MX2007015644A - Heterocyclic compound. - Google Patents

Abstract

A compound represented by the general formula (1') or a salt thereof; and a therapeutic or prophylactic agent for a glucocorticoid-related condition or an 11????HSD1 inhibitor comprising the compound of the salt thereof: (1') wherein the ring A, R², R³, R⁴ and X are as defined in the description.

Description

HETEROCICLIC COMPOSITE TECHNICAL FIELD The present invention relates to heterocyclic compounds, and more particularly, to heterocyclic compounds useful as inhibitors of HSD1.

PREVIOUS TECHNIQUE As typically observed in Cushing's syndrome, the effect of systemic glucocorticoid excess causes metabolic abnormalities such as visceral fat accumulation, characteristic changes in fat distribution in the body, insulin resistance, diabetes, hyperlipidemia, elevated blood pressure. arterial and the like. It has been known for more than half a century that glucocorticoid plays an important role in diabetes and, for example, the removal of the pituitary gland or adrenal gland from diabetic animals results in the relief of most conditions greves of diabetes and decreases blood glucose concentration (see Long, CD and FDW Leukins (1936), "J. Exp. Med." 63: 465-490 and Houssay, BA (1942), "Endocrinology", 30 ,: 884-892). The glucocorticoid is known to be (1) essential for adipocyte differentiation and inhibition program, such as a representative hormone antagonistic to insulin, glucose and lipid metabolism by insulin in several stages, (2) increase in blood pressure via induction of renin substrate production, which is angiotensinogen, improves of the angiotensin II expression receptor and the like, (3) cause hyperorexia and obesity as a potent hormone antagonistic to leptin and the like (see "Rinshoi", vol 30 No. 9, 2004; 1782-1787). Additionally, it has been attracting attention that the effect of abnormally activated glucocorticoids on adipose tissue is involved in the pathology of the metabolic syndrome encompassing multiple metabolic diseases such as diabetes hyperlipidemia, hypertension, fatty liver and the like in a single individual. (See Moller DE, New Drug Targets for Diabetes 2 and Metabolic Syndrome, "Nature" 2001; 414: 821-7). These facts suggest that the reduction of the glucocorticoid effect is beneficial for the treatment or prophylaxis of metabolic diseases such as diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension, fatty liver and the like, and the metabolic syndrome that covers the diseases metabolic in a single individual, and in addition, fatal vascular events represented by cardiac infarction and cerebral apoplexy based on these diseases. The active glucocorticoid (cortisol in humans and corticosterone in rodents) that exhibits the effect of glucocorticoid is produced from cortisone or 11-dehydrocorticosterone being both 11-ketometabolites inactive by the action of a conversion enzyme, dehydrogenase 11 β-hydroxysteroid type 1 (11 ßHSD1), not only in gland adrenal but also the various tissues and cells (see AgurwaI et al., "J. Biol. Chem" 264, 18939-46, 1989). Because the mouse to which 11βHSD1 is administered can not convert an inactive glucocorticoid administered to one of the active type, it has been shown that this enzyme can be the only enzyme that converts the glucocorticoid to the active in the living being (see de Kotelevtsev, and and col .: "Proc. Nati. Acad. Sci." USA, 94 ,: 14924, 1997). There is a report in a case of Cushing's disease of hypophysis with hyperglucocorticoidemia in which the conditions of Cushing's syndrome were not observed due to a significantly lower activity of 11 ßHSD1 by chance (see Tomlinson, JW et al .: "J. Clin Endocrinol, Metab. ", 87: 57, 2002). These results reveal that the regulation of the activity of 11ßHSD1 is significant for the action of the glucocorticoid. In other words, the regulation of the activity of 11 ßHSD1 is beneficial for the treatment or prophylaxis of metabolic diseases such as diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension, fatty liver and the like and the metabolic syndrome that covers the metabolic diseases in a single individual, and in addition, fatal vascular events represented by cardiac infarction and cerebral apoplexy based on these diseases.

It has been clarified that the transgenic mouse, which exhibits overexpression of 11βHSD1, of the same level as that of obese individuals, only in adipose tissue, also has the main factors of metabolic syndromes such as visceral fat type obesity, insulin resistant diabetes , hyperlipidemia, hypertension, fatty liver and the like (see de Masuzaki, H et al .: "Science" 2001; 294: 2166-70 and Masuzaki H et al .: "J. Clin. Invest" 2003; 112: 83- 90). Additionally, while the transgenic mouse exhibiting overexpression of liver-specific 11βHSD1 does not demonstrate a visceral fat type obesity phenotype but demonstrates insulin resistance and pathology of hypertension, fatty liver and the like (see Janice M. Paterson et al .: " PNAS 2004"; 101: 7088-7093). In contrast, the mouse with a null gene for 11 ßHSD1 demonstrates resistance to the enzyme induction of hepatic gneogenesis (PEPCK, G6Pase, etc.) due to stress loading or a diet loaded with a high amount of fat, and demonstrates clear resistance to the onset of diabetes (see Kotelevtsev, Y. et al .: "Proc. Nati. Acad. Sci." USA, 94 ,: 14924, 1997). In addition, the mouse with a nullified gene for 11 ßHSD1 demonstrates a decrease in the level of triglyceride in the blood and an increase in the level of HDL-cholesterol in the blood, because the molecular group expressions related to fat catabolism and its transcription coordination factor PPARa increases notably. The knockout gene for 11βHSD1 has been reported to demonstrate an apparent attenuation of visceral adipose tissue accumulation and attack of abnormalities metabolic induced by the diet loaded with high amount of fat (see Morton NM et al. "J. Biol. Chem." 2001; 44: 41293-301). In fact, because insulin sensitivity is increased by 11 ßHSD1 deficiency, inhibition of the effect of this enzyme is expected to be useful for the treatment or prophylaxis of non-insulin dependent diabetes and obesity (see Seckl, JR et al. "Eur. J. Biochem." 249: 361, 1997 and from Morton NM et al. "Diabetes" 2004; 53: 931-938). These findings state that the reduction of the effect of 11βHSD1 is beneficial for the treatment or prophylaxis of metabolic diseases such as diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension, fatty liver and the like and metabolic syndrome that covers metabolic diseases in a single individual, and in addition, fatal vascular events represented by cardiac infarction and cerebral apoplexy based on these diseases. Removal of the adrenal gland weakens the fasting effect which increases food intake and expression of the hypothalamic Y neuropeptide. This supports the role of the gcorticoid in the increase of food intake and suggests that the inhibition of 11βHSD1 in the brain will increase the level of satiety, and therefore, decreases food intake (see Woods, SC et al (1998) "Science", 280: 1378-1383). That is, it is suggested that the reduction of the effect of 11 ßHSD1 is beneficial for the treatment or prophylaxis of hypererexia. Nerve tensions and gcorticoids affect function cognitive (see de Quervain, D.J.-F., B. Roozendaal, and J.L. McGaugh (1998), "Nature", 394 ,: 787-790). In fact, the mouse with a nullified 11βHSD1 gene demonstrates a marked improvement in the cognitive disorder caused by aging (see Yau JL et al. "PNAS 2001"; 98: 4716-4721), and a recent report has documented that an inhibitor of non-specific ßHSD1, carbenoxolone, is effective for the cognitive disorder of the elderly human being (see Sandeep TC et al PNAS 2004; 101: 6734-6739). In addition, 11 ßHSD1 controls the level of gcorticoid action in the brain, thereby contributing to neurotoxicity (see Rajan, V., CRW Edwards, and JR Seckl, J. (1996), "Neuroscience", 16: 65- 70 and Seckl, JR, "Front. (2000), Neuroendocrinol", 18: 49-99). further, the inhibition of 11ßHSD1 in the brain results in the reduction of anxiety, which is based on the above-mentioned and known effect of the glucocorticoid in the brain (see Tronche, F. et al (1999), "Nature Genetics", 23: 99-103). Overall, therefore, they suggest that the reduction of the effect of 11ßHSD1 in the human brain prevents the reactivation of cortisone to cortisol, and is useful for the treatment or prophylaxis of dysgenesis, neurodegenerative diseases accompanied by disappearance of nerve cells, emotional disorders such as anxiety, depression, mania and the like, schizophrenia, neurodisfunction that includes appetite stimulation and the like. It is a well-known fact that the glucocorticoid suppresses the immunological system. Therefore, it is suggested that the reduction of the effect of 11 ßHSD1 be beneficial for the treatment or prophylaxis of diseases that demonstrate a diminished immunity such as immunodeficiency and the like or for the treatment or prophylaxis of diseases that require an increase in immunity. Recent data suggest that target glucocorticoid receptor and 11 ßHSD1 enzyme levels determine susceptibility to glaucoma (see Stokes, J. et al (2000), "Invest Ophthalmol." 41: 1629-1638). Therefore, it is suggested that the reduction of the effect of 11 ßHSD1 is beneficial for the treatment or prophylaxis of glaucoma. Although the glucocorticoid plays an essential part in the growth and function of the skeleton, the glucocorticoid in excess is harmful. Glucocorticoid-induced bone loss is at least partially induced by the inhibition of bone formation including the suppression of osteoblast growth and collagen synthesis (see Kim, CH, SL Cheng, and GS Kim (1999) , "J. Endocrino!", 162 ,: 371-379). The negative effect on the formation of the bone nodule can be blocked by a non-specific 11βHSD1 inhibitor, carbenoxolone, which suggests an important role of 11βHSD1 in the glucocorticoid effect (see Bellows, CG, A. Ciaccia, and JNM). Heersche, (1998), "Bone", 23: 119-125). Therefore, the reduction of the effect of 11βHSD1 is suggested to be beneficial for the treatment or prophylaxis of osteoporosis. Accordingly, it can be said that a substance that have an activity that reduces the effect of 11βHSD1 is useful as a drug for the treatment or prophylaxis of the pathology involving the glucocorticoid, such as 1) metabolic diseases including diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension and fatty liver, 2) the metabolic syndrome, 3) fatal vascular events represented by cardiac infarction and cerebral apoplexy based on such diseases, 4) hyperorexia, 5) diseases that include dysgenesis, neurodegenerative diseases accompanied by the disappearance of nerve cells , emotional disorders such as anxiety, depression, mania and the like, schizophrenia and neurodisfunction including appetite stimulation, 6) diseases that require treatment or prophylaxis of diminished immunity or increased immunity, such as immunodeficiency and the like, 7) glaucoma , 8) osteoporosis and the like. As the heterocyclic compound, for example, the following is known. For example, WO99 / 43663 describes the following heterocyclic compounds as a compound that possesses NHE1 inhibitory action.

