Heterocyclic modulators of lipid synthesis

Abstract

To provide methods for treating diseases.SOLUTION: Compounds that are fatty acid synthesis modulators are provided. The compounds may be used to treat disorders characterized by dysregulation of the fatty acid synthase function by modulating the function and / or the fatty acid synthase pathway. Methods are also provided for treating such disorders including viral infections such as hepatitis C infection, cancer and metabolic disorders such as non-alcoholic steatohepatitis (NASH).SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of U.S. Provisional Patent Application No. 62 / 574,497, filed October 19, 2017, and also claims priority to earlier-filed U.S. Provisional Patent Application No. 13 / 415,660, filed March 8, 2012, which claims priority to earlier-filed U.S. Provisional Patent Application No. 61 / 450,561, filed March 8, 2011, U.S. Provisional Patent Application No. 61 / 508,611, filed July 16, 2011, and U.S. Provisional Patent Application No. 61 / 585,642, filed January 11, 2012. It is a continuation-in-part of U.S. Patent Application No. 14 / 874,961 (filed October 5, 2015), which is a continuation-in-part of U.S. Patent Application No. 14 / 315,133 (filed June 25, 2014), now abandoned, which is a continuation-in-part of U.S. Patent Application No. 14 / 315,133 (now abandoned), ... No. 9,819 (filed September 11, 2012) and is a continuation of U.S. Patent Application No. 15 / 201,824 (filed July 5, 2016), which is a divisional of U.S. Patent Application No. 14 / 587,908 (filed December 31, 2014) (now U.S. Patent No. 9,428,502), which is a continuation of PCT / US2013 / 048950 (filed July 1, 2013), which claims priority to U.S. Provisional Patent Application No. 61 / 785,933 (filed March 14, 2013); It also claims priority to and the benefit of U.S. Patent Application No. 15 / 349,960 (filed November 11, 2016), which is a continuation-in-part of U.S. Patent Application No. 15 / 110,154 (filed July 7, 2016), which is a U.S. national stage application of PCT / US2015 / 010459 (filed January 7, 2015), filed under 35 U.S.C. 371, which claims priority to earlier-filed U.S. Provisional Patent Application No. 61 / 924,520 (filed January 7, 2014).

[0002] The entire contents of each of these applications are incorporated herein by reference in their entirety for all purposes.

[0003] The present disclosure relates generally to heterocyclic modulators of lipid synthesis and methods of use thereof. The heterocyclic modulators of lipid synthesis can be used to treat disorders characterized by dysregulation of fatty acid synthase function in a subject by modulating the fatty acid synthase pathway and / or fatty acid synthase function. [Background technology]

[0004] Viral diseases are a health concern that threaten a large portion of the human population. Some of the characteristics of viral infections that concern medical professionals include their highly contagious nature (e.g., HIV, SARS, etc.) and high mutability. Some viruses are also oncogenic (e.g., HPV, EBV, and HBV). Viruses are considered to be one of the structurally simplest organisms, but also one of the most difficult to control, presenting a threatening challenge to antiviral drug R&D.

[0005] To date, a number of drugs have been widely used by patients, including several antiviral drugs, such as amantadine and oseltamivir for influenza, acyclovir for HSV-related infections, ganciclovir for CMV infections, and co-formulated drugs (efavirenz, emtricitabine, and tenofovir disoproxifumarate) for AIDS treatment. These drugs have various undesirable neurological, metabolic, and immunological side effects. Therefore, the development of novel antiviral therapies has become a major focus of medical and pharmaceutical research and development.

[0006] Infection with hepatitis C virus (HCV) 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 the leading cause of premature liver-related mortality worldwide.

[0007] The current standard therapeutic treatment regimen for HCV infection includes combination therapy with interferon-alpha and ribavirin, often supplemented with a direct-acting protease inhibitor (telaprevir or boceprevir). This treatment is cumbersome and can have severe, debilitating side effects. For this reason, many patients are not treated early in the disease. In addition, a portion of the patient population does not respond durably to treatment. New and effective methods of treating HCV infection are urgently needed.

[0008] The main therapeutic approaches currently used to treat cancer include surgical removal of the primary tumor, tumor irradiation, and parenteral application of antimitotic cytotoxic agents. Unfortunately, only a relatively small representative subset of cancer patients has tumors that "use" certain pathways and can therefore be treated with newer targeted drugs. The continued predominance of these older therapies reflects the lack of improved survival rates for most cancers. In addition to limited clinical success, classical therapies are associated with strong side effects. Both radiation-based and cytotoxic agent-based therapies result in the destruction of rapidly dividing hematopoietic and intestinal epithelial cells, leading to immune depression, anemia, and nutrient malabsorption. Surgical interventions often result in the release of tumor cells into the circulatory or lymphatic system, from which metastatic tumors can subsequently be established. Methods for improved cancer treatment are needed.

[0009] Nonalcoholic liver disease (NAFLD), a condition in which the liver contains more than 5% fat by weight and is not attributable to alcohol intake, currently affects approximately 20-30% of the population in the United States and Western Europe in general, and is associated with a significantly elevated risk of morbidity that extends beyond the liver to cardiovascular disease (i.e., carotid atherosclerotic plaques and endothelial dysfunction), chronic kidney disease, and malignancies. Obesity and metabolic syndrome are the two major risk factors for NAFLD, characterized by an imbalance between energy utilization and storage. This imbalance results in dysregulation of metabolic pathways and inflammatory responses, which further lead to changes that lead to liver injury and complications. With progression of metabolic syndrome, NAFLD leads to more advanced liver disease, beginning with nonalcoholic steatohepatitis (NASH), which can then progress to significant liver disease, including cirrhosis and hepatocellular carcinoma.

[0010] In subjects with metabolic syndrome and NAFLD, fatty acid synthesis in the liver is increased, a pathway also known as de novo lipogenesis in the liver (DNL) (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 elevated hepatic triglyceride storage, but also contributes to signaling events that increase hepatic inflammation because the fatty acids produced are saturated fatty acid species, mainly palmitic acid (Wei, Y., “Saturated Fatty Acids Induce Endoplasmic Reticulum Stress and Apoptosis Independent ntly 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 IRE1alpha 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 involved in synthesizing palmitic acid. Therefore, DNL is an important pathway for therapeutic intervention to reduce the effects associated with metabolic syndrome and NAFLD. Inhibition of FASN may be a treatment for a wide range of diseases, including cancer, viral diseases, metabolic diseases, NAFLD, NASH, and inflammatory diseases (i.e., rheumatoid arthritis, gout, pulmonary fibrosis, COPD, IBD, and transplant rejection). In addition, inhibition of FASN may provide therapeutic benefits for cardiovascular disease, type II diabetes, and metabolic syndrome. Successful treatment of these diseases remains an unmet need. Although there are treatments available for diabetes and cardiovascular disease, there are currently no drugs approved for the treatment of metabolic syndrome, NAFLD, or NASH. Therefore, there is a need for new and potent small molecule inhibitors of FASN to treat these diseases. [Prior art documents] [Non-patent literature]

[0011] [Non-Patent Document 1] 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 [Non-Patent Document 2] 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 [Non-Patent Document 3] 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 [Non-Patent Document 4] Kakazu, E., et al., “Hepatocytes Release Ceramide-rich Proinflammatory Extracellular Vesicles in an IRE1alpha dependent manner,” Abstract 58. AASLD- The Liver Meeting, San Francisco, CA, USA, 13-17, November, 2015 Summary of the Invention [Means for solving the problem]

[0012] The present disclosure addresses deficiencies in antiviral and anticancer treatments by providing novel heterocyclic modulators of lipid synthesis with improved antiviral and anticancer activity.

[0013] In various embodiments, the present disclosure provides a compound of structure (I): [ka] (I) (In the formula, X, Y and Z are each independently CR or NR′, where R is hydrogen or C 1~6 alkyl, R' is hydrogen, C 1~6 alkyl, or absent; A is CH or N; R 1 is hydrogen, cyano, halo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(=O)N(R 13)(R 14 ), -(CH 2 ) q C(=O)N(R 13 )(R 14 ), C.F. 3 , -OCF 3 , or -S(=O) 2 R 20 and; q is 0, 1, 2, 3 or 4; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 2 is hydrogen, halo, C 1~6 Alkoxy, C 1~6 alkyl, or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl, C 1~6 Alkoxy; or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 4 is hydrogen, heteroaryl, heterocyclyl, -C(=O)N(R 5 R 6 ), -N(R 7 )C(=O)R 8 , -N(R 9 R 10 ), C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20 or R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl; R 11 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 and R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl, or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 12 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 13 and R 14 are each independently hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, alkylamino, -N(R 15 R 16 ), or -S(=O) 2 R 20 and; R 15 and R 16 are each independently hydrogen, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl or alkylamino; R 17 and R 18 are each independently hydrogen or alkyl, or may optionally be joined together to form a bond; n is 1 or 2; m is 0 or 1), or a pharma- ceutically acceptable salt thereof.

[0014] In various embodiments, the present disclosure provides a compound of structure (II): [ka] (II) (In the formula, X, Y and Z are each independently CR or NR′, where R is hydrogen or C 1~6 alkyl, R' is hydrogen, C 1~6 alkyl, or absent; L and D are each independently C or N; R 1 is hydrogen, cyano, halo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(=O)N(R 13 )(R 14 ), -(CH 2 ) q C(=O)N(R 13 )(R 14 ), C.F. 3 , -OCF 3 , or -S(=O) 2 R 20 and; q is 0, 1, 2, 3 or 4; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 2 is hydrogen, halo, C 1~6 Alkoxy, C 1~6 alkyl, or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl, C1~6 Alkoxy; or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 4 is hydrogen, heteroaryl, heterocyclyl, -C(=O)N(R 5 R 6 ), -N(R 7 )C(=O)R 8 , -N(R 9 R 10 ), C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20 or R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl; R 11 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 and R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl, or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 12 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 13 and R 14 are each independently hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, alkylamino, -N(R 15 R 16 ), or -S(=O) 2 R 20 and; R 15 and R 16 are each independently hydrogen, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl or alkylamino; R 17 and R 18 are each independently hydrogen or alkyl, or may optionally be joined together to form a bond; n is 1 or 2; m is 0 or 1), or a pharma- ceutically acceptable salt thereof.

