] R 22 It can be H, halogen, or C1-C2 alkyl;

[1331] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[1332] t is 0 or 1; and

[1333] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1334] s is 0, 1, or 2;

[1335] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[1336] Where R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[1337] (c) Equation (VI-J)

[1338]

[1339] Or its pharmaceutically acceptable salt, wherein:

[1340] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1341] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1342] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1343] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1344] R 3 It can be H, -OH or halogen;

[1345] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[1346] R 22 It is H, halogen, or C1-C2 alkyl;

[1347] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[1348] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[1349] (d) Formula (XII):

[1350]

[1351] Or its pharmaceutically acceptable salt, wherein:

[1352] L-Ar is

[1353] Ar for

[1354] Het is a 5- to 6-membered heteroaryl group;

[1355] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1356] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1357] R 3 For H or F;

[1358] R 11 It is H or -CH3;

[1359] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1360] R 22 It is H, halogen, or C1-C2 alkyl;

[1361] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[1362] t is 0 or 1;

[1363] u is 0 or 1;

[1364] The constraint is that when u is 1, t is 1; and

[1365] Each R 241 Independently H or C1-C2 alkyl; and

[1366] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[1367] (e) Equation (XIII):

[1368]

[1369] Or its pharmaceutically acceptable salt, wherein:

[1370] L-Ar is

[1371] Ar for

[1372] Het is a 5- to 6-membered heteroaryl group;

[1373] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1374] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1375] R 3 For H or F;

[1376] R 11 It is H or -CH3;

[1377] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1378] R 22 It is H, halogen, or C1-C2 alkyl; and

[1379] Each R 24 and R 25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[1380] Each t is independently 0 or 1;

[1381] Each u is independently 0 or 1; and

[1382] Each R 241 Independently H or C1-C2 alkyl; or

[1383] (f) Equation (XIV):

[1384]

[1385] Or its pharmaceutically acceptable salt, wherein:

[1386] L-Ar is

[1387] Ar for The constraint is that when L-Ar is Ar not for

[1388] Het is a 5- to 6-membered heteroaryl group;

[1389] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1390] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1391] R 3 For H or F;

[1392] R 11 It is H or -CH3;

[1393] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1394] R 22 It is H, halogen, or C1-C2 alkyl; and

[1395] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[1396] Each t is independently 0 or 1; and

[1397] Each R 241 Independently H or C1-C2 alkyl; or

[1398] (g) Equation (XV):

[1399]

[1400] Or its pharmaceutically acceptable salt, wherein:

[1401] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50-OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[1402] n is 1, 2, or 3;

[1403] m can be 1 or 2, and the constraint is that n+m≥3;

[1404] L-Ar is

[1405] Ar for The constraint is that when L-Ar is Ar not for

[1406] Het is a 5- to 6-membered heteroaryl group;

[1407] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1408] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1409] R 3 For H or F;

[1410] R 11 It is H or -CH3;

[1411] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[1412] R 22 It is H, halogen, or C1-C2 alkyl; or

[1413] (h) formula (XVI):

[1414]

[1415] Or its pharmaceutically acceptable salt, wherein:

[1416] L-Ar is

[1417] Ar for

[1418] Het is a 5- to 6-membered heteroaryl group;

[1419] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1420] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1421] R 3 For H or F;

[1422] R 11 It is H or -CH3;

[1423] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1424] R 22 It is H, halogen, or C1-C2 alkyl; and

[1425] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[1426] (i) Equation (XVII):

[1427]

[1428] Or its pharmaceutically acceptable salt, wherein:

[1429] L-Ar is

[1430] Ar for The constraint is that when L-Ar is Ar not for

[1431] Het is a 5- to 6-membered heteroaryl group;

[1432] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1433] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1434] R 3 For H or F;

[1435] R 11 It is H or -CH3;

[1436] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1437] R 22 It is H, halogen, or C1-C2 alkyl; and

[1438] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[1439] t is 0 or 1;

[1440] u is 0 or 1;

[1441] The constraint is that when u is 1, t is 1; and

[1442] R 241 It is H or C1-C2 alkyl; or

[1443] (j) Equation (XVIII):

[1444]

[1445] Or its pharmaceutically acceptable salt, wherein:

[1446] L-Ar is

[1447] Ar for The constraint is that when L-Ar is Ar not for

[1448] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[1449] Het is a 5- to 6-membered heteroaryl group;

[1450] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1451] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1452] R 3 For H or F;

[1453] R 11 It is H or -CH3;

[1454] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1455] R 22 It is H, halogen, or C1-C2 alkyl; and

[1456] R 35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[1457] (k) Equation (XIX):

[1458]

[1459] Or its pharmaceutically acceptable salt, wherein:

[1460] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[1461] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[1462] Each R 27 Independently H or C1-C4 alkyl, or two R27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[1463] Ar for

[1464] Het is a 5- to 6-membered heteroaryl group;

[1465] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1466] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1467] R 3 For H or F;

[1468] R 11 It is H or -CH3;

[1469] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[1470] R 22 It is H, halogen, or C1-C2 alkyl; or

[1471] (l) Equation (XX):

[1472]

[1473] Or its pharmaceutically acceptable salt, wherein:

[1474] L-Ar is

[1475] Ar for

[1476] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1477] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1478] R 3 For H or F;

[1479] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1480] R 22 It is H, halogen, or C1-C2 alkyl;

[1481] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[1482] R 25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[1483] (m) Equation (XI):

[1484]

[1485] Or its pharmaceutically acceptable salt, wherein:

[1486] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1487] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1488] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1489] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1490] R 3 It can be H, -OH or halogen;

[1491] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[1492] R 22 It is H, halogen, C1-C2 alkyl; and

[1493] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[1494] In various respects, this disclosure relates to a method for treating liver cancer in a subject of need, the method comprising administering a fatty acid synthase inhibitor having the following formula to the subject of need:

[1495] (a) Equation (IX)

[1496]

[1497] Or its pharmaceutically acceptable salt, wherein:

[1498] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1499] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1500] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1501] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1502] R 3 It can be H, -OH or halogen;

[1503] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[1504] R 22 It is H, halogen, or C1-C2 alkyl;

[1505] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[1506] t is 0 or 1;

[1507] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1508] L 1 For CR 23 Or N;

[1509] L2 For CH or N;

[1510] L 1 or L 2 At least one of them is N; and

[1511] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[1512] (b) Equation (X):

[1513]

[1514] Or its pharmaceutically acceptable salt, wherein:

[1515] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1516] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1517] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1518] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1519] R 3 It can be H, -OH or halogen;

[1520] L 3 For C(R) 60 2. O or NR 50 ;

[1521] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl) or -C(O)-N(R) 601 )2, of which:

[1522] t is 0 or 1; and

[1523] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1524] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t-(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[1525] t is 0 or 1; and

[1526] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1527] n is 1, 2, or 3;

[1528] m is 1 or 2;

[1529] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[1530] R 22 It can be H, halogen, or C1-C2 alkyl;

[1531] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[1532] t is 0 or 1; and

[1533] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1534] s is 0, 1, or 2;

[1535] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[1536] Where R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[1537] (c) Equation (VI-J)

[1538]

[1539] Or its pharmaceutically acceptable salt, wherein:

[1540] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1541] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1542] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1543] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[1544] R 3 It can be H, -OH or halogen;

[1545] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[1546] R 22 It is H, halogen, or C1-C2 alkyl;

[1547] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[1548] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[1549] (d) Formula (XII):

[1550]

[1551] Or its pharmaceutically acceptable salt, wherein:

[1552] L-Ar is

[1553] Ar for

[1554] Het is a 5- to 6-membered heteroaryl group;

[1555] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1556] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1557] R 3 For H or F;

[1558] R 11 It is H or -CH3;

[1559] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1560] R 22 It is H, halogen, or C1-C2 alkyl;

[1561] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[1562] t is 0 or 1;

[1563] u is 0 or 1;

[1564] The constraint is that when u is 1, t is 1; and

[1565] Each R 241 Independently H or C1-C2 alkyl; and

[1566] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[1567] (e) Equation (XIII):

[1568]

[1569] Or its pharmaceutically acceptable salt, wherein:

[1570] L-Ar is

[1571] Ar for

[1572] Het is a 5- to 6-membered heteroaryl group;

[1573] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1574] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1575] R 3 For H or F;

[1576] R 11 It is H or -CH3;

[1577] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1578] R 22 It is H, halogen, or C1-C2 alkyl; and

[1579] Each R 24 and R 25 Independently, it is H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[1580] Each t is independently 0 or 1;

[1581] Each u is independently 0 or 1; and

[1582] Each R 241 Independently H or C1-C2 alkyl; or

[1583] (f) Equation (XIV):

[1584]

[1585] Or its pharmaceutically acceptable salt, wherein:

[1586] L-Ar is

[1587] Ar for The constraint is that when L-Ar is Ar not for

[1588] Het is a 5- to 6-membered heteroaryl group;

[1589] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1590] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1591] R 3 For H or F;

[1592] R 11 It is H or -CH3;

[1593] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1594] R 22 It is H, halogen, or C1-C2 alkyl; and

[1595] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t-O-(C1-C4 alkyl), wherein:

[1596] Each t is independently 0 or 1; and

[1597] Each R 241 Independently H or C1-C2 alkyl; or

[1598] (g) Equation (XV):

[1599]

[1600] Or its pharmaceutically acceptable salt, wherein:

[1601] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[1602] n is 1, 2, or 3;

[1603] m can be 1 or 2, and the constraint is that n+m≥3;

[1604] L-Ar is

[1605] Ar for The constraint is that when L-Ar is Ar not for

[1606] Het is a 5- to 6-membered heteroaryl group;

[1607] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1608] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1609] R 3 For H or F;

[1610] R 11 It is H or -CH3;

[1611] R 21It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[1612] R 22 It is H, halogen, or C1-C2 alkyl; or

[1613] (h) formula (XVI):

[1614]

[1615] Or its pharmaceutically acceptable salt, wherein:

[1616] L-Ar is

[1617] Ar for

[1618] Het is a 5- to 6-membered heteroaryl group;

[1619] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1620] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1621] R 3 For H or F;

[1622] R 11 It is H or -CH3;

[1623] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1624] R 22 It is H, halogen, or C1-C2 alkyl; and

[1625] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[1626] (i) Equation (XVII):

[1627]

[1628] Or its pharmaceutically acceptable salt, wherein:

[1629] L-Ar is

[1630] Ar for The constraint is that when L-Ar is Ar not for

[1631] Het is a 5- to 6-membered heteroaryl group;

[1632] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1633] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1634] R 3 For H or F;

[1635] R 11 It is H or -CH3;

[1636] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1637] R 22 It is H, halogen, or C1-C2 alkyl; and

[1638] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[1639] t is 0 or 1;

[1640] u is 0 or 1;

[1641] The constraint is that when u is 1, t is 1; and

[1642] R 241 It is H or C1-C2 alkyl; or

[1643] (j) Equation (XVIII):

[1644]

[1645] Or its pharmaceutically acceptable salt, wherein:

[1646] L-Ar is

[1647] Ar for The constraint is that when L-Ar is Ar not for

[1648] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[1649] Het is a 5- to 6-membered heteroaryl group;

[1650] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1651] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1652] R 3 For H or F;

[1653] R 11 It is H or -CH3;

[1654] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1655] R 22 It is H, halogen, or C1-C2 alkyl; and

[1656] R 35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[1657] (k) Equation (XIX):

[1658]

[1659] Or its pharmaceutically acceptable salt, wherein:

[1660] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[1661] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[1662] Each R 27 Independently H or C1-C4 alkyl, or two R 27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[1663] Ar for

[1664] Het is a 5- to 6-membered heteroaryl group;

[1665] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1666] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1667] R 3 For H or F;

[1668] R 11 It is H or -CH3;

[1669] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[1670] R 22 It is H, halogen, or C1-C2 alkyl; or