As the known ßHSD1 inhibitors, for example, the following may be indicated. WO2004 / 089470 describes the following compounds as compounds that have an inhibitory action on 11βHSD1: DESCRIPTION OF THE INVENTION There is a strong demand for the development of a compound useful as an agent for the prophylaxis or treatment of diseases metabolic factors such as diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension, fatty liver and the like, and the like, which have more superior properties as a pharmaceutical product in terms of efficacy, duration of action, specificity , low toxicity, oral absorbability, pharmacokinetics and the like. It is therefore an object of the present invention to provide a compound that possesses an HSD1 inhibitory action and the like and is useful as an agent for prophylaxis or treatment of metabolic diseases such as diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension. , fatty liver and the like, which possesses a chemical structure different from that of the known compounds including the mentioned compounds and the use thereof. The present inventors have first found that a heterocyclic compound mentioned below possesses a superior HSD1 inhibitory action, and is useful as an agent for prophylaxis or treatment of metabolic diseases such as diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension, fatty liver and the like. The present inventors have conducted intensive studies based on these results and have completed the present invention. Accordingly, the present invention specifically provides the following. 1. A compound represented by the following formula [1 '] .: wherein ring A is (1) a saturated monocyclic nitrogen-containing heterocyclic group, or (2) a cycloalkyl group, said ring A is optionally substituted with one or more substituents the same or different R1, said substituent R1 is 1) an atom of hydrogen, 2) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a hydrogen atom, (b) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected of the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) an alkyl group of C -? - 6 (said alkyl group of C -? - 6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) hydroxyl group, and (iii) a C 1-6 alkoxy group), and. e) a C 1-6 alkoxy group, (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different Ci-β alkyl groups (said C 1-6 alkyl group is optionally substituted with one or more identical or different substituents selected from the following group: (i) a hydroxyl group, and (i) a C 1-6 alkoxyl group). (d) an alkyl group of C-? 6, said C-? 6 alkyl group is optionally substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group. b) a halogen atom, c) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) alkyl group of C? _6 (said alkyl group of C? -6 is optionally substituted with one or more same or different halogen atoms)). d) -NR20R21 wherein R20 and R21 are the same or different and each is a hydrogen atom, a C1-6alkyl group or a -CO-alkyl group of C-? -6, or R20 and R21 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) a group oxo, and (iv) an alkoxy group of Ci-β), e) an alkoxy group of C6-6, and f) a carboxyl group). (e) -S (= O) 2 -R9 wherein R9 is an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C -? - 6 (said alkyl group of C? --6 is optionally substituted with one or more same or different halogen atoms)), or a C1-6 alkyl group. (f) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of C? -6) b) a -CO-alkyl group of C -? - 6, and. c) an oxo group), (g) an alkoxy group of C-? -6, or (h) an unsaturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more same or different halogen atoms). , or (i) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, or a heterocyclic group which is a fused ring of said heterocycle and a carbon ring (both said heterocyclic groups are optionally substituted with one or more same or different substituents selected from the following a) to i): a) a halogen atom, b) a hydroxyl group, c) an alkyl group of C-α-6 (said C- [alpha] -6 alkyl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxyl group of Ci-β ), d) a carboxyl group, e) a -CO-alkyl group of C? -6 f) -CO-NR22R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of Cl-6, or R22 and R23 optionally form, together with the nitrogen atom at c they are joined, a saturated monocyclic heterocyclic group containing nitrogen, g) an oxo group, h) -NR24R25 wherein R24 and R25 are the same or different and each one is a hydrogen atom, a C1-6 alkyl group, or a -CO-C6-alkyl group, or R24 and R25 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group saturated nitrogen-containing, and i) an alkoxy group of C? -6) 3) -COOR10 wherein R10 is (a) a C1-6 alkyl group (said C? -6 alkyl group is optionally substituted with one or more equal or different substituents selected from the following a) to d): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or an alkyl group of C? 6, or R26 and R27 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, c) a C1-6 alkoxy group, and d) an aryl group), or (b) a saturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one om s the same or different substituents selected from the following a) to c): a) an alkyl group of C? -6l b) a -CO-alkyl group of C-? -6, and c) an oxo group), 4) - COR11 where R11 is (a) an alkyl group of d-6 (said C 1-6 alkyl group is optionally substituted with one or more same or different substituents selected from the following a) to h): a) a halogen atom. b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of a -CO-C6-alkyl group, a -CO-cycloalkyl group, or a -S (= O) 2-C6-alkyl group, or R28 and R29 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, d) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of C? -6, or R30 and R31 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, e) a C6-C6 alkoxy group, f) an aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, (iii) an alkoxy group of C? -6, and (iv) an alkyl group of C-? - 6 (said alkyl group of C? -6 is optionally substituted with one or more same or different halogen atoms)), g) a carboxyl group, and. h) an aryloxy group), (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C1.6 (said alkyl group of C6-6 is optionally substituted with one or more equal halogen atoms) or different)), and. b) an alkyl group of C-? 6 (said C-? 6 alkyl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) a group C6-C6 alkoxy), (c) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of C? -6, b) a -CO-alkyl group of C -? - 6, and c) an oxo group, (d) an aryl group (said aryl group is optionally substituted with one or more identical or different substituents selected of the following (1) to (3): (1) a halogen atom, (2) an alkyl group of C6-6 (said alkyl group of C6-6 is optionally substituted with one or more same or different halogen atoms) ), and (3) an alkoxy group of C? -6), or (e) a carboxyl group, 5) an alkyl group of C? -6 (said C1-6 alkyl group is optionally substituted with one or more equal substitutes or differentials selected from the following (a) to (d): (a) ) a carboxyl group (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, identical or different -CO-NR32R33 wherein R32 and R33 are the same or different and each is a hydrogen atom, an alkyl group of d-6 (said alkyl group of C-? -6 is optionally substituted with one or more equal substitutes or differentials selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of C? -6), or R32 and R33 optionally form, together with the nitrogen atom to which they are attached, a group saturated monocyclic heterocyclic containing niinogen), (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or a C1-6 alkyl group, or R34 and R35 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, and (d) an aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following group: a) an atom of halogen, and b) a group at of C -? - 6 (said alkyl group of C? .e is optionally substituted with one or more equal or different halogen atoms))), 6) a cycloalkyl group, 7) (said C 1-6 alkyl group is optionally substituted with one or more same or different halogen atoms), or an aryl group (said aryl group is optionally substituted with one or more the same or different amino acids selected from the following group: a) an atom of halogen, and b) an alkyl group of C -? - 6 (said C? -6 alkyl group is optionally substituted with one or more same or different halogen atoms)), 8) -C (= NCN) -R13 where R13 is an alkyl group of C? -6, 9) -C (= NCN) NR14R15 wherein R14 and R15 are identical or different and each is a hydrogen atom, or an alkyl group of C -? - 6, or R14 and R15 optionally form, with the nitrogen atom to which they are attached, a monocyclic monocyclic heiroglyclic group containing nihinogen, 10) an aryl group (said aryl group is optionally substituted with one or more identical or selected substitutes). the following (a) to (f): (a) a carboxyl group, (b) a halogen atom, (c) a C 1-6 alkyl group (said alkyl group of C-α-6 is optionally susíiuuido with one or more identical or different susliuyenyes selected from the following group: a) a hydroxyl group, b) an atom of halogen, and c) a C1-6 alkoxy group), (d) -NR38R39 wherein R38 and R39 are the same or different and each one is a hydrogen atom, an alkyl group of C? -6, a -CO-alkyl group of C? -6, -CO-NR 0 R41 wherein R40 and R41 are the same or different and each is a hydrogen atom , an alkyl group of C -6, or an alkoxy group of C6-6, or R40 and R41 optionally form, together with the nylrogen atom to which they are attached, a monocyclic monocyclic heyerocyclic group containing nitrogen, or -S ( = O) 2-R42 wherein R42 is an alkyl group of C-? 6, or R38 and R39 optionally form, together with the niologen atom to which they are attached, a saturated monocyclic heterocyclic group containing nihologen (said heyerocyclic group is optionally substituted with one or more oxo groups), (e) -CO-NR43R44 wherein R43 and R44 are the same or different and each is a hydrogen atom, or an alkyl group of C -? - 6, or R43 and R44 optionally form, together with the nitrogen atom to which they are attached, a salicy monocyclic heterocyclic group which concurs ogen, and (f) a -COO-alkyl group of d-β), or 11) a 5-membered or 6-membered monocyclic monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more the same or different subsitutes selected from the following (a) to (h):. (a) a carboxyl group, (b) an alkyl group of C? -6 (said alkyl group of Cl-6 is optionally substituted with one or more equal or different substituents selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) an alkoxy group of C? -6), (c) a cycloalkyl group, (d) a halogen atom, (e) -CO-NR 5R46 wherein R45 and R46 are the same or different and each is a hydrogen atom, or a C 1-6 alkyl group, or R 45 and R 46 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic helerocyclic group containing nitrogen, (f) a group -COO-C1-6alkyl, (g) a cyano group, and (h) an alkoxy group of C-? -6); -X- is (1) -N (R1) - wherein R1 is the same as defined above, or (2) -C (R7R8) - wherein R7 and R8 are the same or different and each is 1) an hydrogen, 2) -NR16R17 wherein R16 and R17 are the same or different and each is a hydrogen atom, an alkyl group of C? -6, or -CO-NR36R37 wherein R36 and R37 are the same or different and each is a hydrogen atom, or an alkyl group of C? -6, or R36 and R37 optionally form, together with the nitrogen atom to which they are attached, a monocyclic monocyclic heyerocyclic group which contains nitrogen, or R16 and R17 optionally form, june with the nitrogen atom to which they are attached, a group saturated monocyclic heterocyclic that contains nitrogen, 3) -CONR18R19 wherein R18 and R19 are the same or different and each is a hydrogen atom, an alkyl group of C -? - 6 (said C? -6 alkyl group is optionally substituted with one or more carboxyl groups ), or an aryl group (said aryl group is optionally substituted with one or more equal or different subsides selected from the following group: (a) a halogen atom, and (b) an Ci-β alkyl group (said alkyl group of C? -6 is optionally substituted with one or more identical or different halogen atoms), or R18 and R19 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, 4) a heterocyclic group. unsaturated 5-membered or 6-membered monocyclic, or 5) a carboxyl group; R 2 is (1) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following group: 1) a C 1-6 alkyl group (said C? -6 alkyl group is optionally substituted with one or more identical or different substitutes selected from the following group: (a) a hydroxyl group, and (b) a C 1-6 alkoxyl group), and 2) an alkoxy group of C-? -6); and R3 and R4 are the same or different and each is (1) a hydrogen atom, (2) a C 1-6 alkyl group (said C 6 -6 alkyl group is optionally substituted with one or more equal substituents or differentials selected from the following group: 1) a halogen halo, 2) a hydroxyl group, 3) an alkoxy group of and 4) is an -OCO-alkyl group of C? -6), (3) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following 1) to 6):. 1) a halogen atom, 2) a C1-6 alkyl group (said C6-6 alkyl group is optionally substituted with one or more equal or different substituents selected from the following group: (a) a halogen atom, ( b) a hydroxyl group, and (c) a C6-6 alkoxyl group), 3) a C-? -6 alkoxyl group (said C1-6 alkoxy group is optionally susíiuuido with one or more halogen atoms the same or differences). 4) a carboxyl group, 5) a -COO-alkyl group of C? -6, and 6) a cyano group, (4) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more identical or different substituents selected from the following group: 1) a halogen atom, and 2) an alkyl group of C6-6 (said alkyl group of d.6 is optionally substituted with one or more atoms identical or different halogens), (5) a hydroxyl group, or (6) a C 1-6 alkoxyl group, or a salt thereof. 2. A compound represented by the following formula [1]: wherein -X- is (1) -N (R1) - wherein R1 is 1) a hydrogen moiety, 2) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a hydrogen atom (b) an aryl group (said aryl group is optionally substituted with one or more identical or different subsystems selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) a group alkyl of C? -6 (said alkyl group of C? -6 is optionally subsituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxy group of C-? -6), and. e) an alkoxy group of C? -6), (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different C?? 6 alkyl groups (said C 1-6 alkyl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) a C 1-6 alkoxyl group), (d) a C 1-6 alkyl group (said alkyl group of C? -6 is optionally substituted with one or more equal sustiluyeníes or differents selected from the following group: a) a hydroxyl group, b) a halogen halo, c) an aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) a C? -6 alkyl group (said C? -6 alkyl group is optionally susiluted with one or more identical or different halogen atoms), d) -NR20R21 wherein R20 and R21 are the same or different and each is a hydrogen atom, an alkyl group of C? -6, or a -CO-alkyl group of C? -6, or R20 and R21 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group saíurado containing nitrogen (said heterocyclic group is optionally substituted with one or more equal or different substitutes selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) a group oxo, and (iv) an alkoxy group of C? -6), e) an alkoxy group of C? -6, and f) a carboxyl group), (e) -S (= O) 2 -R9 wherein R9 is an aryl group (said aryl group is optionally substituted with one or more equal sustiluyeníes or differents selected from the following (1) and (2): (1) a halogen halo, and (2) an alkyl group of C -? - 6 (said alkyl group of Cl-6 is optionally substituted with one or more same or different halogen atoms), or an alkyl group of d-6, (f) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of d-6, b) a -CO group -alkyl of C-? - 6, and c) an oxo group), (g) a C 1-6 alkoxy group, or (h) an unsaturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally susíiuuido with one or more same or different halogen atoms), or. (i) R5 and R6 optionally form, with the nitrogen atom to which they are attached, a monocyclic monocyclic heyerocyclic group containing nylrogen, or a heterocyclic group which is a fused ring of said heterocycle and a carbon ring (both heterocyclic groups) mentioned are optionally substituted with one or more identical or different subsitutes selected from the following a) to i): a) a halogen atom, b) a hydroxyl group, c) an alkyl group of C1.6 (said alkyl group of C), ? -6 is optionally substituted with one or more equivalent or differential substitutes selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxy group of d.6), d) a carboxyl group, e) a -CO-alkyl group of d-6, f) -CO-NR22R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of d.6l or R22 and R23 optionally form, together with the nitrogen atom at which are attached, a saturated monocyclic heterocyclic group containing nihinogen, g) an oxo group, h) -NR2 R25 wherein R24 and R25 are the same or different and each one is a hydrogen atom, an alkyl group of C? .6, or a -CO-C 1-6 alkyl group, or R 24 and R 25 optionally form, together with the nitrogen atom to which they are bonded, a monocyclic heterocyclic group saturated containing nylrogen, and i) an alkoxy group of d-6), 3) -COOR10 wherein R10 is (a) a C1-6 alkyl group (said alkyl group of .6 is optionally substituted with one or more equal diluents) or different selected from the following a) to d): a) a hydroxyl group, b) -NR 6R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R26 and R27 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group which contains nitrogen, c) a C6-6 alkoxy group, and d) an aryl group), or (b) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more s the same or different subsitutes selected from the following a) to c): a) an alkyl group of C 1-6, b) a group -CO-C 1-6 alkyl, and c) an oxo group), 4) -COR 11 in where R11 is (a) an alkyl group of d-6 (said alkyl group of C6.6 is optionally substituted with one or more equal or different substituents selected from the following a) to h): a) a halogen atom, b) a hydroxyl group. c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of C? -6, a -CO-alkyl group of C-? -6, a -CO-cycloalkyl group , or a group -S (= O) 2-alkyl of d-6, or R28 and R29 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic helerocyclic group containing nitrogen, d) -CO- NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of C-? -6, or R30 and R31 optionally form, together with the nitrogen atom to which they are attached, a group nitrogen-containing saturated monocyclic heterocyclic group, e) a C 1-6 alkoxy group, f) an aryl group (said aryl group is optionally substituted with one or more equal or different substitutes selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, (iii) an alkoxy group of d-6 > and (iv) an alkyl group of d-6 (said alkyl group of d). -6 is optionally substituted with one or more same or different halogen atoms)), g) a carboxyl group, and h) an aryloxy group), (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more equal or different substitutes) selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of C-6 is optionally substituted with uho or more same or different halogen atoms)), and b) an alkyl group of d.6 (said alkyl group of C). ? 6 is optionally substituted with one or more equal or different substituents selected from the following group: (i) a hydroxyl group, and (ii) a C-? 6 alkoxy group), (c) a saturated monocyclic heterocyclic group which it contains nitrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of d-6, b) a -CO-alkyl group of d.6, and c) an oxo group, (d) an aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following (1) to (3): (1) a halogen atom, (2) ) an alkyl group of C -? - 6 (said alkyl group of d.6 is optionally substituted with one or more halogen atoms even s or differentials), and (3) an alkoxy group of d-6), or (e) a carboxyl group, 5) an alkyl group of d-6 (said alkyl group of .6 is optionally substituted with one or more same or different substituents selected from the following (a) to (d): (a) a carboxyl group (b) a cycloalkyl group (said cycloalkyl group is optionally susiiluido with one or more, the same or different ones -CO-NR32R33 where R32 and R33 are the same or different and each is a hydrogen atom, an alkyl group of C1 -6 (said alkyl group of d6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d-6), or R32 and R33 optionally form , June with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen), (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or a group alkyl of C? -6, or R34 and R35 optionally form, together with the Niorogen atom to which they are attached, a saturated monocyclic nitrogen-containing heyerocyclic group, and (d) an aryl group (said aryl group is optionally substituted with one or more identical or different amino-ions selected from the following group: a) a halogen atom , and b) a C 1-6 alkyl group (said alkyl group of d-6 is optionally susíiuuido with one or more same or different halogen atoms))), 6) a cycloalkyl group, 7) -S (= O) 2 -R12 wherein R12 is an alkyl group of d-6 (said C1-6 alkyl group is optionally susíiuuido with one or more same or different halogen atoms), or an aryl group (said aryl group is optionally substituted with one or more equal sustiluyeníes or differents selected from the following group: a) a halogen atom, and b) an alkyl group of d6 (said alkyl group of d ^ is optionally subsituted with one or more equal or different halogen atoms)), 8) -C (= NCN) -R13 wherein R13 is an alkyl group of d.6, 9) -C (= NCN) NR14R15 wherein R14 and R15 are the same or different and each is a hydrogen atom, or an alkyl group of, or R14 and R15 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, 10) an aryl group (said Aryl group is optionally substituted with one or more same or different substituents selected s of the following (a) to (f): (a) a carboxyl group, (b) a halogen atom, (c) an alkyl group of d-6 (said alkyl group of -6 is optionally substituted with one or more equal or different substituents selected from the following group: a) a hydroxyl group, b) a halogen halo, and c) a C6-6 alkoxy group, (d) -NR38R39 wherein R38 and R39 are the same or different and each one is a hydrogen atom, an alkyl group of d-6, a -CO-alkyl group of d.6, -CO-NR40R41 wherein R40 and R41 are the same or different and each is a hydrogen atom, a group alkyl of d.6, or an alkoxy group of. 6, or R40 and R41 optionally form, with the nitrogen atom to which they are attached, a monocyclic heterocyclic group containing nitrogen, or -S (= O) 2 -R42 wherein R42 is an alkyl group of C ?. 6, or R38 and R39 optionally form, together with the niologen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more oxo groups), (e) -CO- NR43R44 wherein R43 and R44 are the same or different and each is a hydrogen atom, or an alkyl group of C-? -6, or R43 and R44 optionally form, together with the nylrogen atom to which they are attached, a group a monocyclic salicylic compound containing nylrogen, and (f) a -COO-alkyl group of d-6), or 1) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more equal or different substituents sele c) of the following (a) to (h): (a) a carboxyl group, (b) an alkyl group of d-6 (said alkyl group of C6-6 is optionally substituted with one or more same or different substituents selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) an alkoxy group of d-6), (c) a cycloalkyl group, (d) a halogen atom, (e) -CO-NR45R46 wherein R45 and R46 are the same or different and each one is a hydrogen atom, or an alkyl group of d-6, or R45 and R46 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, (f) a -COO group -alkyl of d-6, (g) a cyano group, and (h) a C1-6 alkoxy group), or (2) -C (R7R8) - wherein R7 and R8 are the same or different and each is 1) a hydrogen atom, 2) -NR16R17 wherein R16 and R17 are the same or different and each is a hydrogen atom, an alkyl group of d-6, or -CO-NR36R37 wherein R36 and R37 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R36 and R37 optionally form, together with the nitrogen atom to which they are attached, a monocyclic monocyclic heyerocyclic group which conjoins niíróge no, or R16 and R17 optionally form, in June with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, 3) -CONR18R19 wherein R 8 and R19 are the same or different and each is a hydrogen atom, an alkyl group of d-6 (said alkyl group of C? -6 is optionally substituted with one or more carboxyl groups), or an aryl group (said aryl group is optionally susiiuuido with one or more equal or different substituents selected from the following group: (a) a halogen atom, and (b) a C 1-6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms)) , or R18 and R19 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic monocyclic nitrogen-containing heterocyclic group, 4) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group, or 5) a carboxyl group; R2 is (1) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more identical or different substituents selected from the following group: 1) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more equal or different substituents selected from the following group: (a) a hydroxyl group, and (b) a C 1-6 alkoxyl group), and 2) an alkoxyl group of d-β); and R3 and R4 are the same or different and each is (1) a hydrogen atom, (2) an alkyl group of C6-6 (said alkyl group of -6 is optionally substituted with one or more the same or different sustiluyeníes selected from the following group: 1) a halogen atom, 2) a hydroxyl group, 3) an alkoxy group of d.6, and 4) a group that is -OCO-alkyl (3) an aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following 1) to 6): 1) a halogen atom, 2) an alkyl group of C? _6 (said group C- [alpha] -6 alkyl is optionally substituted with one or more same or different substituents selected from the following group: (a) a halogen halo, (b) a hydroxyl group, and (c) a C1-6 alkoxy group) , 3) an alkoxy group of d-6 (said alkoxy group of C? -6 is optionally substituted with one or more same or different halogen atoms), 4) a carboxyl group, 5) a group -COO-C1- alkyl- 6, and 6) a cyano group), (4) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following group: 1) an asyme of halogen, and 2) an alkyl group of d.6 (said alkyl group of d-6 is optionally its iíuido with one or more identical or diferenles áíomos halogens)), (5) a hydroxyl group, or (6) an alkoxy group of d-6], or a salt thereof. 3. The compound according to any of the aforementioned 1 and 2, wherein the -X- is a -C (R7R8) - wherein R7 and R8 are the same as those defined in 1 above., or a salt thereof. 4. The compound according to any of 1 to 3 indicated above, wherein R8 is 1) -NR16R17 wherein R16 and R17 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R16 and R17 optionally form, together with the nylrogen atom to which they are bonded, a saturated monocyclic heterocyclic group containing nitrogen. 2) -CONR18R19 wherein R18 and R19 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R18 and R19 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, or 3) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group, or a salt thereof. 5. The compound according to 1 or 2 indicated above, wherein -X- is -N (R1) - wherein R1 is equal to that defined in 1 above, or a salt thereof. 6. The compound according to any of 1, 2 and 5 indicated above, wherein R 1 is 1) a hydrogen atom, 2) -CONR 5 R 6 wherein R 5 and R 6 are the same or different and each is (a) a hydrogen atom (b) an aryl group (said aryl group is supported by one or more identical or different subsitutes selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) an alkyl group of d-6 (said alkyl group of C-? -6 is optionally susiiuuid with one or more identical or different substrates selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) a alkoxy group of d-6) and e) an alkoxy group of d-6), (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more equal or different C? -6 alkyl groups (said alkyl group of d-6 is optionally susíiluido with one or more equal or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d-6), (d) an alkyl group of d-6 (said C1.6 alkyl group is substituted with one or more identical substituents or different selected from following group: a) a hydroxyl group, b) a halogen atom, c) an aryl group (said aryl group is optionally substituted with one or more equal or differential substitutes selected from the following (1) and (2): (1) ) a halogen atom, and (2) a C 1-6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms)), d) -NR 20 R 21 wherein R 20 and R 21 are Equal or different and each is a hydrogen atom, an alkyl group of d-6, or a -CO-alkyl group of C-? -6, or R20 and R21 optionally form, June with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nylrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following (i) to (iv): (i) a halogen halo, (ii) a hydroxyl group, (iii) an oxo group, and (iv) an alkoxy group of Ci-e), e) an alkoxy group, e C1-6, and f) a carboxyl group), (e) -S (= O) 2 -R9 wherein R9 is an aryl group (said aryl group is optionally substituted with one or more equal or different substituents) selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more same halogen atoms or different)), or an alkyl group of C? -6, or (f) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally susliluted with one or more equal or different substituents selected from the following a) to c) : a) an alkyl group of d.6, b) a -CO-alkyl group of d-6, and c) an oxo group, or (g) a non-saturated, monocyclic heliccyclic group containing nitrogen (said heyerocyclic group is optionally substituted with one or more same or different halogen atoms), or (h) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more equal substituents s or different selected from the following a) to i): a) a halogen atom, b) a hydroxyl group. c) an alkyl group of d-6 (said C? -6 alkyl group is optionally substituted with one or more substituents the same or different selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d-β), d) a carboxyl group, e) a -CO-alkyl group of d-6, f) -CO-NR22R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R22 and R23 optionally form, together with the nylrogen atom to which they are attached, a monocyclic monocyclic heterocyclic group which contains nitrogen, g) an oxo group, h) -NR24R25 wherein R24 and R25 are the same or different and each is a hydrogen atom, an alkyl group of Cl-6, or a -CO-alkyl group of C-? -6 , or R24 and R25 optionally form, together with the nitrogen moiety to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, and i) a C1-6 alkoxy group (with the proviso that R5 and R6 are not simultaneously atoms of hydrogen), 3) -COOR10 wherein R10 is (a) an alkyl group of C? _6 (said alkyl group of C-? -6 is optionally substituted with one or more same or different substituents selected from the following a) to d): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R26 and R27 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, c) an alkoxy group of d-6, and. d) an aryl group), or (b) a saturated monocyclic heterocyclic group containing nylrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of C1.6, b) a -CO-alkyl group of d.6, and c) an oxo group), 4) -COR11 wherein R11 is (a) a C1-6 alkyl group (said alkyl group of C-? -6 is optionally substituted with one or more equal or different substituents selected from the following a) to h): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of d-6, a -CO-alkyl group of C? -6, a -CO-cycloalkyl group, or a group -S (= O) 2-alkyl of d, 6, or R28 and R29 optionally form, together with the nitrogen atom to which they are attached, a monocyclic monocyclic heyerocyclic group containing nihinogen, d) -CO-NR30R31 wherein R30 and R3 1 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R30 and R31 optionally they form, June with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, e) an alkoxy group of d-6. f) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, (iii) an alkoxy group of d-6 , and (iv) an alkyl group of d-6 (said C1-6 alkyl group is optionally substituted with one or more same or different halogen atoms)), g) a carboxyl group, and h) an aryloxy group), (b) ) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms) ), and b) an alkyl group of d-6 (said alkyl group of C -? - 6 is optional) ionalmenie subsituted with one or more identical or different substitutes selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d-6), or (c) a monocyclic, monocyclic, heyerocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more identical or different substitutes selected from the following a) to c): a) an alkyl group of d, b) a group - CO-alkyl of d-6, and c) an oxo group), (d) an aryl group (said aryl group is substituted by one or more identical or different subsitutes selected from the following (1) to (3): (1) a halogen atom, (2) a C 1-6 alkyl group (said alkyl group of d 6 is optionally substituted with one or more equal or different halogen atoms), and (3) an alkoxy group of de), or ( e) a carboxyl group, 5) an alkyl group of d-6 (said Cie alkyl group is optionally substituted with one or more equal substitutes or differentials selected from the following (a) to (d): (a) a carboxyl group , (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different -CO-NR32R33 wherein R32 and R33 are the same or different and each is a hydrogen atom, an alkyl group of d.6 (said alkyl group of -6 is optionally substituted with one or more identical or different substituents selected of the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of Ci-e), or R32 and R33 optionally form, June with the nitrogen to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen), (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or an alkyl group of d.6, or R34 and R35 optionally form, together with the nihologen atom to which they are joined, a monocyclic heterocyclic group containing nilrogen, and (d) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) a halogen atom, and b) a group alkyl of d.6 (said alkyl group of C6-6 is optionally substituted with one or more equal or different halogen atoms))), 6) a cycloalkyl group. 7) -S (= O) 2 -R12 wherein R12 is an alkyl group of C6-6 (said C1-6 alkyl group is optionally susiiuuided with one or more equal or different halogen atoms), or an aryl group ( said aryl group is optionally susiiuuid with one or more same or different substituents selected from the following group: a) a halogen alloy, and b) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more halogen atoms the same or different)), 8) -C (= NCN) -R13 wherein R13 is a C1-6 alkyl group, 9) -C (= NCN) NR1 R15 where R14 and R15 are the same or different and each is a hydrogen atom, or an alkyl group of C -? - 6, or R14 and R15 optionally form, together with the nitrogen atom to which they are attached, a monocyclic salicyclic group which contains nilrogen, 10) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (a) to (f): (a) a carboxyl group, (b) ) a halogen atom, (c) an alkyl group of d-6 (said alkyl group of C6 .6 is optionally substituted with one or more identical or different susligens selected from the following group: a) a hydroxyl group, b) a halogen atom, and c) an alkoxy group of d-6), (d) -NR38R39 wherein R38 and R39 are the same or different and each is a hydrogen atom, a C1-6 alkyl group, a -CO group -alkyl of C? -6, -CO-NR40R41 wherein R40 and R41 are the same or different and each is a hydrogen atom, an alkyl group of d-6I or an alkoxy group of Ci. 6, or R40 and R41 optionally form, together with the niologen atom to which they are attached, a saturated monocyclic heyerocyclic group containing nitrogen, or -S (= O) 2 -R42 wherein R42 is an alkyl group of d-β ), or R38 and R39 optionally form, together with the nitrogen moiety to which they are attached, a nitrogen-containing saturated monocyclic helerocyclic group (said heterocyclic group is optionally substituted with one or more oxo groups). (e) -CO-NR43R44 wherein R43 and R44 are the same or different and each is a hydrogen atom, or a C1-6 alkyl group, or R43 and R44 optionally form, together with the nitrogen atom to which they are attached; United, a saturated monocyclic nitrogen-containing heterocyclic group, and (f) a -COO-alkyl group of d-6), or 11) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more equal or differential substitutes selected from the following (a) to (h): (a) a carboxyl group, (b) an alkyl group of d-6 (said alkyl group of C-α-6 is optionally substituted with one or more equal or differential substitutes selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) an alkoxy group of d-6), (c) a cycloalkyl group, and (d) ) a halogen atom, (e) -CO-NR45R46 wherein R45 and R46 are the same or different and each is a hydrogen atom, or a C1-6 alkyl group > or R 45 and R46 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nilrogen, (f) a -COO-C 1-6 alkyl group, (g) a cyano group, and ( h) a C1-6 alkoxy group, or a salt thereof. 7. The compound according to any of the 1, 2 and 5 indicated above, wherein R1 is 1) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a hydrogen atom, (b) a group aryl (said aryl group is optionally substituted with one or more identical or different susliluyeníes selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) an alkyl group of d-6 ( said alkyl group of .6 is optionally substituted with one or more identical substituents or differentiations selected from the following group: (i) a halogen halo, (ii) a hydroxyl group, and (iii) a C6-6 alkoxy group), and e) a C1-6 alkoxy group) > (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more identical or different C? -6 alkyl groups (said C? 6 alkyl group is optionally substituted with one or more identical or different substituents selected from the group; following group: (i) a hydroxyl group, and (ii) an alkoxy group of d.6)), (d) an alkyl group of C? .6 (said C? -6 alkyl group is optionally susíiuuido with one or more susíiíuyenles equal or different selected from the following group: a) a hydroxyl group, b) a halogen atom, c) an aryl group (said aryl group is optionally substituted with one or more identical or different substitutes selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C1.6 (said alkyl group of C6 is optionally substituted with one or more same or different halogen atoms), d) -NR 0R21 wherein R20 and R21 are the same or different and each is a hydrogen atom, an alkyl group of d.6, or a -CO-alkyl group of C? -6, or R20 and R21 optionally form, together with the nihologen atom to which they are attached, a group saturated monocyclic heyerocyclic containing nihologen (said helerocyclic group is optionally substituted with one or more same or different substituents selected from the following (i) to (iv): (i) a halogen atom, (i) a hydroxyl group, ( iii) an oxo group, and (iv) a C 1-6 alkoxy group), e) a C 1-6 alkoxy group, and f) a carboxyl group), (e) -S (= O) 2 -R 9 wherein R9 is an aryl group (said aryl group is optionally susíiuuido with one or more identical or different susíiluyeníes selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C1.6 (said C1-6 alkyl group is optionally substituted with one or more same halogen atoms or differents)), or an alkyl group of C1-6, or (f) a monocyclic monocyclic salt group containing nitrogen (said heterocyclic group is optionally substituted with one or more equal substitutes or differentials selected from the following a) to c): a) an alkyl group of C? 6, b) a -CO-alkyl group of d-6, and c) an oxo group, (g) an alkoxy group of d-6, or (h) an unsaturated monocyclic heterocyclic group which contains nitrogen (said heterocyclic group) is optionally subsumed with one or more same or different halogen atoms), or (i) R5 and R6 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more substitutes the same or different selected from the following a) to i): a) a halogen atom, b) a hydroxyl group, c) an alkyl group of C? .6 (said alkyl group of -6 is optionally Substitute c on one or more equal or different subsitutes selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of C? .6), d) a carboxyl group, e) a -CO-alkyl group of d.6, f) -CO- NR22R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of C? .6) or R22 and R23 optionally form, together with the nihologen atom to which they are attached, a heyerocyclic group monocyclic salt containing nitrogen, g) an oxo group, h) -NR R25 wherein R24 and R25 are the same or different and each is a hydrogen atom, an alkyl group of d.6, or a -CO-alkyl group of C1-6, or R24 and R25 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, and i) an alkoxy group of d.6) (with the proviso that R5 and R6 they are not any combination of substituents selected from the following group: (i) a hydrogen atom, and (ii) an alkyl group of d.6 unsubstituted). 2) -COOR10 wherein R10 is (a) an alkyl group of d-6 (said alkyl group of -6 is substituted with one or more same or different substituents selected from the following a) to d): a) a hydroxyl group , b) -NR2bR27 where R26 and R27 are the same or different and each one is a hydrogen atom, or an alkyl group of d.6, or R26 and R27 optionally form, together with the nitrogen atom to which they are bonded, a saturated monocyclic heterocyclic group containing nitrogen, c) an alkoxy group of C1 .6, and d) an aryl group), or (b) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more equal or different substituents selected from the following a) to c): a) a alkyl group of C1.6, b) a -CO-alkyl group of C? -6, and c) an oxo group), 3) -COR11 wherein R11 is (a) a C1-6 alkyl group (said alkyl group of C 1-6 is substituted with one or more equal or differential sustiluyeníes selected from the following a) to h): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of d.6, a -CO-alkyl group of d-6, a -CO-cyclic group oalkyl, or a group -S (= O) 2-alkyl of d.6, or R28 and R29 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, d) -CO -NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or a C 1-6 alkyl group, or R 30 and R 31 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heliccyclic group containing nihologen, e) an alkoxy group of C1-6, f) an aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, (iii) a C 1-6 alkoxy group, and (iv) a C 1-6 alkyl group (said C 1-6 alkyl group is optionally substituted with one or more same or different halogen atoms) )), g) a carboxyl group, and h) an aryloxy group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) a group aryl (said aryl group is optionally substituted with one or more equal or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said group C 1-6 alkyl is optionally substituted with one or more equal or different halogen atoms)), and b) an alkyl group of -6 (said C-? 6 alkyl group is optionally substituted with one or more identical or different substituents selected of the following group: (i) a hydroxyl group, and (ii) a group alkoxy of d.6)), or (c) a monocyclic saturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of d.6, b) a -CO-alkyl group of d.61 and c) an oxo group, (d) an aryl group (said aryl group is optionally substituted with one or more identical or different substitutes selected from the following ( 1) to (3): (1) a halogen atom, (2) an alkyl group of C6-6 (said alkyl group of d6 is optionally substituted with one or more same or different halogen atoms), and (3) a alkoxy group of d-6), or (e) a carboxyl group, 4) a C 1-6 alkyl group (said C 1-6 alkyl group is substituted with one or more equal or different substituents selected from the following (a) a (d): (a) a carboxyl group (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more s, the same or different -CO-NR32R33 wherein R32 and R33 are the same or different and each is a hydrogen atom, an alkyl group of d.6 (said C1-6 alkyl group is optionally substituted with one or more substituents equal or different selected from the following group: (i) a hydroxyl group, and (ii) a group Ci-e alkoxy), or R32 and R33 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing niinogen), (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R34 and R35 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, and (d) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) a halogen atom, and b) a C1.6 alkyl group (said C1-6 alkyl group is optionally substituted with one or more same or different halogen atoms))), 5) a cycloalkyl group. 6) -S (= O) 2 -R12 wherein R12 is an alkyl group of d.6 (said alkyl group of d.6 is substituted with one or more same or different halogen atoms), or an aryl group (said group aryl is optionally substituted with one or more same or different substituents selected from the following group: a) a halogen atom, and b) a C 1-6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more halogen atoms) same or different)), 7) -C (= NCN) -R13 wherein R13 is a C1-6 alkyl group, 8) -C (= NCN) NR14R15 wherein R14 and R15 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R14 and R15 optionally they form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, or 9) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group (said heterocyclic group is susíiluido with one or more susilyuyeníes equal or differential selected from the following (a) to (g): (a) a C 1-6 alkyl group (said C? -6 alkyl group is substituted with one or more same or different substituents selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) an alkoxy group of d-6). (b) a cycloalkyl group, (c) a halogen atom, (d) -CO-NR45R46 wherein R45 and R46 are the same or different and each is a hydrogen atom, or an alkyl group of Cl-6, or R45 and R46 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nilrogen, (e) a -COO-alkyl group of d-6, (f) a cyano group, and (g) ) a -β-alkoxy group, or a salt thereof. 8. The compound according to any of 1, 2 and 5 indicated above, wherein R1 is 1) -CONR) 5 ° DR6D where R and R are the same or different and each is (a) a hydrogen atom, (b) an aryl group (said aryl group is substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a halogen halo, c) a carboxyl group, d) an alkyl group of C1-6 (said alkyl group of -6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxy group of de), and e) a C 1-6 alkoxy group, (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more identical or different d-6 alkyl groups (said alkyl group of d 6 is optionally substituted with one or more equal or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d-β), (d) an alkyl group of d-6 (said alkyl group of -6) is substituted with one or more equal or differential susliluyeníes selected from the following group nte: a) a hydroxyl group, b) a halogen atom. c) an aryl group (said aryl group is optionally susiiuido with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d. 6 (said alkyl group of C6 is optionally substituted with one or more same or different halogen atoms), d) -NR20R21 wherein R20 and R21 are the same or different and each is a hydrogen atom, an alkyl group of d-6, or a -CO-alkyl group of C-? -6, or R20 and R21 optionally form, with the nitrogen atom to which they are bonded, a saturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) an oxo group, and (iv) a group d-β alkoxy). e) a C 1-6 alkoxyl group, and f) a carboxyl group), (e) -S (= O) 2 -R 9 wherein R 9 is an aryl group (said aryl group is optionally susliluted with one or more identical substituents or different selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C1.6 (said alkyl group of d.6 is optionally substituted with one or more same halogen atoms) or different)), or an alkyl group of C? -6, or (f) a saturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more identical or different substitutes selected from the following a) to c): a) an alkyl group of C? .6, and b) a -CO-alkyl group of C? .6, and c) an oxo group, or (g) an unsaturated monocyclic heliccyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more halogen atoms). same or different), or (h) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected of the following a) to i): a) a halogen atom, b) a hydroxyl group, c) a C 1-6 alkyl group (said C 6 alkyl group is optionally substituted with one or more substituents i) or different groups selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of C? .6), d) a carboxyl group, e) a -CO-alkyl group of C? .6, f) -CO-NR22R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of d.6, or R22 and R23 optionally form, together with the nitrogen atom to which they are attached , a saturated monocyclic heterocyclic group containing nitrogen, g) an oxo group, h) -NR24R25 wherein R24 and R25 are the same or different and each is a hydrogen atom, an alkyl group of d.6, or a group - CO-alkyl of d-6, or R 24 and R 25 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nylrogen, and i) an alkoxy group of C- | 6) (with the condition that R5 and R6 are not simultaneously hydrogen atoms), 2) -COOR10 wherein R10 is (a) a C1-6 alkyl group (said alkyl group of d.6 is substituted with one or more same or different substituents selected from the following a) to d): a) a hydroxyl group, b) -NR26R27 where R26 and R27 are the same or different and each is a hydrogen atom, or an alkyl group of d.6, or R26 and R27 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nihologen, c) a group C-α6 alkoxy, and d) an aryl group), or (b) a nitrogen-containing saturated monocyclic heterocyclic group (said heterocyclic group is optionally susiiluted with one or more equal or different substituents selected from the following a) to c): a) an alkyl group of d.6, b) a group -CO-C-6 alkyl, and c) an oxo), 3) -COR11 group wherein R11 is (a) an alkyl group of d.6 (said alkyl group of d.6 is substituted with one or more same or different substituents selected from the following a) to h): a) a halogen atom, b) a hydroxyl group, c) -NR 8R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of C? -6, a group -CO-C 1-6 alkyl, a -CO-cycloalkyl group, or a group -S (= O) 2-C? .6 alkyl, or R28 and R29 optionally form, June with the nitrogen homage to which they are attached, a nitrogen-containing saturated monocyclic heterocyclic group, d) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R30 and R31 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, e) an alkoxy group of d.6, f) an aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, (iii) an alkoxyl group of C -? - 6, and (v) an alkyl group of d.6 (said alkyl group of C? -6 is optionally substituted with one or more same or different halogen atoms)), g) a carboxyl group, and h) an aryloxy group, (b) a cycloalkyl group (said cycloalkyl group) is optionally substituted with one or more identical or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more identical or different substitutes selected from the following (1) and (2) ): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of C6-6 is optionally substituted with one or more halogen atoms that are different or different), and b) a group alkyl of d6 (said alkyl group of -6 is optionally substituted with one or more substituents or selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d-β), or (c) a nitrogen-containing saturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more susíiuyenles equal or different selected from the following a) to c): a) an alkyl group of C -? - 6, b) a -CO-C 1-6 alkyl group, and c) an oxo group, (d) an aryl group (said aryl group is optionally susliluted with one or more the same or different subscripts selected from the following (1) to (a) 3): (1) a halogen atom, (2) an alkyl group of C? .6 (said alkyl group of d.6 is optionally substituted with one or more same or different halogen atoms), and (3) a group alkoxyl of d.6), or (e) a carboxyl group, 4) an alkyl group of C6-6 (said alkyl group of -6 is substituted with one or more same or different substituents selected from the following (a) to ( d): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, or different or -CO-NR32R33 wherein R32 and R33 are equal or different and each is a hydrogen atom, an alkyl group of d.6 (said alkyl group of -6 is optionally susíiluido with one or more identical or different subsitutes selected from the group the following: (i) a hydroxyl group, and (ii) an alkoxyl group of d-β), or R32 and R33 optionally form, together with the nitrogen atom to which they are attached, a monocyclic monocyclic nitrogen-containing heterocyclic group) , (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or a C1-6 alkyl group, or R34 and R35 optionally they form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, and (d) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) a halogen atom, and b) an alkyl group of d-6 (said alkyl group of d6 is optionally substituted with one or more halogen atoms) Equal or different))), 5) a cycloalkyl group, 6) -S (= O) 2 -R12 wherein R12 is an alkyl group of C? .6 (said alkyl group of C? _6 is substituted with one or more identical or different halogen atoms), or an aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following group: a) a halogen atom, and b) an alkyl group of d-6 (said alkyl group of C6 is optionally substituted with one or more same or different halogen atoms), 7) -C (= NCN) -R13 wherein R13 is an alkyl group of C6.6) -C (= NCN) NR 4R15 wherein R 14 and R 15 are the same or different and each is a hydrogen atom, or an alkyl group of d 6, or R 14 and R 15 optionally form, together with the nitrogen atom to which they are attached, a heterocyclic group monocyclic saline containing nitrogen, or 9) an unsaturated monocyclic 5-membered or 6-membered monocyclic helerocyclic group (said heterocyclic group Substituted with one or more identical or different substituents selected from the following (a) to (g): (a) an alkyl group of d-6 (said alkyl group of C6-6 is substituted with one or more equal or different substituents selected from the following a) to c): a) a halogen atom, b) a hydroxyl group , and c) an alkoxy group of dd), (b) a cycloalkyl group, (c) a halogen atom, (d) -CO-NR45R46 wherein R45 and R46 are the same or different and each is a hydrogen atom, or an alkyl group of C? .6, or R45 and R46 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing niinogen, (e) a -COO-C- alkyl group? .6, (f) a cyano group, and (g) an alkoxy group of dd), or a salt thereof. 9. The compound according to any of 1 to 8 indicated above, wherein R2 is a cyclopropyl group or is a 1-methylcyclopropyl group, or a salt thereof. 10, the compound according to any of 1 to 9 indicated above, wherein R3 and R4 are the same or different and each is (1) a hydrogen atom, (2) an alkyl group of d.6 (said alkyl group of C1-6 is substituted with one or more identical or different substituents selected from the following group: 1) a halogen atom, and 2) an -OCO-alkyl group of d_ 6), (3) an aryl group (said aryl group is substituted with one or more same or different substituents selected from the following 1) to 5): 1) an alkyl group of C? _6 (said alkyl group of C? 6 is substituted with one or more same or different substituents selected from the following group: (a) a halogen atom, and (b) a hydroxyl group), 2) a C6_6 alkoxyl group (said C1_6 alkoxy group) is substituted with one or more same or different halogen atoms), 3) a carboxyl group, 4) a -COO-alkyl group of d6, and 5) a cyano group), or (4) a non-saturated monocyclic heterocyclic group of 5 members or 6 members (said helerocyclic group is substituted with one or more equal or different substituents selected from the following group: 1) a halogen atom, and 2) an alkyl group of d-6 (said alkyl group of Ci. 6 is optionally subsituted with one or more same or different halogen atoms)), (provided that R3 and R4 are not simultaneously hydrogen atoms), or a salt thereof. 11. The compound of 1 indicated above, where R1 is 1) -CONR? 5 ° rR- > 6D where R and R ° are the same or different and each is (a) a hydrogen atom, (b) an aryl group (said aryl group is substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) an alkyl group of C? _6 (said alkyl group of C-? - 6 is optionally substituted with one or more same or different substituents selected from the group following: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxy group of C? .6), and e) an alkoxy group of C? _6), (c) a cycloalkyl group (said The cycloalkyl group is optionally substituted with one or more identical or different C6-6 alkyl groups (said alkyl group of d6 is optionally substituted with one or more identical or different subsitutes selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of C6-6), (d) an alkyl group of C6.6 (said C1-6 alkyl group) is unsolded with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) an aryl group (said aryl group is optionally substituted with one or more identical or different subsitutes selected from the following (1) and (2): (1) a halogen atom, and (2) ) an alkyl group of d6 (said alkyl group of d.6 is optionally substituted with one or more halogen atoms which are different or different), d) -NR20R21 wherein R20 and R21 are identical or different and each is an atom of hydrogen, an alkyl group of C -? - 6, or a -CO-alkyl group of d.6, or R20 and R21 optionally form, with the nitrogen atom to which they are attached, a nitrogen-containing monocyclic heliccyclic group (said heterocyclic group is optionally substituted with one or more identical or different substituents selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) an oxo group, and (iv) an alkoxy group of de), e) an alkoxy group of d.6, and f) a carboxyl group, (e) -S (= O) 2 -R9 wherein R9 is an aryl group (said aryl group is optionally substituted with one or more same or different substitute selected from the following (1) and (2): (1) a halogen atom , and (2) an alkyl group of C? _6 (said alkyl group of C? _6 is optionally substituted with one or more same or different halogen atoms)), or an alkyl group of (f) a saturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more identical or different substituents selected from the following a) to c): a) an alkyl group of C? .6, b) a group -CO-alkyl of d.6, and c) an oxo group), (g) an alkoxy group of C? .6, or (h) an unsaturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more same or different halogen atoms), or (i) R5 and R6 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more Equal or different substrates selected from the following a) to i): a) a halogen atom, b) a hydroxyl group, c) an alkyl group of C? .6 (said alkyl group of C-? -6 is optionally susíiuuido with one or more equal or different subscripts selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxy group of d.6), d) a carboxyl group, e) a -CO-alkyl group of d.6, f) -CO-NR22R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of C1. 6, or R22 and R23 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, g) an oxo group, h) -NR2 R25 wherein R24 and R25 are the same or different and each is a hydrogen atom, an alkyl group of d.6, or a -CO-alkyl group of d.6, or R24 and R25 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group saturated nitrogen-containing, and i) an alkoxy group of C? .6) (with the proviso that R5 and R6 are not simultaneously hydrogen atoms), 2) -COOR10 wherein R10 is (a) an alkyl group of d.6 (said alkyl group of .6 is subsumed with one or more equal or different substitutes selected from the following a) to d): a) a group hydroxyl, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or an alkyl group of d.6, or R26 and R27 optionally form, together with the nitrogen atom to which they are attached , a saturated monocyclic heterocyclic group containing niinogen, c) an alkoxy group of d.6, and d) an aryl group), or (b) a nitrogen-containing saturated monocyclic heterocyclic group (said heyerocyclic group is optionally substituted with one or more identical substitutes or differentials selected from the following a) to c): a) an alkyl group of C-? 6, b) a -CO-alkyl group of d.6, and c) an oxo group), 3) -COR11 wherein R11 is (a) a group C.sub.6 alkyl (said C.sub.6 alkyl group is substituted with one or more identical or different substituents selected from the following a) to h): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, a C1-6 alkyl group, a -CO-C6-alkyl group, a -CO-cycloalkyl group, or a group -S (= O) 2-C1-6alkyl, or R28 and R29 optionally form, together with the nitrogen atom to which they are attached, a monocyclic monocyclic heyerocyclic group which contains nilrogen, ) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R30 and R31 optionally form, together with the nylrogen atom to which they are attached, a saturated monocyclic helerocyclic group containing nitrogen, e) an alkoxy group of d-6, f) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, (iii) an alkoxy group of d-6, and (iv) an alkyl group of d.6 (said alkyl group of C6.6 is optionally substituted with one or more halogen atoms which are different or different)), g) a carboxyl group, and h) a loxyl group), (b) a cycloalkyl group (said cycloalkyl group is optionally susliluted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more identical or different substrates selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d.6 (said alkyl group of d.6 is optionally substituted with one or more same or different halogen atoms)), and b) an alkyl group of C_6 (said alkyl group of C-? _6 is optionally substituted with one or more identical substitutes or differentials selected from the group following: (i) a hydroxyl group, and (ii) an alkoxyl group of d-β), or (c) a nitrogen-containing saturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more equal or different substituents selected from the following a) to c): a) an alkyl group of C? .6, b) a -CO-alkyl group of d.6, and c) an oxo group, (d) a aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following (1) to (3): (1) a halogen atom, (2) an alkyl group of d6 (said alkyl group of C1-6 is optionally substituted with one or more same or different halogen atoms), and (3) an alkoxy group of d_6), or (e) a carboxyl group, 4) an alkyl group of d-6 (said alkyl group of .6 is substituted with one or more identical or different substitutes selected from the following (a) to (d): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different -CO-NR32R33 wherein R32 and R33 are the same or different and each is a hydrogen atom, an alkyl group of d-6 (said alkyl group of is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) a C 1-6 alkoxyl group), or R32 and R33 optionally form, June with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen), (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or an alkyl group of C? -6, or R34 and R35 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nilrogen, and (d) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) a halogen atom, and b) a group alkyl of d-6 (said alkyl group of C? -6 is optionally substituted with one or more same or different halogen atoms))), 5) a cycloalkyl group, 6) -S (= O) 2 -R12 wherein R12 is an alkyl group of d-6 (said alkyl group of d.6 is substituted with one or more equal or different halogen atoms), or an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the group following group: a) a halogen atom, and b) an alkyl group of C1-6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms)), 7) -C (= NCN) -R13 wherein R13 is a C1-6 alkyl group, 8) -C (= NCN) NR14R15 wherein R14 and R15 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R14 and R15 optionally form, June with the nitrogen atom to which they are attached; united, a saturated monocyclic hei- nocyclic group containing nitrogen, 9) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (a) to (f): (a) a carboxyl group, (b) a halogen atom, (c) a C 1-6 alkyl group (said alkyl group of C6 is optionally substituted with one or more identical or different substrates selected from the following group: a) a hydroxyl group, b) a halogen atom, and c) a C6.6 alkoxy group, (d) -NR38R39 wherein R38 and R39 are the same or different and each is a hydrogen atom, an alkyl group of C1.6, a -CO-alkyl group of C? -6, -CO-NR40R41 wherein R40 and R4 are the same or different and each is a hydrogen atom, an alkyl group of d-6, or an alkoxy group of Ci. 6, or R40 and R41 optionally form, with the niilogen atom to which they are attached, a monocyclic monocyclic heterocyclic group containing nihologen, or -S (= O) 2 -R42 wherein R42 is an alkyl group of d.6 ), or R38 and R39 optionally form, together with the nylrogen atom to which they are attached, a monocyclic salicylicheterocyclic group containing nihologen (said helerocyclic group is optionally substituted with one or more oxo groups), (e) -CO-NR43R44 wherein R43 and R44 are the same or different and each is a hydrogen atom, or an alkyl group of C? .e, or R43 and R44 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group Saíurado that conliene nilrógeno, and (f) a group -COO-alkyl of d.6), or 10) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group (said heterocyclic group is substituted with one or more same or different substituents selected from the following (a) to (h): (a) a carboxyl group, (b) ) an alkyl group of d.sub.6 (said alkyl group of C-? 6 is optionally substituted with one or more identical or different subsitutes selected from the following a) to c): a) a halogen atom, b) a group hydroxyl, and c) an alkoxy group of C? .6), (c) a cycloalkyl group, (d) a halogen atom, (e) -CO-NR 5R46 wherein R45 and R46 are the same or different and each is a hydrogen atom, or an alkyl group of Cl-6, or R45 and R46 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic helerocyclic group containing nitrogen, (f) a -COO-alkyl group of C -6, (g) a cyano group, and (h) an alkoxy group of C? .6), or a salt thereof. 12. The compound of 1 indicated above, or a salt thereof, which is selected from the following: (1) 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl ]-3- (pyridin-3-yl) pyrrolidine, (2) 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole-4-carbonyl] - [(S) -3- (2) hydrochloride] -rifluoromethylphenyl)] pyrrolidine, (3) 1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (4) 1- [1- (1-carbamoylpiperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl] - [(S) -3 - (2-l-trifluoromethylphenyl)] pyrrolidine, (5) 1-. { 1- [1- (2-carboxyphenylcarbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (6) 1-. { 5-cyclopropyl-1- [1- (2-hydroxymethylphenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (7) 1-. { 5-Cyclopropyl-1- [1- (1-hydroxymethylcyclopropylcarbamoyl) -piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)) pyrrolidine, (8) 1 -. { 5-cyclopropyl-1 - [1 - (2-hydroxy-ylcarcarmoyl) piperidin-4-yl] -H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (9) 1 -. { 5-cyclopropyl-1 - [1 - (2-hydroxy-1,1-dimethylyarylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (10) 1 -. { 1 - [1 - (2-Acetylaminoethylcarbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (11) 1- hydrochloride. { 1- [1- (2-Aminoarylcarbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (12) 1 -. { 5-cyclopropyl-1 - [1 - (1,1-dioxoyiomorpholine-4-carbonyl) -piperidin-4-yl] -1 H -pyrazole-4-carbonylH (S) -3- (2-l-trifluoromethyl-phenyl)] pyrrolidine, (13) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (2-dimethylamino-ethylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (14) 1-. { 5-Cyclopropyl-1- [1- (4-hydroxypiperidine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (15) 1-. { 1- [1- (azeidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (16) 1-. { 5-Cyclopropyl-1- [1- (3-hydroxypyrrolidine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-nifluoromethylphenyl)] pyrrolidine, (17) 1-. { 5-cyclopropyl-1- [1- (2-piperidin-1-yl-eylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (18) 1-. { 5-Cyclopropyl-1- [1- (4,4-difluoropiperidine-1-carbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (19) 1 -. { 5-cyclopropyl-1 - [1 - (3,3-difluoropyrrolidin-1 -carbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (20) 1-. { 5-Cyclopropyl-1- [1- (3-hydroxyazelidin-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (21) 1- (5-cyclopropyl-1-. {1 - [(R) -3-hydroxypyrrolidine-1-carbonyl] -piperidin-4 -yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine, (22) 1- (5-cyclopropyl-1- { 1 - [( S) -3-hydroxypyrrolidine-1-carbonyl] -piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-yltrluoromethyl-phenyl)] pyrrolidine, (23) 1 - (5-cyclopropyl-1- { 1 - [(S) -2-hydroxy-1-mellylerylcarbamoyl] -piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (24) 1-. { 5-Cyclopropyl-1- [1- (4-hydroxymethylpiperidine-1-carbonyl) -piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (25) 1-. { 1- [1- (4-carboxypiperidine-1-carbonyl) piperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (26) 1-. { 5-Cyclopropyl-1- [1- (3-oxopiperazine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (27) 1- (5-cyclopropyl-1- { 1 - [(S) -2-hydroxymethylpyrrolidine-1-carbonyl] -piperidin-4 -yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (28) 1-. { 5-Cyclopropyl-1- [1- (3-hydroxymethylazeidin-1-carbonyl) -pipehdin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (29) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (4-methyl-piperazine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (30) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (4-isopropylpiperazine-1-carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] - pyrrolidine, (31) 1-. { 1- [1- (4-Ailylpiperazin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)) pyrrolidine, (32) 1- (5-cyclopropyl-1- { 1 - [(R) -3-hydroxypiperidine-1-carbonyl] -piperidin-4 -yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (33) 1-. { 1- [1- (4-carbamoylpiperidine-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (34) 1-. { 1- [1- (3-carbamoylazelidin-1-carbonyl) piperidin-4-yl] -5- cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)) pyrrolidine, (35) hydrochloride of 1-. { 1- [1- (4-aminopiperidine-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (36) 1- hydrochloride. { 1- [1- (3-aminopyrrolidine-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (37) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (piperidin-4-yl-carbamoyl) -piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-lrifluoromethylphenyl)] pyrrolidine, (38) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (4-dimethylaminopipehdin-1-carbonyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-nifluoromethylphenyl)] - pyrrolidine, (39) 1-. { 1- [1- (4-Acetylaminopiperidine-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (40) 1-. { 1- [1- (3-Acetylaminopyrrolidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (41) hydrochloride of 1-. { 5-cyclopropyl-1- [1- (3-dimethylaminopyrrolidin-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (42) hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (1-methyl-piperidin-4-yl-carbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (43) 1-. { 1- [1- (1-Acetylpiperidin-4-yl-carbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (44) 1-. { 5-Cyclopropyl-1- [1- (4-oxopiperidine-1-carbonyl) piperidin-4-yl) - 1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (45) 1 -. { 1 - [1 - (3-Acetylaminoazeidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (46) 1 -. { 5-cyclopropyl-1 - [1- (3-oxopyrrolidin-1-carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (47) 1-. { 5-Cyclopropyl-1- [1- (2,2,2-l-trifluoroethylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (48) 1-. { 5-Cyclopropyl-1- [1- (3,3,4,4-terephluoropyrrolidine-1-carbonyl) -piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (49) 1- (5-cyclopropyl-1- { 1 - [(S) -1-hydroxymethyl-2-methylpropyl-carbamoyl] piperidin- 4-yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-l-trifluoromethyl-phenyl)] -pyrrolidine, (50) 1- (1- { 1 - [(S) -1-benzyl-2-hydroxy-ylcarbamoyl] piperidin-4-yl.} - 5-cyclopropyl-1 H-pyrazole-4-carbonyl) - [(S) -3- (2-l-trifluoromethyl-phenyl)] pyrrolidine(51) 1- (5-cyclopropyl-1- { 1 - [(S) -2-hydroxy-1-phenylethylcarbamoyl] -piperidin-4-yl}. -1H-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (52) 1- (5-cyclopropyl-1 -. {1 - [(S) -1-hydroxymethyl-3-methylbutyl-carbamoyl] piperidin-4 -yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-l-trifluoromethyl-phenyl)] -pyrrolidine, (53) 1-. { 5-Cyclopropyl-1- [1- (2-hydroxyphenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (54) 1-. { 5-Cyclopropyl-1- [1- (1-hydroxymethylcyclopenylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (55) 1- [1- (1-Benzenesulfonylaminocarbonylpiperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl] - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (56) 1- [5-Cyclopropyl-1- (1-melansulfonylaminocarbonylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (57) 1- [ 5-Cyclopropyl-1- (1-meioxycarbonylpiperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine, (58) 1-. { 5-Cyclopropyl-1- [1- (2-hydroxyethoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (59) hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (2-dimethylaminoethoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-lrifluoromethyl-phenyl)] pyrrolidine, (60) hydrochloride of 1 -. { 5-cyclopropyl-1 - [1 - (2-piperidin-1-yl-ethoxycarbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] - pyrrolidine, (61) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (piperidin-4-yl-oxycarbonyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (62) hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (1-methyl-piperidin-4-yl-oxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-irifluoromethylphenyl)] - pyrrolidine, (63) 1 -. { 1 - [1 - (1-Acetylpiperidin-4-yl-oxycarbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (64) 1- [1- (1-cyclopropancarbonylpiperidin-4-yl) -5-cyclopropyl-1 H- pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (65) 1-. { 5-Cyclopropyl-1- [1- (2-hydroxyacelyl) p.peridin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (66) 1- (5-cyclopropyl-1- { 1- [1- (4-fluorophenyl) cyclopropanecarbonyl] -piperidin-4-yl} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine) (67) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (2-dimethylamino-acetyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (68) 1-. { 1- [1- (2-Acetylaminoacetyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (69) 1 -. { 5-cyclopropyl-1 - [1 - (1-methylcyclopropancarbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (70) 1-. { 1- [1- (2-Acetylamino-2-methylpropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (71) 1 - (1 -. {1 - [(S) -2-acetylaminopropionyl] pipehdin-4-yl.} - 5-cyclopropyl -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (72) 1- (1- { 1 - [(S) -2-acetylamino-3- meilynylpyryl] piperidin-4-yl.} - 5-cyclopropyl-1 H-pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine, (73) 1-. { 5-Cyclopropyl-1- [1- (3,3,3-if-trifluoropropionyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (74) 1- (5-cyclopropyl-1- { 1 - [(S) -5-oxopyrrolidin-2-carbonyl] piperidin- 4- Fig. H -1-pyrazole-4-carbonyl) - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (75) 1-. { 1- [1- (3-Arylaminopropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (76) 1-. { 5-Cyclopropyl-1- [1- (3-hydroxy-2,2-dimethypropyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (77) 1- hydrochloride. { 1- [1- (2-aminoacetyl) piperidin-4-yl] -5-cyclopropyl-1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)) pyrrolidine, (78) 1-. { 5-Cyclopropyl-1- [1- (1-hydroxymethylcyclopropancarbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (79) 1- hydrochloride. { 1- [1- (2-amino-2-methylpropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (80) 1-. { 5-Cyclopropyl-1- [1- (4-hydroxybuliryl) piperidin-4-yl) -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (81) 1- (5-cyclopropyl-1- { 1 - [(S) -pyrrolidine-2-carbonyl] piperidin-4-hydrochloride il.}. 1 H -pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (82) 1- (5-cyclopropyl-1. (S) -1-Melylpyrrolidin-2-carbonyl] piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-l-trifluoromethyl-phenyl)] -pyrrolidine, (83) 1- hydrochloride. { 1- [1- (3-aminopropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (84) 1- (1. {1 - [(S) -2-amino-3-meityylbutyryl]] pipepdin-4-yl hydrochloride} - 5-cyclopropyl-1H-pyrazole-4-carbonyl) - [(S) -3- (2-l-trifluoromethyl-phenyl)] pyrrolidine, (85) -hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (2-methylaminoacetyl) -piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (86) 1- hydrochloride. { 5-cyclopropyl-1- [1- (piperidine-4-carbonyl) - piperidin-4-yl] -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (87) 1-. { 5-Cyclopropyl-1- [1- (2-isobuyrylaminoacetyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (88) 1-. { 1- [1- (2-cyclopropanecarbonylaminoacetyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (89) 1- (1-. {1 - [(S) -1-acetylpyrrolidine-2-carbonyl] piperidin-4-yl}. -5-cyclopropyl-1 H-pyrazole-4-carbonyl) - [(S) -3- (2-irifluoromethyl-phenyl)] pyrrolidine, (90) 1-. { 5-Cyclopropyl-1- [1- (2-methanesulfonylaminoacetyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (91) 1-. { 1- [1- (1-Acelylpiperidine-4-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)) pyrrolidine, (92) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (1-methyl-piperidin-4-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] - pyrrolidine, (93) 1-. { 1- [1- (3-carbamoylpropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (94) 1- [1- (1-carbamoylmethylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] hydrochloride] - [(S) -3- (2-irifluoromethylphenyl)] pyrrolidine, (95) 1- [5-cyclopropyl-1- (1-methylcarbamoylmethylpiperidin-4-yl) -1 H-pyrazole-4-carbonyl hydrochloride] - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (96) 1- hydrochloride. { 1- [1- (1-carbamoyl-1-methylethyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (97) 1- hydrochloride. { 1- [1- (2-carbamoylyl) piperidin-4-yl] -5- cyclopropyl-1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (98) 1- [5-cyclopropyl-1- (1-cyclopropylmethylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] hydrochloride] [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (99) 1- [5-cyclopropyl-1- (1-cyclopropylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [] hydrochloride (S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (100) 1- [5-cyclopropyl-1- (1-dimethylcarbamoylmethyl-piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [] hydrochloride (S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (101) 1- [1- (1-carboxymethylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [hydrochloride S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (102) 1- [1- (1-carboxy-piperidin-4-yl) -5-cyclopropyl-1H-pyrazole-4-carbonyl] - [(S) hydrochloride ) -3- (2-trifluoromethylphenyl)] pyrrolidine, (103) hydrochloride of 1-. { 1- [1- (1-carbamoylyl) piperidin-4-yl] -5-cyclopropyl-1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (104) 1- hydrochloride. { 1- [1- (2-carboxy-2-methylpropyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (105) 1- hydrochloride. { 1- [1- (2-carbamoyl-2-methylpropyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (106) 1- hydrochloride. { 1- [1- (1-carbamoylcyclopropylmethyl) pipe? Din-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (107) 1- (5-Cyclopropyl-M-. {1- [1- (2-hydroxy-ethylcarbamoyl) -cyclopropylmethyl] -piperidin-4-yl hydrochloride] .}. -1 H -pyrazole-4-carbonyl) - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (108) 1- [5-cyclopropyl-1- (1-ylfluoromenessulfonylpiperidin-4-yl) -1 HOUR- pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)) pyrrolidine, (109) 1-. { 5-cyclopropyl-1- [1- (2,2,2-trifluoroenesulfonyl) piperidin-4-yl) -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (110) 1-. { 1- [1- (1-cyanoiminoethyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (111) 1- (1-. {1- [cyanoimino (methylamino) meily] piperidin-4-yl}. -5-cyclopropyl-1 H-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (112) 1-. { 1- [1- (N-cyanocarbamimidoyl) piperidin-4-yl] -5-cyclopropyl-1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (113) 4- (4-. {5-cyclopropyl-4- [3- (2-ylfluoromethyl-phenyl) -pyrrolidin-1-carbonyl] -pyrazol- 1-yl.] Piperidin-1-yl) benzoic acid, (114) 3- (4-. {5-cyclopropyl-4- [3- (2-trifluoromethyl-phenyl) -pyrrolidin-1-carbonyl] -pyrazol-1- il.}. piperidin-1-yl) benzoic acid(115) 5- (4-. {5-Cyclopropyl-4- [3- (2-l-trifluoromethylphenyl) pyrrolidine-1-carbonyl] pyrazol-1-yl} piperidin-1-yl) thiophen-2 carboxylic acid, (116) 2- (4-. {5-cyclopropyl-4- [3- (2-ylfluoromethyl-phenyl) -pyrrolidin-1-carbonyl] pyrazol-1-yl} -piperidin-1-yl) -iazole -4-carboxylic, (117) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (5-methyl-4 H- [1, 2,4] triazol-3-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (118) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (5-cyclopropyl-4H- [1, 2,4] -yriazol-3-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (119) 1- hydrochloride. { 5-cyclopropyl-1- [1- (5-hydroxymethyl-4H- [1, 2,4] iriazol-3-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (120) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (5-ylfluoromethyl-4H- [1, 2,4] iriazol-3-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (121) 1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(R) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (122) 1-. { 5-Cyclopropyl-1- [1- (1-methylcyclopropylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(R) -3- (2-fluorifomomethylphenyl)] pyrrolidine, (123) 1-. { 5-Cyclopropyl-1- [1- (1-isopropylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(R) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (124) 1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (125) 1-. { 5-Cyclopropyl-1- [1- (1-isopropylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (126) 1-. { 5-cyclopropyl-1- [1- (1-meitylcyclopropylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (127) (-) - 3- (4-fluorophenyl) -3-hydroxymethyl-1- hydrochloride. { 5- (1-Methylcyclopropyl) -1- [1- (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -pyrrolidine, (128) (+) - 3- (4-fluorophenyl) -3-hydroxymeryl-1- hydrochloride. { 5- (1-meitylcyclopropyl) -1- [1- (pihmidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -pyrrolidine, (129) 1- [5-cyclopropyl-1- (1-pyrazin-2-yl-piperidin-4-yl) -1 H-pyrazole-4-carbonyl] - [(S) -3- (2- trifluoromethylphenyl)] pyrrolidine, (130) 1- [1- (trans-4-carbamoylcyclohexyl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (11) 1- [5-cyclopropyl-1- (rans-4-ureidocyclohexyl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (132) 1 -. { 5-cyclopropyl-1- [trans -4- (1 H-leyrazol-5-yl) cyclohexyl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (133) 1-. { 5- (1-Methylcyclopropyl) -1- [1- (4-trifluoromethylphenylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (pirridin-3-yl) pyrrolidine, (134) 1-. { 1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl) -5- (1-meloxycyclopropyl) -1 H -pyrazole-4-carbonyl} -3- (2-trifluoromethylphenyl) pyrrolidine, (135) 1-. { 1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -5- (1-methylcyclopropyl) -1H-pyrazole-4-carbonyl} 3-phenyl-3-trifluoromethyl-pyrrolidine, (136) 3- (2-chlorophenyl) -1-. { 5-cyclopropyl-1- [1- (2,4-difluorophenyl-carbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} pyrrolidine, (137) 3- (2-chloropyridin-3-yl) -1-. { 5-Cyclopropyl-1- [1- (2-fluorophenyl-carbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} pyrrolidine, (138) 1-. { 1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -5- (2, 2,3,3-tetramethylcyclopropyl) -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (139) 1-. { 5-Cyclohexyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (140) 1-. { 5-Cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] - 1 H-pyrazole-4-carbonyl} -3- (2-trifluoromethioxyphenyl) pyrrolidine, (141) 1-. { 5-Cyclopropyl-1- [1- (4-trifluoromethylphenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (2-fluorifomethylphenyl) pyrrolidine, (142) 1- (5-cyclopropyl-1-. {1 - [((S) -1-carboxy-2-meitylpropyl) -methylcarbamoyl] piperidin-4-yl} -1 H-pyrazole-4-carbonyl) -3- (2-ylfluoromethylphenyl) -pyrrolidine, (143) 1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3-meioxy-3- (2-ylfluoromethylphenyl) pyrrolidine, (144) 1-. { 1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -5- (1-hydroxymethylcyclopropyl) -1 H-pyrazole-4-carbonyl} -3- (2-nifluoromethylphenyl) pyrrolidine, (145) 1-. { 5-Cyclopropyl-1- [1- (Iiazol-2-ylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (2-l-trifluoromethylphenyl) pyrrolidine, (146) 1-. { 1- [1- (isopropoxycarbamoyl) piperidin-4-yl] -5- (1-methyl-cyclopropyl) -1 H-pyrazole-4-carbonyl} -3- (2-fluorifomethylphenyl) pyrrolidine, (147) 1-. { 5-Cyclopropyl-1- [1- (4-fluorobenzylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine, (148) 1-. { 1- [1- (2,3-dihydroindol-1-carbonyl) piperidin-4-yl] -5- (1-methylcyclopropyl) -1H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (149) 1-. { 1- [1- (2,3-dihydro [1,4] oxazin-4-carbonyl) piperidin-4-yl] -5- (1-methyl-cyclopropyl) -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (150) 1-. { 5-Cyclopropyl-1- [1- (2,6-dichloropyridin-3-ylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (2-l-trifluoromethylphenyl) pyrrolidine, (151) 1-. { 5- (1-meitylcyclopropyl) -1- [1- (2,3,4,5-letrahydrobenzo [b] - azepine-1-carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (152) Ethyl 4- (4-. {5-cyclopropyl-4- [3- (2-ylfluoromethyl-phenyl) pyrrolidin-1-carbonyl] pyrazol-1-yl} piperidin-1-yl) benzole, ( 153) 1- [1- (1-benzyloxycarbonyl-piperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] -3- (pyridin-3-yl) pyrrolidine, (154) 1-. { 1- [1- (3-carboxy-3-methyl-bulyryl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (2-trifluoromethylphenyl) pyrrolidine, (155) 1-. { 5-cyclopropyl-1- [1- (2-phenoxyacetyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (156) 1 -. { 1 - [1 - (3-chlorobenzoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (157) 1 -. { 1 - [1 - (2-Chlorobenzoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (158) 1- [5-cyclopropyl-1- (1-oxalylpiperidin-4-yl) -1H-pyrazole-4-carbonyl] -3- (2-trifluoromethylphenyl) pyrrolidine, (159) 1-. { 1- [1- (4-chlorobenzoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (160) 1- (5-cyclopropyl-1- {1- [2- (4-fluorophenyl) acetyl] piperidin-4-yl} -1 H -pyrazol-4-carbonyl) -3- (pyridin-3-yl) pyrrolidine, (161) 1-. { 5-Cyclopropyl-1- [1- (3-l-trifluoromethylbenzoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (162) 1-. { 5-Cyclopropyl-1- [1- (3-meioxybenzoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (163) 1- hydrochloride. { 1- [1- (4-fluorobenzyl) piperidin-4-yl] -5- (1-methylcyclopropyl) -1 H-pyrazole-4-carbonyl} -3- (2-trifluoromethylphenyl) pyrrolidine, (164) 1- [1- (1-benzenesulfonyl-piperidin-4-yl) -5-cyclopropy! -1 H -pyrazole-4-carbonyl] -3- (pyridine- 3-yl) pyrrolidine, (165) 1-. { 1- [1- (4-carbamoylphenyl) piperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine, (166) 1-. { 5-cyclopropyl-1- [1- (4-hydroxymethylphenyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine, (167) 1-. { 1- [1- (5-carbamoyl-pyridin-2-yl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (2-if-trifluoromethylphenyl) pyrrolidine, (168) 1 -. { 1 - [1 - (4-aminophenyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine, (169) 1- (5-cyclopropyl-1- {1- [4- (2-oxooxazolidin-3-yl) phenyl] piperidin-4-yl}. 1 H-pyrazole-4-carbonyl) -3- (2-ylfluoromethylphenyl) pyrrolidine, (170) 1- (5-cyclopropyl-1 - { 1 - [4- (3-meioxyureido) phenyl] piperidin-4- 1: 1 H-pyrazole-4-carbonyl) -3- (2-ylfluoromethylphenyl) pyrrolidine, (171) 1-. { 5-Cyclopropyl-1- [1- (4-melansulfonylaminophenyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine, (172) 1- [1- (1-eioxycarbamoylpipehdin-4-yl) -5- (1-methylcyclopropyl) -1 H -pyrazole-4-carbonyl] -3- (2 -rifluoromethylphenyl) pyrrolidine, (173) 1- [1- (5-chloropyridin-2-yl) azetidin-3-yl] -5-cyclopropyl-1 H -pyrazole-4-carbonyl] -3- (2-ylfluoromethylphenyl) pyrrolidine, (174) 1-. { 1- [1- (5-chloro-pihdin-2-yl) piperdin-4-yl] -5- (1- meilyylcyclopropyl) -1H-pyrazole-4-carbonyl} -3-meioxymethyl-3-phenylpyrrolidine, (175) 1-. { 1- [1- (5-Cyano-pyridin-2-yl) piperidin-4-yl] -5-cyclopropyl-1H-pyrazole-4-carbonyl} -3- (2-fluorifomethylphenyl) pyrrolidine, (176) 3- (2-acetoxyethyl) -3- (4-fluorophenyl) -1- hydrochloride. { 5- (1-Melylcyclopropyl) -1- [1- (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -pyrrolidine, (177) hydrochloride. { (3S *, 4R *) - 3-meilyl-1-. { 5- (1-meitylcyclopropyl) -1- [1- (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -4-phenylpyrrolidine, (178) 6- (4-. {5-cyclopropyl-4- [3- (2-l-trifluoromethyl-phenyl) -pyrrolidin-1 -carbonyl] -pyrazol-1-yl}. P -peridin-1- il) nicoíinato de meíilo, (179) 2-. { 1- [5- (1-Meilyylcyclopropyl) -1- (1-pyrimidin-2-yl-piperidin-4-yl) -1 H -pyrazole-4-carbonyl] pyrrolidin-3-yl} Melyl benzoate, (180) 3- (2-hydroxymethylphenyl) -1- hydrochloride. { 5- (1-Methylcyclopropyl) -1- [1- (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -pyrrolidine, (181) 1- [5-cyclopropyl-1- (1-pyridin-2-yl-piperidin-4-yl) -1 H -pyrazole-4-carbonyl] -3-hydroxy-3- (pyridin- 3-yl) pyrrolidine, (182) 1-. { 1- [1- (4-acetylaminophenyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (2-irifluoromethylphenyl) pyrrolidine, (183) 4- (4-. {5-cyclopropyl-4- [3- (2-ylfluoromethyl-phenyl) -pyrrolidin-1-carbonyl] pyrazol-1-yl}. Piperidin -1-yl) -3-fluorobenzoaio sodium, (184) 3- (2-cyanophenyl) -1-. { 5-Cyclopropyl-1- [1- (2-fluorophenyl-carbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} pyrrolidine, (185) 3-hydroxymethyl-1- hydrochloride. { 1- [1- (4-meioxypyrimidin-2-yl) piperidin-4-yl] -5- (1-meilyylcyclopropyl) -1H-pyrazole-4-carbonyl} -3-phenylpyrrolidine, (186) 3- (3,5-difluorophenyl) -3-hydroxymethyl-1- hydrochloride. { 5- (1-meitylcyclopropyl) -1- [1- (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -pyrrolidine, (187) 1-. { 1- [1- (3-Chloro-pyridin-2-yl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (188) 1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (thiazol-2-yl) pyrrolidine, (189) (S) -2 - [(trans-4. {5-cyclopropyl-4- [3- (2-trifluoromethylphenyl) -pyrrolidin-1} carbonyl] -pyrazol-1-yl.}. -cyclohexancarbonyl) -methylamino] -3-methylbuiiric, (190) 1-. { 5- (1-meitylcyclopropyl) -1- [lrans-4- (2-fluorophenylcarbamoyl) -cyclohexyl] -1H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine, and (191) cis-4 acid. { 5- (1-Meyylcyclopropyl) -4- [3- (2-l-trifluoromethylphenyl) -pyrrolidine-1-carbonyl] -pyrazol-1-yl) -cyclohexanecarboxylic acid. 13. A pharmaceutical composition comprising a compound according to any of 1 to 12 indicated above or a salt thereof. 14. An 11 ßHSD1 inhibitor comprising a compound according to any of 1 to 12 indicated above or a salt thereof. 15. An agency for the treatment or prophylaxis of a pathology which comprises a glucocorticoid comprising a compound according to any one of the 1 to 12 indicated precedeniemenie or a salt thereof. 16. The agenle of 15 indicated above, wherein the pathology involving the glucocorticoid is (1) a metabolic disease including diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a metabolic syndrome , (3) a faial vascular event that includes cardiac infarction or cerebral stroke, (4) a hyperorexia, (5) a neurodisfunctional disease including dysgenesis, neurodegenerative disease, emotional disorders, schizophrenia or esystimus of the apex, (6) a disease associated with the decreased immunity function, (7) glaucoma, or (8) osteoporosis. 17. A method for inhibiting 11βHSD1 comprising administering a pharmaceutically effective amount of a compound according to any of 1 to 12 above or a salt thereof. 18. A method for bringing or preventing a pathology involving glucocorticoid which comprises administering a pharmaceutically effective of a compound according to any of 1 to 12 indicated above or a salt thereof. 19. The method of 18 indicated above, wherein the pathology involving the glucocorticoid is (1) a meiabolic disease that includes diabeles, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a megalolic syndrome , (3) a fatal vascular event that includes cardiac infarction or cerebral stroke, (4) a hyperorexia, (5) a neurodisfunctional disease that includes dysgenesis, neurodegenerative disease, emotional disorders, schizophrenia or appetite stimulation, (6) a disease associated with the function of diminished immunity, (7) glaucoma, or (8) osieoporosis. 20. The use of a compound according to any one of 1 to 12 indicated above or a salt thereof for the production of an inhibitor of 11βHSD1. 21. The use of a compound according to any of 1 to 12 indicated above or a salt thereof for the production of a agent for the treatment or prophylaxis of a pathology involving glucocorticoid. 22. The use of the above indicated 21, where the pathology involving the glucocorticoid is (1) a diabolic disease that includes diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a metabolic syndrome , (3) a faíal vascular event that includes cardiac infarction or cerebral apoplexy, (4) hypererexia, (5) a neurodisfunctional disease that includes dysgenesis, neurodegenerative disease, emotional disorders, schizophrenia or apex stimuli, (6) a disease associated with impaired immunity function, (7) glaucoma, or (8) osteoporosis. 23. A commercial package comprising a written material stating that the above-described pharmaceutical composition of 13 can or should be used for the treatment or prophylaxis of a disease selected from (1) a metabolic disease that includes diabetes, resis- tance to insulin, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a meiabolic syndrome, (3) a fatal vascular event that includes cardiac infarction or cerebral stroke, (4) hyperorexia, (5) a neurodisfunctional disease that includes dysgenesis, neurodegenerative disease, emotional disorders, schizophrenia or appetite stimulation, (6) a disease associated with decreased immunity function, (7) glaucoma, or (8) osteoporosis. 24. The pharmaceutical composition of the 13 indicated preceded by the use in combination with 1 to 3 agents selected from the following (1) to (5): (1) an agent for irritation or prophylaxis of hyperlipidemia, (2) an agent for the Iralamienlo or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 25. The inhibitor of 11 ßHSD1 indicated above in 14, a be used in combination with 1 to 3 agencies selected from the following (1) to (5): (1) a agent for the traumatization or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) a agent for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 26. The indicated agent preceded by 15 or 16, which will be used in combination with 1 to 3 agents selected from the following (1) to (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 27. The method of the preceding indicated 17, which comprises also administering 1 to 3 agents selected from the following (1) to (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) a agent for the treatment or prophylaxis of obesity, (3) an agent for the dialysis or prophylaxis of diabei, (4) an agent for the treatment or prophylaxis of complications diabetics, (5) an agent for the irradiation or prophylaxis of hypertension. 28. A pharmaceutical agent comprising 1 to 3 agents selected from the following (1) to (5) and a compound according to any of 1 to 12 indicated above or a salt thereof in combination: (1) an agent for the Iralamienlo or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the traumatization or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 29. A method for treating or preventing a pathology involving the glucocorticoid of 18 or 19 indicated above, which further comprises administering from 1 to 3 agents selected from the following (1) to (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabebes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 30. The use of the 20 indicated above, which will be combined with the use of 1 to 3 agents selected from the following (1) a (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the irradiation or prophylaxis of obesity, (3) an agent for the dialysis or prophylaxis of diabei, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 31. The use of 21 or 22 indicated above, which will be combined with the use of 1 to 3 agents selected from the following (1) a (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the tralación or prophylaxis of diabetic complications, (5) an agent for the tralación or prophylaxis of hypertension. 32. The pharmaceutical composition of the aforementioned 13 which is used to suppress the increase of the level of glucocorticoid in the blood by use in combination with a pharmaceutical agent that raises the level of glucocorticoid in the blood. 33. The 11βHSD1 inhibitor of 14 indicated above that is used to suppress the increase in the glucocorticoid level of the Blood by use of a combination with a pharmaceutical agent raises the level of glucocorticoid in the blood. 34. The method of 17 indicated above, which further comprises administering a pharmaceutical agent that raises the level of glucocorticoid in the blood. 35. The use of the above-indicated 21 to suppress the increase in blood glucocorticoid level using a combination with a pharmaceutical agent that raises the level of glucocorticoid in the blood. 36. A method for suppressing the increase in blood glucocorticoid level comprising administering a pharmaceutical agent that raises the level of glucocorticoid in the blood and the inhibitor of 11 ßHSD1 of 14 indicated above. 37. Dimethyl 2 - [(S) -2-nylro-1- (2-yltrluoromethylphenyl) ethyl] malonaiole. 38. Methyl (S) -2-oxo-4- (2-trifluoromethylphenyl) pyrrolidin-3-carboxylate. 39. (S) -4- (2-trifluoromethylphenyl) pyrrolidin-2-one. 40. (S) -3- (2-trifluoromethylphenyl) pyrrolidine or a salt thereof. 41. A method for producing dimellyl 2 - [(S) -2-nylro-1- (2-yltrluoromethylphenyl) elyl] malonation comprising a step to react 1 - ((E) -2-niirovinyl) -2- trifluoromethylbenzene with malonation of dimethyls in the presence of 1- (3,5-bis-trifluoromethylphenyl) -3 - ((1S, 2S) -2- dimethylaminocyclohexyl) -iourea. 42. A method for producing (S) -2-oxo-4- (2-l-trifluoromethyl-phenyl) -pyrrolidin-3-carboxylic acid mephile which comprises an elapa for the reduction and closure of the ring of 2 - [(S) -2-nilro Dimethyl -1- (2-trifluoromethylphenyl) ethyl] malonate. 43. A method for producing (S) -4- (2-ylfluoromethylphenyl) pyrrolidin-2-one comprising a step for the hydrolysis and decarbonation of (S) -2-oxo-4- (2-ylfluoromethylphenyl) pyrrolidin-3. -carboxilaío of meíilo. 44. A method for producing a salt of (S) -3- (2-ylfluoromethylphenyl) pyrrolidine comprising a step for the reduction of (S) -4- (2-trifluoromethylphenyl) pyrrolidin-2-one and an elapa to remove the resulting compound with an acid to form a salt. The present invention also covers the following. 45. A compound represented by the following formula [2]: wherein -X- is (1) -N (R1) - wherein R1 is 1) a hydrogen atom, 2) -CONR5R6 wherein R5 and R6 are the same or different and each one is (a) a hydrogen atom, (b) an aryl group (said aryl group is optionally substituted with one or more identical or different substitutes selected from the following group: a) a hydroxyl group, b) a halogen atom, ) a carboxyl group, d) an alkyl group of d.6 (said C1-6 alkyl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxy group of d-6), and e) an alkoxy group of d-6), (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more C1-6 alkyl groups) equal or different (said alkyl group of d-6 is optionally susíiuuido with one or more equal or differentiated susíiuyeníes selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d-6)), (d) a C 1-6 alkyl group (said alkyl group of -6 is optionally substituted with one or more identical or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d. 6 (said alkyl group of d6 is optionally substituted with one or more same or different halogen atoms), d) -NR20R21 wherein R20 and R21 are the same or different and each is a hydrogen atom, an alkyl group of Cl- 6, or a -CO-alkyl group of C-? -6, or R20 and R21 optionally form, together with the nitrogen atom to which they are attached, a monocyclic hei-cyclic saturated group which contains nylrogen (said heterocyclic group is optionally substituted with one or more identical or different substituents selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) an oxo group, and (iv) a C-alkoxy group. ? .6), e) an alkoxy group of d.6, and f) a carboxyl group, (e) -S (= O) 2 -R9 wherein R9 is a group or aryl (said aryl group is optionally substituted with one or more identical or different substitutes selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of d.6 is optionally substituted with one or more equal or different halogen atoms), or an alkyl group of C? -6, or (f) a salified monocyclic heyerocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more equal or different substitutes selected from the following a) to c): a) an alkyl group of C? .6, b) a -CO-alkyl group of d-6, and c) an oxo group), or (g) R5 and R6 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group which it contains nickel, or a heyerocyclic group which is a fused ring of said heterocycle and a carbon ring (both mentioned heterocyclic groups are optionally subsided by one or more identical or different substituents selected from the following a) to i): a) an atom of halogen, b) a hydroxyl group, c) a C 1-6 alkyl group (said alkyl group of 6 is optionally substituted with one or more identical or different substituents selected from the following group: (i) an atomic alkogen, (ii) a hydroxyl group, and (iii) an alkoxyl group of Ci-e), d) a carboxyl group, e) a -CO-alkyl group of d-6, f) -CO-NR22R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of C? _6, or R22 and R23 optionally form, together with the nitrogen atom to which they are attached, a monocyclic monocyclic heyerocyclic group which contains nihinogen, g) an oxo group, h) -NR 24 R 25 wherein R 24 and R 25 are the same or different and each is a hydrogen atom , an alkyl group of C? -6, or a -CO-C6 alkyl group, or R24 and R25 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, and ) an alkoxy group of d.6), 3) -COOR10 wherein R10 is (a) an alkyl group of C-? -6 (said C1-6 alkyl group is optionally substituted with one or more of the same or different substitutes selected of the following a) to c): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or an alkyl group of d6, or R26 and R27 optionally form , June with the nitrogen atom to which they are attached, a mono heterocyclic group salicylic cyclic containing nihologen, and c) a C 1-6 alkoxy group), or (b) a nitrogen-containing saturated monocyclic heyerocyclic group (said heterocyclic group is optionally substituted with one or more equal or different substituents selected from the following a) to c): a) an alkyl group of d-6, b) a -CO-alkyl group of d.6, and c) an oxo group), 4) -COR11 wherein R11 is (a) an alkyl group of C6.6 (said alkyl group of C-? 6 is optionally subsumed with one or more identical or different subscripts selected from the following a) to g): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of d-6, a -CO-C6 alkyl group, a group -CO-cycloalkyl, or a group -S (= O) 2-C-6 alkyl, or R28 and R29 optionally form, with the nylrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, ) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R30 and R31 optionally form, June with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nylrogen, e) an alkoxy group of d-6, f) an aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following group: (i) an halogen, (ii) a hydroxyl group, (iii) an alkoxy group of d.6, and (iv) an alkyl group of C1.6 (said g alkyl radical of d.6 is optionally substituted with one or more halogen atoms or different)), and g) a carboxyl group), (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group) is optionally substituted with one or more identical or different substrates selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of d-6) optionally substituted with one or more same or different halogen atoms), and b) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more identical or differentiated substances selected from the following group: ) a hydroxyl group, and (ii) an alkoxy group of C? -6)), or (c) a monocyclic monocyclic heyerocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more identical or different subsystems selected from follow ienis a) to c): a) an alkyl group of C? .6 > b) a -CO-C 1-6 alkyl group, and c) an oxo group), 5) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more same or different substituents selected from the following (a) to (d): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different ones -CO-NR32R33 wherein R32 and R33 are the same or different and each is a hydrogen atom, an alkyl group of d-6 (said alkyl group of C6-6 is optionally substituted with one or more identical or different substitutes selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d-β ), or R32 and R33 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heyerocyclic group containing niinogen), (c) -CO-NR3 R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R34 and R35 optionally form, together with the niologen atom to which they are bonded, a monocyclic salicyclic nitrogen-containing heyerocyclic group, and (d) an aryl group ( said aryl group is optionally subsituted with one or more identical or different substitutes selected from the following group: a) a halogen atom, and b) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms)) ), 6) a cycloalkyl group, 7) -S (= O) 2 -R12 wherein R12 is an alkyl group of d-6 (said alkyl group of d.6 is optionally substituted with one or more same or different halogen atoms) ), or an aryl group (said aryl group is optionally substituted with one or more identical or different substitutes selected from the following group: a) a halogen atom, and b) an alkyl group of C6. (said alkyl group of d-6 is optionally substituted with one or more identical halogen atoms) or different)), 8) -C (= NCN) -R13 wherein R13 is an alkyl group of d_6, 9) -C (= NCN) NR14R15 wherein R14 and R15 are the same or different and each is an hydrogen, or an alkyl group of C? -6, or R14 and R15 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, 10) an aryl group (said aryl group is optionally Substituted with one or more identical or different substrates selected from the following (a) to (f): (a) a carboxyl group, (b) a halogen atom, (c) an alkyl group of C? _6 (said alkyl group of -6 is optionally substituted with one or more same or different substituents selected of the following group: a) a hydroxyl group, b) a halogen atom, and c) an alkoxy group of d.6), (d) -NR38R39 wherein R38 and R39 are the same or different and each is an hydrogen, an alkyl group of d-6, a -CO-alkyl group of C-? -6, -CO-NR40R41 wherein R40 and R41 are the same or different and each is a hydrogen atom, an alkyl group of C ? .6, or an alkoxy group of d. 6, or R40 and R41 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, or -S (= O) 2 -R42 wherein R42 is an alkyl group of d.6), or R38 and R39 optionally form, together with the nihilogen atom to which they are united, a saturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally susiiuuid with one or more oxo groups), (e) -CO-NR 3R44 wherein R43 and R44 are the same or different and each is an hydrogen, or an alkyl group of C1.6, or R43 and R44 optionally form, together with the nitrogen atom to which they are bonded, a saturated monocyclic heterocyclic group containing niinogen, and (f) a -COO-alkyl group of d .6), or 11) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more equal or different substituents selected from the following (a) to (g): (a) ) a carboxyl group, (b) a group a 6-alkyl (said alkyl group of 6 is optionally substituted with one or more same or different substituents selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) an alkoxyl group of d.6), (c) a cycloalkyl group, (d) a halogen atom, (e) -CO-NR45R46 wherein R45 and R46 are the same or different and each is a hydrogen atom, or an alkyl group of C6.6 or R45 and R46 optionally form, together with the nitrogen atom to which they are attached; bound, a saturated monocyclic nitrogen-containing heterocyclic group, (f) a -COO-C-6 alkyl group, and (g) a cyano group), or (2) -C (R7R8) - wherein R7 and R8 they are the same or different and each is 1) a hydrogen atom, 2) -NR16R17 wherein R16 and R17 are the same or different and each is a hydrogen atom, an alkyl group of C? _6, or -CO-NR36R37 wherein R36 and R37 are the same or different and each is a hydrogen atom, or an alkyl group of C-? 6, or R36 and R37 optionally form, with the nitrogen atom to which they are attached, a heterocyclic group saturated monocyclic nitrogen-containing, or R16 and R17 optionally form, together with the niologen atom to which they are bonded, a saturated monocyclic helerocyclic group containing nitrogen, 3) -CONR18R19 wherein R18 and R19 are the same or different and each is a hydrogen atom, an alkyl group of d.6 (said C? -6 alkyl group is optionally susíiuuido with one or more groups carboxyl), or an aryl group (said aryl group is optionally susliuid with one or more identical or different subscripts selected from the following group: (a) a halogen atom, and (b) an alkyl group of d6 (said alkyl group of d6) is optionally substituted with one or more halogen atoms the same or different), or R18 and R19 optionally form, together with the nihologen atom to which they are attached, a monocyclic monocyclic heyerocyclic group which contains nihologen, 4) an unsaturated monocyclic heterocyclic group of 5 members or 6 members, or 5) a carboxyl group; R2 is (1) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more identical or different C6-6 alkyl groups (said C6-6 alkyl group is optionally susiluted with one or more identical or different substituents selected from following group: (a) a hydroxyl group, and (b) an alkoxy group of d6)); and R3 and R4 are the same or different and each is (1) a hydrogen atom, (2) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more identical or differential substrates selected of the following group: 1) a halogen atom, 2) a hydroxyl group, and 3) an alkoxy group of d.6), (3) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following 1) to 6): 1) a halogen atom, 2) an alkyl group of d.sub.6 (said C.sub.6 alkyl group is optionally substituted with one or more identical or different substituents selected from the following group: (a) a halogen atom, (b) a hydroxyl group, and (c) an alkoxy group of d.6), 3) an alkoxy group of d-6 (said alkoxy group of d.6 is optionally susíiuuido with one or more same or different halogen atoms) ), 4) a carboxyl group, 5) a -COO-alkyl group of d.6, and 6) a cyano group, or (4) a 5-membered or 6-membered unicylated monocyclic heyerocyclic group (said heterocyclic group) it is optionally substituted with one or more identical or different subsystems selected from the following group: 1) a halogen atom, and 2) a C1.6 alkyl group (said alkyl group of d-6 is optionally susíiluido with one or more halogen atoms). Equal or different)), or a salt thereof. 46. The compilation of the above indicated 45 which is represented by the following formula [2]: wherein -X- is (1) -N (R1) - wherein R1 is 1) a hydrogen atom, 2) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a hydrogen atom , (b) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) a group C.sub.1-6 alkyl (said C.sub.6 alkyl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) a group alkoxy of d.6), and e) an alkoxy group of C-? 6), (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different d6 alkyl groups (said alkyl group of d. 6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d-d)), (d) an alkyl group of C6.6 (said C6-6 alkyl group is optionally susiiuuid with one or more equal or different susligens selected from the following group: a) a hydroxyl group, b) a halogen atom, c) an aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 ( said alkyl group of d.6 is optionally substituted with one or more same or different halogen atoms)), d) -NR20R21 wherein R20 and R21 are the same or different and each is a hydrogen atom, an alkyl group of or a -CO-alkyl group of d.6, or R20 and R21 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nihologen (said heterocyclic group is optionally substituted with one or more substituents equal or different selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) an oxo group, and (iv) an alkoxy group of d.6), and e) an alkoxy group of d-6), (e) -S (= O) 2 -R9 wherein R9 is an aryl group (said aryl group) is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C? -6 (said alkyl group of C? _6 is optionally substituted with one or more same or different halogen atoms)), or a C? -6 alkyl group, or (f) a nitrogen-containing saturated monocyclic heterocyclic group (said helerocyclic group is optionally substituted with one or more substituents same or different selected from the following a) to c): a) an alkyl group of C? .6, b) a -CO-alkyl group of C? -6, and c) an oxo group), or (g) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said helerocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to i): a ) a halogen atom, b) a hydroxyl group, c ) a C 1-6 alkyl group (said alkyl group of -6 is optionally substituted with one or more equal or different subsides selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d-6) , d) a carboxyl group, e) a group -CO-C 1-6 alkyl, f) -CO-NR 22 R 23 wherein R 22 and R 23 are the same or different and each is a hydrogen atom, or an alkyl group of d 6, or R 22 and R 23 optionally they form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group which contains nihinogen, g) an oxo group, h) -NR24R25 wherein R24 and R25 are the same or different and each is a hydrogen atom , an alkyl group of C? -6, or a -CO-alkyl group of d.6, or R24 and R25 optionally form, together with the nitrogen atom to which they are attached, a monocyclic monocyclic saciracyclic group containing nitrogen, and i) an alkoxy group of d.6), 3) -COOR10 wherein R10 is, (a) a C1-6 alkyl group (said alkyl group of d.6 is optionally substituted with one or more identical or different substituents selected from the following a) to c): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or a group C.sub.6 alkyl, or R 26 and R 27 optionally form, together with the nylrogen atom to which they are attached, a saturated monocyclic helerocyclic group which contains nihinogen, and c) an alkoxy group of d.6), or (b) an saturated monocyclic helerocyclic group containing Ni-halogen (said heterocyclic group is optionally substituted with one or more identical or different subsites selected from the following a) to c): a) an alkyl group of d-6, b) a -CO-alkyl group of C? 6, and c) an oxo), 4) -COR11 group wherein R11 is, (a) an alkyl group of d-6 (said alkyl group of .6 is optionally susíiuuido with one or more identical or different subsystems selected from the following a) to e): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of d-6, a group - CO-C 1-6 alkyl, a -CO-cycloalkyl group, or a group -S (= O) 2-C 1-6 alkyl or R 28 and R 29 optionally form, June with the nitrogen atom to which they are attached , a salicy monocyclic heyerocyclic group containing nii-gen, d) -CO-NR30R31 where R30 and R31 are the same or different and each is a hydrogen atom, or a group C? -6 alkyl, or R30 and R31 optionally form, together with the niologen atom to which they are attached, a saturated monocyclic heterocyclic group which contains nihinogen, and e) an alkoxy group of d.6), (b) a group cycloalkyl (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) a C 1-6 alkyl group (said alkyl group of d 6 is optionally substituted with one or more same or different halogen atoms)), and b) a C 1-6 alkyl group (said C 1-6 alkyl group) is optionally substituted with one or more equal or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d.6)), or (c) a saturated monocyclic heterocyclic group containing nitrogen ( said heterocyclic group is optionally susliluted with one or more same or different substituents selected from the following a) to c): a) a C 1-6 alkyl group, b) a -CO-C 1-6 alkyl group, and c) a oxo group), 5) an alkyl group of d-6 (said alkyl group of -6 is optionally subsituted on one or more substitutes identical or different selected from the following (a) to (c): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different) -NR32R33 where R32 and R33 are the same or different and each is an atom of hydrogen, an alkyl group of C?-6 (said alkyl group of C -? _6 is optionally substituted with one or more identical or different amino acids selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d-ß), or R32 and R33 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen), and (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R34 and R35 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen), 6) a group cycloalkyl, 7) -S (= O) 2 -R12 wherein R12 is an alkyl group of C-? -6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms), 8) -C (= NCN) -R13 wherein R13 is an alkyl group of de, 9) -C (= NCN) NR14R15 wherein R14 and R15 are equal or different and each is a hydrogen atom, or a C 1-6 alkyl group, or R 14 and R 15 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic helerocyclic group containing nitrogen, 10) an aryl group (said aryl group is optionally substituted with one or more equal or differential substitutes selected from the following (1) to (3): (1) a halogen atom, (2) an alkyl group of d6 (said alkyl group of d-6 is optionally substituted with one or more halogen atoms the same or different), and (3) a carboxyl group), or 11) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more other or different substituents selected from the group consisting of the following (a) to (c): (a) a carboxyl group, (b) an alkyl group of d.6 (said alkyl group of d.6 is optionally substituted with one or more equal or different subsides selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) an alkoxyl group of d.6), and (c) a cycloalkyl group), or (2) -C (R7R8) - in where R7 and R8 are the same or different and each is 1) a hydrogen atom, 2) -NR16R17 wherein R16 and R17 are the same or different and each is a hydrogen atom, an alkyl group of d.6, or -CO-NR36R37 wherein R36 and R37 are the same or different and each is a hydrogen atom, or an alkyl group of C? .6, or R36 and R37 optionally they form, together with the nihorogen atom to which they are bound, a monocyclic heterocyclic group containing nitrogen, or R16 and R17 optionally form, with the nucleus of nihilogen to which they are attached, a group monocyclic salt-containing monocyclic ether, 3) -CONR18R19 wherein R18 and R19 are the same or different and each is a hydrogen atom, or a C1-6 alkyl group, or R18 and R19 optionally form, together with the nitrogen to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, or 4) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group; R 2 is (1) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more equal or different C 1-6 alkyl groups); and R3 and R4 are the same or different and each is (1) a hydrogen atom, (2) an alkyl group of d6 (said alkyl group of d.6 is optionally substituted with one or more identical or different substituents selected from the group following: (i) a hydroxyl group, and (ii) an alkoxy group of d-6), (3) an aryl group (said aryl group is optionally substituted with one or more identical or different substituents selected from the following 1) and 2): 1) a halogen atom, and 2) an alkyl group of d.6 (said alkyl group of d.6 is optionally substituted with one or more identical halogen atoms or different)), or (4) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group, or a salt thereof. 47. The compound of 45 or 46 indicated above, wherein -X- is -C (R7R8) - wherein R7 and R8 is the same as defined in 46 above, or a salt thereof. 48. The compound according to any of 45 to 47 indicated above, wherein R8 is 1) -NR16R17 wherein R16 and R17 are the same or different and each is a hydrogen moiety, or an alkyl group of d-6, or R16 and R17 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, 2) -CONR18R19 wherein R18 and R19 are the same or different and each is a hydrogen atom, or an alkyl group of C1.6, or R18 and R19 optionally form, together with the niologen atom to which they are attached, a monocyclic heterocyclic group saturated with nihologen, or 3) a monocyclic monocyclic, unsaturated group of 5 or 6 members. members), or a salt thereof. 49. The compound of 45 or 46 indicated above, where -X- is -N (R1) - where R1 is equal to that defined in 46) indicated above, or a salt thereof. 50. The compound according to any of 45, 46 and 49 indicated above, wherein R1 is 1) a hydrogen atom, 2) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a hydrogen atom , (b) an aryl group (said aryl group is substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) an alkyl group of C? .6 (said C1-6 alkyl group is optionally substituted with one or more identical or different substituents selected from the following group: ) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxy group of C? -6), and e) an alkoxy group of d6), (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more identical or different alkyl groups of d.sub.6 (said alkyl group of d-6 is optionally substituted with one or more identical or different subsides selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group from (d) an alkyl group of C? .6 (said alkyl group of -6 is substituted with one or more same or different substituents selected from following group: a) a hydroxyl group, b) a halogen atom, c) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) ) a halogen atom, and (2) an alkyl group of C-? _ 6 (said alkyl group of C? _6 is optionally substituted with one or more same or different halogen atoms)), d) -NR20R21 wherein R20 and R21 they are the same or different and each is a hydrogen atom, an alkyl group of d-6, or a -CO-alkyl group of d-6, or R20 and R21 optionally form, June with the nitrogen atom to which they are attached , a saturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more equal or different substituents selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group , (iii) an oxo group, and (iv) an alkoxy group of C? -6), and e) an alkoxy group e d.6), (e) -S (= O) 2 -R9 wherein R9 is an aryl group (said aryl group is optionally subsituted with one or more identical or different substitutes selected from the following (1) and (2) ): (1) a halogen atom, and (2) a alkyl group of C? _6 (said alkyl group of C? _6 is optionally susliluido with one or more same or different halogen atoms)), or an alkyl group of (f) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more identical or different substitutes selected from the following a) to c): a) an alkyl group of d6, b) a -CO group -alkyl of d_6, and c) an oxo group), or (g) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nylrogen (said helerocyclic group is optionally substituted with one or more equal or different substituents selected from the following a) to i): a) a halogen atom, b) a hydroxyl group, c) an alkyl group of d6 (said C-? 6 alkyl group is optionally substituted with one or more identical or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d.6), d) a carboxyl group, e) a -CO-alkyl group of -β, f) -CO-NR22R23 where R22 and R23 are i different or different each is a hydrogen atom, or an alkyl group of C? -6, or R22 and R23 optionally form, together with the nihologen atom to which they are attached, a monocyclic monocyclic heyerocyclic group containing nylrogen, g) an oxo group , h) -NR24R25 wherein R24 and R25 are the same or different and each is a hydrogen atom, a C1-6 alkyl group, or a -CO-C6-alkyl group, or R24 and R25 optionally form , together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, and i) an alkoxy group of d-6) (with the proviso that R5 and R6 are not simultaneously hydrogen atoms), 3) - COOR10 wherein R10 is (a) a C1-6 alkyl group (said C6 alkyl group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom no, or a C 1-6 alkyl group, or R 26 and R 27 optionally form, with the nitrogen atom to which they are attached, a monocyclic heterocyclic group containing nitrogen, and c) an alkoxy group of d-β), or (b) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more similar or differentiated selected from the following a) to c): a) an alkyl group of d-6, b) a -CO-alkyl group of d-6, and c) an oxo group), 4) -COR11 wherein R11 is (a) an alkyl group of C6-6 (said C1-6 alkyl group is optionally susliuid with one or more the same or different subtyls selected from the following a) to e): a ) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of d-6, a -CO-alkyl group of C ? -6, a -CO-cycloalkyl group, or a group -S (= O) 2-d-β alkyl, or R28 and R29 optionally form, with the nitrogen atom to which they are attached, a monocyclic heterocyclic group saturated nylogen-containing, d) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R30 and R31 optionally form, together with the nitrogen to which they are attached, a monocyclic salicylicheterocyclic group containing nitrogen, and e) an alkoxy group of d-6), (b) a cycloalkyl group (said g The cycloalkyl radical is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more identical or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d. 6 (said alkyl group of C-? 6 is optionally substituted with one or more same or different halogen atoms)), and b) an alkyl group of C? .6 (said alkyl group of d-6 is optionally substituted with one or more equal or different substitutes selected from the following group: (i) a hydroxyl group, and (ii) a C 1-6 alkoxyl group), or (c) a saturated monocyclic heterocyclic group containing nylrogen (said helerocyclic group is optionally substituted with one or more identical or different substituents selected from the following a) to c): a) a C 1-6 alkyl group, b) a -CO-alkyl group of d.6, and c) an oxo group), 5) an alkyl group of d.6 (said alkyl group of d-6 is optionally substituted with one or more identical substituents or di selected from the following (a) to (c): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different ones -CO-NR32R33 wherein R32 and R33 they are the same or different and each is a hydrogen atom, an alkyl group of C? .6 (said alkyl group of C? .6 is optionally substituted with one or more identical or different subsitutes selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d.6), or R32 and R33 optionally form, together with the nitrogen atom to which they are joined, a monocyclic monocyclic heicyclic group containing nitrogen), and (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R34 and R35 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing niinogen), 6) a cycloalkyl group, 7) -S (= O) 2 -R12 wherein R12 is an alkyl group of C? _6 (said C1_6 alkyl group is optionally substituted with one or more same or different halogen atoms), 8) -C (= NCN) -R13 where R13 is a C1-6 alkyl group, 9) -C (= NCN) NR1 R15 where R14 and R15 are the same or different and each is a hydrogen atom, or a group alkyl of d-6, or R14 and R15 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group which contains nitrogen, 10) an aryl group (said aryl group is optionally substituted with one or more substituents) same or different selected from the following (1) to (3): (1) a halogen atom, (2) an alkyl group of d-6 (said alkyl group of d-6 is optionally susíiuuido with one or more halogen atoms) same or different), and (3) a carboxyl group), or 11) a 5-membered or 6-membered uncyclic monocyclic heyerocyclic group (said heterocyclic group is optionally susiiluted with one or more identical or different susliluyeníes selected from the following (a) to (c): (a) a carboxyl group, ( b) an alkyl group of d-6 (said alkyl group of C-6 is optionally substituted with one or more same or different substituents selected from the following a) to c): a) a halogen atom, b) a hydroxyl group , and c) a C 1-6 alkoxy group, and (c) a cycloalkyl group), or a salt thereof. 51. The compound according to any of the aforementioned 45, 46 and 49, wherein R1 is 1) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a hydrogen atom, (b) a aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) a C 1-6 alkyl group (said C? -6 alkyl group is optionally substituted with one or more identical or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxyl group of C? .6), and e) an alkoxy group of d.6), (c) a cycloalkyl group (said cycloalkyl group is optionally susíiuuido with one or more alkyl groups of the same or different d.6 (said alkyl group of d.6 is optionally susiiluted with one or more identical or different substituents selected from the following group: (i) a hydroxyl group, and (ii) a C1-alkoxy group. 6)), (d) an alkyl group of d.6 (said C6-C6 alkyl group is optionally substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a hydroxyl group, halogen, c) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C? .6 (said alkyl group of d.6 is optionally substituted with one or more same or different halogen atoms)), d) -NR20R21 wherein R20 and R2 are the same or different and each is a hydrogen atom, an alkyl group of C? -6, or a group -CO- C.sub.6 alkyl, or R20 and R21 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more identical or different substitutes selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) an oxo group, and (iv) an alkoxy group of d.6), and e) an alkoxy group of d_6), (e) -S (= O) 2 -R9 wherein R9 is an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C6-6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms), or an alkyl group of (f) a monocyclic monocyclic salt group containing nitrogen (said heterocyclic group is optionally substituted with one or more equal or different substituents selected from the following a) to c): a) an alkyl group of C? .6, b) a group -CO-alkyl of d-6, and c) an oxo group), or (g) R5 and R6 optionally form, together with the nitrogen to which they are attached, a monocyclic monocyclic nitrogen-containing heyerocyclic group (said heterocyclic group is optionally susiiluted with one or more identical or different subsitutes selected from the following a) to i): a) a halogen atom, b) a group hydroxyl, c) a C 1-6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more identical or different substitutes selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of C? -6), d) a carboxyl group, e) a -CO-alkyl group of C? _6, f) -CO-NR22R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of d.6, or R22 and R23 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, g) an oxo group, h) -NR24R25 wherein R24 and R25 they are the same or different and each one is a hydrogen atom, a alkyl group of d-6, or a -CO-alkyl group of C? -6, or R24 and R25 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, and i) a alkoxyl group of d.6) (with the proviso that R5 and R6 do not they are simultaneously hydrogen atoms and unsubstituted d.6 alkyl group), 2) -COOR10 wherein R10 is (a) a C1-6 alkyl group (said alkyl group of d.6 is substituted with one or more like substituents or different selected from the following a) to c): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R26 and R27 optionally form, together with the niologen atom to which they are attached, a salified monocyclic heliccyclic group containing nitrogen, and c) an alkoxy group of d6), or (b) a nitrogen-containing saturated monocyclic heterocyclic group (such group heterocyclic is optionally substituted with one or more equal or different substituents selected from the following a) to c): a) an alkyl group of d.6, b) a -CO-alkyl group of C-> 6 > and c) an oxo), 3) -COR11 group wherein R11 is (a) an alkyl group of C6-6 (said alkyl group of d6 is substituted with one or more same or different substituents selected from the following a) e): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of d.6, a -CO-alkyl group of d.6, a group - CO-cycloalkyl, or a group -S (= O) 2-alkyl of d-6, or R28 and R29 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, d) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of C1.6, or R30 and R31 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group saturated with nylrogen, and e) an alkoxy group of de), (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more identical or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d.6 (said C1-6 alkyl group is optionally susíiuuido with one or more same or different halogen atoms)), and b) an alkyl group of d.sub.6 (said C 1-6 alkyl group is optionally substituted with one or more identical or different substances selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of C? _6)), or (c) a saturated monocyclic heterocyclic group containing nihologen (said heterocyclic group is optionally substituted with one or more identical or different subsitutes selected from the following a) to c): a) an alkyl group of d-6, b) a group -CO-alkyl of d.6, and c) an oxo group), 4) an alkyl group of C6-6 (said alkyl group of d6 is substituted with one or more same or different substituents selected from the following (a) to (a) c): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different ones -CO-NR32R33 wherein R32 and R33 are the same or different and each is an atom of hydrogen, an alkyl group of d-6 (said alkyl group of C6-6 is optionally substituted with one or more equal or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of -ß), or R32 and R33 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen), and (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or an alkyl group of d-6 , or R34 and R35 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing niinogen), 5) a cycloalkyl group, 6) -S (= O) 2 -R12 wherein R12 is an alkyl group of -β (said alkyl group of C6-6 is substituted with one or more equal or different halogen atoms), ) -C (= NCN) -R13 wherein R13 is an alkyl group of C ^, 8) -C (= NCN) NR1 R15 where R14 and R15 are identical or different and each is a hydrogen atom, or an alkyl group of d-6, or R 14 and R 5 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group which contains nilrogen, or 9) an unsaturated monocyclic 5-membered heterocyclic group or 6 members (said heterocyclic group is substituted with one or more same or different substituents selected from the following (a) and (b): (a) an alkyl group of d.6 (said C1-6 alkyl group is substituted with one or more equal or differentiated substituents selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) an alkoxy group of C? .6), and (b) a cycloalkyl group), or a salt thereof. 52. The compound according to any of 45, 46 and 49 indicated above, wherein R1 is 1) -CONR5R6 wherein R5 and R6 are the same or different and each one is (a) a hydrogen atom, (b) an aryl group (said aryl group is substituted with one or more identical or different substitutes selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) a C 1-6 alkyl group (said alkyl group of d 6 is optionally substituted with one or more identical or different subsystems selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxy group of C6-6), and e) an alkoxy group of d-6), (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more alkyl groups of the same or different d.6). (said alkyl group of C6-6 is optionally substituted with one or more identical or different substitutes selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of C-? 6), (d) a alkyl group of C? _6 (said alkyl group of C? _6 is substituted with one or more substituents ales or different selected from the following group: a) a hydroxyl group, b) a halogen atom, c) an aryl group (said aryl group is optionally susíiuuido) with one or more equal or different substitutes selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C-? 6 (said C-? alkyl group). 6 is optionally susíiluido with one or more same or different halogen atoms)), d) -NR20R21 where R20 and R21 are the same or different and each is a hydrogen atom, an alkyl group of d.6, or an -CO-alkyl group of d-6, or R20 and R21 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said group The heterocyclic compound is optionally substituted with one or more identical substituents or differentials selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) an oxo group, and (iv) an alkoxy group of C? .6), and e) an alkoxy group of d.6), (e) -S (= O) 2 -R9 wherein R9 is an aryl group (said aryl group is optionally substituted with one or more, they replace the same or different ones selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of d-β is optionally substituted with one or more equal or different halogen atoms), or an alkyl group of (f) a salicy monocyclic helerocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of d.6, b) a -CO-C1.6 alkyl group, and ) an oxo group), or (g) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nilrogen (said heterocyclic group is optionally substituted with one or more substituents the same or different selected from the following a) to i): a) a halogen atom, b) a hydroxyl group, c) a C-? 6 alkyl group (said C? _6 alkyl group is optionally substituted with one or more substituents same or different selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d-6), d) a carboxyl group, e) a -CO-alkyl group of d-β, f) - CO-NR22R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or a g alkyl group of d-6, or R22 and R23 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heyerocyclic group containing nihologen, g) an oxo group, h) -NR2 R25 wherein R24 and R25 are the same or different and each is a hydrogen atom, an alkyl group of C? -6, or a -CO-C1-6 alkyl group, or R24 and R25 optionally form , together with the nitrogen atom to which they are bonded, a salicy monocyclic helerocyclic group containing nilrogen, and i) an alkoxy group of d-6) (with the proviso that R5 and R6 are not simultaneously hydrogen atoms and C-alkyl group). ? 6 unsubstituted), 2) -COOR 10 wherein R 10 is (a) an alkyl group of C? -6 (said alkyl group of C? _6 is substituted with one or more equal or different substituents selected from the following a) to c): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or a C1-6 alkyl group, or R26 and R27 optionally form, together with the nitrogen atom to which they are bonded, a saturated monocyclic heterocyclic group containing nitrogen, and c) an alkoxy group of d_6) , or (b) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of C-6, b) a -CO-alkyl group of d.6, and c) an oxo group, 3) -COR11 wherein R11 is (a) an alkyl group of d.6 (said C6.6 alkyl group is substituted with one or more same or different substituents selected from the following a) to e): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of C? .6, a group -CO-alkyl of d.6, a -CO-cycloalkyl group, or a group -S (= O) 2-alkyl of C? _6, or R28 and R29 optionally form, together with the nitrogen atom to which they are attached , a nitrogen-containing saturated monocyclic heterocyclic group, d) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of C? -6, or R30 and R31 optionally form , together with the nitrogen atom to which they are attached, a monocyclic monocyclic heyerocyclic group containing nitrogen, and e) an alkoxy group of CIT), (b) a cycloalkyl group (said group) The cycloalkyl group is optionally substituted with one or more identical or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more identical or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C- | .6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms)), and b) an alkyl group of d-6 (said C1.6 alkyl group is optionally substituted with one or more identical substituents or selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d.6)), or (c) a nitrogen-containing saturated monocyclic helerocyclic group (said helerocyclic group is optionally substituted with one or more identical or different substitutes selected from the following a) to the ): a) an alkyl group of C? _6, b) a -CO-alkyl group of C1.6, and c) an oxo group), 4) an alkyl group of C-? -6 (said alkyl group of d- 6 is substituted with one or more identical or different subsitutes selected from the following (a) to (c): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different -CO-NR32R33 wherein R32 and R33 are the same or different and each is a hydrogen atom, an alkyl group of C? _6 (said alkyl group of d-? is optionally substituted with one or more identical or different substituents selected of the following group: (i) a hydroxyl group, and (ii) an alkoxy group of C? .6), or R32 and R33 optionally They form, together with the atom of niigogen to which they are bound, a monocyclic monocyclic heyerocyclic group containing nitrogen), and (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or a C1-6 alkyl group , or R34 and R35 optionally form, together with the nitrogen atom to which they are attached, a salified monocyclic heyerocyclic group containing nitrogen), 5) a cycloalkyl group, 6) -S (= O) 2 -R12 wherein R12 is an alkyl group of C1.6 (said alkyl group of d.6 is susliluido with one or more same or different halogen atoms), 7) -C (= NCN) -R13 wherein R13 is a C1-6 alkyl group, 8) -C (= NCN) NR14R15 wherein R14 and R15 are the same or different and each is a hydrogen atom, or an alkyl group of C? -6, or R14 and R15 optionally form, together with the nitrogen atom to which they are bound, a saturated monocyclic heterocyclic group containing nitrogen, or 9) a 5 m unsaturated monocyclic heterocyclic group members or 6 members (said heterocyclic group is substituted with one or more equal or different substituents selected from the following (a) and (b): (a) an alkyl group of d-6 (said alkyl group of d-6 is substituted with one or more identical or different substituents selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) an alkoxy group of d-β), and (b) a cycloalkyl group), or a salt thereof. 53. The compound according to any of 45 to 52 indicated above, wherein R2 is a cyclopropyl group or is a 1-methylcyclopropyl group, or a salt thereof. 54. The compound according to any of 45 to 53 indicated above, wherein R3 and R4 are the same or different and each is (1) a hydrogen atom, (2) an alkyl group of C6-6 (said alkyl group of -6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of Ci-e), (3) a phenyl group (said phenyl group is optionally subsumed with one or more identical or different substrates selected from the following 1) and 2): 1) a halogen atom, and 2) an alkyl group of d-6 (said alkyl group of -6 is optionally susíiuido with one or more same or different halogen atoms), or (4) a 5-membered or 6-membered monocyclic monocyclic heyerocyclic group, or a salt of it. 55. The compound of 45 indicated above or a salt thereof which is selected from the following: (1) 1 - [5-cyclopropyl-1 - (piperidin-4-yl) -1 H -pyrazole-4-carbonyl] - 3- (pyridin-3-yl) pyrrolidine, (2) 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- hydrochloride] (2-ylfluoromethyl phenyl)] pyrrolidine, (3) 1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine, (4) 1- [1- (1-carbamoylpiperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl] - [(S) -3 - (2-trifluoromethylphenyl)] pyrrolidine, (5) 1-. { 1- [1- (2-carboxyphenylcarbamoyl) piperidin-4-yl] -5-cyclopropyl-1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (6) 1-. { 5-Cyclopropyl-1- [1- (2-hydroxymethylphenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (7) 1-. { 5-Cyclopropyl-1- [1- (1-hydroxymethylcyclopropylcarbamoyl) -piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (8) 1-. { 5-cyclopropyl-1- [1- (2-hydroxyielylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (9) 1-. { 5-cyclopropyl-1- [1- (2-hydroxy-1,1-dimethylyarylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (10) 1 -. { 1 - [1 - (2-Acetylamino-eylcarbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (11) 1- hydrochloride. { 1- [1- (2-aminoethylcarbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (12) 1 -. { 5-cyclopropyl-1 - [1 - (1, 1-dioxothiomorpholine-4-carbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (13) hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (2-dimethylaminoethylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)) pyrrolidine, (14) 1-. { 5-Cyclopropyl-1- [1- (4-hydroxypiperidine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (15) 1-. { 1- [1- (azetidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (16) 1-. { 5-Cyclopropyl-1- [1- (3-hydroxypyrrolidine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (17) hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (2-piperidin-1-yl-ethylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (18) 1-. { 5-Cyclopropyl-1- [1- (4,4-difluoropiperidine-1-carbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (19) 1-. { 5-Cyclopropyl-1- [1- (3,3-difluoropyrrolidin-1-carbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (20) 1-. { 5-cyclopropyl-1- [1- (3-hydroxyazeidin-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (21) 1- (5-cyclopropyl-1- { 1 - [(R) -3-hydroxypyrrolidin-1 -carbonyl] - piperidin-4-il} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (22) 1- (5-cyclopropyl-1-. {1 - [(S) -3- hydroxypyrrolidine-1-carbonyl] -piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethyl-phenyl)] pyrrolidine, (23) 1 - (5-cyclopropyl -1 - { 1 - [(S) -2-hydroxy-1-methyeylarbamoyl] -piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2 -trifluoromethylphenyl)] pyrrolidine, (24) 1-. { 5-cyclopropyl-1- [1- (4-hydroxymethylpiperidine-1-carbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonylH (S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine, (25) 1-. { 1- [1- (4-carboxypiperidine-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (26) 1-. { 5-Cyclopropyl-1- [1- (3-oxopiperazine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (27) 1- (5-cyclopropyl-1- { 1 - [(S) -2-hydroxymethylpyrrolidine-1-carbonyl] piperidin-4- Fig. H -1-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethyl-phenyl)] -pyrrolidine, (28) 1 -. { 5-cyclopropyl-1 - [1- (3-hydroxymethylazeidin-1 -carbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (29) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (4-methyl-piperazine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (30) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (4-isopropylpiperazine-1-carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-lrifluoromethylphenyl)] - pyrrolidine, (31) 1-. { 1- [1- (4-Acetylpiperazine-1-carbonyl) piperidin-4-yl] -5- cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (32) 1- (5-cyclopropyl-1- { 1 - [(R) -3-hydroxypiperidine-1-carbonyl] -piperidin-4 -yl.}. 1 H-pιrazol-4-carbonyl) - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidinal (33) 1-. { 1- [1- (4-carbamoylpipeden-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (34) 1-. { 1- [1- (3-carbamoylazeidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (35) hydrochloride of 1-. { 1- [1- (4-aminopiperidine-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (36) 1- hydrochloride. { 1- [1- (3-aminopyrrolidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (37) 1- hydrochloride. { 5-cyclopropyl-1- [1- (piperidin-4-yl-carbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethyl-phenyl)] -pyrrolidine, (38) -hydrochloride of 1-. { 5-cyclopropyl-1- [1- (4-dimethylaminopiperidine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (39) 1 -. { 1 - [1 - (4-Acetylaminopiperidin-1 -carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (40) 1-. { 1- [1- (3-Acetylaminopyrrolidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (41) hydrochloride of 1-. { 5-cyclopropyl-1- [1- (3-dimethylamino-pyrrolidin-1-carbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-lrifluoromethylphenyl)] - pyrrolidine, (42) hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (1-methylpiperidin-4-yl-carbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (43) 1-. { 1- [1- (1-Acetylpiperidin-4-yl-carbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (44) 1-. { 5-Cyclopropyl-1- [1- (4-oxopiperidine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (45) 1-. { 1- [1- (3-Acetylaminoazelidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (46) 1-. { 5-cyclopropyl-1- [1- (3-oxopyrrolidin-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (47) 1-. { 5-Cyclopropyl-1- [1- (2,2,2-if-fluoro-alkylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (48) 1-. { 5-cyclopropyl-1- [1- (3, 3,4,4-leirafluoropyrrolidin-1-carbonyl) -piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (49) 1- (5-cyclopropyl-1- { 1 - [(S) -1-hydroxymethyl-2-methylpropylcarbamoyl] piperidin- 4-yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethyl-phenyl)] -pyrrolidine, (50) 1 - (1 - { 1 - [(S) -1-benzyl-2-hydroxy-ylcarbamoyl] piperidin-4-yl.} - 5-cyclopropyl-1 H-pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine, (51) 1- (5-cyclopropyl-1 - { 1 - [(S) -2-hydroxy-1-phenylerylcarbamoyl] -piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [(S ) -3- (2-nifluoromethylphenyl)] pyrrolidine, (52) 1- (5-cyclopropyl-1- { 1 - [(S) -1-hydroxymethyl-3-methyl-bulylcarbamoyl) piperidin-4-yl} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-irifluoromethyl-phenyl)] -pyrrolidine, (53) 1-. { 5-cyclopropyl-1- [1- (2-hydroxyphenylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (54) 1-. { 5-cyclopropyl-1- [1- (1-hydroxymethylcyclopenylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (55) 1- [1- (1-benzenesulfonylaminocarbonylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [( S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (56) 1- [5-cyclopropyl-1- (1-methanesulfonylaminocarbonylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) - 3- (2-trifluoromethylphenyl)] pyrrolidine, (57) 1- [5-cyclopropyl-1- (1-methoxycarbonylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- ( 2-fluoriforomethylphenyl)] pyrrolidine, (58) 1-. { 5-cyclopropyl-1- [1- (2-hydroxyeloxycarbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)) pyrrolidine, (59) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (2-dimethylaminoethoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (60) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (2-piperidin-1-yl-ethoxycarbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-lrifluoromethylphenol)] - pyrrolidine, (61) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (piperidin-4-yl-oxycarbonyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenol)] - pyrrolidine, (62) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (1-methyl-piperidin-4-yl-oxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (63) 1-. { 1- [1- (1-Acetylpiperidin-4-yl-oxycarbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (64) 1- [1- (1-cyclopropancarbonylpiperidin-4-yl) -5-cyclopropyl-1H-pyrazole-4-carbonyl] - [(S ) -3- (2-if-trifluoromethylphenyl)] pyrrolidine, (65) 1-. { 5-cyclopropyl-1- [1- (2-hydroxyacetyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (66) 1- (5-cyclopropyl-1- { 1- [1- (4-fluorophenyl) cyclopropanecarbonyl] -piperidin-4-yl} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (67) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (2-dimethylaminoacetyl) -piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (68) 1-. { 1- [1- (2-Acetylaminoacetyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomomethylphenyl)] pyrrolidine, (69) 1-. { 5-cyclopropyl-1- [1- (1-methylcyclopropancarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (70) 1-. { 1- [1- (2-Acetylamino-2-methylpropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (71) 1- (1-. {1 - [(S) -2-acetylaminopropionyl] piperidin-4-yl}. -5-cyclopropyl -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (72) 1- (1- { 1 - [(S) -2-acetylamino-3- meilylbuiliryl) piperidin-4-yl} -5- cyclopropyl-1 H-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (73) 1-. { 5-Cyclopropyl-1- [1- (3,3,3-trifluoropropionyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (74) 1- (5-cyclopropyl-1- { 1 - [(S) -5-oxopyrrolidin-2-carbonyl] piperidin-4- Fig. 1H-pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (75) 1-. { 1- [1- (3-acetylaminopropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (76) 1-. { 5-Cyclopropyl-1- [1- (3-hydroxy-2,2-dimethypropyl) pipepdin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (77) 1- hydrochloride. { 1- [1- (2-Aminoacelyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)) pyrrolidine, (78) 1-. { 5-Cyclopropyl-1- [1- (1-hydroxymethylcyclopropancarbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (79) 1- hydrochloride. { 1- [1- (2-amino-2-methylpropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (80) 1-. { 5-Cyclopropyl-1- [1- (4-hydroxybutyryl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (81) 1- (5-cyclopropyl-1- { 1 - [(S) -pyrrolidin-2-carbonyl] piperidin-4- hydrochloride 1 H-pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethyl-phenyl)] -pyrrolidine, (82) 1- (5-cyclopropyl-1-. {1- [(S) -1-methylpyrrolidin-2-carbonyl] picperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethyl-phenyl)] -pyrrolidine, (83) hydrochloride of 1-. { 1- [1- (3-aminopropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (84) 1- (1- { 1 - [(S) -2-amino-3-meityylbuiryl] piperidin-4-yl}. -5-cyclopropyl-1 H-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine hydrochloride, (85) hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (2-meylaminoacetyl) -p -peridin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (86) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (piperidin-4-carbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (87) 1-. { 5-Cyclopropyl-1- [1- (2-isobutylaminoacelyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (88) 1-. { 1- [1- (2-cyclopropanecarbonylaminoacetyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (89) 1- (1-. {1 - [(S) -1-acetylpyrrolidine-2-carbonyl] piperidin-4-yl}. -5-cyclopropyl-1 H-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (90) 1 -. { 5-Cyclopropyl-1 - [1- (2-menesulfonylaminoacetyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (91) 1 -. { 1 - [1 - (1-Acetylpipehdin-4-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (92) hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (1-methylpiperidine-4-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine, (93) 1-. { 1- [1- (3-carbamoylpropionyl) piperidin-4-yl] -5-cyclopropyl-1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (94) 1- [1- (1-carbamoylmethylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine hydrochloride, ( 95) hydrochloride of 1- [5-cyclopropyl-1- (1-methyl-carbamoylmethylpiperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine, ( 96) hydrochloride of 1-. { 1- [1- (1-carbamoyl-1-methyl-ethyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (97) hydrochloride of 1-. { 1- [1- (2-carbamoylyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (98) 1- [5-cyclopropyl-1- (1-cyclopropylmethylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] hydrochloride] [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (99) hydrochloride of 1 - [5-cyclopropyl-1- (1-cyclopropylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [ (S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (100) 1- [5-cyclopropyl-1- (1-dimethylaminocarbamoylmethylpiperidin-4-yl) -1 H-pyrazole-4-carbonyl] hydrochloride] - [(S) -3- (2-trifluoromethylphenyl)] - pyrrolidine, (101) 1- [1- (1-carboxymethylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] hydrochloride] - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (102) 1- [1- (1-carboxy-ylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [] hydrochloride (S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (103) hydrochloride of 1-. { 1- [1- (1-carbamoylethyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (104) 1- hydrochloride. { 1- [1- (2-carboxy-2-methylpropyl) piperidin-4-yl] - 5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (105) 1- hydrochloride. { 1- [1- (2-carbamoyl-2-meitylpropyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (106) 1- hydrochloride. { 1- [1- (1-carbamoylcyclopropylmethyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine, (107) 1- (5-Cyclopropyl-1- {1,3- [1- (2-hydroxyethyl-carbamoyl) cyclopropylmethyl] piperidin-4-yl} -1-H-pyrazole-4-carbonyl hydrochloride) - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (108) 1- [5-cyclopropyl-1- (1-trifluoromethylsulfonylpiperidin-4-yl) -1 H-pyrazole-4-carbonyl] - [(S ) -3- (2-lrifluoromethylphenyl)] pyrrolidine, (109) 1-. { 5-Cyclopropyl-1- [1- (2,2,2-lrifluoroelansulfonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (110) 1 -. { 1 - [1 - (1-cycliniminoethyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-lrifluoromethylphenyl)] pyrrolidine(111) 1- (1-. {1- [cyanoimino (methylamino) meily] piperidin-4-yl}. -5-cyclopropyl-1 H -pyrazole-4-carbonyl) - [(S) -3 - (2-ylfluoromethylphenyl)] pyrrolidine, (112) 1-. { 1- [1- (N-cyanocarbamimidoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (113) 4- (4-. {5-cyclopropyl-4- [3- (2-trifluoromethylphenyl) pyrrolidin-1-carbonyl] pyrazole- 1-yl.] Piperidin-1-yl) benzoic acid, (114) 3- (4-. {5-cyclopropyl-4- [3- (2-l-trifluoromethylphenyl) pyrroidin-1-carbonyl] pyrazole-1- il.}. piperidin-1-yl) benzoic acid, (115) 5- (4-. {5-cyclopropyl-4- [3- (2-ylfluoromethylphenyl) pyrrolidin- 1-carbonyl] pyrazol-1-yl} piperidin-1-yl) thiophene-2-carboxylic acid, (116) 2- (4-. {5-cyclopropyl-4- [3- (2-trifluoromethyl-phenyl) -pyrrolidin-1 -carbonyl] -pyrazol-1-ylpi-piperidin- 1-yl) thiazole-4-carboxylic acid, (117) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (5-methyl-4H- [1, 2,4] idriazol-3-yl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine, (118) hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (5-cyclopropyl-4H- [1,2,4] triazol-3-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)) pyrrolidine, (119) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (5-hydroxymethyl-4H- [1, 2,4] iriazol-3-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)) pyrrolidine, (120) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (5-trifluoromethyl-4H- [1, 2,4] idriazol-3-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (121) 1-. { 5-Cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(R) -3- (2-ylfluoromethylphenyl)] pyrrolidine, (122) 1-. { 5-Cyclopropyl-1- [1- (1-methyl-cyclopropylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(R) -3- (2-irifluoromethylphenyl)] pyrrolidine, (123) 1-. { 5-Cyclopropyl-1- [1- (1-isopropylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(R) -3- (2-trifluoromethylphenyl)] pyrrolidine, (124) 1-. { 5-Cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (125) 1-. { 5-Cyclopropyl-1- [1- (1-isopropylcarbamoyl) piperidin-4-yl] -1 H- pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (126) 1-. { 5-Cyclopropyl-1- [1- (1-methylcyclopropylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, (127) (-) - 3- (4-fluorophenyl) -3-hydroxymethyl-1- hydrochloride. { 5- (1-Methylcyclopropyl) -1- [1- (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -pyrrolidine, (128) (+) - 3- (4-fluorophenyl) -3-hydroxymethyl-1- hydrochloride. { 5- (1-Melylcyclopropyl) -1- [1- (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -pyrrolidine, (129) 1- [5-cyclopropyl-1- (1-pyrazin-2-yl-piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- hydrochloride] (2-trifluoromethylphenyl)] pyrrolidine, (130) 1- [1- (trans-4-carbamoylcyclohexyl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-thfluoromethylphenyl) ] pyrrolidine, (131) 1- [5-cyclopropyl-1- (trans-4-ureidocyclohexyl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine, and ( 132) 1-. { 5-cyclopropyl-1- [trans -4- (1 H -e-erazolol-5-yl) cyclohexyl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine. 56. A pharmaceutical composition comprising a compound according to any of 45 to 55 indicated above or a salt thereof. 57. An 11βHSD1 inhibitor comprising a compound according to any of 45 to 55 indicated above or a salt thereof. 58. An agent for the treatment or prophylaxis of a pathology involving glucocorticoid comprising a compound according to any of 45 to 55 indicated above or a salt thereof. 59. The agent indicated above, 58 wherein the pathology involving glucocorticoid is (1) a metabolic disease that includes diabetes, insulin resistance, diabolic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a metabolic syndrome, (3) a fatal vascular event that includes cardiac infarction or cerebral apoplexy based on such diseases, (4) hyperorexia, (5) a neurodisfunctional disease that includes dysgenesis, neurodegenerative diseases accompanied by the disappearance of nerve cells, emotional disorders that include anxiety, depression or mania, schizophrenia or appetite stimulus, (6) a disease that requires treatment or prophylaxis of diminished immunity or increased immunity, including immunodeficiency, (7) glaucoma, or (8) osteoporosis. 60. A method for inhibiting 11βHSD1 comprising administering a pharmaceutically effective amount of a compound of according to any of 45 to 55 indicated above or one salt thereof. 61. A method of irradiating or preventing a pathology involving glucocorticoid which comprises administering a pharmaceutically effective amount of a compound according to any of 45 to 55 indicated above or a salt thereof. 62. The method of 61 indicated above, wherein the pathology involving glucocorticoid is (1) a metabolic disease that includes diabei, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a meiabolic syndrome, (3) a falal vascular event that includes cardiac infarction or cerebral apoplexy based on the same diseases, (4) hypererexia, (5) a neurodisfunctional disease that includes dysgenesis, neurodegenerative diseases accompanied by disappearance of nerve cells, emotional disorders that include anxiety, depression or mania, schizophrenia, or esystichy of the apex. , (6) a disease that requires treatment or prophylaxis of diminished immunity or increased immunity, including immunodeficiency, (7) glaucoma, or (8) osteoporosis. 63. The use of a compound according to any of 45 to 55 indicated above or a salt thereof for the production of an inhibitor of 11βHSDL 64. The use of a compound according to any of 45 to 55 indicated above or a salt thereof for the production of an agent for the processing or prophylaxis of a pathology involving the glucocorticoid. 65. The use of 64 indicated above, wherein the pathology involving glucocorticoid is (1) a metabolic disease that includes diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a metabolic syndrome, (3) a fatal vascular event that includes cardiac infarction or cerebral apoplexy based on these diseases, (4) hypererexia, (5) a neurodisfunctional disease that includes dysgenesis, neurodegeneral diseases accompanied by the disappearance of nerve cells, emotional disorders that include anxiety, depression or mania, schizophrenia or appetite stimulation, (6) a disease that requires treatment or prophylaxis of diminished immunity or increased immunity, including immunodeficiency, (7) glaucoma, or (8) osteoporosis. 66. A commercial package comprising a written material declaring that the above-described pharmaceutical composition can or should be used for the irradiation or prophylaxis of a disease selected from (1) a metabolic disease that includes diabetes, insulin resistance, diabetic complications , obesity, hyperlipidemia, hypertension or fatty liver, (2) a metabolic syndrome, (3) a faíal vascular event that includes cardiac infarction or cerebral apoplexy based on the same diseases, (4) hyperorexia, (5) a neurodisfunctional disease that includes dysgnosis , neurodegenerative diseases accompanied by disappearance of nerve cells, emotional disorders that include anxiety, depression or mania, schizophrenia or apeil stimulation, (6) a disease that requires treatment or prophylaxis of diminished immunity or increased immunity, including immunodeficiency, (7) glaucoma, and (8) osteoporosis. 67. The pharmaceutical composition of the indicated 56 prior to being used in combination with 1 to 3 agents selected from the following (1) to (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, ( 3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 68. The inhibitor of 11 ßHSD1 of the 57 indicated above, to be used in combination with 1 to 3 agents selected from the following (1) to (5): (1) an agent for the irritation or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the dialysis or prophylaxis of diabeles, (4) an agent for the treatment or prophylaxis of diabetic complications; (5) an agent for the treatment or prophylaxis of hypertension. 69. The agent of 58 or 59 indicated above, which will be used in combination with 1 to 3 agencies selected from the following (1) to (5): (1) an agent for the trailing or prophylaxis of hyperlipidemia, ( 2) an agent for the tracing or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 70. The method of 60 indicated above, which also includes administering from 1 to 3 agencies selected from the following (1) a (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 71. A pharmaceutical agent comprising 1 to 3 agents selected from the following (1) to (5) and a compound according to any of 45 to 55 indicated above or a salt thereof in a combination: (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabei, (4) an agent for the treatment or prophylaxis of diabolic complications, (5) ) an agent for the treatment or prophylaxis of hypertension. 72. A method of treating or preventing a pathology that involves glucocorticoid according to 61 or 62 indicated above, which also comprises administering from 1 to 3 agencies selected from the following (1) to (5): (1) an agent for the traiamienio or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the dialysis or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 73. The use of the 63 indicated above, which will be combined with the use of 1 to 3 agents selected from the following (1) to (5): (1) an agent for the eradication or prophylaxis of hyperlipidemia, (2) a agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 74. The use of 64 or 65 indicated above, which will be combined with the use of 1 to 3 agents selected from the following (1) a (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the eradication or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the dialysis or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 75. The pharmaceutical composition of the aforementioned 56, which will be used to suppress the increase of glucocorticoid level of the blood used in combination with a pharmaceutical agent that raises the level of glucocorticoid in the blood. 76. The above-mentioned 11 ßHSD1 inhibitor of 57, which is used to suppress the increase in glucocorticoid level of the blood used in combination with a pharmaceutical agent that raises the level of glucocorticoid in the blood. 77. The method of 60 indicated above, which also comprises administering a pharmaceutical agent that raises the blood glucocorticoid level. 78. The use of 64 indicated above, to suppress the increase in the glucocorticoid level of the blood used in combination with a pharmaceutic agent that raises the blood glucocorticoid level. 79. A method for suppressing the increase in blood glucocorticoid level comprising administering a pharmaceutical agent that raises the level of glucocorticoid in the blood and the inhibitor of 11 ßHSD1 of the above indicated 57. The present invention also comprises the following. 80. A compound represented by the following formula [3]: wherein R1 is (1) -CONR5R6 wherein R5 and R6 are the same or different and each is 1) a hydrogen atom, 2) an alkyl group of d-6, 3) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more C? _6 alkyl groups the same or different), or 4) an aryl group (said aryl group is optionally susíiuuido with one or more same or different halogen atoms), (2) an aryl group (said aryl group) optionally subsumed with one or more carboxyl groups), or (3) a 5-membered or 6-membered unscreened monocyclic heterocyclic group (said heterocyclic group is optionally susiiuid with one or more carboxyl groups); R2 is (1) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more equal or different C 1-6 alkyl groups); and R3 and R4 are the same or different and each is (1) a hydrogen atom, (2) an alkyl group of d.6 (said alkyl group of C6.6 is optionally substituted with one or more hydroxyl groups), (3) an aryl group (said aryl group is optionally substituted with one or more equal or different substitutes selected from a halogen atom and an optionally substituted C 1-6 alkyl group with one or more halogen atoms), or (4) an unsaturated monocyclic 5-membered or 6-membered heterocyclic group, or a pharmaceutically acceptable salt thereof. 81. The compound of 80 indicated above, wherein R 1 is (1) -CONR 5 R 6 wherein R 5 and R 6 are the same or different and each is 1) a hydrogen atom, 2) a C 1-6 alkyl group, 3) a cyclopropyl group (said cyclopropyl group is optionally substituted with one or more equal or different C 1-6 alkyl groups), or 4) a phenyl group (said phenyl group is optionally substituted with one or more same or different halogen atoms), (2) a phenyl group (said phenyl group is optionally substituted with one or more carboxyl groups), or (3) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group ( said heterocyclic group is optionally substituted with one or more carboxyl groups), or a pharmaceutically acceptable salt thereof. 82. The compound of the 80 indicated above, wherein R2 is a cyclopropyl group or a meilyylcyclopropyl group, or a pharmaceutically acceptable salt thereof. 83. The compound of 80 indicated above, wherein R3 and R4 are the same or different and each is (1) a hydrogen atom, (2) an alkyl group of d-6 (such group, alkyl of -6 is optionally substituted with one or more hydroxyl groups), (3) a phenyl group (said phenyl group is optionally substituted with one or more equal or different susligens selected from a halogen atom and an alkyl group of C6.6 optionally substituted with one or more halogen atoms), or (4) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group, or a pharmaceutically acceptable salt thereof. 84. The compound of 80 indicated above, or a pharmaceutically acceptable salt that is selected from the following: (1) 1-. { 5-Cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - (3-pyridin-3-yl) pyrrolidine, (2) 1-. { 5-Cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -. { (R) -3- (2-trifluoromethylphenyl)} pyrrolidine, (3) 1-. { 5-Cyclopropyl-1- [1- (1-methylcyclopropylcarbamoyl) piperidin-4-yl) -1H-pyrazole-4-carbonyl} -. { (R) -3- (2-trifluoromethylphenyl)} pyrrolidine, (4) 1-. { 5-Cyclopropyl-1- [1- (1-isopropylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -. { (R) -3- (2-ylfluoromethylphenyl)} pyrrolidine, (5) 1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -. { (S) -3- (2-nifluoromethylphenyl)} pyrrolidine, (6) 1 -. { 5-cyclopropyl-1 - [1 - (1-isopropylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -. { (S) -3- (2-trifluoromethylphenyl)} pyrrolidine, (7) 1-. { 5-Cyclopropyl-1- [1- (1-methyl-cyclopropylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -. { (S) -3- (2-nifluoromethylphenyl)} pyrrolidine, (8) hydrochloride of (-) 1-. { 5- (1-meitylcyclopropyl) -1 - [(1-pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (4-fluorophenyl) -3-hydroxymethylpyrrolidine, (9) Hydrochloride of (+) - 1. { 5- (1-meitylcyclopropyl) -1 - [(1-pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (4-fluorophenyl) -3-hydroxymethylpyrrolidine, (10) 4- (4-. {5-cyclopropyl-4- [3- (2-ylfluoromethyl-phenyl) -pyrrolidine-1-carbonyl] -pyrazol-1-yl .}. piperidin-1-yl) benzoic acid, (11) 3- (4-. {5-cyclopropyl-4- [3- (2-ylfluoromethylphenyl), pyrrolidin-1-carbonyl] pyrazol-1-yl} pipehdin-1-yl) benzoic, (12) 5- (4-. {5-Cyclopropyl-4- [3- (2-ylfluoromethyl-phenyl) -pyrrolidin-1-carbonyl] -pyrazol-1-yl} -piperidin-1-yl) -thiophen-2-acid carboxylic, and (13) 2- (4-. {5-cyclopropyl-4- [3- (2-l-trifluoromethylphenyl) pyrrolidin-1-carbonyl] pyrazol-1-yl}. piperidin-1-yl) -iazole -4-carboxylic acid. 85. A pharmaceutical composition comprising the compound according to any of 80 to 84 indicated above, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 86. An inhibitor of 11βHSD1 comprising the compound according to any of 80 to 84 indicated above, or a pharmaceutically acceptable salt thereof, as an active ingredient. 87. An agency for the irradiation or prophylaxis of a pathology involving a glucocorticoid comprising the compound according to any of 80 to 84 indicated above, or a pharmaceutically acceptable salt thereof, as an active ingredient. 88. The agent of 87 indicated above, wherein the pathology involving glucocorticoid is (1) a metabolic disease that includes diabei, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a metabolic syndrome, (3) a fatal vascular event that includes cardiac infarction or cerebral apoplexy based on these diseases, (4) hyperorexia, (5) a neurodysfunctional disease that includes dysgenesis, neurodegenerative diseases accompanied by disappearance of nerve cells, emotional disorders that include anxiety, depression or mania, schizophrenia or stimulation of the apeile, (6) a disease that requires treatment or prophylaxis of decreased immunity or increased immunity, including immunodeficiency, (7) glaucoma, or (8) osteoporosis. 89. The pharmaceutical composition of 85 indicated above, to be used in combination with 1 to 3 agents selected from the following (1) to (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the dialysis or prophylaxis of obesity, (3) an agent for the dialysis or prophylaxis of diabei, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 90. The 11 ßHSD1 inhibitor of 86 indicated above, to be used in combination with 1 to 3 agents selected from the following (1) to (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the dialysis or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 91. The agent according to 87 or 88 indicated above, which is to be used in combination with 1 to 3 agencies selected from the following (1) to (5): (1) an agency for the treatment or prophylaxis of hyperlipidemia , (2) an organism for the eradication or prophylaxis of obesity, (3) an agency for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the dialysis or hypertension prophylaxis. 92. The pharmaceutic composition of 85 indicated above, which is used to suppress the increase in glucocorticoid level of blood used in combination with a pharmaceutic agent that raises the level of glucocorticoid in the blood. 93. The 11βHSD1 inhibitor of 86 indicated above, which is used to suppress the increase in glucocorticoid level of the blood used in combination with a pharmaceutical agent that raises the level of glucocorticoid in the blood.