[0015] In various embodiments, the present disclosure provides a compound of structure (III): [ka] (III) (In the formula, X, Y and Z are each independently CR or NR′, where R is hydrogen or C 1~6 alkyl, R' is hydrogen, C 1~6 alkyl, or absent; Q is C or N; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl, C 1~6 alkoxy, or when Q is N, R 3 is non-existent; R 4is hydrogen, heteroaryl, heterocyclyl, -C(=O)N(R 5 R 6 ), -N(R 7 )C(=O)R 8 , -N(R 9 R 10 ), C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20 or R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl; R 11 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 and R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl, or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 12 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 13 and R 14 are each independently hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, alkylamino, -N(R 15 R 16 ), or -S(=O) 2 R 20 and; R 15 and R 16 are each independently hydrogen, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl or alkylamino; R 17 and R 18 are each independently hydrogen or alkyl, or may optionally be joined together to form a bond; R 19 is aryl, heteroaryl, cycloalkyl, or heterocyclyl; n is 0, 1 or 2; m is 0 or 1), or a pharma- ceutically acceptable salt thereof.

[0016] In various embodiments, the present disclosure provides a compound of structure (IV-A), (IV-B) or (IV-C): [ka] (In the formula, L 1 , L 2 , L 3 , L 4 and A are each independently CH or N; R 1 is hydrogen, cyano, halo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(=O)N(R 13 )(R 14 ), -(CH 2 )q C(=O)N(R 13 )(R 14 ), C.F. 3 , -OCF 3 , or -S(=O) 2 R 20 and; q is 0, 1, 2, 3 or 4; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 2 is hydrogen, halo, C 1~6 Alkoxy or C 1~6 is alkyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl or C 1~6 is alkoxy; R 21 and R 22 are each independently hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, CF 3 , -OCF 3 , or -S(=O) 2 R 20 and; R 23 is hydrogen, -N(R 13 )(R 14 ), C 1 ~ 6 Alkyl, C 1 ~ 6 Alkoxy, L 1 If N then it is non-existent, otherwise R 23 and R 24 together with the atoms to which they are attached, join together to form a heterocyclyl, heteroaryl, or cycloalkyl; R 24 is hydrogen, -N(R 13 )(R 14 ), C 1 ~ 6 Alkyl, C 1 ~ 6Alkoxy, -(C 1 ~ 6 alkoxy)(heterocyclyl), heterocyclyl, or R 23 and R 24 together with the atoms to which they are attached, join together to form a heterocyclyl, heteroaryl, or cycloalkyl; R 26 is hydrogen, heteroaryl, heterocyclyl, -N(R 13 )(R 14 ), or -S(=O) 2 R 20 and; R 13 and R 14 are each independently hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, alkylamino, -N(R 15 R 16 ), or -S(=O) 2 R 20 and; R 25 is hydrogen, C 1~6 Alkyl or C 1~6 is alkoxy; R 15 and R 16 are each independently hydrogen, C 1~6 Alkyl, C 1~6 alkoxy, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl or alkylamino) or a pharma- ceutically acceptable salt thereof.

[0017] In various embodiments, the present disclosure provides a compound of structure (V): [ka] (V) (In the formula, L 7 is N or O, in which case L 7 If is O, then R 30 is non-existent; A is CH or N; R 1 is hydrogen, cyano, halo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(=O)N(R 13 )(R 14 ), -(CH 2 ) q C(=O)N(R 13 )(R 14 ), C.F. 3 , -OCF 3 , or -S(=O) 2 R 20 and; q is 0, 1, 2, 3 or 4; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 2 is hydrogen, halo, C 1~6 Alkoxy or C 1~6 is alkyl; R 3 Halo, C 1~6 Alkyl or C 1~6 is alkoxy; R 21 and R 22 are each independently hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, CF 3 , -OCF 3 , or -S(=O) 2 R 20 and; R 29 and R 30 are each independently hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, hydroxyalkyl, heteroaryl, heterocyclyl, -N(R 15 R 16 ), -C(=O)R 46 , -R 48 C(=O)R 47 or R 29 and R 30together with the atoms to which they are attached, join together to form a heteroaryl or heterocyclyl, in which case R 30 , L 7 If is O then it does not exist; R 46 and R 47 are each independently hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, -N(R 15 R 16 ), or -S(=O) 2 R 20 and; R 48 is alkyl or absent; R 31 is hydrogen, C 1~6 Alkyl or C 1~6 is alkoxy; R 13 and R 14 are each independently hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, alkylamino, -N(R 15 R 16 ), or -S(=O) 2 R 20 and; R 15 and R 16 are each independently hydrogen, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, or alkylamino; and v is 0 or 1, or a pharma- ceutically acceptable salt thereof.

[0018] In various embodiments, the present disclosure provides a compound of structure (VI-A) or (VI-B): [ka] (In the formula, L 13 , L 14 , L 15and A are each independently CH or N; R 1 is hydrogen, cyano, halo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(=O)N(R 13 )(R 14 ), -(CH 2 ) q C(=O)N(R 13 )(R 14 ), C.F. 3 , -OCF 3 , or -S(=O) 2 R 20 and; q is 0, 1, 2, 3 or 4; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 2 is hydrogen, halo, C 1~6 Alkoxy or C 1~6 is alkyl; R 3 Halo, C 1~6 Alkyl or C 1~6 is alkoxy; R 21 and R 22 are each independently hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, CF 3 , -OCF 3 , or -S(=O) 2 R 20 and; R 34 is hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, cycloalkyl, hydroxyl, hydroxyalkyl, aryl, heterocyclyl, heteroaryl, alkylamino, CF 3 , -OCF 3 , -S(=O) 2 R 20 , or -N(R 15 R 16 ) and; R 35 is hydrogen, C 1~6 Alkyl or C 1~6 is alkoxy; R 36 is hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 15 R 16 ), heterocyclyl or heteroaryl; R 13 and R 14 are each independently hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, alkylamino, -N(R 15 R 16 ), or -S(=O) 2 R 20 and; R 15 and R 16 are each independently hydrogen, C 1~6 Alkyl, C 1~6 alkoxy, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl or alkylamino) or a pharma- ceutically acceptable salt thereof.

[0019] In various embodiments, the present disclosure provides a compound of structure (VI-J): [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~ C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 straight or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof.

[0020] In some embodiments of structure (VI-J), R 3 is H or a halogen.

[0021] In some embodiments of structure (VI-J), R 1 is halogen, -CN or C 1 ~C 2 It is haloalkyl.

[0022] In some embodiments of structure (VI-J), R 22 is C 1 ~C 2 It is an alkyl.

[0023] In some embodiments of structure (VI-J), R 21is cyclobutyl, and R 22 is C 1 ~C 2 It is an alkyl.

[0024] In some embodiments of structure (VI-J), R 21 is cyclobutyl.

[0025] In some embodiments of structure (VI-J), R 3 is H or F.

[0026] In some embodiments of structure (VI-J), R 1 is -CN.

[0027] In some embodiments of structure (VI-J), R 1 -CF 3 It is.

[0028] In some embodiments of structure (VI-J), R 22 is H, methyl or ethyl.

[0029] In some embodiments of structure (VI-J), R 22 is H.

[0030] In some embodiments of structure (VI-J), R 22 is methyl.

[0031] In some embodiments of structure (VI-J), R 35 is -C(O)-NHR 351 It is.

[0032] In some embodiments of structure (VI-J), R 351 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.

[0033] In some embodiments of structure (VI-J), R 351 is (R)-(tetrahydrofuran) -2-yl)methyl or (S)-(tetrahydrofuran-2-yl)methyl.

[0034] In some embodiments of structure (VI-J), R 1 is -CN, and each R 2 is hydrogen and R 3 is H or F, and R 21 is C 3 ~C 4 cycloalkyl, R 22 is H and R 35 is -C(O)-NHR 351 where R 351 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.

[0035] In some embodiments of structure (VI-J), R 35 is -C(O)-OR 351 It is.

[0036] In some embodiments of structure (VI-J), R 351 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.

[0037] In some embodiments of structure (VI-J), R 1 is -CN, and each R 2 is H and R 3 is H or F, and R 21 is C3 ~C 4 cycloalkyl, R 22 is H and R 35 is -C(O)-OR 351 where R 351 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.

[0038] In some embodiments of structure (VI-J), R 351 is (R)-3-tetrahydrofuranyl or (S)-3-tetrahydrofuranyl.

[0039] In some embodiments of structure (VI-J), the compound is [ka] The compound has a structure selected from the group consisting of:

[0040] In various embodiments, the present disclosure provides a compound of structure (VII-A) or (VII-B): [ka] (In the formula, L 16 is C or N, in which case L 16 If N, then R 41 is non-existent; L 17 , L 18 and A are each independently CH or N; R 1 is hydrogen, cyano, halo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(=O)N(R 13 )(R 14 ), -(CH 2 ) q C(=O)N(R13 )(R 14 ), C.F. 3 , -OCF 3 , or -S(=O) 2 R 20 and; q is 0, 1, 2, 3 or 4; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 2 is hydrogen, halo, C 1~6 Alkoxy or C 1~6 is alkyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl or C 1~6 is alkoxy; R 21 and R 22 are each independently hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, CF 3 , -OCF 3 , or -S(=O) 2 R 20 and; R 40 , R 42 and R 43 are each independently hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20 , -C(=O)R, hydroxyalkyl, hydroxyl, -N(R 13 R 14 ) or R 41 and R 42 together with the atoms to which they are attached, join together to form a heteroaryl or heterocyclyl; R 41 is hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20, -C(=O)R, hydroxyalkyl, hydroxyl, -N(R 13 R 14 ) and R 41 , L 16 If N then it is non-existent, otherwise R 41 and R 42 together with the atoms to which they are attached, join together to form a heteroaryl or heterocyclyl; R is hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, -N(R 15 R 16 ) or -S(=O) 2 R 20 and; R 39 is hydrogen, C 1~6 Alkyl or C 1~6 is alkoxy; R 13 and R 14 are each independently hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, alkylamino, -N(R 15 R 16 ), or -S(=O) 2 R 20 and; R 15 and R 16 are each independently hydrogen, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl or alkylamino) or a pharma- ceutically acceptable salt thereof.