[1671] (l) Equation (XX):

[1672]

[1673] Or its pharmaceutically acceptable salt, wherein:

[1674] L-Ar is

[1675] Ar for

[1676] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1677] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1678] R 3 For H or F;

[1679] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1680] R 22 It is H, halogen, or C1-C2 alkyl;

[1681] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[1682] R 25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[1683] (m) Equation (XI):

[1684]

[1685] Or its pharmaceutically acceptable salt, wherein:

[1686] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1687] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1688] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1689] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[1690] R 3 It can be H, -OH or halogen;

[1691] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[1692] R 22 It is H, halogen, C1-C2 alkyl; and

[1693] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[1694] In various respects, this disclosure relates to a method for treating a disease or condition in a subject of need with elevated interleukin 1β (IL1β) levels, the method comprising administering to the subject of need a fatty acid synthase inhibitor having the following formula:

[1695] (a) Equation (IX)

[1696]

[1697] Or its pharmaceutically acceptable salt, wherein:

[1698] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1699] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1700] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1701] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1702] R 3 It can be H, -OH or halogen;

[1703] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[1704] R22 It is H, halogen, or C1-C2 alkyl;

[1705] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[1706] t is 0 or 1;

[1707] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1708] L 1 For CR 23 Or N;

[1709] L 2 For CH or N;

[1710] L 1 or L 2 At least one of them is N; and

[1711] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[1712] (b) Equation (X):

[1713]

[1714] Or its pharmaceutically acceptable salt, wherein:

[1715] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1716] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1717] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1718] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1719] R 3 It can be H, -OH or halogen;

[1720] L 3 For C(R) 60 2. O or NR50 ;

[1721] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl) or -C(O)-N(R) 601 )2, of which:

[1722] t is 0 or 1; and

[1723] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1724] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[1725] t is 0 or 1; and

[1726] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1727] n is 1, 2, or 3;

[1728] m is 1 or 2;

[1729] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[1730] R 22 It can be H, halogen, or C1-C2 alkyl;

[1731] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[1732] t is 0 or 1; and

[1733] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1734] s is 0, 1, or 2;

[1735] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[1736] Where R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[1737] (c) Equation (VI-J)

[1738]

[1739] Or its pharmaceutically acceptable salt, wherein:

[1740] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1741] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1742] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1743] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1744] R 3 It can be H, -OH or halogen;

[1745] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[1746] R 22 It is H, halogen, or C1-C2 alkyl;

[1747] R 35 -C(O)-R 351-C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[1748] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[1749] (d) Formula (XII):

[1750]

[1751] Or its pharmaceutically acceptable salt, wherein:

[1752] L-Ar is

[1753] Ar for

[1754] Het is a 5- to 6-membered heteroaryl group;

[1755] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1756] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1757] R 3 For H or F;

[1758] R 11 It is H or -CH3;

[1759] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1760] R 22 It is H, halogen, or C1-C2 alkyl;

[1761] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -Ou -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[1762] t is 0 or 1;

[1763] u is 0 or 1;

[1764] The constraint is that when u is 1, t is 1; and

[1765] Each R 241 Independently H or C1-C2 alkyl; and

[1766] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[1767] (e) Equation (XIII):

[1768]

[1769] Or its pharmaceutically acceptable salt, wherein:

[1770] L-Ar is

[1771] Ar for

[1772] Het is a 5- to 6-membered heteroaryl group;

[1773] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1774] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1775] R 3 For H or F;

[1776] R 11 It is H or -CH3;

[1777] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1778] R 22 It is H, halogen, or C1-C2 alkyl; and

[1779] Each R 24and R 25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[1780] Each t is independently 0 or 1;

[1781] Each u is independently 0 or 1; and

[1782] Each R 241 Independently H or C1-C2 alkyl; or

[1783] (f) Equation (XIV):

[1784]

[1785] Or its pharmaceutically acceptable salt, wherein:

[1786] L-Ar is

[1787] Ar for The constraint is that when L-Ar is Ar not for

[1788] Het is a 5- to 6-membered heteroaryl group;

[1789] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1790] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1791] R 3 For H or F;

[1792] R 11 It is H or -CH3;

[1793] R 21It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1794] R 22 It is H, halogen, or C1-C2 alkyl; and

[1795] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[1796] Each t is independently 0 or 1; and

[1797] Each R 241 Independently H or C1-C2 alkyl; or

[1798] (g) Equation (XV):

[1799]

[1800] Or its pharmaceutically acceptable salt, wherein:

[1801] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[1802] n is 1, 2, or 3;

[1803] m can be 1 or 2, and the constraint is that n+m≥3;

[1804] L-Ar is

[1805] Ar for The constraint is that when L-Ar is Ar not for

[1806] Het is a 5- to 6-membered heteroaryl group;

[1807] R1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1808] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1809] R 3 For H or F;

[1810] R 11 It is H or -CH3;

[1811] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[1812] R 22 It is H, halogen, or C1-C2 alkyl; or

[1813] (h) formula (XVI):

[1814]

[1815] Or its pharmaceutically acceptable salt, wherein:

[1816] L-Ar is

[1817] Ar for

[1818] Het is a 5- to 6-membered heteroaryl group;

[1819] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1820] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1821] R 3 For H or F;

[1822] R 11 It is H or -CH3;

[1823] R 21It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1824] R 22 It is H, halogen, or C1-C2 alkyl; and

[1825] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[1826] (i) Equation (XVII):

[1827]

[1828] Or its pharmaceutically acceptable salt, wherein:

[1829] L-Ar is

[1830] Ar for The constraint is that when L-Ar is Ar not for

[1831] Het is a 5- to 6-membered heteroaryl group;

[1832] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1833] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1834] R 3 For H or F;

[1835] R 11 It is H or -CH3;

[1836] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1837] R 22 It is H, halogen, or C1-C2 alkyl; and

[1838] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -Ou -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[1839] t is 0 or 1;

[1840] u is 0 or 1;

[1841] The constraint is that when u is 1, t is 1; and

[1842] R 241 It is H or C1-C2 alkyl; or

[1843] (j) Equation (XVIII):

[1844]

[1845] Or its pharmaceutically acceptable salt, wherein:

[1846] L-Ar is

[1847] Ar for The constraint is that when L-Ar is Ar not for

[1848] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[1849] Het is a 5- to 6-membered heteroaryl group;

[1850] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1851] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1852] R 3 For H or F;

[1853] R 11 It is H or -CH3;

[1854] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1855] R 22 It is H, halogen, or C1-C2 alkyl; and

[1856] R 35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[1857] (k) Equation (XIX):

[1858]

[1859] Or its pharmaceutically acceptable salt, wherein:

[1860] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[1861] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[1862] Each R 27 Independently H or C1-C4 alkyl, or two R 27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[1863] Ar for

[1864] Het is a 5- to 6-membered heteroaryl group;

[1865] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1866] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1867] R 3 For H or F;

[1868] R 11 It is H or -CH3;

[1869] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[1870] R 22 It is H, halogen, or C1-C2 alkyl; or

[1871] (l) Equation (XX):

[1872]

[1873] Or its pharmaceutically acceptable salt, wherein:

[1874] L-Ar is

[1875] Ar for

[1876] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1877] Each R 2 Independently, it is H, halogen, or C1-C4 alkyl;

[1878] R 3 For H or F;

[1879] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1880] R 22 It is H, halogen, or C1-C2 alkyl;

[1881] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[1882] R25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[1883] (m) Equation (XI):

[1884]

[1885] Or its pharmaceutically acceptable salt, wherein:

[1886] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1887] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1888] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1889] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1890] R 3 It can be H, -OH, or a halogen;

[1891] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[1892] R 22 It is H, halogen, C1-C2 alkyl; and

[1893] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[1894] In various respects, this disclosure relates to a method for treating a disease or condition in which a subject in need has elevated levels of t-helper (Th) cells, the method comprising administering to the subject in need a fatty acid synthase inhibitor having the following formula:

[1895] (a) Equation (IX)

[1896]

[1897] Or its pharmaceutically acceptable salt, wherein:

[1898] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1899] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1900] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1901] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1902] R 3 It can be H, -OH, or a halogen;

[1903] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[1904] R 22 It is H, halogen, or C1-C2 alkyl;

[1905] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[1906] t is 0 or 1;

[1907] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1908] L 1 For CR 23 Or N;

[1909] L 2 For CH or N;

[1910] L 1 or L 2 At least one of them is N; and

[1911] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[1912] (b) Equation (X):

[1913]

[1914] Or its pharmaceutically acceptable salt, wherein:

[1915] R 1The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1916] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1917] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1918] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[1919] R 3 It can be H, -OH or halogen;

[1920] L 3 For C(R) 60 2. O or NR 50 ;

[1921] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl) or -C(O)-N(R) 601 )2, of which:

[1922] t is 0 or 1; and

[1923] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1924] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[1925] t is 0 or 1; and

[1926] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1927] n is 1, 2, or 3;

[1928] m is 1 or 2;

[1929] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[1930] R 22 It can be H, halogen, or C1-C2 alkyl;

[1931] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[1932] t is 0 or 1; and

[1933] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[1934] s is 0, 1, or 2;

[1935] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[1936] Where R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[1937] (c) Equation (VI-J)

[1938]

[1939] Or its pharmaceutically acceptable salt, wherein:

[1940] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[1941] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[1942] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[1943] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[1944] R 3 It can be H, -OH or halogen;

[1945] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[1946] R 22 It is H, halogen, or C1-C2 alkyl;

[1947] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[1948] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[1949] (d) Formula (XII):

[1950]

[1951] Or its pharmaceutically acceptable salt, wherein:

[1952] L-Ar is

[1953] Ar for

[1954] Het is a 5- to 6-membered heteroaryl group;

[1955] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1956] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1957] R 3 For H or F;

[1958] R 11 It is H or -CH3;

[1959] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1960] R 22 It is H, halogen, or C1-C2 alkyl;

[1961] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[1962] t is 0 or 1;

[1963] u is 0 or 1;

[1964] The constraint is that when u is 1, t is 1; and

[1965] Each R 241 Independently H or C1-C2 alkyl; and

[1966] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[1967] (e) Equation (XIII):

[1968]

[1969] Or its pharmaceutically acceptable salt, wherein:

[1970] L-Ar is

[1971] Ar for

[1972] Het is a 5- to 6-membered heteroaryl group;

[1973] R 1It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1974] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1975] R 3 For H or F;

[1976] R 11 It is H or -CH3;

[1977] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[1978] R 22 It is H, halogen, or C1-C2 alkyl; and

[1979] Each R 24 and R 25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[1980] Each t is independently 0 or 1;

[1981] Each u is independently 0 or 1; and

[1982] Each R 241 Independently H or C1-C2 alkyl; or

[1983] (f) Equation (XIV):

[1984]

[1985] Or its pharmaceutically acceptable salt, wherein:

[1986] L-Ar is

[1987] Ar for The constraint is that when L-Ar is Ar not for

[1988] Het is a 5- to 6-membered heteroaryl group;

[1989] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[1990] Each R2 is independently H, halogen, or C1-C4 alkyl;

[1991] R 3 For H or F;

[1992] R 11 It is H or -CH3;

[1993] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[1994] R 22 It is H, halogen, or C1-C2 alkyl; and

[1995] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[1996] Each t is independently 0 or 1; and

[1997] Each R 241 Independently H or C1-C2 alkyl; or

[1998] (g) Equation (XV):

[1999]

[2000] Or its pharmaceutically acceptable salt, wherein:

[2001] L 3-CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[2002] n is 1, 2, or 3;

[2003] m can be 1 or 2, and the constraint is that n+m≥3;

[2004] L-Ar is

[2005] Ar for The constraint is that when L-Ar is Ar not for

[2006] Het is a 5- to 6-membered heteroaryl group;

[2007] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2008] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2009] R 3 For H or F;

[2010] R 11 It is H or -CH3;

[2011] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[2012] R 22 It is H, halogen, or C1-C2 alkyl; or

