RU2003106190A - METHOD FOR ALLERGY TREATMENT USING SUBSTITUTED PYRAZOLES - Google Patents

Claims (9)

1. A method of treating a subject with an allergic disease, which comprises administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a compound of formula (I)

where the dashed line adjacent to CR ⁶ is absent or represents an sp ² bond; Y represents nitrogen or R ²⁰ C; Z represents nitrogen or R ²¹ C; T represents nitrogen or R ² C; S represents nitrogen or R ³ C; with the proviso that from 0 to 3 of S, T, Y and Z are nitrogen; and further provided that one of S, T, Y, and Z may be = N ⁺ -O ^- , where the remaining three are not nitrogen; R ²⁰ selected from hydrogen, halogen, C _1-5 alkoxy, hydroxy, C _1-5 alkyl, cyano, nitro, C _1-5 halogenated, R ^o R ^p N, R ^o R ^p NC = O, C _2-8 acyl, 4-7 membered heterocyclyl, (4-7 membered heterocyclyl) -C _1-5 alkylene, phenyl, (phenyl) C _1-5 alkylene, R ¹⁴ OC = O, R ¹⁴ S, R ¹⁴ SO and R ¹⁴ SO ₂ ; R ^{21 is} selected from hydrogen, halogen, C _1-5 alkoxy, hydroxy, C _1-5 alkyl, cyano, nitro, C _1-5 halogenated, R ^c R ^d N, R ^c R ^d NC = O, C _2-8 acyl, 4-7 membered heterocyclyl, (4-7 membered heterocyclyl) -C _1-5 alkylene, phenyl, (phenyl) C _1-5 alkylene, R ¹⁵ OC = O, R ¹⁵ S, R ¹⁵ SO and R ¹⁵ SO ₂ ; R ^{2 is} selected from hydrogen, halogen, C _1-5 alkoxy, hydroxy, C _1-5 alkyl, cyano, nitro, C _1-5 halogenated, R ^e R ^f N, R ^e R ^f NC = O, C _2-8 acyl, 4-7 membered heterocyclyl, (4-7 membered heterocyclyl) -C _1-5 alkylene, phenyl, (phenyl) C _1-5 alkylene, R ¹⁶ OC = O, R ¹⁶ S, R ¹⁶ SO and R ¹⁶ SO ₂ ; R ^{3 is} selected from hydrogen, halogen, C _1-5 alkoxy, hydroxy, C _1-5 alkyl, cyano, nitro, C _1-5 haloalkyl, R ^g R ^h N, C _2-8 acyl, 4-7 membered heterocyclyl , (4-7 membered heterocyclyl) -C _1-5 alkylene, phenyl, (phenyl) C _1-5 alkylene, R ¹⁷ OC = O, R ^m R ⁿ NC = O, R ^m R ⁿ NSO ₂ , R ¹⁷ S, R ¹⁷ SO and R ¹⁷ SO ₂ ; R ⁵ and R ^{6 are} independently selected from hydrogen and C _1-5 alkyl; R ⁷ and R ⁸ independently represent hydrogen, C _1-5 alkyl, C _1-5 alkenyl, C _1-5 alkoxy, C _1-5 alkylthio, halogen or 4-7 membered carbocyclyl or heterocyclyl; alternatively, R ⁷ and R ⁸ may be taken together to form an optionally substituted 5-7 membered carbocyclic or heterocyclic ring, which may be unsaturated or aromatic; said ring is optionally substituted with 1-3 substituents independently selected from halogen, hydroxy, cyano, nitro, amino, R ^t , R ^t O-, R ^t S-, R ^t O (C _1-5 alkylene) -, R ^t O (C = O) -, R ^t (C = O) -, R ^t (C = S) -, R ^t (C = O) O-, R ^t O (C = O) (C = O) -, R ^t SO ₂ , NHR ^u (C = NH) -, NHR ^u SO ₂ - and NHR ^u (C = O) -; R ^t represents C _1-6 alkyl, phenyl, benzyl, phenethyl or C _2-5 heterocyclyl, (C _1-5 heterocyclyl) C _1-6 alkylene, NH ₂ , mono- or di (C _1-6 alkyl) N -, or R ⁴⁹ OR ⁵⁰ -, where R ⁴⁹ represents H, C _1-5 alkyl, C _2-5 alkenyl, phenyl, benzyl, phenethyl, C _1-5 heterocyclyl or (C _1-5 heterocyclyl) C _{1- 6} alkylene, and R ⁵⁰ represents C _1-5 alkylene, phenylene or divalent C _1-5 heterocyclyl; R ^u may be H in addition to the values for R ^t ; R ^c represents hydrogen, C _1-5 