[0041] In various embodiments, the present disclosure provides a compound of structure (VIII-A), (VIII-B) or (VIII-C): [ka] (In the formula, L 19 and A are each independently CH or N; R 1is hydrogen, cyano, halo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(=O)N(R 13 )(R 14 ), -(CH 2 ) q C(=O)N(R 13 )(R 14 ), C.F. 3 , -OCF 3 , or -S(=O) 2 R 20 and; q is 0, 1, 2, 3 or 4; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 2 is hydrogen, halo, C 1~6 Alkoxy or C 1~6 is alkyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl or C 1~6 is alkoxy; R 21 and R 22 are each independently hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, CF 3 , -OCF 3 , or -S(=O) 2 R 20 and; R 39 is hydrogen, C 1~6 Alkyl or C 1~6 is alkoxy; R 44 and R 45 are each independently hydrogen, C 1~6 Alkyl, C 1~6 Alkoxy, cycloalkyl, hydroxyalkyl, aryl, heterocyclyl, heteroaryl, alkylamino, -S(=O) 2 R 20 , -C(=O)R, or -N(R 13 R14 ) and; R 13 and R 14 are each independently hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, alkylamino, -N(R 15 R 16 ), or -S(=O) 2 R 20 and; R 15 and R 16 are each independently hydrogen, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl or alkylamino) or a pharma- ceutically acceptable salt thereof.

[0042] In various embodiments, a compound of structure (IX): [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 Cycloal It is a kill, in this case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof is provided.

[0043] In some embodiments of structure (IX), R 24 is C 1 ~C 4 Linear or branched alkyl or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 straight or branched chain alkyl), where t is 0 or 1.

[0044] In some embodiments of structure (IX), R 21 is a halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 Cycloalkyl (in this case, C 3 ~C 5 Cycloalkyl optionally contains an oxygen or nitrogen heteroatom, -S(O) u -(C 1 ~C 4 straight or branched chain alkyl) (where u is 0 or 2), or -S(O) u -(C 3 ~C 5 cycloalkyl) (wherein u is 0 or 2).

[0045] In some embodiments of structure (IX), R 3 is H or a halogen.

[0046] In some embodiments of structure (IX), R 1 is halogen, -CN or C 1 ~C 2 It is haloalkyl.

[0047] In some embodiments of structure (IX), L 1 and L 2 Both are N.

[0048] In some embodiments of structure (IX), R 21 is C 1 ~C 2 Alkyl or C3 ~C 5 cycloalkyl, R 22 is C 1 ~C 2 It is an alkyl.

[0049] In some embodiments of structure (IX), R 21 is C 3 ~C 5 cycloalkyl, R 22 is C 1 ~C 2 It is an alkyl.

[0050] In some embodiments of structure (IX), R 24 is -(C 1 ~C 2 Alkyl) t -O-(C 1 ~C 2 alkyl), where t is 0 or 1.

[0051] In some embodiments of structure (IX), R 21 is C 3 ~C 5 cycloalkyl, R 22 is C 1 ~C 2 is alkyl, R 24 is C 1 ~C 2 It is an alkyl.

[0052] In some embodiments of structure (IX), R 21 is cyclobutyl, and R 22 is C 1 ~C 2 is alkyl, R 24 is C 1 ~C 2 It is an alkyl.

[0053] In some embodiments of structure (IX), R 21 is cyclobutyl.

[0054] In some embodiments of structure (IX), R 3is H or F.

[0055] In some embodiments of structure (IX), R 1 is -CN.

[0056] In some embodiments of structure (IX), R 1 -CF 3 It is.

[0057] In some embodiments of structure (IX), R 22 is H, methyl or ethyl.

[0058] In some embodiments of structure (IX), R 22 is H.

[0059] In some embodiments of structure (IX), R 22 is methyl.

[0060] In some embodiments of structure (IX), R 1 is -CN, and each R 2 is H and R 3 is H or F, and R 21 is C 3 ~C 4 cycloalkyl, R 22 is methyl, L 1 and L 2 is N and R 24 are methyl, ethyl, hydroxymethyl, methoxymethyl, and 2-methoxyethyl.

[0061] In some embodiments of structure (IX), R 1 is -CN, and each R 2 is H and R 3 is H or F, and R 21 is C 3 ~C 4 cycloalkyl, R 22 is methyl, L 1 and L 2 is N and R 24 is methoxy or ethoxy.

[0062] In some embodiments of structure (IX), R 1 is -CN, and each R 2 is H and R 3 is H or F, and R 21 is C 3 ~C 4 cycloalkyl, R 22 is methyl, L 1 is CH, and L 2 is N and R 24 is methyl, ethyl, hydroxymethyl, methoxymethyl, or 2-methoxyethyl.

[0063] In some embodiments of structure (IX), R 1 is -CN, and each R 2 is H and R 3 is H or F, and R 21 is C 3 ~C 4 cycloalkyl, R 22 is methyl, L 1 is N and L 2 is CH and R 24 is methyl, ethyl, hydroxymethyl, methoxymethyl, or 2-methoxyethyl.

[0064] In some embodiments of structure (IX), the compound is [ka] The compound has a structure selected from the group consisting of:

[0065] In various embodiments, a compound of structure (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 )2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 Straight or branched chain alkyl and; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof is provided.

[0066] In some embodiments of structure (X), R 21 is a halogen, C 1 ~C 4 Straight or branched chain alkyl or C 3 ~C 5 It is cycloalkyl.

[0067] In some embodiments of structure (X), R 3 is H or a halogen.

[0068] In some embodiments of structure (X), R 1 -CN or C 1 ~C 2 It is haloalkyl.

[0069] In some embodiments of structure (X), R 3 is H or F.

[0070] In some embodiments of structure (X), R 1 is -CN.

[0071] In some embodiments of structure (X), R 1 -CF 3 It is.

[0072] In some embodiments of structure (X), n is 1.

[0073] In some embodiments of structure (X), n is 2.

[0074] In some embodiments of structure (X), m is 1.

[0075] In some embodiments of structure (X), m is 2.

[0076] In some embodiments of structure (X), R 21 is C 1 ~C 2 Alkyl or C 3 ~C 5 cycloalkyl, R 22 is C 1 ~C 2 It is an alkyl.

[0077] In some embodiments of structure (X), R 21 is C 3 ~C 5 cycloalkyl, R 22 is C 1 ~C 2 It is an alkyl.

[0078] In some embodiments of structure (X), n is 2, m is 1, and L 3 is -NC(O)-O-(C 1 ~C 2 alkyl).

[0079] In some embodiments of structure (X), L 3 is NR 50 and R 50 is C 1 ~C 2 is alkyl, R 21 is cyclobutyl, and R 22 is H or methyl, R3 is H and R 1 is -CN, m is 2, and n is 1 or 2.

[0080] In some embodiments of structure (X), n is 2, m is 1, and L 3 is O and s is 0.

[0081] In some embodiments of structure (X), R 22 is H, methyl or ethyl.

[0082] In some embodiments of structure (X), R 22 is methyl.

[0083] In some embodiments of structure (X), R 22 is H.

[0084] In some embodiments of structure (X), R 1 is -CN, and each R 2 is H and R 3 is H or F, and R 21 is C 3 ~C 4 cycloalkyl, R 22 is methyl, n is 2, and L 3 is NR 50 where R 50 is methyl or ethyl.

[0085] In some embodiments of structure (X), R 1 is -CN, and each R 2 is H and R 3 is H or F, and R 21 is C 3 ~C 4 cycloalkyl, R 22 is methyl, n is 2, and L 3 is O.

[0086] In some embodiments of structure (X), the compound is [ka] The compound has a structure selected from the group consisting of:

[0087] In various embodiments, a compound of structure (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention also provides a compound comprising:

[0088] In some embodiments of structure (XI), R 3 is H or a halogen.

[0089] In some embodiments of structure (XI), R 1 is halogen, -CN or C 1 ~C 2 It is haloalkyl.

[0090] In some embodiments of structure (XI), R 21 is C 3 ~C 4 cycloalkyl, R 22 is C 1 ~C 2 It is an alkyl.

[0091] In some embodiments of structure (XI), R 21 is cyclobutyl, and R 22 is C 1 ~C 2 It is an alkyl.

[0092] In some embodiments of structure (XI), R 21 is cyclobutyl.

[0093] In some embodiments of structure (XI), R 3 is H or F.

[0094] In some embodiments of structure (XI), R 1 is -CN.

[0095] In some embodiments of structure (XI), R 1 -CF 3 It is.

[0096] In some embodiments of structure (XI), R 22 is H, methyl or ethyl.

[0097] In some embodiments of structure (XI), R 22 is H.

[0098] In some embodiments of structure (XI), R 22 is methyl.

[0099] In some embodiments of structure (XI), R 1 is -CN, and each R 2 is H and R 3 is H or F, and R 21 is cyclobutyl, and R 22 is methyl, R 351 is methyl or ethyl.

[0100] In some embodiments of structure (XI), the compound is [ka] and [ka] The compound has a structure selected from the group consisting of:

[0101] In various aspects, the disclosure provides a pharmaceutical composition comprising any one of the compounds of structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X) or (XI) and a pharma- ceutically acceptable carrier, excipient or diluent.

[0102] In various embodiments, the disclosure provides a method of treating a condition characterized by dysregulation of fatty acid synthase function in a subject, comprising administering to a subject in need of such treatment an effective amount of any one of the compounds of structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X) or (XI). In various embodiments, the condition characterized by dysregulation of fatty acid synthase function is a viral infection or cancer. In various embodiments, any one of the compounds of structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X) or (XI) is used in combination with one or more additional antiviral treatments to treat a viral infection. In various embodiments, a compound of any one of structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X) or (XI) is used in combination with one or more additional cancer treatments to treat cancer. In various embodiments, the viral infection is Hepatitis C.