PREFERRED MODALITIES OF THE BNVENCIOM The present invention will be described in detail below. In the present invention, the definitions of the substituents to be used are the following. The "Cto alkyl group" is a straight or branched chain alkyl group possessing 1 to 6 carbon atoms and, for example, may be indicated by the methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-buíilo group, íer-buíilo group, penlilo group, isopenlilo group, neopeníilo group, íer-peníilo group, group 1, 2-dimeyil-propyl, group hexilo, group 1, 3-dimethyl-butilo and the similar, giving preference to a straight or branched chain alkyl group having 1 to 4 carbon atoms For R1, the preferred "d6-alkyl group" is methyl group, ethyl group, isopropyl group or isobutyl group For R3 or R4, the "Preferred alkyl group of d-6" is metyl group For R5 or R6, the preferred "d6 alkyl group" is ethyl group, isopropyl group, tert-butyl group, 1,2-dimethylaryl group or group 1, 3-dimethyryl buylyl For R 9, the preferred "d-6 alkyl group" is the methyl group For R 10, the preferred "d-6 alkyl group" is upo methyl or ethyl group. For R11, the "Ci-d alkyl group" preferable is meiyl group, ethyl group, propyl group, isopropyl group, isobulyl group or iero-buyl group.

For R12, the "preferable CiA alkyl group is meiyl group or ethyl group." For R13, the preferred "d.6 alkyl group" is methyl group For R14 or R15, the preferred "d6 alkyl group" is methyl group The "C2.6 alkenyl group" is a straight or branched chain alkenyl group having 2 to 6 carbon atoms and, for example, vinyl group, n-propenyl group, isopropenyl group, n-buenyl group, isobuenyl group, sec-butenyl group, ter-bulenyl group, n-pennyl group, isopennyl group, neopentenyl group, group 1 mepropropenyl, n-hexenyl group, isohexenyl group, group 1, 1-dimethylbulenyl, 2,2-dimethylobutenyl group, 3,3-dimethylobuhenyl group, 3,3-dimethylpropenyl group, 2-ethylbulenyl group and the like. The "C1-6 alkoxy group" is an alkoxy group wherein the alkyl moiety is the "Cl-6 alkyl group" defined above and, for example, meloxyl group, eloxyl group, propoxyl group, isopropyloxy group, buioxyl group, isobuyloxyl group, io-buyloxy group, penyloxy group, hexyloxy group and the like. The "halogen atom" is fluorine atom, chlorine atom, bromine atom or iodine atom. The preferred one is fluorine atom or chlorine atom and more preferred is the fluorine atom. The "aryl group" is an aromatic hydrocarbon group having 6 to 14 carbon atoms and, for example, phenyl group, group may be indicated naphthyl, anthryl group, azulenyl group, fenanyryl group and the like. The preferred is phenyl group. The "aryloxy group" is an aryloxy group in which the aryl moiety is the "aryl group" defined above and, for example, phenoxy group, naphthyloxy group and the like can be exemplified. The "cycloalkyl group" is a cycloalkyl group having 3 to 8 carbon atoms and, for example, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, cycloocyl group and the like can be exemplified. Preferred are cycloalkyl group possessing 3 to 6 carbon atoms, as cyclopropyl group, cyclobuyl group, cyclopenyl group and cyclohexyl group. Particularly preferred are cyclopropyl group and cyclopentyl group. The "5-membered or 6-membered unscreened monocyclic heterocyclic group" is a 5-membered or 6-membered monocyclic monocyclic heterocyclic group possessing, in addition to the carbon atom, at least one, preferably 1 to 4, selected heteroarylanes. of the nitrogen atom, oxygen atom and sulfur atom. Non-saturation includes partial unsaturation and complete unsaturation. For example, a 5-membered monoalkyl aromatic heterocyclic group such as furyl group, thienyl group, pyrrolyl group, pyrazolyl group, imidazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isoiazolyl group, triazolyl group, oxadiazolyl group, teryrazolyl group may be indicated. , thiadiazolyl group and the like, and a 6-membered aromatic monocyclic heterocyclic group such as pyridyl group, pyridazinyl group, pyrimidinyl group, pyrazinyl group, iriazinyl group, ziazinyl group, oxadiazinyl group, pyranyl group, lyopyranyl group and the like. As a monocyclic aromatic monocyclic 5-membered group, the thienyl group or thiazolyl group is preferable. As the 6-membered monocyclic aromatic heterocyclic group, the pyridyl group or pyrimidinyl group is preferable. For R1, the "unsaturated 5-membered or 6-membered unscreened monocyclic heterocyclic group is pyridyl group, thiozolyl group, thiazolyl group, triazolyl group (particularly preferably group 1, 2,4-Iriazolyl), tetrazolyl group, pyrimidinyl group or group pyrazinyl, for R3 or R4, the "uncured monocyclic heterocyclic group of 5-membered or 6-membered "pyridyl group" or "pyridyl group." More preferable is "pyridyl group." The "nitrogen-containing monocyclic heterocyclic heterocyclic group is, for example, a 4-membered, monocyclic monocyclic 9-membered heterocycle having at least a niologen atom, eg as azeidinyl group, pyrrolidinyl group, imidazolidinyl group, pyrazolidinyl group, oxazolidinyl group, 2-oxopyrrolidinyl group, isozolidinyl group, iso-aiazolidinyl group, piperidyl group, piperazinyl group, morpholinyl group, liomorpholinyl group, 2-oxopiperidinyl group, 4-oxopiperidinyl group, 2,6-dioxopiperidinyl group and the like. The "preferred monocyclic monocyclic heterocyclic group" is an azetidinyl group, pyrrolidinyl group, piperidyl group, piperazinyl group or iomorpholinyl group.

For -NR5R6, the preferred "monocyclic monocyclic heyrocyclic group which contains nihologen" is azetidinyl group, pyrrolidinyl group, piperidyl group, piperazinyl group or thiomorpholinyl group (said heterocyclic group is optionally susíiluido with one or more identical or different substituents selected from the following group: halogen atom, hydroxyl group, d-6 alkyl group optionally substituted with one or more hydroxyl groups, carboxyl group, acetyl group, carbamoyl group, amino group optionally substituted with one or more same or different substituents selected from the C? _6 alkyl group and acetyl group, and oxo groups). For -NR20R21, the preferred "nitrogen-containing saturated monocyclic heterocyclic group" is azetidinyl group, pyrrolidinyl group or piperidyl group (said heterocyclic group is optionally substituted with one or more the same or different substituents selected from the halogen atom and hydroxyl group). For -NR26R27, the "preferred monocyclic monocyclic heyerocyclic group which contains nihinogen" is piperidyl group or pyrrolidinyl group, more preferably piperidyl group. For R10, the nitrogen-containing saturated monocyclic heterocyclic group "preferable is piperidyl group." For R11, the preferable "saturated monocyclic monocyclic heterocyclic group" is pyrrolidinyl group or piperidyl group (said heterocyclic group is optionally substituted with one or more like substituents). or different selected from the group C alquilo .6 alkyl, -CO-C-_6 alkyl group and oxo group) The meaning of "optionally substituted with one or more substituents" implies without substituting or optionally substituted at least one with the The maximum acceptable number of substituents, for example, in the case of methyl group, means that it is optionally substituted with 1 to 3 substituents, and in the case of ethyl group, it means that it is optionally substituted with 1 to 5 substituents. The case of substilution with two or more employees may be the same or different and is not particularly limited to positions of substituents and can be of any position. The "alkyl group of d-6 optionally substituted with one or more, the same or different substituents" is preferably C 1-6 alkyl group optionally substituted with 1 to 3 identical or different substituents. Particularly, the "alkyl group of d-6 optionally substituted with one or more same or different halogen atoms" is preferably optionally substituted C 1-6 alkyl group with 1 to 3 halogen atoms, more preferably a C 1-6 alkyl group optionally susliluted with three halogen atoms, and more preferably trifluoromethyl group or 2,2,2-trifluoroethyl group. The preferable groups of each group are the following. Preferred Ring A Ring A is (1) a saturated monocyclic nitrogen-containing heterocyclic group (i.e., -X- is -N (R1) -), or (2) a cycloalkyl group (ie, -X- is -C (R7R8) -), and preferably (1) an azetidinyl group or a piperidyl group, or (2) a cyclohexyl group. Preferred R2 is preferably a cyclopropyl group or an optionally susiiluted cyclohexyl group with one or more identical or different substituents selected from an alkyl group of d-6 (said alkyl group of d6 is optionally substituted with a hydroxyl group) and an alkoxy group of C? .6. More preferably, it is a cyclopropyl group or an optionally substituted cyclohexyl group with one or more methyl groups (said meiyl group is optionally substituted with a hydroxyl group) or methoxyl groups. Particularly preferably, it is cyclopropyl group, meilyylcyclopropyl group, methoxycyclopropyl group, tetramethylcyclopropyl group, hydroxymethylcyclopropyl group or cyclohexyl group.

Preferred R3 and R4 R3 and R4 are preferably not hydrogen atoms at the same time. More preferably, one of R3 and R4 is a hydrogen atom, a hydroxyl group, an alkyl group of d-6 (said C1-6 alkyl group is optionally substituted with one or more identical substituents or differentials selected from the halogen atom, group hydroxyl, meioxyl group and acetyloxy group) or a C 1-6 alkoxyl group, and the other is not a hydrogen atom. Even more preferably, one of R3 and R4 is a hydrogen atom, a hydroxyl group, an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more equal sustiluyeníes or differentials selected from the halogen halo, hydroxyl group, methoxyl group and acetyloxy group) or an alkoxy group of d-6, and the other is a substituent selected from the following group, which is optionally substituted with one or more same or different substituents selected from the halogen atom, alkyl group of d-6 (said alkyl group of C6-6 is optionally substituted with one or more, the same or different halogen atoms or hydroxyl group), C6-6 alkoxyl group (said alkoxy group of d6 is optionally substituted with one or more identical or different halogen atoms), C1.6 alkoxycarbonyl group and cyano group: phenyl group, pyridyl group, and thiazolyl group.

Particularly preferably, one of R3 and R4 is a hydrogen atom, a hydroxyl group, an alkyl group of C6.6 (said C1-6 alkyl group is substituted with one or more identical or different susiiluyeníes selected from the halogen atom, group hydroxyl, methoxyl group and acetyloxy group) or a methoxyl group, and the other is a substituent selected from the following group, which is optionally substituted with one or more same or different substituents selected from the halogen atom, trifluoromethyl group, trifluoromethoxy group, methoxycarbonyl group , hydroxymethyloyl group and cyano group: phenyl group, pyridyl group, and thiazolyl group. Preferred R5 and R6 R5 and R6 are preferably identical or different and each is a hydrogen atom, a phenyl group optionally substituted with one or more equal or different subsitutes selected from the hydroxyl group, halogen atom, carboxyl group and C-alkyl group. ? 6 (said alkyl group of C? -6 is optionally substituted with one or more hydroxyl groups or halogen atoms), a cycloalkyl group possessing 3 to 6 carbon atoms (said cycloalkyl group is optionally substituted by an alkyl group of C? .6 optionally suspended with one or more hydroxyl groups), an optionally substituted d.6 alkyl group with one or more equal or different subsitutes selected from the hydroxyl group, halogen atom, phenyl group (said phenyl group is optionally substituted by halogen atom), the carboxyl group and the -NR20R21 (wherein R20 and R21 are the same as defined for formula [1]), -S (= O) 2 -R9 wherein R9 is phenyl group or C? .6 alkyl group) optionally substituted d6-alkoxy group, pyridinyl group optionally substituted with halogen atom in the 2-position and 6-position, an unsaturated heterocyclic group optionally containing nilrogen susíiluido, or a nitrogen-containing saturated monocyclic heterocyclic group optionally substituted with one or more same or different substituieles, selected from the C-alkyl group ? 6 and -CO-alkyl group of C? .6 > or R5 and R6 can form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group selected from the azetidinyl group, pyrrolidinyl group, piperidyl group, piperazinyl group, and thiomorpholinyl group, or a heterocyclic group selected from the group dihydroindolyl group, dihydro [1,4] oxazinyl group, and tetrahydrobenzo [b] azepinyl group, which is a fused ring of said heterocycle and a carbon ring (both mentioned heterocyclic groups are optionally substituted with one or more identical or different substrates) selected from the following group: halogen atom, hydroxyl group, optionally substituted d6 alkyl group with one or more hydroxyl groups, carboxyl group, acetyl group, carbamoyl group, amino group optionally substituted with one or more identical subsitutes or differentials selected from the alkyl group of d.6 and acelyl group, and oxo group). More preferably, R5 and R6 are the same or different and each is a hydrogen atom, a phenyl group optionally suspended in orlo position and / or position for substituents selected from the hydroxyl group, halogen atom, carboxyl group and alkyl group of d. 6 (said alkyl group of d.6 is optionally substituted with one or more hydroxyl groups or halogen atoms), a cyclopropyl group or an optionally substituted cyclopentyl group with d-6 alkyl group optionally substituted with one or more hydroxyl groups, an alkyl group of C6.6 substituted with one or more same or different substituents, selected from the hydroxyl group, halogen atom, phenyl group (said phenyl group is optionally substituted by halogen atom), carboxyl group and -NR 0R21 (wherein R20 and R21 are the same as defined for formula [1]), -S (= O) 2 -R9 wherein R9 is a phenyl group or a meiyl group, an alkoxy group of C? .6, a pyridinyl group susíiluido with halogen atom in the position 2 and position 6, an optionally substituted thiazolyl group, or a piperidin-4-yl group optionally susíiluido in the position 1 with a suslituyenle selected from the alkyl group of d.6 and group -CO-alkyl of d-6, or R5 and R6 can form, with the nitrogen atom to which they are bonded, a saturated monocyclic heterocyclic group containing nitrogen selected from the azetidin-1-yl group, pyrrolidin-1-yl group , piperidin-1-yl group, piperazin-1-yl group, and thiomorpholin-4-yl group, or a heterocyclic group selected from the dihydroindol-1-yl group, dihydro [1,4] oxazin-1-yl group, and tetrahydrobenzo [b] azepin-1-yl group which is a fused ring of said heterocycle and a carbon ring (both mentioned heterocyclic groups are optionally substituted with one or more identical or different substituents selected from the following group: halogen atom, hydroxyl group, optionally substituted C 1-6 alkyl group with one or more hydroxyl groups, carboxyl group, acetyl group, carbamoyl group, amino group optionally substituted with one or more same or different substituents selected from the group of C 1-6 alkyl and acetyl group , and oxo group). Even more preferably, R5 and R6 are the same or different and each is a hydrogen atom, a substituted phenyl group in the ortho and / or position for susyituyenyes selected from the hydroxyl group, halogen atom, carboxyl group and alkyl group of d. 6 (said C1.6 alkyl group is optionally substituted with one or more hydroxyl groups or halogen atoms), a cyclopropyl group or a cyclopenyl group suspended by a C6 alkyl group subsided with one or more hydroxyl groups, an alkyl group of d.6 suspended by a substituent selected from the hydroxyl group, halogen atom, phenyl group (said phenyl group is optionally susiiuid by halogen atom), carboyl group and -NR20R21 (wherein R20 and R2 are the same as defined for the Formula 1]), -S (= O) 2 -R9 wherein R9 is a phenyl group or a meityl group, an alkoxy group of C6.6 a pyridin-3-yl group subsumed with halogen atom in the 2-position and the 6-position, a thiazolyl group, or a piperidin-4-yl group optionally substituted at the 1-position with a -CO-alkyl group of d6, or R5 and R6 can form, together with the niologen atom to which they are attached, a heterocyclic monocyclic group saturated nitrogen containing nitrogen selected from the group azetidin-1-yl, pyrrolidin-1-yl group, piperidin-1-yl, piperazin-1-yl group, and thiomorpholin-4-yl group, or a heterocyclic group selected from the dihydroindole group 1-yl, dihydro [1,4] oxazin-1-yl group, and the letter hydro-benzo [b] azepin-1-yl group, which is a fused ring of said heterocycle and a carbon ring (both mentioned helerocyclic groups are optionally Substituted with one or more identical substituents or differentials selected from the following group: halogen atom, hydroxyl group, C? _6 alkyl group optionally susiiuid with one or more hydroxyl groups, carboxyl group, acetyl group, carbamoyl group, amino group optionally substituted with one or more same or different substitutes selected from the group C alquilo_6 alkyl and acetyl group, and oxo group). Particularly preferably, R5 and R6 are the same or different and each is a hydrogen atom, 2-fluorophenyl group, 2-carboxyphenyl group, 2-hydroxymethylphenyl group, 1-hydroxymethylcyclopropyl group, 2-hydroxylethyl group, 2-hydroxy-1 group, 1-dimethyleryl, 2-acetylaminoethyl group, 2-aminoethyl group, 2-dimethylamino-yl group, 2-piperidin-1-yl-elyl group, 2-hydroxy-1-methyleryl group, pipehdin-4-yl group, 1-methyl group -piperidin-4-yl, 1-acetyl-piperidin-4-yl group, 2,2,2-ylfluoroethyl group, 1-hydroxymethyl-2-meipylpropyl group, group 1-hydroxymethyl-2-phenylethyl, 2-hydroxy-1-phenylethyl group, 1-hydroxymethyl-3-methylbuyl group, 2-hydroxyphenyl group, 1-hydroxymethyl-cyclopentyl group, benzenesulfonyl group, 4-trifluoromethylphenyl group, group 2, 4-difluorophenyl, 1-carboxy-2-methylpropyl group, iazol-2-yl group, isopropoxyl group, 4-fluorobenzyl group, 2,6-dichloropyridin-3-yl group, eioxyl group, or mesyl group, or R5 and R6 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen or a heterocyclic group which is a fused ring of said helerocycle and a carbon ring which is selected from the following group: azetidin-1 group -yl, 3-hydroxyazetidin-1-yl group, 3-hydroxymethylazetidin-1-yl group, 3-acetylazetidin-1-yl group, 3-Acetylaminoazetidin-1-yl group, 3-hydroxypyrrolidin-1-yl group, 3,3-difluoropyrrolidin-1-yl group, 3,3,4,4-tetrafluoropyrrolidin-1-yl group, 2-hydroxymethylpyrrolidin-1 group -yl, 2-aminopyrrolidin-1-yl group, 2-acetylaminopyrrolidin-1-yl group, 2-dimethylaminopyrrolidin-1-yl group, 3-oxo-pyrrolidin-1-yl group, 4-hydroxypiperidin-1-yl group, 4,4-difluoropiperidin-1-yl group, 4-hydroxymethylpiperidin-1-yl group, 4-carboxypiperidin-1-yl group, 3-hydroxypipehdin-1-yl group, 4-carbamoylpiperidin-1-yl group, 4-aminopiperidin-1-yl group, 4-dimethylaminopiperidine group 1 -yl, 4-acetylaminopiperidin-1-yl group, 4-methylpiperazin-1-yl group, 4-isopropylpiperazin-1-yl group, 4-acetylpiperazin-1-yl group, group 1, 1-dioxothiomorpholin-4-yl , 3-oxo-piperidin-1-yl group, 4-oxo-piperidin-1-yl group, 2,3-dihydroindol-1-yl group, 2,3-dihydro [1,4] oxazin-1-yl group, and 2,3,4,5-teirahydrobenzo group [b] azepin-1-yl. Even more preferably, R5 and R6 are not at the same time hydrogen atoms. More preferably, one of R 5 and R 6 is a hydrogen atom and the one is not a hydrogen atom. Preferred R10 R10 is preferably an alkyl group of d6 (said alkyl group of C6 is optionally substituted with one or more equal or different subsitutes selected from the hydroxyl group, phenyl group and -NR26R27 wherein R26 and R27 are the same or different and each is an alkyl group of d-6, or R26 and R27 optionally form a piperidyl group together with the nitrogen atom attached thereto), or a piperidyl group (said piperidyl group is optionally substituted with one or more identical substituents or different selected from the alkyl group of d.6 and -CO-alkyl group of d.6). R 10 is more preferably an alkyl group of d 6 (said alkyl group of d 6 is optionally substituted with one or more equal substituents or differentials selected from the hydroxyl group, phenyl group and -NR 26 R 27 wherein R 26 and R 27 are the same or different and each is the alkyl group of C -? - 6, or R26 and R27 optionally form a piperidyl group together with the niologen atom attached thereto), or a piperidin-4-yl group (said piperidin-4-yl group is optionally substituted with one or more equal or different sustiluyeníes selected from the alkyl group of d .6 and -CO-alkyl group of d.6). R10 is preferably an alkyl group of C6-6 (said C1-6 alkyl group is substituted with one or more same or different substituents selected from the hydroxyl group, phenyl group and -NR26R27 wherein R26 and R27 are the same or different and each one is C1-6 alkyl group, or R26 and R27 optionally form a piperidyl group together with the nitrogen atom attached thereto), or a piperidin-4-yl group (said piperidin-4-yl group is optionally substituted with one or more identical or different substitutes selected from the C1.6 alkyl group and -CO-alkyl group of R 10 is particularly preferably a melyl group, a 2-hydroxyaryl group, a 2-dimethylaminoethyl group, a 2-piperidin-1-ethyl group, a piperidin-4-yl group, a 1-methyl-piperidin-4-yl group, a benzyl group, or 1-Acetyl-piperidin-4-yl group.