alkyl, phenyl, C _2-5 heterocyclyl, C _2-8 acyl, aroyl, R ¹⁰ OC = O-, R ⁱ R ^j NC = O, R ¹⁰ SO-, R ¹⁰ SO ₂ - and R ⁱ R ^j NSO ₂ ; R ^e represents hydrogen, C _1-5 alkyl, phenyl, C _2-5 heterocyclyl, C _2-8 acyl, aroyl, R ⁴⁰ OC = O, R ⁴³ R ⁴⁴ NC = O, R ⁴⁰ SO, R ⁴⁰ SO ₂ and R ⁴³ R ⁴⁴ NSO ₂ ; R ^m represents hydrogen, C _1-5 alkyl, phenyl, C _2-5 heterocyclyl, C _2-8 acyl, aroyl, R ⁴¹ OC = O, R ⁴⁵ R ⁴⁶ NC = O, R ⁴¹ SO, R ⁴¹ SO ₂ and R ⁴⁵ R ⁴⁶ NSO ₂ ; R ^o represents hydrogen, C _1-5 alkyl, phenyl, C _2-5 heterocyclyl, C _2-8 acyl, aroyl, R ⁴² OC = O, R ⁴⁷ R ⁴⁸ NC = O, R ⁴² SO, R ⁴² SO ₂ and R ⁴⁷ R ⁴⁸ NSO ₂ ; each R ^d , R ^f , R ⁿ and R ^{p are} independently selected from hydrogen, C _1-5 alkyl, phenyl and C _2-5 heterocyclyl; in addition, R ^c and R ^d , R ^e and R ^f , R ^m and R ⁿ or R ^o and R ^p , independently, may be taken together to form an optionally substituted 4-7 membered heterocyclic ring which may be saturated, unsaturated or aromatic; each R ⁹ , R ¹⁰ , R ¹¹ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ⁴⁰ , R ⁴¹ and R ⁴² independently represents C _1-5 alkyl, phenyl or C _2-5 heterocyclyl; each R ⁱ and R ^j , R ^k and R ^l , R ⁴³ and R ⁴⁴ , R ⁴⁵ and R ⁴⁶ , R ⁴⁷ and R ⁴⁸ independently represents hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl or C _2-5 heterocyclyl; in addition, R ⁱ and R ^j , and R ^k and R ^l , R ⁴³ and R ⁴⁴ , R ⁴⁵ and R ⁴⁶ , and R ⁴⁷ and R ⁴⁸ , independently, can be taken together to form an optionally substituted 4-7 membered a heterocyclic ring which may be saturated, unsaturated or aromatic; R ^g represents hydrogen, C _1-5 alkyl, phenyl or C _2-5 heterocyclyl, C _2-8 acyl, aroyl, R ⁹ OC = O, R ¹⁸ R ¹⁹ NC = O, R ⁹ SO, R ⁹ SO ₂ or R ¹⁸ R ¹⁹ NSO ₂ ; R ^h represents hydrogen, C _1-5 alkyl, phenyl or C _2-5 heterocyclyl; alternatively, R ^g and R ^h may be taken together to form an optionally substituted 4-7 membered heterocyclic ring, which may be saturated, unsaturated or aromatic; R ¹⁸ and R ¹⁹ independently represent hydrogen, C _1-5 alkyl, phenyl or C _2-5 heterocyclyl; alternatively, R ¹⁸ and R ¹⁹ may be taken together to form an optionally substituted 4-7 membered heterocyclic ring, which may be saturated, unsaturated or aromatic; n is 0, 1 or 2; G is C _3-6 alkenediyl or C _3-6 alkanediyl optionally substituted with hydroxy, halogen, C _1-5 alkyl, C _1-5 alkoxy, oxo, hydroxyimino, CO ₂ R ^k , NR ^k R ^l , (L) -C _1-4 alkylene, R ^k R ^l NCO ₂ , [(L) -C _1-5 alkylene] amino, N ₃ or (L) -C _1-5 alkoxy; L is amino, mono- or di-C _1-5 alkylamino, pyrrolidinyl, morpholinyl, piperidinyl, homopiperidinyl or piperazinyl, where available ring nitrogen atoms may optionally be substituted with C _1-5 alkyl, benzyl, C _2-5 acyl, C _1-5 alkylsulfonyl or C _1-5 alkoxycarbonyl; Ar is a monocyclic or bicyclic aryl or heteroaryl ring optionally substituted with 1-3 substituents independently selected from halogen, C _1-5 alkoxy, C _1-5 alkyl, C _2-5 alkenyl, cyano, azido, nitro, R ²² R ²³ N, R ²² S, R ²² SO, R ²² SO ₂ , R ²² OC = O, R ²² R ²³ NC = O, C _1-5 haloalkyl, C _1-5 haloalkoxy, C _1-5 haloalkylthio and C _{1 -5} alkylthio; R ²² represents hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl, C _2-5 heterocyclyl, C _2-8 acyl, aroyl, R ¹¹ OC = O, R ²⁴ R ²⁵ NC = O, R ¹¹ S, R ¹¹ SO, R ¹¹ SO ₂ or R ²⁴ R ²⁵ NSO ₂ ; R ²³ represents hydrogen, C _1-5 alkyl, phenyl, benzyl or C _2-5 heterocyclyl; alternatively, R ²² and R ²³ may be taken together to form an optionally substituted 4-7 membered heterocyclic ring, which may be saturated, unsaturated or aromatic; R ²⁴ and R ²⁵ independently represent hydrogen, C _1-5 alkyl, phenyl, benzyl or C _1-5 heteroaryl; alternatively, R ²⁴ and R ²⁵ may be taken together to form an optionally substituted 4-7 membered carbocyclic or heterocyclic ring, which may be saturated, unsaturated or aromatic; R ³² represents hydrogen, C _1-5 alkyl, cyano, C _1-5 hydroxyalkyl, C _2-8 acyl, - (C = O) NR ^v R ^x , CHO, or C _1-6 alkoxycarbonyl, where each R ^v and R ^{x are} independently selected from H, C _1-5 alkyl, C _1-5 hydroxyalkyl, C _1-5 heterocyclyl, (C _1-5 heterocyclyl) C _1-5 alkylene, C _1-5 aminoalkylene, C _3-8 acyloxy, CHO, C _1-6 alkoxycarbonyl and cyano; Q represents NR ³³ , S or O; R ³³ represents hydrogen, C _1-5 alkyl, phenyl, benzyl, phenethyl, C _2-5 heterocyclyl, (C _2-5 heterocyclyl) C _1-5 alkylene, C _2-8 acyl, aroyl, R ³⁵ OC = O R ³⁶ R ³⁷ NC = O, R ³⁵ SO, R ³⁵ S, R ³⁵ SO ₂ or R ³⁶ R ³⁷ NSO ₂ ; R ^{35 is} selected from hydrogen, C _1-5 alkyl, phenyl, benzyl, phenethyl and C _2-5 heteroaryl; each R ³⁶ and R ³⁷ is independently selected from hydrogen, C _1-5 alkyl, phenyl or C _2-5 heteroaryl; alternatively, R ³⁶ and R ³⁷ may be taken together to form an optionally substituted 4-7 membered heterocyclic ring, which may be saturated, unsaturated or aromatic; where each of the above hydrocarbon or heterocarbon groups, unless otherwise indicated, and, in addition to any specific substituents, is optionally and independently substituted by 1-3 substituents selected from methyl, halogenmethyl, hydroxymethyl, halogen, hydroxy, amino, nitro, cyano, C _1-5 alkyl, C _1-5 alkoxy, -COOH, C _2-6 acyl, [di (C _1-4 alkyl) amino] C _2-5 alkylene, [di (C _1-4 alkyl) amino] C _2-5 alkyl-NH-CO- and C _1-5 haloalkoxy; or a pharmaceutically acceptable salt, amide or ester thereof, or a stereoisomeric form thereof. 2. The method according to claim 1, where R ²⁰ and R ²¹ are independently selected from hydrogen, halogen, C _1-5 alkoxy, C _1-5 alkyl, cyano, nitro, 4-7 membered heterocyclyl, and R ^o R ^p N or R ^c R ^d N, respectively. 3. The method according to claim 1, where Y represents nitrogen or R ²⁰ C; Z represents nitrogen or R ²¹ C; T represents nitrogen or R ² C; S represents nitrogen or R ³ C; with the proviso that from 0 to 2 of S, T, Y and Z are nitrogen; R ² represents hydrogen, halogen, hydroxy, C _1-5 alkoxy, C _1-5 alkyl, 5-6-membered heterocyclyl or R ^e R ^f N; R ³ represents hydrogen, halogen, C _1-5 alkoxy, hydroxy, C _1-5 alkyl, 5-6 membered heterocyclyl or R ^g R ^h N; each R ⁵ and R ⁶ represents H; R ⁷ and R ^{8 are} independently taken together to form an optionally substituted 5-7 membered unsaturated heterocyclic ring; each R ^a , R ^e , R ^m and R ^{o