[0103] In various aspects, the disclosure provides a method of treating fatty liver disease in a subject in need thereof, comprising administering to a subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -( C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl requires an oxygen or nitrogen heteroatom. Depending on the R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 straight or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 is -CH 2 -, -CHR 50 -, -O-, -NR 50 -, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 and R 25 each independently represents H, -C 1 ~C 4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241 is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O) 2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C 1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24 is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25 is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0104] In various aspects, the present disclosure provides a method of treating non-alcoholic steatohepatitis (NASH) in a subject in need thereof, comprising administering to a subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched chain alkane Kill, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 straight or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 is -CH 2 -, -CHR 50 -, -O-, -NR 50 -, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 and R 25 each independently represents H, -C 1 ~C 4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241 is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O) 2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C 1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24 is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25 is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0105] In various embodiments, the present disclosure provides a method of treating non-alcoholic fatty liver disease (NAFLD) in a subject in need thereof, comprising administering to the subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched chain alkane Kill, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6straight or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl)t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 )2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 -CH 2 -, -CHR 50 -, -O-, -NR 50 -, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 and R 25 each independently represents H, -C 1 ~C 4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241 is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O) 2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C 1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24 is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0106] In various aspects, the present disclosure provides a method of treating metabolic syndrome in a subject in need thereof, comprising administering to a subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched chain alkane Kill, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 linear or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u-(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 )2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 is -CH 2 -, -CHR 50 -, -O-, -NR 50 -, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 and R 25 each of which is independently H, -C 1 ~C 4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241is H or C 1 ~C 2 alkyl); or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O) 2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C 1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25 is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0107] In various aspects, the present disclosure provides a method of treating cirrhosis in a subject in need thereof, comprising administering to the subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched chain alkane Kill, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 linear or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl)t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 is -CH 2 -, -CHR 50 -, -O-, -NR 50 -, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 and R 25 each of which is independently H, -C 1 ~C4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241 is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O)2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C 1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24 is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25 is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0108] In various aspects, the present disclosure provides a method of treating liver fibrosis in a subject in need thereof, comprising administering to a subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms;3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched chain alkane Kill, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 straight or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 -CH 2 -, -CHR 50 -, -O-, -NR 50-, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1~C 2 is alkyl; R 24 and R 25 each of which is independently H, -C 1 ~C 4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -Ou -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241 is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O) 2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24 is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25 is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0109] In various aspects, the present disclosure provides a method of treating liver cancer in a subject in need thereof, comprising administering to a subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched chain alkane Kill, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 linear or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 is -CH 2 -, -CHR 50 -, -O-, -NR 50 -, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 and R 25 each of which is independently H, -C 1 ~C 4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -Ou -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241 is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O) 2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C 1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24 is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25 is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0110] In various embodiments, the present disclosure provides a method of treating a disease or condition in which interleukin 1 beta (IL1β) levels are elevated in a subject in need thereof, comprising administering to a subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 straight or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 -CH 2 -, -CHR 50 -, -O-, -NR 50 -, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 and R 25 each independently represents H, -C 1 ~C 4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241 is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O) 2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C 1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24 is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25 is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0111] In various embodiments, the present disclosure provides a method for the treatment of T helper cells (T h A method of treating a disease or condition in which elevated levels of a marker for inflammatory bowel disease or a neurodegenerative disease are present in a subject in need thereof, comprising administering to a subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 straight or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 is -CH 2 -, -CHR 50 -, -O-, -NR 50 -, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 and R 25 each independently represents H, -C 1 ~C 4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241 is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O) 2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C 1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24 is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25 is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0112] In various embodiments, the present disclosure provides a method for the treatment of cancer by using regulatory T cells (T reg ) is reduced or inhibited in a subject in need thereof, comprising administering to a subject in need thereof (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C1 ~C 6 straight or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 is -CH 2 -, -CHR 50 -, -O-, -NR 50 -, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 and R 25 each of which is independently H, -C 1 ~C 4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241 is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O) 2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C 1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24 is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0113] In various aspects, the present disclosure provides a method of reversing established non-alcoholic steatohepatitis (NASH), comprising administering to a subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched chain alkane Kill, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 linear or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u-(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 )2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 is -CH 2 -, -CHR 50 -, -O-, -NR 50 -, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 and R 25 each independently represents H, -C 1 ~C 4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O) 2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C 1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25 is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0114] In various aspects, the present disclosure provides a method of reducing fibrosis gene expression, comprising administering to a subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5 Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched chain alkane Kill, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 linear or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl)t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 is -CH 2 -, -CHR 50 -, -O-, -NR 50 -, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 and R 25 each independently represents H, -C 1 ~C4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241 is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O)2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C 1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24 is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25 is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0115] In various aspects, the present disclosure provides a method of treating skin fibrosis, comprising administering to a subject in need thereof: (a) Formula (IX) [ka] (IX) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Linear or branched alkyl, -(C 1 ~C 4 Alkyl) t -OH, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 cycloalkyl), or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 linear or branched chain alkyl), in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; L 1 CR 23 or N; L 2 is CH or N; L 1 or L 2 at least one of is N; R 23 is H or C 1 ~C 4 straight or branched chain alkyl) or a pharma- ceutically acceptable salt thereof; or (b) Formula (X): [ka] (X) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; L 3 is C(R 60 ) 2 , O or NR 50 and; Each R 60 are independently H, -OH, -CN, -O t -(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 straight or branched chain alkyl), or -C(O)-N(R 601 ) 2 In this case, t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; Each R 50 are independently H, -C(O)-O t -(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 3 ~C 5 cyclic alkyl), optionally containing oxygen or nitrogen heteroatoms; 3 ~C 5Cyclic alkyl, -C(O)-N(R 501 ) 2 , C 1 ~C 4 is a straight or branched chain alkyl, in which t is 0 or 1; C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; n is 1, 2 or 3; m is 1 or 2; R 21 H, halogen, C 1 ~C 4 Straight or branched chain alkyl, C 3 ~C 5 cycloalkyl, in which case C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 22 H, halogen, C 1 ~C 2 is alkyl; Each R 26 are independently -OH, -CN, halogen, C 1 ~C 4 Linear or branched chain alkane Kill, -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 Straight or branched chain alkyl), -C(O)-O t -(C 1 ~C 4 alkyl), or -C(O)-N(R 501 ) 2 In this case, t is 0 or 1; C 3 ~C 5Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; s is 0, 1 or 2; Each R 601 and R 501 are independently H or C 1 ~C 4 is a straight or branched chain alkyl; Here, R 26 , R 60 , R 50 , R 501 and R 601 Two of the groups may be optionally linked to form a ring, in which case R 26 , R 60 , R 50 , R 501 and R 601 Two of them are R 26 , two R 60 , two R 50 , two R 501 or two R's 601 or a pharma- ceutically acceptable salt thereof; or (c) Formula (VI-J) [ka] (VI-J) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Linear or branched alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R 21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 35 is -C(O)-R 351 , -C(O)-NHR 351 , -C(O)-OR 351 Or S(O) 2 R 351 and; R 351 is C 1 ~C 6 linear or branched chain alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (d) a group of formula (XII): [ka] (XII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case , R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is H, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 6 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; Each R 241 are independently H or C 1 ~C 2 is alkyl; R 25 is halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 2 alkyl or cyclopropyl) or a pharma- ceutically acceptable salt thereof; or (e) Formula (XIII): [ka] (XIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; Each R 24 and R 25 are independently H, halogen, -CN, -(C 1 ~C 4 Alkyl)-CN, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O u -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; each u is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or its pharma- ceutical acceptable salts an acceptable salt; or (f) Formula (XIV): [ka] (XIV) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl) t -N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O t -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -O t -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl) t -O-(C 1 ~C 4 alkyl), in which each t is independently 0 or 1; Each R 241 are independently H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (g) Formula (XV): [ka] (XV) (In the formula, L 3 is -CH 2 -, -CHR 50 -, -O-, -NR 50-, -NC(O)R 50 -OR-NC(O)OR 50 - In this case, R 50 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; n is 1, 2 or 3; m is 1 or 2, with the proviso that n+m≧3; L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (h) Formula (XVI): [ka] (XVI) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1~C 2 is alkyl; R 24 and R 25 each independently represents H, -C 1 ~C 4 alkyl or halogen) or a pharma- ceutically acceptable salt thereof; or (i) Formula (XVII): [ka] (XVII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 , H, C 1 ~C 4 Alkyl, -(C 1 ~C 4 alkyl)-OH, -(C 1 ~C 4 Alkyl)-N(R 241 ) 2 , -(C 1 ~C 4 Alkyl) t -O u -(C 3 ~C 5 Cycloalkyl), -(C 1 ~C 4 Alkyl) t -Ou -(4- to 6-membered heterocycle) or -(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), in which t is 0 or 1; u is 0 or 1; where u is 1, then t is 1; R 241 is H or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (j) Formula (XVIII): [ka] (XVIII) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] , [ka] , [ka] , [ka] or [ka] where L-Ar is [ka] When , Ar is [ka] rather than; L 2 -NHR 35 or -C(O)NHR 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 is cycloalkyl, 4-6 membered heterocycle, aryl or heteroaryl; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2is alkyl; R 35 is -C(O)R 351 , -C(O)NHR 351 , C(O)OR 351 Or S(O) 2 R 351 In this case, R 351 is C 1 ~C 6 Alkyl, C 3 ~C 5 cycloalkyl, 4-6 membered heterocycle, aryl, or heteroaryl) or a pharma- ceutically acceptable salt thereof; or (k) Formula (XIX): [ka] (XIX) (In the formula, Each W, X, Y and Z is independently -N- or -CR 26 -, with the proviso that not more than two of W, X, Y, and Z are -N-; Each R 26 are independently H, C 1 ~C 4 Alkyl, -O-(C 1 ~C 4 alkyl), -N(R 27 ) 2 , -S(O) 2 -(C 1 ~C 4 alkyl), or -C(O)-(C 1 ~C 4 alkyl); Each R 27 are independently H or C 1 ~C 4 alkyl, or R 27 are both C 1 ~C 4 alkyl, which, together with the N to which they are attached, are linked to each other to form a 3- to 6-membered ring, wherein the ring optionally contains one oxygen atom as one of the ring members; Ar is [ka] , [ka] , [ka] , [ka] or [ka] and; Het is 5-6 membered heteroaryl; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(4-6 membered heterocycle), -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 11 is H or -CH 3 and; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 alkyl) or a pharma- ceutically acceptable salt thereof; or (l) Formula (XX): [ka] (XX) (In the formula, L-Ar is [ka] , [ka] or [ka] and; Ar is [ka] and; R 1 H, -CN, halogen, C 1 ~C 4 Alkyl, -O-(C 3 ~C 5 cycloalkyl), -O-(4- to 6-membered heterocycle) or -O-(C 1 ~C 4 alkyl), in which case R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently hydrogen, halogen or C 1 ~C 4 is alkyl; R 3 is H or F; R 21 H, halogen, C 1 ~C 4 Alkyl, C 3 ~C 5 cycloalkyl or a 4- to 6-membered heterocycle; R 22 is H, halogen or C 1 ~C 2 is alkyl; R 24 is -O-(C1 ~C 4 alkyl), -O-(C 1 ~C 4 Alkyl)-O-(C 1 ~C 4 alkyl), -O-(C 3 ~C 5 -cycloalkyl), or -O-(4- to 6-membered heterocycle), in which case R 24 is optionally substituted with one or more hydroxyls or halogens; R 25 H, halogen, C 1 ~C 4 Alkyl or C 3 ~C 5 cycloalkyl, where R 25 is optionally substituted with one or more halogens) or a pharma- ceutically acceptable salt thereof; or (m) Formula (XI): [ka] (XI) (In the formula, R 1 H, -CN, halogen, C 1 ~C 4 Straight or branched chain alkyl, -O-(C 3 ~C 5 Cycloalkyl), -O-(C 1 ~C 4 linear or branched alkyl), in which C 3 ~C 5 Cycloalkyl optionally contains oxygen or nitrogen heteroatoms; R 1 When is not H, -CN, or halogen, R 1 is optionally substituted with one or more halogens; Each R 2 are independently H, halogen or C 1 ~C 4 is a straight or branched chain alkyl; R 3 is H, -OH or a halogen; R21 is cyclobutyl, azetidin-1-yl, or cyclopropyl; R 22 H, halogen, C 1 ~C 2 is alkyl; R 351 is C 1 ~C 2 Alkyl or C 2 -O-(C 1 Or C 2 The present invention relates to methods of treating a patient suffering from a chronic obstructive pulmonary disease (COPD) comprising administering to the patient a fatty acid synthase inhibitor having the formula:

[0116] In various embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as described in Table 1 can be used in the manufacture of a medicament for treating nonalcoholic steatohepatitis (NASH) or a symptom of NASH. In further embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as described in Table 1 can be used to treat nonalcoholic steatohepatitis (NASH) or a symptom of NASH.

[0117] In various embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as described in Table 1 can be used in the manufacture of a medicament for treating non-alcoholic fatty liver disease (NAFLD). In further embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as described in Table 1 can be used to treat non-alcoholic fatty liver disease (NAFLD).

[0118] In various embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or a compound as described in Table 1 can be used in the manufacture of a medicament for treating metabolic syndrome. In further embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or a compound as described in Table 1 can be used to treat metabolic syndrome.

[0119] In various embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or a compound as described in Table 1 can be used in the manufacture of a medicament for treating cirrhosis of the liver. In further embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or a compound as described in Table 1 can be used to treat cirrhosis of the liver.

[0120] In various embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or as described in Table 1, can be used in the manufacture of a medicament for treating liver fibrosis. In further embodiments, compounds having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as set forth in Table 1 can be used to treat liver fibrosis.

[0121] In various embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or a compound as described in Table 1 can be used in the manufacture of a medicament for treating liver cancer. In further embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or a compound as described in Table 1 can be used to treat liver cancer.

[0122] In various embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as described in Table 1 can be used in the manufacture of a medicament for treating liver fibrosis. In further embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as described in Table 1 can be used to treat liver fibrosis.

[0123] In various embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as described in Table 1 can be used in the manufacture of a medicament for treating a disease or condition in which interleukin 1 beta (IL1β) levels are elevated. In further embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as described in Table 1 can be used to treat a disease or condition in which interleukin 1 beta (IL1β) levels are elevated.

[0124] In various embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or a compound as described in Table 1 is administered to T helper cells (T hIn a further embodiment, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or a compound as described in Table 1 can be used in the manufacture of a medicament for treating a disease or condition in which the levels of T helper cells (T h The compounds can be used to treat diseases or conditions in which there are elevated levels of

[0125] In various embodiments, a compound having the structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI), or a compound as described in Table 1 is administered to a subject in need of treatment with a regulatory T cell (T reg In a further embodiment, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as set forth in Table 1 can be used in the manufacture of a medicament for treating a disease or condition in which regulatory T cells (Tregs) are reduced or inhibited.

[0126] In various embodiments, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as set forth in Table 1 can be used in the manufacture of a medicament for treating or reversing established nonalcoholic steatohepatitis (NASH). In further embodiments, compounds having structures (I), (II), (III), (IV), (V), (VI), (VII), (VIII) can be used in the manufacture of a medicament for treating or reversing established nonalcoholic steatohepatitis (NASH). Compounds having the formula (IX), (X), (XI), or compounds as described in Table 1 can be used to treat or reverse nonalcoholic steatohepatitis (NASH).

[0127] In various embodiments, compounds having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as described in Table 1 can be used in the manufacture of a medicament for reducing fibrosis gene expression. In further embodiments, compounds having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or as described in Table 1 can be used to reduce fibrosis gene expression.

[0128] In various embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or a compound as described in Table 1 can be used in the manufacture of a medicament for treating skin fibrosis. In further embodiments, a compound having structure (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) or a compound as described in Table 1 can be used to treat skin fibrosis. [Brief description of the drawings]