[2013] (h) formula (XVI):

[2014]

[2015] Or its pharmaceutically acceptable salt, wherein:

[2016] L-Ar is

[2017] Ar for

[2018] Het is a 5- to 6-membered heteroaryl group;

[2019] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2020] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2021] R 3 For H or F;

[2022] R 11 It is H or -CH3;

[2023] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2024] R 22 It is H, halogen, or C1-C2 alkyl; and

[2025] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[2026] (i) Equation (XVII):

[2027]

[2028] Or its pharmaceutically acceptable salt, wherein:

[2029] L-Ar is

[2030] Ar for The constraint is that when L-Ar is Ar not for

[2031] Het is a 5- to 6-membered heteroaryl group;

[2032] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1Optionally replaced by one or more halogens;

[2033] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2034] R 3 For H or F;

[2035] R 11 It is H or -CH3;

[2036] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2037] R 22 It is H, halogen, or C1-C2 alkyl; and

[2038] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[2039] t is 0 or 1;

[2040] u is 0 or 1;

[2041] The constraint is that when u is 1, t is 1; and

[2042] R 241 It is H or C1-C2 alkyl; or

[2043] (j) Equation (XVIII):

[2044]

[2045] Or its pharmaceutically acceptable salt, wherein:

[2046] L-Ar is

[2047] Ar for The constraint is that when L-Ar is Ar not for

[2048] L 2 -NHR 35 or -C(O)NHR 351 , where R351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[2049] Het is a 5- to 6-membered heteroaryl group;

[2050] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2051] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2052] R 3 For H or F;

[2053] R 11 It is H or -CH3;

[2054] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[2055] R 22 It is H, halogen, or C1-C2 alkyl; and

[2056] R 35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[2057] (k) Equation (XIX):

[2058]

[2059] Or its pharmaceutically acceptable salt, wherein:

[2060] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[2061] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[2062] Each R 27 Independently H or C1-C4 alkyl, or two R 27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[2063] Ar for

[2064] Het is a 5- to 6-membered heteroaryl group;

[2065] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2066] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2067] R 3 For H or F;

[2068] R 11 It is H or -CH3;

[2069] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[2070] R 22 It is H, halogen, or C1-C2 alkyl; or

[2071] (l) Equation (XX):

[2072]

[2073] Or its pharmaceutically acceptable salt, wherein:

[2074] L-Ar is

[2075] Ar for

[2076] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2077] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2078] R 3 For H or F;

[2079] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2080] R 22 It is H, halogen, or C1-C2 alkyl;

[2081] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[2082] R 25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[2083] (m) Equation (XI):

[2084]

[2085] Or its pharmaceutically acceptable salt, wherein:

[2086] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2087] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2088] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2089] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[2090] R 3 It can be H, -OH or halogen;

[2091] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[2092] R 22It is H, halogen, C1-C2 alkyl; and

[2093] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[2094] In all respects, this disclosure relates to a regulatory T cell (T cell) for treating a subject in need. reg A method for reducing or suppressing a disease or condition, the method comprising administering to the subject in need a fatty acid synthase inhibitor having the following formula:

[2095] (a) Equation (IX)

[2096]

[2097] Or its pharmaceutically acceptable salt, wherein:

[2098] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2099] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2100] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2101] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[2102] R 3 It can be H, -OH or halogen;

[2103] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[2104] R 22 It is H, halogen, or C1-C2 alkyl;

[2105] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[2106] t is 0 or 1;

[2107] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2108] L 1 For CR 23 Or N;

[2109] L 2 For CH or N;

[2110] L 1 or L 2 At least one of them is N; and

[2111] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[2112] (b) Equation (X):

[2113]

[2114] Or its pharmaceutically acceptable salt, wherein:

[2115] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2116] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2117] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2118] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[2119] R 3 It can be H, -OH or halogen;

[2120] L 3 For C(R) 60 2. O or NR 50 ;

[2121] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl), or -C(O)-N(R) 601 )2, of which:

[2122] t is 0 or 1; and

[2123] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2124] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[2125] t is 0 or 1; and

[2126] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2127] n is 1, 2, or 3;

[2128] m is 1 or 2;

[2129] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[2130] R 22 It can be H, halogen, or C1-C2 alkyl;

[2131] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[2132] t is 0 or 1; and

[2133] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2134] s is 0, 1, or 2;

[2135] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[2136] Where R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[2137] (c) Equation (VI-J)

[2138]

[2139] Or its pharmaceutically acceptable salt, wherein:

[2140] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2141] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2142] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2143] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[2144] R 3 It can be H, -OH or halogen;

[2145] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[2146] R 22 It is H, halogen, or C1-C2 alkyl;

[2147] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[2148] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[2149] (d) Formula (XII):

[2150]

[2151] Or its pharmaceutically acceptable salt, wherein:

[2152] L-Ar is

[2153] Ar for

[2154] Het is a 5- to 6-membered heteroaryl group;

[2155] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2156] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2157] R 3 For H or F;

[2158] R 11 It is H or -CH3;

[2159] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2160] R 22 It is H, halogen, or C1-C2 alkyl;

[2161] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[2162] t is 0 or 1;

[2163] u is 0 or 1;

[2164] The constraint is that when u is 1, t is 1; and

[2165] Each R 241 Independently H or C1-C2 alkyl; and

[2166] R25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[2167] (e) Equation (XIII):

[2168]

[2169] Or its pharmaceutically acceptable salt, wherein:

[2170] L-Ar is

[2171] Ar for

[2172] Het is a 5- to 6-membered heteroaryl group;

[2173] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2174] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2175] R 3 For H or F;

[2176] R 11 It is H or -CH3;

[2177] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2178] R 22 It is H, halogen, or C1-C2 alkyl; and

[2179] Each R 24 and R 25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[2180] Each t is independently 0 or 1;

[2181] Each u is independently 0 or 1; and

[2182] Each R 241 Independently H or C1-C2 alkyl; or

[2183] (f) Equation (XIV):

[2184]

[2185] Or its pharmaceutically acceptable salt, wherein:

[2186] L-Ar is

[2187] Ar for The constraint is that when L-Ar is Ar not for

[2188] Het is a 5- to 6-membered heteroaryl group;

[2189] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2190] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2191] R 3 For H or F;

[2192] R 11 It is H or -CH3;

[2193] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[2194] R 22 It is H, halogen, or C1-C2 alkyl; and

[2195] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t-(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[2196] Each t is independently 0 or 1; and

[2197] Each R 241 Independently H or C1-C2 alkyl; or

[2198] (g) Equation (XV):

[2199]

[2200] Or its pharmaceutically acceptable salt, wherein:

[2201] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[2202] n is 1, 2, or 3;

[2203] m can be 1 or 2, and the constraint is that n+m≥3;

[2204] L-Ar is

[2205] Ar for The constraint is that when L-Ar is Ar not for

[2206] Het is a 5- to 6-membered heteroaryl group;

[2207] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2208] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2209] R 3 For H or F;

[2210] R 11 It is H or -CH3;

[2211] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[2212] R 22 It is H, halogen, or C1-C2 alkyl; or

[2213] (h) formula (XVI):

[2214]

[2215] Or its pharmaceutically acceptable salt, wherein:

[2216] L-Ar is

[2217] Ar for

[2218] Het is a 5- to 6-membered heteroaryl group;

[2219] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2220] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2221] R 3 For H or F;

[2222] R 11 It is H or -CH3;

[2223] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[2224] R 22 It is H, halogen, or C1-C2 alkyl; and

[2225] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[2226] (i) Equation (XVII):

[2227]

[2228] Or its pharmaceutically acceptable salt, wherein:

[2229] L-Ar is

[2230] Ar for The constraint is that when L-Ar is Ar not for

[2231] Het is a 5- to 6-membered heteroaryl group;

[2232] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2233] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2234] R 3 For H or F;

[2235] R 11 It is H or -CH3;

[2236] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[2237] R 22 It is H, halogen, or C1-C2 alkyl; and

[2238] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[2239] t is 0 or 1;

[2240] u is 0 or 1;

[2241] The constraint is that when u is 1, t is 1; and

[2242] R 241It is H or C1-C2 alkyl; or

[2243] (j) Equation (XVIII):

[2244]

[2245] Or its pharmaceutically acceptable salt, wherein:

[2246] L-Ar is

[2247] Ar for The constraint is that when L-Ar is Ar not for

[2248] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[2249] Het is a 5- to 6-membered heteroaryl group;

[2250] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2251] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2252] R 3 For H or F;

[2253] R 11 It is H or -CH3;

[2254] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[2255] R 22 It is H, halogen, or C1-C2 alkyl; and

[2256] R 35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[2257] (k) Equation (XIX):

[2258]

[2259] Or its pharmaceutically acceptable salt, wherein:

[2260] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[2261] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[2262] Each R 27 Independently H or C1-C4 alkyl, or two R 27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[2263] Ar for

[2264] Het is a 5- to 6-membered heteroaryl group;

[2265] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2266] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2267] R 3 For H or F;

[2268] R 11 It is H or -CH3;

[2269] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[2270] R 22It is H, halogen, or C1-C2 alkyl; or

[2271] (l) Equation (XX):

[2272]

[2273] Or its pharmaceutically acceptable salt, wherein:

[2274] L-Ar is

[2275] Ar for

[2276] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2277] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2278] R 3 For H or F;

[2279] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[2280] R 22 It is H, halogen, or C1-C2 alkyl;

[2281] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[2282] R 25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[2283] (m) Equation (XI):

[2284]

[2285] Or its pharmaceutically acceptable salt, wherein:

[2286] R 1The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2287] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2288] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2289] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[2290] R 3 It can be H, -OH, or a halogen;

[2291] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[2292] R 22 It is H, halogen, C1-C2 alkyl; and

[2293] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[2294] In various respects, this disclosure relates to a method for reversing definitive nonalcoholic steatohepatitis (NASH), the method comprising administering a fatty acid synthase inhibitor having the following formula to a subject in need:

[2295] (a) Equation (IX)

[2296]

[2297] Or its pharmaceutically acceptable salt, wherein:

[2298] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2299] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2300] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2301] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[2302] R 3 It can be H, -OH, or a halogen;

[2303] R21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[2304] R 22 It is H, halogen, or C1-C2 alkyl;

[2305] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[2306] t is 0 or 1;

[2307] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2308] L 1 For CR 23 Or N;

[2309] L 2 For CH or N;

[2310] L 1 or L 2 At least one of them is N; and

[2311] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[2312] (b) Equation (X):

[2313]

[2314] Or its pharmaceutically acceptable salt, wherein:

[2315] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2316] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2317] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2318] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[2319] R 3 It can be H, -OH or halogen;

[2320] L 3 For C(R) 60 2. O or NR 50 ;

[2321] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl), or -C(O)-N(R) 601 )2, of which:

[2322] t is 0 or 1; and

[2323] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2324] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[2325] t is 0 or 1; and

[2326] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2327] n is 1, 2, or 3;

[2328] m is 1 or 2;

[2329] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[2330] R 22 It can be H, halogen, or C1-C2 alkyl;

[2331] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R)501 )2, of which:

[2332] t is 0 or 1; and

[2333] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2334] s is 0, 1, or 2;

[2335] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[2336] Where R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[2337] (c) Equation (VI-J)

[2338]

[2339] Or its pharmaceutically acceptable salt, wherein:

[2340] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2341] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2342] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2343] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[2344] R 3 It can be H, -OH, or a halogen;

[2345] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[2346] R 22 It is H, halogen, or C1-C2 alkyl;

[2347] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[2348] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[2349] (d) Formula (XII):

[2350]

[2351] Or its pharmaceutically acceptable salt, wherein:

[2352] L-Ar is

[2353] Ar for

[2354] Het is a 5- to 6-membered heteroaryl group;

[2355] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2356] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2357] R 3 For H or F;

[2358] R 11 It is H or -CH3;