are} independently selected from hydrogen, C _1-5 alkyl, C _2-8 acyl, (C _1-5 alkyl) OC = O and the corresponding RRNC = O, RSO, RSO ₂ and RRNSO ₂ groups; each R ^b , R ^f , R ⁿ and R ^{p are} independently selected from hydrogen and C _1-5 alkyl; each R ⁹ , R ¹¹ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ⁴⁰ , R ⁴¹ and R ⁴² independently represents C _1-5 alkyl; each R ^c , R ^d , R ⁱ , R ^j , R ⁴³ , R ⁴⁴ , R ⁴⁵ , R ⁴⁶ , R ⁴⁷ , R ^k and R ^l independently represents hydrogen or C _1-5 alkyl; R ^g represents hydrogen or C _1-5 alkyl, C _2-8 acyl, R ⁹ OC = O, R ¹⁸ R ¹⁹ NC = O, R ⁹ SO, R ⁹ SO ₂ or R ¹⁸ R ¹⁹ NSO ₂ ; R ^h represents hydrogen or C _1-5 alkyl; alternatively, R ^g and R ^h may be taken together to form an optionally substituted 4-7 membered carbocyclic or heterocyclic ring, which may be saturated, unsaturated or aromatic; R ¹⁸ and R ¹⁹ independently represent hydrogen or C _1-5 alkyl; n is 0 or 1; G represents C _3-4 alkenediyl or C _3-4 alkanediyl optionally substituted with hydroxy, halogen, C _1-5 alkyloxy, oxo, hydroxyimino, CO ₂ R ^k , R ^k R ^l NCO ₂ , N ₃ or (L) - C _1-5 alkoxy; L is amino, mono- or di-C _1-5 alkylamino, pyrrolidinyl, morpholinyl, piperidinyl, homopiperidinyl or piperazinyl, where the available ring nitrogen atoms are optionally substituted with C _1-5 alkyl, benzyl, C _2-5 acyl or C _{1- 5} alkoxycarbonyl; R ²⁰ and R ^{21 are} independently selected from hydrogen, halogen, C _1-5 alkoxy, C _1-5 alkyl, cyano, nitro and R ^o R ^p N; alternatively, R ³ and R ²⁰ or R ³ and R ²¹ may be taken together to form an optionally substituted 5-6 membered carbocyclic or heterocyclic ring, which may be saturated, unsaturated or aromatic; Ar is a monocyclic or bicyclic aryl or heteroaryl ring, optionally substituted with hydrogen, halogen, C _1-5 alkoxy, C _1-5 alkyl, cyano, nitro, R ²² R ²³ N, R ²⁴ SO ₂ , R ²⁴ OC = O, R ²⁵ R ²⁶ NC = O, CF ₃ , OCF ₃ , SCF ₃ or C _1-5 alkylthio; R ²² represents hydrogen, C _1-5 alkyl, phenyl, benzyl, phenethyl, C _2-5 heteroaryl, C _2-8 acyl, aroyl, R ²⁴ O (C = O), R ²⁵ R ²⁶ NC = O, R ²⁴ SO, R ²⁴ SO ₂ or R ²⁵ R ²⁶ NSO ₂ ; R ²³ represents hydrogen or C _1-5 alkyl; alternatively, R ²² and R ²³ may be taken together to form an optionally substituted 4-7 membered carbocyclic or heterocyclic ring, which may be saturated, unsaturated or aromatic; R ²⁴ represents hydrogen or C _1-5 alkyl; R ²⁵ and R ²⁶ independently represent hydrogen or C _1-5 alkyl; or alternatively, R ²⁵ and R ²⁶ may be taken together to form an optionally substituted 4-7 membered carbocyclic or heterocyclic ring, which may be saturated, unsaturated or aromatic; R ³² represents hydrogen, C _1-5 alkyl, C _1-5 hydroxyalkyl, CHO, C _2-6 acyl, C _1-6 alkoxycarbonyl, or ^{- (C = O) NR v} R x, wherein each of R ^v R ^x independently selected from H, C _1-5 alkyl, C _1-5 hydroxyalkyl, C _3-8 acyloxy, (amino) C _1-6 alkylene, (C _1-5 heterocyclyl) C _1-5 alkylene or C _1-6 alkoxycarbonyl ; Q represents NR ³³ or S; R ³³ represents hydrogen, C _1-5 alkyl, phenyl, benzyl, (C _2-5 heterocyclyl) C _1-5 alkylene, C _2-8 acyl, aroyl, R ³⁵ OC = O, R ³⁶ R ³⁷ NC = O, R ³⁵ SO ₂ or R ³⁶ R ³⁷ NSO ₂ ; R ^{35 is} selected from hydrogen and C _1-5 alkyl; each R ³⁶ and R ^{37 are} independently selected from hydrogen and C _1-5 alkyl. 