[0129] [Figure 1] This illustrates the correlation between FASN inhibition and HCV inhibition. [Diagram 2] 1 shows images of liver tissue samples stained with Oil Red O or Masson staining from C57BL / 6NCrSim mice treated with vehicle or 10 mg / kg of Compound 364A. The results show that treatment with the FASN inhibitor Compound 364A inhibited the development of steatosis. [Diagram 3] Shown are images of liver tissue samples stained with Oil Red O from C57BL / 6J mice treated with vehicle for 28 days, vehicle for 57 days, or vehicle for 28 days followed by 10 mg / kg of compound 364A for 29 days. The results show that treatment with the FASN inhibitor compound 364A inhibited the development of hepatic steatosis. [Figure 4]1 is a graph showing IL-1β levels in untreated rats and rats treated with vehicle, 60 mg / kg compound 6B, or 100 mg / kg compound 6B. The results show that treatment with compound 6B reduces serum IL-1β beta levels after feeding in fasted rats. [Diagram 5] 1 is a graph showing IL-1β levels in rats treated with vehicle, 60 mg / kg of compound 6B, or 100 mg / kg of compound 6B. The results show that treatment with compound 6B reduces serum IL-1β beta levels 22 hours after feeding in fasted rats. [Figure 6A] FIG. 1 is a graph showing IL-1β levels in mice treated with vehicle, 3 mg / kg Compound 364A, or 10 mg / kg Compound 364A after 14 days of high fat diet feeding. [Figure 6B] 1 is a graph showing IL-1β levels in mice treated with vehicle, 3 mg / kg Compound 364A, or 10 mg / kg Compound 364A after 37 days of high fat diet.Compound 364A-treated mice had reduced IL-1β levels both before and after diet reintroduction at both 14 and 37 days compared to mice receiving vehicle. [Figure 7] FIG. 7A is a graph showing IL-1β secretion levels from human PBMCs after 24 hours of stimulation with either lipopolysaccharide (LPS) or lipoteichoic acid (LTA) when treated with vehicle or 10 μM of compound 242A. FIG. 7B is a graph showing IL-1β secretion levels from human monocytes after 24 hours of stimulation with either lipopolysaccharide (LPS) or lipoteichoic acid (LTA) when treated with vehicle or 10 μM of compound 242A. In monocytes, compound 242A treatment reduced IL-1β levels resulting from LTA stimulation, but only a slight reduction was observed after LPS stimulation. In PBMCs, compound 242A treatment reduced IL-1β levels resulting from both LTA and LPS stimulation. [Figure 8]8A and 8B are plots showing the results of flow cytometry analysis of mouse T cells treated with vehicle (DMSO) or 50 nM of compound 364A. FASN inhibition of mouse CD4+ naive T cells under Th17 differentiation conditions for 4 days inhibits Th17 cell differentiation and stimulates Treg differentiation. [Figure 9A-B] Figures 9A and 9B are plots showing the results of flow cytometry analysis of human T cells from donor 1 treated with vehicle (DMSO) or 50 nM of compound 364A. Figures 9C and 9D are plots showing the results of flow cytometry analysis of human T cells from donor 2 treated with vehicle (DMSO) or 50 nM of compound 364A. FASN inhibition by compound 364A of human CD4+ naive T cells from two different donors under Th17 differentiation conditions for 4 days inhibits TH17 cell differentiation and stimulates Treg differentiation. [Figure 9C-D] Figures 9A and 9B are plots showing the results of flow cytometry analysis of human T cells from donor 1 treated with vehicle (DMSO) or 50 nM of compound 364A. Figures 9C and 9D are plots showing the results of flow cytometry analysis of human T cells from donor 2 treated with vehicle (DMSO) or 50 nM of compound 364A. FASN inhibition by compound 364A of human CD4+ naive T cells from two different donors under Th17 differentiation conditions for 4 days inhibits TH17 cell differentiation and stimulates Treg differentiation. [Figure 10A-B] Figures 10A and 10B are plots showing the results of flow cytometry analysis of human T cells from donor 1 treated with vehicle (DMSO) or 50 nM of compound 152. Figures 10C and 10D are plots showing the results of flow cytometry analysis of human T cells from donor 2 treated with vehicle (DMSO) or 50 nM of compound 152. FASN inhibition by compound 152 of human CD4+ naive T cells from two different donors under Th17 differentiation conditions for 4 days inhibits TH17 cell differentiation and stimulates Treg differentiation. [Figure 10C-D]Figures 10A and 10B are plots showing the results of flow cytometry analysis of human T cells from donor 1 treated with vehicle (DMSO) or 50 nM of compound 152. Figures 10C and 10D are plots showing the results of flow cytometry analysis of human T cells from donor 2 treated with vehicle (DMSO) or 50 nM of compound 152. FASN inhibition by compound 152 of human CD4+ naive T cells from two different donors under Th17 differentiation conditions for 4 days inhibits TH17 cell differentiation and stimulates Treg differentiation. [Figure 11] FIG. 1 is a schematic diagram of the study design and administration groups of compound 364A and pirfenidone in Example 10. [Figure 12A] 1 is a plot of plasma alanine aminotransferase (ALT) in response to treatment with Compound 364A and / or pirfenidone. [Figure 12B] 1 is a plot of plasma aspartate aminotransferase (AST) in response to treatment with Compound 364A and / or pirfenidone. [Figure 12C] 1 is a plot of plasma total cholesterol (TC) in response to treatment with Compound 364A and / or pirfenidone. [Figure 13] Figure 13A is a plot of liver triglycerides in response to treatment with Compound 364A and / or pirfenidone.Figure 13B is a plot of liver cholesterol in response to treatment with Compound 364A and / or pirfenidone. [Figure 14A-B] Figure 14A is a plot of the change in hepatic steatosis after administration of vehicle (control). Figure 14B is a plot of the change in hepatic steatosis after administration of compound 364A. Figure 14C is a plot of the change in hepatic steatosis after administration of pirfenidone. Figure 14D is a plot of the change in hepatic steatosis after administration of compound 364A and pirfenidone. [Fig. 14C-D]Figure 14A is a plot of the change in hepatic steatosis after administration of vehicle (control). Figure 14B is a plot of the change in hepatic steatosis after administration of compound 364A. Figure 14C is a plot of the change in hepatic steatosis after administration of pirfenidone. Figure 14D is a plot of the change in hepatic steatosis after administration of compound 364A and pirfenidone. [Figure 15A-B] Figure 15A is a plot of the change in liver inflammation after administration of vehicle (control). Figure 15B is a plot of the change in liver inflammation after administration of compound 364A. Figure 15C is a plot of the change in liver inflammation after administration of pirfenidone. Figure 15D is a plot of the change in liver inflammation after administration of compound 364A and pirfenidone. [Figure 15C-D] Figure 15A is a plot of the change in liver inflammation after administration of vehicle (control). Figure 15B is a plot of the change in liver inflammation after administration of compound 364A. Figure 15C is a plot of the change in liver inflammation after administration of pirfenidone. Figure 15D is a plot of the change in liver inflammation after administration of compound 364A and pirfenidone. [Figure 16A-B] Figure 16A is a plot of the change in liver ballooning after administration of vehicle (control). Figure 16B is a plot of the change in liver ballooning after administration of compound 364A. Figure 16C is a plot of the change in liver ballooning after administration of pirfenidone. Figure 16D is a plot of the change in liver ballooning after administration of compound 364A and pirfenidone. [Fig. 16C-D] Figure 16A is a plot of the change in liver ballooning after administration of vehicle (control). Figure 16B is a plot of the change in liver ballooning after administration of compound 364A. Figure 16C is a plot of the change in liver ballooning after administration of pirfenidone. Figure 16D is a plot of the change in liver ballooning after administration of compound 364A and pirfenidone. [Figure 17A-B]Figure 17A is a plot of the change in liver fibrosis after administration of vehicle (control). Figure 17B is a plot of the change in liver fibrosis after administration of compound 364A. Figure 17C is a plot of the change in liver fibrosis after administration of pirfenidone. Figure 17D is a plot of the change in liver fibrosis after administration of compound 364A and pirfenidone. [Fig. 17C-D] Figure 17A is a plot of the change in liver fibrosis after administration of vehicle (control). Figure 17B is a plot of the change in liver fibrosis after administration of compound 364A. Figure 17C is a plot of the change in liver fibrosis after administration of pirfenidone. Figure 17D is a plot of the change in liver fibrosis after administration of compound 364A and pirfenidone. [Figure 18A-B] Figure 18A is a plot of the change in liver NAFLD activity score (NAS) after administration of vehicle (control). Figure 18B is a plot of the change in liver NAFLD activity score (NAS) after administration of compound 364A. Figure 18C is a plot of the change in liver NAFLD activity score (NAS) after administration of pirfenidone. Figure 18D is a plot of the change in liver NAFLD activity score (NAS) after administration of compound 364A and pirfenidone. [Fig. 18C-D] Figure 18A is a plot of the change in liver NAFLD activity score (NAS) after administration of vehicle (control). Figure 18B is a plot of the change in liver NAFLD activity score (NAS) after administration of compound 364A. Figure 18C is a plot of the change in liver NAFLD activity score (NAS) after administration of pirfenidone. Figure 18D is a plot of the change in liver NAFLD activity score (NAS) after administration of compound 364A and pirfenidone. [Figure 19] 1 is a plot of the change in hepatic collagen gene expression following administration of vehicle (control), Compound 364A, pirfenidone, or Compound 364A and pirfenidone. [Figure 20]2D plot of changes in hepatic collagen gene expression by genetic analysis of liver biopsies following administration of vehicle (control), Compound 364A, pirfenidone, or Compound 364A and pirfenidone. [Figure 21] FIG. 1 is a schematic diagram of the study design and dosing groups for Example 11. [Figure 22] 1 is a plot of the change in mouse skin collagen content as a function of the dose of compound 364A in Example 11. [Figure 23A] 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 is a plot of Col 1a1 mRNA expression. Figure 23B is a plot of αSMA mRNA expression. Figure 23C is a plot of βPDGFR mRNA expression. Figure 23D is a plot of TGFbR1 mRNA expression. Figure 23E is a plot of TIMP1 mRNA expression. Figure 23F is a plot of TIMP2 mRNA expression. Figure 23G is a plot of MMP2 mRNA expression. [Figure 23B] 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 is a plot of Col 1a1 mRNA expression. Figure 23B is a plot of αSMA mRNA expression. Figure 23C is a plot of βPDGFR mRNA expression. Figure 23D is a plot of TGFbR1 mRNA expression. Figure 23E is a plot of TIMP1 mRNA expression. Figure 23F is a plot of TIMP2 mRNA expression. Figure 23G is a plot of MMP2 mRNA expression. [Figure 23C]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 is a plot of Col 1a1 mRNA expression. Figure 23B is a plot of αSMA mRNA expression. Figure 23C is a plot of βPDGFR mRNA expression. Figure 23D is a plot of TGFbR1 mRNA expression. Figure 23E is a plot of TIMP1 mRNA expression. Figure 23F is a plot of TIMP2 mRNA expression. Figure 23G is a plot of MMP2 mRNA expression. [Figure 23D] 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 is a plot of Col 1a1 mRNA expression. Figure 23B is a plot of αSMA mRNA expression. Figure 23C is a plot of βPDGFR mRNA expression. Figure 23D is a plot of TGFbR1 mRNA expression. Figure 23E is a plot of TIMP1 mRNA expression. Figure 23F is a plot of TIMP2 mRNA expression. Figure 23G is a plot of MMP2 mRNA expression. [Figure 23E] 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 is a plot of Col 1a1 mRNA expression. Figure 23B is a plot of αSMA mRNA expression. Figure 23C is a plot of βPDGFR mRNA expression. Figure 23D is a plot of TGFbR1 mRNA expression. Figure 23E is a plot of TIMP1 mRNA expression. Figure 23F is a plot of TIMP2 mRNA expression. Figure 23G is a plot of MMP2 mRNA expression. [Figure 23F]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 is a plot of Col 1a1 mRNA expression. Figure 23B is a plot of αSMA mRNA expression. Figure 23C is a plot of βPDGFR mRNA expression. Figure 23D is a plot of TGFbR1 mRNA expression. Figure 23E is a plot of TIMP1 mRNA expression. Figure 23F is a plot of TIMP2 mRNA expression. Figure 23G is a plot of MMP2 mRNA expression. [Figure 23G] 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 is a plot of Col 1a1 mRNA expression. Figure 23B is a plot of αSMA mRNA expression. Figure 23C is a plot of βPDGFR mRNA expression. Figure 23D is a plot of TGFbR1 mRNA expression. Figure 23E is a plot of TIMP1 mRNA expression. Figure 23F is a plot of TIMP2 mRNA expression. Figure 23G is a plot of MMP2 mRNA expression. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0130] The present disclosure addresses deficiencies in the treatment of conditions characterized by dysregulation of FASN function in a subject, such as viral infections, cancer, and metabolic disorders, by providing novel heterocyclic modulators of lipid synthesis.

[0131] In certain embodiments, the present disclosure provides compositions and methods for the treatment of viral infections.Generally, the compositions and methods for the treatment of viral infections relate to the modulation of fatty acid synthesis pathway.This fatty acid synthesis pathway is involved in the replication of viruses into host cells.The present invention embodies methods for the treatment of viral infections, such as hepatitis C infection, yellow fever infection and human rhinovirus infection, or any virus that targets fatty acid synthesis pathway.

[0132] In certain embodiments, the present disclosure provides compositions and methods for the treatment of cancer.Fatty acid synthase is involved in the conversion of malonyl-CoA to long-chain fatty acid, which is the initial reaction in fatty acid biosynthesis.Fatty acid synthase is overexpressed in many cancer cells.Without being bound to any particular theory, it is hypothesized that the inhibition of fatty acid synthase expression or fatty acid synthase activity selectively suppresses the proliferation of cancer cells, induces cell death of cancer cells, and has little toxicity to normal cells.

[0133] Furthermore, the present 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 host cell targets. Thus, compounds that modulate, e.g., inhibit, the activity of non-viral proteins, e.g., host cell proteins, e.g., components of the fatty acid synthesis pathway, may be used as antiviral pharmaceuticals.

[0134] definition Chemical moieties that are referred to as univalent chemical moieties (e.g., alkyl, aryl, etc.) also encompass multivalent moieties where structurally permitted, as will be understood by those of skill in the art. For example, an "alkyl" moiety generally refers to a univalent radical (e.g., CH 3 CH 2 -), except that in appropriate circumstances the "alkyl" moiety may refer to a divalent radical (e.g., -CH 2 CH 2 -, which is equivalent to an "alkylene" group. Similarly, in situations where a divalent moiety is required, it will be understood by those of skill in the art that the term "aryl" refers to the corresponding divalent arylene group.

[0135] All atoms are understood to have their normal valence for bond formation (e.g., Carbon is 4, N is 3, O is 2, S is 2, 4 or 6 depending on the oxidation state of the atom). Sometimes a moiety is referred to as, for example, (A) aB (where a is 0 or 1). In such a case, when a is 0, the moiety is B, and when a is 1, the moiety is AB.

[0136] The substituents may vary in the number of atoms or groups of the same type (e.g., an alkyl group may be C 1 , C 2 , C 3 etc.), the number of repeating atoms or groups can be set within a range (e.g., C 1 ~C 6 alkyl), which includes each and every number within this range, and any and all subranges. For example, C 1 ~C 3 Alkyl is C 1 , C 2 , C 3 , C 1~2 , C 1~3 and C 2~3 Contains alkyl.

[0137] "Alkanoyl" refers to a carbonyl group bearing a lower alkyl group as a substituent.

[0138] "Alkylamino" refers to an amino group substituted by an alkyl group.

[0139] "Alkoxy" refers to an O atom substituted by an alkyl group as defined herein, e.g., methoxy [-OCH 3 , C 1 The term "C 1~6 "Alkoxy" is C 1 Alkoxy, C 2 Alkoxy, C 3 Alkoxy, C 4 Alkoxy, C 5 Alkoxy, C 6 Alkoxy, and any subrange thereof.