[2359] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[2360] R 22 It is H, halogen, or C1-C2 alkyl;

[2361] R 24H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[2362] t is 0 or 1;

[2363] u is 0 or 1;

[2364] The constraint is that when u is 1, t is 1; and

[2365] Each R 241 Independently H or C1-C2 alkyl; and

[2366] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[2367] (e) Equation (XIII):

[2368]

[2369] Or its pharmaceutically acceptable salt, wherein:

[2370] L-Ar is

[2371] Ar for

[2372] Het is a 5- to 6-membered heteroaryl group;

[2373] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2374] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2375] R 3 For H or F;

[2376] R 11 It is H or -CH3;

[2377] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2378] R 22 It is H, halogen, or C1-C2 alkyl; and

[2379] Each R 24 and R 25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[2380] Each t is independently 0 or 1;

[2381] Each u is independently 0 or 1; and

[2382] Each R 241 Independently H or C1-C2 alkyl; or

[2383] (f) Equation (XIV):

[2384]

[2385] Or its pharmaceutically acceptable salt, wherein:

[2386] L-Ar is

[2387] Ar for The constraint is that when L-Ar is Ar not for

[2388] Het is a 5- to 6-membered heteroaryl group;

[2389] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2390] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2391] R 3 For H or F;

[2392] R 11 It is H or -CH3;

[2393] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2394] R 22 It is H, halogen, or C1-C2 alkyl; and

[2395] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[2396] Each t is independently 0 or 1; and

[2397] Each R 241 Independently H or C1-C2 alkyl; or

[2398] (g) Equation (XV):

[2399]

[2400] Or its pharmaceutically acceptable salt, wherein:

[2401] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[2402] n is 1, 2, or 3;

[2403] m can be 1 or 2, and the constraint is that n+m≥3;

[2404] L-Ar is

[2405] Ar for The constraint is that when L-Ar is Ar not for

[2406] Het is a 5- to 6-membered heteroaryl group;

[2407] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2408] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2409] R 3 For H or F;

[2410] R 11 It is H or -CH3;

[2411] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[2412] R 22 It is H, halogen, or C1-C2 alkyl; or

[2413] (h) formula (XVI):

[2414]

[2415] Or its pharmaceutically acceptable salt, wherein:

[2416] L-Ar is

[2417] Ar for

[2418] Het is a 5- to 6-membered heteroaryl group;

[2419] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2420] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2421] R 3 For H or F;

[2422] R 11 It is H or -CH3;

[2423] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2424] R 22 It is H, halogen, or C1-C2 alkyl; and

[2425] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[2426] (i) Equation (XVII):

[2427]

[2428] Or its pharmaceutically acceptable salt, wherein:

[2429] L-Ar is

[2430] Ar for The constraint is that when L-Ar is Ar not for

[2431] Het is a 5- to 6-membered heteroaryl group;

[2432] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2433] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2434] R 3 For H or F;

[2435] R 11 It is H or -CH3;

[2436] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2437] R 22 It is H, halogen, or C1-C2 alkyl; and

[2438] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[2439] t is 0 or 1;

[2440] u is 0 or 1;

[2441] The constraint is that when u is 1, t is 1; and

[2442] R 241 It is H or C1-C2 alkyl; or

[2443] (j) Equation (XVIII):

[2444]

[2445] Or its pharmaceutically acceptable salt, wherein:

[2446] L-Ar is

[2447] Ar for The constraint is that when L-Ar is Ar not for

[2448] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[2449] Het is a 5- to 6-membered heteroaryl group;

[2450] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2451] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2452] R 3 For H or F;

[2453] R 11 It is H or -CH3;

[2454] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2455] R 22 It is H, halogen, or C1-C2 alkyl; and

[2456] R 35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[2457] (k) Equation (XIX):

[2458]

[2459] Or its pharmaceutically acceptable salt, wherein:

[2460] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[2461] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[2462] Each R 27 Independently H or C1-C4 alkyl, or two R 27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[2463] Ar for

[2464] Het is a 5- to 6-membered heteroaryl group;

[2465] R1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2466] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2467] R 3 For H or F;

[2468] R 11 It is H or -CH3;

[2469] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[2470] R 22 It is H, halogen, or C1-C2 alkyl; or

[2471] (l) Equation (XX):

[2472]

[2473] Or its pharmaceutically acceptable salt, wherein:

[2474] L-Ar is

[2475] Ar for

[2476] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2477] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2478] R 3 For H or F;

[2479] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2480] R 22 It is H, halogen, or C1-C2 alkyl;

[2481] R24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[2482] R 25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[2483] (m) Equation (XI):

[2484]

[2485] Or its pharmaceutically acceptable salt, wherein:

[2486] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2487] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2488] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2489] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[2490] R 3 It can be H, -OH or halogen;

[2491] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[2492] R 22 It is H, halogen, C1-C2 alkyl; and

[2493] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[2494] In various respects, this disclosure relates to a method for reducing fibrosis gene expression, said method comprising administering a fatty acid synthase inhibitor having the following formula to a subject in need:

[2495] (a) Equation (IX)

[2496]

[2497] Or its pharmaceutically acceptable salt, wherein:

[2498] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2499] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2500] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2501] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[2502] R 3 It can be H, -OH or halogen;

[2503] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[2504] R 22 It is H, halogen, or C1-C2 alkyl;

[2505] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl), wherein:

[2506] t is 0 or 1;

[2507] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2508] L 1 For CR 23 Or N;

[2509] L 2 For CH or N;

[2510] L 1 or L 2 At least one of them is N; and

[2511] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[2512] (b) Equation (X):

[2513]

[2514] Or its pharmaceutically acceptable salt, wherein:

[2515] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2516] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2517] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2518] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[2519] R 3 It can be H, -OH or halogen;

[2520] L 3 For C(R) 60 2. O or NR 50 ;

[2521] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl), or -C(O)-N(R) 601 )2, of which:

[2522] t is 0 or 1; and

[2523] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2524] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[2525] t is 0 or 1; and

[2526] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2527] n is 1, 2, or 3;

[2528] m is 1 or 2;

[2529] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[2530] R 22 It can be H, halogen, or C1-C2 alkyl;

[2531] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[2532] t is 0 or 1; and

[2533] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2534] s is 0, 1, or 2;

[2535] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[2536] Where R 26 R 60 R 50 R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[2537] (c) Equation (VI-J)

[2538]

[2539] Or its pharmaceutically acceptable salt, wherein:

[2540] R1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2541] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2542] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2543] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[2544] R 3 It can be H, -OH or halogen;

[2545] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[2546] R 22 It is H, halogen, or C1-C2 alkyl;

[2547] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[2548] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[2549] (d) Formula (XII):

[2550]

[2551] Or its pharmaceutically acceptable salt, wherein:

[2552] L-Ar is

[2553] Ar for

[2554] Het is a 5- to 6-membered heteroaryl group;

[2555] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1Optionally replaced by one or more halogens;

[2556] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2557] R 3 For H or F;

[2558] R 11 It is H or -CH3;

[2559] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2560] R 22 It is H, halogen, or C1-C2 alkyl;

[2561] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[2562] t is 0 or 1;

[2563] u is 0 or 1;

[2564] The constraint is that when u is 1, t is 1; and

[2565] Each R 241 Independently H or C1-C2 alkyl; and

[2566] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[2567] (e) Equation (XIII):

[2568]

[2569] Or its pharmaceutically acceptable salt, wherein:

[2570] L-Ar is

[2571] Ar for

[2572] Het is a 5- to 6-membered heteroaryl group;

[2573] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2574] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2575] R 3 For H or F;

[2576] R 11 It is H or -CH3;

[2577] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2578] R 22 It is H, halogen, or C1-C2 alkyl; and

[2579] Each R 24 and R 25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[2580] Each t is independently 0 or 1;

[2581] Each u is independently 0 or 1; and

[2582] Each R 241 Independently H or C1-C2 alkyl; or

[2583] (f) Equation (XIV):

[2584]

[2585] Or its pharmaceutically acceptable salt, wherein:

[2586] L-Ar is

[2587] Ar for The constraint is that when L-Ar is Ar not for

[2588] Het is a 5- to 6-membered heteroaryl group;

[2589] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2590] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2591] R 3 For H or F;

[2592] R 11 It is H or -CH3;

[2593] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2594] R 22 It is H, halogen, or C1-C2 alkyl; and

[2595] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t -N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[2596] Each t is independently 0 or 1; and

[2597] Each R 241 Independently H or C1-C2 alkyl; or

[2598] (g) Equation (XV):

[2599]

[2600] Or its pharmaceutically acceptable salt, wherein:

[2601] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[2602] n is 1, 2, or 3;

[2603] m can be 1 or 2, and the constraint is that n+m≥3;

[2604] L-Ar is

[2605] Ar for The constraint is that when L-Ar is Ar not for

[2606] Het is a 5- to 6-membered heteroaryl group;

[2607] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2608] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2609] R 3 For H or F;

[2610] R 11 It is H or -CH3;

[2611] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[2612] R 22 It is H, halogen, or C1-C2 alkyl; or

[2613] (h) formula (XVI):

[2614]

[2615] Or its pharmaceutically acceptable salt, wherein:

[2616] L-Ar is

[2617] Ar for

[2618] Het is a 5- to 6-membered heteroaryl group;

[2619] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2620] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2621] R 3 For H or F;

[2622] R 11 It is H or -CH3;

[2623] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2624] R 22 It is H, halogen, or C1-C2 alkyl; and

[2625] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[2626] (i) Equation (XVII):

[2627]

[2628] Or its pharmaceutically acceptable salt, wherein:

[2629] L-Ar is

[2630] Ar for The constraint is that when L-Ar is Ar not for

[2631] Het is a 5- to 6-membered heteroaryl group;

[2632] R 1It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2633] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2634] R 3 For H or F;

[2635] R 11 It is H or -CH3;

[2636] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2637] R 22 It is H, halogen, or C1-C2 alkyl; and

[2638] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[2639] t is 0 or 1;

[2640] u is 0 or 1;

[2641] The constraint is that when u is 1, t is 1; and

[2642] R 241 It is H or C1-C2 alkyl; or

[2643] (j) Equation (XVIII):

[2644]

[2645] Or its pharmaceutically acceptable salt, wherein:

[2646] L-Ar is

[2647] Ar for The constraint is that when L-Ar is Ar not for

[2648] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[2649] Het is a 5- to 6-membered heteroaryl group;

[2650] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2651] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2652] R 3 For H or F;

[2653] R 11 It is H or -CH3;

[2654] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2655] R 22 It is H, halogen, or C1-C2 alkyl; and

[2656] R 35 -C(O)R 351 -C(O)NHR 351 C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[2657] (k) Equation (XIX):

[2658]

[2659] Or its pharmaceutically acceptable salt, wherein:

[2660] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[2661] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[2662] Each R 27 Independently H or C1-C4 alkyl, or two R 27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[2663] Ar for

[2664] Het is a 5- to 6-membered heteroaryl group;

[2665] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2666] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2667] R 3 For H or F;

[2668] R 11 It is H or -CH3;

[2669] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[2670] R 22 It is H, halogen, or C1-C2 alkyl; or

[2671] (l) Equation (XX):

[2672]

[2673] Or its pharmaceutically acceptable salt, wherein:

[2674] L-Ar is

[2675] Ar for

[2676] R 1It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2677] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2678] R 3 For H or F;

[2679] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2680] R 22 It is H, halogen, or C1-C2 alkyl;

[2681] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[2682] R 25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[2683] (m) Equation (XI):

[2684]

[2685] Or its pharmaceutically acceptable salt, wherein:

[2686] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2687] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2688] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2689] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[2690] R 3It can be H, -OH or halogen;

[2691] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[2692] R 22 It is H, halogen, C1-C2 alkyl; and

[2693] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[2694] In various respects, this disclosure relates to a method for treating skin fibrosis, the method comprising administering a fatty acid synthase inhibitor having the following formula to a subject in need:

[2695] (a) Equation (IX)

[2696]

[2697] Or its pharmaceutically acceptable salt, wherein:

[2698] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2699] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2700] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2701] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[2702] R 3 It can be H, -OH or halogen;

[2703] R 21 H, halogen, C1-C4 straight-chain or branched alkyl, C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms;

[2704] R 22 It is H, halogen, or C1-C2 alkyl;

[2705] R 24 It can be H, C1-C4 straight-chain or branched alkyl, or -(C1-C4 alkyl). t -OH, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl) or -(C1-C4 alkyl) t-O-(C1-C4 straight-chain or branched alkyl), wherein:

[2706] t is 0 or 1;

[2707] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2708] L 1 For CR 23 Or N;

[2709] L 2 For CH or N;

[2710] L 1 or L 2 At least one of them is N; and

[2711] R 23 It is an H or C1-C4 straight-chain or branched alkyl group; or

[2712] (b) Equation (X):

[2713]

[2714] Or its pharmaceutically acceptable salt, wherein:

[2715] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2716] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2717] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2718] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[2719] R 3 It can be H, -OH or halogen;

[2720] L 3 For C(R) 60 2. O or NR 50 ;

[2721] Each R 60 Independently H, -OH, -CN, -O t -(C3-C5 cycloalkyl), -O-(C1-C4 straight-chain or branched alkyl), or -C(O)-N(R) 601 )2, of which:

[2722] t is 0 or 1; and

[2723] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2724] Each R 50 Independently H, -C(O)-O t -(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C3-C5 cyclic alkyl), -C3-C5 cyclic alkyl optionally containing oxygen or nitrogen heteroatoms, -C(O)-N(R) 501 2. C1-C4 straight-chain or branched alkyl groups, wherein:

[2725] t is 0 or 1; and

[2726] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2727] n is 1, 2, or 3;

[2728] m is 1 or 2;

[2729] R 21 The components are H, halogen, C1-C4 straight-chain or branched alkyl, or C3-C5 cycloalkyl, wherein the C3-C5 cycloalkyl optionally includes oxygen or nitrogen heteroatoms.

[2730] R 22 It can be H, halogen, or C1-C2 alkyl;

[2731] Each R 26 Independently -OH, -CN, halogen, C1-C4 straight-chain or branched alkyl, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O-(C1-C4 straight-chain or branched alkyl group), -C(O)-O t -(C1-C4 alkyl) or -C(O)-N(R) 501 )2, of which:

[2732] t is 0 or 1; and

[2733] The C3-C5 cycloalkyl group optionally includes oxygen or nitrogen heteroatoms;

[2734] s is 0, 1, or 2;

[2735] Each R 601 and R 501 Independently, it is an H or C1-C4 straight-chain or branched alkyl group; and

[2736] Where R 26 R 60 R 50R 501 and R 601 The two in R are optionally joined to form a loop, where R 26 R 60 R 50 R 501 and R 601 The two in can be two R. 26 Two Rs 60 Two Rs 50 Two Rs 501 Or two Rs 601 ;or

[2737] (c) Equation (VI-J)

[2738]

[2739] Or its pharmaceutically acceptable salt, wherein:

[2740] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2741] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2742] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2743] Each R 2 Independently, it is H, halogen, or C1-C4 straight-chain or branched alkyl;

[2744] R 3 It can be H, -OH or halogen;

[2745] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[2746] R 22 It is H, halogen, or C1-C2 alkyl;

[2747] R 35 -C(O)-R 351 -C(O)-NHR 351 -C(O)-OR 351 or S(O)2R 351 ;and

[2748] R 351 It is a C1-C6 straight-chain or branched alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group; or

[2749] (d) Formula (XII):

[2750]

[2751] Or its pharmaceutically acceptable salt, wherein:

[2752] L-Ar is

[2753] Ar for

[2754] Het is a 5- to 6-membered heteroaryl group;

[2755] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2756] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2757] R 3 For H or F;

[2758] R 11 It is H or -CH3;

[2759] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2760] R 22 It is H, halogen, or C1-C2 alkyl;

[2761] R 24 H, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C6 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[2762] t is 0 or 1;

[2763] u is 0 or 1;

[2764] The constraint is that when u is 1, t is 1; and

[2765] Each R 241 Independently H or C1-C2 alkyl; and

[2766] R 25 It is a halogen, -CN, -(C1-C4 alkyl)-CN, C1-C2 alkyl, or cyclopropyl; or

[2767] (e) Equation (XIII):

[2768]

[2769] Or its pharmaceutically acceptable salt, wherein:

[2770] L-Ar is

[2771] Ar for

[2772] Het is a 5- to 6-membered heteroaryl group;

[2773] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2774] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2775] R 3 For H or F;

[2776] R 11 It is H or -CH3;

[2777] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2778] R 22 It is H, halogen, or C1-C2 alkyl; and

[2779] Each R 24 and R 25 Independently, it can be H, halogen, -CN, -(C1-C4 alkyl)-CN, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl)-N(R). 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t-O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[2780] Each t is independently 0 or 1;

[2781] Each u is independently 0 or 1; and

[2782] Each R 241 Independently H or C1-C2 alkyl; or

[2783] (f) Equation (XIV):

[2784]

[2785] Or its pharmaceutically acceptable salt, wherein:

[2786] L-Ar is

[2787] Ar for The constraint is that when L-Ar is Ar not for

[2788] Het is a 5- to 6-membered heteroaryl group;

[2789] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2790] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2791] R 3 For H or F;

[2792] R 11 It is H or -CH3;

[2793] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2794] R 22 It is H, halogen, or C1-C2 alkyl; and

[2795] R 24 It can be H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, or -(C1-C4 alkyl). t-N(R 241 2, -(C1-C4 alkyl) t -O t -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O t -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl rings) t -O-(C1-C4 alkyl), wherein:

[2796] Each t is independently 0 or 1; and

[2797] Each R 241 Independently H or C1-C2 alkyl; or

[2798] (g) Equation (XV):

[2799]

[2800] Or its pharmaceutically acceptable salt, wherein:

[2801] L 3 -CH2-, -CHR 50 -、-O-、-NR 50 -、-NC(O)R 50 -OR-NC(O)OR 50 -, where R 50 It is a C1-C6 alkyl, C3-C5 cycloalkyl, or a 4- to 6-membered heterocyclic ring;

[2802] n is 1, 2, or 3;

[2803] m can be 1 or 2, and the constraint is that n+m≥3;

[2804] L-Ar is

[2805] Ar for The constraint is that when L-Ar is Ar not for

[2806] Het is a 5- to 6-membered heteroaryl group;

[2807] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2808] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2809] R 3 For H or F;

[2810] R 11 It is H or -CH3;

[2811] R 21 It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[2812] R 22 It is H, halogen, or C1-C2 alkyl; or

[2813] (h) formula (XVI):

[2814]

[2815] Or its pharmaceutically acceptable salt, wherein:

[2816] L-Ar is

[2817] Ar for

[2818] Het is a 5- to 6-membered heteroaryl group;

[2819] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2820] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2821] R 3 For H or F;

[2822] R 11 It is H or -CH3;

[2823] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[2824] R 22 It is H, halogen, or C1-C2 alkyl; and

[2825] R 24 and R 25 Each is independently H, -C1-C4 alkyl, or halogen; or

[2826] (i) Equation (XVII):

[2827]

[2828] Or its pharmaceutically acceptable salt, wherein:

[2829] L-Ar is

[2830] Ar for The constraint is that when L-Ar is Ar not for

[2831] Het is a 5- to 6-membered heteroaryl group;

[2832] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2833] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2834] R 3 For H or F;

[2835] R 11 It is H or -CH3;

[2836] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2837] R 22 It is H, halogen, or C1-C2 alkyl; and

[2838] R 24 H, C1-C4 alkyl, -(C1-C4 alkyl)-OH, -(C1-C4 alkyl)-N(R) 241 2, -(C1-C4 alkyl) t -O u -(C3-C5 cycloalkyl), -(C1-C4 alkyl) t -O u -(4- to 6-membered heterocyclic rings) or -(C1-C4 alkyl)-O-(C1-C4 alkyl), wherein:

[2839] t is 0 or 1;

[2840] u is 0 or 1;

[2841] The constraint is that when u is 1, t is 1; and

[2842] R 241 It is H or C1-C2 alkyl; or

[2843] (j) Equation (XVIII):

[2844]

[2845] Or its pharmaceutically acceptable salt, wherein:

[2846] L-Ar is

[2847] Ar for The constraint is that when L-Ar is Ar not for

[2848] L 2 -NHR 35 or -C(O)NHR 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl;

[2849] Het is a 5- to 6-membered heteroaryl group;

[2850] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2851] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2852] R 3 For H or F;

[2853] R 11 It is H or -CH3;

[2854] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycles;

[2855] R 22 It is H, halogen, or C1-C2 alkyl; and

[2856] R 35 -C(O)R 351 -C(O)NHR 351C(O)OR 351 or S(O)2R 351 , where R 351 It is a C1-C6 alkyl, C3-C5 cycloalkyl, 4- to 6-membered heterocyclic, aryl or heteroaryl; or

[2857] (k) Equation (XIX):

[2858]

[2859] Or its pharmaceutically acceptable salt, wherein:

[2860] Each of W, X, Y, and Z is independently -N- or -CR. 26 -, with the constraint that no more than two of W, X, Y, and Z are -N-;

[2861] Each R 26 Independently H, C1-C4 alkyl, -O-(C1-C4 alkyl), -N(R) 27 2. -S(O)2-(C1-C4 alkyl) or -C(O)-(C1-C4 alkyl);

[2862] Each R 27 Independently H or C1-C4 alkyl, or two R 27 All are C1-C4 alkyl groups and are bonded together to form a 3- to 6-membered ring with the N atom to which it is attached, wherein the ring optionally includes an oxygen atom as one of the members of the ring;

[2863] Ar for

[2864] Het is a 5- to 6-membered heteroaryl group;

[2865] R 1 The derivatives are H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle), -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2866] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2867] R 3 For H or F;

[2868] R 11 It is H or -CH3;

[2869] R 21It is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocycle; and

[2870] R 22 It is H, halogen, or C1-C2 alkyl; or

[2871] (l) Equation (XX):

[2872]

[2873] Or its pharmaceutically acceptable salt, wherein:

[2874] L-Ar is

[2875] Ar for

[2876] R 1 It can be H, -CN, halogen, C1-C4 alkyl, -O-(C3-C5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1-C4 alkyl), wherein when R 1 When R is not H, -CN or halogen, 1 Optionally replaced by one or more halogens;

[2877] Each R2 is independently H, halogen, or C1-C4 alkyl;

[2878] R 3 For H or F;

[2879] R 21 It can be H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl, or 4- to 6-membered heterocyclic rings;

[2880] R 22 It is H, halogen, or C1-C2 alkyl;

[2881] R 24 It is -O-(C1-C4 alkyl), -O-(C1-C4 alkyl)-O-(C1-C4 alkyl), -O-(C3-C5 cycloalkyl) or -O-(4- to 6-membered heterocycle), wherein R 24 Optionally substituted with one or more hydroxyl groups or halogens; and

[2882] R 25 It is H, halogen, C1-C4 alkyl or C3-C5 cycloalkyl, wherein R 25 Optionally replaced by one or more halogens; or

[2883] (m) Equation (XI):

[2884]

[2885] Or its pharmaceutically acceptable salt, wherein:

[2886] R 1 The following are possible values: H, -CN, halogen, C1-C4 straight-chain or branched alkyl, -O- (C3-C5 cycloalkyl), -O- (C1-C4 straight-chain or branched alkyl), wherein:

[2887] C3-C5 cycloalkyl groups optionally include oxygen or nitrogen heteroatoms; and

[2888] When R 1 When it is not H, -CN or a halogen, it may be optionally substituted with one or more halogens;

[2889] Each R2 is independently H, halogen, or C1-C4 straight-chain or branched alkyl;

[2890] R 3 It can be H, -OH, or a halogen;

[2891] R 21 It is cyclobutyl, azircyclobutyl-1-yl, or cyclopropyl;

[2892] R 22 It is H, halogen, C1-C2 alkyl; and

[2893] R 351 It is a C1-C2 alkyl or C2-O-(C1 or C2 alkyl).