4. The method according to claim 1, where one of R ⁵ and R ⁶ represents H; R ⁷ and R ⁸ are taken together to form an optionally substituted 6-membered carbocyclic or heterocyclic ring; and Ar is a monocyclic ring optionally substituted with 1-2 substituents selected from halogen, C _1-5 alkyl, cyano, nitro, R ²² R ²³ N, CF ₃ and OCF ₃ . 5. The method according to claim 4, where R ²² and R ²³ , taken together, independently are morpholinyl, piperidyl or pyrrolidinyl, optionally substituted. 6. The method according to claim 1, where the specified connection is selected from: 1- [4- (5-chloro-1H-indol-3-yl) piperidin-1-yl] -3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [ 4,3-c] pyridin-1-yl] propan-2-ol; 1- [4- (7-chloro-1H-indol-3-yl) piperidin-1-yl] -3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [ 4,3-c] pyridin-1-yl] propan-2-ol; 1- [4- (5-chloro-2-methyl-1H-indol-3-yl) piperidin-1-yl] -3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6, 7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propan-2-ol; 1- {4- [6-chloro-1 (2-morpholin-4-yl-ethyl) -1H-indol-3-yl] piperidin-1-yl} -3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propan-2-ol; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (1H-pyrrolo [3, 2-c] pyridin-3-yl) piperidin-1-yl] propan-2-ol; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (1H-pyrrolo [2, 3-b] pyridin-3-yl) piperidin-1-yl] propan-2-ol; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (5-morpholin-4- yl-1H-pyrrolo [2,3-c] pyridin-3-yl) piperidin-1-yl] propan-2-ol; 1- [4- (6-dimethylamino-1H-pyrrolo [3,2-c] pyridin-3-yl) piperidin-1-yl] -3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4, 5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propan-2-ol; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (6-morpholin-4- yl-1H-pyrrolo [3,2-c] pyridin-3-yl) piperidin-1-yl] propan-2-ol; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (6-morpholin-4- yl-5-hydroxy-1H-pyrrolo [3,2-c] pyridin-3-yl) piperidin-1-yl] propan-2-ol; 6-fluoro-3- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1 (2-hydroxyethyl) amide -yl] propyl} piperidin-4-yl) benzo [b] thiophene-2-carboxylic acid; (2-aminoethyl) amide 6-fluoro-3- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1 -yl] propyl} piperidin-4-yl) benzo [b] thiophene-2-carboxylic acid; and 6-fluoro-3- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] (2-morpholin-4-yl-ethyl) amide ] pyridin-1-yl] propyl} piperidin-4-yl) benzo [b] thiophene-2-carboxylic acid. 7. The method according to claim 1, where the specified connection is selected from: 1- [1- {2-hydroxy-3- [4- (1H-indol-3-yl) piperidin-1-yl] propyl} -3- (4-trifluoromethylphenyl) -1,4,6,7-tetrahydropyrazolo [4,3-c] pyridin-5-yl] ethanone; 1- [4- (5-fluoro-1H-indol-3-yl) piperidin-1-yl] -3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [ 4,3-c] pyridin-1-yl] propan-2-ol; 1- [3- (4-bromophenyl) -5-methanesulfonyl-4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (5-chloro-1H- indol-3-yl) piperidin-1-yl] propan-2-ol; 