[0140] "Alkoxycarbonyl" refers to a carbonyl group bearing an alkoxy group as a substituent.

[0141] "Alkyl", "alkenyl" and "alkynyl" refer to optionally substituted straight and branched chain aliphatic groups having 1 to 30 carbon atoms, preferably 1 to 15 carbon atoms, 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, isobutenyl, ethynyl and propynyl. The term "heteroalkyl" as used herein contemplates alkyl having one or more heteroatoms.

[0142] "Alkylene" refers to an optionally substituted divalent group that is a branched or unbranched hydrocarbon fragment containing the specified number of carbon atoms and having two points of attachment. An example is propylene [-CH 2 CH 2 CH 2 -, C 3 alkylene].

[0143] "Amino" is -NH 2 Refers to the group.

[0144] "Aryl" refers to an optionally substituted aromatic group having at least one ring having a conjugated pi-electron system, including carbocyclic aryl and biaryl groups, all of which may be optionally substituted. Phenyl and naphthyl groups are preferred carbocyclic aryl groups.

[0145] "Aralkyl" or "arylalkyl" refers to an alkyl-substituted aryl group. Examples of aralkyl groups include butylphenyl, propylphenyl, ethylphenyl, methylphenyl, 3,5-dimethylphenyl, and tert-butylphenyl.

[0146] As used herein, "carbamoyl" refers to the structure [ka] (In the formula, R N is hydrogen, -OH, C 1 ~C 12 Alkyl, C 1 ~C 12 The groups contemplated are selected from the group consisting of heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, sulfonyl, sulfonate, and sulfonamido.

[0147] "Carbonyl" has the structure [ka] Refers to the group.

[0148] "Cycloalkyl" refers to an optionally substituted ring composed entirely of carbon, which may be saturated or unsaturated and may be monocyclic, bicyclic or tricyclic. Examples of cycloalkyl groups include those having 5 carbons (C 5 ) an unsaturated cycloalkyl group, a cyclopentenyl group (C 5 H 7 -).

[0149] "Heterocycle" refers to an optionally substituted 5- to 7-membered cycloalkyl ring system containing 1, 2 or 3 heteroatoms and optionally one double bond, where the heteroatoms may be the same or different and selected from N, O or S.

[0150] "Halogen" refers to an atomic radical of chlorine, bromine, fluorine, or iodine. The term "halogen" also contemplates the terms "halo" or "halide."

[0151] "Heteroatom" refers to a non-carbon atom, with boron, nitrogen, oxygen, sulfur and phosphorus being preferred heteroatoms, with nitrogen, oxygen and sulfur being particularly preferred heteroatoms in the compounds of the present disclosure.

[0152] "Heteroaryl" refers to an optionally substituted aryl group having from 1 to 9 carbon atoms, the remainder of which are heteroatoms, including the heterocyclic systems described in "Handbook of Chemistry and Physics," 49th edition, 1968, RC Weast, editor; The Chemical Rubber Co., Cleveland, Ohio. See especially Section C, Rules for Naming Organic Compounds, B. Fundamental Heterocyclic Systems. Suitable heteroaryls include thienyl, pyrrolyl, furyl, pyridyl, pyrimidyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, imidazolyl, thiazolyl, pyranyl, tetrazolyl, pyrrolyl, pyrrolinyl, pyridazinyl, triazolyl, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyridazinyl, oxadiazolyl, benzoxazolyl, benzoxadiazolyl, thiadiazolyl, benzothiazolyl, benzothiadiazolyl, and the like.

[0153] An "optionally substituted" moiety may be substituted with 1 to 4, preferably 1 to 3, and more preferably 1 or 2 non-hydrogen substituents. Unless otherwise specified, when the substituent is on a carbon, it is selected from the group consisting of -OH, -CN, -NO 2 , halogen, C 1 ~C 12 Alkyl, C 1 ~C 12 The substituent is selected from the group consisting of heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, substituted sulfonyl, sulfonato, sulfonamido, and amino, none of which are further substituted. Unless otherwise specified, when a substituent is on a nitrogen, it is selected from the group consisting of C 1 ~C 12 Alkyl, C 1 ~C 12It is selected from the group consisting of heteroalkyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, sulfonyl, sulfonate, and sulfonamido, none of which are further substituted.

[0154] The term "sulfone" as used herein refers to a compound having the structure [ka] (In the formula, R N is hydrogen, -OH, C 1 ~C 12 Alkyl, C 1 ~C 12 Groups having an alkyl group selected from the group consisting of heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocycle, aryl, heteroaryl, aralkyl, alkoxy, alkoxycarbonyl, alkanoyl, carbamoyl, substituted sulfonyl, sulfonate, and sulfonamide are contemplated.

[0155] The term "sulfonate" as used herein means a compound having the structure [ka] (In the formula, R s is hydrogen, C 1 ~C 10 Alkyl, C 2 ~C 10 Alkenyl, C 2 ~C 10 Alkynyl, C 1 ~C 10 Alkanoyl, or C 1 ~C 10 alkoxycarbonyl) are contemplated.

[0156] As used herein, "sulfonyl" as used alone or as part of another group means SO 2 Refers to the SO group. 2 The moieties are optionally substituted.

[0157] The compounds of the present disclosure may exist as stereoisomers where asymmetric or chiral centers exist. Stereoisomers are designated as (R) or (S) depending on the configuration of the substituents around the chiral carbon atom. As used herein, the terms (R) and (S) refer to the configurations as defined in IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, Pure Appl. Chem., (1976), 45:13-30, which is incorporated herein by reference. The present disclosure contemplates various stereoisomers and mixtures thereof, and are expressly included within the scope of the present disclosure. Stereoisomers include enantiomers, diastereomers, and mixtures of enantiomers or diastereomers. Individual stereoisomers of the compounds of the present disclosure can be prepared by synthesis from commercially available starting materials that contain asymmetric or chiral centers, or by preparation of racemic mixtures followed by resolution as is well known to those skilled in the art. These resolution methods are exemplified by (1) binding the enantiomeric mixture to a chiral auxiliary, separating the resulting diastereomeric mixture by recrystallization or chromatography, and liberating the optically pure product from the auxiliary, or (2) directly separating the optical enantiomeric mixture on a chiral chromatographic column.

[0158] Additionally, moieties disclosed herein that exist in multiple tautomeric forms include all such forms encompassed by a given tautomeric structure.

[0159] The individual atoms in the compounds of the present disclosure may be any isotope of that element, for example hydrogen may be in the form of deuterium.

[0160] "Pharmaceutically acceptable" means for use in animals and more specifically for use in humans. "substance" means that the material is approved or can be approved by a federal or state regulatory agency, or is listed in the United States Pharmacopeia or other generally recognized pharmacopoeia. It can be a material that is not biologically or otherwise undesirable, i.e., that the material can be administered to an individual without producing any undesirable biological effects or interacting adversely with any of the components of the composition that contains it.

[0161] The term "pharmaceutically acceptable salt" of a compound means a salt that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. Such salts include, for example, acid addition salts and base addition salts.

[0162] "Acid addition salts" according to the present disclosure are formed with inorganic acids such as, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or with organic acids such as, for example, 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, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 1,2-ethanes ... It is formed using acids, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 4-methylbicyclo-[2.2.2]oct-2-ene-1-carboxylic acid, glucoheptonic acid, 4,4'-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, etc.

[0163] A "base addition salt" according to the present disclosure is formed when an acidic proton present in the parent compound is replaced by a metal ion, such as an alkali metal ion, an alkaline earth ion, or an aluminum ion, or is coordinated to an organic base. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine, and the like. Acceptable inorganic bases include aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, sodium hydroxide, and the like. Reference to a pharmaceutically acceptable salt should be understood to include its solvent addition forms or crystal forms, particularly solvates or polymorphs. Solvates contain either stoichiometric or non-stoichiometric amounts of a solvent and are often formed during the process of crystallization. Hydrates are formed when the solvent is water, and alcoholates are formed when the solvent is alcohol. Polymorphs include different crystal packing arrangements of the same elemental composition of a compound. Polymorphs usually have different X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability and solubility. Various factors such as recrystallization solvent, crystallization rate and storage temperature can cause a single crystalline form to predominate.

[0164] The term "treating" includes administering the compounds or agents of the present invention to a subject to prevent or delay, alleviate, or stop or inhibit the onset of symptoms or conditions associated with fatty acid synthase-related disorders, such as tumor growth associated with cancer. A skilled medical practitioner knows how to use standard methods to determine whether a patient suffers from a disease associated with fatty acid synthase activity, such as by examining the patient and determining whether the patient suffers from a disease known to be associated with fatty acid synthase activity, or by assaying for fatty acid synthase levels in the plasma or tissues of an individual suspected of suffering from a fatty acid synthase-related disease and comparing the fatty acid synthase levels in the plasma or tissues of an individual suspected of suffering from a fatty acid synthase-related disease with the fatty acid synthase levels in the plasma or tissues of a healthy individual. An increase in securin levels is indicative of disease. Thus, the present invention relates, inter alia, to a method of administering the compounds of the present invention to a subject and a method of determining fatty acid synthase activity in a subject. Fatty acid synthase activity in a subject can be determined before and / or after administration of the compound.

[0165] "Therapeutically effective amount" or "pharmacologically effective amount" refers to an amount that produces the effect of administration when administered to a subject. For example, a "therapeutically effective amount" is an amount that, when administered to a subject to inhibit fatty acid synthase activity, is sufficient to inhibit fatty acid synthase activity. A "therapeutically effective amount" is an amount that, when administered to a subject to treat a disease, is sufficient to effect treatment for the disease.

[0166] Unless otherwise stated, the term "subject" or "patient" is used interchangeably and refers to mammals, such as human patients and non-human primates, as well as experimental animals, such as rabbits, rats and mice, and other animals. Thus, the term "subject" or "patient" as used herein means any mammalian patient or subject to which the compounds of the present invention can be administered. In an exemplary embodiment of the present invention, to identify a subject patient for treatment with the method of the present invention, acceptable screening methods are used to determine risk factors associated with the subject 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, conventional workups to determine risk factors associated with the subject or suspected disease or condition. These and other routine methods allow the clinician to select patients who require treatment using the methods and formulations of the present invention.