Preferred R11 R11 is preferably an alkyl group of d.6 (said C-? 6 alkyl group is optionally substituted with one or more identical or different substitutes selected from the following a) to g): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of d-6, a -CO-C1-6 alkyl group, a group - CO-cycloalkyl, or -S (= O) 2-C-6 alkyl group, d) a carbamoyl group, e) a carboxyl group. f) a phenoxy group, and g) a fluorophenyl group). a cycloalkyl group (said cycloalkyl group is optionally susiifuid with one or more identical or different substrates selected from the following a) and b): a) an aryl group optionally substituted with one or more same or different halogen atoms, and. b) an alkyl group of d-6 optionally substituted with one or more hydroxyl groups), an aryl group (said aryl group is optionally substituted with one or more identical or different subsystems selected from the following a) to c) ..: a) one or more same or different halogen atoms. b) an alkyl group of d-6 optionally substituted with one or more same or different halogen atoms, and c) a C 1-6 alkoxy group). a carboxyl group, or a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of C? _6. b) a -CO-alkyl group of d-6, and c) an oxo group). R11 is more preferably an alkyl group of d-6 (said C1-6 alkyl group is substituted with one or more same or different substituents selected from the following a) to g): a) a halogen atom, b) a group hydroxyl, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of C6.6, a -CO-C1-6 alkyl group, a -CO-cycloalkyl group , or group -S (= O) 2-alkyl of d.6. d) a carbamoyl group, e) a carboxyl group, f) a phenoxy group, and g) a fluorophenyl group, a cyclopropyl group (said cyclopropyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group optionally susiiluted with one or more equal or different halogen atoms, and b) an optionally substituted d-6 alkyl group with one or more hydroxyl groups), a phenyl group (said phenyl group is optionally substituted with one or more equal or different substituents selected from the following a) to c): a) one or more halogen atoms equal or different. b) an alkyl group of C? -6 optionally substituted with one or more same or different halogen atoms, and c) an alkoxy group of d-6). a carboxyl group, or a saturated monocyclic helerocyclic group containing nitrogen selected from a pyrrolidinyl group and a piperidyl group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c):. a) an alkyl group of d-6, b) a -CO-C 1-6 alkyl group, and c) an oxo group). R11 is preferably also a C1-6 alkyl group (said alkyl group of d-6 is substituted with one or more same or different substituents selected from the following a) to g): a) a halogen atom, b) a group hydroxyl, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of C-? -6, a -CO-C1-6 alkyl group, a group -CO- cycloalkyl, or -S (= O) 2-C-6 alkyl group, d) a carbamoyl group, e) a carboxyl group, f) a phenoxy group, and g) a fluorophenyl group, a cyclopropyl group (said group cyclopropyl is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group optionally substituted with one or more same or different halogen atoms, and b) an optionally substituted d6-alkyl group with one or more hydroxyl groups), a phenyl group (said phenyl group is substituted with one or more substituents ales or differentials selected from the following a) to c): a) one or more same or different halogen atoms, b) an alkyl group of d-6 optionally substituted with one or more identical or different halogen atoms, and c) an alkoxy group of d-6), a carboxyl group, or a group saturated monocyclic heterocyclic containing nitrogen selected from a pyrrolidin-2-yl group and a piperidin-4-yl group (said heterocyclic group is optionally substituted with one or more identical substitutes or differentiates selected from the following a) to c): a) a C 1-6 alkyl group, b) a -CO-alkyl group of d-6, and c) an oxo group). R1 is particularly preferably 2,2,2-trifluoro-ethyl group, hydroxymethyl group, 3-hydroxypropyl group, 2-hydroxy-1,1-dimethyl-ethyl group, aminomethyl group, 2-amino-elyl group, 1-amino-1 group. -methyl-ethyl, 1-amino-2-meiyl-propyl group. meylamino-meityl group, dimethylamino-methyl group, acetylamino-methyl group, 1-acetylamino-ylyo group, 2-acetylamino-ylyo group, 1-acetylamino-1-methylyloyl group. 1-acetylamino-2-methyl-propyl group, isobutyrylamino-methyl group, cyclopropanecarbonyl-amino-meityl group, methanesulfonylamino-meityl group, 2-carbamoyl-ylyl group, cyclopropyl group, 1 - (4-fluoro-phenyl) -cyclopropyl group , 1-methyl-cyclopropyl group, 1-hydroxymethyl-cyclopropyl group, pyrrolidin-1-yl group, pyrrolidin-2-yl group, piperidin-4-yl group, 1-methyl-pyrrolidin-2-yl group, group 1 - methyl-piperidin-4-yl, 1-acetyl-pyrrolidin-2-yl group, 1-acetyl-piperidin-4-yl group, 2-carboxy-2-meitylpropyl group, phenoxymethyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, carboxyl group, 4-fluorobenzyl group, 3-trifluoromethylphenyl group, 3-mexoxyphenyl group, or 5-oxo-pyrrolidin-2-yl group. The salt of the compound of the present invention is preferably a pharmaceutically acceptable salt. The salt of the compound of the present invention represented by the formula [1 '] can be produced by means of a conventional method. The salt of the compound of the present invention represented by the formula [1 '] can be obtained by reacting the compound [1'] (more in the present, the compound [1 '] and the salts thereof are also collectively referred to as the compound of the present invention) with, for example, inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid and the like; organic acids such as oxalic acid, malonic acid, citric acid, fumaric acid, lactic acid, malic acid, succinic acid, iartaric acid, acetic acid, gluconic acid, uralfluoroacetic acid, ascorbic acid, measulfonic acid, benzenesulfonic acid and the like; the inorganic bases such as sodium hydroxide, poiasium hydroxide, calcium hydroxide, magnesium hydrate, ammonium hydroxide and the like; the organic bases such as melilamine, diethylamine, Iriethylamine, triethanolamine, ethylenediamine, tris (hydroxymethyl) methylamine, guanidine, choline, cinchonine and the like; the amino acids such as lysine, arginine, alanine and the like, and the like. The present invention also encompasses water containing products, hydrates and solvates of the compound of the present invention. Additionally, the compound of the present invention has several isomers. For example, the form E and form Z may be present as geometric isomers, when an asymmetric carbon atom is present, the enantiomers and diastereomers are present as stereoisomers based thereon, and the tautomers may also be present. Accordingly, the present invention embraces all such isomers and mixtures thereof. In addition, the present invention encompasses, in addition to the compound of the present invention, the prodrug compounds and mebolbolium compounds of these compounds as well as the equivalent compounds. As used in the present, "prodrug" is a derivative that has a group that can be chemically or metabolically decomposed which demonstrates a pharmaceutical activity in the decomposition by hydrolysis or solvolysis or under physiological conditions. For example, a prodrug is used to improve absorption by oral administration or achieve the objective site. Since the group that can be decomposed chemically or meiabically, and the modality in which the group is produced in a compound has been sufficiently well known in the field of pharmaceutics, known technical techniques can be used. employ in the present invention. As the fraction to be modified to produce a prodrug, for example, highly reactive functional groups such as hydroxyl group, carboxyl group, amino group, liol group and the like in the compound of the present invention can be indicated. For example, a derivative may be indicated wherein a substituent such as a group -CO-C 1-6 alkyl, -CO 2 -alkyl group, -CONH-C 1-6 alkyl group-, -CO-alkenyl group of C 2-6, -CO 2 -alkenyl group of C 2-6, -CONH-alkenyl group of C 2-6, -CO-aryl group, -CO 2 -aryl group, -CONH-aryl group, -CO-heterocyclic group, group -CO2-heyerocyclic, -CONH-heyerocyclic group (C1-6 alkyl group, C2-6 alkenyl group, aryl group and helerocyclic group are optionally each substituted with halogen atom, d-6 alkyl group, hydroxyl group, group alkoxyl d-β, carboxyl group, amino group, amino acid residue, -PO3H2, -SO3H, residue of -CO-polyethylene glycol, residue of -CO2-polyethylene glycol, residue of -CO-polyethylene glycol monoalkyl ether, a residue of -CO2- polyethylene glycol monoalkyl ether and the like) and the like has been introduced into a hydroxyl group. Additionally, a derivative may be indicated wherein a substituent as the -CO-alkyl group of d-6, -CO2-alkyl group of d.6, -CO-alkenyl group of C2_6, -CO2-alkenyl group of C2.6, -CO-aryl group, -CO2-aryl group, -CO-heterocyclic group, -CO2-heterocyclic group (C1.6 alkyl group, C2-6 alkenyl group, aryl group and heterocyclic group are optionally substituted each with atom halogen, alkyl group of d. 6, hydroxyl group, C6.6 alkoxyl group, carboxyl group, amino group, amino acid residue, -POaH2, -SO3H, residue of -CO-polyethylene glycol, residue of -C-2-polyethylene glycol, residue of - CO-polyethylene glycol monoalkyl ether, residue of -CO2-polyallylene glycol monoalkyl ether, -POsH2 and the like) and the like can be introduced into an amino group. In addition, a derivative may be indicated wherein a susliiuyenie lal as C6 .6 alkoxy group, aryloxy group (C6.6 alkoxy group and aryloxy group each is optionally substituted with halogen atom, d6 alkyl group, hydroxyl group, alkoxyl group of d.6, carboxyl group, amino group, amino acid residue, -PO3H2, -SO3H, polyethylene glycol residue, polyethylene glycol monoalkyl ether residue and the like) and the like has been introduced into a group carboxyl. In the above, the "heterocyclic group" is a monocyclic heyerocyclic group (including partial unsaturation and complete unsaturation) of 5 members or of 6 members saturated or unsaturated which has, in addition to the carbon atom, at least one, preferably 1 to 4, heteroatoms selected from the nitrogen atom, oxygen atom and sulfur atom, or a fused ring group of the heierocycles or a fused ring group of the heterocycle and a carbon ring selected from benzene, cyclopeniane and hexamethylene. As the "monocyclic monocyclic 5-membered or 6-membered monocyclic group", for example, pyrrolidinyl group, leirahydrofuryl group, teirahydroiienyl group, imidazolidinyl group, group may be indicated pyrazolidinyl, group 1, 3-dioxolanyl, group 1, 3-oxaioyranyl, oxazolidinyl group, ziazolidinyl group, piperidinyl group, piperazinyl group, leirahydropyranyl group, tetrahydroiopyranyl group, dioxanyl group, morpholinyl group, iomorpholinyl group, 2-oxopyrrolidinyl group, group 2 -oxopiperidinyl, 4-oxopiperidinyl group, 2,6-dioxopiperidinyl group and the like. As the "unsaturated 5-membered or 6-membered monocyclic heterocyclic group", for example, pyrrolyl group, furyl group, thienyl group, imidazolyl group, 1,2-dihydro-2-oxoimidazolyl group, pyrazolyl group, group may be indicated diazolyl, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, triazolyl group (group 1, 2,4-triazolyl, group 1, 2,3-triazolyl), tetrazolyl group, group 1, 3,4-oxadiazolyl, group 1 , 2,4-oxadiazolyl, group 1, 3,4-thiadiazolyl, 1,2,4-diazodiazolyl group, furazanyl group, pyridyl group, pyrimidinyl group, 3,4-dihydro-4-oxopyrimidinyl group, pyridazinyl group, pyrazinyl group , group 1, 3,5-iriazinyl, imidazolinyl group, pyrazolinyl group, oxazolinyl group (2-oxazolinyl group, 3-oxazolinyl group, 4-oxazolinyl group), isooxazolinyl group, iiazolinyl group, iso-aliazolinyl group, pyranyl group, group 2 oxopyranyl, 2-oxo-2,5-dihydrofuranyl group and 1, 1-dioxo-1 H-isoiazolyl group. As the "heyerocyclic group which is a fused ring", for example, indolyl group (eg, 4-indolyl group, 7-indolyl group, eic), isoindolyl group, 1,3-dihydro-1,3-group may be indicated. - dioxoisoindolyl, benzofuranyl group (for example, 4-benzofuranyl group, 7-benzofuranyl group), indazolyl group, isobenzofuranyl group, benzoyl phenyl group (for example, 4-benzoyl phenyl group, 7-benzoyl phenyl group, etc.), benzooxazolyl group (for example, 4-benzooxazolyl group, 7-benzooxazolyl group etc.), benzimidazolyl group (for example, 4-benzimidazolyl group, 7-benzimidazolyl group etc. ), benzothiazolyl group (for example, 4-benzoliazolyl group, 7-benzoliazolyl group eic), indolizinyl group, quinolyl group, isoquinolyl group, 1,2-dihydro-2-oxoquinolyl group, quinazolinyl group, quinoxalinyl group, cinnolinyl group, group phthalazinyl, quinolizinyl group, puryl group, pteridinyl group, indolinyl group, isoindolinyl group, 5,6,7,8-teirahydroquinolyl group, group 1, 2,3,4-eeryhydroquinolyl, group 2-oxo-1, 2,3, 4-telrahydroquinolyl group, benzo [1,3] dioxolyl group, 3,4-methylenedioxypyridyl group, 4,5-ethylenedioxypyrimidinyl group, chromenyl group, chromanyl group, isochromanyl group and the like. The "pharmaceutical composition" includes, in addition to what is termed a "composition" comprising an active ingredient such as a pharmaceutical agent and a combination drug and the like, a combination agent with another drug, and the like. It is unnecessary to say that the pharmaceutical composition of the present invention can be used concurrently with any other drug within the acceptable range in clinical situations. Accordingly, the present pharmaceutical composition can also be considered a pharmaceutical composition to be combined with another drug. In addition, the pharmaceutical composition of the present invention can not only be administered to humans but also to others mammals (ralon, rat, marmot, rabbit, cat, dog, bovine, equine, sheep, monkey, eic). Accordingly, the pharmaceutical composition of the present invention is also useful as a pharmaceutical for animals, not to mention the human being. The compound of the present invention or a salt thereof can be mixed with a pharmaceutically acceptable carrier, and is administered orally or parenterally as a pill, pill, powder, granule, suppository, injection, eye drop, liquid, capsule, lozenge, aerosol, elixir , suspension, emulsion, syrup and the like. As the "pharmaceutically acceptable vehicle", various organic or inorganic carrier substances conventionally used as preparation materials can be used., which are added as a vehicle, lubricant, binder, disintegrator, solvent, dissolution aid, suspension agent, isotonization agent, coloring agent, anesthesia and the like. When necessary, additives of preparation such as preservative, antioxidant, coloring agent, sweetener and similar can also be used. As examples of the vehicle indicated above, there may be mentioned lactose, sucrose, D-mannitol, starch, chrysalis cellulose, light silicic anhydride and the like. As a lubricant indicated above, for example, magnesium stearate, calcium stearate, selenium, colloidal silica and the like may be mentioned. As the examples of binder indicated above, polymer compounds such as crystalline cellulose can be mentioned, sucrose, D-mannitol, dexyrin, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone and the like. As examples of the foregoing indicated disintegrator, starch, carboxymethylcellulose, calcium carboxymethylcellulose, croscaramellose, sodium carboxymethyl, sodium starch and the like may be mentioned. As examples of the solvent indicated above, water for injection, alcohol, propylene glycol, macrogol, sesame oil, corn oil, propylene glycol fatty acid esters and the like may be indicated. As examples of the above-mentioned dissolution aids, polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate and the like can be mentioned. As the examples of the above-mentioned suspension agent, surfactants such as stearylamine, sodium lauryl sulfate, lauryl aminopropionic acid, lecithin, benzalkonium chloride, benzeonium chloride, glyceryl monosaraze and the like can be indicated; polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, melilcellulose, hydroxymethylcellulose and the like. As examples of the isotonization agent indicated above, sodium chloride, glycerol, D-mannitol and the like may be indicated. As the examples of the buffer indicated above, buffers such as phosphate, acetate, carbonate, citrate and the like, and the like may be indicated. As the examples of the anesthetizing agent indicated above, benzyl alcohol and the like may be mentioned. As the examples of conservator indicated above, paraoxibenzoaios, chlorobutanol, benzyl alcohol, phenethyl alcohol, sorbic acid, dehydroacetic acid and the like may be mentioned. As the examples of the antioxidant indicated above, sulfur, ascorbic acid and the like may be mentioned. As examples of the sweetening agent indicated above, there may be mentioned aspartame, sodium saccharin, stevia and the like. As the examples of the coloring agent indicated above, edible dyes such as Yellow Edible Color No. 5, Red Edible Color No. 2 and Blue Comessable Color No. 2 and the like, color in edible lacquer, iron oxide and the like can be indicated. Similary. The "inhibitor of 11βHSD1" means disappearance or attenuation of the activity of 11βHSD1 by specific inhibition of the function thereof as an enzyme, and means, for example, the specific inhibition of the function of 11βHSD1 under the conditions of the example Experimental 1 indicated below, and preferably means the concentration necessary to achieve 50% inhibition of 11 ßHSD1 under the conditions of Experimental Example 1 indicated below of less than 10 μM, preferably less than 1 μM, more preferably less than 100 nM , and even more preferably less than 10 nM. For example, "pathology involving glucocorticoid" means (1) a metabolic disease that includes diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a melabolic syndrome, (3) a faíal vascular event that includes cardiac infarction or cerebral apoplexy, (4) hyperorexia, (5) a neurodisfunctional disease that includes dysgenesis, neurodegenerative disease, emotional disorders, schizophrenia or attachment stimulation, (5) 6) a disease associated with diminished immunity function, (7) glaucoma, or (8) osteoporosis and the like. When the compound of the present invention is used as an irradiation drug or prophylaxis of a pathology demonstrating that the glucocorticoid is involved, it can be administered sysmally or topically, and orally or parenterally. While the dose varies, depending on age, body weight, condition, effect of irradiation and the like, for example, it can generally be administered within the range of 0.1 mg to 1 g per administration to an adult once or several times per day. The compound of the present invention can also be used as a drug for the treatment or prophylaxis of the diseases indicated above, without mentioning the human being, in animals other than humans, particularly in mammals. The same thing applies to the use of the compound of the present invention as a drug for irradiation or prophylaxis of (1) a meiabolic disease including diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver. (2) a metabolic syndrome. (3) a fatal vascular event that includes cardiac infarction or cerebral stroke, (4) hypererexia, (5) a neurodysfunctional disease that includes dysgenesis, neurodegenerative disease, emotional disorders, schizophrenia or appetite stimulation, (6) a disease associated with the decreased immunity function. (7) glaucoma, or (8) osteoporosis. and the similar. To produce a preparation of the compound of the present invention as a solid composition or liquid composition for oral administration, or an injection for parenteral administration and the like, the compound can be mixed with other additives as a convenient diluent, a dispersion agent, a adsorbent, a solubilizer and the like. Additionally, the pharmaceutical composition of the present invention It may have a known form such as table, pill, powder, granule, suppository, injection, eye drop, liquid, capsule, pill, aerosol, elixir, suspension, emulsion, syrup and the like. When the pharmaceutical composition of the present invention, for example, is a solid preparation such as table, pill, powder, granule, the additive includes, for example, lactose, mannilol, glucose, hydroxypropylcellulose, microclyslase cellulose, starch, polyvinylpyrrolidone, aluminomeilosilicate. of magnesium, silicic anhydride powder and the like. When a table or pill is to be prepared, a film coating of gastrosoluble or enriched substance such as sucrose, gelatin, hydroxypropylcellulose, or hydroxymethylcellulose phthalate can be applied. as necessary, or a multiple layer lable can be produced that has two or more layers. The compound, pharmaceutical composition, or drug of the present invention can be used in a combination with (more in the present also referred to as the use of a combination) or other pharmaceutical composition or drug (hereinafter also referred to as a drug). combination). The administration planning of the pharmaceutical composition or drug of the present invention, and a combination drug is not limited, and they may be administered to the subject of administration in the form of a combination drug, may be concurrently mimicked, or may be be adimised from a alternated way In addition, a pharmaceutical agent which is characteristically a device containing the pharmaceutical composition or drug of the present invention and a combination drug can be administered. The dose of the combination drug can be a clinically employed one which can be determined depending appropriately on the subject of administration, age and body weight of the administration subject, condition, time of administration, presentation of the medication, method of administration, combination and Similary. The mode of administering the combination drug is not particularly limited, and can be any with the proviso that the pharmaceutical or drug composition of the present invention, and a combination drug are combined. A pharmaceutical agent comprising 1 to 3 agents selected from the following (1) to (5) and the compound of the present invention or a salt thereof in combination: (1) an agent for the tracing or prophylaxis of hyperlipidemia, ( 2) an agent for the treatment or prophylaxis of obesity. (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the irradiation or prophylaxis of diabetic complications. (5) an agent for the treatment or prophylaxis of hypertension means pharmaceutical agents such as a case in which the "Pharmaceutical agent" is a combination drug, a case in which the "Pharmaceutical agent" is a kit that contains a drug containing said "1 to 3 agents selected from (1) to (5)" and a drug that contains the compound of the present invention, a case in which the "pharmaceutical agent" and the drug containing the compound of the present invention are administered simultaneously or at certain intervals, and the like. This pharmaceutical agent is preferably an agent for the irradiation or prophylaxis of a pathology involving glucocorticoid. As the combination drug, an agent for the tracing or prophylaxis of hyperlipidemia can be indicated (1). (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, and. (5) an agent for the treatment or prophylaxis of hypertension, and 1 to 3 of the same agents and the compound of the present invention can be used in combination. As the "agent for the administration or prophylaxis of hyperlipidemia", for example, it may be indicated, (1) fiber drugs (PPAR a receptor agonists), (2) PPAR-d receptor agonists, (3) inhibitors of prolein transfer of microsomal glyceride (MTP). (4) cholesyl ester ester protein transfer inhibitors (CETP), (5) esaline drugs (reductase inhibitors HMG-CoA), (6) anion exchange resins, (7) probucol. (8) nicoinic acid drugs, (9) phyloesiol, (10) apolipoprolein-A1 (Apo-A1) inducers, (11) lipoproiein lipase (LPL) adjuvants, (12) endoihelial lipase inhibitors, (13) ezeimibe , (14) IBAT inhibitors, (15) squalene synase inhibitors, (16) ACAT inhibitors, (17) LXR receptor agonis, (18) FXR receptor agonis, (19) FXR receptor antagonists, and ( 20) adenosine A1 agonists and specifically, clofibraine, bezafibraio, fenofibralo, lovastatin, simvasiaíina, pravasíaíina, fluvastatin, aíorvasíatina, pitavastaíina, rosuvaslaíina, cerivasíaíina, colesíiramina, colestimida, nicotinaio of iooferol, nicomol, niceriírol, soisíerol, orizanol gamma and the similar they can be indicated. As the "agent for the treatment or prophylaxis of obesity", for example, one may indicate (1) leptin drugs. (2) pancreatic lipase inhibitors, (3) noradrenaline seroïonin reuptake inhibitors, (4) cannabinoid receptor aniagonisms, (5) monoamine reuptake inhibitors, (6) diacylglycerol acyltransferase (DGAT) inhibitors, (7) Angiogonists of glucose dependent insulinotropic polypeptide receptor (GIP). (8) leptin receptor agonists. (9) bombesin receptor subtype 3 agonis (BRS-3), (10) perilipine inhibitors, (11) acetyl-CoA carboxylase 1 (ACC1) inhibitors, (12) acetyl-CoA carboxylase 2 (ACC2) inhibitors . (13) inhibitors of fatty acid synase, (14) acyltransferase inhibitors of sn-1-acyl-glycerol-3-phosphate (AGPAT), (15) inhibitors of pancreatic phospholipase A2 (pPLA2), (16) receptor agonists melanocortin (MC), (17) antagonists of the neuropeptide receptor Y5 (NPY5), (18) inducers or activators of decoupling protein (UCP), (19) camillin acylivants O-palmitoyltransferase 1 (CPT-1), (20) CCK1 agonists (CCKA), (21) Neurohypophilic ciliary factor (CNTF), (22) agonisias of CRF 2, (23) anolygonias of the neuropepidoid receptor Y2 (NPY2), (24) neuropeptide receptor anaphylaxis Y4 (NPY4), (25) agonislas bela of thyroid hormone receptor, (26) somatotropic hormones, (27) inhibitors of cyclase lyase ATP, (28) antagonisms of 5-HT6, and (29) agonists of 5-HT2C, and specifically , it can be indicated leptin, oriistat, sibutramine, rimonabant, and mazindol and the like. As the "agent for the travailization or prophylaxis of diabeids," for example, it may be indicated (1) insulin preparations (injection), (2) oral preparations of low molecular weight insulin, (3) sulfonylurea receptor agonisias ( agenís SU), (4) insulin secretagogues that are not sulfonylurea (SU agentes), (5) ATP-dependent potassium channel openers (KATP), (6) glucosidase inhibitors, (7) maltin inhibitors, (8) insulin sensitizer, (9) low molecular weight tGLP-1 receptor agonists, (10) Ippi-1 peptide analogs, (11) dipeplidyl pepidase IV (DPP-IV) inhibitors, (12) glucagon receptor anolygonias, (13) glucocorticoid receptor analogues, (14) biguanides, (15) SGLUT inhibitors. (16) inhibitors of fructose-1,6-bisphosphatase (FBPase), (17) inhibitors of glycogen kinase 3 synthase (GSK-3), (18) inhibitors of phosphoenolpyruvate carboxykinase (PEPCK), (19) inhibitors of the protein tyrosine phosphatase 1 B (PTPase 1 B), (20) Inositol phosphalase inhibitors containing SH2 domain (SHIP2), (21) glycokinase phosphorylase (GP) inhibitors, (22) glucokinase activators, (23) GPR40 receptor agonists, (24) kinase pyruvate dehydrogenase inhibitors (PDHK), (25) glutamine inhibitors: Fructose-6-phosphate aminotransferase (GFAT). (26) antioxidants; nitric oxide scavengers, (27) carniína inhibitors O-palmitoillransferasa 1 (CPT-1), (28) growth hormone releasing factors (GHRF). (29) lipase triacylglycerol inhibitors (lipase-sensitive hormone), (30) PPAR? Receptor agonists, (31) PPAR? Receptor antagonists, (32) PPAR a? Receptor agonists (33) activators of AMP-activated protein kinase (AfvIPK), (34) adiponectin receptor agonists, and (35) ß3 adrenaline receptor agonists, and specifically, insulin, íolbumamide, glyclopyramide, acelohexamide, chlorpropamide, glibuzol, glibenclamide, gliclazide, glimepiride, miiglineide, repaglinide, naieglinide, voglibose, acarbose, migliole, malevolent of rosiglyzazone, melformin hydrochloride, pioglitazone hydrochloride, buformin hydrochloride and the like. As the "agent for the treatment or prophylaxis of diabetic complications", for example, it may be indicated (1) inhibitor of protein kinase Cβ (PKCß), (2) angiotensin II receptor anangonist, (3) inhibitor of aldose reductase , (4) inhibitor of the enzyme that converts angioeensin (AS), (5) inhibitors of the production of advanced glycation end products (AGE), (6) therapeutic agents for neuropathy, and (7) therapeutic agents for diabetic nephropathy , and specifically, epalrestat (kinedak), hydrochloride mexileíina, imidapril hydrochloride and the like. As the "agent for the treatment or prophylaxis of hypertension," for example, one may indicate (1) diuretics of iazide, (2) diuretics similar to iazide, (3) loop diuretics, (4) diuretics of K maintenance, (5) ß blockers, (6) a blockers, ß, (7) blockers of a, (8) central sympathetic neurosuppressors, (9) peripheral sympathetic neurosuppressors (rauwolfia preparations). (10) Ca (benzoyiazepine) antagonism, (11) Ca (dihydropyridine) aniiagonisies, (12) vasodilators, (13) Angioinensin converting angioinensin (AS) enzyme inhibitors, (14) angiogonis II receptor angiogonists, ( 15) nilraio drug, (16) ETA endothelin receptor aniiagoniasis, (17) endothelin-converting enzyme inhibitors; Neprilysin inhibitors, (18) prostaglandin; FP prosianoid agonists. (19) renin inhibitors, (20) NOS3 expression enhancers; analogues of proslacyclin. (21) phosphodiesierase V (PDE5A) inhibitors, (22) prostacyclin analogues, and (23) aldosterone antagonists, and specifically, hydrochlorothiazide, ichlormethiazide, benzylhydrochlorothiozide, meicizan, indapamide, iripamide, chlorthalidone, mefruside, furosemide, spironolaclone, ioleylerene, alenolol, fumarole of bisoprolol, hydrochloride of bexololol, hydrochloride of bevantolol, iartrate of metoprolol, hydrochloride of acebutolol, hydrochloride of celiprolol, nipradilol, hydrochloride of tilisolol, Nadolol, hydrochloride of propranolol, hydrochloride of indenolol, hydrochloride of carteolol, pindolol, prolonged-release pindolol preparation, buniirolol hydrochloride, penbuiolol sulfate, bopindolol malonate, amosulalol hydrochloride, aroinolol hydrochloride, carvedilol, labeyalol hydrochloride, urapidil, terazosin hydrochloride, doxazosin mesylate, bunazosin hydrochloride, prazosin hydrochloride, feniolamine mesylate, clonidine hydrochloride, guanfacine hydrochloride, acetyl of guanabenz, methyldopa, reserpine, rescinamine, amlodipine besilate, aranidipine, efonidipine hydrochloride, cilnidipine, nicardipine hydrochloride, nisoldipine, nitrendipine, nifedipine, prolonged-release nifedipine preparation, nilvadipine, bamidipine hydrochloride, felodipine, benidipine hydrochloride, Manidipine hydrochloride, azelnidipine, hydrochloride of diliazem, hydrazine hydrochloride, allralazine hydrochloride, budralazine, cadralazine, capipril, enalapril malignan, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, trandolapril, erbumine of perindopril, candesartancilexetil, valsarían, termisartan, medoxomil olmesartan, sodium nitroprusside, niíroglycerin and the like. As the combination drug, a drug that raises the level of glucocorticoid in the blood, such as adrenal corticosteroid and the like, can be indicated. The glucocorticoid of the blood not only means endogenous glucocorticoids, such as corticosterone, cortisol and the like, but also exogenous glucocorticoids due to the administration of adrenal corticosteroid. One to three agents thereof and the compound of the present invention can be used in combination. Some examples of the production methods of the compounds of the present invention will be illustrated below. However, the production methods of the compounds of the present invention are not limited to these examples. Even in the absence of a description of the production method, effective production can be carried out, when necessary, by introducing a protective group into a functional group followed by disprovection in a subsequent stage, by interchanging the order of respective steps. As the protecting group, for example, a carboxyl protecting group (in the present case, the carboxyl protecting group generally means those used in the field of organic syn- thenic chemistry, as a meyyl group, ethyl group, propyl group, tert-butyl group, benzyl group, p-methoxybenzyl group and the like, which is in the form of esters capable of being easily converted to the carboxylic acid by hydrolysis, catalytic hydrogenation and the like) , an amino protecting group (in the present, amino-protecting group generally means those used in the organic synthesis chemistry field, such as the io-buoxycarbonyl group, benzyloxycarbonyl group, benzyl group and the like which can easily be transformed to an amino group by hydrolysis, catalytic hydrogenation and the like), a hydroxyl group protecting group (in the present, the hydroxyl group protecting group generally means those used in the field of organic synthesis chemistry, such as lelrahydropyranyl group, meioxymeryl group , meioxy-oxy-xyloyl group, benzyloxymethyl group, benzyl group, p-methoxybenzyl group, p-nitrobenzyl group, pyrimethylsilyl group, p-buyldimethylsilyl group, acetyl group, benzoyl group, allyl group, isobutyl group and the like which can be easily converted to a hydroxyl group by hydrolysis, catalytic hydrogenation and the like), and the like can be indicated. The preparation after the reaction in each step can be applied by an optical method, where the isolation and purification is carried out by selecting or combining conventional methods as necessary, such as crystallization, recrystallization, silica gel chromatography, preparative HPLC and Similary.

Production method 1 In the compound [1 '] of the present invention, a compound wherein -X- is -NH- can be produced by the following steps. disproportion Stage 5 wherein R 'is a carboxyl group (herein, the carboxyl group generally means those used in the field of organic synthesis chemistry, such as methyl group, ethyl group, propyl group, tert-butyl group, group benzyl, p-methoxybenzyl group and the like) which is in the form of esters capable of being easily transformed to the carboxylic acid by hydrolysis, calalytic hydrogenation and the like, R "is an amino protecting group (here, the group protection Amino usually means those used in the field of organic synthesis chemistry, such as the tert-buioxycarbonyl group, benzyloxycarbonyl group, benzyl group and the like) which can be easily removed by hydrolysis, calalytic hydrogenation and the like, and the other symbols They are the same as those defined above.

Step 1: Compound (3) can be obtained by reacting β-cyanoester (1) synthelised by a known method with dimethylacetal dimeylylformamide (2) in a solvent or in the absence of solvency. As solven, it may be indicated meianol, benzoic acid, benzene, toluene, xylene, lerahydrofuran, 1,4-dioxane, N, N-dimethylformamide, and a solven mixture thereof and the like. The reaction temperature is generally from 20 ° C to 250 ° C. The reaction time is generally from 1 h to 24 h. The amount of dimethylacetal dimeylylformamide (2) to be used is generally about 1.5 - about 3 mol, per 1 mol of β-ceioester (1). The amount of the solvent to be used is not particularly limited and can be determined by appropriately depending on the lipo and the use of the reaction substance (β-ceioésier (1) and dimethylacetal dimethylformamide (2)), reaction time, reaction time and the similar (the same applies to the amount of the solvent to be used in each stage to be explained later).

Stage 2: Eyelid for the construction of the pyrazole ring. The compound (5) is obtained by reacting hydrazine (4) syntheiZed by a known method with the compound (3) in a solvent.

As solven, meianol, elanol, n-propanol, n-butanol, isopropanol, acetoniiryl, diethyl ether, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, dichloromelan, chloroform, benzene, toluene, xylene, may be indicated. and a solvent mixture thereof and the like. The reaction temperature is generally from 20 ° C to 250 ° C. The reaction time is usually from 1 h to 24 h. The amount of hydrazine (4) to be used is generally about 1 - about 2 mole, per 1 mole of compound (3).

When the hydrazine (4) is a salt, the reaction is carried out in the presence of a base (the basic quantity to be used is generally about 10%). 1 - . 1 - about 2 mole, per 1 mole of compound (3)), such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide, potassium hydroxide, sodium hydroxide, hydroxide poiasium, lithium hydroxide, iaryrylamine, N, N-diisopropylethylamine, pyridine and the like. Step 3: Deprotection stage of carboxyl protecting group. The compound (6) is obtained by removing the carboxyl protecting group R 'of the compound (5) by a known method. Step 4: Amidation elapa The compound (8) is obtained by reacting the compound (6) with amine (7) in a solvent in the presence of a condensing agent and an additive. As the condensing agent, dicyclohexylcarbodiimide (DCC), hydrochloride of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (WSC «HCI), diisopropylcarbodiimide, 1,1'-carbonyldiimidazole (CDI), diphenylphosphoryl azide (DPPA) can be indicated ) and the similar. As an additive, 1-hydroxybenzoyriazole (HOBT), N-hydroxysuccinic acid (HOSu), 4-dimethylaminopyridine (DMAP) and the like may be indicated. As a solvent, dichloromelan, chloroform, acetylonitrile, ureahydrofuran, 1,4-dioxane, N, N-dimetylformamide, and a solven mixture thereof and the like may be indicated. The reaction temperature is generally 20 ° C to 100 ° C. The reaction time is generally from 1 h to 24 h. The amount of amine (7) to be used is generally about 1 - about 1.5 mole per 1 mole of compound (6). Additionally, the quality of the condensing agent and the additive to be used is generally about 1-about 1.5 mol and about 1-about 1.5 mol, respectively, per 1 mol of compound (6). When the amine (7) is a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium acid carbonate, potassium hydrogen carbonate, sodium acetyl, poasium acetyl, sodium hydroxide. , potassium hydroxide, lithium hydroxide, iarythylamine, N, N-diisopropylethylamine, pyridine and the like. In the first place, the carboxylic acid (6) can be converted to an acid halide or an acid mixture anhydride and reacted with amine (7) in the presence of a base. The basic quantity to be used is generally about 1 - about 1.5 mol per 1 mol of compound (6). Step 5: Aminopropagation group deprovection step Compound (9) is obtained by removing the amino protecting group R "of the compound (8) by a known method.When necessary, it can be converted to a salt by a known method .

Production method 2. In the compound [V] of the present invention, a compound wherein -X- is -N (R1) - and R1 is -CONR5R6 wherein R5 is a hydrogen atom can be produced by the following stages . 9" where each symbol is equal to the one defined above.

Stage 1: Stage of ureation 1) when R6 is different from hydrogen. The compound (11) is obtained by reacting the compound (9) with isocyanal (10) in a solvenie. As the solvent, acetonitrile, diethyl ether, 1-hydrohydrofuran, 1,4-dioxane, N, N-dimethylformamide, dimethylsulfoxide, dichloromelan, chloroform, benzene, toluene, xylene, and a Solve mixture of them and similar. The reaction temperature is generally from 0 ° C to 100 ° C. The reaction time is usually from 1 h to 24 h. The amount of isocyanate (10) to be used is generally about 1 - about 2 mol per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out in the presence of an alkaline base such as eryrylamine, N, N-diisopropylethylamine, pyridine and the like (the amount of the base to be used is generally about 1. -approximately 2 mol per 1 mol of compound (9)). Alternately, compound (9) can be reacted with 1,1'-carbonyldiimidazole (CDI) (The amount of CDI to be used is generally about 1 - about 3 mol per 1 mol of compound (9)), and then it is reacted with the corresponding amine. When R6 is an alkyl group, cycloalkyl group, aryl group, heterocyclic group etc. which has a functional group, it can be protected appropriately with a protective group and, after the ureation, is unprotected. When the alkyl group, cycloalkyl group, aryl group, helerocyclic group and the like have substituents, they can be converted, after ureation, to other functional groups by known methods. For example, the conversion of the hydroxyl group to the alkoxyl or ketone group, of the amino group to the alkylamino group, alkylcarbonylamino group or alkylsulfonylamino group, of the alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and sulfur to the sulphone or sulfoxide. 2) when R6 is hydrogen. The compound (11) is caused by reacting the compound (9) with the cyanate in a solvent. As the solvent, acetonilryl, diethyl ether, teirahydrofuran, 1,4-dioxane, N, N-dimethylaminformamide, water, acetic acid, and a mixed solvent thereof and the like may be indicated. The reaction temperature is generally 0 ° C to 100 ° C. The reaction time is generally from 1 h to 24 h. The amount of grain to be used is generally about 1 - about 10 mol, per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium carbonate, sodium carbonate, potassium hydroxide, sodium acetate, potassium acetate, sodium hydroxide. , potassium hydroxide, lithium hydroxide, triethylamine, N, N-diisopropylethylamine, pyridine and the like (the amount of the base to be used is generally about 1 - about 2 mole, per 1 mole of compound (9)).

Production period 3. The compound of the present invention [V] wherein -X- is -N (R1) - and R1 is -CONR5R6 can be produced by the following labels. eleven 11 where each symbol is equal to the one defined above.

Stage 1: Stage of phenylcarbamation.

The compound (13) is obtained by reacting the compound (9) with 4-nitrophenyl chloroformate (12) in a solvent in the presence of a base. As the solvent, acetonitrile, diethyl ether, may be indicated, telrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, dimethylsulfoxide, dichloromelan, chloroform, benzene, toluene, xylene, and a solvenie mixture of the same and the similar. As the base, it can be indicated, eryrylamine, N, N-diisopropylethylamine, pyridine and the like. The reaction time is generally from 0 ° C to 100 ° C. The reaction time is generally from 1 h to 24 h. The amount of 4-nitrophenyl chloroformate (12) to be used is generally about 1 - about 2 mol per 1 mol of compound (9). The amount of the base to be used is generally about 1 - about 2 mole, per 1 mole of compound (9). When the amine (9) is a salt, the reaction is carried out with a base in a quantity of about 2 - about 4 mol per 1 mol of compound (9).

Stage 2: Ureation stage. The compound (11) is obtained by reacting the intermediate compound of phenylcarbamate (13) with the amine (14) in a solvent. As solved, acetonitrile, diethyl ether, ureahydrofuran, 1,4-dioxane, N, N-dimellylformamide, N-methylpyrrolidone, dimethyl sulfoxide, dichloromethane, chloroform, benzene, toluene, xylene, and a mixed solvent thereof can be indicated and the similar. The reaction temperature is generally from 0 ° C to 150 ° C. The reaction time is generally from 1 h to 24 h. The amount of amine (14) to be used is generally about 1 - about 3 mol per 1 mol of compound (9). When the amine (14) is a salt, the reaction is carried out in the presence of an alkaline base such as arylamine, N-diisopropylethylamine, pyridine and the like (the quality of the base to be used is generally about 1 - about 3 mol per 1 mol of compound (13)). As a different method, as illustrated in formula 2), the compound (15) is obtained in elapa 1 by reacting the amine (14) with 4-nitrophenyl chloroformate (12) in a solven, and the compound (15). ) is reacted with the amine (9) in step 2 to give the compound (11). In addition, other chloroformates or 1,1'-carbonyldiimidazole (CDI) can be used in place of 4-nyl-phenyl chloroformate (12). When R5 and / or R6 are / is an alkyl group, a cycloalkyl group, an aryl group, a heyerocyclic group ele. that have a functional group, they are appropriately protected with a protective group and, after ureation, they are disproved. When the alkyl group, cycloalkyl group, aryl group, heterocyclic group and the like have substitution (s), they can be converted to other functional groups after ureation by a known method. For example, the conversion of the hydroxyl group to the alkoxyl or celone group, of the amino group to the alkylamino group, alkylcarbonylamino group or alkylsulfonylamino group, alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and of the sulfide to the sulfone or sulfoxide.

Production method 4. In the compound [1 '] of the present invention, a compound wherein -X- is -N (R1) -, R1 is -CONR5R6 wherein R5 is an atom of hydrogen, and It can be produced by the following stages. 9 17 where each symbol is equal to the one defined above. Step 1: Sulfonilureation step The compound (17) is forced by reacting the compound (9) with sulfonyl isocyanate (16) in a solvenie. As solved, there may be indicated anionyl, diethyl ether, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, benzene, toluene, xylene, and a mixed solvent thereof and the like. The reaction temperature is generally from 0 ° C to 100 ° C. The reaction time is usually from 1 h to 24 h. The amount of sulfonyl isocyanal (16) to be used is generally about 1 - about 2 mole per 1 mole of compound (9). When the amine (9) is a salt, the reaction is carried out in the presence of a base such as triethylamine, N, N-diisopropylethylamine, pyridine and the like (the amount of the base to be used is generally about 1 - about 2. mol per 1 mol of compound (9)).

Production method 5. In the compound [1 '] of the present invention, a compound wherein -X- is -N (R1) - and R1 is -COOR10 can be produced by the following steps. 13 where each symbol is the same as defined above.

Step 1: Carbamation elapa The compound (20) is caused by reacting the compound (9) with chlorocarbonate (18) or carbonate (19) in the presence of a base, in a solvent or solvent. As the solvent, acetonyryl, diethyl ether, hydrohydrofuran, 1,4-dioxane, N, N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene, and a solven mixture thereof and the like may be indicated. As the base, it can be indicated и -rylamine, N, N-diisopropylethylamine, pyridine and the like. The reaction time is usually 0 ° C to 150 ° C. The reaction time is generally of 1 h to 24 h. The amount of chlorocarbonate (18) or carbonate (19) to be used is generally about 1 - about 2 mol per 1 mol of compound (9). The amount of the base to be used is generally about 1 - about 2 mole per 1 mole of compound (9). When the amine (9) is a salt, the reaction is carried out with a base in an amount of about 2-about 4 mol per 1 mol of compound (9). When R10 is alkyl group, cycloalkyl group, aryl group, heterocyclic group ele. which has a functional group, they are appropriately protected with a protective group and, after carbamation, are unprotected. When the alkyl group, cycloalkyl group, aryl group, heterocyclic group and the like are susíiuyenyen (s), they can be converted to other functional groups after carbamation by a known method. For example, the conversion of the hydroxyl group to the alkoxy or celone group, of the amino group to the alkylamino group, alkylcarbonylamino group or alkylsulfonylamino group, of the alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and of the sulfide to the sulphone or sulfoxide. As a different method, as illustrated in formula 2), the intermediate of phenylcarbamazole (13) obtained in Production Period 3, elapa 1 is reacted with alcohol (21) in a solvent, in the presence of a base to give Compound (20). As solvenie, it may indicate acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, dichloromethane, chloroform, benzene, toluene, xylene, and a solvent mixture thereof and the like. As the base, sodium hydride, potassium hydride, sodium carbonate, potassium carbonate, sodium hydroxide, poiasium hydroxide, lithium hydroxide, triethylamine, N, N-diisopropylethylamine, pyridine and the like. The reaction temperature is generally from 0 ° C to 150 ° C. The reaction time is generally from 1 h to 24 h. The amount of alcohol (21) to be used is generally about 1 - about 3 mol per 1 mol of phenylcarbamate intermediate (13). The amount of the base to be used is generally about 1 - about 2 mol per 1 mol of the phenylcarbamate intermediate (13). When R10 is alkyl group, cycloalkyl group, aryl group, heterocyclic group, etc. which has a functional group, they are appropriately protected with a protective group and, after carbamation, are unprotected. When the alkyl group, cycloalkyl group, aryl group, heterocyclic group and the like have substituent (s), they can be converted to other functional groups after carbamation by a known method. For example, the conversion of the hydroxyl group to the alkoxyl or ketone group, of the amino group to the alkylamino group, alkylcarbonylamino group or alkylsulfonylamino group, of the alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and sulfur to the sulfone or sulfoxide.

Production method 6. In compound [1 '] of the present invention, a compound wherein -X- is -N (R1) -, and R1 is -COR11 can be produced by the following steps. where each symbol is equal to the one defined above. Stage 1: Amidation stage The compound (23) is made by reacting the compound (9) with carboxylic acid (22) in a solvent in the presence of a condensing agent and an additive. As the condensing agent, dicyclohexylcarbodiimide (DCC), 1-elyll-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSCxHCI), diisopropylcarbodiimide, 1,1'-carbonyldiimidazole (CDI), diphenylphosphoryl azide (DPPA) and the similar. As an additive, 1-hydroxybenzolyriazole (HOBT), N-hydroxysuccinic acid (HOSu), 4-dimethylaminopyridine (DMAP) and the like may be indicated. As the solvent, dichloromethane, chloroform, acetonitrile, leirahydrofuran, 1,4-dioxane, N, N-dimeiylformamide, and a solvent mixture thereof and the like. The reaction temperature is generally 20 ° C to 100 ° C. The reaction time is generally from 1 h to 24 h. The amount of carboxylic acid (22) to be used is generally from about 1 to about 1.5 mol per 1 mol of compound (9). Additionally, the quality of the condensation agent and the additive to be used is generally from about 1 to about 1.5 mol, respectively, per 1 mol of compound (9). When the compound (9) is a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium acceleration, poasium acelate, sodium hydroxide. , potassium hydroxide, lithium hydroxide, triethylamine, N, N-diisopropylethylamine, pyridine and the like. In addition, the carboxylic acid (22) can be conducted to an acid halide or an acid mixture anhydride and can be reacted with the compound (9) in the presence of a base. The amount of the base to be used is generally from about 1 to about 1.5 mol per 1 mol of compound (9) When R11 is alkyl group, cycloalkyl group, aryl group, heyerocyclic group, eic. that has a functional group, they are appropriately proiected with a protecting group and, after the amidation, they are disproved. When the alkyl group, cycloalkyl group, aryl group, heterocyclic group and the like have a substituent (s), they can be converted to other functional groups after the amidation by a known method. For example, the conversion of the hydroxyl group to the alkoxyl or ketone group, of the amino group to the alkylamino group, alkylcarbonylamino group or alkylsulfonylamino group, alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and the sulfide to sulfone can be mentioned or sulfoxide.

Production method 7 In the compound [1 '] of the present invention, a compound wherein -X- is -N (R1) - and R1 is Ci-β alkyl group or cycloalkyl group which can be produced by the following steps . 9 25 where X 'is a halogen atom and the other symbols are the same as those defined above.

Stage 1: Elapa of N-alkylation. The compound (25) is obtained by reacting the compound (9) with alkylhalide (24) in a solvent in the presence of a base. As the base, sodium carbonate, potassium carbonate, carbonate can be indicated Sodium acid, potassium acid carbonate, sodium acetate, poasium acetate, sodium hydroxide, polasium hydroxide, lithium hydroxide, sodium hydride, potassium hydride, urea, N, N-diisopropylethylamine, pyridine and the like. As the solvent, acetonitrile, acetone, diethyl ether, leirahydrofuran, 1,4-dioxane, N, N-dimethylformamide, dimethylsulfoxide, dichloromene, chloroform, benzene, toluene, xylene, and a mixed solvent thereof and the like can be indicated . The reaction time generally is from 0 ° C to 100 ° C. The reaction time is generally 30 min to 24 h. The amount of alkylhalide (24) to be used is generally from about 1 to about 2 mole per 1 mole of compound (9). The amount of the base to be used is generally from about 1 to about 2 mole per 1 mole of compound (9). When the amine (9) is a salt, the reaction is carried out with a base in a quantity of about 2 to about 4 mol per 1 mol of compound (9). It is also possible to perform reductive amination of the compound (9) with the corresponding aldehyde, ketone, or an equivalent thereof. When R1 is an alkyl group having a functional group, it is appropriately protected with a protecting group and, after N-alkylation, is deprotected. When the alkyl group has substituent (s), it can be converted to another functional group after N-alkylation by a known method. For example, the conversion of the hydroxyl group to the alkoxyl or ketone group, from the amino group to the alkylamino group, can be indicated, alkylcarbonylamino group or alkylsulfonylamino group, alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and from the sulfide to the sulfone or sulfoxide.

Production method 8. In the compound [1 '] of the present invention, a compound wherein -X- is -N (R1) - and R1 is -S (= O) 2R12 can be produced by means of the following steps. 9 27 where each symbol is equal to the one defined above.

Step 1: Sulfonylation step The compound (27) can be obtained by reacting the compound (9) with sulfonyl chloride (26) in a solvent in the presence of a base. As the base, sodium carbonate, potassium carbonate, sodium acid carbonate, potassium hydrogen carbonate, sodium acetylate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydride, hydride, may be indicated. of potassium, eryrylamine, N, N-diisopropylethylamine, pyridine and the like. As the solvent, it can be indicated acetonitrile, acetone, diethyl ether, tetrahydrofuran, 1,4-dioxane, N, N-dimellylformamide, dimethyl sulfoxide, dichloromethane, chloroform, benzene, toluene, xylene, and a mixed solvent thereof and the like. The reaction temperature is generally from 0 ° C to 100 ° C. The reaction time is generally 30 min to 24 h. The amount of sulfonyl chloride (26) to be used is generally from about 1 to about 2 mol per 1 mol of compound (9). The amount of the base to be used is generally from about 1 to about 2 mol per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out with a base in a quantity of about 2 to about 4 mol per 1 mol of compound (9). Additionally, the compound (9) can be reacted with the corresponding sulfonic anhydride. When R 2 is an alkyl group having a functional group, it is appropriately protected with a protecting group and, after sulfonylation, are deprotected. When the alkyl group has substitution (s), it can be converted to another functional group after sulfonylation by a known method. For example, the conversion of the hydroxyl group to the alkoxyl or ketone group, of the amino group to the alkylamino group, alkylcarbonylamino group or alkylsulfonylamino group, of the alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and sulfur to the sulphone or sulfoxide.

Production period 9. In the compound [1 '] of the present invention, a compound wherein -X- is -N (R1) - and R1 is -C (= NCN) R13 can be produced by the following steps. where each symbol is equal to the one defined above. Step 1: Stage of N-cyanoamidine production The compound (29) is made by reacting the compound (9) with N-cyanoimidoacety (28) in a solvent. As the solvent, there may be indicated acetyloiryl, diethyl ether, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, dimellysulfoxide, dichloromean, chloroform, benzene, toluene, xylene, and a mixed solvent thereof and the like. The reaction temperature is generally 0 ° C to 100 ° C. The reaction time is generally from 1 h to 24 h. The amount of N-cyanoimidoacetamide (28) to be used is generally from about 1 to about 2 mol per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out in the presence of a base such as triethylamine, N, N-diisopropylethylamine, pyridine and the like (the canity of the The base to be used is generally approximately 1 has approximately 2 mol per 1 mol of compound (9)).

Production method 10. In compound [1 '] of the present invention, a compound wherein -X- is represented by -N (R1) - and R1 is -C (= NCN) NR14R15 can be produced by the following steps . 31 33 wherein the Ph is a phenyl group and the other symbols are the same as those defined above.

Step 1 The compound (31) is made by reacting the compound (9) with diphenyl N-cyanocarbonimide (30) in a solvenie. As solvenie, it it may indicate acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene, and a solvent mixture thereof and the like. The reaction time is usually 0 ° C to 100 ° C. The reaction time is generally from 1 h to 24 h. The amount of diphenyl N-cyanocarbonimide (30) to be used is generally from about 1 to about 2 mole per 1 mole of compound (9). When the amine (9) is a salt, the reaction is carried out in the presence of a base such as erytylamine, N, N-diisopropylethylamine, pyridine and the like (the amount of the base to be used is generally from about 1 to about 2. mol per 1 mol of compound (9)).

Stage 2: Stage of production of N-cyanoguanidine. The compound (33) is obtained by reacting the compound (31) with the amine (32) in a solvent. As the solvent, there may be indicated acetonitrile, diethyl ether, ureahydrofuran, 1,4-dioxane, N, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, dichloromethane, chloroform, benzene, toluene, xylene, and a solven mixture thereof and the similar. The reaction temperature is generally from 0 ° C to 150 ° C. The reaction time is usually from 1 h to 24 h. The amount of amine (32) to be used is generally from about 1 to about 5 mol per 1 mol of compound (31). When the amine (32) is a salt, the reaction is carried out in the presence of a base such as erytylamine, N, N- diisopropylethylamine, pyridine and the like (the amount of the base to be used is generally from about 1 to about 20 mole per 1 mole of compound (31)).

Production method 11. In the compound [1 '] of the present invention, a compound wherein -X- is -N (R1) - and R1 is an aryl group or 5-member or 6-membered unscreened monocyclic heliccyclic group It can be produced by the following stages. where each symbol is equal to the one defined above.

Stage 1: Elapa for the construction of the pyrazole ring from hydrazine (34) and compound (3) The compound (35) is obtained by reacting hydrazine (34) synthesized by a known method with the compound (3) obtained in Production Method 1, step 1, in a solvent. As the solvent, it may be indicated meianol, eneol, n-propanol, n-buanol, isopropanol, acetylonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, dichloromethane, chloroform, benzene, toluene, xylene, and a solvent mixture thereof and the like. The reaction temperature is generally from 20 ° C to 250 ° C. The reaction time is generally from 1 h to 24 h. The amount of hydrazine (34) to be used is generally from about 1.5 to about 3 mole per 1 mole of compound (3). When the hydrazine (34) is a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium carbonate, sodium carbonate, potassium hydroxide, sodium acetate, potassium acetate, sodium hydroxide. , polasium hydroxide, lithium hydroxide, eryrylamine, N, N-diisopropylethylamine, pyridine and the like (the amount of the base to be used is generally from about 1.5 to about 3 mole per 1 mole of compound (3)).

Step 2: Deprotection stage of carboxyl protecting group R 'The compound (36) is obtained by removing the carboxyl protecting group R' by a known method.

Elapa 3: Amidation stage. The compound (37) is caused by reacting the compound (36) with the amine (7) in a solvent in the presence of a condensing agent and an additive. As the condensing agent, dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSC * HCI), diisopropylcarbodiimide, can be indicated, 1, 1'-carbonyldiimidazole (CDI), diphenylphosphoryl azide (DPPA) and the like. As the additive, 1-hydroxybenzotriazole (HOBT), N-hydroxysuccinic acid (HOSu), 4-dimethylaminopyridine and the like may be indicated. As the solvent, dichloromethane, chloroform, acetonitrile, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, and a mixed solvent thereof and the like may be indicated. The reaction temperature is generally 20 ° C to 100 ° C. The reaction time is usually from 1 h to 24 h. The amount of amine (7) to be used is generally from about 1 to about 1.5 mole per 1 mole of compound (36). Additionally, the amount of the condensing agent and the additive to be used is generally from about 1 to about 1.5 mole and about 1 to about 1.5 mole, respectively, per 1 mole of compound (36). When the amine (7) is a salt, the reaction is carried out in the presence of an alkaline base such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, carbonated poasium acid, sodium acelate, potassium acetate, sodium hydroxide. , potassium hydroxide, lithium hydroxide, irytylamine, N, N-diisopropylethylamine, pyridine and the like. Additionally, the carboxylic acid (36) can be converted to an acid halide and then reacted with the amine (7) in the presence of a base. The amount of the base to be used is generally from about 1 to about 1.5 mole per 1 mole of compound (36). When R1 is an aryl group or an unsaturated monocyclic 5-membered or 6-membered monocyclic group possessing a functional group, it is appropriately protected with a proiecting group and after that is disproved. When the uncured monocyclic aryl group or monocyclic 5-membered or 6-membered heteroaryclic group can be converted to another functional group by a known method after that stage. For example, the conversion of the hydroxyl group to the alkoxyl group or ketone, of the amino group to the alkylamino group, alkylcarbonylamino group or alkylsulfonylamino group, of the alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and of the sulfide to the sulfone or sulfoxide.

Production method 12. In the compound [1 '] of the present invention, a compound wherein -X- is -N (R1) - and R1 is a 5-membered or 6-membered monocyclic aryl group or monocyclic heyerocyclic group It can be produced by the following stages. where each symbol is equal to the one defined above.

Eypa 1: Buchwald / Hartwig amination stage caíalizada by palladium. Compound (39) is obtained by reacting the compound (9) obtained in Production Period 1 and aromatic halide (38) in a solvent in the presence of a palladium catalyst and a base. As a palladium caulkizer, a mixture of palladium acetate and 2,2'-bis (diphenylphosphino) -1,1-biphenyl, bis (diphenylphosphino) ferrocene palladium (II) bichloride, tris (dibenzylidene ketone) dipalladium and the similar. As the base, it is possible to indicate phosphate of iodide (K3PO4), sodium carbonate, carbonate of potassium, carbonate of cesium, carbonate of sodium acid, carbonaceous acid of polasium, ter-butoxide of potassium and the like. As the solvent, 1, 2-dimethoxyethane, 1-hydrofuran, 1,4-dioxane, benzene, toluene, xylene, tert-butanol, and a mixed solvent thereof and the like may be indicated. The reaction time is generally 20 ° C to 250 ° C. The reaction time is generally from 1 h to 24 h. The amount of aromatic halide (38) to be used is generally from about 1 to about 1.5 mol per 1 mol of compound (9). The caníidad of the palladium cauliflower and the base to be used is generally from about 0.01 to about 0.1 mol and about 1 has to about 2 mol, respectively, per 1 mol of compound (9). When R1 is an aryl group or a 5-membered or 6-membered unsaturated monocyclic heyerocyclic group that possesses a functional group, it is appropriately protected with a protecting group and thereafter is deprotected. When the aryl group or a monocyclic monocyclic 5-membered or 6-membered monocyclic group is susíiuyenne (s), it can be converted to another functional group after the elapa by a known method. For example, the conversion of the hydroxyl group to the alkoxyl group or ketone, of the amino group to the alkylamino group, alkylcarbonylamino group or alkylsulfonylamino group, alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and sulfur to sulfone or sulfoxide.

Production method 13. In the compound [1 '] of the present invention, a compound wherein -X- is -N (R1) - and R1 is an aryl group or unsaturated monocyclic 5-membered or 6-membered heterocyclic group It can be produced by the following stages. wherein R '"is a susíiuuyenie (for example, ethoxycarbonyl group, benzoyl group, 9-fluorenylmeloxycarbonyl group and the like) on the nylrogen atom, and the other symbols are the same as those defined above.

Step 1: Ureation step Compound (41) is obtained by reacting the compound (9) obtained in Production method 1 with isothiocyanate (40) in a solvent and removing the substituent (R '") at the nylrogen atom by A known method, such as isothiocyanate (40), may be indicated as ethoxycarbonylisoiocyanate, benzoylisoiocyanate, 9-fluorenylmethioxycarbonyl-isoiocyanate and the like.As the solvent, there may be indicated acetylisoryl, diethyl ether, tetrahydrofuran, 1,4-dioxane, NN-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene, and a solvenide mixture of the same and the similar. The reaction temperature is generally from 0 ° C to 100 ° C. The reaction time is usually from 1 h to 24 h. The amount of isoliocyanate (40) to be used is generally from about 1 to about 2 mol per 1 mol of compound (9). It is possible to react the compound (9) with thiophosgene (the amount of thiophosgene to be used is generally from about 1 to about 1.5 mole per 1 mole of compound (9)), followed by an ammonium treatment.

Stage 2: Eyelid for construction of the thiazole ring. The compound (43) is obtained by reacting the compound (41) with Halomelilcelona (42) in a solvenie. As the solven, meianol, elanol, n-propanol, n-buanol, isopropanol, acetylonitrile, diethyl ether, ureahydrofuran, 1,4-dioxane, N, N-dimethylformamide, dichloromene, chloroform, benzene, toluene, xylene, and a solveni mix of the same and similar. The reaction time is generally 20 ° C to 250 ° C. The reaction time is generally from 1 h to 24 h. The amount of halomeylceyone (42) to be used is generally from about 1 to about 1.5 mol per 1 mol of compound (41). A thiazolyl group having a functional group can be appropriately protected with a protecting group and after that it is protected. When the thiazolyl group has substituent (s), it can be converted to another functional group after this step by a known method. For example, the conversion of the hydroxyl group to the alkoxyl group or ketone, from the amino group to the alkylamino group, alkylcarbonylamino group or alkylsulfonylamino group, from the alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and from the sulfide to the sulphone or sulfoxide.

Production method 14. In the compound [1 '] of the present invention, a compound wherein -X- is -N (R1) - and R1 is a 5-membered or 6-membered unsaturated monocyclic heterocyclic group can be produced by the following stages. wherein X 'is a halogen atom, Alkyl is an alkyl group of C? -6, R is a carboxyl group, an alkyl group of d-6 (said alkyl group of it is optionally substituted with one or more identical or different substitutes selected from the halogen atom and hydroxyl group), or a cycloalkyl group and the other symbols are the same as those defined previously.

Step 1 The isothiourea hydrohalide (45) is obtained by reacting the compound (41) obtained in Production Method 13, step 1 with alkylhalide (44) in a solvenie. As solvenie, may be indicated acetyloiryl, acetone, diethyl ether, teirahydrofuran, 1,4-dioxane, N, N-dimethylarformamide, dimethylsulfoxide, dichloromean, chloroform, benzene, toluene, xylene, and a solvent mixture thereof and the like . The reaction lemperairy is generally from 0 ° C to 100 ° C. The reaction time is generally 30 min to 24 h. The amount of alkylhalide (44) to be used is generally about 1 to about 2 mol per 1 mol of compound (41).