[2894] In various respects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 may be used to manufacture agents for treating non-alcoholic steatohepatitis (NASH) or symptoms of NASH. In other respects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 may be used to treat non-alcoholic steatohepatitis (NASH) or symptoms of NASH.

[2895] In various aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to manufacture agents for the treatment of non-alcoholic fatty liver disease (NAFLD). In other aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to treat non-alcoholic fatty liver disease (NAFLD).

[2896] In various respects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 may be used to manufacture medicaments for the treatment of metabolic syndrome. In other respects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 may be used to treat metabolic syndrome.

[2897] In various aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to manufacture agents for the treatment of cirrhosis. In other aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to treat cirrhosis.

[2898] In various aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to manufacture agents for the treatment of liver fibrosis. In other aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to treat liver fibrosis.

[2899] In various aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to manufacture agents for treating liver cancer. In other aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to treat liver cancer.

[2900] In various aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to manufacture agents for the treatment of liver fibrosis. In other aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to treat liver fibrosis.

[2901] In all respects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 may be used to manufacture agents for treating diseases or conditions with elevated interleukin-1β (IL1β) levels.

[2902] In all respects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to manufacture agents for treating diseases or conditions with elevated t-helper (Th) cell levels. h Diseases or conditions with elevated cellular levels.

[2903] In all respects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to manufacture compounds for the treatment of regulatory T cells (T cells). reg Drugs for diseases or conditions in which regulatory T cells (Tregs) are reduced or suppressed. In each respect, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 may be used for diseases or conditions in which regulatory T cells (Tregs) are reduced or suppressed.

[2904] In various respects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 may be used to manufacture agents for the treatment or reversal of definitive nonalcoholic steatohepatitis (NASH). In other respects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 may be used to treat or reverse definitive nonalcoholic steatohepatitis (NASH).

[2905] In various respects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or as provided in Table 1, may be used to manufacture agents for reducing the expression of fibrosis genes. In other respects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or as provided in Table 1, may be used to reduce the expression of fibrosis genes.

[2906] In various aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to manufacture agents for treating skin fibrosis. In other aspects, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as provided in Table 1 can be used to treat skin fibrosis. Attached Figure Description

[2907] Figure 1 The correlation between FASN inhibition and HCV inhibition is shown.

[2908] Figure 2 Images are shown of liver tissue samples taken from C57BL / 6NCrSim mice treated with the medium or 10 mg / kg compound 364A, stained with Oil Red O or Masson's stain. Results show that treatment with the FASN inhibitor compound 364A inhibited the development of steatosis.

[2909] Figure 3Images of liver tissue samples taken from C57BL / 6J mice stained with Oil Red O and treated with the medium for 28 days, 57 days, or 28 days followed by treatment with compound 364A at 10 mg / kg for 29 days are shown. Results indicate that treatment with the FASN inhibitor compound 364A inhibited the development of hepatic steatosis.

[2910] Figure 4 A graph showing IL-1β levels in untreated rats and rats treated with the medium, 60 mg / kg compound 6B, or 100 mg / kg compound 6B. Results showed that treatment with compound 6B reduced serum IL-1β levels in fasted rats.

[2911] Figure 5 A graph showing IL-1β levels in rats treated with the medium, 60 mg / kg compound 6B, or 100 mg / kg compound 6B. Results showed that treatment with compound 6B reduced serum IL-1β levels 22 hours after feeding to fasted rats.

[2912] Figure 6A A graph showing IL-1β levels in mice fed a high-fat diet for 14 days and then treated with a mediator, 3 mg / kg compound 364A, or 10 mg / kg compound 364A. Figure 6B A graph showing IL-1β levels in mice fed a high-fat diet for 37 days and then treated with a mediator, 3 mg / kg of compound 364A, or 10 mg / kg of compound 364A. Compared with mice receiving the mediator, mice treated with compound 364A had reduced IL-1β levels on days 14 and 37, both before and after reintroduction of food.

[2913] Figure 7A A graph showing the levels of IL-1β secreted from human PBMCs 24 hours after stimulation with lipopolysaccharide (LPS) or lipoteichoic acid (LTA) in the absence of stimulation or after treatment with a medium or 10 μM compound 242A. Figure 7B A graph illustrating the levels of IL-1β secreted from human monocytes after 24 hours of stimulation with lipopolysaccharide (LPS) or lipoteichoic acid (LTA), either with a mediator or with 10 μM compound 242A. For monocytes, treatment with compound 242A reduced IL-1β levels induced by LTA stimulation, while only a slight reduction was observed after LPS stimulation. For PBMCs, treatment with compound 242A reduced IL-1β levels induced by both LTA and LPS stimulation.

[2914] Figure 8A and Figure 8BA graph showing the results of flow cytometry analysis of mouse T cells treated with either DMSO or 50 nM compound 364A. (The graph shows the results of flow cytometry analysis of mouse T cells treated with DMSO or 50 nM compound 364A for 4 days.) 17 Differentiation conditions inhibited FASN inhibition of mouse CD4+ primary T cells, thus suppressing Th... 17 Cell differentiation and stimulation of T cells reg Differentiation.

[2915] Figure 9A and Figure 9B A graph showing the results of flow cytometry analysis of human T cells from donor 1 treated with a medium (DMSO) or 50 nM compound 364A. Figure 9C and Figure 9D A graph showing the results of flow cytometry analysis of human T cells from donor 2 treated with either DMSO or 50 nM compound 364A. (The graph depicts the results of flow cytometry analysis of human T cells from donor 2 treated with either DMSO or 50 nM compound 364A.) 17 Under differentiation conditions, compound 364A inhibited FASN in human CD4+ primary T cells from two different donors, thus suppressing TH. 17 Cell differentiation and stimulation of T cells reg Differentiation.

[2916] Figure 10A and Figure 10B A graph showing the results of flow cytometry analysis of human T cells from donor 1 treated with a medium (DMSO) or 50 nM compound 152. Figure 10C and Figure 10D A graph showing the results of flow cytometry analysis of human T cells from donor 2 treated with either DMSO or 50 nM compound 152. (The graph depicts the results of flow cytometry analysis of human T cells from donor 2 treated with either DMSO or 50 nM compound 152.) 17 Under differentiation conditions, compound 152 inhibited FASN inhibition in human CD4+ primary T cells from two different donors, thus suppressing TH. 17 Cell differentiation and stimulation of T cells reg Differentiation.

[2917] Figure 11 This is a schematic diagram of the study design and dosage group for compound 364A and pirfenidone in Example 10.

[2918] Figure 12A A graph showing the changes in plasma alanine aminotransferase (ALT) with treatment with compound 364A and / or pirfenidone. Figure 12B A graph showing the changes in plasma aspartate aminotransferase (AST) with treatment with compound 364A and / or pirfenidone. Figure 12C A graph showing the change in plasma total cholesterol (TC) with treatment with compound 364A and / or pirfenidone.

[2919] Figure 13AA graph showing the changes in liver triglycerides with treatment with compound 364A and / or pirfenidone. Figure 13B A graph showing the changes in liver cholesterol with treatment with compound 364A and / or pirfenidone.

[2920] Figure 14A This is a diagram showing the changes in hepatic steatosis after administration of a medium (control). Figure 14B A graph showing the changes in hepatic steatosis after administration of compound 364A. Figure 14C A diagram showing the changes in hepatic steatosis after administration of pirfenidone. Figure 14D A diagram showing the changes in hepatic steatosis after administration of compound 364A and pirfenidone.

[2921] Figure 15A A graph showing the changes in liver inflammation after administration of a mediator (control). Figure 15B A graph showing the changes in liver inflammation after administration of compound 364A. Figure 15C A graph showing the changes in liver inflammation after administration of pirfenidone. Figure 15D A graph showing the changes in liver inflammation after administration of compound 364A and pirfenidone.

[2922] Figure 16A A diagram showing the changes in liver ballooning after administration of a mediator (control). Figure 16B A diagram showing the changes in liver ballooning after administration of compound 364A. Figure 16C A diagram showing the changes in liver ballooning after administration of pirfenidone. Figure 16D A diagram showing the changes in liver ballooning after administration of compound 364A and pirfenidone.

[2923] Figure 17A A graph showing the changes in liver fibrosis after administration of a mediator (control). Figure 17B A graph showing the changes in liver fibrosis after administration of compound 364A. Figure 17C A graph showing the changes in liver fibrosis after administration of pirfenidone. Figure 17D A graph showing the changes in liver fibrosis after administration of compound 364A and pirfenidone.

[2924] Figure 18A A graph showing the changes in liver NAFLD activity score (NAS) after administration of the mediator (control). Figure 18B A graph showing the change in liver NAFLD activity score (NAS) after administration of compound 364A. Figure 18C A graph showing the changes in liver NAFLD activity score (NAS) after administration of pirfenidone. Figure 18DA graph showing the changes in liver NAFLD activity score (NAS) after administration of compound 364A and pirfenidone.

[2925] Figure 19 A graph showing the changes in liver collagen gene expression after administration of a mediator (control), compound 364A, pirfenidone, or a combination of compounds 364A and pirfenidone.

[2926] Figure 20 is a 2-D diagram showing the changes in liver collagen gene expression obtained by gene analysis of liver biopsy sections after administration of the mediator (control), compound 364A, pirfenidone, or compound 364A and pirfenidone.

[2927] Figure 21 This is a schematic diagram of the study design and dosage group in Example 11.

[2928] Figure 22 The graph shows the change in collagen content in mouse skin with the dosage of compound 364A in Example 11.

[2929] Figure 23 shows the relative mRNA expression of fibrosis genes in immortalized human hepatic stellate cells (LX-2 cells) after treatment with compound 364A or sorafenib. Figure 23A A diagram showing the mRNA expression of Col 1a1. Figure 23B This is a diagram showing the mRNA expression of αSMA. Figure 23C This is a diagram showing the mRNA expression of βPDGFR. Figure 23D This is a diagram showing the mRNA expression of TGFbR1. Figure 23E This is a diagram showing the mRNA expression of TIMP1. Figure 23F This is a diagram showing the mRNA expression of TIMP2. Figure 23G This is a diagram showing the mRNA expression of MMP2. Invention Details

[2930] This disclosure addresses the shortcomings in treating conditions characterized by FASN dysfunction (such as viral infections, cancer, and metabolic disorders) by providing novel heterocyclic regulators of lipid synthesis.

[2931] In some aspects, this disclosure provides compositions and methods for treating viral infections. Generally, the compositions and methods for treating viral infections target the regulation of fatty acid synthesis pathways. Fatty acid synthesis pathways are involved in viral replication into host cells. This invention implements methods for treating viral infections such as hepatitis C infection, yellow fever infection, and human rhinovirus infection, or any virus targeting fatty acid synthesis pathways.

[2932] In some respects, this disclosure provides compositions and methods for treating cancer. Fatty acid synthase is responsible for converting malonyl-CoA into long-chain fatty acids, an early reaction in fatty acid biosynthesis. Fatty acid synthase is overexpressed in many cancer cells. Without being bound by any particular theory, it is assumed that selective inhibition of fatty acid synthase expression or activity inhibits cancer cell proliferation and induces cancer cell death with minimal toxicity to normal cells.

[2933] Furthermore, this disclosure provides compounds and methods for modulating host cell targets targeted by viruses. Such modulation of host cell targets may include activation or inhibition of the host cell targets. Therefore, compounds that modulate (e.g., inhibit) the activity of non-viral proteins (e.g., host cell proteins, such as components of fatty acid synthesis pathways) can be used as antiviral agents.