[0167] FASN pathway modulators One embodiment of the present disclosure includes a method of inhibiting viral infection or treating cancer by contacting cells with an agent that modulates fatty acid synthesis pathway.The method of inhibiting viral infection or treating cancer can be performed in vitro by contacting virally infected cells / cancerous cells with an agent that modulates fatty acid synthesis pathway, or can be performed in vivo by administering an agent that modulates fatty acid synthesis pathway to a subject infected with a virus / subject with cancer.In one embodiment, the agent can be an inhibitor of fatty acid synthesis pathway.

[0168] Examples of inhibitors of the fatty acid synthesis pathway that can be used in the methods and compositions of the disclosure are listed below.

[0169] Compounds of structure (I) In various embodiments, the present disclosure provides a compound of structure (I): [ka] (I) (In the formula, X, Y and Z are each independently CR or NR′, where R is hydrogen or C 1~6 alkyl, R' is hydrogen, C 1~6 alkyl, or absent; A is CH or N; R 1 is hydrogen, cyano, halo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(=O)N(R 13 )(R 14 ), -(CH 2 ) q C(=O)N(R 13 )(R 14 ), C.F. 3 , - OCF 3 , or -S(=O) 2 R 20 and; q is 0, 1, 2, 3 or 4; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 2 is hydrogen, halo, C 1~6 Alkoxy, C 1~6 alkyl, or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl, C 1~6 Alkoxy; or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 4 is hydrogen, heteroaryl, heterocyclyl, -C(=O)N(R 5 R 6 ), -N(R 7 )C(=O)R 8, -N(R 9 R 10 ), C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20 or R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl; R 11 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 and R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl, or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 12 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 13 and R 14 are each independently hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, alkylamino, -N(R 15R 16 ), or -S(=O) 2 R 20 and; R 15 and R 16 are each independently hydrogen, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl or alkylamino; R 17 and R 18 are each independently hydrogen or alkyl, or may optionally be joined together to form a bond; n is 1 or 2; m is 0 or 1), or a pharma- ceutically acceptable salt thereof.

[0170] In certain embodiments of structure (I), R 3 is F.

[0171] In certain embodiments of structure (I), A is CH.

[0172] In certain embodiments of structure (I), A is N.

[0173] In certain embodiments of structure (I), X, Y and Z are NR'.

[0174] In certain embodiments of structure (I), R 4 is heteroaryl, heterocyclyl, -C(=O)N(R 5 R 6 ), -N(R 7 )C(=O)R 8 , -N(R 9 R 10 ), C 1 ~ 6 Alkyl, C 1 ~ 6 Alkoxy; or R 4 and R 11 together with the atoms to which they are attached join together to form a heteroaryl.

[0175] In certain embodiments of structure (I), R 5 is hydrogen and R 6 is aryl or heteroaryl.

[0176] In certain embodiments, the compound of structure (I) has the following structure (IA) or (IB): : [ka] (In the formula, X, Y and Z are each independently CR or NR′, where R is hydrogen or C 1~6 alkyl, R' is hydrogen, C 1~6 alkyl, or absent; R 1 is hydrogen, cyano, halo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(=O)N(R 13 )(R 14 ), -(CH 2 ) q C(=O)N(R 13 )(R 14 ), C.F. 3 , -OCF 3 , or -S(=O) 2 R 20 and; q is 0, 1, 2, 3 or 4; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 2 is hydrogen, halo, C 1~6 Alkoxy, C 1~6 alkyl, or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl, C 1~6 Alkoxy; or R2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 4 is hydrogen, heteroaryl, heterocyclyl, -C(=O)N(R 5 R 6 ), -N(R 7 )C(=O)R 8 , -N(R 9 R 10 ), C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20 or R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl; R 11 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 and R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl, or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 12 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 5 , R 6, R 7 , R 8 , R 9 , R 10 , R 13 and R 14 are each independently hydrogen, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, hydroxyalkyl, alkylamino, -N(R 15 R 16 ), or -S(=O) 2 R 20 and; R 15 and R 16 are each independently hydrogen, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl or alkylamino; R 17 and R 18 are each independently hydrogen or alkyl, or may be optionally linked together to form a bond), or a pharma- ceutically acceptable salt thereof.

[0177] In certain embodiments, the compound of structure (I) has the following structure (IC) or (ID): : [ka] (In the formula, X, Y and Z are each independently CR or NR′, where R is hydrogen or C 1~6 alkyl, R' is hydrogen, C 1~6 alkyl, or absent; R 2 is hydrogen, halo, C 1~6 Alkoxy, C 1~6 alkyl, or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl, C 1~6 Alkoxy; or R2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 4 is hydrogen, heteroaryl, heterocyclyl, -C(=O)N(R 5 R 6 ), -N(R 7 )C(=O)R 8 , -N(R 9 R 10 ), C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20 or R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 11 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 or R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl; R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are each independently H, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylamino, or -N(R 15 R 16 ) and; R 15 and R 16are each independently H, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, or alkylamino) or a pharma- ceutically acceptable salt thereof.

[0178] In certain embodiments, the compound of structure (I) has the following structure (IE), (IF), (IG), (IH): [ka] (In the formula, R 2 is hydrogen, halo, C 1~6 Alkoxy, C 1~6 alkyl, or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl, C 1~6 Alkoxy; or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 4 is hydrogen, heteroaryl, heterocyclyl, -C(=O)N(R 5 R 6 ), -N(R 7 )C(=O)R 8 , -N(R 9 R 10 ), C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20 or R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 11 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 and R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl, or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 12 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 13 and R 14 are each independently H, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylamino, or -N(R 15 R 16 ) and; R 15 and R 16 are each independently H, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, or alkylamino) or a pharma- ceutically acceptable salt thereof.

[0179] In certain embodiments, the compound of structure (I) has the following structure (II), (IJ) or (IK): [ka] (In the formula, X and Y are each independently CR or NR′, where R is H or C 1~6 alkyl, and R' is H, C 1~6 alkyl, or absent; R 1 is hydrogen, cyano, halo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(=O)N(R 13 )(R 14 ), -(CH 2 ) q C(=O)N(R 13 )(R 14 ), C.F. 3 , -OCF 3 , or -S(=O) 2 R 20 and; q is 0, 1, 2, 3 or 4; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 2 is hydrogen, halo, C 1~6 Alkoxy, C 1~6 alkyl, or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl, C 1~6 Alkoxy; or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 11 is hydrogen, halo, cyano, C 1~6 Alkyl, C1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , or -S(=O) 2 R 20 and; R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are each independently H, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylamino, or -N(R 15 R 16 ) and; R 15 and R 16 are each independently H, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, or alkylamino) or a pharma- ceutically acceptable salt thereof.

[0180] In certain embodiments, the compound of structure (I) has the following structure (IL) or (IM): [ka] (In the formula, X and Y are each independently CR or NR′, where R is H or C 1~6 alkyl, and R' is H, C 1~6 alkyl, or absent; R 4 is hydrogen, heteroaryl, heterocyclyl, -C(=O)N(R 5 R 6 ), -N(R 7 )C(=O)R 8 , -N(R 9 R 10 ), C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20 or R 4 and R11 are joined together with the atoms to which they are attached to form a heteroaryl; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 11 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 or R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl; R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are each independently H, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylamino, or -N(R 15 R 16 ) and; R 15 and R 16 are each independently H, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, or alkylamino) or a pharma- ceutically acceptable salt thereof.

[0181] In certain embodiments, the compound of structure (I) has the following structure (IN) or (IO): [ka] or a pharma- ceutically acceptable salt thereof.

[0182] In certain embodiments, the compound of structure (I) has the following structure (IP): [ka] (IP) (In the formula, R 2 is hydrogen, halo, C 1~6 Alkoxy, C 1~6 alkyl, or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl, C 1~6 Alkoxy; or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 4 is hydrogen, heteroaryl, heterocyclyl, -C(=O)N(R 5 R 6 ), -N(R 7 )C(=O)R 8 , -N(R 9 R 10 ), C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20 or R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 11 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF3 , -S(=O) 2 R 20 and R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl, or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 12 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 13 and R 14 are each independently H, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylamino, or -N(R 15 R 16 ) and; R 15 and R 16 are each independently H, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, or alkylamino) or a pharma- ceutically acceptable salt thereof.

[0183] In certain embodiments, the compound of structure (I) has the following structure (IQ), (IR) or (IS): [ka] or a pharma- ceutically acceptable salt thereof.

[0184] In certain embodiments, the compound of structure (I) has the following structure (IT): [ka] (IT) (In the formula, X, Y and Z are each independently CR or NR′, where R is H or C 1~6 alkyl, and R' is H, C 1~6 alkyl, or absent; R 1 is hydrogen, cyano, halo, C 1~6 Alkyl, C 1~6 Alkoxy, -C(=O)N(R 13 )(R 14 ), -(CH 2 ) q C(=O)N(R 13 )(R 14 ), C.F. 3 , -OCF 3 , or -S(=O) 2 R 20 and; q is 0, 1, 2, 3 or 4; R 20 is hydrogen or C 1~6 Alkyl, C 1~6 Alkoxy, or -N(R 13 )(R 14 ) and; R 2 is hydrogen, halo, C 1~6 Alkoxy, C 1~6 alkyl, or R 2 and R 3 together with the atoms to which they are attached form a 5-membered heterocyclyl; R 3 is hydrogen, hydroxyl, halo, C 1~6 Alkyl, C 1~6 Alkoxy; or R 2 and R 3together with the atoms to which they are attached form a 5-membered heterocyclyl; R 4 is hydrogen, heteroaryl, heterocyclyl, -C(=O)N(R 5 R 6 ), -N(R 7 )C(=O)R 8 , -N(R 9 R 10 ), C 1~6 Alkyl, C 1~6 Alkoxy, -S(=O) 2 R 20 or R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl; R 11 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 and R 4 and R 11 are joined together with the atoms to which they are attached to form a heteroaryl, or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 12 is hydrogen, halo, cyano, C 1~6 Alkyl, C 1~6 Alkoxy, -N(R 13 R 14 ), C.F. 3 , -OCF 3 , -S(=O) 2 R 20 or R 11 and R 12 are joined together with the atoms to which they are attached to form a heteroaryl; R 5 , R 6 , R 7 , R8 , R 9 , R 10 , R 13 and R 14 are each independently H, C 1~6 Alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, alkylamino, or -N(R 15 R 16 ) and; R 15 and R 16 are each independently H, C 1~6 alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, or alkylamino) or a pharma- ceutically acceptable salt thereof.

[0185] In certain embodiments, the compound of structure (...

Claims

[Claim 1] The invention as depicted in the drawings.

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