Step 2: Step for the construction of the iriazole ring from isoiourea and hydrazide. Compound (47) can be obtained by reacting isoiourea hydrohalide (45) with hydrazide (46) synthesized by a known method in a solvent in the presence of a base. As a solvent, methanol, eneol, n-propanol, isopropanol, n-buanol, acetylonitrile, diethyl ether, ureahydrofuran, 1,4-dioxane, NN-dimethylformamide, dimethylsulfoxide, dichloromethane, 1,2-dichloroethane, chloroform, benzene may be indicated. , chlorobenzene, O-dichlorobenzene, ileol, xylene, pyridine, 2,6-lulidine, 2,4,6-collidine, acid acetic acid, water, and a solvent mixture of the same and similar. As the base, sodium hydroxide, poasium hydroxide, lithium hydroxide, sodium carbonate, carbonate of potassium, sodium carbonate, potassium hydrogen carbonate, sodium acelate, potassium hydroxide, sodium hydride, hydride can be indicated of polasium, iarythylamine, N, N-diisopropylethylamine, pyridine and the like. The reaction temperature is generally from 20 ° C to 250 ° C. The reaction time is generally 30 min to 24 h. The amount of hydrazide (46) to be used is generally from about 1 to about 2 mole per 1 mole of isoiourea hydrohalide (45). The amount of base to be used is generally from about 1 to about 2 mole per 1 mole of isothiourea hydrohalide (45). When the hydrazide (46) is a salt, the reaction is carried out with a base in a quantity of about 2 to about 4 mol per 1 mol of isothiourea hydrohalide (45). A triazolyl group that possesses a functional group that can be appropriately protected with a protecting group and thereafter is deprotected. When the triazolyl group is susíiuyenyen (s), the sustiluyenie (s) can be converted by a known method to another functional group after espa elapa. For example, the conversion of the hydroxyl group to the alkoxyl group or ketone, of the amino group to the alkylamino group, alkylcarbonylamino group or alkylsulfonylamino group, alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and the sulfide to sulfone can be indicated. or sulfoxide.

Production Period 15 In compound [1 '] of the present invention, a compound wherein -X- is -N (R') - can be produced by the following steps. where each symbol is equal to the one defined above.

Step 1: Deprotection stage of amino protecting group. Compound (48) is obtained by removing the amino protecting group R "from the compound (5) obtained in Production Period 1, step 2.

Step 2: Introduction of R1 The compound (49) is obtained by introducing R1 into the compound (48) by a method similar to Production Methods 2 to 10, and Production Methods 12 to 14.

Step 3: Deprotection stage of carboxyl protecting group Compound (50) is obtained by removing the carboxyl protecting group R 'of the compound (49) by a known method.

Stage 4: Amidation stage. The compound (51) is obtained by reacting the compound (50) with the amine (7) in a solvent in the presence of a condensing agent and an additive. As the condensing agent, dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSCxHCI), diisopropylcarbodiimide, 1,1'-carbonyldiimidazole (CDI), diphenylphosphoryl azide (DPPA) and the similar. As an additive, 1-hydroxybenzotriazole (HOBT), N-hydroxysuccinic imide (HOSu), 4-dimethylaminopyridine (DMAP) and the like may be indicated. As a solvent, dichloromethane, chloroform, tetrahydrofuran, acetonylyl, 1,4-dioxane, N, N-dimethylformamide, and a mixed solvent thereof and the like may be indicated. The reaction time is generally 20X at 100 ° C. The reaction time is usually from 1 h to 24 h. The amount of amine (7) to be used is generally about 1 to about 1.5 mol per 1 mol of compound (50). Additionally, the quality of the condensation agent and the additive to be used is generally from about 1 to about 1.5 mol and about from 1 to about 1.5 mol, respectively, per 1 mol of compound (50). When the amine (7) is a salt, the reaction is carried out in presence of a base such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium acetate, poasium acetate, sodium hydroxide, polasium hydroxide, lithium hydroxide, triethylamine, N, N- diisopropylethylamine, pyridine and the like (the amount of the base to be used is generally from about 1 to about 1.5 mole per 1 mole of compound (50)). The R1 having a functional group is appropriately protected with a protecting group and thereafter is deprotected. When R1 has substituent (s), it can be converted to another functional group after this step by a known method. For example, the conversion of the hydroxyl group to the alkoxyl group or ketone, of the amino group to the alkylamino group, alkylcarbonylamino group or alkylsulfonylamino group, of the alkoxycarbonyl group to the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethyl group, and of the sulfide to the sulphone or sulfoxide.

Production method 16 In compound [1 '] of the present invention, a compound wherein -X- is -C (R7R8) - can be produced by the following stages. 61 wherein each symbol is the same as defined above where R "" is a carboxyl protecting group (herein, the carboxyl group generally means those used in the field of organic synthesis chemistry, eg as methyl group, ethyl group, propyl group, iber-builyl group, benzyl group, p-meioxybenzyl group and the like, which is in the form of esters capable of being readily transformed to the carboxylic acid by hydrolysis, catalytic hydrogenation and the like).

Step 1: Reductive Alkylation Compound (54) is obtained by reacting the ceíone (52) with tert-buíyl carbazole (53) in a solven in the presence of a reducing agent. As the reducing agent, sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, borane complex and the like may be indicated. As the solvent, it may be indicated methanol, ethanol, n-propanol, n-bulanol, isopropanol, dichloromethane, chloroform, diethyl ether, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, benzene, toluene,? acélico, and a solvent mixture of the same and the similar. The reaction time is usually 0 ° C to 100 ° C. The reaction time is generally from 1 h to 24 h. The amount of the reducing agent to be used is generally from about 2 to about 5 mol, per 1 mol of compound (52). Step 2: des-BOC (tert-butoxycarbonyl group). The compound (54) is reacted with 4N hydrochloric acid solution in ethyl acetate, or 4N hydrochloric acid solution in 1,4-dioxane to give the hydrazine hydrochloride (55). Additionally, after des-BOC by the action of trifluoroacetic acid in a solution, it can be converted to hydrochloride. As a solvent, dichloromean, chloroform and the like may be indicated.

Step 3: Step for the construction of the pyrazole ring from hydrazine hydrochloride (55) and compound (3) The compound (56) is obtained by reacting the hydrazine hydrochloride (55) with the compound (3) in a solvent in the presence of a base. As the solvent, meianol, eneol, n-propanol, n-buanol, isopropanol, acetylonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, dichloromean, chloroform, benzene, toluene, xylene, and a solvent mixture of the same and similar. As the base, sodium carbonate, potassium carbonate, sodium acid carbonate, carbonate, potassium hydrogen, sodium acetyl, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N, N may be indicated. -diisopropylethylamine, pyridine and the like. The reaction time generally is 20 ° C to 250 ° C. The reaction time is generally from 1 h to 24 h. The amount of hydrazine hydrochloride (55) to be used is generally about 1 to about 2 mole per 1 mole of compound (3). The amount of the base to be used is generally from about 1 to about 2 mol per 1 mol of compound (3).

Step 4: Deprotection step of carboxyl protecting group Compound (57) is forced by removing the carboxyl group R 'from the compound (56) by a known method.

Step 5: Amidation stage. The compound (58) is obtained by reacting the compound (57) with the amine (7) in a solvent in the presence of condensation agent and an additive. As the condensing agent, dicyclohexylcarbodiimide (DCC), hydrochloride of 1-ethyI-3- (3-dimethylaminopropyl) carbodiimide (WSCxHCI), diisopropylcarbodiimide, 1,1'-carbonyldiimidazole (CDI), diphenylphosphoryl azide (DPPA) and the similar. As the additive, 1-hydroxybenzotriazole (HOBT), N-hydroxysuccinic acid (HOSu), 4-dimethylaminopyridine (DMAP) and the like may be indicated. As solvenie, dichloromean may be indicated, chloroform, acetylonitrile, iorahydrofuran, 1,4-dioxane, N, N-dimethylformamide, and a mixed solvent thereof and the like. The reaction temperature is generally 20 ° C to 100 ° C. The reaction time is usually from 1 h to 24 h. The amount of amine (7) to be used is generally from about 1 to about 1.5 mol per 1 mol of compound (57). Additionally, the amount of the condensing agent and the additive to be used is generally from about 1 to about 1.5 mole and about 1 mole to about 1.5 mole, respectively, per 1 mole of compound (57). When the amine (7) is a salt, the reaction is carried out in the presence of an alkaline base such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, carbon dioxide, sodium acetate, potassium acetate, sodium hydroxide. , potassium hydroxide, lithium hydroxide, triethylamine, N, N-diisopropylethylamine, pyridine and the like. Additionally, carboxylic acid (57) can be converted to an acid halide or a mixic acid anhydride and reacted with the amine (7) in the presence of a base. The The amount of the base to be used is generally from about 1 to about 1.5 mol per 1 mol of compound (57).

Step 6: Propagation step of carboxyl propellant group The carboxylic acid (59) is obtained by removing the carboxyl group R "" from the compound (58) by a known method.

Stage 7: Amidation stage. The compound (61) is obtained by reacting the carboxylic acid (59) with the amine (60) in a solvent in the presence of a condensing agent and an additive. As the condensing agent, dicyclohexylcarbodiimide (DCC), 1-eyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSCxHCI), diisopropylcarbodiimide, 1,1'-carbonyldiimidazole (CDI) or, diphenylphosphoryl azide (DPPA) and the similar. As an additive, 1-hydroxybenzotriazole (HOBT), N-hydroxysuccinic acid (HOSu), 4-dimethylaminopyridine (DMAP) and the like may be indicated. As the solvent, dichloromean, chloroform, acetylonitrile, tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, and a solven mixture thereof and the like may be indicated. The reaction temperature is generally 20 ° C to 100 ° C. The reaction time is generally from 1 h to 24 h. The amount of amine (60) to be used is generally about 1 to about 1.5 mole per 1 mole of carboxylic acid (59). Additionalmene, the amount of the condensing agent and the additive to be used is generally from about 1 to about 1.5 mol and about 1 to about 1.5 mol, respectively, per 1 mol of compound (59). When the amine (60) is a salt, the reaction is performed in the presence of a base such as sodium carbonate, carbonate of poiasio, carbonaio acid of sodium, carbonalo hydrogen of polasio, acetate sodium, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, eryrylamine, N, N-diisopropylethylamine, pyridine and the like.

In addition, the carboxylic acid (59) can be converted to an acid halide or a mixed acid anhydride and can be reacted with amine (60) in presence of a base. The amount of the base to be used is generally from about 1 to about 1.5 mol per 1 mol of acid carboxylic (59).

Production method 17 In the compound [1 '] of the present invention, a compound in where -X- is -C (R7R8) - can be produced by the following steps. 62 Stage 1 where each symbol is equal to the one defined above.

Step 1: Ease of ureation. The carboxylic acid (59) is reacted with diphenylphosphoryl azide (DPPA) in a solvent in the presence of a base to obtain an isocyanate which is reacted with the amine (62) to give the urea (63). As the solvent, dichloromethane, chloroform, iorahydrofuran, 1,4-dioxane, N, N-dimethylaminformamide, benzene, toluene, xylene and the like may be indicated. As the base, it can be indicated iahlylamine, N, N-diisopropylethylamine, pyridine and the like. The reaction temperature for the isocyanate producing step is generally from 20 ° C to 150 ° C, and the step to give urea is generally from 0 ° C to 100 ° C. The reaction time is generally from 1 h to 24 h for both phases. The amount of DPPA to be used is generally from about 1 has to about 2 mol per 1 mol of carboxylic acid (59). The amount of the base to be used is generally from about 1 to about 2 mole per 1 mole of carboxylic acid (59). The amount of amine (62) to be used is generally about 1 to about 5 mol per 1 mol of carboxylic acid (59).

Production Period 18 In compound [1 '] of the present invention, a compound wherein -X- is -C (R7R8) - can be produced by the following steps. 61 65 i where each symbol is equal to the one defined above. Step 1: Cycle analysis. The niírilo (64) is obtained by reacting the amide (61) with a dehydration agent in a solvent in the presence of a base. As the dehydration agent, trifluoromethanesulfonic acid anhydride, p-toluenesulfonyl chloride, trichloroacetyl chloride, ureaifluoroacetic acid anhydride, phosphorus oxychloride, thionyl chloride and the like may be indicated. As the base, triethylamine, N, N-diisopropylethylamine, pyridine and the like may be indicated. As a solvent, dichloromethane, chloroform, iorahydrofuran, 1,4-dioxane, N.N-dimeiylformamide, pyridine, and a mixed solvent thereof and the like may be indicated. The reaction temperature is generally from 20 ° C to 100 ° C. The reaction time is usually from 1 h to 24 h. The amount of the dehydration agent to be used is generally from about 1 to about 2 mole per 1 mole of amide (61). The amount of the base to be used is generally from about 1 to about 2 mole, per 1 mole of amide (61).

Step 2: Step for the construction of the terazole ring The nitrile (64) is reacted in a solvent in the presence of an azidation reagent to give telrazole (65). As the azide reaclivo, azide of soda, azidotrimethylsilene, azidotributyltin, azidotrimethylsilane and the like may be indicated. As the solvent, dichloromean, chloroform, tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, N, N-dimethylformamide, benzene, toluene, xylene, and a solvent mixture thereof and the like. The reaction temperature is generally from 20 ° C to 150 ° C. The reaction time is generally from 1 h to 24 h. The amount of the azidation reagent to be used is generally from about 1 to about 2 mole per 1 mole of nitrile (64). The methods of production described in this description are examples of the production methods of the compound of the present invention, and the different compounds of those explained above can be produced by combining the conventional methods known in the field of organic synthesis chemistry.

EXAMPLES The heterocyclic compounds and production methods thereof of the present invention are explained in detail below with reference to the Examples, which should not be interpreted as limiting thereof.

EXAMPLE -8 Production of 1-f5-cyclopropyl-1-Ibperidin-4 ° 1) -HH-pyrazy @ P-4-carb [piD81-3- (pyrid'n-3-yl) pyrrolidine Epaque 1 Production of 2-cyclopropylcarbonyl-3-dimethylaminoacrylate of meityl 3-cyclopropyl-3-oxopropionate of meityl (2.0 g) was dissolved in uenole (20 ml). Dimeyylformamide of dimethylacetyl (3.0 ml) was added to the obtained solution and the mixture was heated at reflux for 3 h. The reaction mixture was cooled and was concentrated under reduced pressure, and the residue obtained was purified by silica gel chromatography (n-hexane: aceilone = 2: 1) to produce the compound of the extract as a yellow oil (2.61 g). .

Stage 2 Production of methyl 1- (1-benzyloxycarbonylpiperidin-4-yl) -5-cyclopropyl-1H-pyrazole-4-carboxylate Methyl 2-cyclopropylcarbonyl-3-dimethylaminoacrylate (1.0 g) produced in the earlier stage was synthesized, and hydrochloride 4-hydrazinopiperidin-1-carboxyl benzyl (1.49 g) synthesized by a known method, were suspended in elanol. To the obtained suspension was added iarythylamine (0.78 ml) and the mixture was heated to reflux for 3.5 h.

Water was added to the reaction mixture and the mixture was extracted with diethyl ether. The diethyl ether layer was washed with water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (n-henose: ellyl acetate = 2.5: 1) to yield the title compound as a yellow oil (1.58 g).

Step 3 Production of 1- (1-benzyloxycarbonylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carboxylic acid 1- (1-Benzyloxycarbonylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole- 4-carboxylamino methyl (1.58 g) produced in the previous step was dissolved in tetrahydrofuran (5 ml), methanol (5 ml) and water (10 ml), lithium hydroxide monohydrate (834 mg) was added and the mixture it was stirred at 50 ° C for 6 h. The reaction mixture was concentrated under reduced pressure, water was added to the obtained residue, acidified with 2N hydrochloric acid, and extracted with ethyl ether. The ethyl epicarium layer was washed with saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To the obtained residue were added diethyl ether and n-hexane, and the precipitated solid was collected by filtration, and dried to yield the title compound as a white amorphous solid (1.27 g).

Step 4 Production of 1- [1- (1-benzyloxycarbonylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] -3- (pyridin-3-yl) pyrrolidine 1- (1-benzyloxycarbonylpiperidine) -4-yl) -5-cyclopropyl-1H-pyrazole-4-carboxylic acid (800 mg) produced in the previous step, 1-hydroxybenzoiriazole (332 mg) and 1-eyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride (498 mg) were dissolved in N, N-dimellylformamide (10 ml), and the mixture was stirred by 15 min. To the obtained solution were added 3- (pyridin-3-yl) pyrrolidine (330 mg) and 4-dimethylaminopyridine (catalytic amount) and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The ethyl ether layer was washed with saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: methanol = 11: 1) to yield the thioule compound as a white amorphous solid (1.06 g).

Epaque 5 Production of 1- [5-cyclopropyl-1- (piperidin-4-yl) -l H -pyrazole-4-carbonyl] -3- (pyridin-3-yl) pyrrolidine 1- [1- (1-Benzyloxycarbonylpiperidine -4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl] -3- (pyridin-3-yl) pyrrolidine (970 mg) produced in the anterior layer was dissolved in meianol (12 ml), palladium carbon to 10% (50% water content) (200 mg) was added, and the mixture was stirred under a hydrogen atmosphere for 2.5 h. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue obtained was purified by chromatography (neulra alumina) (chloroform: melanol = 7: 1) to produce the title compound as a white amorphous solid (718 mg).

EXAMPLE 2 Hydrochloride production of 5 < nelopropyl-1M-piperidiote ^ ° * flHlH ° p '[rg? z® "- - carbonin-f (S) -3- (2-trifluoromethylphenol) lpyrrolidfl Ba Stage 1 Production of (S) -3-acetyl-4-isopropy-5, 5-diphenyloxazolidin-2-one Under an argon atmosphere, (S) -4-isopropyl-5,5-diphenyloxazolidin-2-one (1.56 g) was suspended. in tetrahydrofuran (22 ml), and 1.6M (n-butyllithium / n-hexane) solution (3.64 ml) was added under an ice bath.

After 10 min., Acetyl chloride (0.47 ml) was added, and the mixture was stirred overnight while allowing the mixture to gradually return to ambient temperature. A saturated solution of ammonium chloride in water was added to the reaction mixture, and the mixture was concentrated under reduced pressure. Water was added to the obtained residue and the mixture was extracted with acellium. The ethyl acetate layer was washed with 1N hydrochloric acid, washed with water, then with saturated sodium hydrogen carbonate solution and water, and dried over anhydrous magnesium sulfate. The Ethyl acetate layer was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (n-hexane: elylar acetyl = 4: 1) to yield the title compound as white crlisles (1.69 g).

Epa 2 Production of (S) -4-isopropyl-3 - [(S) -4-nylro-3- (2-ylfluoromethyl-phenyl) butyryl] -5,5-diphenyloxazolidin-2-one (S) -3-Acetyl- 4-isopropyl-5,5-diphenyloxazolidin-2-one (4.74 g) produced in the lower layer was dissolved in dichloromethane (73 ml) under an argon atmosphere, and titanium terachloride (3.17 ml) and N, N-diisopropylethylamine were added. (3.06 ml) at -78 ° C. The mixture was gradually heated to 0 ° C in 30 min, again cooled to -78 ° C and a solution of 1- [(E) -2-nitrovinyl] -2-trifluoromethylbenzene (3.50 g) in dichloromethane (27 ml) was added. Litanium dioxide chloride (3.17 ml) was added and, after 2 h, a saturated solution of ammonium chloride in water was added to the reaction mixture. The mixture was extracted with ethyl acetate, and the ethyl acetate layer was washed with 1N hydrochloric acid, with water, with a saturated solution of sodium hydrogen carbonate in water and with water, and dried over anhydrous magnesium sulfate. The mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (n-hexane: ethyl acetate = 5: 1) and crystallized with diethyl ether: n-penanium to produce the title compound as crystals. whites (2.62 g).

Stage 3 Production of (S) -4- (2-fluorifomethylphenyl) pyrrolidin-2-one Ethylene (35 ml) and ethyl acetyl (35 ml) were added to (S) -4-isopropyl-3 - [(S) -4-Nitro-3- (2-trifluoromethylphenyl) butyryl] -5,5-diphenyloxazolidin-2-one (2.51 g) produced in the previous step, and Raney nickel (50% water) (2.8 g) was added. After stirring overnight under a hydrogen atmosphere, the insoluble material was filtered through celite, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (chloroform: melanol = 20: 1) to produce the title compound as white crystals (850 mg).

Step 4 Production of (S) -3- (2-trifluoromethylphenyl) pyrrolidine A (S) -4- (2-ylfluoromethylphenyl) pyrrolidin-2-one (803 mg) produced in the previous step was added lelrahydrofuran (7 ml) , and lithium aluminum hydride (200 mg) was added. After heating under reflux for 1.5 h, water (0.2 ml), 4N sodium hydroxide solution in water (0.2 ml) and water (0.4 ml) were added under an ice bath. Anhydrous magnesium sulfate was added, the insoluble material was filtered through celite, and the filtrate was concentrated under reduced pressure to produce the title compound as a pale-yellow oil (722 mg). [a] 25D = + 23.9 (c = 0.504; EtOH) EIApa 5 Production of 1- [1- (1-benzyloxycarbonylpiperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine Acid was dissolved 1- (1-Benzyloxycarbonylpiperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carboxylic acid (235 mg) produced in Example 1, steppe 3, 1-hydroxybenzoyriazole (127 mg) and 1-eyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride (159 mg) in N, N-dimellylformamide (6 ml), and the mixture was agitated for 15 min. To the obtained solution was added (S) -3- (2-fluorifomethylphenyl) pyrrolidine (151 mg) produced in the previous step and 4-dimethylaminopyridine (78 mg), and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water, with 1 N potassium hydrogen sulfate in water, with saturated sodium carbonate acid solution in water and with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (ethyl alcohol: methanol = 40: 1) to produce the compound of the product as a white amorphous solid (287 mg).

Step 6 Production of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine hydrochloride 1- [ 1- (1-Benzyloxycarbonylpiperidin-4-yl) -5-cyclopropyl-1H-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (2.0 g) produced in the previous step was dissolved in methanol (14 ml), palladium carbon hydroxide (0.2 g) was added, and the mixture was stirred under a hydrogen atmosphere for 15 h. The catalyst was removed by filtration with celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in meianol (6.4 ml), and a 4N solution of hydrochloric acid in ethyl acetate (1.32 ml) was added. The mixture was concentrated under reduced pressure, and crystallized with ethyl acetate + diisopropyl ether to yield the title compound as white crystals (1.45 g).

Step 7 (S) -3- (2-trifluoromethylphenyl) pyrrolidine produced in step 4 above and a hydrochloride thereof can also be produced according to the following steps.

Step 7-1 Production of dimellyl 2 - [(S) -2-nitro-1- (2-ylfluoromethylphenyl) elyl] malonale Indole (40 ml) was added to 1 - ((E) -2-nitrovinyl) -2 - 27 trifluoromethylbenzene (4.34 g), and dimethylo malonate (3.4 ml) and 1- (3,5-bis-trifluoromethylphenyl) -3 - ((1S.2S) -2-dimethylaminocyclohexyl) -iourea (413 mg) described in WO2005 / 000803 and "J. Am. Chem. Soc", 2005, 127, 1 19-125 were added under an ice bath. The mixture was stirred under an ice bath for 24 h. The reaction mixture was concentrated under reduced pressure, and the residue was crystallized from 2-propanol to yield the title compound (5.31 g) as white crystals. This reaction can also be performed using arrays described in "J. Am. Chem. Soc.", 1999, 121, 10215-10216, "J. Am. Chem. Soa", 2005, 127, 9958-9959, "J. Am. Chem. Soc ", 2006, 128, 1454-1455 and the like, instead of 1- (3,5-bis-1-trifluoromethylphenyl) -3 - ((1S.2S) -2-dimethylaminocyclohexyl) -iourea.

Step 7-2 Production of (S) -2-oxo-4- (2-trifluoromethylphenyl) pyrrolidin-3-carboxylalkyl 2- [(S) -2-niiro-1- (2-trifluoromethylphenyl) eyl] malonale dimethyl (4.0 g) produced in the lower layer was added to a suspension of Raney nickel (2.0 g) in tetrahydrofuran (10 ml) / meihanol (10 ml), and the mixture was stirred under 3,616 kg / cm 2 of hydrogen at ambient temperature. last 24 hours The insoluble materials were removed by filtration through celile. The filtrate and the washing were combined and concentrated under reduced pressure. Toluene was added to the residue, and the mixture was washed with 10% solution of potassium carbonate in water and with water, and the organic layer was concentrated under reduced pressure. The residue was crystallized from toluene + n-hexane to produce the compound of the extract (2.38 g) as white cristels. This reaction can also be carried out using palladium carbon instead of Raney nickel with an acid such as acetic acid, tosyl acid, mesyl acid and / or something similar.

EIAP 7-3 Production of (S) -4- (2-l-trifluoromethylphenyl) pyrrolidin-2-one Meianol (3.8 ml) was added to (S) -2-oxo-4- (2-trifluoromethylphenyl) pyrrolidin-3- Melyl carboxylate (1.0 g) produced in the lower layer was also added a 1N solution of sodium hydroxide in water (3.8 ml), and the mixture was poured at 65 ° C for 1 h. The reaction mixture was concentrated under reduced pressure, and the residue obtained was acidified with 1N hydrochloric acid under an ice bath and extracted twice with builayl acetal. The organic layers were combined, washed with saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Buíilo acephalous (10 ml) was added to the residue, and the mixture was stirred overnight at 100 ° C. The reaction mixture was concentrated under reduced pressure, and the residue was crystallized with n-hexane to yield the title compound (667 mg) as white cristels.

EIAP 7-4 Production of (S) -3- (2-trifluoromethylphenyl) pyrrolidine hydrochloride To a solution of (S) -4- (2-trifluoromethylphenyl) pyrrolidin-2-one (22.9 g) produced in the lower layer in THF (100 ml) was added a 1M solution of aluminum hydride in THF (100 g). ml) under an argon atmosphere at 85 ° C for 1 h, and the mixture was agitated at the same time for 1 h. After allowing to cool, a 50% aqueous solution of Rochelle's salt was added under an ice bath, and the mixture was partitioned between water and ethyl acetate. The organic layer was separated and concentrated under reduced pressure. The residue was partitioned between water and ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Ethyl acetate (60 ml) was added to the residue, a 4N solution of hydrochloric acid in ethyl acetate (37.5 ml) was added under an ice bath, and the mixture was stirred at ambient temperature. The precipitated crystals were collected by filtration to give the title compound (20.6 g) as white crystals. [a] 25D = +10.3 (c = 0.55; MeOH) EXAMPLE 3 Production of 1 ° f 5-cyclopropylene-H-1-2-fluoro-phenylenecarbamate]) piperidi-1-γ-1 H-pyrrazol-4-carbonyl} ° 3- (p¡ridin ° 3 ° i¡) pirrol§di [rag? 1- [5-Cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole-4-carbonyl] -3- (pyridin- 3-yl) pyrrolidine (100 mg) produced in example 1, step 5 was dissolved in chloroform (2 ml), triethylamine (38 ml) and 2-fluorophenylisocyanate (34 ml) were added, and the mixture was stirred at ambient temperature. for 3 h. The reaction mixture was concentrated under reduced pressure, and the residue obtained was purified by silica gel chromatography (chloroform: methanol = 11: 1) to yield the title compound as a white amorphous solid (111 mg).

EXAMPLE 4 Production of 1-f1-f1-carbamoylpiperid? N-4-B8) -5 ° € icloprop ~ B-1H-pyrgi2g) 0 ° 4- carbonyl1-r (S) -3 - ([2 rfluoromethylfeniC) 1 pyrrolid5riia 1- [5-Cyclopropyl-1- (piperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (1.0 g) produced by a similar method to that of example 1Step 5 was dissolved in acetic acid (3 ml) and water (6 ml), and an aqueous solution (6 ml) of sodium cyanide (300 mg) was added at room temperature. The mixture was stirred at ambient temperature for 6 hours while sodium cyanide (750 mg total) was added thereto. The mixture was extracted with ethyl acetate, and the ethyl acetate layer was washed with 1 N hydrochloric acid, with water, with saturated sodium carbonate solution in water, with water and saline, and dried over magnesium sulfate. anhydrous. The mixture was concentrated under reduced pressure, and the obtained residue was purified by gel chromatography of silica (chloroform: melanol = 10: 1). Diethyl ether (10 ml) was added, and the mixture was stirred at ambient temperature for 2 h. The precipitated solid was collected by filtration and dried to yield the title compound as white crystals (581 mg).

EXAMPLE S Production of 1-. { 1 1 ° F 2 -carboxyphenylcarbamate) ii) pñperñdin? ^ - iil - @ - ecyclopropyl-1H-pyrazole-4-carbonyl > -f (S) -3 - ([2-tpfluoromet »¡fepi¡! npirr © nc ñ [p? a 1- [5-Cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine hydrochloride (703 mg) of Example 2 was suspended in chloroform (7 ml), and triethylamine (0.23 ml) was added. Under an ice bath, 2-methoxycarbonylphenyl isocyanate (292 mg) was added, and the mixture was stirred at room temperature for 2 h. The mixture was concentrated under reduced pressure, and the residue obtained was purified by silica gel chromatography (chloroform: methanol = 30: 1) to give 1-. { 5-Cyclopropyl-1- [1- (2-meioxycarbonylphenylcarbamoyl) pipehdin-4-yl] -1H-pyrazole-4-carbonylH (S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (992 mg) as a white amorphous solid . The 1 -. { 5-cyclopropyl-1 - [1- (2-meloxycarbonylphenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonylH (S) -3- (2-ylfluoromethylphenyl)) pyrrolidine (244 mg) obtained was dissolved in Hydrohydrofuran (0.4 ml) and melanol (0.2 ml); A 4N solution of sodium hydroxide in water (0.4 ml) was added, and the mixture was stirred at 60 ° C for 4 h. The mixture was concentrated under reduced pressure, and the residue obtained was dissolved in water. Under an ice bath, the mixture was acidified with 2N hydrochloric acid and extracted with chloroform. The chloroform layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. N-hexane was added to the residue to give crystal precipitation. The obtained crystal was washed with n-hexane and dried under reduced pressure to produce the title compound as a white amorphous solid (181 mg).

EXAMPLE 6 Production of 1-f5-cyclopropyl-1-p-f2-hydroxBm? Ethylfen5Pearbarrii @ plll) - piperidin-1-l-1-H-pyrazo8-4-carboniB -r (SD 3 - (; 2 ° triflyoroiipetilphen l)] pyrrolidine 1-. { 5-Cyclopropyl-1- [1- (2-methoxycarbonylphenylcarbamoyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (213 mg) obtained in example 5 it was dissolved in teirahydrofuran (2 ml) and ethanol (2 ml), and lithium chloride (30 mg) and sodium borohydride (26 mg) was added under an ice bath. The mixture was stirred overnight at ambient temperature. The precipitated insoluble material was collected by filtration, and washed with chloroform. The filtrate and washing were combined, and the mixture was washed with water, with a saturated solution of sodium chloride in water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. He The obtained residue was purified by silica gel chromatography (chloroform: melanol = 30: 1) to produce the title compound as a white amorphous solid (109 mg).

EXAMPLE 7 Production of 1-f-5-cyclopropiB-1 1 - (1-hydroxymethyl-cycloBopropycarbam-BI "piperidin-4-yl] -1H-pyrazole-4-carbonylHyS!) - 3 - ([2-trifluoromethylphenyl)] pyrrol8-dine By a method similar to that of Example 5, the compound of the title was obtained as a white amorphous solid (530 mg) of hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4. -carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] - pyrrolidine (1.07 g) of example 2.

EXAMPLE S Production of 1 -. { S-ecyclopropii-11 - [1 - (2-hydroxyethylcarba? T? 8I]) piperi -iip? 4-yN-1H-pyrazole -carbonylH (S] > -3- (2-trifluoromethylpheniolpSrrolidB g? For a similar method as in Example 5, the title compound was obtained as a white amorphous solid (202 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4- hydrochloride. carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] - pyrrolidine (206 mg) of example 2.

EXAMPLE 9 Production of 1-5-cyclopropyl-142-. DroxM A -dimet-B-ethylcarbapp @ D) -piperidin-B-MBH-pyrazole-4-carbonyl »HIS]) - 3 ° (1-trifluoroimethylphenyl)) lpyrrolidBna By a method similar to that of Example 5, the title compound was obtained as a white amorphous solid (341 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-hydrochloride. -carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] -pyrrolidine (350 mg) of example 2.

EXAMPLE 10 Production of 1 1 1 - (2-acetylaminoethylcarbamoBl) pip®? T5di? P-440-i-cyclopropyl-1H-pyrazole-4-carbonill > 4 (S) -342-trifiuoromethylBrn) lpyrrG) [lDg.5? P? A Stage 1 Production of 1-. { 5-Cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine To the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) - 3- (2-trifluoromethylphenyl)] pyrrolidine (5.04 g) of Example 2 was added chloroform (50 ml), N, N-diisopropylethylamine (4.68 ml) and chloroform of 4-nylphenyl (2.39 g) was added under an ice bath , and the mixture was agitated at ambient temperature for 1 h. The mixture was concentrated under reduced pressure, acidified with 1 N hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (chloroform: methanol = 20: 1) to yield the title compound as a pale yellow amorphous susland (5.41 g).

Eíapa 2 Production of 1-. { 1- [1- (2-Acetylaminoethylcarbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine 1-. { 5-Cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg) produced in the previous step was dissolved in N-meitylpyrrolidone (1 ml), and N- (2-amino-ethyl) -acetamide (96 ml) was added. ). The mixture was stirred overnight at 80 ° C. After allowing to cool, 10% aqueous solution of poasium carbonate was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water, with 1N hydrochloric acid and with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: melanol = 15: 1) to yield the title compound as a white amorphous solid (65 mg).

EXAMPLE 1 Production of 1,4-aminoethylearbam (5i) piperB] g hydrochloride [ffl- -5B1 ° β-cyclopropyl-1H-pyrazolecarbonyl} 4 (S-342-tri luorometiPfeni8 1pi [r? R (a) BDdi [p? A 1-. { 5-Cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg) produced in example 10, step 1 and t-butyl (2-aminoethyl) carbamazo (160 mg) were dissolved in acetoniiril (1 ml) , and the mixture was stirred overnight and was heated under reflux. The mixture was diluted with chloroform, and the mixture was washed with water, with aqueous solution of carbonated acid, with water and saline, and dried over anhydrous magnesium sulfate. The mixture was concentrated under reduced pressure, and the residue obtained was purified by silica gel chromatography (chloroform: melanol = 10: 1). The amorphous solid obtained was dissolved in ethyl acetate (1 ml), and 4N hydrochloric acid solution in ethyl acetate (4 ml) was added. The precipitated solid was filtered off and dried to yield the title compound as a white amorphous solid (111 mg).

EXAMPLE 12 Production of 145-cyclopropyl8-1-14.1-dioxothio orfo3cp? A-4-ca piperidin-44n-1H-pyrazoyl-4-carbonylH (S) -342 ° trifluoromethylphen? BD11 ° pyrrolidine 1-. { 5-Cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (250 mg) produced in example 10, step 1, and thiomorpholine (0.13 ml) were dissolved in N-methylpyrrolidone (1 ml), and the mixture was stirred Go through the night at 100 ° C. After allowing the cooling, the mixture was diluted with diethyl ether, was washed with water, 5% aqueous solution of potassium carbonate and saline, and was dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (ethyl acetate: methanol = 30: 1) to give 1-. { 5-cyclopropyl-1- [1- (thiomorpholine-4-carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine as a white amorphous solid (224 mg). This was dissolved in chloroform (4 ml), and m-chloroperbenzoic acid (319 mg) was added under an ice bath. The mixture was stirred for 3 h while it was allowed to gradually return to ambient air. Aqueous aqueous solution of sodium iosulfate and saturated aqueous solution of sodium hydrogen carbonate were added, and the mixture was extracted with chloroform. The chloroform layer was washed with saline and dried over anhydrous sodium sulphonate. The mixture was concentrated under reduced pressure, and the residue obtained was purified by silica gel chromatography (add elly: methanol = 30: 1) to thereby produce the title compound as a white amorphous solid (198 mg).

EXAMPLE 3 Production of 145-cycloBopropyB 1 1 142-dBftnetBlamiiii® © ®ftiB-carbamoiHpiperidin-4n-1H-pyrazoB ^ 4-arboni-BIS) -3- (? 2 ° trifBuoroBnetylphenyl) 1pirroBidine By a method similar to that of Example 10, the compound of the product was obtained as a yellow amorphous solid (130 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-lrifluoromethylphenyl)) pyrrolidine (200 mg).

EXAMPLE 4 Production of 145-cyclopropyl-1 144-hydroxypiperidine? M-carb?) IpiDll *) - piperidine-44ll-1H-pyrazo8 ^ 4 -carboni8H (S) -342 rgfluor © me1tilfenDnD1- By a method similar to that of Example 10, the title compound was obtained as a white amorphous solid (176 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 15 Production of 4141 azetidin-1-carbonyl) piperidin-4B1 ° S-sky (?) PoC-1-pyrazole-4-carbonyl > - [(S) -342-trifluoromethylphenol-1pgrro8id8na By means of a method similar to that of Example 10, the title compound was obtained as a white amorphous solid (150 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 16 Production of 145-cyclopropyl-41 3-hydroxypyrroBdi? P? 1-earb? [Rii6B | ° piperidin-44ll-1H-pyrazoylcarbon] > 4 < S) -342 rifluoromethylphenBD1- By a method similar to that of Example 10, the title compound was obtained as a white amorphous solid (175 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l fluoromethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 17 Production of 145-c5clopropB8- 142 ° hydrochloride piperidirB-1-5D- eti »carbamoyl) piperBdin ^ 44IMH-pyrazo8-4-carboniBVlSl > -342- triflyorometüfenimpirroiidina By a method similar to that of Example 10, the title compound was obtained as a pale yellow amorphous solid (170 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomomethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 1® Production of 145 <; ielopropiB- 41 4.4-diflluoropip@rñcfo°1- plperidln-4-ITI-1H-pyrazole-4-carbon? IH (Sl-342- trifluoiromethylphenyrrolidine By a method similar to that of Example 10, the title compound was obtained as a pale yellow amorphous solid (132 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 19 Production of 1-5-cyclopropy8-141 3.3-dif8uoropyridine β1- € air piperidin-4ll-1H-pyrazole-4-carbon (IHfS) -342-trifluoroB, r? Et SlfenBB]) 1-pyrrolidine By a method similar to that of Example 10, the title compound was obtained as a pale yellow amorphous solid (152 mg) of 1-. { 5-cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl) -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 20 Production of 14S-ciciopropi8-14143-hydroxyazetBdBrii ° lHearbQriiñD]) - piperidin-44IMH-pyrazole-4-carbonylH (S) ~ 342-trifluoroB raeti8fenB By a method similar to that of Example 10, the compound of the title was obtained as a white amorphous solid (158 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 21 Production of 1 5-cyclopropyl-1414 (R) -3-hydroxypyr8Bdnn-1 ° ea piperidine ^ 44l) -1H-pyrazoM-carboniBH (S-342-trif8yor? I? Neti8fe? Rp? ND11 ° pyrrolidine By a method similar to that of Example 10, the title compound was obtained as a white amorphous solid (171 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 22 Production of 1-5-CyclopropiB-414 (S) -3-HydroxypyrroBid 5 [p? -1-ca? I @? PiDl] -piperidin-4l) -1H-pyrazole ^ -earbonBl) 4 (S -342 rifluor © metilfenin]) Tl ° By a method similar to that of Example 10, the compound of the product was obtained as a white amorphous solid (172 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 23 Production of 145-cyclopropiB-414 (SI-2-hydroxy-1-methyl-ethylcarbam-Cl-piperidine-44l> -1H-pyrazole ^ -earboni8) 4 (S-342-trifluoro-methy-B-benBD-1-piirrol-Bina For a similar method as in Example 10, the title compound was obtained as a yellow amorphous solid (60 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 24 Production of 145-cyclopropyl-1-4-hydroxymethyl-pyridine-earbonyl) piperidine-44-MPH-pyrazole-4-carbonym (S-342) trifluoromethylphenhydropyridine For a similar method as in Example 10, the title compound was obtained as a white amorphous solid (94 mg) of 1-. { 5-cyclopropyl-1 - [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (150 mg).

EXAMPLE 25 Production of 141 144 ° < carboxypiperidine-1 -carbonylpiperidine- B [] ll -5- ecyclopropi8-1H-pyrazole-4-carbonylH (S) ° 342 ° trifluoromet88feniB) lpirr @ Dñ l5ina For a similar method as in Example 10, the title compound was obtained as a white amorphous solid (65 mg) of 1-. { 5-cyclopropyl-1 - [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine (172 mg).

EXAMPLE 28 Production of 145-cycloprop8l-141 3-oxopiperaz »8i? 1 -carb) onil | pip? O-5d? P? 44n-1H-pyrazole-4-carbonylH (S) -342-trifluoroethylphenol By a method similar to that of Example 10, the title compound was obtained as a white amorphous solid (143 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 2? Production of 145-cyclopropiM 414 (S | 2-hydroxy? Met88pirroBBd5iit? 1 -carboninpiperidin ^ 4-yl) -1H-pyrazole -carboniB) 4S ^ -342 ° trifluoromethylpheniQlpyrrolidine By a method similar to that of Example 10, the title compound was obtained as a yellow amorphous solid (150 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 28 Production of 145-c-Clopropyl-141 3'HydroxymethylBazetidine-carbonyl) piperidine ^ 4ll-1H-pyrazoi ^ -earboniBHIS1) -342 ° trifluorom? Eti8fenii) lpyrrolBdiit? A By a method similar to that of Example 10, the title compound was obtained as a yellow amorphous solid (178 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nyl-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 28 Production of 145-cycloBopropyl-4-m®ftBBp'pera-ZD [p) -1-earbonyl) piperidine ^ 4n-1H-pyrazoM-carbonylH (Sl ° 342 ° trifluoromethylphenidi-pyridine) By a method similar to that of Example 10, the compound of the isolate was obtained as a white amorphous solid (66 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine (150 mg).

EXAMPLE 30 Production of 14β-cyclopropiB-1-44-propylpiperg-zn hydrochloride [p. 1 ° earbonyl) piperidine ^ 4n-1H-pyrazole ^ -carboniBHtSμ342- trifluoromethylphenhydropyridine By a method similar to that of Example 10, the title compound was obtained as a white amorphous solid (50 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (150 mg).

EXAMPLE 31 Production of 14141 4-aeetiipiperazin-1-earbonyl) pip ridi [p-4-e8clopropyl-1H-pyrazo8 ^ 4-carbonyl > 4 (S) -342 ° trifiuorometiif®nil By a method similar to that of Example 10, the compound of the product was obtained as a white amorphous solid (56 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (150 mg).

EXAMPLE 32 Production of 145-c? C8opropil-1 1 (R) -3-hidroxipBperid8n-1 earboni8lpiperidin-44D) -1H-pirazo¡-4-carbon8IH (Sμ342- trifluo? Rometilfenil)] pyrrolidine By a method similar to that of Example 10, the compound of the product was obtained as a yellow amorphous solid (170 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nyl-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomomethylphenyl)] pyrrolidine (200 mg).

EXAMPLE 33 Production of 1-1414144-carbapnoilpiperidin -carbopillpÉperi Liira toab S- ^ £ iclopropil-1H-pyrazol-4-carbonilH (S]) - 342-trifluorometilfeBi8l) 1p§rr @ BD (] ot to? For a similar method as in Example 10, the title compound was obtained as a white amorphous solid (108 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine (150 mg).

EXAMPLE 34 Production of 3-earbamoilazetBdin 4141 ° 1 carboniB) p5peridg [-4-nb] 1-S- ^ eiclopropi8-1H-pirazo8 -carbonilH (S) ~ 342-tr8fluorometi8feB By a method similar to that of Example 10, the compound of the product was obtained as a white amorphous solid (93 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nyl-phenoxycarbonyl) pipehdin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (171 mg).

EXAMPLE 35 Production of 1 14 4 -hydrochloride to inopi-pyrididyl-1-carbonyl) pipergdin ^ 4481-5-cyclopropi > -1H-p8razoB- -carb @ [pi8 4fS]) - 3 2- trifluoromethylphenidi-pyrrolidine For a similar method as in Example 11, the title compound was obtained as a white amorphous solid (302 mg) of 1 -. { 5-Cyclopropyl-1 - [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (478 mg).

EXAMPLE 38 Production of hydrochloride 1141 3-aminop5rrol5diím-1- carboniB) piperidin-44n-5-c? C¡opropii-1H-pyrazol-4-earbo? N} -r (S) -3 - (? 2- trifluoromethylphenol) pyrroiidine By a method similar to that of Example 11, the title compound was obtained as a pale beige amorphous solid (635 mg) of 1-. { 5-cyclopropyl-1 - [1- (4-niirophenoxycarbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)] pyrrolidine (478 mg).

EXAMPLE 37 Production of 145-cyclopropyl hydrochloride ppp.RTM.RTM. D ° -carbamoyl) piperidin-44H-1H-pyrazole-4-carbonifl > 4 (SI ° 342 ° trifluoromethylphenyl) 1pyrrolidine By a method similar to that of Example 11, the compound of the title was obtained as a white amorphous solid (59 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (478 mg).

EXAMPLE 38 Production of 145-Cs-8-Crop-5-l4-DmitryBannBip-1-piperidine-1-carbonyl) pyrimidin-4-yl-1-H-pyrazole-4-ea-rboriiB8HIS hydrochloride) 3-2-trifluoroethyltetrapyrrolidine By a method similar to that of Example 12, the title compound was obtained as a white amorphous solid (74 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (478 mg).

EXAMPLE 39 Production of 14141 4-acetylaminopiperidine -carboniB | pgperid8rii- eicoropropyl-1H-pyrazo8-4-carbonyl > 4 (S) -342-trif8uorometi8f®ni > By a method similar to that of Example 12, the compound of the product was obtained as a white amorphous solid (100 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-uro-trifluoromethyl-phenyl)] pyrrolidine (478 mg).

EXAMPLE 40 Production of 14 4143-acetyl? Minopyro8 * din-1 -carboni c8opropyl-1H-pyrazo8-4-carboni8H (S) -342-trifluoromethylBf.ni By a method similar to that of Example 12, the title compound was obtained as a white amorphous solid (127 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (478 mg).

EXAMPLE 41 Production of 145-hydropropyl-41 hydrochloride 3- dimethylaminopyrrolidin-1 -carbonyl) piperidin-44B] -1 H-pyranes eol-4-cs vrboml-rÍS | -342 rifluorometho-phenyl)] pyrroiid§ng? By a method similar to that of Example 12, the title compound was obtained as a pale beige amorphous solid (141 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (478 mg).

EXAMPLE 42 Production of 45-cyclopropSB-1 1 -? PrBttiltpperyl lp [p? -4-b-carbamoyl) piperidSn-4-ill-1H-pyrazole-4-carbonyl hydrochloride) - (fS) -342 ° rifl orometilfeniDirrolidina By a method similar to that of Example 12, the compound of the isolate was obtained as a white amorphous solid (116 mg) of 1 -. { 5-cyclopropyl-1 - [1 - (4-nitrophenoxycarbonyl) p.peridin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (181 mg).

EXAMPLE 43 Production of 1414141 -acetylpiperidine-44l-carbap.oilDipaper? Din- "Dini-5-cyclopropi8-1H-pyrazole-4-carbonyl) 4 (S) 342-trif8uoromethy8feni8 By a method similar to that of Example 12, the compound of the isolate was obtained as a white amorphous solid (41 mg) of 1-. { 5-cyclopropyl-1 - [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-nifluoromethylphenyl)] pyrrolidine (181 mg).

EXAMPLE 44 Production of 14β-cyclopropyl-1β-4-oxopiperidine-1-caryl or β-p ?i) pBP®? R? Li? P? -4-in-1H-pyrazole-4-carboni8 > 4 (S) -342-trifluoromethy8fepBB1) 1pir? Roli By a method similar to that of Example 12, the title compound was obtained as a white amorphous solid (155 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) pipehdin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-lrifluoromethylphenyl)] pyrrolidine (540 mg).

EXAMPLE 45 Production of 14141 3 ° aeetitaminoazetidin-1-eaHboniB]) piperBdñ¡¡t) ° cyclopropyl ° 1H-pyrazole -carboni8 > -f (S) ° 342 ° trif8uoronnet§8fen By a method similar to that of Example 12, the title compound it was obtained as a white amorphous solid (68 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (90 mg).

EXAMPLE 46 Production of 145-cyclopropyl-141 3-oxopyridididyl-1-caybonyl) p. 0) (DrS iro-4411-1 H-pyrazoi-4-carbonylH (S? 342-trifluoromethyl-phenyl? For a similar method as in Example 12, the title compound was obtained as a white amorphous solid (155 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl) -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (300 mg).

EXAMPLE 47 Production of 145 ^ Cloprop.M 1 2.2.2-Trifluoroethylcarbamoyl 4-in-1H-pyrazoyl-4-carbonylH (S) -342-trifluoromethylphen Stage 1 Production of (2.2.2-trifluoro-eyl) carbamazo-4-ylorophenyl 2.2.2-Trifluoroethylamine (392 mg) was dissolved in chloroform (4 ml), and pyridine (0.35 ml) and chloroform of 4-niiophenyl (2.39 g) was added under an ice bath. The mixture was stirred at room temperature during 1 hour. The mixture was concentrated under reduced pressure, water was added to the residue obtained, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with 1N hydrochloric acid and with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Diisopropyl ether was added to the obtained residue, and the precipitated solid was filtered off and dried to yield the title compound as a white solid (501 mg).

Stage 2 Production of 1-. { 5-Cyclopropyl-1- [1- (2,2.2-trifluoro-eylcarbamoyl) -piperidin-4-yl] -1 H -pyrazole-4-carbonylH (S) -3- (2-trifluoromethyl-phenyl)] pyrrolidine (2.2.2- trifluoroethyl) carbamate 4-Nitrophenyl (113 mg) produced in the previous step and the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole-4-carbonyl] - [(S ) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg) of example 2 were dissolved in pyridine (1 ml), and the mixture was stirred at 80 ° C for 2 h. After allowing cooling, toluene was added and the mixture was concentrated under reduced pressure. 10% solution of potassium carbonate in water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with 10% potassium carbonate solution in water, with water, with 1N hydrochloric acid and with water again, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: methanol = 15: 1) to yield the title compound as a pale yellow amorphous solid (162 mg).

EXAMPLE 48 Production of 145-cyclopropyl-1 1 3.3.4.4-tetraf8uo? R (pyrrolidDip? -'el) carbonyl) piperidBn ^ 4-ill-1H-pyrazo8 ^ 4-carbonyl) 4 SD-3 - ([2 ° trif8uoro etilfeni8) 1pirroiidina By a method similar to that of Example 47, the title compound was obtained as a pale yellow amorphous solid (138 mg) of hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole- 4-carbonyl] - [(S) -3- (2-trifluoromethyl-phenyl)] pyrrolidine (468 mg) of example 2.

EXAMPLE 49 Production of 145-cycloprop8ll-141l SS) -1-hydroxyl-methyl-2-methylpropylcarbamoyl] piperidin-4-Bl > 1H-pyrazoB-4-carb (i8) 4lIS3 ° ([2- trifluoromethylphenol) pyrroBBdina By a method similar to that of Example 47, the thioule compound was obtained as a white amorphous solid (166 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4- hydrochloride. carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (250 mg) of example 2.

EXAMPLE 5 (Production of 141414 <SM ° benzyl-2-hydroxyetiBcarbam? Bnpiperi? -c8c8opropyl-1H-pyrazole-4-carbonii) 4 (S) -342-trBfluorometB8feniB) 1p By a method similar to that of Example 47, the compound of the product was obtained as a white amorphous solid (140 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4- hydrochloride. carbonyl] - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (300 mg) of example 2.

EXAMPLE 51 Production of 11 -. { S-cyclopropyl-1-f 1 -f (S) -2-hydroxS-1-phenylethylcarbaipiopion-piperidine-8) -1H-pyrazole ^ -carboni04 (SI) -342- trafl oromethylphenyldipyridine By a method similar to that of Example 47, the title compound was obtained as a white amorphous solid (170 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-hydrochloride. -carbonyl] - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine (300 mg) of example 2.

EXAMPLE 52 Production of 1 5-c5clopropyl-14 (S) -1-hydroxymethyl-3-m & amp; 5-butyl-8-carbamoyl-pperidin-448) -1H-pyrazoB ^ -carboniDM (SW-trifiuoromethylphenyl) llpyr? RoBidBna By a method similar to that of Example 47, the title compound was obtained as a yellow amorphous solid (256 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-hydrochloride. -carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (250 mg) of example 2.

EXAMPLE 53 Production of 145-ecyclopropiB-14 2-hBdroxypheneBcarbamoyl) -98p-iH-p-azole-4-carbonyl (S '; - 3- (2-trifluoromethyl-pyrroic; By a method similar to that of Example 47, the title compound was obtained as a white amorphous solid (125 mg) of hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4. -carbonyl] - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 54 Production of 14S-cyclopropyl8-14 1-hydroxymethiB (Sñclopep? Ft50 ° earbamoyl) piperidin-448] -1H-pyrazole ^ -carboniM (# 342- trifluoro eti8phenyl) 1pyrrolidine By a method similar to that of Example 47, the title compound was obtained as a white amorphous solid (92 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4- hydrochloride. carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE §S Production of 141 1- eneensulfonylaminocarbo? Ni8p¡per¡dBn-4-ñB *) - §- cielopropyl ° 1H-pyrazole-4-carbonyl14 (S] > -342-trifluoro? Tp? Eti8f®níl) lpBrr © |] Dsiina Chloroform (3 ml) was added to 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] hydrochloride] pyrrolidine (250 mg) of Example 2, were added eryrylamine (81 ml) and sulfonyl isocyanate (78 ml) and the mixture was stirred for 2 h. The mixture was concentrated under reduced pressure, water was added to the obtained residue, and the mixture was extracted with chloroform. The chloroform layer was washed with saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: melanol = 10: 1). The solid obtained it was recrystallized from acetyl ether to produce the title compound as a pale yellow solid (40 mg).

EXAMPLE 56 Production of 145-cyclopropylamino-1-methanesulfonylBaminoearboo? I8pñp®? RBdDip? -4-yl) -1H-pyrazole-4-carboniB14 (S) -342-trifluoromethylphengB]) 1 pyridine I? Fl5 [p? G ? By a method similar to that of Example 55, the title compound was obtained as a pale yellow amorphous solid (200 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H -pyrazole- 4-carbonyl] - [(S) -3- (2-l-trifluoromethyl-phenyl)] pyrrolidine (500 mg) of example 2.

EXAMPLE 57 Production of 145-cyclopropyl-1-methoxycarboniBpip®ridin-4-ñB!) - H H-pyrazole-4-carbonyl14 (S) -342-trifluoromethyl B-phenylBrimidine 1- [5-Cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethyl-phenyl)] pyrrolidine hydrochloride (200 mg) of Example 2 was suspended in chloroform (2.0 ml), and polasium carbonate (177 mg) was added under an ice bath. The methyl chloroformate (49.4 μl) was added, and the mixture was allowed to return to room temperature and was stirred for 1.5 h. Methyl chloroformate (49.4 ml) was added additionally, and the mixture was stirred at room temperature for 15.5 minutes. h. A saturated solution of sodium hydrogen carbonate in water was added to the reaction mixture, and the mixture was extracted 3 times with ethyl ether. The organic layer was washed with water and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (chloroform: meianol = 30: 1) to yield the compound of the product as a white amorphous solid (210 mg).

EXAMPLE 58 Production of 145-cyclopropyl-1-l, 2-hydroxyethoxycarbootyl) piper5 ln? P? -4-BBl-1H-pyrazole ^ 4-carbonnl > 4IS) -342-trifluoromethylphenylMpyrrolidi ^ a For a similar method to that of Example 57, the title compound was obtained as a white amorphous solid (214 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-hydrochloride. -carbonyl] - [(S) 3- (2-trifluoromethylphenyl)] - pyrrolidine (300 mg) of example 2.

EXAMPLE 59 Production of 14§-eyeloprop5B ° 1 2"di-ethylaminoethoxycarbonyl) piperidine-4 ° ip-1H-pyrazole ° 4-carbon? L> - [f ([i]) ° 3 - ((2 ° rifByoro etilfeniDIpirrolidBna By a method similar to that of Example 10, the title compose it was obtained as a white amorphous solid (166 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (300 mg).

EXAMPLE 80 Production of 145- clopropiB-141 2-Piperidium hydrochloride) "1 -oD ° ethoxycarbonyl) piperidin-4-ip-1H-pyrazo8-4-earbonne] 4fSI-342 ° trifBuoromethylphenol)] pyrrolidine By a method similar to that of Example 10, the title compound was obtained as a white amorphous solid (219 mg) of 1 -. { 5-Cyclopropyl-1 - [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine (300 mg).

EXAMPLE 61 Production of 14β-c¡c8opropy8 ° 1 [H ° Pyridylpyridyl] oxycarbonyl) piperidine ~ 4-in-1H-pJrazoB ^ carbonyl hydrochloride} fS) -342 ° ttrifluoromethylphenyl) 1pyrrolidine By a method similar to that of Example 11, the compound of the title was obtained as a pale yellow amorphous solid (53 mg) of 1-. { 5-cyclopropyl-1 - [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (102 mg).

EXAMPLE 82 Production of 145-bisBopropyB-14-m-tylpiperihydrochloride (di [p) -4-yl-Q-xicarbonyl) pyridin-1-Ib1-1H-pyrazoyl-4-carbonyl) -342"tr5-fluoro-methylphenyl) 1-pyrrolidine For a similar method as in Example 12, the title compound was obtained as a white amorphous solid (64 mg) of 1-. { 5-cyclopropyl-1- [1- (4-nitrophenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-nifluoromethylphenyl)) pyrrolidine (124 mg).

EXAMPLE 63 Production of 14 4 1 -acetylpiperidin-4-α-oxiearbonBB piperidfl'íp? -4 ° DBl-5- Giclopropyl-1H-pirazoB-4-carbonylH (SÍ-342-trifluoro eti8phenyl ^ piFreP5d8na By a method similar to that of Example 12, the title compound was obtained as a white amorphous solid (65 mg) of 1-. { 5-Cyclopropyl-1- [1- (4-niiro-phenoxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomomylphenyl)] pyrrolidine (122 mg).

EXAMPLE 64 Production of 14 1-cyclopropanecarboni8piperidin- -Bl]) ° -cyclo pyrazoi-4-carbonyl4 (S) -342-trifluoromethylpheniB) pyrrolidine? Chloroform (5 ml) and и lilylamine (0.13 ml) were added to hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg) from example 2 and cyclopropanecarboxylic chloride (0.047 ml) was added under an ice bath. After agilling overnight at room temperature, the solvent was removed under reduced pressure, water was added to the ree obtained, and the mixture was extracted with ethyl ether. The ethyl acetate layer was washed with saturated aqueous sodium acid carbonate solution in water and saline, and dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure, and the ree obtained was purified by silica gel chromatography (ethyl ether: methanol = 10: 1) to yield the title compound as a white amorphous solid (170 mg).

EXAMPLE 85 Production of 145-cyclopropyl ° 141 2-hydroxyaceti.) Piperidine "4-dO-HIH-pyrazole ^ -carbonin > -r (S) -342-trifluoromethylfeniB) lpB ^ o8i lBi Chloroform (5 ml) and иrielmylamine (0.16 ml) were added to hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2- trifluoromethylphenyl)] pyrrolidine (250 mg) from Example 2 and acetyxyacetyl chloride (0.069 mL) was added under an ice bath. After stirring the night at ambient temperature, the mixture was concentrated under reduced pressure, water was added to the ree, and the mixture was extracted with acetone. The ethyl acephalic layer was washed with saturated sodium hydrogen carbonate solution in water and saline, and dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure, and the obtained ree was purified by silica gel chromatography (ethyl acetyl: methanol = 10: 1). The amorphous solid obtained was dissolved in tetrahydrofuran (2 ml), methanol (2 ml) and water (4 ml), and lithium hydroxide monohydrate (103 mg) was added. The mixture was stirred at 60 ° C for 4 h. The mixture was concentrated under reduced pressure, 5% aqueous solution of sulphated acid was added to the obtained ree, and the mixture was extracted with ethyl acetate. The oil layer was washed with water and saline, and dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure, and the obtained ree was purified by silica gel chromatography (ellyole: melanol = 20: 1) to yield the title compound as a white amorphous solid (30 mg).