[2934] definition

[2935] As those skilled in the art will understand, chemical moieties referred to as monovalent chemical moieties (e.g., alkyl, aryl, etc.) also encompass structurally permissible polyvalent moieties. For example, while the term "alkyl" generally refers to a monovalent group (e.g., CH3CH2-), in appropriate cases, "alkyl" can also refer to a divalent group (e.g., -CH2CH2-, which is equivalent to "alkylene"). Similarly, where a divalent moieties are required, those skilled in the art will understand that the term "aryl" refers to the corresponding divalent arylene.

[2936] All atoms should be understood to have their normal bonding valences (e.g., carbon 4, N 3, O 2, and S 2, 4, or 6, depending on the oxidation state of the atom). Sometimes, a part may be defined, for example, as (A). a B, where a is 0 or 1. In this case, when a is 0, it is partly B, and when a is 1, it is partly AB.

[2937] If the number of substituents can vary in the same type of atoms or groups (e.g., alkyl groups can be C1, C2, C3, etc.), then the number of repeating atoms or groups can be expressed by a range (e.g., C1-C6 alkyl), which includes each and every number in that range and any and all subranges. For example, C1-C3 alkyl groups include C1, C2, C3, C6, C7, C8, C9 ... 1-2 C 1-3 and C 2-3 alkyl.

[2938] "Alkyl group" refers to a carbonyl group with a low-carbon alkyl group as a substituent.

[2939] "Alkylamino" refers to an amino group that is substituted with an alkyl group.

[2940] "Alkoxy" refers to an O atom substituted with an alkyl group as defined herein, such as a methoxy group [-OCH3, C1 alkoxy]. The term "C..." 1-6 "Alkoxy" encompasses C1 alkoxy, C2 alkoxy, C3 alkoxy, C4 alkoxy, C5 alkoxy, C6 alkoxy, and any of their subranges.

[2941] "Alkoxycarbonyl" refers to a carbonyl group that has an alkoxy group as a substituent.

[2942] "alkyl," "alkenyl," and "ynyl" refer to optionally substituted straight-chain and branched aliphatic groups having 1 to 30 carbon atoms, preferably 1 to 15 carbon atoms, or more preferably 1 to 6 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, pentyl, hexyl, vinyl, allyl, isobutylenyl, ethynyl, and propynyl. As used herein, the term "heteroalkyl" covers alkyl groups having one or more heteroatoms.

[2943] "alkylene" refers to an optionally substituted divalent group, which is a branched or unbranched hydrocarbon segment containing a specified number of carbon atoms and having two connection points. An example is propylene [-CH2CH2CH2-, C3 alkylene].

[2944] "Amino" refers to the group -NH2.

[2945] "Aryl" refers to an optionally substituted aromatic group having at least one ring with a conjugated π-electron system, including carbocyclic aryl and biaryl groups, both of which may be optionally substituted. Phenyl and naphthyl are preferred carbocyclic aryl groups.

[2946] "Arylalkyl" or "arylalkyl" refers to an alkyl-substituted aryl group. Examples of arylalkyl groups include butylphenyl, propylphenyl, ethylphenyl, methylphenyl, 3,5-dimethylphenyl, and tert-butylphenyl.

[2947] As used in this article, "carbamoyl" encompasses structures The group, wherein R N Selected from: hydrogen, -OH, C1 to C 12 Alkyl, C1 to C 12 Heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkylyl, carbamoyl, sulfonyl, sulfonate and sulfonamide.

[2948] "Carbonyl" refers to the structure . group.

[2949] "Cycloalkyl" refers to an optionally substituted ring, which can be saturated or unsaturated and is a monocyclic, bicyclic, or tricyclic ring formed entirely of carbon atoms. An example of a cycloalkyl group is cyclopentenyl (C5H7-), which is a five-carbon (C5) unsaturated cycloalkyl group.

[2950] "Heterocycle" refers to a 5- to 7-membered cyclic alkyl ring system containing 1, 2 or 3 heteroatoms selected from N, O or S that may be the same or different and optionally contain a double bond.

[2951] "Halogen" refers to a group consisting of chlorine, bromine, fluorine, or iodine atoms. The term "halogen" also encompasses the terms "halo" or "halide".

[2952] "Heteroatoms" refers to non-carbon atoms, among which boron, nitrogen, oxygen, sulfur and phosphorus are preferred heteroatoms, and nitrogen, oxygen and sulfur are particularly preferred heteroatoms in the compounds of this invention.

[2953] "Heteroaryl" refers to an aryl group having 1 to 9 carbon atoms with the remaining atoms being heteroatoms, and includes those heterocyclic systems described in "Handbook of Chemistry and Physics," 49th edition, 1968, ed. RCWeast; The Chemical Rubber Co., Cleveland, Ohio. See in particular Chapter C, Rules for Naming Organic Compounds, B. Fundamental Heterocyclic Systems. Suitable heteroaryl groups include thiophene, pyrrolyl, furanyl, pyridyl, pyrimidinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, imidazoleyl, thiazolyl, pyranyl, tetrazolyl, pyrrolyl, pyrrololinyl, pyridazinyl, triazolyl, indoleyl, isoindoleyl, indoleazinyl, benzimidazolyl, quinolinyl, isoquinolinyl, inzolyl, benzotriazolyl, tetrazolpyridazinyl, oxadiazolyl, benzooxazolyl, benzooxadiazolyl, thiazolyl, benzothiazolyl, benzothiazolyl, benzothiazolyl, etc.

[2954] The "optionally substituted" portion may be substituted by 1 to 4, preferably 1 to 3, or more preferably 1 or 2 non-hydrogen substituents. Unless otherwise stated, when the substituent is located on a carbon atom, it is selected from: -OH, -CN, -NO2, halogens, C1 to C2. 12 Alkyl, C1 to C 12 Heteroalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, substituted sulfonyl, sulfonate, sulfonamide, and amino, none of which are further substituted. Unless otherwise stated, when the substituent is on nitrogen, it is selected from C1 to C2. 12 Alkyl, C1 to C 12 Heteroalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, sulfonyl, sulfonate and sulfonamide, none of which are further substituted.

[2955] As used in this article, the term "sulfonamide" encompasses structures The group, wherein R N Selected from: hydrogen, -OH, C1 to C 12 Alkyl, C1 to C 12 Heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, substituted sulfonyl, sulfonate and sulfonamide.

[2956] As used in this article, the term "sulfonate" encompasses structures The group, wherein R S Selected from: hydrogen, C1-C 10 Alkyl, C2-C 10 alkenyl, C2-C 10 Alkyne group, C1-C 10 Alkyl or C1-C 10 Alkoxycarbonyl group.

[2957] As used herein, “sulfonyl” alone or as part of another group refers to the SO2 group. The SO2 moiety may optionally be substituted.

[2958] The compounds disclosed herein can exist as stereoisomers, wherein an asymmetric or chiral center is present. Stereoisomers are referred to as (R) or (S) depending on the configuration of the substituents surrounding the chiral carbon atom. As used herein, the terms (R) and (S) are configurations as defined in Section E of IUPAC 1974 Recommendations, Fundamental Stereochemistry, Pure Appl. Chem., (1976), 45:13-30, which is incorporated herein by reference. This disclosure covers a variety of stereoisomers and mixtures thereof and is specifically included within the scope of this disclosure. Stereoisomers include enantiomers, diastereomers, and mixtures of enantiomers or diastereomers. Individual stereoisomers of the compounds disclosed herein can be synthesized from commercially available starting materials containing an asymmetric or chiral center, or prepared by preparing a racemic mixture followed by resolution as known to those skilled in the art. These separation methods are exemplified as follows: (1) attaching an enantiomer mixture to a chiral additive, separating the resulting diastereomer mixture by recrystallization or chromatography, and precipitating the optically pure product from the additive; or (2) separating the optically enantiomer mixture directly on a chiral chromatography column.

[2959] Furthermore, the portion disclosed herein that exists in various tautomer forms includes all such forms covered by the given tautomer structure.

[2960] Individual atoms in the disclosed compounds may be any isotope of the element. For example, hydrogen may be in the form of deuterium.

[2961] "Pharmaceutical acceptable" means a substance that has been approved or is intended to be approved by a federal or state regulatory agency, or is listed in the United States Pharmacopeia or other generally recognized pharmacopoeia for use in animals and more particularly in humans. It can be a substance that is biologically or otherwise undesirable, meaning that the substance can be administered to a subject without causing any adverse biological effects or interacting harmfully with any component of the composition.

[2962] The term "pharmaceutically acceptable salt" of a compound refers to a salt that is pharmaceutically acceptable and possesses the desired pharmacological activity of the parent compound. These salts include, for example, acid addition salts and base addition salts.

[2963] The "acid addition salt" of this invention is formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, etc. Acids, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 4-methylbicyclo-[2.2.2]oct-2-en-1-carboxylic acid, glucohepanoic acid, 4,4′-methylenebis-(3-hydroxy-2-en-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, mucoconic acid, etc.

[2964] The "base addition salt" of this invention is formed when an acidic proton present in the parent compound is replaced by a metal ion, such as an alkali metal ion, alkaline earth ion, or aluminum ion; or when it coordinates with an organic base. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine, thiocyanate, N-methylglucosamine, etc. Acceptable inorganic bases include aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, sodium hydroxide, etc. It should be understood that references to pharmaceutically acceptable salts include solvation forms or their crystalline forms, particularly solvates or polymorphs. Solvates contain stoichiometric or non-stoichiometric amounts of solvent and are typically formed during crystallization. Hydrates are formed when the solvent is water, or alcohols are formed when the solvent is alcohol. Polymorphs include different crystalline arrangements of the same elemental composition of the compound. Polymorphs typically have different X-ray diffraction patterns, infrared spectra, melting points, densities, hardness, crystal shapes, optical and electrical properties, stability, and solubility. Various factors, such as recrystallization solvent, crystallization rate, and storage temperature, can cause a single crystal form to dominate.

[2965] The term "treatment" includes administering the compounds or agents of the present invention to a subject to prevent or delay, alleviate, or prevent or inhibit the development of symptoms or conditions associated with fatty acid synthase-related disorders, such as tumor growth associated with cancer. Skilled medical professionals should know how to use standard methods to determine whether a patient has a disease associated with fatty acid synthase activity, for example, by examining the patient and determining whether the patient has a known disease associated with fatty acid synthase activity; or by analyzing the fatty acid synthase levels in the plasma or tissues of a subject suspected of having a fatty acid synthase-related disorder and comparing the fatty acid synthase levels in the plasma or tissues of a subject suspected of having a fatty acid synthase-related disorder with those in the plasma or tissues of a healthy subject. Increased serum levels indicate disease. Therefore, the present invention specifically provides a method for administering the compounds of the present invention to a subject and measuring the fatty acid synthase activity in the subject. The fatty acid synthase activity in the subject can be measured before and / or after administration of the compound.

[2966] "Therapeutic effective amount" or "pharmaceutical effective amount" refers to the amount that, when administered to a subject, produces the desired effect. For example, a "therapeutic effective amount" is sufficient to inhibit fatty acid synthase activity when administered to a subject. Similarly, a "therapeutic effective amount" is sufficient to treat a disease when administered to a subject.

[2967] Unless otherwise stated, the terms "subject" or "patient" are used interchangeably and refer to mammals such as human patients and non-human primates, as well as laboratory animals such as rabbits, rats, mice, and other animals. Therefore, as used herein, the terms "subject" or "patient" mean any mammalian patient or subject to whom the compounds of the present invention may be administered. In an exemplary aspect of the invention, to identify subject patients for treatment according to the methods of the present invention, recognized screening methods are used to determine risk factors associated with a target or suspected disease or condition, or to determine the status of an existing disease or condition in the subject. These screening methods include, for example, routine procedures to determine risk factors associated with a target or suspected disease or condition. These and other routine methods enable clinicians to select patients for treatment using the methods and formulations of the present invention.