EXAMPLE 86 Production of 145-cyclopropyl-4141 4-fluor @. { FenñB]) - cyclopropancarbonylpperidin-4-5l > 1H-p8razoB-4-carb? Nil) -lííS]) ° 3-tri luoromethylphenol) "ÍpirroBidBna For a similar method as in Example 64, the title compound was obtained as a pale yellow amorphous solid (193 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole- 4-carbonyl] - [(S) -3- (2-t fluoromethylphenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 87 Production of 145 ° hydrochloride CBclopropiB ° 141 2 ° dimethylaminoaceti8) piperidinyl-1H-pyrazo8 ^ 4-carb @ nil > -r ([S]) ° 342- trifiuoro? methylphenyl) 1pyrrol8d? na By a method similar to that of Example 64, the title compound was obtained as a pale yellow amorphous solid (217 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-hydrochloride. -carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 88 Production of 1414 2-acetylaminoacetyl) piperidine-4 ° BB1 ° §-cñc pyrazole-4-carboni8 > -ffS) -342-trifluoromethy8feniB) lp§ [r? ro8idi? ma By a method similar to that of Example 64, the title compound was obtained as a pale beige amorphous solid (119 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H -pyrazole- hydrochloride. 4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 89 Production of 145-cyclopropyl-141 1-methyl-cBopropane? Rbo? IBB ') p? I [r5dBip? -4-in-1H-pyrazoyl-4-carboni8 > 4 (S) -342-trifluoromethylfei gB]) lpir [ro8B (di ^ g? By a method similar to that of Example 64, the compound of the isolate was obtained as a pale yellow amorphous solid (178 mg) of hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H -pyrazole- 4-carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 70 Production of 14141 2-acetylamino-2-methylpropioniBi piperidBn ° ° or B1 ° 5 ° cyclopropyl-1H-pyrazole-4-carboni8 > 4 (S) -342-trifluorometBlfeninipi? By a method similar to that of Example 64, the title compose it was obtained as a pale beige amorphous solid (94 mg) of hydrochloride of 1- [5-cyclopropyl-1- (pipehdin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- ( 2-fluorifomethyl phenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 71 Production of 1 1414 IHS-2-acetylaminopropioniQpBp®ridBn-4 ° p-l-iic8opropyl-1H-pyrazole-4-carbonyl) 4 (S) -342 ° trif8uorom? EtB8phenyl) 1pirroBodlina By a method similar to that of Example 64, the title compound was obtained as a white amorphous solid (183 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-hydrochloride. -carbonyl] - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 72 Production of 1 1414.sup.-2-acetylamino-3-methylBbutyrenB1pgpergdin-44n.,5-cyclopropyl-1H-pyrazoyl-4-carbonyl) 4 (S) -342-trif8uorometB8phenyl) lpir [r (5) 0p] 8nai By a method similar to that of Example 64, the title compound was obtained as a pale yellow amorphous solid (212 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H -pyrazole- 4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 73 Production of 145-cycloBropropB-14 3.3.3-trifluoropropi@Gig |) piper5 l5? P? - -0- 1H-pyrazoM-carbonyl > 4Y) -342-trifluoromethylphengl ^ lpyrrolid? Ctiii By a method similar to that of Example 64, the title compound was obtained as a pale yellow amorphous solid (151 mg) of hydrochloride of 1 - [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole- 4-carbonyl) - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (150 mg) of example 2.

EXAMPLE 74 Production of 1- (S-cyclopropyl-1 (S) -5-oxopyrrolidone-2-carbo-p-piperidin-4-yl) -1H-pyrazoB-4-carboniB -r (§ -342- fcrifluorometilfeng |) 1pirro8idSna By a method similar to that of Example 64, the title compound was obtained as a white amorphous solid (127 mg) of hydrochloride of 1- [5-cyclopropyl-1- (piperid? N-4-? L) -1 H- pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethyl-phenyl)] -pyrrolidine (200 mg) of example 2.

EXAMPLE 75 Production of 14141 3-acetylaminopropioni8) piperidin-4-5l'i-5- (B 1 H-pyrazole ^ 4-carbonBB 4 (S) -342-trifluoronr? Eti8pheniolpyrrolidi ^ For a similar method to that of Example 64, the title compound was obtained as a pale yellow amorphous solid (263 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole- hydrochloride. 4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (355 mg) of example 2.

EXAMPLE 76 Production of 145-c * e »opropyl-1 1 3-h8droxi°2.2-dim@tilpropio [r fl]) ° p¡peridin-4-in-1H-p¡razole -carbonIH (S) -342- trifiuorometi8feniB) 1pyrrolBdina By a method similar to that of Example 65, the compound of the isolate was obtained as a white amorphous solid (238 mg) of hydrochloride of 1- [5-cyclopropyl-1- (pipehdin-4-yl) -1H-pyrazole-4 -carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] -pyrrolidine (250 mg) of example 2.

EXAMPLE 77 Production of 1,11-aminoacetyl hydrochloride piiperidin-4-cyclopropyl-1H-pyrazo8 ^ 4-earboniB > 4fS) -342-trifluoropnet§8f®ngl) 1pi By a method similar to that of Example 65, the title compound was obtained as a pale yellow amorphous solid (219 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H -pyrazole- hydrochloride. 4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 78 45-cyclopropyl-41 1-hydroxymethylcyclopropanecarbonylpiperidip? -44BTl-1B-a-pyrazole-4-carbonyl | -f (S) -342-trifluoromethylphenyl) lpyrrolidBna By a method similar to that of Example 65, the compound of the extract was obtained as white crystals (168 mg) of hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl ] - [(S) -3- (2-trifluoromethylphenyl)] - pyrrolidine (250 mg) of example 2.

EXAMPLE 71 Production of 1,141 hydrochloride 2-amino-2-me 4-in-5-cyclopropyl-1H-pyrazoi ^ -carbonylH (Sl) "342-ftr'fluoromethylphenyl)] pyrro8idine By a method similar to that of Example 65, the thioule compound was obtained as a pale yellowish amorphous yellow solid (154 mg) of 1 - [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole hydrochloride. -4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 80 Production of 145-skypropy-141 4-hydroxybutyrateB) pdp® rdg- -SDTl-1C-fl-pyrazo8-4-carboniiH (S) -342-trifluoromethylphen5 By a method similar to that of Example 65, the title compound was obtained as a white amorphous solid (166 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-hydrochloride. -carbonyl) - [(S) -3- (2-trifluor? methylphenyl)] - pyrrolidine (200 mg) of example 2.

EXAMPLE 81 Production of 145-ecyclopro8-14-14 S) -pyridine-2-carboninpiperidin-4-yl-H-p-arazoB-4-earbonBl]) 4fS hydrochloride) -342 ° trifluoromethylphenidi-pyridine By a method similar to that of Example 65, the title compound was obtained as a pale yellow amorphous solid (569 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole- hydrochloride. 4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine from example 2 (450 mg).

EXAMPLE 82 Production of 145-cgclopropi8-1 14 (S *) - ° Bn? EtiBpBirroBD iin-2-carbopyi-piperid toii-H-pyrazo B-4-carbonyloxy-3X3X2-riflyoromethylphenyl) lpyrrolid5? P? A By a method similar to that of Example 65, the compound of the product was obtained as a pale yellow amorphous solid (192 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole- 4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine from example 2 (450 mg).

EXAMPLE 83 Production of 1-l-1,43-aminopropioniB]) piperidi? P? - 4ni-5-cyclopropyl-1H-pyrazole-4-carbonylH (S) -342-ftrifluoro etS0feniB]) lpgg hydrochloride, Bj © DD (di p) a By a method similar to that of Example 65, the thioule compound was obtained as a pale yellow amorphous solid (414 mg) of hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4 -carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (355 mg) of example 2.

EXAMPLE 84 Production of 1 1414 S) -2-am5no-3-metgBbutirillpñp®? RBdflip? -44I 5-cyclopropyl-1H-pyrazole-4-carboniQ4fS]) - 342- triflouroylmethylphenyl]] pyrro? Bd5na hydrochloride For a similar method as in Example 65, the title compound was obtained as a pale chestnut yellow amorphous solid (182 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole hydrochloride. -4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (150 mg) of example 2.

EXAMPLE 85 Production of 145-ccclopropgB-2-methylaminoacetyl) piperidine-44IMH-pyrazo8- -carboipiben hydrochloride > 4 (S) -3 2- trifluoromethylphenidepyridine For a similar method to that of Example 65, the compound of the extract was obtained as pale brown yellow amorphous solid (183 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole- 4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (150 mg) of example 2.

EXAMPLE 88 Production of 145-cyclopropiB-1 14pgper5di? P? -4-carbonyl) pyrimidin-4-ip-1H-pyrazole-4-earboni8) 4 'S) -342 ° trifluorornethylpheniDlpyrrolidine hydrochloride For a similar method to that of Example 65, the compound was obtained as a pale yellowish amorphous yellow solid (478 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole -4-carbonyl] - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (404 mg) of example 2.

EXAMPLE 87 Production of 145-cyclopropyl-41-BS-butylBaminoae®tBl) piperig-o [p) -4- 1H-pyrazole ^ 4-carbonyl > 4 ([S) -3- (2-trifluoromethylpheniBD1PBrroi By a method similar to that of Example 65, the compound of the product was obtained as a pale yellowish amorphous yellow solid (214 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole -4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 88 Production of 1 14 2-cyclopropanecarbonylaminoacetiB]) piperidi [p? ° -ñB1-5- cyclopropyl-1H-pyrazole-4-carbonyl > 4 (S) -342-trifluorom? EtSBfeniB) 1pirroD5 lBna By a method similar to that of Example 65, the compound of the isolate was obtained as a pale yellow amorphous solid (190 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole- 4-carbonyl] - [(S) -3- (2-irifluoromethyl-phenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 89 Production of 1 1 14 (S) -1-acetylpyrrolidine-2-earbonylpperidylBTi ^ DV5- cyclopropyl8-1H-pyrazoyl-4-earbonyl) 4 (S) -342-trifluoromethylphenhydrophenol [] g lBna By a method similar to that of Example 65, the title compound it was obtained as a pale yellow amorphous solid (189 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- ( 2-trifluoromethylphenyl)] pyrrolidine from example 2 (450 mg).

EXAMPLE 90 Production of 145-cycloEpropy8-14 2-methanesulfoniBaminoae®ftoB]) ° piperidine-44p ° 1H-pyrazole-4-carboni8H (Sμ342- trifluoromethylphenB) 1pyrrol5dine By a method similar to that of Example 65, the title compound was obtained as a white amorphous solid (134 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-hydrochloride. -carbonyl] - [(S) -3- (2-trifluoromethyl-phenyl)] -pyrrolidine from example 2 (152 mg).

EXAMPLE 91 Production of 1414141-acetylpiperidine-4-carbonifl) p5perdin-44TO-§-ecyclopropyl-1H-pyrazole-4-earbonyl > - [(YES-342-trifluoroi? Betglffenil) 1pirB '© D? D¡na By a method similar to that of Example 65, the compound of the product was obtained as a pale yellow amorphous solid (145 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole- 4-carbonyl] - [(S) -3- (2-trifluoromethyl-phenyl)] pyrrolidine (404 mg) of example 2.

EXAMPLE 92 Production of 145-CBC.opropñ8- 4141-? Rp > hydrochloride ®tilpipe carbonyl) piperidin-4-ip-1H-pirazoB ^ 4 ° carboniBHfS) -342 ° By a method similar to that of Example 65, the title compound was obtained as a pale yellowish amorphous yellow solid (151 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole hydrochloride. -4-carbonyl] - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine (404 mg) of example 2.

EXAMPLE 93 Production of 1 1 1 3 ° carbamoylpropiongi) piperid5n «4 ° 5B] -5-cicBoprop5B ° 1H-pyrazoM-carbonylH (S ^ -342-trifluoroethylphenyl)) lpyrro8idB ^ g] By a method similar to that of Example 65, the title compound was obtained as a white amorphous solid (61 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4 -carbonyl] - [(S) -3- (2-trifluoromethyl-phenyl)] -pyrrolidine (200 mg) of example 2.

EXAMPLE 94 Production of 14141-carbamo8BmetiBpiperidgn-B]) 5-cyclopropyl-1H-pyrazole-4-carbon8p4 (S) -342-trifluoronnetiiphenyl] -1p8! Rr @ l] ínline.

Chlorhydrate of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethyl-phenyl)] pyrrolidine (200 mg) of Example 2 was dissolved in N, N-dimethylformamide (2.5 ml), and potassium carbonate (93 mg) and 2-bromoacetamide (50.7 mg) were added. The mixture was stirred at ambient temperature for 2 h. Water was added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with water and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (chloroform: melanol = 20: 1) to give 1- [1- (1-carbamoylmethylpiperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (167 mg) as a white amorphous solid. 1- [1- (1-Carbamoylmethylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (154 mg) obtained in The above step was dissolved in ethyl acetate (2 ml), and 4N hydrochloric acid solution in ethyl acetate (159 ml) was added. The mixture was stirred for 10 min. The precipitated crystals were separated by filtration and dried to produce the title compound as a white amorphous solid (109 mg).

EXAMPLE 95 Production of 145-ecyclopropiB-1 1-methylcababa hydrochloride [pp) @ o1 ° methylpiperid8n ^ -i8HH-pyrazo »-4-carbonitl4 (§ 342- trifluoromethylfeniB) 1 pyrrolidine. 1- [5-Cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine hydrochloride (2.5 g) was dissolved. Example 2 in N, N-dimethylformamide (20 ml), and potassium carbonate (1.62 g) and ethylene bromoacety (0.98 g) were added. The mixture was stirred at ambient temperature for 1 h. Water was added to the reaction mixture, and the mixture was extracted twice with acetyl ether. The organic layer was washed with water and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (chloroform: melanol = 25: 1) to give 1-. { 5-cyclopropyl-1- [1- (ethoxycarbonylmethyl) piperidin-4-yl] -1 H-pyrrazol-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (2.79 g) as a white amorphous solid. 1-. { 5-Cyclopropyl-1- [1- (eloxycarbonylmethyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (1.4 g) obtained in the previous step was dissolved in iohydrofuran (5.5 ml) and meianol (2.7 ml), and a 4N sodium hydroxide solution was added to the solution. water (1.4 ml). The mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure, and the obtained residue was dissolved in water.

The aqueous layer was washed twice with diethyl ether, adjusted to pH 5-6 with 2N hydrochloric acid under an ice bath, and expelled 3 times with chloroform. The chloroform layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and n-hexane was added to the obtained residue. The precipitated solid was collected by filtration, and dried to give 1- [1- (1-carboxymethylpiperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl] - [(S) -3- ( 2-fluorifomethyl phenyl)] pyrrolidine (1.17 g) as a white solid. N, N-Dimethylformamide (3.0 ml) was added to 1- [1- (1-carboxymethylpiperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl] - [(S) -3- (2 -lifluoromethylphenyl)] pyrrolidine (150 mg) obtained in the previous step, were added 1-hydroxybenzotriazole (61 mg) and the hydrochloride of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (76 mg), and the mixture was stirred at ambient temperature during 1 hour. A 40% solution of meilylamine in water (106 ml) was added, and the mixture was stirred for 5 h, a 40% solution of methylamine in water (318 ml) was added, and the mixture was stirred at ambient temperature. 13 h. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with saturated sodium hydrogen carbonate solution in water, water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (chloroform: methanol = 20: 1). The amorphous solid obtained was dissolved in ethyl acetate (2.0 ml), 4N hydrochloric acid solution in ethyl acetate (100 ml) was added, and the mixture was stirred for 10 minutes. min. The precipitated crystals were separated by filtration and dried to yield the title compound as a white amorphous solid (16.9 mg).

EXAMPLE 96 Production of 1,141 1-carba hydrochloride oiB-1 ° Bn-5-cyclopropyl-1H-pyrazoB-4-earbonylHyS)) 342-trBfBuoromethylphenyl) pyrroBidine Cummylamine (1.1 g) and eryrylamine (1.2 ml) were dissolved in chloroform (10 ml), and a solution of 2-bromoisobutyryl bromide (1.0 ml) in chloroform (2 ml) was added under an ice bath for 5 min. The mixture was agitated at room temperature for 15 min. The mixture was concentrated under reduced pressure, ethyl acetate was added to the obtained residue, and the mixture was washed with water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The white solid obtained was washed with diisopropyl ether, and dried to give 2-bromo-2-methyl-N- (1-methyl-1-phenylethyl) propylamide as a white solid (1.73 g). 1- [5-Cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethyl-phenyl)] pyrrolidine hydrochloride of example 2 was dissolved in teirahydrofuran (5.5 ml), and 60% sodium hydride (104 mg) was added.

The mixture was stirred at 60 ° C for 1 h and at ambient temperature for 5 min. 2-Bromo-2-methyl-N- (1-meityl-1-phenyletyl) -propylamide was added (329 mg) produced in the anterior layer, and the mixture was shaken at 60 ° C for 22 hours. After allowing to cool, water was added to the reaction mixture, and the mixture was extracted with ethyl ether. The acetyl ether layer was washed with saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: melanol = 20: 1) to give 1- (5-cyclopropyl-1 - { 1- [1-methyl-1 - (1-methyl-1 - phenylearylcarbamoyl) eyl] piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine as a pale yellow amorphous solid (78 mg). It was dissolved 1- (5-cyclopropyl-1- { 1- [1-meityl-1- (1-meityl-1-phenylethylcarbamoyl) eyl] piperidin-4-yl.} -1 H-pyrazole-4- carbonyl) - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine produced in an anterior step in hydrochloroic acid (2 ml), and the mixture was stirred at 80 ° C for 8 h. The hydrolyzoic acid (1 ml) was added and the mixture was stirred at 80 ° C for 8 h. After allowing to cool, the mixture was concentrated under reduced pressure, and the residue obtained was dissolved in ethyl acetate. The ether oil layer was washed with sodium carbonate acidic saline solution in water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: acetyone = 4: 5? Chloroform: meianol = 10: 1). The residue obtained was dissolved in ethyl acetate (1 ml), and a 4N solution of hydrochloric acid in ethyl acetate (1 ml) and diethyl ether (1.5 ml) was added. The solid obtained was separated by filtration and dried to produce the compound of the extract as a pale yellow solid (36 mg).

EXAMPLE 97 Production of hydrochloride d® 1 141 2-earbamoiletiOpiper * din- -oflT) ° §sic8opropyl-1H-pyrazo8-4-carbonylH (S) -342-trifluoromethylphenyl) 1pyrropD] gna By a method similar to that of Example 94, the title compound was obtained as a white amorphous solid (149 mg) of hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole-4. -carbonyl] - [(S) -3- (2-trifluoromethyl-phenyl)] -pyrrolidine (200 mg) of example 2.

EXAMPLE 98 Production of 145-c'cloprop hydrochloride "B ° 1 1-eieB? Propiirp) ® Phi pi-piper-d-n-4-ylH-pyrazole-4-carbonyl] 4 (S? 342-tri-8-oromethyl-phenyl? 8 ) lp8rroi5dina By a method similar to that of Example 94, the title compound was obtained as white crystals (133 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl hydrochloride. ] - [(S) -3- (2-trifluoromethylphenyl)] - pyrrolidine (150 mg) of example 2.

EXAMPLE 99 Production of 145-CBclopropSB-1 1-c5gBopropiipip iB) -1H-pyrazole ^ 4-carbonyl-1-r (S) -342-trifluorornethylphenyl hydrochloride] By a method similar to that of Example 94, the title compound was obtained as a pale brown yellowish amorphous solid (144 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole hydrochloride. -4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (200 mg) of example 2.

EXAMPLE 100 Production of 45-eic8opropii ° 1-f1 ° dimeti8carb§ methylpiperidine ^ 4-iB) -1H-pyrazoM-carbonyl14ISD-342- trif8uoro eti8phenyl) 1pirroB5dina hydrochloride By a method similar to that of Example 95, the title compound was obtained as a white amorphous solid (20 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4- carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] - pyrrolidine (2.5 g) of example 2.

EXAMPLE HI Production of 141 -carboximetiBpiperidin-cyclopropi-1H-pyrazole-4-earbonin4 (S) -342-trifiuoromet-Bfeni hydrochloride The compound of the title was obtained as a white amorphous solid (24 mg) of 1- [1- (1-carboxymethylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) - 3- (2-trifluoromethylphenyl)] pyrrolidine (112 mg) produced in Example 95.

EXAMPLE 102 Production of 141 1-carboxyethylpipe [Ridin-4-5l]) - §-cyclopropyl 1H-pyrazo8-4-carbonin4 (S) -3- (2-trifluorop ?? etg8feniBppirr @ DpdBna) hydrochloride By a method similar to that of Example 95, the title compound was obtained as a pale yellow amorphous solid (295 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole- 4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine from example 2 (350 mg).

EXAMPLE 103 Production of 1 141 1-carbamoyethex8 hydrochloride) pBperid®B cyclopropyl 1H-pyrazoB-4-carboni8 > 4 (S) ° 342 ° trifluoromethyBphenyl]) 1pg? Ro, (?) LlB l5na By a method similar to that of Example 95, the title compound it was obtained as a pale yellow amorphous solid (146 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2 -lifluoromethylphenyl)] pyrrolidine from example 2 (350 mg).

EXAMPLE 104 Production of 14141 2-carboxy hydrochloride 2-meti8pr @ piB) pipe? RD (lñBt? - - gll-5-c8clopropgl-1H-pyrazole ^ -carbonyl) 4 (S]) ° 342- trifluoromethylpheniQlpyrrolidine By a method similar to that of Example 95, the title compound was obtained as a pale yellow amorphous solid (71 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole- 4-carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine from example 2 (400 mg).

EXAMPLE 105 Production of 1,141 hydrochloride 2-earbamogl-2- 4-yl-1-5-cyclopropy-1H-pyrazoB 4-carboni! > 4 (S1) ° 342 ° trifluorornethylpheniD-pyrrolidine For a similar method to that of Example 95, the compound of the title was obtained as a white amorphous solid (52 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4 -carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] -pyrrolidine from example 2 (400 mg).

EXAMPLE 106 Production of 14 1 ° carbaii? IioBB-cycloBropropylmet-8l) piperidine-4-ill-5-cyclopropyl-1H-pyrazc? 8 '(garbonyl] - [f ([S]) - 3 | 2-trifluoromethylphenyl )] pyrrolidine By a method similar to that of Example 95, the title compound was obtained as a white amorphous solid (82 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole-4 -carbonyl] - [(S) -3- (2-l-trifluoromethyl-phenyl)] -pyrrolidine from example 2 (400 mg).

EXAMPLE 107 Production of Hydrochloride of 1-γ-1-Bopropii-1 14-Hydro-5®-D-Carbamoyl-Cyclopropylmethylpiperidine-4 ° i8 > -1H-pyrazo8-4-carbonB8í4 (! S ^ -342- triflyorometilfeniB) 1pyrrolgdine By a method similar to that of Example 95, the title compound was obtained as a white amorphous solid (84 mg) of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-hydrochloride. -carbonyl) - [(S) -3- (2-ylfluoromethyl-phenyl)] -pyrrolidine of example 2 (400 mg).

EXAMPLE 108 Production of 145-cyclopropyl-1-trifluoromethansulfonyl-p-5-piperidByridi-gyl-1H-pyrazo8-4-carbonip4fS) -3- (2-trifluoromethylpheniBlpByr8ddBB'Ba 1- [5-Cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethylphenyl)) pyrrolidine hydrochloride (200 mg) was dissolved. Example 2 in methylene chloride (2.0 ml), and under an argon atmosphere, the solution was cooled to -78 ° C, triethylamine (178 ml) and urea fluoride (78.8 ml) were added, and the mixture was stirred. for 2.5 h. In addition, anhydride of trifluoromethanesulfonic acid (78.8 ml) was added and the mixture was agitated for 2 h. A saturated solution of sodium hydrogen carbonate in water was added to the reaction mixture at -78 ° C, and the mixture was extracted with chloroform. The organic layer was washed with hydrochloric acid 1, water and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (chloroform: methanol = 20: 1) to produce the title compound as a yellow amorphous (192 mg).

EXAMPLE 109 Production of 145-cyclopropyl-14142.2.2-trifluoroethaneBbon8l) pip®? Rii 44n-1H-pyrazole-4-carbonyl > 4 (S) -342-trifluoromethylfenBB] i1pyrididyl-aa By a method similar to that of Example 108, the title compound was obtained as a yellow amorphous solid (29 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4- carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] -pyrrolidine (200 mg) of example 2.

EXAMPLE 10 Production of 1414141 ° cyanoiminoeti8) piperBdin-4-i8l ° 5 ° @ icflopro [) gO-1IH-pyrazole-4-carbonyl > 4 (S) -342-trif8uoronnetilphenyl) lpictolBdina 1- [5-Cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine hydrochloride from example 2 was dissolved (300 mg) in chloroform (5 ml), and were added eryrylamine (97 ml) and N-cyanoaceyimide of meilyl (66 ml). After stirring at room temperature for 30 min and at 45 ° C for 1.5 h, in addition were added erytylamine (97 ml) and methyl N-cyanoacetoimidate (66 ml), and the mixture was stirred at 45 ° C for 2 h. The mixture was concentrated under reduced pressure, and the residue obtained was purified by silica gel chromatography (chloroform: melanol = 15: 1) to produce the compound of the product as a pale yellow amorphous solid (214 mg).

EXAMPLE 111 Production of 1 141 cyanoimpopo (methyamino))? TBB1pñp @ ndin-4 ° ñD]} -d ° eic8opropyl-1H-pyrazo8-4-carbonyl) 4 (S) -342-trifluoromethylf® [r? il) 1pyrr @ D5 l8ng? Step 1: Production of 1- (1-. {1- [cyanoimino (phenoxy) -methyl] piperidin-4-yl}. -5-cyclopropyl-1H-pyrazole-4-carbonyl) - [(S) -3 - (2-trifluoromethylphenyl)] pyrrolidine Chloroform (5 ml) was added to the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) - 3- (2-ylfluoromethylphenyl)] pyrrolidine from example 2 (500 mg) and eryrylamine (0.162 ml) and diphenyl N-cyanocarbonimide (284 mg) was added. The mixture was stirred for 1.5 h. The mixture was concentrated under reduced pressure, and the residue obtained was purified by silica gel chromatography (chloroform: acelone = 1: 1 → 2: 3 → 1: 2) to produce the title compound as a pale yellow amorphous form ( 575 mg).

Step 2 Production of 1- (1-. {1- [cyanoimino (methylamino) methyl] piperidin-4-yl}. -5-cyclopropyl-1 H -pyrazole-4-carbonyl) - [(S) -3 - (2-nifluoromethylphenyl)] pyrrolidine It was dissolved 1- (1- {1- [cyanoimino (phenoxy) -methyl] piperidin-4-yl} - 5-cyclopropyl-1 H -pyrazole-4-carbonyl) - [(S) -3- (2-nifluoromethylphenyl)] pyrrolidine (575 mg) produced in the lower layer in chloroform (10 ml), methylamine hydrochloride (81 mg) and triethylamine (0.31 ml) were added, and the mixture was added. It was stirred at ambient temperature for 30 min and at 55 ° C for 5 h. Methylamine hydrochloride (81 mg) and eryrylamine (2 ml) were added and the mixture was stirred at 55 ° C for 1 h and at 60 ° C for 30 min. Methylamine hydrochloride (162 mg) was added and the mixture was stirred at 60 ° C for 2.5 h. After allowing to cool, the mixture was concentrated under reduced pressure, and the obtained residue was dissolved in chloroform, and the mixture was washed with water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (chloroform: methanol = 10: 1) to yield the title compound as a white amorphous solid (242 mg).

EXAMPLE 112 Production of 1 141 N-c5-carbamimidoi8) p5peridin ° 4 ° ñBl-5-c5cB © pyr 1H-pyrazole-4-carbonyl (S) -342-trifluoromethylphenglolPBrrolidBng? By a method similar to that of Example 111, the title compound was obtained as a pale yellow amorphous solid (249 mg) of the hydrochloride of 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole- 4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine from example 2 (302 mg).

EXAMPLE 113 Production of acid 44445-skypropiB-4-33 - ([2-trifluoromethylphenyl) pyrrolidine-1-carbonylpyrazole-1-BB pBperd BB [p?-1-Epaque 1 Production of 1- [1- (4-eioxycarbonylphenyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carboxylic acid urea-2-cyclopropylcarbonyl-3-dimethylaminoacrylate (1.12 g) produced by a method similar to that of the example 1, stage 1 and ethyl 4- (4-hydrazinopiperidin-1-yl) benzoate hydrochloride (692 mg) produced by known method in ethanol (15 ml). Iriethylamine was added (0.81 ml) to the suspension obtained, and the mixture was stirred overnight under reflux. The reaction mixture was concentrated under reduced pressure, water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The elly acetate layer was washed with water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (n-hexane: ethyl acetate = 3: 1) to yield the title compound as a yellow oil (673 mg).

Stage 2 Production of 1- [1- (4-ethoxycarbonylphenyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carboxylic acid It was dissolved 1- [1- (4-ethoxycarbonylphenyl) piperidin-4-yl] -5-cyclopropyl-1H-pyrazole-4-carboxylic acid tert-butyl ester (673 mg) produced in the previous step in chloroform (4 ml ), trifluoroacetic acid (4 ml) was added under an ice bath, and the mixture was stirred at 40 ° C for 2 h. The reaction mixture was concentrated under reduced pressure, water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To the obtained residue were added diethyl ether and n-hexane, and the precipitated solid was filtered off and dried to yield the title compound as a white solid (556 mg).

Step 3 Production of 5-cyclopropyl-1-. { 1- [1- (4-ethoxycarbonylphenyl) piperidin-4-ylj-1 H-pyrazole-4-carbonyl} -. { 3- (2-trifluoromethylphenyl)} pyrrolidine 5-Cyclopropyl-1- [1- (4-eioxycarbonyl-phenyl) -piperidin-4-yl] -1H-pyrazole-4-carboxylic acid (550 mg) produced in the previous step, 1-hydroxybenzoyriazole (285 mg) was dissolved. ) and 1-eyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride (357 mg) in N, N-dimethylformamide (8 ml). 3- (2-urea-fluorophenyl) pyrrolidine (308 mg) was added to the obtained solution and the mixture was stirred overnight at room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated acid carbonate solution of sodium in water and saline, dried over anhydrous magnesium sulphide, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (ethyl acetate) to produce the title compound as a white amorphous solid (757 mg).

Step 4 Production of 4- (4-. {5-cyclopropyl-4- [3- (2-ylfluoromethylphenyl) -pyrrolidin-1-carbonyl] pyrazol-1-yl} piperidin-1-yl) benzoic acid 1 -. { 1- [1- (4-Ethoxycarbonylphenyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -. { 3- (2-trifluoromethylphenyl)} pyrrolidine (720 mg) produced in the previous step was dissolved in ureahydrofuran (3 ml) and melanol (1.5 ml), and 4N sodium hydroxide solution in water (1.2 ml) was added. The mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated under reduced pressure, and the residue obtained was dissolved in water. The aqueous layer was washed with diethyl ether, acidified with 2N hydrochloric acid under an ice bath, and extracted with ethyl acetate. The ether oil layer was washed with water and saline, dried over anhydrous magnesium sulphide, and concentrated under reduced pressure. Diethyl ether: n-hexane (1: 1) was added to the obtained residue and the precipitated solid was filtered off and dried to yield the title compound as a white solid (600 mg).

EXAMPLE 114 Production of 34445-cyclopropyl-44342-trifluoromethylphenyl) pyrrolidin-1-carbonylpyrazole B- -ifi) piperndBn ° 1 acid-Hbsirazoic acid 1- [5-Cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] -3- (2-trifluoromethylphenyl) pyrrolidine (195 mg) produced by a method similar to that of Example 1 and 3 - elylobenzoate (142 mg) were dissolved in 1,4-dioxane (1 ml) and tert-butanol (1 ml), and tris (dibenzylideneacetone) dipalladium (14.2 mg), 2-dicyclohexylphosphino-2 '- ( N, N-dimethylamino) biphenyl (24.3 mg) and cesium carbonate (235 mg). The mixture was stirred overnight and heated under reflux. After allowing to cool, the insoluble material was filtered through celite, and the filtrate was concentrated under reduced pressure. A saturated solution of sodium hydrogen carbonate in water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The ethyl ether layer was washed with saline solution, it was dried over anhydrous sodium sulfate, and was concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (n-hexane: acelone = 1: 1) to give 3- (4-. {5-cyclopropyl-4- [3- (2-ylfluoromethylphenyl) -pyrrolidin-1 -carbonyl] pyrazol-1-yl.}. piperidin-1-yl) benzoyl ether as a white amorphous solid (179 mg). Ethylyl 3- (4-. {5-cyclopropyl-4- [3- (2-lrifluoromethyl-phenyl) pyrrolidin-1-carbonyl] pyrazol-1-yl} piperidin-1-yl) benzoate was dissolved (179 mg ) produced in the previous stage in hydrohydrofuran (1 ml) and eneol (1 ml), and one was added 4N solution of sodium hydroxide in water (1 ml). The mixture was heated under reflux for 2 h. The reaction mixture was concentrated under reduced pressure, and the obtained residue was dissolved in water, and was acidified with 2N hydrochloric acid under an ice bath. The precipitated solid was collected by filtration, washed with water and dried under reduced pressure to yield the title compound as a white solid (165 mg).

EXAMPLE 115 Production of 54445-cyclopropy B 44342 ° trgf1uoyron-ethyl phe-pB) pyrroBidin ° 1 -carbonyl] pyra8-1-5l) piperidine 1-i8-t8ofen ° 2-carboxc05 (5? 1- [5-Cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carbonyl] -3- (2-irifluoromethyl-phenyl) pyrrolidine (220 mg) produced by a method similar to that of Example 1 were dissolved and ethyl 5-bromothiophene-2-carboxylate (137 mg) in toluene (4 ml), and palladium acetate (13 mg), 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (36 mg) were added. and cesium carbonate (265 mg). The mixture was heated under reflux for 6 h. After allowing to cool, the insoluble material was filtered through celite, and the filtrate was concentrated under reduced pressure. A saturated solution of sodium hydrogen carbonate in water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The ethyl ether layer was washed with saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (n-hexane: acetyone = 1: 1) to give 5- (4-. {5-cyclopropyl-4- [3- (2-trifluoromethylphenyl) -pyrrolidin-1-carbonyl] pyrazole-1- il.) piperidin-1-yl) thiophene-2-carboxylic acid (162 mg) as a white amorphous solid. 5- (4-. {5-Cyclopropyl-4- [3- (2-trifluoromethyl-phenyl) -pyrrolidin-1-carbonyl] -pyrazol-1-yl}. Piperidin-1-yl) thiophene-2-carboxylate was dissolved. ethyl (162 mg) produced in the above step in tetrahydrofuran (1 ml) and ethanol (1 ml), and a 4N solution of sodium hydroxide in water (1 ml) was added. The mixture was heated under reflux for 3 h. The reaction mixture was concentrated under reduced pressure, and the obtained residue was dissolved in water, and acidified with 2N hydrochloric acid under an ice bath. The precipitated solid was collected by filtration, washed with water and dried under reduced pressure. The solid obtained was purified by silica gel chromatography (chloroform: acetone = 6: 1), and recrystallized from the ethyl ether to yield the title compound as pale green solid (28 mg).

EXAMPLE 116 Production of acid 24445-cyclopropyl-44342-trñflu® ro etiBf®pñDi) -pyrrolidin-1 -carbonylpyrazolo-1-yl) piperidine ° 14B) thiazoB-4-carboxoBoe @ Stage 1 Production of 4-. { 5-cyclopropyl-4- [3- (2-l-trifluoromethylphenyl) pyrrolidin-1 -carbonyl] pyrazol-1-yl} piperidin-1-thiocarboxamide It was dissolved 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole-4- carbonyl] -3- (2-ylfluoromethylphenyl) pyrrolidine (420 mg) produced by a similar method to that of Example 1 in chloroform (10 ml), and were added irylamyl amine (0.139 ml) and 9-fluorenylmeloxycarbonylisothiocyanate (285 mg) at room temperature . The mixture was stirred for 1 h. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (chloroform: melanol = 50: 1). The obtained purified product was dissolved in N, N-dimethylylformamide (7 ml), and piperidine (0.7 ml) was added at room temperature. The mixture was stirred for 1 h and was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, and the mixture was washed with water and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The diethyl ether was added to the residue obtained, and the precipitated solid was separated by filtration, washed with water and dried under reduced pressure to yield the title compound as a white solid (287 mg).

Step 2 Production of 2- (4- {5-cyclopropyl-4- [3- (2-trifluoromethyl-phenyl) -pyrrolidin-1-carbonyl] pyrazol-1-yl} piperidin-1-yl) thiazole- acid 4-carboxylic was suspended 4-. { 5-cyclopropyl-4- [3- (2-trifluoromethyl-phenyl) -pyrrolidine-1-carbonyl] pyrazol-1-yl} piperidin-1-thiocarboxamide (280 mg) produced in the lower layer in ethanol (5 ml), and ethyl bromopyruvate (0.09 ml) was added to the obtained suspension. The mixture was heated to reflux for 2 h. The reaction mixture was concentrated under reduced pressure, was Water was added to the residue obtained, and the mixture was extracted with chloroform. The chloroform layer was washed with saturated sodium carbonate acid solution in water and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: meianol = 20: 1) to give 2- (4-. {5-cyclopropyl-4- [3- (2-lrifluoromethylphenyl) pyrrolidin-1- carbonyl] pyrazol-1-yl.}. piperidin-1-yl) -iazole-4-carboxylic acid ether (361 mg) as a white amorphous solid. 2- (4-. {5-Cyclopropyl-4- [3- (2-l-trifluoromethyl-phenyl) -pyrrolidin-1-carbonyl] pyrazol-1-yl}. Piperidin-1-yl) thiazole-4-carboxylate was dissolved. ethyl (355 mg) produced in the earlier stage in telrahydrofuran (0.6 ml) and methanol (0.3 ml), and 4N solution of sodium hydroxide in water (0.57 ml) was added to temperalura ambienie. The mixture was stirred for 3 h. The reaction mixture was concentrated under reduced pressure, and a 1 N solution of sodium hydroxide in water was added to the residue obtained, and the mixture was washed with diethyl ether. The aqueous layer was acidified with 2N hydrochloric acid, and the precipitated solid was collected by filtration, washed with water and dried under reduced pressure to yield the title compound as a white solid (272 mg).

EXAMPLE 1 Production of 145-C-ClopropH-141 S-motil-H4H.2 hydrochloride. triazol-3-yl) piperidine ^ 4n-1H-pgrazoB-4-earboniBH (! S) ° 342- Stage 1 Iodine production of 4-. { 5-Cyclopropyl-4 - [(S) -3- (2-trifluoromethylphenyl) pyrrolidin-1-carbonyl] pyrazol-1-yl} methyl piperidin-1-imidothiocarboxylale was dissolved 4-. { 5-Cyclopropyl-4 - [(S) -3- (2-ylfluoromethyl-phenyl) -pyrrolidine-1-carbonyl] pyrazol-1-yl} piperidin-1-lyocarboxamide (500 mg) produced by a similar method to that of example 116, step 1 in chloroform (5 ml), and me yl iodide (0.1 ml) was added. The mixture was stirred all night at ambient air. The mixture was concentrated under reduced pressure, diethyl ether was added to the residue obtained, and the precipitated solid was separated by filtration and dried to produce the title compound as a pale yellow solid (654 mg).

Stage 2 Production of 1- hydrochloride. { 5-Cyclopropyl-1- [1- (5-meityl-4H- [1.2.4] triazol-3-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine 4-iodohydrate was suspended. { 5-cyclopropyl-4 - [(S) -3- (2- trifluoromethylphenyl) pyrrolidine-1-carbonyl] pyrazol-1-yl} piperidin-1-imidoiiocarboxylane of meiílo (317 mg) produced in the previous stage, aceric acid hydrazide (50 mg) and sodium acephalous (43 mg) in dioxane (2 ml) and water (0.4 ml), and the mixture was stirred overnight and heated under reflux. The solvent was removed under reduced pressure, water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saline and dried over anhydrous magnesium sulfate. The mixture was concentrated under reduced pressure, and the residue obtained was purified by silica gel chromatography (chloroform: meianol = 10: 1). The amorphous solid obtained was dissolved in ethyl acetate (1 ml), and a 4N solution of hydrochloric acid in elilo acelate (0.4 ml) was added. The precipitated solid was separated by filtration and dried to yield the title compound as white cristels (72 mg).

EXAMPLE 118 Production of 1 5-C8-8-propyl-1-1-yl-iopropBn-4E-a-ri.2.41-triazol-3-piperidine ^ -in-1H-pyrazoU-earboniBr (S? 342? Trifluoron-ethyl-phenyl-pyrrolidipa For a similar method to that of example 117, the title compound was obtained as cristeles (253 mg) of the iodine hydrate of 4. { 5-Cyclopropyl-4 - [(S) -3- (2-frifluoromethyl-phenyl) -pyrrolidine-1-carbonyl] pyrazol-1-yl} methyl pipehdin-1-imidoiocarboxylate (475 mg).

EXAMPLE 119 Production of 145-cyclopropyl-1- [[145-hydroxyme] hydrochloride < ai-4H-ri.2.4nriazol-3-yl) piperidin ^ 4-in-1H-pyrazoB-4-carboraiBVrfS] l-3- (f2 ° trifiuoromethyl-phenyl)] pyrroiidine.

By a method similar to that of Example 117, the compound of the isolate was obtained as chrysolics (25 mg) of the iodohydrate of 4. { 5-cyclopropyl-4 - [(S) -3- (2-trifluoromethylphenyl) pyrrolidine-1-carbonyl] pyrazol-1-yl} methyl piperidin-1-imido-thiocarboxylate (317 mg).

EXAMPLE 12 © Production of 145-cyclopropi8-141 hydrochloride 5-t? RDffDuoropri (s n.2.4ltriazole-3-yl) piperidn-t-in-1H-plrazole-4-carbonyl (S ) -342- trifluoromethylphenyl)] pyrrolidine By a method similar to that of Example 117, the title compound was obtained as white chrysolics (130 mg) of the iodine hydrate of 4. { 5-cyclopropyl-4 - [(S) -3- (2-ylfluoromethylphenyl) pyrrolidine-1-carbonyl] pyrazol-1-yl} -piperidin-1-imidothiocarboxylane of meylyl (317 mg).

EXAMPLE 121 Production of 145-cyclo-8-propyl-141-2-fluorophen-8-carbamopB) pip® i 5p-1-Ib-1H-pyrazole-4-carbonylH (RI-342-trifluoromet-8-inipipS) Eyelid 1 Production of 5-cyclopropyl-1- (piperidin-4-yl) -1 H -pyrazole-4-carboxylalkyl was dissolved 1- (1-benzyloxycarbonylpiperidin-4-yl) -5-cyclopropyl-1 H-pyrazole Methyl-4-carboxylate (15.9 g) produced in Example 1, step 2 in melanol (12 ml), and palladium carbon (1.5 g) was added. The mixture was agitated overnight under a hydrogen atmosphere. The catalyst was filtered, and the filtrate was concentrated under reduced pressure. N-Hexane was added to the obtained residue, and filtration yielded the title compound as a white amorphous solid (9.66 g).

Step 2: Production of 5-cyclopropyl-1 - [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carboxylamino of me yl. 5-Cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carboxylane of methyl (2.82 g) produced in the lower layer was dissolved in chloroform (28 ml) and triethylamine (1.58 ml) was added. 2-Fluorophenylisocyanate (1.4 ml) was added to the mixture obtained under an ice bath and the mixture was stirred at room temperature environment for 1 h. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (n-hexane: ethyl acetyl = 2: 3) to yield the title compound as a white amorphous solid (4.23 g) .

Step 3: Production of 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carboxylic acid. It was dissolved 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carboxylic acid methyl ester (4.23 g) produced in the earlier stage in iron-hydrofuran (11 ml) and melanol (5 ml), and a 4N solution of sodium hydroxide in water (11 ml) was added. The mixture was agitated at 60 ° C for 6 hours. The reaction mixture was allowed to cool and was concentrated under reduced pressure. The residue obtained was dissolved in water. The aqueous layer was washed with diethyl ether, and acidified with concentrated hydrochloric acid under an ice bath. The precipitated solid was separated by filtration, washed with water and n-hexane, and dried under reduced pressure to yield the title compound as a white solid (3.89 g).

Eíapa 4 Production of 1-. { 5-Cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} -. { (R) -3- (2-fluorifomethylphenyl)} pyrrolidine. 5-Cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) - piperidin-4-yl] -1H-pyrazole-4-carboxylic acid (101 mg) produced in the previous step, 1-hydroxybenzothazole (46 mg) and 1-elyll-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride (57 mg) in NN-dimellilformamide (15 ml). (R) -3- (2-ylfluoromethylphenyl) pyrrolidine (65 mg) * and 4-dimethylaminopyridine (37 mg) were added to the obtained solution and the mixture was stirred overnight at room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated solution of sodium hydrogen carbonate in water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: methanol = 20: 1) to yield the title compound as a white amorphous solid (136 mg). [a] 25D = + 10.9 (c = 0.495; E1OH). * (R) -3- (2-Trifluoromethylphenyl) pyrrolidine was produced by a similar method as in Example 2, step 1 to step 4 and using (R) -4-isopropyl-5,5-diphenyloxazolidin-2-one. [a] 25D = -21.0 (c = 0.500; EíOH), EXAMPLE 122 Production of 145-cyclopropyl-1 1-metiBe8e8op? RopgBearba @oll)) - piperidin-4-B8MH-pyrazole-4- ^ arbonylH (] ¡342- trifluoromethylBphenii) 1pyrrolidine Epaque 1 Production of 5-cyclopropyl-1- [1- (1-methyl-cyclopropylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carboxylamino-methyla. 1-Methylcyclopropane-1-carboxylic acid (1.81 g), diphenylphosphoryl azide (4.67 ml) and iaryrylamine (2.77 ml) were dissolved in toluene (30 ml), and the mixture was heated under reflux for 1 h to produce the isocyanate. 5-Cyclopropyl-1- (piperidin-4-yl) -1H-pyrazole-4-carboxylic acid methylated (1.50 g) produced in example 121, isopa 1 and erytylamine (0.84 ml) in tetrahydrofuran (15 ml) were dissolved. and an Isocyanate solution in Ioluene prepared beforehand was added to the starting material, (1- (Pipe-din-4-yl) -5-cyclopropyl-1H-pyrazole-4-carboxylic acid-methyl), disappear. The reaction mixture was concentrated under reduced pressure, water was added to the obtained residue, and the mixture was extracted with chloroform. The chloroform layer was washed with a saturated solution of sodium acid carbonate in water and saline, and dried over anhydrous magnesium sulfate. The residue obtained was purified by silica gel chromatography (chloroform: melanol = 15: 1) to produce the compound of the product as a white amorphous solid (1.92 g).

Step 2 Production of 5-cyclopropyl-1- [1- (1-methylcyclopropyl-carbamoyl) piperidin-4-yl] -1H-pyrazole-4-carboxylic acid. It was dissolved methyl 5-cyclopropyl-1- [1- (1-methylcyclopropylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carboxylate (1.92 g) produced in the lower layer in teirahydrofuran (20 ml) and methanol (10 ml), and a 4N solution of sodium hydroxide in water (15 ml) was added. The mixture was stirred to 60 ° C for 6 h. The reaction mixture was allowed to cool and was concentrated under reduced pressure. The obtained residue was dissolved in water and the aqueous layer was washed with diethyl ether. Under an ice bath, the mixture was acidified with concentrated hydrochloric acid and extracted with chloroform. The chloroform layer was washed with saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The ellyl acetate was added to the obtained residue, and the precipitated solid was filtered off and dried to yield the title compound as a white solid (1.68 g). Eíapa 3 Production of 1-. { 5-Cyclopropyl-1- [1- (1-methylcyclopropylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(R) -3- (2-ylfluoromethylphenyl)) pyrrolidine 5-Cyclopropyl-1- [1- (1-methyl-cyclopropyl-carbamoyl) piperidin-4-yl] -1H-pyrazole-4-carboxylic acid was dissolved. 91 mg) produced in the previous step, 1-hydroxybenzoyriazole (46 mg) and hydrochloride of 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide (57 mg) in N, N-dimethylformamide (1.5 ml).

(R) -3- (2-trifluoromethylphenyl) pyrrolidine (65 mg) and 4-dimethylaminopyridine (37 mg) were added to the obtained solution and the mixture was agitated overnight at ambient temperature. Water was added to the reaction mixture, and the mixture was exalted with elyl acelaide. The ethyl acetate layer was washed with a saturated solution of sodium acid carbonate in water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: methanol = 15: 1) to yield the title compound as a white amorphous solid (123 mg). [α] 25 D = + 13.1 (c = 0.495, EtOH).

EXAMPLE 123 Production of 145-C8clopropi8-14141 ° isoprop5learbar? P? OiB]) pipepdñ6] -X! -? Bl- 1H-pyrazole-4-carboni8 > 4 (R) ° 342-trifBuoromethylphenol) lpiriro8id8na Stage 1 Production of 5-cyclopropyl-1- [1- (1-isopropylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carboxylamino-methylic was 5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole-4-carboxylane of meilyl (1.87 g) produced in Example 121, step 1 in chloroform (20 ml), and triethylamine (1.05 ml) was added. Isopropyl isocyanate (0.7 ml) was added to the mixture obtained under an ice bath and the mixture was stirred at room temperature for 1 h. The mixture of The reaction was concentrated under reduced pressure, and the residue obtained was purified by silica gel chromatography (chloroform: methanol = 15: 1) to produce the title compound as a white amorphous solid (2.00 g).

Stage 2 Production of 5-cyclopropyl-1- [1- (1-isopropylcarbamoyl) -piperidin-4-yl] -1 H -pyrazole-4-carboxylic acid. 5-Cyclopropyl-1- [1- (1-isopropylcarbamoyl) was dissolved. ) piperidin-4-yl] -1 H-pyrazole-4-carboxylane of meylyl (2.00 g) produced in the previous step in tetrahydrofuran (6 ml) and methanol (3 ml), and a 4N sodium hydroxide solution was added. in water (6 ml). The mixture was agitated at 60 ° C for a duration of 4.5 h. The reaction mixture was allowed to cool and was concentrated under reduced pressure. The residue obtained was dissolved in water and the aqueous layer was washed with diethyl ether, and acidified with concentrated hydrochloric acid under an ice bath. The mixture was extracted with chloroform. The chloroform layer was washed with saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. N-Hexane was added to the obtained residue, and the precipitated solid was filtered off and dried to yield the title compound as a white solid (1.58 g).

Stage 3 Production of 1-. { 5-cyclopropyl-1- [1- (1-isopropylcarbamoyl) - pperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(R) -3- (2-trifluoromethylphenyl)] pyrrolidine 5-Cyclopropyl-1- [1- (1-isopropylcarbamoyl) -piperidin-4-yl] -1 H -pyrazole-4-carboxylic acid was dissolved. (88 mg) produced in the previous step, 1-hydroxybenzotriazole (46 mg) and 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride (57 mg) in N, N-dimellylformamide (1.5 ml). (R) -3- (2-fluorifomethylphenyl) pyrrolidine (65 mg) and 4-dimethylaminopyridine (37 mg) were added to the obtained solution and the mixture was stirred overnight at ambient temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated acid sodium carbonate solution in water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: meianol = 15: 1) to produce the title compound as a white amorphous solid (120 mg). [a] 25D = + 14.2 (c = 0.500; EtOH) EXAMPLE 124 Production of 145-cyclopropyl-1 2-fluorophenearbanm @ BÍ) piperg lg [p) -4-iB1- 1 H -pyrazo -earbonyl > 4fS) -342-trifluoromethylpheniB) 1pyrrolidiB ^ g? By a method similar to that of example 121, step 4, the title compound was obtained as a white amorphous solid (127 mg) of 5-cyclopropyl-1 - [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] - 1 H-pyrazole-4-carboxylic acid (123 mg) and (S) -3- (2-l-trifluoromethylphenyl) pyrrolidine (78 mg). [a] 5D = -10.8 (c = 0.510; EtOH) EXAMPLE 125 Production of 145-cyclopropi8 ° 1 1 1 -isopropylcarbam)? BB) pipergdlB [p? - 4Bl-1H-pyrazole-4-carboni8 > 4IS) -342-trifluoroethylfenE8]) lp¡rroiidgpg? By a method similar to that of example 123, step 3, the thioule compound was obtained as a white amorphous solid (123 mg) of 5-cyclopropyl-1- [1- (1-isopropylcarbamoyl) piperidin-4-yl] - 1 H-pyrazole-4-carboxylic acid (107 mg), (S) -3- (2-l-trifluoromethylphenyl) pyrrolidine (79 mg). (a] 25D = -13.2 (c = 0.515; EtOH) EXAMPLE 128 Production of 145-cycloBopropyB-141 1- eti8eicBopropBBearbann (O) DÍ]) ° piperid8n-4-Bll-1H-PBrazoi-4-carbongBM (; S) ° 342 ° trifluoromethylphenhydropyridine By a method similar to that of example 122, step 3, the title compound was obtained as a white amorphous solid (149 mg) of 5-cyclopropyl-1- [1- (1-methyl-cyclopropylcarbamoyl) piperidin-4-yl] - 1 H-pyrazole-4-carboxylic acid (107 mg), (S) -3- (2-ylfluoromethylphenyl) pyrrolidine (76 mg). [a] 25D = -13.6 (c = 0.500; EtOH) EXAMPLE 127 Production of f -) - 344-fluorophen-B) -3-idrox5methyl-1 541-B-ethylcyclopropyl-1-pyrimidin-2-yl) piperdin-4-Bn-1 H-pyrazoB-carbonyl >hydrochloride; pyrroBidine Step 1. Production of ethyl cyano- (4-fluorophenyl) acetate. Toluene (40 ml) was added to 4-fluorophenylacetonitrile (15.0 g) and diethyl carbonate (66.9 ml) and sodium ethoxide (8.30 g) was added. The mixture was agitated for 2 h while the solvent evaporated from 110 ° C to 130 ° C. After allowing to cool, the reaction mixture was poured into water, and acetic acid (13 ml) was added. The mixture was stirred during 5 min, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with water and saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the thiol compound as a pale yellow oil (25.0 g).

Epa 2 Production of 2-cyano-2- (4-fluorophenyl) succinate-di-lily. It was added leirah id no break (40 ml) at 60% sodium hydride. (2.12 g), and a cyano- (4-fluorophenyl) ethyl acid (10.0 g) solution produced in the previous step was added in anhydrous form (40 ml) under an ice bath. The mixture was agitated for 40 min and was added bromoacetyl of ethyl (6.4 ml) under an ice bath. The mixture was stirred at ambient temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with water and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (n-hexane: ethyl acetate = 5: 1) to yield the title compound as a pale yellow oil (14.7 g).

Step 3 Production of ethyl 3- (4-fluorophenyl) -5-oxo-pyrrolidin-3-carboxylate A solution of diethyl 2-cyano-2- (4-fluorophenyl) succinate (7.0 g) produced in the bottle was added. The mixture was stirred overnight in elanol (50 ml) to Raney nickel (7.0 g), and the mixture was stirred overnight under a hydrogen atmosphere. The reaction mixture was filtered through celile, and filtering and washing were combined and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (chloroform: melanol = 25: 1) and a solvent mixture of diethyl ether and n-hexane was added to the solid residue obtained. The mixture was filigreed and dried to yield the title compound as white crystals (3.96 g).

Step 4 Production of 1-benzyl-3- (4-fluorophenyl) -5-oxo-pyrrolidin-3-carboxylaryl of elyle was added, read no breakage (25 ml) to 60% sodium hydride (1.63 g), and a solution of ethyl 3- (4-fluorophenyl) -5-oxo-pyrrolidin-3-carboxylate (10.3 g) produced in the lower layer in tetrahydrofuran (30 ml) / N, N-dimethylformamide (10 ml) was slowly added. ) under an ice bath.

The mixture was stirred for 10 min. Under an ice bath, benzyl bromide (4.86 ml) was added. The mixture was agitated at the same time for 30 min and at room temperature for 3.5 h. The reaction mixture was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with water and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (n-hexane: elylar acetyl = 2: 1) to produce the compound of the eluate as a pale yellow oil (12.1 g).

Stage 5 Production of 1-benzyl-3- (4-fluorophenyl) -3-hydroxymethylpyrrolidine. Hydro-furan (20 ml) was added to lithium aluminum hydride. (1.16 g) and a solution of 1-benzyl-3- (4-luo-phenyl) -5-oxo-pyrrolidin-3-carboxylate of ellyl (4.16 g) produced in the above elapsed in tetrahydrofuran (20 ml) under a ice bath. The mixture was shaken under reflux for 3.5 h. After allowing to cool, water (0.9 ml), 4N sodium hydroxide solution in water (0.9 ml) and water (2.7 ml) were added successively under an ice bath, and diethyl ether and magnesium sulphide were added. The mixture was agitated for 20 min. and it was filtered through Celite. Filtering and washing were combined and concentrated under reduced pressure to yield the title compound as a pale yellow oil (3.18 g).

Step 6 Production of 3- (4-fluorophenyl) -3-hydroxymethylpyrrolidine To a solution of 1-benzyl-3- (4-fluorophenyl) -3-hydroxymethyl-pyrrolidine (3.18 g) produced in the previous step in methanol (30 ml ) palladium hydroxide (300 mg) was added, and the mixture was agitated overnight under a hydrogen atmosphere (3 atm). The reaction mixture was filtered through Celite, and the filtrate and washing were combined and concentrated under reduced pressure to yield the title compound as a pale yellow oil (2.30 g).

Step 7 Production of 3- (4-fluorophenyl) -3-hydroxymethyl-pyrrolidine-1-carboxylate of tert-butyl A 3- (4-fluorophenyl) -3-hydroxymethylpyrrolidine (2.30 g) produced in the previous step was added tetrahydrofuran ( 40 ml) and triethylamine (5.7 ml), and Di-tertiary-butylcarbonate (4.60 g) was added under an ice bath. The mixture was stirred all night at ambient air. The reaction mixture was concentrated under reduced pressure, and etiol acelaide was added. The mixture was washed with water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (n-hexane: elyel acetate = 2: 1) to yield the title compound as a colorless oil (2.70 g).

Step 8 Production of (-) - 3- (4-fluorophenyl) -3-hydroxymethylpyrrolidine Al 3- (4-fluorophenyl) -3-hydroxymethyl-pyrrolidine-1-carboxylate of tertbutyl (1.02 g) produced in the previous step was added chloroform (10 ml), eryrylamine (962 ml) and 4-dimethylaminopyridine (421 mg), and (S) - (+) - 3.3.3-urea, 2-phenylpropionyl chloride (969 ml) was added. under an ice bath. The mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure, water was added to the residue, and the mixture was expelled 3 times with elyl acelaide. The organic layer was washed with an aqueous solution of potassium acid sulfate, with water, with a solution of sodium hydrogen carbonate in water and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (n-hexane: diethyl ether = 5: 3) to give the less polar diastereomer as a colorless oil (871 mg). Additionally, the more polar diastereomer was obtained as a colorless oil (781 mg). The colorless oil (871 mg) of the less polar diastereomer was dissolved in tetrahydrofuran (4 ml) and methanol (2 ml), and 4N sodium hydroxide solution in water (2.6 ml) was added. The mixture was stirred at 60 ° C for 40 min. The reaction mixture was concentrated under reduced pressure and water was added to the residue. The mixture was extracted 3 times with diethyl ether. The organic layer was washed with saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a colorless oil (481 mg). Methanol (3 ml) and a 4N solution of hydrochloric acid in ethyl acetate (3.3 ml) were added to the colorless oil obtained (481 mg) and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure and water was added to the residue. The mixture was washed with diethyl ether, and the aqueous layer was made alkaline with a 2N solution of sodium hydroxide in water. The mixture was extracted 5 times with chloroform. The organic layer was washed with saline, dried over anhydrous sodium sulfate, concentrated under reduced pressure to yield the title compound as a colorless oil (312 mg). [a] 25D = -9.70 (c = 0.598; EtOH) Production of (+) - 3- (4-fluorophenyl) -3-hydroxymethylpyrrolidine By a method similar to the production of (-) - 3- (4-fluorophenyl) 3-hydroxymethylpyrrolidine and using the colorless oil (781 mg) of the more polar diastereomer, the title compound was obtained as a colorless oil (251 mg).

Step 9 Production of 5- (1-meyylcyclopropyl) -1- (1-pyrimidin-2-yl-piperidin-4-yl) -1 H -pyrazole-4-carboxylate of ione-buíyl. 5- (1-methylcyclopropyl) were dissolved. ) -1- (piperidin-4-yl) -1H-pyrazole-4-carboxylic acid tert-butyl ester (1.15 g) produced by a method similar to that of example 121, isopa 1 and 2-chloropyrimidine (700 mg) in 1 , 4-dioxane (12 ml), and palladium acetate (85 mg), 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (352 mg) and cesium carbonate (1.84 g) were added. The mixture was heated under reflux for 3 h. After allowing to cool, the insoluble material was filtered through celite, and the filtrate was concentrated under reduced pressure. A saturated solution of sodium hydrogen carbonate in water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The ethyl ether layer was washed with saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (n-hexane: ethyl acetate = 2: 1) to yield the thioule compound as a white amorphous solid (922 mg).

Step 10 Production of 5- (1-methylcyclopropyl) -1- (1-pyrimidin-2-yl-piperidin-4-yl) -1H-pyrazole-4-carboxylic acid hydrochloride. 5- (1-methylcyclopropyl) was dissolved. -1- (1-pyrimidin-2-yl-piperidin-4-yl) - 1 H-pyrazole-4-carboxylic acid tert-butyl ester (922 mg) produced in the previous step in chloroform (2 ml), and ureaifluoroacetic acid (4 ml) was added. The mixture was stirred overnight at ambient temperature. The reaction mixture was concentrated under reduced pressure, and the obtained cristel was dissolved in the hydrofuran. A 4N solution of hydrochloric acid in ellyl acetyl (2 ml) was added, and the mixture was concentrated under reduced pressure. The obtained crystalline residue was milled by washing with ethyl acetate (10 ml) for 1 h to yield the compound of the same as a white solid (800 mg).