[2968] FASN pathway modulators

[2969] One aspect of the invention includes a method for inhibiting viral infection or treating cancer by contacting cells with an agent that regulates fatty acid synthesis pathways. This method of inhibiting viral infection or treating cancer can be carried out in vitro by contacting virus-infected cells / cancer cells with an agent that regulates fatty acid synthesis pathways, or in vivo by administering the agent to a subject infected with a virus / having cancer. In one aspect, the agent may be an inhibitor of the fatty acid synthesis pathway.

[2970] Examples of inhibitors of fatty acid synthesis pathways that can be used in the methods and compositions of the present invention are described below.

[2971] Compounds with structure (I)

[2972] In several respects, this disclosure provides compounds of structure (I) or pharmaceutically acceptable salts thereof:

[2973]

[2974] in:

[2975] X, Y, and Z are each independently CR or NR′, where R is hydrogen or C. 1-6 Alkyl group and R′ is hydrogen, C 1-6 Alkyl groups may not be present;

[2976] A is CH or N;

[2977] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[2978] q can be 0, 1, 2, 3, or 4;

[2979] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 Alkyl or -N(R) 13 (R) 14 );

[2980] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[2981] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[2982] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[2983] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[2984] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[2985] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, alkylamino, -N(R) 15 R 16 ) or -S(=O)2R 20 ;

[2986] R 15 and R 16 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino;

[2987] R 17 and R 18 Each is independently hydrogen or alkyl, or optionally bonded together to form a bond;

[2988] n is 1 or 2; and

[2989] m is 0 or 1.

[2990] In some aspects of structure (I), R3 is F.

[2991] In some aspects of structure (I), A is CH.

[2992] In some aspects of structure (I), A is N.

[2993] In certain aspects of structure (I), X, Y, and Z are NR′.

[2994] In some aspects of structure (I), R4 is a heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), or -N(R7)C(=O)R8. 10 C 1-6 Alkyl, C 1-6 Alkoxy, or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups.

[2995] In some aspects of structure (I), R5 is hydrogen and R6 is aryl or heteroaryl.

[2996] In some respects, compounds of structure (I) or pharmaceutically acceptable salts thereof have one of the following structures (IA) or (IB):

[2997]

[2998] in:

[2999] X, Y, and Z are each independently CR or NR′, where R is hydrogen or C. 1-6 Alkyl group and R′ is hydrogen, C 1-6 Alkyl groups may not be present;

[3000] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[3001] q can be 0, 1, 2, 3, or 4;

[3002] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 Alkyl or -N(R) 13 (R) 14 );

[3003] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[3004] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[3005] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3006] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3007] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3008] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, hydroxyalkyl, alkylamino, -N(R) 15 R 16 ) or -S(=O)2R 20 ;

[3009] R 15 and R16 Each independently is hydrogen, C 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino; and

[3010] R 17 and R 18 Each is independently hydrogen or alkyl, or may optionally be bonded together to form a bond.

[3011] In some respects, compounds of structure (I) or pharmaceutically acceptable salts thereof have one of the following structures (IC) or (ID):

[3012]

[3013] in:

[3014] X, Y, and Z are each independently CR or NR′, where R is hydrogen or C. 1-6 Alkyl group and R′ is hydrogen, C 1-6 Alkyl groups may not be present;

[3015] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[3016] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[3017] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3018] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 Alkyl or -N(R) 13 (R) 14 );

[3019] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3020] R5, R6, R7, R8, R9 and R 10 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16 );and

[3021] R 15 and R 16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino.

[3022] In some respects, compounds of structure (I) or pharmaceutically acceptable salts thereof have one of the following structures: (IE), (IF), (IG), (IH):

[3023]

[3024] in:

[3025] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[3026] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[3027] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3028] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[3029] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3030] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3031] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16 );and

[3032] R 15 and R 16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino.

[3033] In some respects, compounds of structure (I) or pharmaceutically acceptable salts thereof have one of the following structures (II), (IJ), or (IK):

[3034]

[3035] in:

[3036] X and Y are each independently CR or NR′, where R is H or C. 1-6 Alkyl group and R′ is H or C 1-6 Alkyl groups may not be present;

[3037] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2)q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[3038] q can be 0, 1, 2, 3, or 4;

[3039] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[3040] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[3041] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[3042] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[3043] R5, R6, R7, R8, R9 and R 10 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16 );and

[3044] R 15 and R 16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino.

[3045] In some respects, compounds of structure (I) or their pharmaceutically acceptable salts have one of the following structures (IL) or (IM):

[3046]

[3047] in:

[3048] X and Y are each independently CR or NR′, where R is H or C.1-6 Alkyl group and R′ is H or C 1-6 Alkyl groups may not be present;

[3049] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3050] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[3051] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3052] R5, R6, R7, R8, R9 and R 10 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16 );and

[3053] R 15 and R 16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino.

[3054] In some respects, compounds of structure (I) or pharmaceutically acceptable salts thereof have one of the following structures (IN) or (IO):

[3055]

[3056]

[3057] In some respects, compounds of structure (I) or pharmaceutically acceptable salts thereof have the following structure (IP):

[3058]

[3059] in:

[3060] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[3061] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[3062] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3063] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[3064] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3065] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3066] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16 );and

[3067] R 15 and R 16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino.

[3068] In some respects, compounds of structure (I) or pharmaceutically acceptable salts thereof have one of the following structures (IQ), (IR), or (IS):

[3069]

[3070]

[3071] In some respects, compounds of structure (I) or pharmaceutically acceptable salts thereof have the following structure (IT):

[3072]

[3073] in:

[3074] X, Y, and Z are each independently CR or NR′, where R is H or C. 1-6 Alkyl group and R′ is H or C 1-6 Alkyl groups may not be present;

[3075] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[3076] q can be 0, 1, 2, 3, or 4;

[3077] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[3078] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[3079] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[3080] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3081] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3082] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3083] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16 );and

[3084] R 15 and R16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino.

[3085] In some respects, compounds of structure (I) or pharmaceutically acceptable salts thereof have the following structure (IU):

[3086]

[3087] In some respects, compounds of structure (I) or pharmaceutically acceptable salts thereof have one of the following structures (IV):

[3088]

[3089] in:

[3090] X, Y, and Z are each independently CR or NR′, where R is H or C. 1-6 Alkyl group and R′ is H or C 1-6 Alkyl groups may not be present;

[3091] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(O)2R 20 ;

[3092] q can be 0, 1, 2, 3, or 4;

[3093] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[3094] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[3095] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[3096] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3097] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3098] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3099] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16 );and

[3100] R 15 and R 16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino.

[3101] In some respects, compounds of structure (I) or pharmaceutically acceptable salts thereof have the following structures (IW):

[3102]

[3103] In some respects, the compound of structure (I) or a pharmaceutically acceptable salt thereof has one of the following structures: (IX), (IY), (IZ), (I-AA), (I-AB), (I-AC), (I-AD), (I-AF), (I-AG), or (I-AH):

[3104]

[3105]

[3106]

[3107]

[3108] Compounds with structure (I)

[3109] In several respects, this disclosure provides compounds of structure (II) or pharmaceutically acceptable salts thereof:

[3110]

[3111] in:

[3112] X, Y, and Z are each independently CR or NR′, where R is H or C. 1-6 Alkyl group and R′ is H or C 1-6 Alkyl groups may not be present;

[3113] L and D are each independently C or N;

[3114] R1 is hydrogen, cyano, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, -C(=O)N(R) 13 (R) 14 -(CH2) q C(=O)N(R 13 (R) 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[3115] q can be 0, 1, 2, 3, or 4;

[3116] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[3117] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[3118] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[3119] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3120] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3121] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3122] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16 );

[3123] R 15 and R 16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino;

[3124] R 17 and R 18 Each is independently hydrogen or alkyl, or optionally bonded together to form a bond;

[3125] n is 1 or 2; and

[3126] m is 0 or 1.

[3127] In some respects, compounds of structure (II) or pharmaceutically acceptable salts thereof have the following structure (II-A):

[3128]

[3129] in:

[3130] X, Y, and Z are each independently CR or NR′, where R is H or C. 1-6 Alkyl group and R′ is H or C 1-6 Alkyl groups may not be present;

[3131] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[3132] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[3133] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3134] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[3135] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3136] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3137] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16 );and

[3138] R 15 and R 16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino.

[3139] In some respects, compounds of structure (II) or pharmaceutically acceptable salts thereof have the following structure (II-B):

[3140]

[3141] in:

[3142] X and Y are each independently CR or NR′, where R is H or C. 1-6 Alkyl group and R′ is H or C 1-6 Alkyl groups may not be present;

[3143] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6 Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[3144] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[3145] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3146] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[3147] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3148] R5, R6, R7, R8, R9 and R 10 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16 );and

[3149] R 15 and R 16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino.

[3150] In some respects, compounds of structure (II) or pharmaceutically acceptable salts thereof have one of the following structures: (II-C), (II-D), or (II-E):

[3151]

[3152] in:

[3153] X and Y are each independently CR or NR′, where R is H or C. 1-6 Alkyl group and R′ is H or C 1-6 Alkyl groups may not be present;

[3154] R2 is hydrogen, halogen, or C. 1-6 Alkoxy, C 1-6Alkyl groups, or R2 and R3 together with the atoms they are attached to, form 5-membered heterocyclic groups;

[3155] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy groups, or R2 and R3 together with the atoms they are attached to, form a 5-membered heterocyclic group;

[3156] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3 or -S(=O)2R 20 ;

[3157] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[3158] R5, R6, R7, R8, R9 and R 10 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16 );and

[3159] R 15 and R 16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino.

[3160] In some respects, compounds of structure (II) or pharmaceutically acceptable salts thereof have the following structures (II-F):

[3161]

[3162] Compounds with structure (III)

[3163] In several respects, this disclosure provides compounds of structure (III) or pharmaceutically acceptable salts thereof:

[3164]

[3165] in:

[3166] X, Y, and Z are each independently CR or NR′, where R is H or C. 1-6 Alkyl group and R′ is H or C 1-6 Alkyl groups may not be present;

[3167] Q is either C or N;

[3168] R3 represents hydrogen, hydroxyl group, halogen, or C. 1-6 Alkyl, C 1-6 Alkoxy group, or if Q is N, then R3 does not exist;

[3169] R4 represents hydrogen, heteroaryl, heterocyclic, -C(=O)N(R5R6), -N(R7)C(=O)R8, -N(R9R6), etc. 10 C 1-6 Alkyl, C 1-6 Alkyl group, -S(=O)2R 20 , or R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3170] R 20 It is hydrogen or C 1-6 Alkyl, C 1-6 alkoxy or -N(R) 13 (R) 14 );

[3171] R 11 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 R4 and R 11 Together with the atoms they are attached to, they bond together to form heteroaryl groups, or R. 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3172] R 12 It is hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, -N(R) 13 R 14 ), CF3, -OCF3, -S(=O)2R 20 , or R 11 and R 12 Together with the atoms they are attached to, they bond together to form heteroaryl groups;

[3173] R5, R6, R7, R8, R9, R 10 R 13 and R 14 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkylamino, or -N(R) 15 R 16);

[3174] R 15 and R 16 Each independently represents H and C. 1-6 Alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, or alkylamino;

[3175] R 17 and R 18 Each is independently hydrogen or alkyl, or optionally bonded together to form a bond;

[3176] R 19 It is aryl, heteroaryl, cycloalkyl, or heterocyclic;

[3177] n is 0, 1, or 2; and

[3178] m is 0 or 1.

[3179] In some respects, compounds of structure (III) or pharmaceutically acce...

Claims

1. Use of a fatty acid synthase inhibitor in the preparation of a medicament for treating a disease or condition with elevated interleukin 1β (IL1β) levels, wherein said disease or condition is acne, and said fatty acid synthase inhibitor is Or its pharmaceutically acceptable salt.

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