Step 11 Production of (-) - 3- (4-fluorophenyl) -3-hydroxymethyl-1- hydrochloride. { 5- (1-Methylcyclopropyl) -1- [1- (pyrimidin-2-yl) piperidin-4-yl] -1 H -pyrazole-4-carbonyljpyrrolidine 5- (1-Methylcyclopropyl) -1- hydrochloride was dissolved (1-pyrimidin-2-yl-piperidin-4-yl) -1 H-pyrazole-4-carboxylic acid (150 mg) produced in the previous step, 1-hydroxybenzotriazole (81 mg) and 1-eyl-3-hydrochloride (3-dimethylaminopropyl) -carbodiimide (102 mg) in N, N-dimethylylformamide (3 ml). (-) - 3- (4-fluorophenyl) -3-hydroxymethylpyrrolidine (88 mg) produced in step 8, triethylamine (0.057 ml) and 4-dimethylaminopyridine (50 mg) was added to the solution obienida, and the mixture was agiíáda All night at ambienie temperaíura. Water was added to the reaction mixture, and the mixture was extracted with acetyl elyl. The ethyl acetate layer was washed with a saturated solution of sodium hydrogen carbonate in water and saline solution, dried over anhydrous magnesium sulphide, and was concentrated under reduced pressure. The residue was purified by silica gel chromatography (chloroform: methanol = 20: 1) and the obtained free base was dissolved in meianol (3 ml). A 4N solution of hydrochloric acid in 1,4-dioxane (0.2 ml) was added, and the mixture was concentrated under reduced pressure. The obtained crislallic residue was sprayed by washing with ethyl agar (3 ml) for 15 min to yield the title compound as white crystals (203 mg). [a] 25D = -21.3 (c = 0.506; MeOH) EXAMPLE 28 Producer of (HH-344-fluorofenyl) -3-hydroxymethyl-1, 4f541-methylcyclopropyl) -41 pyridin-2-iD) piperidin-4-iBTl-1 H-pirazoB- carbonyl D-pyrrolidine By a method similar to that of Example 127, elapa 11, the title compound was obtained as white crystals (198 mg) of 5- (1-methylcyclopropyl) -1- (1-pyrimidin-2-yl-piperidin-) hydrochloride. 4-yl) -1 H-pyrazole-4-carboxylic acid (150 mg), (+) - 3- (4-fluorophenyl) -3-hydroxymethylpyrrolidine (88 mg) produced in example 127, step 8. [a] 25D = + 26.0 (c = 0.508; MeOH) EXAMPLE 129 Production of 145-cyclopropiB-1 - ([1 ° pyrazoln 24l-pipe? Ró (5p? -4-Bl) -1H-pyrazole-4-carbonip- [fS) -342-trifluoromethylferi) hydrochloride ) SpBrro8ñdBriia The thioule compound was obtained as a yellow amorphous solid (165 mg) of 1- [5-cyclopropyl-1- (1-pyrazin-2-yl-piperidin-4-yl) -1H-pyrazole-4-hydrochloride. -carboxylic acid (281 mg) produced by a method similar to that of example 127.

EXAMPLE 130 Production of 14 trans-4-carbamoylcyclohexill-5 ° cchlopr © pil ° 1 H-porazoC-4-carbonip4 (SI-342-trifluoror? Ethylphenyl) pyrimidine? Step 1: Production of ethyl rans-4- (2-ione-buloxycarbonylhydrazino) -cyclohexanecarboxylate. 4-Cyclohexanecarboxylate of eiyl (8.0 g) and carbazane of ler-bulyl (6.2 g) in chloroform (150 ml) were dissolved and added. acetic acid (5.4 ml) and sodium triacetoxyborohydride (30 g) under an ice bath. The mixture was gradually returned to ambient temperature, and the mixture was stirred for 7 h. The reaction mixture was poured into a saturated solution of sodium hydrogen carbonate in water, and the mixture was extracted with elyl acelaide. The organic layer was washed with water and saline, it was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (n-hexane: ethyl acetate = 4: 1) to yield the title compound as a white solid (4.63 g).

Step 2: Production of ethyl trans-4-hydrazicyclohexane carboxylate hydrochloride. Trans-4- (2-iver-buzoxycarbonylhydrazino) cyclohexanecarboxylane was dissolved (4.63 g) produced in the previous step in ethanol (30 ml), and A 4N solution of hydrochloric acid in ethyl acetate (82 ml) was added. The mixture was stirred for 5.5 h. The mixture was concentrated under reduced pressure, and diethyl ether was added to the residue obtained. The mixture was filtered and dried to yield the title compound as a white powder (3.86 g).

Step 3: Production of 1 - (trans-4-eioxycarbonylcyclohexane) -5-cyclopropyl-1 H-pyrazole-4-carboxylic acid urea-ethyl ester. Ethyl rans-4-hydrazin-cyclohexanecarboxylate hydrochloride (3.80 g) obtained in the previous step and tert-butyl 2-cyclopropylcarbonyl-3-dimethylaminoacrylate (3.71 g) synthesized by a similar method to that of example 1, elapa 1 in elanol (50 ml), and added triethylamine (4.32 ml). The mixture was stirred under reflux for 1 h. After allowing to cool, the mixture was concentrated under reduced pressure, and water was added to the residue. The mixture was extracted 3 times with ethyl acetate. The organic layer was washed with water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (n-hexane: ethyl ether = 5: 1) to produce the compound of the product as a yellow liquid (4.80 g).

Stage 4 Production of 1- (trans-4-yloxycarbonyl-cyclohexane) -5-cyclopropyl-1H-pyrazole-4-carboxylic acid To a solution of 1- (trans-4-eioxycarbonyl-cyclohexane) -5-cyclopropyl-1H-pyrazole- 4-Butoyl-4-carboxylate (4.80 g) obtained in the lower layer in chloroform (14 ml) was added trifluoroacetic acid (14 ml), and the mixture was heated to 40X and stirred for 1.5 h. After allowing to cool, the mixture was concentrated under reduced pressure and azeotropically with toluene. Ethyl acetate was added to the residue to allow the precipitation of cristel. The mixture was concentrated under reduced pressure, n-hexane was added to the residue, and the chrysolics were filtered off and dried to yield the title compound as a white powder (3.09 g).

Stage 5 Production of 1 -. { 5-cyclopropyl-1 - (lrans-4-ethoxycarbonylcyclohexyl) -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine 1- (lrans-4-eioxycarbonylcyclohexane) -5-cyclopropyl-1 H-pyrazole-4-carboxylic acid (1.50 g) produced in the lower layer was dissolved.

(S) -3- (2-nifluoromethylphenyl) pyrrolidine (1.16 g) in N, N-dimethylformamide (15 ml), and 1-hydroxybenzoyriazole (825 mg), 1-ethyl-3- (3-dimethylaminopropyl hydrochloride ) -carbodiimide (1.03 g) and 4-dimethylaminopyridine (658 mg).

The mixture was stirred at ambient temperature for 14 hours. The ethyl acetate was added to the reaction mixture and the mixture was washed twice with water. The organic layer was washed with 1N hydrochloric acid, with water, with a saturated solution of sodium acid carbonate in water, with water and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: methanol = 20: 1) to yield the title compound as a amorphous, amorphous substance (2.34 g).

EIApa 6 Production of 1- [1- (rans-4-carboxycyclohexyl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine It was dissolved 1 -. { 5-cyclopropyl-1 - (trans-4-yloxycarbonylcyclohexyl) -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine (2.34 g) produced in the previous step in tetrahydrofuran (12 ml) and methanol (6 ml), and was add a solution of monohydroxy hydroxide (973 mg) in water (12 ml). The mixture was stirred at 45 ° C for 1 h. The mixture was concentrated under reduced pressure, and water was added to the obtained residue. The mixture was washed twice with diethyl ether, and the aqueous layer was acidified with 2N hydrochloric acid and expelled 3 times with ethyl acetate. The organic layer was washed with water and saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Ethyl acetate and n-hexane were added to the obtained residue, and the precipitated solid was separated by filtration and dried to yield the title compound as a milky white solid (2.13 g).

Step 7 Production of 1- [1- (trans-4-carbamoylcyclohexyl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine Was dissolved 1- [ 1- (trans-4-carboxycyclohexyl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine (300 mg) produced in the lower layer in N, N-dimethylformamide (3.5 ml), and 1-hydroxybenzolyrolzole (106 mg), 1-elyll-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride (133 mg), ammonium chloride (80 mg) and eryrylamine (0.105) were added. ml). The mixture was stirred at room temperature for 15 h. The ethyl acetate was added to the reaction mixture, and the mixture was washed sequentially with water, with 1 N hydrochloric acid, with water, with a saturated solution of sodium hydrogen carbonate or water, with water and with water. saline solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Diethyl ether was added to the solid residue obtained and the mixture was stirred for 10 min. The solid was separated by filtration and dried to yield the title compound as a white amorphous solid (171 mg).

EXAMPLE 131 Production of 145-cycloBBropropB-14trans-4-ureidoeicBohexHHH-pBraz @ D-4-carbonyl14 (S) -342-trifluoromethylphen81) lpirro8idBff Ioluene (3.0 mL) was added to 1- [1- (lrans-4-carboxycyclohexyl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine ( 200 mg) produced in Example 130, step 6, and were added eryrylamine (76 ml) and diphenylphosphonic azide (118 ml) under an argon aosphere. The mixture was heated under reflux for 2 h. After allowing to cool, the toluene solution was slowly added to a solution of 28% ammonia in water (10 ml) and ethyl acetate (4 ml) under an ice bath, and the mixture was stirred at the same temperature during 30 min. Water was added to the reaction mixture, and the mixture was extracted 3 times with chloroform. The organic layer was washed with water and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (chloroform: meianol = 10: 1). The diethyl ether was added to the solid residue obtained and the mixture was stirred for 10 min. The solid was separated by filtration and drying to yield the compound of the product as a white amorphous solid (135 mg).

EXAMPLE 132 Production of 145-cyclopropiB-1-ftrans ^ -d H-teirazoxtXX or / te > : Xto-pyrazoi-4-carbonyl) 4 (S) -342-trifluoromethylphenol) lpyrroBidine Step 1: Production of 1- [1- (trans-4-cyanocyclohexyl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl] - [(S) -3- (2-fluorouromethylphenyl)] pyrrolidine Was dissolved 1- [ 1- (trans-4-carbamoylcyclohexyl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine (514 mg) produced in example 130, step 7 in teirahydrofuran (6 ml), and pyridine (180 μl) and trifluoromethanesulfonic acid anhydride (220 μl) were added. The mixture was stirred at room temperature for 1 h. Pyridine (180 μl) and trifluoromethanesulfonic acid anhydride (220 μl) were added, and the mixture was stirred at room temperature for 1 h. The mixture was concentrated under reduced pressure, and a 1 N aqueous solution of postasium acid sulfate was added. The mixture was extracted with acetyl ether. The oil layer was washed with water, dried over anhydrous magnesium sulphide, and concentrated under reduced pressure. The obtained residue was purified by chromatography (chloroform: methanol = 15: 1) to yield the title compound as a pale yellow amorphous solid (207). mg).

Eíapa 2 Production of 1-. { 5-cyclopropyl-1- [rans-4- (1 H -etrazol-5-yl) -cyclohexyl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine 1- [1- (trans-4-cyanocyclohexyl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3 was dissolved. - (2-trifluoromethylphenyl)] pyrrolidine (207 mg) produced in the previous step in 1,4-dioxane (2.5 ml), and azido-rhipidyl-styrene (188 mg) was added. The mixture was heated overnight under reflux. Azido-isobutyltin (94 mg) was added and the mixture was heated under reflux for 4 h. The mixture was concentrated under reduced pressure, 1N hydrochloric acid was added, and the mixture was extracted twice with chloroform. The chloroform layer was dried over anhydrous magnesium sulphide, and was concentrated under reduced pressure. The residue obtained was purified by chromatography (chloroform: methanol = 25: 2) and concentrated under reduced pressure. Diisopropyl ether was added to the obtained residue, and the precipitated solid was collected by filtration, and dried to yield the title compound as a white amorphous solid (122 mg).

EXAMPLE 133 Production of 1 541-? -methylcyclopropyl) -1,14-trifluo? R @ met5lfe? RaDD-garbamoyl) piperidin-4-yl] -1H-p5razole-4-carbonyl > -3 - ([piridin ° 3-i8) pir? R © BD lgíp? A By a method similar to that of Example 3, the title compound was obtained from the corresponding starting compound.

EXAMPLE 134 Production of 141-p 2-f8-uorophenylearbamoyl-piperidr-5-4-yl-1-S-1-methoxycyclopropyl) -1H-pyrazole-4-carbonyl} ° 342- triflluoromethylphenylUpyrrolineine For a similar method as in Example 3, the title compound was obtained from the corresponding starting compound.

EXAMPLE 135 Production of 1414 42-fluorophenylenebamoyl8 piperid5Bt? -4-i methy8cyclopropyl) -1H-pyrazole-4-earbonyl) 3-pheny8-3 tr5fluoromethyl- By a method similar to that of Example 3, the title compound was obtained from the corresponding start compound.

EXAMPLE 136 Production of 342-chloropheniB-1,45-eBcBopropiB-2,4-difluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazo-4-caB'b @ riig8 > pirro¡5 lñot? g? By a method similar to that of Example 3, the title compound was obtained from the corresponding starting compound.

EXAMPLE 137 Production of 342-eEopyridin-3-yl) -145-skyprop8D ° 14H2 ° f] uorophenylcarbamoyl) pipend5n-4-yl-1H-p-tetrazo-4-carbongi} pirro8i (lg? riia For a similar method as in Example 3, the title compound was obtained from the corresponding starting compound.

EXAMPLE 138 Production of 14141 2-fBuorophenylcarbamo5l) p-peridiene-4-Bl1-542.2.3.3- tetramethylcyclopropyl] > -1H ° pirazoi- -carbonyl} -3- (piridiñ-3 ° iiB) p¡rrol¡ lñ [a? A By a method similar to that of Example 3, the title compound was obtained from the corresponding start compound.

EXAMPLE 139 Production of 145-cyclohexyl-141 2-fluorophenBlearbam @ gBto-peridonium-5IT1- 1H-pyrazole-carbonyl) -34pyridin-34l) pyrrolBd8one By a method similar to that of Example 3, the compound of the particle was obtained from the corresponding beginning compound.

EXAMPLE 140 Production of 14S-cyclopropyB-141-f2-f8uoropheniBcarbaitne5B | pip @ rid? Ii? - -iB1- 1H-pyrazo8-4-carbonyl > "342-trifluoromethoxyfeniB) pprro8idDna By a method similar to that of Example 3, the compound of the isolate was obtained from the corresponding starting compound.

EXAMPLE 141 Production of 4S-sky-propyl-1-f 1 4-trifluoromethoxyl? P? ÑBcarbaprii @ ñB *) - piperidin-4-ip-1H-pyrazo8- -carbonyl-342-trifiuoromethoxyphenyl) pprr © Bg lBíp? A For a similar method as in Example 3, the title compound was obtained from the corresponding starting compound.

EXAMPLE 142 Production of 1-5-cycloBopropy8-141-yl (SI-1-carboxy-2-methylearbamoipiperidin-44l) -1H-pyrazoi-4-e trifluoroimethylpheniBIpirroBidiBTia By a method similar to that of Example 12, the title compound was obtained from the corresponding starting compound.

EXAMPLE 143 Production of 145-cyclopropiM 41 2-fluoropheni8carbaiitnoiBlpiperid? P? -44l1 ° 1H-pyrazofi-4-carbonyl > -3-methoxy-342-trifluoromethylphen} pirroB¡dó [p? a By a method similar to that of Example 3, the compound of the thioule was obtained from the corresponding starting compound.

EXAMPLE 144 Production of 14141 2-fluorophenylcarbamo8l) pipergdiifl-4B1-S 1] -hydroxymethylcyclopropyl) -1H-pyrazole-4-carboniB} -342- ftrifluoromet »lphenyl) pyrrolidgna By a method similar to that of Example 3, the compound of the extract was obtained from the corresponding starting compound.

EXAMPLE 145 Production of 145-cyclopropyl8-1 1 thiazoB-2-58carbamogi pBperidin ^ -D? 1-1H-pyrazo8-4-carbonyl) -342-trifluoromethylphenyl) p8rroBi lBna By a method similar to that of Example 10, the title compound was obtained from the corresponding start compound.

EXAMPLE 146 Production of 1414 483? Propoxycarbamoi8 | p5perido? ¡^ - 8B1-5 - ([1- ethyl cyclopropyl) -1H-pyrazoB-4-carbonyl-342-trifluoromethylf®o? By a method similar to that of Example 10, the title compound was obtained from the corresponding starting compound.

EXAMPLE 147 Production of 145-cyclopropyl-141 4-fluorobencglcarbapri (3 > il) pipe? RB < lBip? - - in-1H-pyrazole-4-carbonyl-342-trifluoromethylphenolBDiolrolidine By a method similar to that of Example 10, the title compound was obtained from the corresponding starting compound.

EXAMPLE 148 Production of 141 2,3-dihydroindol-1-carbonyl) piperidin-4-yr.-5 H -methylcyclopropyl-H-p-arazoB-4-carbonyl) -34-pyridin-3-gB] > pirroiidiri) g) By a method similar to that of Example 10, the title compound was obtained from the corresponding start compound.

EXAMPLE 149 Production of 1414 42.3-dihtdrop .41-oxazin-4-carboniB *] pBperidin-4 ° SD1-g1-methyl-8-propyl) -1H-pyrazole-4-carboni8) -34p »ridip-34Blpyrroli lDCi? A By a method similar to that of Example 10, the title compound was obtained from the corresponding start compound.

EXAMPLE 150 Production of 145-cyclopropii-14 2.S-dichloropyridin-3-Bicarb? Pp? gD]) - piperidin-4-yl] - -1H-pyrazo8-4 carbonyl) ° 342-trifluoromethylphenyl) pyrroDB lDiDa For a similar method as in Example 10, the title compound was obtained from the corresponding start compound.

EXAMPLE 151 Production of 14541 -methylcylopropyl]) - 141 2,3,4,5-tetra ^ 5drob @ Bi) z @ ÍM-azepin-1-carbonyl) piper8din-4-i -1H-pirazo8-4- € arbon5l > -34piridBin ° 34llD ° By a method similar to that of Example 10, the compound of the equation was obtained from the corresponding start compound.

EXAMPLE 152 Production of 44445-cyclopropy8-44342-trifluoromethyl-phenyl) pyrrole8? Gil5? P) -1l-carbonyl-1-pyrazol-1-ii} piperidin-1-yl) benzoate By a method similar to that of Example 114, the title compound was obtained from the corresponding start compound.

EXAMPLE 153 Production of 141 1-beneilox5carbon? L-pipergdin-4-ñB ° § ° sic¡opropD [l ° 1H ° pyrazole-4-earbonill-34pyridin-3-5 > ) pyrrolidide-i) a By a method similar to that of Example 1, step 4, the title compound was obtained.

EXAMPLE 154 Production of 14141 3-carboxy-3-methyl-butyryl) piperdin-g-1-cyclopropyl-1H-pyrazole-4-carboniB > -3-f2-trifluoromet-5lfei, 6gB) pir? Roii By a method similar to that of Example 65, the title compound was obtained from the corresponding starting compound.

EXAMPLE 155 Production of 145-cyclopropyl-141- (2-phenoxy »acetyi) p» p @ r5dip? -4-gni1-H -pyrazole-4-carboni8) -34pyr5din-3-i8) pyrro8id8? T) g ? For a similar method as in Example 64, the composition of the particle was obtained from the corresponding starting compound.

EXAMPLE 156 Production of 14141 3-chlorobenzoiHpiperidin-4-yl] -5-eDelopropDl] H-M-pyrrazol-4-carbonyl > -3- (pyridin-3-yi) pyrro8idi ??? g? For a similar method as in Example 64, the compound of the compound was obtained from the corresponding starting compound.

EXAMPLE 157 Production of 14 41 2-cBorobenzoyl) piperid5n-4-iB1-5-oprop58-1 H-pyrazole-4-carboni8 > -34pyridin-3-i8]) pgrro8idine For a similar method as in Example 64, the compilation of the index was obtained from the corresponding starting compound.

EXAMPLE 158 Production of 145-cyclopropyl 8-1-p1-oxalylpiperidine-44B]) 1H-pi? Ra @ P-4-carbonii1-342-trgfluoromethylpheniHp8rrolidine By a method similar to that of Example 65, the title compound was obtained from the corresponding starting compound.

EXAMPLE 159 Production of 14141 4-eBorobenzoyl) pyrimidin-4B'I-g-oprQPBB-H H-pirazoi-4-carbongl) -34-pyridin-3-yi) pyrroxylation] By a method similar to that of Example 64, the title compound was obtained from the corresponding start compound.

EXAMPLE 160 Production of 145-cyclopropiB ° 14142444luorofenny) aeetiBT1piperidi [t) -4-5B 1H-pirazo -earbonil) -34pyridin-3-iB] | pyrroBidÍB, i) a By a method similar to that of Example 64, the title compound was obtained from the corresponding starting compound.

EXAMPLE 161 Production of 145-cyclopropi8- 41 3-trifluoromethylbenzogB]) piperidium- -5B1- 1H-p.razoB-4-carbonyl 3,4-pyridin-3-gQp? RroBidB By a method similar to that of Example 64, the title compound was obtained from the corresponding starting compound.

EXAMPLE 162 Production of 145-cyclopropiB-1 1 3-methoxybenzoi8) pip @? Rdin-4 °? B] 1 ° 1 M ° pyrazole-4-carbonyl-34 pyridin-3-yl) pyrrolidine By a method similar to that of Example 64, the compound of the title was obtained from the corresponding starting compound.

EXAMPLE 163 Production of 141 1 4-fluorobenzyl hydrochloride) pip @ ridin-4 ml g - ([1- Bt? Ethylcyclopropy8) -1 H -pyrazo8-4-carbonSI > --342 ° trgfBuoroppsetJ8fenil) pirr @ [lñ (] 5ng? For a similar period as in Example 94, the composition of the title was obtained from the corresponding starting compound.

EXAMPLE 164 Production of 1 41-benzene-3-sulfonyl-piperidine-4-BB | 5-s5eloprop-B-1-CHl-pyrazole-4-carbonyl-3-4-pyr »din-3-5l-pyrro-8-B-5ng? For a similar method as in Example 108, the compound of the extract was obtained from the corresponding starting compound.

EXAMPLE 165 Production of 141 -H-garbamoylfeng8) piperidin-4-β1-g-elopr @ PD? -1"H- pyrazoB-4-carboni8> -342-trifBuoromethylfeniB) p5rrQD5dina By a method similar to that of Example 113, the compound of the equation was obtained from the corresponding starting compound.

EXAMPLE 166 Production of 145-cyclopropiB-141 4-hydroxyethylpheniB) pyrprididene-4-DB1-1IH-pyrazole-4-carbonyl-342-trifluoromethoxyphenyl) p5rroBBdine By a method similar to that of Example 113, the title compound was obtained from the corresponding start compound.

EXAMPLE 167 Production of 141 1 -f 5-carbamoyB-pyridin-2-8B | pBperidin-4-i8T¡ ° g- cyclopropy8-1H-pyrazole-4-carboni8 > -342-trifluoroB, net5lfeií By a method similar to that of Example 113, the title compound was obtained from the corresponding starting compound.

EXAMPLE 168 Production of 14141 4-aminopheniHpiperidin-4-i1-i-c5sBopropgg ° 1lH-pyrazole-4-carboniB) -342-trifluoromethylpheniB) pBrrol5dine By a method similar to that of Example 113, the compound of the title was obtained from the corresponding starting compound.

EXAMPLE 169 Production of 145-CyBopropyD-1 4442-OxooxazolgdIB3-iBKeraS [] piperidin-4-y1) -1H-pyrazole-4-carbonyl) -342-trifluoromethyl-8BBB By a method similar to that of Example 113, the title compound was obtained from the corresponding starting compound.

EXAMPLE 170 Production of 145-cyclopropiB-41- [443-methoxyureido) frisriB1 piperndlñ [p? - - Bl > -1H-pyrazocarboniB) -342-trif8uoromethylfeninp5r? R © lidi0? A For a similar method to that of Example 113, the compilation of the tíulo was obtained from the corresponding beginning compound.

EXAMPLE 171 Production of 145-cyclopropii-1-1-4-methanesulfon-5-phenyl-phenyl-pyr) -radio-4-pyridyl-4-carbonyl) 3- (2-trifluoromethyl-phenyl) pnr [rolidgna By a method similar to that of Example 113, the compound of the thiule was obtained from the corresponding starting compound.

EXAMPLE 172 Production of 1414-ethoxycarbamoylpiperidin-4-i8l) -S- (f 1 -thi 1 H-pyrazole-4-carbonin-342-trifluoromethylBPhenyl)) pBrirQBidine By a method similar to that of Example 10, the title compound was obtained from the corresponding starting compound.

EXAMPLE 17 Production of 1 1 5-chloropyridin-2-iB) azetidin-3-Bll-g-e5 oprop5B-1] ll-3-pyrazole-4-carbongB3-342-trifluoromethylphenyl) pgrrol5dine By a method similar to that of Example 113, the title compound was obtained from the corresponding starting compound.

EXAMPLE 174 Production of I-f -IS-Chloro-pyridine-1-phenyl-4-carbonyl-3-methoxymethyl-1-pyroxy-4-carbonyl.

By a method similar to that of Example 113, the compound of the extract was obtained from the corresponding start compound.

EXAMPLE 175 Production of 14141 5-cyano-pyridin-2-yl) piperidin-4-ii1-5 ° © ñciopro [! 3ñB-1C-! L-p¡razole-4-earbonyl) -342-trifluoromethylphenyl) pyrroBBd5na By a method similar to that of Example 113, the title compound was obtained from the corresponding start compound.

EXAMPLE 176 Production of 342-ketoxyethoxy-44-fluorofonyl-4,44-methyl-8-propyl-141-pyrimidin-2-ii) piperidin-8-H-pyrazole-4-carbonyl8-pyrrolidine hydrochloride By a method similar to that of Example 113, the title compound was obtained from the corresponding starting compound.

EXAMPLE 177 Production of f < hydrochloride 3S \ 4R *) - 3-methylM 541-methylcyc 1 1 pyrimidin-2 ° il) piperidin "4-yl] ° 1 H-pBrazole-4-carboni8.

By a method similar to that of Example 113, the compound of the compound was obtained from the corresponding start compound.

EXAMPLE 178 Production of 64445-cyclopropyl-44342-trifluoro etiBfe? PgBÍpirroBgdlDi¡t? -1- sarbonil1pirazo8-1-ii) piperidin-1-yl *) metiBo nicotinate By a method similar to that of Example 113, the compound of! The product was obtained from the corresponding starting compound.

EXAMPLE 179 Production of 2414541-methy8cyclopropyH-141-pyrimidine-24l-piperDd5? P? -4- 5l) -1H-pyrazoB-4-carbonylpyrrolidin-3-yl > roetiflo benzoate By a method similar to that of Example 113, the thioule compound was obtained from the corresponding starting compound.

EXAMPLE 180 Production of 342-hydroxymethylpheniol)) - 14541-methylcyclopropyl) -1414-pyrimidin-2-iB) piperidin-4-i81-1H pyrazole By a method similar to that of Example 113, the thioule compound was obtained from the corresponding starting compound.

EXAMPLE 181 Production of 145-cyclopropiB-1 1 -pyridin-2-dB-p5peridip) -4-BB)) - 1 H -pyrazoP 4 -carbonip-3-hgdroxy-34pyridin-3-iB) pyrroliding? By a method similar to that of Example 113, the title compound was obtained from the corresponding starting compound.

EXAMPLE 182 Production of 141 144-acetylaminophenyl) piperidin-4-iBl ° g ° snclopro [9DB-1 H-pyrazole-4-carbon5l} -342-trifluoromethiBfen5l) pirroBidgna By a method similar to that of Example 114, the compound of the compound was obtained from the corresponding starting compound.

EXAMPLE 83 Production of 44445-cyclopropyl-44342-trifluoronnetiifengB) pyrroBg lo? P? -1-carbonyl-1-pyrazol-1-yl} pipe? ridin-1-Bl) ° 3-fluorobenzoate of sodc © By a method similar to that of Example 114, the title compound was obtained from the corresponding start compound.

EXAMPLE 184 Production of 342-cyanophen * 8 -14§-cyclopropyl-1 1 2-iFBuorofeot? Ñn-earbamoyl) piperidin-4-iBl-1H-pyrazo8-4-carbenil) pyr? R @ Bidina By a method similar to that of Example 121, the title compound was obtained from the corresponding starting compound.

EXAMPLE 185 Production of 3-h8droxymethiB-1414144-methoxyp? R5mBdlp? P) 2-5l) piperidin-4-ip-541-methyletic8oprop88 | -1H-pyrazole-4-earbonifl -3 ° phenylpyrrolidone hydrochloride By a method similar to that of Example 127, the compound of the compound was obtained from the corresponding start compound.

EXAMPLE 186 Production of 343.5- Difluorophen-BH 3 hydrochloride -hydrox 5 -met-B 14? -41-etH-cyclopropyl) -141 pgrimidin-2-yl) piperidin-4-yl-1H-p-5-carboxyl-carbonylpyrrolidine By a method similar to that of Example 127, the title compound was obtained from the corresponding starting compound.

EXAMPLE 187 Production of 1 1 143-eloro ° pyridin ° 2-i!) Piperidin-44Bl-§ "clopropylal] -1H-pyrazole-4-carbonyl-1-pyridin-3-yl) pyrrolidin? By a method similar to that of Example 113, the title compound was obtained from the corresponding starting compound.EXAMPLE 188 Production of 145-cyclopropi-4142-fluorofeniBcarbamnogB | piperid5? P? 4-5B1- 1H-pyrazole-4-carboni8) -34thiazo8-2-iB) pyrrolidine By a method similar to that of Example 121, the compound of the title was obtained from the corresponding beginning compound.

EXAMPLE 189 Production of (S) -2-f [trans] 45 -cyclopropyl-4-f342-Wfluorom-tlpB-phenyl) -pyrro-8-idin-1-carbonyl-1-pyrazoi-148-B-chlorhexancarbora-5-aminocarbonyl) -methyl-a ? priipr? o] - 3-cnethylbutyral By a method similar to that of Example 130. the title compound was obtained from the corresponding starting compound.

EXAMPLE 190 Production of 1 5411 Hpnethylcyclopropyl) -14trans ^ 42- (fluoroff? I) ill-earbamoyl) cyclohexyl-1H-pyrazo-4-earbonp-342-trifluoroBThyetllfeni8] | pgrrolidgna For a similar method to that of Example 130. the title compound was obtained from the corresponding starting compound.

EXAMPLE 191 Production of cis-44541-methylBopropgB]) - 44342-trifluoromethyl-phenyl) -pyrro-8-idin-1-carbonyl-B-pyrazB--58) - eicBohexancarboxylic acid By a method similar to that of Example 130, the title compound was obtained from the corresponding start compound. The structural formula and the values of the compound properties of each example are illustrated in Table 1 below.

TABLE 1 (CONTINUED) TABLE 1 flCQNTBNUACBQN]) TABLE 1 CONTINUATION) TABLE 1 CONTACT8NUACBQN) TABLE 1 INDEXUACIQW TABLE 1 ÍCQNTBNUACDTNI) TABLE 1 fCONTiNUACBQND TABLE 1 CONTINUATION!) TABLE 1 (CONTINUED) TABLE 1 (CONTINUED) TABLE 1 (CONTINUED) TABLE 1 CONTINUATION TABLE 1 (CONTINUED) TABLE 1 (CONTBNUACIQNi) m) TABLE 1 «CONTONUACITN *) d: m); d: d: d: d: TABLE 1 (CQNTBNUACBQND TABLE 1 (CONTINUED) TABLE 1 (CQNTINUACBONIi TABLE 1 (CONTINUED) TABLE 1 (CQNT8NUAC80N) The present invention will now be concretely described by the following formulation examples, which should not be construed as limiting thereof.

Example of fformuBae'on 1 (production of caps 1) compound of example 1 30 mg 2) crystalline cellulose 10 mg 3) lactose 19 mg 4) magnesium stearate 1 mg 1), 2), 3) and 4) were mixed and filled into a gelatin capsule.

Formulation example 2 (production of ftafeBata]) 1) compound of example 1 30 g 2) lactose 50 g 3) corn starch 15 g 4) calcium carboxymethyl cellulose 44 g 5) magnesium stearate 1 g The total amount of 1), 2), 3) and 30 g of 4) was kneaded with water, dried under reduced pressure and sieved. The screened powder was mixed with 14 g of 4) and 1 g of 5), and formed into a tablet with a tabletting machine. In this manner, 1000 tablets containing 30 mg per tablet of the compound of example 1 are obtained. In the same way as in the formulation example 1 or the formulation example 2 indicated above, the compounds of the Examples 2 to 191 can also be used to produce capsules or tablets.

EXPERMENTAL EXAMPLE i Inhibitory activity of the action of HSD-1 (idroxiesteroidl © isa 11 in The inhibitory activity of the action of HSD-1 was determined by quantification of the inhibition of conversion of cortisone to cortisol by a SPA system (scintillation proximity assay) and using, as an enzyme source, human HSD-1 (below) in the present recombinant HSD-1) expressed using baculovirus system. Reagents (100 μl) were added to a 96-well plate (Opti-plates ™ -96 (Packard)) at a final concentration illustrated below and the reaction was carried out at room temperature for 90 to 120 min. As a reaction mixture, 5-100 ng / well of recombinant HSD-1, 500 μM of NADPH and 10 nM 3H of cortisone (American Radiolabeled Chemicals Inc., 50 Ci / mmol) were dissolved in PBS containing 0.1% BSA (Sigma), and the test substance was 2 μl of a compound solution (dissolved in DMSO). After the reaction, 50 μl of PBS (containing 0.1% BSA (Sigma)) containing 0.2 μg of anticortisol mouse monoclonal antibody (East Coast Biologics), 500 μg of anti-mouse antibodies bound to PVT SPA in beads (Amersham Biosciences ) and 133 μM of carbenoxolone (Sigma) were added to the reaction mixture to stop the reaction. After the reaction was carried out, the mixture was incubated at room temperature for at least 2 h, and the radioactivity was measured with Topcount (Packard). As the control, the well values were used with aggregates of 2 μl of DMSO instead of the test substance (0% inhibition) and, as a positive control, the values of the wells to which carbenoxolone was added ( final concentration 100 μM) instead of the test substance (100% inhibition). The inhibition (%) of the test substance was calculated from ((control value - test substance value) / (control value - positive control value)) x 100 (%). The IC50 value was calculated from the inhibition ratio of two points that cross 50% inhibition. The results obtained are illustrated in table 2 below.

TABLE 2 CONTINUATION)] PICTURE 2 CONTACTUBUACBQN1 In the previous tables, ++ means IC50 values that do not exceed 30 nM.

INDUSTRIAL APLBCAC8QN The heterocyclic compounds of the present invention possess a superior HSD1 inhibitory action and are useful as an agent for prophylaxis or treatment of metabolic diseases such as diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension, fatty liver and the like . This application is based on patent applications Nos. 2005-168901 and 2006-027097 registered in Japan, and 60 / 692,039 and 60 / 772,734 registered in E.U.A, its contents are incorporated herein by reference.

Claims (191)

NEW OF THE BNVENCIOM £ IVNDICATIONS
1. A compound represented by the following formula [1 ']: wherein: ring A is (1) a saturated monocyclic nitrogen-containing heterocyclic group, or (2) a cycloalkyl group, said ring A is optionally substituted with one or more substituents the same or different R1, said substituent R is 1) a hydrogen atom, 2) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a hydrogen atom, (b) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) an alkyl group d-6 (said C-? 6 alkyl group is optionally substituted with one or more equal or different substituents selected from the following group: (i) a halogen atom, (ii) hydroxyl group, and (iii) an alkoxy group of Ci-β), and e) a C 1-6 alkoxy group, (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more alkyl groups of C1-6 equal or different (said alkyl group of C -6 is optionally substituted with one or more identical or different substituents selected from the following group: (i) a hydroxyl group, and (ii) a C 1-6 alkoxyl group), (d) an alkyl group of Cl-6 (said C 1 -C 6 alkyl group) -? - 6 is optionally substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) an aryl group (said aryl group is optionally substituted with one or more substituents same or different selected from the following (1) and (2): (1) a halogen atom, and (2) C-? -6 alkyl group (said C? _6 alkyl group is optionally substituted with one or more halogen atoms the same or different)), d) -NR20R21 wherein R20 and R21 are the same or different and each is a hydrogen atom, an alkyl group of C-? 6, or a -CO-alkyl group of C? .6, or R20 and R21 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing n itrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) an oxo group, and (iv) a C1-6 alkoxy group), e) a C6-6 alkoxy group, and f) a carboxyl group, (e) -S (= O) 2 -R9 wherein R9 is an aryl group ( said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) a C 1-6 alkyl group (said alkyl group of C -? - 6 is optionally substituted with one or more same or different halogen atoms)), or a C? -6 alkyl group, (f) a saturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of C? -6, b) a -CO-alkyl group of C-? - 6, and c) an oxo group), (g) a C? -6 alkoxy group, or (h) an unsaturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different halogen atoms) ), or (i) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, or a heterocyclic group which is a fused ring of said heterocycle and a carbon ring ( both indicated heterocyclic groups are optionally substituted with one or more same or different substituents selected from the following a) to i): a) a halogen atom, b) a hydroxyl group, c) an alkyl group of C? -6 (said alkyl group of C? -6 is option is substituted with one or more identical or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxy group of C -? - 6), d) a carboxyl group, e) a -CO-alkyl group of C -? - 6, f) -CO-NR2 R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of C-? -6, or R22 and R23 optionally form, together with the nitrogen atom to which they are attached, a group nitrogen-containing saturated monocyclic heterocycle, g) an oxo group, h) -NR2 R25 wherein R24 and R25 are the same or different and each is a hydrogen atom, an Ci-β alkyl group, or a -CO- group C-6 alkyl, or R 24 and R 25 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, and i) a C 1-6 alkoxy group, 3) -COOR 10 wherein R 10 is (a) a C? -6 alkyl group (said C? -6 alkyl group is optionally substituted with one or more identical or different substituents selected from the following a) to d): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or a group C? -6 alkyl, or R26 and R27 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, c) a C6-6 alkoxy group and d) an aryl group) , or (b) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of C? -6, b ) a group -CO-C 1-6 alkyl, and c) an oxo group), 4) -COR 11 wherein R 11 is (a) an alkyl group of C? -6 (said alkyl group of C? -6 is optionally substituted with one or more same or different substituents selected from the following a) to h): a) a halogen atom, b ) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, a C1-6 alkyl group, a -CO-C1-6 alkyl group, a -CO group -cycloalkyl, or a group -S (= O) 2-C-6 alkyl, or R28 and R29 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, d) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of C-6, or R30 and R31 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, e) a C? -6 alkoxy group, f) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, (iii) an alkoxyl group of d-β, and (iv) a C 1-6 alkyl group (said C grupo-alkyl group) 6 is optionally substituted with one or more same or different halogen atoms)), g) a carboxyl group, and h) an aryloxy group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C? -6 (said alkyl group of d-β is optionally substituted with one or more same or different halogen atoms), and b) an alkyl group of C6-6 (said alkyl group of Ci is optionally substituted with one or more equal or different substituents selected from the following group: i) a hydroxyl group, and (ii) a C6-C6 alkoxyl group), (c) a nitrogen-containing saturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the group consisting of following a) to c): a) an alkyl group of Ci. 6, b) a -CO-C 1-6 alkyl group, and c) an oxo group, (d) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) a (3): (1) a halogen atom,
2. (2) a C? -6 alkyl group (said C? -6 alkyl group is optionally substituted with one or more same or different halogen atoms), and (3) a C? -6 alkoxy group, or ( e) a carboxyl group, 5) an alkyl group of C6-6 (said C1-6 alkyl group is optionally substituted with one or more same or different substituents selected from the following (a) to (d): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different -CO-NR32R33 wherein R32 and R33 are the same or different and each is a hydrogen atom, an alkyl group of d-6 (said C? -6 alkyl group is optionally substituted with one or more substituents equal or different selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d-6), or R32 and R33 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group saturated nitrogen-containing), (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or an alkyl group of C? -6, or R34 and R35 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, and (d) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) an halogen, and b) an alkyl group of d -6 (said C1-6 alkyl group is optionally substituted with one or more same or different halogen atoms))), 6) a cycloalkyl group, 7) -S (= O) 2 -R12 wherein R12 is an alkyl group of d-6 (said C? -6? alkyl group optionally substituted with one or more identical or different halogen atoms), or an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) a halogen atom, and b) an alkyl group of d-6 ( said C1-6 alkyl group is optionally substituted with one or more same or different halogen atoms)), 8) -C (= NCN) -R13 wherein R13 is a C1-6 alkyl group, 9) -C (= NCN) NR14R15 wherein R14 and R15 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R14 and R15 optionally form, together with the nitrogen atom to which they are attached, a group saturated monocyclic nitrogen-containing heterocyclic, 10) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (a) to (f): (a) a carboxyl group, (b) a halogen atom, (c) an alkyl group of C? -6 (said alkyl group of Ci ^ is optionally and substituted with one or more identical or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, and c) an alkoxyl group of d-6), (d) -NR38R39 wherein R38 and R39 are same or different and each is a hydrogen atom, a C1-6 alkyl group, a -CO-alkyl group of C? -6, -CO-NR40R41 wherein R40 and R41 are the same or different and each is a hydrogen atom, an alkyl group of C? -6, or an alkoxy group of d-6, or R40 and R4 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, or -S (= O) 2-R42 wherein R42 is an alkyl group of d-6, or R38 and R39 optionally form, together with the nitrogen to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more oxo groups), (e) -CO-NR 3R44 wherein R43 and R44 are equal or different and each is a hydrogen atom, or an alkyl group of -6, or R43 and R44 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, and (f) a -COO- group alkyl of d-6), or 11) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following (a) to (h): (a) a carboxyl group, (b) a C 1-6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an atom of halogen, b) a hydroxyl group, and c) an alkoxy group of C? -6), (c) a cycloalkyl group, (d) a halogen atom, (e) -CO-NR45R46 wherein R45 and R46 are the same or different and each is an hydrogen, or an alkyl group of d-6, or R45 and R46 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, (f) a -COO-alkyl group of d. 6, (g) a cyano group, and (h) a C 1-6 alkoxy group); -X- is (1) -N (R1) - wherein R1 is the same as defined above, or (2) -C (R7R8) - wherein R7 and R8 are the same or different and each is 1) an hydrogen, 2) -NR16R17 wherein R16 and R17 are the same or different and each is a hydrogen atom, a C1-6 alkyl group, or -CO-NR36R37 wherein R36 and R37 are the same or different and each is a hydrogen atom, or an alkyl group of d.6, or R36 and R37 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen), or R16 and R17 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, 3) -CONR18R19 wherein R18 and R19 are the same or different and each is a hydrogen atom, a group C? _6 alkyl (said alkyl group of d ^ is optionally substituted with one or more carboxyl groups), or an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: (a) a halogen atom, and (b) an alkyl group of (said alkyl group of d-6) is optionally substituted with one or more same or different halogen atoms)), or R 8 and R 19 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, 4) a monocyclic heterocyclic group is not saturated with 5 members or with 6 members, or 5) a carboxyl group; R2 is (1) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following group: 1) an alkyl group of d-6 (said C? -6 alkyl group is optionally substituted with one or more identical or different substituents selected from the following group: (a) a hydroxyl group, and (b) an alkoxyl group of d-6), and 2) an alkoxy group of d-β); and R3 and R4 are identical or different and each is (1) a hydrogen atom, (2) an alkyl group of
3. C.sub.6 (said alkyl group of d-6 is optionally substituted with one or more identical or different subsides selected from the following group: 1) halogen atom, 2) a hydroxyl group, 3) an alkoxy group of C-? 6 , and 4) a group -OCO-C 1-6 alkyl), (3) an aryl group (said aryl group is optionally substituted with one or more identical or different susliluyeníes selected from the following 1) to 6): 1) a halogen atom, 2) an alkyl group of d-6 (said alkyl group of d-β is optionally substituted with one or more same or different substituents selected from the following group: (a) a halogen atom, (b) a group hydroxyl, and (c) a C 1-6 alkoxyl group), 3) a C 1-6 alkoxy group (said alkoxy group of d-6 is optionally substituted with one or more same or different halogen atoms), 4) a group carboxyl, 5) a -COO-alkyl group of d-6, and 6) a cyano group, (4) an unsaturated monocyclic 5-membered or 6-membered heterocyclic group mbros (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following group: 1) a halogen atom, and 2) a C 1-6 alkyl group (said C? -6 alkyl group is optionally substituted with one or more same or different halogen atoms), (5) a hydroxyl group, or (6) an alkoxy group of Cl-6], or a salt thereof. 2. A compound represented by the following formula [1]: wherein: -X- is (1) -N (R1) - wherein R1 is 1) a hydrogen atom, 2) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a moiety of hydrogen, (b) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) a C 1-6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) a alkoxyl group of d-6), and e) an alkoxy group of C? -6), (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more equal or different C1.6 alkyl groups (said alkyl group of d-6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) a alkoxy group of d-6)), (d) an alkyl group of d-6 (said C 1-6 alkyl group is optionally susiiuuided with one or more identical or different subsitutes selected from the following group: a) a hydroxyl group, ) a halogen atom, c) an aryl group (said aryl group is optionally substituted with one or more identical or different substitutes selected from the following (1) and (2): (1) a halogen atom, and (2) a alkyl group of d-6 (said C1-6 alkyl group is optionally substituted with one or more same or different halogen atoms)), d) -NR20R21 wherein R20 and R21 are the same or different and each is a hydrogen atom , an alkyl group of C ^, or a -CO-alkyl group of d-6, or R20 and R21 optionally form, together with the nitrogen atom to which they are ated, a monocyclic monocyclic heyerocyclic group which contains nihologen (said heterocyclic group) is optionally substituted with one or more identical or different substituents selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) an oxo group, and (iv) a alkoxy group of C? -6), e) a C 1-6 alkoxyl group, and f) a carboxyl group), (e) -S (= O) 2 -R 9 wherein R 9 is an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms), or an alkyl group of d-6, (f) a saturated monocyclic heyerocyclic group containing nitrogen (said group The heterocyclic compound is optionally substituted with one or more identical or different substituents selected from the following a) to c): a) an alkyl group of d.6, b) a -CO-alkyl group of C? -6, and c) an oxo group, (g) an alkoxy group of d-6, or (h) an unsaturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group) is optionally substituted with one or more same or different halogen atoms), or (i) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group saturated nitrogen-containing, or a heterocyclic group which is a fused ring of said heterocycle and a carbon ring (both mentioned heterocyclic groups are optionally substituted by one or more identical or differentiated substances selected from the following a) to i): a) a halogen atom, b) a hydroxyl group, c) an alkyl group of d-6 (said C1-6 alkyl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen, (ii) a hydroxyl group, and (iii) a C6-C6 alkoxy group, d) a carboxyl group, e) a -CO-C6 alkyl group, f) -CO-NR22R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of d-6 > or R22 and R23 optionally form, together with the nitrogen atom to which they are bonded, a saturated monocyclic nitrogen-containing heterocyclic group, g) an oxo group, h) -NR24R25 wherein R24 and R25 are the same or different and each is a hydrogen atom, an alkyl group of C? -6, or a -CO-alkyl group of d-6, or R24 and R25 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group which contains nitrogen, and i) an alkoxy group of Ci-e), 3) -COOR10 wherein R10 is (a) an alkyl group of C6-6 (said C6 -6 alkyl group is optionally substituted with one or more like substituents or differentials selected from the following a) to d): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or a C1-6 alkyl group, or R26 and R27 optionally form, together with the nitrogen atom to which they are attached, a heterocyclic group saturated monocyclic nitrogen-containing, c) an alkoxy group of d-6, and d) an aryl group), or (b) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more substitutes the same or different selected from the following a) to c): a) a C 1-6 alkyl group, b) a -CO-C 1-6 alkyl group, and c) an oxo group, 4) -COR 11 wherein R 1 'is (a) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more equal or different substituents selected from the following a) to h): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of d-β. a -CO-C-? -6 alkyl group, a -CO-cycloalkyl group, or a -S (= O) 2-C-? -6 alkyl group, or R28 and R29 optionally form, together with the atom of nitrogen to which they are attached, a nitrogen-containing saturated monocyclic heterocyclic group, d) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R30 and R31 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, e) a Cl-6 alkoxy group, f) an aryl group (said aryl group is optionally substituted with one or more equal or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, (iii) an alkoxy group of d-6, and (iv) an alkyl group of C? _6 (said alkyl group of -6 is optionally substituted with one or more same or different halogen atoms), g) a carboxyl group, and h) an arylox group ilo), (b) a group cycloalkyl (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following ( 1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of C6-6 is optionally susiiuuido with one or more equal or different halogen atoms)), and b) an alkyl group of C? -6 (said alkyl group of C-? -6 is optionally substituted with one or more equal or differential subsylines selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d-6), (c) a nitrogen-containing saturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c) a) an alkyl group of d-6, b) a -CO-alkyl group of Cl-6, and c) an oxo group, (d) an aryl group (said aryl group is optionally susíiuuido with one or more identical subsides) or different selected from the following (1) to (3): (1) a halogen atom, (2) a C 1-6 alkyl group (said C? -6 alkyl group is optionally substituted with one or more halogen atoms) same or different), and (3) an alkoxy group of d-6), or (e) a carboxyl group, 5) an alkyl group of C?, 6 (said alkyl group of d-6 is optionally substituted with one or more, they substitute the same or different ones selected from the following (a) to (d): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optional) entity substituted with one or more, -CO-NR32R33 same or different where R32 and R33 are the same or different and each one is a hydrogen atom, a C1-6 alkyl group (said alkyl group of is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of or R32 and R33 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heyerocyclic group which contains nitrogen), (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is an atom of hydrogen, or an alkyl group of d-6, or R34 and R35 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, and (d) an aryl group (said aryl group) is optionally substituted with one or more identical or different substitutes selected from the following group: a) a halogen atom, and b) an alkyl group of said alkyl group of C 6 is optionally substituted with one or more same or different halogen atoms ))), 6) a cycloalkyl group, 7) -S (= O) 2 -R12 wherein R 2 is an alkyl group of C ^ (said alkyl group of d-6 is optionally substituted with one or more identical halogen atoms) or different), or an aryl group (said g The aryl group is optionally susliluted with one or more same or different substituents selected from the following group: a) a halogen atom, and b) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more atoms halogens the same or different)), 8) -C (= NCN) -R13 wherein R13 is an alkyl group of C? -6, 9) -C (= NCN) NR1 R15 wherein R14 and R15 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R14 and R15 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, 10) an aryl group (said aryl group is optionally substituted with one or more identical or different substituents selected from the following (a) to (f) (a) a carboxyl group, (b) a halogen atom, (c) a C1-6 alkyl group (said alkyl group of is optionally substituted with one or more equal or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, and c) a C 1-6 alkoxyl group, (d) -NR38R39 wherein R38 and R39 are the same or different and each is a hydrogen atom, an alkyl group of -6, a -CO-alkyl group of d.6, -CO-NR40R41 wherein R40 and R41 are the same or different and each is a hydrogen atom, an alkyl group of -6, or an alkoxy group of d- 6, or R40 and R41 optionally form, together with the nitrogen moiety to which they are attached, a monocyclic heterocyclic group salified nitrogen-containing cyclic, or -S (= O) 2-R42 wherein R42 is an alkyl group of d-6, or R38 and R39 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group saturated nitrogen-containing (said heterocyclic group is optionally substituted with one or more oxo groups), (e) -CO-NR43R44 wherein R43 and R44 are the same or different and each is a hydrogen atom, or an alkyl group of - 6, or R43 and R44 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nilrogen, and (f) a -COO-C-6 alkyl group), or 11) a 5-member or 6-member monocyclic uncured heliccyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following (a) to (h): (a) a carboxyl group, (b) an alkyl group of d-6 (said alkyl group of C6.6 is optionally substituted with one or more identical or different substituents selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) a C 1-6 alkoxy group, (c) a cycloalkyl group, (d) a halogen atom, (e) -CO-NR45R46 wherein R45 and R46 are the same or different and each is a hydrogen atom, or a C1-6 alkyl group, or R45 and R46 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group which contains nihologen, (f) a -COO-alkyl group of d. 6, (g) a cyano group, and (h) an alkoxy group of d.6)), or (2) -C (R7R8) - where R7 and R8 are the same or different and each is 1) a of hydrogen, 2) -NR16R17 wherein R16 and R17 are the same or different and each is a hydrogen atom, an alkyl group of d-6, or -CO-NR36R37 wherein R36 and R37 are the same or different and each is a hydrogen atom, or an alkyl group of, or R36 and R37 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, or R16 and R17 optionally form, June with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, 3) -CONR18R19 wherein R18 and R19 are the same or different and each is a hydrogen atom, an alkyl group of d-6 (said alkyl group of C 1-6 is optionally substituted with one or more carboxyl groups), or an aryl group (said aryl group is optionally substituted do with one or more substitute same or different selected from the following group: (a) a halogen atom, and (b) an alkyl group of C6-6 (said C6.6 alkyl group is optionally substituted with one or more halogen atoms) equal or different)), or R18 and R19 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nilrogen,
4. 4) a non-saturated 5-membered or 6-membered monocyclic heterocyclic group, or
5. 5) a carboxyl group; R2 is (1) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following group: 1) an alkyl group of d-6 (said C? -6 alkyl group is optionally substituted with one or more identical or different substituents selected from the following group: (a) a hydroxyl group, and (b) an alkoxy group of Ci-e), and 2) an alkoxy group of d-6); and R3 and R4 are the same or different and each is (1) a hydrogen atom, (2) an alkyl group of C6-6 (said alkyl group of d6 is optionally substituted with one or more substituents the same or different selected from the following group: 1) a halogen atom, 2) hydroxyl group, 3) an alkoxy group of d-6, and 4) an -OCO-C-6 alkyl group, (3) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following 1) to 6): 1) a halogen atom, 2) a C 1-6 alkyl group (said C 1-6 alkyl group is optionally substituted with one or more identical or different substituents selected from the following group: (a) a halogen atom, (b) a hydroxyl group, and (c) an alkoxy group of C?
6. 6), 3) a C1-6 alkoxy group (said alkoxy group of d-6 is optionally substituted with one or more same or different halogen atoms), 4) a carboxyl group, 5) a -COO-C1 alkyl group -6, and 6) a cyano group), (4) a 5-membered or 6-membered unsaturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following group: 1) a halogen atom, and 2) an alkyl group of C6-6 (said C1-6 alkyl group is optionally substituted with one or more same or different halogen atoms), (5) a hydroxyl group, or (6) a group C? -6] alkoxy, or a salt thereof. 3. The compound according to any of claims 1 and 2, further characterized in that -X- is -C (R7R8) - wherein R7 and R8 are the same as defined in claim 1, or a salt thereof. 4. The compound according to any of claims 1 to 3, further characterized in that R8 is 1) -NR16R17 wherein R16 and R17 are the same or different and each is a hydrogen atom, or an alkyl group of C? _6 , or R16 and R17 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group which contains nitrogen, 2) -CONR18R19 wherein R18 and R19 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R18 and R19 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group which contains nitrogen, or 3) a monocyclic monocyclic 5-membered or 6-membered monocyclic group, or a salt thereof. 5. The compound according to claim 1 or 2, further characterized in that -X- is -N (R1) - wherein R1 is equal to that defined in claim 1, or a salt thereof. 6. The composite according to any of claims 1, 2 and 5, further characterized in that R1 is 1) a hydrogen atom, 2) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a hydrogen atom, (b) an aryl group (said aryl group is substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a halogen halo, c) a carboxyl group, d) an alkyl group of d-6 (said alkyl group of C? -6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, ( ii) a hydroxyl group, and (iii) an alkoxy group of d-6) and e) an alkoxy group of d-6), (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more C-alkyl groups) The same or different alkyl groups (said alkyl group of C6 is optionally substituted with one or more identical or different substitutes selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d-6) (d) an alkyl group of d-6 (said alkyl group of d6 is substituted with one or more identical or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a aryl group (said aryl group is optionally susíiuuido with one or more equal or differential substitutes selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of C6.6 is optionally substituted with one or more identical or different halogen atoms), d) -NR20R21 wherein R20 and R21 are the same or different and each is a hydrogen atom, an alkyl group of d-6, or a -CO-alkyl group of C-? -6, or R20 and R21 optionally form, together with the nitrogen moiety to which they are attached, a saturated monocyclic heterocyclic group containing nihologen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following (i ) a (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) an oxo group, and (iv) a C 1-6 alkoxyl group), e) an alkoxy group of d-6 , and f) a carboxyl group, (e) -S (= O) 2 -R9 wherein R9 is an aryl group (said aryl group is optionally substituted with one or more substituents ig or different selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said C1-6 alkyl group is optionally substituted with one or more atoms identical or different halogens), or an alkyl group of C? _6, or (f) a nitrogen-containing saturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more equal or different substituents selected from the following a) to c): a) an alkyl group of C? -6, b) a -CO-alkyl group of d.6, and c) an oxo group, or (g) an unsaturated monocyclic heterocyclic group containing nitrogen (said group) heterocyclic is optionally substituted with one or more same or different halogen atoms), or (h) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nihologen (said heterocyclic group is optionally susiiluted with one or more identical or different substituents selected from the following a) to i): a) an atom of halogen, b) a hydroxyl group, c) an alkyl group of d.6 (said C1.6 alkyl group is optionally substituted with one or more equal or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of d.6), d) a carboxyl group, e) a -CO-alkyl group of d-6, f) -CO-NR22R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or a C1.6 alkyl group, or R22 and R23 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, g) an oxo group, h) - NR2 R25 where R24 and R25 are the same or different and each one is an atom or of hydrogen, an alkyl group of d.6, or a -CO-C 1-6 alkyl group, or R 24 and R 25 optionally form, together with the nihologen atom to which they are bonded, a saturated monocyclic helerocyclic group containing nitrogen , and i) a C 1-6 alkoxy group (with the proviso that R 5 and R 6 are not simultaneously hydrogen atoms), 3) -COOR 10 wherein R 10 is (a) an alkyl group of d-6 (said alkyl group of d.6 is optionally substituted with one or more same or different substituents selected from the following a) to d): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is an hydrogen, or an alkyl group of C-? 6, or R 26 and R 27 optionally form, together with the nihilogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, c) a C? -6 alkoxy group, and d) an aryl group), or (b) a nitrogen-containing saturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more equal or different substituents selected from the following a) to c): a) an alkyl group of d.6, b) a -CO-alkyl group of d-6, and c) an oxo group), 4) -COR11 wherein R11 is (a) an alkyl group of d-6 (said alkyl group of d.6 is optionally substituted with one or more equal substitutes or differentials selected from the following a) to h): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of d-6, a -CO-alkyl group of d-6, a group -CO-cycloalkyl, or a group -S (= O) 2-C? -6 alkyl, or R28 and R29 optionally form, together with the nitrogen atom to which they are attached, a monocyclic nitrogen-containing heterocyclic heterocyclic group, d) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R30 and R31 optionally form, together with the nitrogen atom to which they are attached , a nitrogen-containing monocyclic heterocyclic group, e) an alkoxy group of -6, f) an aryl group (said aryl group is optionally substituted with one or more equal or different substituys selected from the following group: (i) an halogen, (ii) a hydroxyl group, (iii) an alkoxy group of d-6, and (iv) an alkyl group of d-6 (said group at of d-6 is optionally susíiluido with one or more same or different halogen atoms)), g) a group carboxyl, and h) an aryloxy group), (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally subsituted with one or more identical or different substitutes selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said C1-6 alkyl group is optionally substituted with one or more same or different halogen atoms), and b) an alkyl group of d-6 (said alkyl group of d6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group , and (ii) an alkoxy group of d.6)), or (c) a nitrogen-containing saturated monocyclic heterocyclic group (said heterocyclic group is optionally substituted with one or more equal or different substituents selected from the following a) c): a) a gru po alkyl of d. 6, b) a -CO-C 1-6 alkyl group, and c) an oxo group, (d) an aryl group (said aryl group is substituted with one or more same or different substituents selected from the following (1) a (3): (1) a halogen atom, (2) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms), and (3) a group C 1-6 alkoxy), or (e) a carboxyl group, 5) an alkyl group of d-β (said C 6 -6 alkyl group is optionally substituted with one or more equal or different substitutes selected from the following (a ) a (d): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different ones -CO-NR32R33 wherein R32 and R33 are the same or different and each is a hydrogen atom, a C1-6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a group hydroxyl, and (ii) a C 1-6 alkoxyl group), or R32 and R33 optionally form, with the nitrogen atom to which they are attached, a salicy monocyclic heyerocyclic group containing nitrogen), (c) -CO-NR3 R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R34 and R35 optionally form, together with the nihologen atom to which they are bonded, a monocyclic heterocyclic group saturated nitrogen-containing, and (d) an aryl group (said aryl group is optionally substituted with one or more equal or differential substitutes selected from the following group: a) a halogen atom, and b) an alkyl group of d-6 ( said alkyl group of C -? - 6 is optionally substituted with one or more same or different halogen atoms))), 6) a cycloalkyl group,
7. 7) -S (= O) 2 -R12 wherein R12 is an alkyl group of d-6 (said alkyl group of d- 6 is optionally substituted with one or more same or different halogen atoms), or an aryl group (said aryl group is optionally substituted with one or more identical or different substitutes selected from the following group: a) a halogen atom, and b) a group alkyl of d-6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms)),
8. 8) -C (= NCN) -R13 wherein R13 is a C1-6 alkyl group,
9. 9) -C (= NCN) NR14R15 wherein R14 and R15 are identical or different and each is a hydrogen atom, or an alkyl group of C -? - 6, or R14 and R15 optionally form, in June with the niologen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group,
10. 10) an aryl group (said aryl group is optionally substituted with one or more equal or different substituys selected from the following (a) to (f): (a) a carboxyl group, (b) a halogen atom, (c) an alkyl group of d-6 (said alkyl group of d-6 is optionally subsituted with one or more identical or different substitutes selected from the following group: a) a hydroxyl group, b) a halogen atom, and c) an alkoxy group of d-6), (d) -NR38R39 wherein R38 and R39 are the same or different and each is a hydrogen atom, an alkyl group of d-6, a -CO-alkyl group of C? -6, -CO-NR40R41 wherein R40 and R41 are the same or different and each is a hydrogen atom, an alkyl group of, or an alkoxy group of d-6, or R40 and R41 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, or -S (= O) 2 -R42 wherein R42 is an alkyl group of d. 6, or R38 and R39 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more oxo groups), (e) -CO-NR43R44 wherein R43 and R44 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R43 and R44 optionally form a saturated monocyclic heterocyclic group with the nihologen atom to which they are attached. which contains nitrogen, and (f) a -COO-alkyl group of d ^), or
11. 11) a monocyclic heterocyclic group is not saluted with 5 members or with 6 members (said hei-cyclic group is optionally substituted with one or more equal or different substituents selected from the following (a) to (h): (a) a carboxyl group, (b) an alkyl group of -6 (said alkyl group of d.6 is optionally substituted with one or more identical or different substitutes selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) an alkoxy group of C -? - 6), (c) a cycloalkyl group, and (d) a halogen halo, (e) -CO-NR45R46 wherein R45 and R46 are the same or different and each is a hydrogen atom, or a C 1-6 alkyl group, or R 45 and R 46 optionally form, together with the nylrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, (f) a -COO-Ci-6 alkyl group, (g) ) a cyano group, and (h) an alkoxy group of C -? 6), or a salt thereof. 7. The compound according to any of claims 1, 2 and 5, further characterized in that R1 is 1) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a hydrogen atom, (b) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) an alkyl group of d6 ( said C- [alpha] -6 alkyl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) a C1-6 alkoxy group 6), and e) an alkoxy group of d-6), (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more identical or different C1-6 alkyl groups (said C6_6 alkyl group is optionally substituted with one or more identical or different substitutes selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d.6)), (d) an alkyl group of d-6 (said alkyl group of d6 is optionally substituted with one or more identical or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) an aryl group (said aryl group is optionally substituted with one or more identical or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) a group C 1-6 alkyl (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms), d) -NR 20 R 21 wherein R 20 and R 21 are the same or different and each is a hydrogen atom, an alkyl group of d-6, or a -CO-C 1-6 alkyl group, or R 20 and R 21 optionally form, j together with the niologen atom to which they are attached, a monocyclic monocyclic helerocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (ii) an oxo group, and (v) an alkoxy group of d-6), e) an alkoxy group of d-6, and f) a carboxyl group), (e) -S (= O) 2 -R9 wherein R9 is an aryl group (said aryl group is optionally substituted with one or more same or different substitute selected from the following (1) and (2): (1) a halogen atom, and (2) a C 1-6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more identical or dipole halogen atoms), or a group C 1-6 alkyl, or (f) a saturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more identical or different substitutes selected from the following a) to c): a) an alkyl group of -6, b) a -CO-alkyl group of C? -6, and c) an oxo group, (g) a C1-6 alkoxy group, or (h) an unsaturated monocyclic heterocyclic group conforming nihologen (said heterocyclic group is optionally substituted with one or more same or different halogen atoms), or (i) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group which contains nitrogen (said heterocyclic group is optionally substituted with one or more equal or different substituents selected from the following ) to i): a) a halogen atom, b) a hydroxyl group, c) an alkyl group of d.6 (said alkyl group of d.6 is optionally susiiuid with one or more identical susiiluyeníes or differents selected from the following group) (i) a hydroxyl group, and (ii) an alkoxy group of d-6), d) a carboxyl group, e) a -CO-C 1-6 alkyl group, f) -CO-NR 22 R 23 wherein R 22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R22 and R23 optionally form, together with the nitrogen atom to which they are bound, a saturated monocyclic helerocyclic group containing nitrogen, g) an oxo group, h) -NR24R25 where R24 and R25 are equal or you differentiate and each is a hydrogen atom, an alkyl group of C? -6, or a -CO-alkyl group of d-6, or R24 and R25 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic helerocyclic group that contains nitrogen, and i) an alkoxy group of C? -6) (with the proviso that R5 and R6 are not any combination of substituents selected from the following group: (i) a hydrogen atom, and (ii) an alkyl group of d- 6 unsubstituted), 2) -COOR 10 wherein R 10 is (a) an alkyl group of (said C 1-6 alkyl group is substituted with one or more identical or different substituents selected from the following a) to d): a ) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or a C1-6 alkyl group, or R26 and R27 optionally form, together with the nitrogen atom at which are attached, a saturated monocyclic heterocyclic group containing nitrogen, c) an alkoxyl group of d-β, and d) an aryl group), or (b) a saturated monocyclic heterocyclic group containing nylrogen (said heyerocyclic group is optionally substituted with one or more identical or different substituents selected from the following a) to c): a) an alkyl group of d-6, b) a -CO-alkyl group of d-6, and c) an oxo group), 3) -COR11 wherein R11 is (a) an alkyl group of d -6 (said alkyl group of C-? -6 is substituted with one or more identical substituents or differentiates selected from the following a) to h): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 in where R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of d-6, a -CO-alkyl group of d-6, a -CO-cycloalkyl group, or a group -S (= O) 2-C 1-6 alkyl, or R 28 and R 29 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group containing nylogen, d) -CO-NR 30 R 31 where R 30 and R 31 are the same or different and each one is a part of hydrogen, or an alkyl group of d-6, or R30 and R31 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group which contains nihologen, e) an alkoxy group of d-6, f) an aryl group (said aryl group is optionally substituted with one or more identical or different subsitutes selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, (iii) an alkoxy group of d.6, and (iv) a C 1-6 alkyl group (said alkyl group of d 1 is optionally substituted with one or more equal or different halogen atoms), g) a carboxyl group, and h) an aryloxy group, (b) a group cycloalkyl (said cycloalkyl group is optionally substituted with one or more same or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following ( 1) and (2): (1) a halogen atom, and (2) a C 1-6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more, the same halogen atoms or different)), and b) an alkyl group of d-6 (said alkyl group of d.6 is optionally substituted with one or more equal or different substitutes selected from the following group: (i) a hydroxyl group, and (i) an alkoxy group of d-6)), or (c) a heterocyclic group saturated monocyclic nitrogen-containing (said hei-cyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of Ci. 6, b) a -CO-alkyl group of C? -6, and c) an oxo group, (d) an aryl group (said aryl group is optionally susiiluted with one or more the same substituents or various selected from the following (1) to (3): (1) a halogen atom, (2) an alkyl group of C? -6 (said alkyl group of d-6 is optionally substituted with one or more identical halogen atoms) or differents), and (3) an alkoxy group of d-6), or (e) a carboxyl group, 4) a C 1-6 alkyl group (said alkyl group of d-6 is substituted with one or more like substituents) or different selected from the following (a) to (d): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more the same or different ones -CO-NR32R33 wherein R32 and R33 they are the same or different and each one is a hydrogen atom, an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxy group of C? 6), or R32 and R33 optionally form, together with the niologen atom to which they are attached, a saturated monocyclic nitrogen-containing heliccyclic group), (c) -CO-NR ^ R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R34 and R35 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group which contains nitrogen, and (d) a group aryl (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) a halogen atom, and b) an alkyl group of C-? -6 (said alkyl group of d-6 is optionally substituted with one or more halogen atoms the same or different s))), 5) a cycloalkyl group, 6) -S (= O) 2 -R12 wherein R12 is an alkyl group of d.6 (said alkyl group of d, 6 is substituted with one or more same or different halogen atoms), or an aryl group (said aryl group is optionally substituted with one or more identical or different substitutes selected from the following group: a) an atom of halogen, and b) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms)), 7) -C (= NCN) -R13 wherein R13 is a group C 1-6 alkyl, 8) -C (= NCN) NR 1 R 15 wherein R 14 and R 15 are the same or different and each is a hydrogen halo, or an alkyl group of C? -6, or R 14 and R 15 optionally form , together with the niologen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, or 9) an unsaturated 5-membered or 6-membered monocyclic heterocyclic group (said heterocyclic group is substituted with one or more identical substituents or different selected from the following (a) to (g): (a) a group d-6 alkyl (said C 1-6 alkyl group is substituted with one or more same or different substituents selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) a group d-6 alkoxy), (b) a cycloalkyl group, (c) a halogen atom, (d) -CO-NR45R46 wherein R45 and R46 are the same or different and each is a hydrogen atom, or a group C 1-6 alkyl, or R 45 and R 46 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, (e) a -COO-C 1-6 alkyl group, (f) a cyano group, and (g) an alkoxy group of d-6), or a salt thereof. 8. The compose of according to any of the claims 1, 2 and 5, further characterized in that R1 is 1) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a hydrogen atom, (b) an aryl group (said aryl group is substituted with one or more identical or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) an alkyl group of C? -6 (said C1-6 alkyl group is optionally substituted with one or more identical or different substitutes selected from the following group: (i) a halogen halo, (ii) a hydroxyl group, and (iii) an alkoxy group of d.6), and e) an alkoxy group of d -6), (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more identical or different C-? -6 alkyl groups (said alkyl group of d-6 is optionally substituted with one or more equal substituents or Differences selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d-β )), (d) an alkyl group of d-β (said C 1-6 alkyl group is substituted with one or more identical or different substitutes selected from the following group: a) a hydroxyl group, b) a halogen atom, ) an aryl group (said aryl group is optionally substituted with one or more equal or different sustiluyeníes selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said C1-6 alkyl group is optionally substituted with one or more halogen atoms which are different or different)), d) -NR 0R21 wherein R20 and R21 are the same or different and each is a hydrogen atom, an alkyl group of d-6, or a -CO-C 1-6 alkyl group, or R 20 and R 21 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heliccyclic group containing nylrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group. (iii) an oxo group, and (iv) an alkoxy group of Ci-β), e) an alkoxy group of d-6, and f) a carboxyl group, (e) -S (= O) 2 -R 9 in wherein R9 is an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of C 1-6 is optionally substituted with one or more halogen atoms equal or different)), or an alkyl group of C? -6, or (f) a saturated monocyclic heliccyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of d-6, and b) a -CO-alkyl group of d-6, and c) an oxo group), or (g) an unsaturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more same or different halogen atoms), or (h) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nylrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to i): a) a atom of halogen, b) a hydroxyl group, c) a C 1-6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more equal or different substituents selected from the group following: (i) a hydroxyl group, and (ii) a C 1-6 alkoxyl group), d) a carboxyl group, e) a -CO-C 1-6 alkyl group, f) -CO-NR 22 R 23 where R 22 and R23 are the same or different and each is a hydrogen atom, or a C1-6 alkyl group, or R22 and R23 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen , g) an oxo group, h) -NR 24 R 25 wherein R 24 and R 25 are the same or different and each is a hydrogen atom, a C 1-6 alkyl group, or a -CO-C 1-6 alkyl group, or R24 and R25 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nilrogen, and i) a C1-6 alkoxy group (with the proviso that R5 and R6 are not simultaneously hydrogen atoms) ), 2) -COOR10 wherein R10 is (a) an alkyl group of d-6 (said C1-6 alkyl group is substituted with one or more identical substituents or difer selected entities of the following a) to d): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R26 and R27 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group containing nitrogen, c) an alkoxy group of C6-6, and d) an aryl group), or (b) a monocyclic heterocyclic group saturated nitrogen-containing (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following a) to c): a) an alkyl group of C-? -6, b) a -CO-alkyl group of d-6, and c) an oxo group), 3) -COR11 wherein R11 is (a) an alkyl group of d-6 (said alkyl group of C -? - 6 is substituted with one or more identical or different substituents selected from the following a) to h): a) a halogen atom, b) a hydroxyl group, c) -NR 8R29 wherein R28 and R29 are the same or different and each is a hydrogen atom, an alkyl group of d-6, a group -CO-C 1-6 alkyl, a -CO-cycloalkyl group, or a group -S (= O) 2-alkyl of C? -6, or R28 and R29 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, d) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R30 and R31 optionally form, together with the nitrogen atom to which they are attached, a monocyclic heterocyclic group containing nitrogen, e) an alkoxyl group of -β , f) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, (iii) an alkoxyl group of d-β, and (iv) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more identical or different halogen atoms)), g) a carboxyl group, and h) an aryloxy group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more equal or different substituents selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of C? -6 (said alkyl group of C? _6 is optionally substituted with one or more same or different halogen atoms)), and b) a C.sub.1-6 alkyl group (said C.sub.6 alkyl group is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d-?) , or (c) a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more equal or different substitutes selected from the following a) to c): a) an alkyl group of d. 6, b) a -CO-alkyl group of d.6, and c) an oxo group, (d) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) to (3): (1) a halogen atom, ( 2) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms), and (3) an alkoxy group of d-6), or (e) a group carboxyl, 4) an alkyl group of d-β (said alkyl group of d6 is substituted with one or more same or different substituents selected from the following (a) to (d): (a) a carboxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more, the same or different -CO-NR32R33 wherein R32 and R33 are the same or different and each is a hydrogen atom, a C1-6 alkyl group (said alkyl group of C1-6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) ) an alkoxyl group of d-β), or R32 and R33 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen), (c) -CO-NR34R35 wherein R34 and R35 they are the same or different and each one is an atom of hydrogen, or a C1-6 alkyl group, or R34 and R35 optionally form, together with the nitrogen atom to which they are attached, a monocyclic monocyclic heyerocyclic group which contains nihologen, and (d) an aryl group (said aryl group is optionally substituted with one or more identical or different substituents selected from the following group: a) a halogen atom, and b) an alkyl group of d-6 (said C1-6 alkyl group is optionally substituted with one or more halogen atoms the same or differential))), 5) a cycloalkyl group, 6) -S (= O) 2 -R 12 wherein R 12 is an alkyl group of d-6 (said C 1-6 alkyl group is substituted with one or more identical halogen atoms) or different), or an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following group: a) a halogen atom, and b) an alkyl group of d-6 (said alkyl group of C). ? -6 is optionally substituted with one or more atoms halogens the same or different)), 7) -C (= NCN) -R13 wherein R13 is a C1-6 alkyl group, 8) -C (= NCN) NR1 R15 wherein R14 and R15 are the same or different and each one is a hydrogen moiety, or an alkyl group of .6, or R14 and R5 optionally form, together with the nitrogen atom to which they are attached, a monocyclic monocyclic nitrogen-containing heterocyclic group, or 9) a monocyclic heterocyclic group unsaturated of 5 members or of 6 members (said heterocyclic group is substituted with one or more same or different substituents selected from the following (a) to (g): (a) an alkyl group of d-6 (said alkyl group of d-6 is substituted with one or more identical or different substituents selected from the following a) to c): a) a halogen atom, b) a hydroxyl group, and c) an alkoxy group of C. Q), (b) a cycloalkyl group, (c) a halogen atom, (d) -CO-NR 5R46 wherein R45 and R46 they are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R45 and R46 optionally form, with the nitrogen atom to which they are attached, a monocyclic monocyclic heyerocyclic group containing nitrogen, ( e) a -COO-alkyl group of C? -6 > (f) a cyano group, and (g) an alkoxy group of d-6), or a salt thereof. 9. The compound according to any of claims 1 to 8, further characterized in that R2 is a cyclopropyl group or a 1-methylcyclopropyl group, or a salt thereof. 10. The compound according to any of claims 1 to 9, further characterized in that R3 and R4 are the same or different and each is (1) a hydrogen atom, (2) an alkyl group of C? -6 (said C.sub.1-6 alkyl group is substituted by one or more same or different substituents selected from the following group: 1) a halogen atom, and 2) an -OCO- C-6 alkyl group), (3) an aryl group (said aryl group is substituted with one or more identical or different substituents selected from the following 1) to 5): 1) a C 1-6 alkyl group (said alkyl group of d-6 is substituted with one or more identical substituents or Differences selected from the following group: (a) a halogen atom, and (b) a hydroxyl group), 2) an alkoxyl group of d-β (said C1.6 alkoxyl group is substituted with one or more halogen atoms the same or differents), 3) a carboxyl group, 4) a -COO-C 1-6 alkyl group, and 5) a cyano group, or (4) a 5-membered or 6-membered unsaturated monocyclic heicyclic group (said heterocyclic group is substituted with one or more same or different substituents selected from the following group: 1) a halogen atom, and 2) an alkyl group of C? -6 (said alkyl group of C6 is optionally substituted with one or more same or different halogen atoms), (with the proviso that R3 and R4 are not simultaneously hydrogen atoms), or a salt thereof. 11. The compound according to claim 1, further characterized in that R1 is 1) -CONR5R6 wherein R5 and R6 are the same or different and each is (a) a hydrogen atom, (b) an aryl group (said aryl group is substituted with one or more same or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, c) a carboxyl group, d) an alkyl group of d.6 (said alkyl group of d-6 is optionally substituted with one or more equal or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxyl group of C? -6), and e) an alkoxy group of d-β), (c) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more same or different d-6 alkyl groups (said alkyl group of C1 -6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d-6), (d) an alkyl group of d-6 ( said alkyl group of d ^ is substituted with one or more equal or different substituents selected from the following group : a) a hydroxyl group, b) a halogen atom, c) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) a group alkyl of d-β (said alkyl group of d 6 is optionally substituted with one or more same or different halogen atoms), d) -NR 20 R 21 wherein R 20 and R 21 are the same or different and each is a hydrogen atom, an alkyl group of d.6, or a -CO-alkyl group of C-6, or R20 and R21 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more same or different substituents selected from the following (i) to (iv): (i) a halogen atom, (ii) a hydroxyl group, (iii) an oxo group, and (iv) a alkoxy group of d ^), e) a C 1-6 alkoxy group) and f) a carboxyl group), (e) -S (= O) 2 -R 9 wherein R 9 is an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) and (2): (1) a halogen atom, and (2) an alkyl group of d-6 (said alkyl group of C? -6 is optionally substituted with one or more same or different halogen atoms)), or an alkyl group of d-6, or (f) a saturated monocyclic heterocyclic group containing nylrogen (said heterocyclic group is optionally substituted with one or more equal or different substituents selected from the following a) to c): a) an alkyl group of d-6, b) a -CO-alkyl group of C? -6, and c) an oxo group) , (g) an alkoxy group of d-6, or (h) an unsaturated monocyclic heterocyclic group containing nitrogen (said group heterocyclic is optionally substituted with one or more same or different halogen atoms), or (i) R5 and R6 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more identical or different substituents selected from the following a) to i): a) a halogen atom, b) a hydroxyl group, c) an alkyl group of d-6 (said alkyl group of d.6 is optionally substituted with one or more same or different substituents selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, and (iii) an alkoxy group of C? -6), d) a carboxyl group, e) a -CO-alkyl group of d.6, f) -CO-NR 2 R23 wherein R22 and R23 are the same or different and each is a hydrogen atom, or an alkyl group of C-? -6, or R22 and R23 optionally form, together with the nitrogen atom to which they are attached, a group nitrogen-containing saturated monocyclic heterocyclic, g) an oxo group, h) -NR2 R25 wherein R24 and R25 are the same or different and each is a hydrogen atom, an alkyl group of d-6, or a group -CO- C? -6 alkyl, or R24 and R25 optionally form, together with the nylrogen alose to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, and i) an alkoxy group of d-6) (with the proviso that R5 and R6 are not simultaneously hydrogen atoms), 2) -COOR10 wherein R10 is (a) an alkyl group of d. 6 (said alkyl group of d-6 is substituted with one or more identical or different substrates selected from the following a) to d): a) a hydroxyl group, b) -NR26R27 wherein R26 and R27 are the same or different and each is a hydrogen atom, or an alkyl group of d-6, or R 26 and R 27 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heyerocyclic group containing nitrogen, c) an alkoxy group of d-, 6, and d) an aryl group), or (b) a monocyclic saturated monocyclic group containing nitrogen (said heterocyclic group is optionally substituted with one or more identical or different substitutes selected from the following a) to c): a) a group d-6 alkyl, b) a -CO-C6 alkyl group, and c) an oxo), 3) -COR11 group wherein R11 is (a) an alkyl group of d-6 (said alkyl group of d-6 is susiluted with one or more identical or different substituents selected from the following a) to h): a) a halogen atom, b) a hydroxyl group, c) -NR28R29 wherein R28 and R29 are the same or different and each is an hydrogen, an alkyl group of d-6, a -CO-alkyl group of d-6, a -CO-cycloalkyl group, or a group -S (= O) 2-alkyl of C? -6, or R28 and R29 optionally they form, together with the nihologen atom to which they are attached, a saturated monocyclic helerocyclic group containing nihologen, d) -CO-NR30R31 wherein R30 and R31 are the same or different and each is a hydrogen atom, or a group alkyl of C? -6, or R30 and R31 optionally form, with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, e) an alkoxy group of d-6, f) a group Aryl (said aryl group is optionally substituted with one or more equal or different substitutes selected from the following group: (i) a halogen atom, (ii) a hydroxyl group, (iii) a C 1-6 alkoxyl group, and ( iv) an alkyl group of d-6 (said C 1-6 alkyl group is optionally susíiuuido with one or more same or different halogen atoms), g) a carboxyl group, and h) an aryloxyl group, (b) a cycloalkyl group (said cycloalkyl group is optionally substituted with one or more equal or differential substitutes selected from the following a) and b): a) an aryl group (said aryl group is optionally substituted with one or more equal or different substitutes selected from the following (1) and (2): (1) a halogen atom, and (2) a C 1-6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more equal or different halogen atoms)), and b) an alkyl group of d-6 (such group alkyl of d-6 is optionally substituted with one or more the same or different subluclyles selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d-6), or (c) a monocyclic heterocyclic group saíurado that coníiene niírógeno (said group heíerocí is optionally subsumed with one or more identical or different subscripts selected from the following a) to c): a) a C 1-6 alkyl group, b) a -CO-C 1-6 alkyl group, and c) an oxo group ), (d) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (1) to (3): (1) a halogen atom, (2) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more same or different halogen atoms), and (3) an alkoxy group of d-6). or (e) a carboxyl group, 4) an alkyl group of C? -6 (said alkyl group of C? -6 is substituted with one or more equal or different substituents selected from the following (a) to (d): ( a) a carboxyl group, (b) a cycloalkyl group (said Cycloalkyl group is optionally substituted by one or more, the same or different ones -CO-NR32R33 wherein R32 and R33 are the same or different and each is a hydrogen atom, an alkyl group of C6-6 (said alkyl group of d-6) is optionally substituted with one or more equal or different substituents selected from the following group: (i) a hydroxyl group, and (ii) an alkoxyl group of d-β), or R32 and R33 optionally form, with the nitrogen atom at which are joined, a saturated monocyclic heliccyclic group containing nitrogen), (c) -CO-NR34R35 wherein R34 and R35 are the same or different and each is a hydrogen atom, or an alkyl group of C? -6, or R34 and R35 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group, and (d) an aryl group (said aryl group is optionally substituted with one or more equal or different substitutes selected fromfollowing group: a) a halogen atom, and b) a C 1-6 alkyl group (said C 1-6 alkyl group is optionally subsumed with one or more equal or differential halogen atoms))), 5) a cycloalkyl group, 6) -S (= O) 2 -R 12 wherein R 12 is an alkyl group of d 6 (said alkyl group of C 6 is substituted with one or more same or different halogen atoms), or an aryl group (said group aryl is optionally substituted with one or more same or different substituents selected from the following group: a) a halogen atom, and b) an alkyl group of C-α-6 (said alkyl group of d ^ is optionally substituted with one or more atoms halogens the same or different)), 7) -C (= NCN) -R13 wherein R13 is a C1-6 alkyl group, 8) -C (= NCN) NR14R15 wherein R14 and R15 are the same or different and each is a hydrogen atom, or an alkyl group of C? -6) or R14 and R15 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen, ) an aryl group (said aryl group is optionally substituted with one or more same or different substituents selected from the following (a) to (f): (a) a carboxyl group, (b) a halogen atom, (c) a C? -6 alkyl group (said alkyl group of d-6 is optionally substituted with one or more equal or different substituents selected from the following group: a) a hydroxyl group, b) a halogen atom, and c) an alkoxy group of d.6), (d) -NR38R39 wherein R38 and R39 are the same or different and each is a hydrogen atom, an alkyl group of d-6, a -CO-alkyl group of d-6, -CO-NR 0 R41 wherein R40 and R41 are the same or different and each is a hydrogen atom, a C1-6 alkyl group, or a C1-6 alkoxy group , or R40 and R41 optionally form together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nylrogen, or -S (= O) 2 -R42 wherein R42 is a C1-6 alkyl group), or R38 and R39 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic nitrogen-containing heterocyclic group (said heterocyclic group is optionally substituted with one or more oxo groups), (e) -CO-NR43R44 wherein R43 and R44 are the same or different and each is a hydrogen atom, or an alkyl group of, or R43 and R44 optionally form, June with the nitrogen atom to which they are attached, a saturated monocyclic helerocyclic group containing nitrogen, and (f) a group - COO-alkyl of d ^), or 10) a 5-membered or 6-membered unsaturated monocyclic heliccyclic group (said heterocyclic group is substituted with one or more same or different substituents selected from the following (a) to (h): (a) a carboxyl group, (b) an alkyl group of d-6 (said alkyl group of d-6 is optionally substituted with one or more equal substitutes or differentials selected from the following a) to c): a) an atom of halogen, b) a hydroxyl group, and c) an alkoxy group of (c) a cycloalkyl group, (d) a halogen atom, (e) -CO-NR45R46 wherein R45 and R46 are the same or different and each is a hydrogen atom, or an alkyl group of C? -6, or R 45 and R 46 optionally form, together with the nitrogen atom to which they are attached, a saturated monocyclic heterocyclic group containing nitrogen), (f) a -COO-C 1-6 alkyl group, (g) a cyano group, and (h) an alkoxy group of d-6). or a salt of it. The compound according to claim 1, or a salt thereof, further characterized in that it is selected from the following: (1) 1- [5-cyclopropyl-1- (piperidin-4-yl) -1 H-pyrazole -4-carbonyl] -3- (pyridin-3-yl) pyrrolidine; (2) 1- [5-cyclopropyl-1- (p -peridin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine hydrochloride; (3) 1 -. { 5-cyclopropyl-1 - [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (4) 1- [1- (1-carbamoylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (5) 1 -. { 1 - [1 - (2-carboxyphenyl-carbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H -pyrazole-4-carbonylH (S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine; (6) 1-. { 5-cyclopropyl-1- [1- (2-hydroxymethylphenyl- carbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] - pyrrolidine; (7) 1-. { 5-Cyclopropyl-1- [1- (1-hydroxymethylcyclopropylcarbamoyl) -piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (8) 1-. { 5-cyclopropyl-1- [1- (2-hydroxyethylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (9) 1-. { 5-Cyclopropyl-1- [1- (2-hydroxy-1,1-dimethylarylcarbamoyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (10) 1-. { 1- [1- (2-Arylaminoethylcarbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (11) 1- hydrochloride. { 1- [1- (2-aminoethylcarbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
12. 12) 1-. { 5-cyclopropyl-1- [1- (1,1-dioxoyiomorpholine-4-carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
13. 13) hydrochloride of 1-. { 5-cyclopropyl-1- [1- (2-dimethylaminoethylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
14. 14) 1 -. { 5-Cyclopropyl-1 - [1- (4-hydroxypiperidin-1-carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine; (
15. 15) 1-. { 1- [1- (azelidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H -pyrazole-4-carbonylH (S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine; (
16. 16) 1-. { 5-Cyclopropyl-1- [1- (3-hydroxypyrrolidine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-if-trifluoromethylphenyl)] pyrrolidine; (
17. 17) 1-. { 5-cyclopropyl-1- [1- (2-piperidin-1-yl-elylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethyl-phenyl)] -pyrrolidine; (
18. 18) 1-. { 5-Cyclopropyl-1- [1- (4,4-difluoropiperidine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
19. 19) 1 -. { 5-Cyclopropyl-1- [1- (3,3-difluoropyrrolidin-1-carbonyl) piperidin-4-yl] -1 H-pyrazole-4- carbonyl} - [(S) -3- (2-if-trifluoromethylphenyl)] pyrrolidine; (
20. 20) 1-. { 5-cyclopropyl-1- [1 - (3-hydroxyazelidin-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
21. 21) 1- (5-cyclopropyl-1- { 1 - [(R) -3-hydroxypyrrolidine-1-carbonyl] piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [ (S) -3- (2-trifluoromethylphenyl)] - pyrrolidine; (
22. 22) 1- (5-cyclopropyl-1- { 1 - [(S) -3-hydroxypyrrolidine-1-carbonyl] piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [ (S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
23. 23) 1 - (5-cyclopropyl-1- { 1 - [(S) -2-hydroxy-1-melyeyilarbamoyl] piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [ (S) -3- (2-nifluoromethylphenyl)] pyrrolidine; (
24. 24) 1-. { 5-cyclopropyl-1 - [1- (4-hydroxyethylpiperidine-1-carbonyl) pipehdin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
25. 25) 1-. { 1- [1- (4-carboxypiperidine-1-carbonyl) -piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] - pyrrolidine; (
26. 26) 1 -. { 5-cyclopropyl-1 - [1- (3-oxopiperazin-1 -carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-if-trifluoromethylphenyl)] pyrrolidine; (
27. 27) 1 - (5-cyclopropyl-1 - { 1 - [(S) -2-hydroxymethylpyrrolidin-1 -carbonyl] piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [ (S) -3- (2-nifluoromethylphenyl)] pyrrolidine; (
28. 28) 1-. { 5-cyclopropyl-1 - [1- (3-hydroxymethylazeine-diene-1-carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
29. 29) hydrochloride of 1-. { 5-cyclopropyl-1 - [1- (4-methyl-piperazine-1-carbonyl) piperidin-4-yl] -1 H-pyrrazol-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
30. 30) hydrochloride of 1-. { 5-cyclopropyl-1 - [1- (4-isopropylpiperazin-1 -carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
31. 31) 1-. { 1- [1- (4-Acetylpiperazine-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
32. 32) 1- (5-cyclopropyl-1- { 1 - [(R) -3-hydroxypiperidine-1-carbonyl] piperidin-4-yl.} -1 H- pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
33. 33) 1-. { 1- [1- (4-carbamoylpiperidine-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
34. 34) 1-. { 1- [1- (3-carbamoylazetidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
35. 35) 1- hydrochloride. { 1- [1- (4-aminopiperidine-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
36. 36) 1- hydrochloride. { 1- [1- (3-aminopyrrolidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-if-trifluoromethylphenyl)] pyrrolidine; (
37. 37) hydrochloride of 1-. { 5-cyclopropyl-1- [1- (piperidin-4-yl-carbamoyl) pipehdin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] - pyrrolidine; (
38. 38) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (4-dimethylaminopiperidine-1-carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine; (
39. 39) 1-. { 1- [1- (4-Acetylaminopiperidine-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
40. 40) 1-. { 1- [1- (3-Acetylaminopyrrolidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
41. 41) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (3-dimethylaminopyrrolidine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine; (
42. 42) hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (1-methylpiperidin-4-yl-carbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine; (
43. 43) 1-. { 1- [1- (1-Acetyl] iperidin-4-yl-carbamoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
44. 44) 1-. { 5-Cyclopropyl-1- [1- (4-oxopiperidine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-fluorifomethylphenyl)) - pyrrolidine; (
45. 45) 1-. { 1- [1- (3-Acetylaminoazetidin-1-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-if-trifluoromethylphenyl)] pyrrolidine; (
46. 46) 1-. { 5-cyclopropyl-1- [1- (3-oxopyrrolidin-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
47. 47) 1-. { 5-cyclopropyl-1- [1 - (2,2,2-if-fluoroethylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
48. 48) 1 -. { 5-Cyclopropyl-1 - [1 - (3,3,4,4-lelrafluoro-pyrrolidine-1-carbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
49. 49) 1- (5-cyclopropyl-1 - { 1 - [(S) -1-hydroxymethyl-2-methylpropylcarbamoyl] pyridin-4-yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
50. 50) 1- (1- { 1 - [(S) -1-benzyl-2-hydroxyethylcarbamoyl] -piperidin-4-yl.} - 5-cyclopropyl-1 H-pyrazole-4-carbonyl ) - [(S) -3- (2-trifluoromethyl-phenyl)] -pyrrolidine; (
51. 51) 1- (5-cyclopropyl-1- { 1 - [(S) -2-hydroxy-1-phenylethylcarbamoyl] piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [ (S) -3- (2-trifluoromethylphenyl)) pyrrolidine; (
52. 52) 1 - (5-Cyclopropyl-1- { 1 - [(S) -1-hydroxymethyl-3-methylbutylcarbamoyl] piperidin-4-yl.} -1H-pyrazole-4-carbonyl) - [ (S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
53. 53) 1-. { 5-cyclopropyl-1- [1- (2-hydroxyphenylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
54. 54) 1-. { 5-Cyclopropyl-1- [1- (1-hydroxymethylcyclopenyl-carbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine; (
55. 55) 1 - [1 - (1-benzenesulfonylaminocarbonylpiperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine; (
56. 56) 1- [5-cyclopropyl-1- (1-methanesulfonylaminocarbonylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
57. 57) 1- [5-cyclopropyl-1- (1-methoxycarbonylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylenelfenyl)] - pyrrolidine; (
58. 58) 1-. { 5-Cyclopropyl-1- [1- (2-hydroxyethoxycarbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
59. 59) hydrochloride of 1-. { 5-cyclopropyl-1 - [1 - (2-dimethylaminoethoxycarbonyl) piperidin-4-yl] -1 H -pyrazole-4-carbonylH (S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
60. 60) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (2-piperidin-1-yl-eioxycarbonyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-irifluoromethylphenyl)] pyrrolidine; (
61. 61) hydrochloride of 1-. { 5-Cyclopropyl-1- [1- (piperidin-4-yl-oxycarbonyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
62. 62) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (1-methyl-piperidin-4-yl-oxycarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
63. 63) 1-. { 1- [1- (1-Acetylpiperidin-4-yl-oxycarbonyl) -piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] - pyrrolidine; (
64. 64) 1- [1- (1-cyclopropancarbonylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
65. 65) 1 -. { 5-cyclopropyl-1- [1- (2-hydroxyacetyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
66. 66) 1- (5-cyclopropyl-1- { 1- [1- (4-fluorophenyl) -cyclopropanecarbonyl] piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [(S ) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
67. 67) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (2-dimethylaminoacetyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
68. 68) 1 -. { 1 - [1 - (2-Acetylaminoacetyl) piperidin-4-yl] -5-cyclopropyl-1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
69. 69) 1-. { 5-Cyclopropyl-1- [1- (1-methylcyclopropancarbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
70. 70) 1 -. { 1 - [1 - (2-Acetylamino-2-methylpropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2- trifluoromethylphenyl)] pyrrolidine; (
71. 71) 1- (1- { 1 - [(S) -2-Acelylaminopropionyl] piperidin-4-yl.} - 5-cyclopropyl-1H-pyrazole-4-carbonyl) - [(S) -3 - (2-trifluoromethylphenyl)] pyrrolidine; (
72. 72) 1- (1- { 1 - [(S) -2-acetylamino-3-methylbutyryl] piperidin-4-yl.} - 5-cyclopropyl-1 H-pyrazole-4-carbonyl) - [ (S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
73. 73) 1-. { 5-Cyclopropyl-1- [1- (3,3,3-if-trifluoropropionyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
74. 74) 1- (5-cyclopropyl-1- { 1 - [(S) -5-oxopyrrolidin-2-carbonyl] piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [ (S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine; (
75. 75) 1-. { 1- [1- (3-Acetylaminopropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
76. 76) 1 -. { 5-Cyclopropyl-1- [1- (3-hydroxy-2,2-dimethypropyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
77. 77) 1- hydrochloride. { 1- [1- (2-Aminoacelyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
78. 78) 1-. { 5-cyclopropyl-1-t1- (1-hydroxymethyl-cyclopropancarbonyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-Fluoro-methylphenyl)] pyrrolidine; (
79. 79) hydrochloride of 1-. { 1- [1- (2-amino-2-meityylpropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
80. 80) 1-. { 5-Cyclopropyl-1- [1- (4-hydroxybuliryl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-if-trifluoromethylphenyl)] pyrrolidine; (
81. 81) hydrochloride of 1- (5-cyclopropyl-1- { 1 - [(S) -pyrrolidin-2-carbonyl] piperidin-4-yl}. -1H-pyrazole-4-carbonyl) - [( S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
82. 82) hydrochloride of 1- (5-cyclopropyl-1- { 1 - [(S) -1-methylpyrrolidine-2-carbonyl] piperidin-4-yl.} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
83. 83) 1- hydrochloride. { 1- [1- (3-aminopropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2- trifluoromethylphenyl)] pyrrolidine; (
84. 84) 1- (1. {1 - [(S) -2-amino-3-methylbuyryl] piperidin-4-yl.} - 5-cyclopropyl-1H-pyrazole-4-carbonyl hydrochloride) - [(S) -3- (2-irifluoromethylphenyl)] pyrrolidine; (
85. 85) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (2-mellylaminoacetyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
86. 86) hydrochloride of 1-. { 5-cyclopropyl-1- [1- (piperidin-4-carbonyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] - pyrrolidine; (
87. 87) 1 -. { 5-cyclopropyl-1 - [1 - (2-isobuyrylaminoacetyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine; (
88. 88) 1-. { 1- [1- (2-cyclopropanecarbonylaminoacetyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
89. 89) 1- (1- { 1 - [(S) -1-Acetylpyrrolidine-2-carbonyl] piperidin-4-yl.} - 5-cyclopropyl-1 H -pyrazole-4-carbonyl) - [ (S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
90. 90) 1-. { 5-Cyclopropyl-1- [1- (2-menesulfonylaminoacelyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
91. 91) 1-. { 1- [1- (1-acetylpiperidine-4-carbonyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-irifluoromethylphenyl)] pyrrolidine; (
92. 92) 1- hydrochloride. { 5-Cyclopropyl-1- [1- (1-methylpiperidine-4-carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
93. 93) 1-. { 1- [1- (3-carbamoylpropionyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
94. 94) 1- [1- (1-carbamoylmeiylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-yltrluoromethylphenyl)] pyrrolidine hydrochloride; (
95. 95) 1- [5-cyclopropyl-1- (1-methylcarbamoylmethylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2-yltrluoromethylphenyl)] pyrrolidine hydrochloride; (
96. 96) 1- hydrochloride. { 1- [1- (1-carbamoyl-1- methyleryl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
97. 97) hydrochloride of 1-. { 1- [1- (2-carbamoylethyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
98. 98) 1- [5-Cyclopropyl-1- (1-cyclopropylmethylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethylphenyl)] -pyrrolidine hydrochloride; (
99. 99) hydrochloride of 1- [5-cyclopropyl-1- (1-cyclopropylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2-l-trifluoromethyl-phenyl)] pyrrolidine; (
100. 100) 1- [5-cyclopropyl-1- (1-dimethylarylcarbamoylmethylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine hydrochloride; (
101. 101) 1- [1- (1-Carboxymethylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-yltrluoromethylphenyl)] pyrrolidine hydrochloride; (
102. 102) 1- [1- (1-carboxyethylpiperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine hydrochloride; (
103. 103) 1- Hydrochloride. { 1- [1- (1-carbamoylethyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
104. 104) 1- hydrochloride. { 1- [1- (2-carboxy-2-methylpropyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
105. 105) 1- hydrochloride. { 1- [1- (2-carbamoyl-2-methylpropyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine; (
106. 106) 1- hydrochloride. { 1- [1- (1-carbamoylcyclopropylmethyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
107. 107) 1- (5-Cyclopropyl-1- {1- [1- (2-hydroxyethylcarbamoyl) cyclopropylmethyl) piperidin-4-yl hydrochloride} -1 H-pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine; (
108. 108) 1- [5-cyclopropyl-1- (1-ylfluoromenessulfonylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2- trifluoromethylphenyl)] pyrrolidine; (
109. 109) 1-. { 5-cyclopropyl-1- [1 - (2,2,2-ír-fluoro-ureanesulfonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
110. 110) 1-. { 1- [1- (1-cyanoimino-eyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
111. 111) 1- (1-. {1- [Cyanoimino (meitylamino) meily] piperidin-4-yl}. -5-cyclopropyl-1 H -pyrazole-4-carbonyl) - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
112. 112) 1-. { 1- [1- (N-cyanocarbamimidoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
113. 113) 4- (4-. {5-Cyclopropyl-4- [3- (2-trifluoromethylphenyl) pyrrolidin-1-carbonyl] pyrazol-1-yl} piperidin-1-yl) benzoic acid; (
114. 114) 3- (4-. {5-Cyclopropyl-4- [3- (2-trifluoromethylphenyl) pyrrolidin-1-carbonyl] pyrazol-1-yl} piperidin-1-yl) benzoic acid; (
115. 115) 5- (4-. {5-Cyclopropyl-4- [3- (2-ylfluoromethyl-phenyl) -pyrrolidin-1 -carbonyl] -pyrazol-1-l.}. Piperidin-1-yl) -iiophen-2 -carboxylic; (
116. 116) 2- (4-. {5-Cyclopropyl-4- [3- (2-ylfluoromethyl-phenyl) -pyrrolidin-1-carbonyl] pyrazol-1-yl) -piperidin-1-yl) -libol-4-carboxylic acid; (
117. 117) 1- Hydrochloride. { 5-Cyclopropyl-1- [1- (5-meityl-4H- [1, 2,4] idriazol-3-yl) piperidin-4-yl] -1 H-prazol-4-carbonylH (S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
118. 118) 1- hydrochloride. { 5-cyclopropyl-1- [1- (5-cyclopropyl-4H- [1, 2,4] triazol-3-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
119. 119) 1- Hydrochloride. { 5-Cyclopropyl-1- [1- (5-hydroxymethyl-4H- [1, 2,4] idriazol-3-yl) piperidin-4-yl] -1 H -pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
120. 120) 1- Hydrochloride. { 5-Cyclopropyl-1- [1- (5-ylfluoromethyl-4 H- [1, 2,4] iriazol-3-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
121. 121) 1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl) -1 H-pyrazole-4-carbonylH (R) -3- (2- trifluoromethylphenyl)] pyrrolidine; (
122. 122) 1-. { 5-Cyclopropyl-1- [1- (1-methylcyclopropyl-carbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(R) -3- (2-ylfluoromethyl-phenyl)] -pyrrolidine; (
123. 123) 1-. { 5-Cyclopropyl-1- [1- (1-isopropylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(R) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
124. 124) 1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-ylfluoromethylphenyl)] pyrrolidine; (
125. 125) 1-. { 5-Cyclopropyl-1- [1- (1-isopropylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
126. 126) 1-. { 5-Cyclopropyl-1- [1- (1-methyl-cyclopropylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-l-trifluoromethylphenyl)] pyrrolidine; (
127. 127) (-) - 3- (4-fluorophenyl) -3-hydroxymethyl-1- hydrochloride. { 5- (1-Methylcyclopropyl) -1- [1- (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} pyrrolidine; (
128. 128) (+) - 3- (4-fluorophenyl) -3-hydroxymethyl-1- hydrochloride. { 5- (1-Methylcyclopropyl) -1- [1- (pyrimidin-2-yl) picperidin-4-yl] -1 H-pyrazole-4-carbonyl} pyrrolidine; (
129. 129) 1- [5-Cyclopropyl-1- (1-pyrazin-2-yl-piperidin-4-yl) -1H-pyrazole-4-carbonyl] - [(S) -3- (2- irifluoromethyl] phenyl)] - pyrrolidine; (
130. 130) 1- [1- (trans-4-carbamoyl-cyclohexyl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
131. 131) 1 - [5-cyclopropyl-1 - (rans-4-ureidocyclohexyl) -1 H -pyrazole-4-carbonyl] - [(S) -3- (2-ylfluoromethyl-phenyl)] pyrrolidine; (
132. 132) 1-. { 5-cyclopropyl-1- [trans -4- (1 H-tetrazol-5-yl) cyclohexyl] -1 H-pyrazole-4-carbonyl} - [(S) -3- (2-trifluoromethylphenyl)] pyrrolidine; (
133. 133) 1-. { 5- (1-Melylcyclopropyl) -1- [1- (4-ír-trifluoromethyl-phenylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (
134. 134) 1-. { 1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -5- (1-meloxycyclopropyl) -1H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine; (
135. 135) 1-. { 1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -5- (1-methylcyclopropyl) -1 H- pyrazole-4-carbonyl} 3-phenyl-3-l-trifluoromethyl-pyrrolidine; (
136. 136) 3- (2-chlorophenyl) -1 -. { 5-cyclopropyl-1- [1- (2,4-difluorophenylcarbamoyl) piperidin-4-yl] -1 H -pyrazole-4-carbonyljpyrrolidine; (
137. 137) 3- (2-chloropyridin-3-yl) -1 -. { 5-cyclopropyl-1 - [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} pyrrolidine; (
138. 138) 1-. { 1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -5- (2,2,3,3-tetramethylcyclopropyl) -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (
139. 139) 1-. { 5-cyclohexyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (
140. 140) 1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (2-urea-fluorophenoxy) pyrrolidine; (
141. 141) 1-. { 5-Cyclopropyl-1 - [1- (4-l-trifluoromethylphenylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine; (
142. 142) 1- (5-cyclopropyl-1- { 1 - [((S) -1-carboxy-2-meitylpropyl) -merylcarbamoyl] piperidin-4-yl.} -1 H-pyrazole-4-carbonyl ) -3- (2-ylfluoromethylphenyl) pyrrolidine; (
143. 143) 1-. { 5-Cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3-meioxy-3- (2-ylfluoromethyl-phenyl) pyrrolidine; (
144. 144) 1-. { 1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -5- (1-hydroxymethylcyclopropyl) -1 H-pyrazole-4-carbonyl} -3- (2-uro-trifluoromethylphenyl) pyrrolidine; (
145. 145) 1-. { 5-cyclopropyl-1 - [1 - (liazol-2-ylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine; (
146. 146) 1-. { 1- [1- (isopropoxycarbamoyl) piperidin-4-yl] -5- (1-methyl-cyclopropyl) -1 H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine; (
147. 147) 1-. { 5-Cyclopropyl-1- [1- (4-fluorobenzylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (2-l-trifluoromethylphenyl) pyrrolidine; (
148. 148) 1-. { 1- [1- (2,3-dihydroindol-1-carbonyl) piperidin-4-yl] -5- (1-meitylcyclopropyl) -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (
149. 149) 1-. { 1- [1- (2,3-dihydro [1,4] oxazin-4-carbonyl) piperidin-4-yl] -5- (1- meilyylcyclopropyl) -1H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (
150. 150) 1-. { 5-Cyclopropyl-1- [1- (2,6-dichloropyridin-3-ylcarbamoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine; (
151. 151) 1-. { 5- (1-Melylcyclopropyl) -1- [1- (2,3,4,5-eeryhydrobenzo [b] azepine-1-carbonyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (
152. 152) 4- (4-. {5-Cyclopropyl-4- [3- (2-trifluoromethyl-phenyl) -pyrrolidin-1-carbonyl] pyrazol-1-yl} -piperidin-1-yl) -benzoaie of eiyl; (
153. 153) 1- [1- (1-benzyloxycarbonyl-piperidin-4-yl) -5-cyclopropyl-1 H -pyrazole-4-carbonyl] -3- (pyridin-3-yl) pyrrolidine; (
154. 154) 1-. { 1- [1- (3-carboxy-3-meityl-buryryl) -piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (2-l-trifluoromethylphenyl) -pyrrolidine; (
155. 155) 1-. { 5-cyclopropyl-1- [1- (2-phenoxyacelyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (
156. 156) 1 -. { 1 - [1 - (3-chlorobenzoyl) piperidin-4-yl) -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (
157. 157) 1-. { 1- [1- (2-chlorobenzoyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (
158. 158) 1- [5-cyclopropyl-1- (1-oxalylpiperidin-4-yl) -1 H -pyrazole-4-carbonyl] -3- (2-ylfluoromethylphenyl) pyrrolidine; (
159. 159) 1-. { 1- [1- (4-chlorobenzoyl) -piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) -pyrrolidine; (
160. 160) 1- (5-cyclopropyl-1 - { 1 - [2- (4-fluorophenyl) acetyl] piperidin-4-yl}. -1 H-pyrazole-4-carbonyl) -3- (pyridine -3-yl) pyrrolidine; (
161. 161) 1 -. { 5-cyclopropyl-1 - [1- (3-trifluoromethylbenzoyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) -pyrrolidine; (
162. 162) 1-. { 5-Cyclopropyl-1- [1- (3-meioxybenzoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (
163. 163) 1- hydrochloride. { 1- [1- (4-fluorobenzyl) piperidin-4-yl] -5- (1-meitylcyclopropyl) -1H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine; (
164. 164) 1- [1- (1-benzenesulfonyl-piperidin-4-yl) -5- cyclopropyl-1 H-pyrazole-4-carbonyl] -3- (pyridin-3-yl) pyrrolidine; (
165. 165) 1-. { 1- [1- (4-carbamoylphenyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine; (
166. 166) 1 -. { 5-cyclopropyl-1 - [1- (4-hydroxymethylphenyl) -piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (2-ylfluoromethylphenyl) pyrrolidine; (
167. 167) 1-. { 1- [1- (5-carbamoyl-pyridin-2-yl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (2-uro-trifluoromethylphenyl) pyrrolidine; (
168. 168) 1-. { 1- [1- (4-aminophenyl) piperidin-4-yl] -5-cyclopropyl-1H-pyrazole-4-carbonyl} -3- (2-trifluoromethylphenyl) pyrrolidine; (
169. 169) 1- (5-cyclopropyl-1- { 1- [4- (2-oxooxazolidin-3-yl) phenyl] piperidin-4-yl}. -1 H -pyrazole-4-carbonyl) - 3- (2-ylfluoromethylphenyl) pyrrolidine; (
170. 170) 1- (5-cyclopropyl-1 - { 1 - [4- (3-meioxyureido) phenyl] piperidin-4-yl}. -1 H-pyrazole-4-carbonyl) -3- (2 -rifluoromethylphenyl) -pyrrolidine; (
171. 171) 1-. { 5-cyclopropyl-1- [1- (4-methanesulfonylaminophenyl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -3- (2-trifluoromethylphenyl) pyrrolidine; (
172. 172) 1- [1- (1-ethoxycarbamoyl-piperidin-4-yl) -5- (1-methyl-cyclopropyl) -1 H -pyrazole-4-carbonyl] -3- (2-ylfluoromethyl-phenyl) -pyrrolidine; (
173. 173) 1- [1- (5-chloropyridin-2-yl) azeidin-3-yl] -5-cyclopropyl-1 H -pyrazole-4-carbonyl] -3- (2-trifluoromethyl-phenyl) -pyrrolidine; (
174. 174) 1-. { 1- [1- (5-Chloro-pyridin-2-yl) piperidin-4-yl] -5- (1-methylcyclopropyl) -1 H-pyrazole-4-carbonyl} -3-methoxymethyl-3-phenylpyrrolidine; (
175. 175) 1-. { 1- [1- (5-Cyano-pyridin-2-yl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (2-l-trifluoromethylphenyl) pyrrolidine; (
176. 176) 3- (2-Acetyxyethyl) -3- (4-fluorophenyl) -1- hydrochloride. { 5- (1-methylcyclopropy) -1 - [1 - (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} pyrrolidine; (
177. 177) hydrochloride. { (3S *, 4R *) - 3-methyl-1-. { 5- (1-Melylcyclopropyl) -1- [1- (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -4-phenylpyrrolidine; (
178. 178) 6- (4-. {5-cyclopropyl-4- [3- (2-ylfluoromethyl-phenyl) -pyrrolidin-1 -carbonyl] -pyrazol-1-yl} -piperidin-1-yl) -omyolone meiilo; (
179. 179) 2-. { 1- [5- (1-Meilyylcyclopropyl) -1- (1-pyrimidin-2-yl-piperidin-4-yl) -1 H -pyrazole-4-carbonyl] pyrrolidin-3-yl} methyl benzoate; (
180. 180) 3- (2-hydroxymethylphenyl) -1- hydrochloride. { 5- (1-meitylcyclopropyl) -1- [1- (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} pyrrolidine; (
181. 181) 1- [5-cyclopropyl-1- (1-pyridin-2-yl-piperidin-4-yl) -1 H -pyrazole-4-carbonyl] -3-hydroxy-3- (pyridin-3-yl) pyrrolidine; (
182. 182) 1-. { 1 - [1- (4-Acetylaminophenyl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (2-l-trifluoromethylphenyl) pyrrolidine; (
183. 183) 4- (4-. {5-cyclopropyl-4- [3- (2-ylfluoromethylphenyl) -pyrrolidin-1-carbonyl] pyrazol-1-yl}. Piperidin-1-yl) -3-fluorobenzoal of sodium; (
184. 184) 3- (2-cyanophenyl) -1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} pyrrolidine; (
185. 185) 3-hydroxymethyl-1- hydrochloride. { 1- [1- (4-meioxypyrimidin-2-yl) piperidin-4-yl] -5- (1-methylcyclopropyl) -1 H-pyrazole-4-carbonyl} -3-phenylpyrrolidine; (
186. 186) 3- (3,5-difluorophenyl) -3-hydroxymethyl-1- hydrochloride. { 5- (1-meitylcyclopropyl) -1 - [1 - (pyrimidin-2-yl) piperidin-4-yl] -1 H-pyrazole-4-carbonyl} -pyrrolidine; (
187. 187) 1-. { 1- [1- (3-Chloro-pyridin-2-yl) piperidin-4-yl] -5-cyclopropyl-1 H-pyrazole-4-carbonyl} -3- (pyridin-3-yl) pyrrolidine; (
188. 188) 1-. { 5-cyclopropyl-1- [1- (2-fluorophenylcarbamoyl) piperidin-4-yl] -1H-pyrazole-4-carbonyl} -3- (Iiazol-2-yl) pyrrolidine; (
189. 189) (S) -2 - [(rans-4. {5-cyclopropyl-4- [3- (2-irifluoromethyl-phenyl) -pyrrolidin-1-carbonyl] -pyrazol-1-yl}. cyclohexanecarbonyl) -methylamino] -3-meityylbuiric; (
190. 190) 1-. { 5- (1-methylcyclopropyl) -1- [rans-4- (2-fluorophenylcarbamoyl) -cyclohexyl] -1H-pyrazole-4-carbonyl} -3- (2-trifluoromethylphenyl) pyrrolidine; and (
191. 191) cis-4- acid. { 5- (1-Melylcyclopropyl) -4- [3- (2-l-trifluoromethylphenyl) -pyrrolidine-1-carbonyl] -pyrazol-1-yl) -cyclohexanecarboxylic acid. 13. A pharmaceutical composition comprising a compound as claimed in any of claims 1 to 12, or a salt thereof. 14. An 11βHSD1 inhibitor comprising a compound as claimed in any of claims 1 to 12, or a salt thereof. 15. An agent for the tracing or prophylaxis of a glucocorticoid-involving pathology, comprising a compound as claimed in any of claims 1 to 12, or a salt thereof. 16. The agent according to claim 15, further characterized in that the pathology involving glucocorticoid is (1) a metabolic disease that includes diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a metabolic syndrome, (3) a fatal vascular event that includes cardiac infarction or cerebral apoplexy, (4) hyperorexia, (5) a neurodisfunctional disease that includes dysgenesis, neurodegenerative disease, emotional disorders, schizophrenia or appetite stimulation, (6) a disease associated with diminished immunity function, (7) glaucoma, or (8) osteoporosis. 17. The use of a compound as claimed in any one of claims 1 to 12, or a salt thereof, for preparing a pharmaceutical composition useful for inhibiting 11 ßHSD, wherein the pharmaceutical composition is an inhibitor of 11 ßHSD. 18. The use of a compound such as that claimed in any of claims 1 to 12, or a salt thereof, for preparing a pharmaceutical composition useful for preventing or preventing a palolo- gy involving glucocorticoid 19. The use as claimed in claim 18, wherein the pal- laology involving glucocorticoid is ( 1) a metabolic disease that includes diabetes, insulin resistance, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a metabolic syndrome, (3) a fatal vascular event that includes cardiac infarction or cerebral apoplexy, (4) ) hyperorexia, (5) a neurodisfunctional disease that includes dysgenesis, neurodegenerative disease, emotional disorders, schizophrenia or appetite stimulation, (6) a disease associated with impaired immunity function, (7) glaucoma, or (8) osteoporosis. 20. A commercial package comprising a written material that declares that the pharmaceutical composition claimed in claim 13 can or should be used for the treatment or prophylaxis of a disease selected from (1) a metabolic disease that includes diabeles, resistance to insulin, diabetic complications, obesity, hyperlipidemia, hypertension or fatty liver, (2) a metabolic syndrome, (3) a fatal vascular event that includes cardiac infarction or cerebral apoplexy, (4) hyperorexia, (5) a neurodisfunctional disease that includes dysgnosis , neurodegenerative disease, emotional disorders, schizophrenia or appetite stimulation, (6) a disease associated with the function of decreased immunity, (7) glaucoma, or (8) osteoporosis. The pharmaceutical composition according to claim 13, further characterized in that it is used in combination with 1 to 3 agents selected from the following (1) to (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, ( 2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the irradiation or prophylaxis of diabetic complications, (5) an agent for the irradiation or prophylaxis of hypertension. 22. The 11βHSD1 inhibitor according to claim 14, further characterized because it is used in combination with 1 to 3 agents selected from the following (1) to (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agency for the treatment or prophylaxis of hypertension. 23. The agent according to claim 15 or 16, further characterized in that it is to be used in combination with 1 to 3 agents selected from the following (1) to (5): (1) an agent for the irradiation or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agency for the treatment or prophylaxis of diabetic complications, (5) an organism for treatment or hypertension prophylaxis. 24. Use as claimed in claim 17, wherein the pharmaceutical composition is formulated to be administrable from 1 to 3 agents selected from the following (1) to (5): (1) an agent for the treatment or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity , (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the treatment or prophylaxis of hypertension. 25. A pharmaceutical agent comprising 1 to 3 agents selected from the following (1) to (5) and a compound as claimed in any of claims 1 to 12 or a salt thereof, in combination: (1) ) an agency for the treatment or prophylaxis of hyperlipidemia, (2) an organism for the treatment or prophylaxis of obesity, (3) an agent for the treatment or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications , (5) an agent for the treatment or prophylaxis of hypertension. 26. The use as claimed in claim 18 or 19, wherein the pharmaceutical composition is formulated to be administrable from 1 to 3 agents selected from the following (1) to (5): (1) an agent for irradiation or prophylaxis of hyperlipidemia, (2) an agent for the treatment or prophylaxis of obesity, (3) an agent for the dialysis or prophylaxis of diabetes, (4) an agent for the treatment or prophylaxis of diabetic complications, (5) an agent for the idramiento or prophylaxis of hypertension. 27. The pharmaceutical composition according to claim 13, further characterized in that it is used to suppress the increase in the level of glucocorticoid in the blood, used in combination with a pharmaceutical agent that raises the level of glucocorticoid in the blood. 28. The 11 ßHSD1 inhibitor according to claim 14, further characterized in that it is used to suppress the increase in the level of glucocorticoid in the blood, used in combination with a pharmaceutical agent that raises the level of glucocorticoid in the blood. 29. The method claimed in claim 17, wherein the pharmaceutical composition is formulated to be administrable a pharmaceutical agent that raises the level of glucocorticoid in the blood. 30. The use of a pharmaceutical agent that raises the level of glucocorticoid in the blood and the inhibitor of 11βHSD1 which is claimed in claim 14, to prepare a pharmaceutical composition useful to suppress the increase of the level of glucocorticoid in the blood. 31. 2 - [(S) -2-Nitro-1- (2-trifluoromethylfronyl) ethyl] dimethyl ester. 32. (S) -2-Oxo-4- (2-trifluoromethylphenyl) pyrrolidin-3-carboxylic acid methyl. 33. (S) -4- (2-Trifluoromethylphenyl) pyrrolidin-2-one. 34. (S) -3- (2-Trifluoromethylphenyl) pyrrolidine or a salt thereof. 35. A method for producing dimethyl 2 - [(S) -2-niiro-1- (2-ylfluoromethylphenyl) ely] malonation, comprising a step to react 1 - ((E) -2-n-ylvinyl) -2 -rifluoromethylbenzene with malonation of dimethyl in the presence of 1- (3,5-bis-1-trifluoromethylphenyl) -3 - ((1S, 2S) -2-dimethylaminocyclohexyl) -iourea. 36. A method for producing methyl (S) -2-oxo-4- (2-trifluoromethylphenyl) pyrrolidin-3-carboxylate, comprising a step for reducing and closing the ring of 2 - [(S) -2-nitro] Dimethyl (1-dimethyl-2-fluoromethyl-phenyl) -yl] -mononate. 37. A method for producing (S) -4- (2-trifluoromethylphenyl) pyrrolidin-2-one, which comprises an elapa for hydrolysis and decarbonation of (S) -2-oxo-4- (2-trifluoromethylphenyl) pyrrolidin-3. -Methyl carboxylate. 38. A method for producing a salt of (S) -3- (2-trifluoromethylphenyl) pyrrolidine, comprising a step for reducing (S) -4- (2-trifluoromethylphenyl) pyrrolidin-2-one and a step to treat the compound resulted with an acid to form a salt.