1- [3- (4-bromophenyl) -5-methanesulfonyl-4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (5-chloro-2- methyl-1H-indol-3-yl) piperidin-1-yl] propan-2-ol; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (5-methyl-1H- indol-3-yl) piperidin-1-yl] propan-2-ol; 3- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidine -4-yl) -1H-indol-5-carbonitrile; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (5-methoxy-1H- indol-3-yl) piperidin-1-yl] propan-2-ol; 3- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl ethyl ester } piperidin-4-yl) -1H-indole-5-carboxylic acid; 1- [4- (6-chloro-1H-indol-3-yl) piperidin-1-yl] -3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [ 4,3-c] pyridin-1-yl] propan-2-ol; 1- [1- (3- {4- (6-chloro-1- (2-morpholin-4-yl-ethyl) -1H-indol-3-yl] piperidin-1-yl} -2-hydroxypropyl) - 3- (4-trifluoromethylphenyl) -1,4,6,7-tetrahydropyrazolo [4,3-c] pyridin-5-yl] ethanone; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (1H-pyrrolo [3, 2-b] pyridin-3-yl) piperidin-1-yl] propan-2-ol; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (1H-pyrrolo [2, 3-c] pyridin-3-yl) piperidin-1-yl] propan-2-ol; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (5-hydroxy-1H- pyrrolo [3,2-c] pyridin-3-yl) piperidin-1-yl] propan-2-ol; 1- [4- (5-dimethylamino-1H-pyrrolo [3,2-b] pyridin-3-yl) piperidin-1-yl] -3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4, 5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propan-2-ol; 1- [4- (5-dimethylamino-1H-pyrrolo [2,3-c] pyridin-3-yl) piperidin-1-yl] -3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4, 5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propan-2-ol; 3- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidine -4-yl) -1H-pyrrolo [2,3-b] pyridin-6-carbonitrile; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- {4- [1- (2-morpholine -4-yl-ethyl) -1H-pyrrolo [2,3-b] pyridin-3-yl) piperidin-1-yl] propan-2-ol; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (7-morpholin-4- yl-1H-pyrrolo [2,3-c] pyridin-3-yl) piperidin-1-yl] propan-2-ol; 1- [4- (6-fluoro-2-hydroxymethyl-benzo [b] thiophen-3-yl) piperidin-1-yl] -3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4.5, 6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propan-2-ol; 6-fluoro-3- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl ] propyl} piperidin-4-yl) benzo [b] thiophene-2-carbaldehyde; 6-fluoro-3- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1 methyl ester -yl] propyl} piperidin-4-yl) benzo [b] thiophene-2-carboxylic acid; 6-fluoro-3- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl amide}} piperidin-4-yl) benzo [b] thiophene-2-carboxylic acid; and ethylamide 6-fluoro-3- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl } piperidin-4-yl) benzo [b] thiophene-2-carboxylic acid. 8. The method according to claim 1, where the specified connection is selected from: 1- {4- [6-chloro-1- (2-morpholin-4-yl-ethyl) -1H-indol-3-yl) piperidin-1-yl] -3- [5-methanesulfonyl-3- (4 trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propan-2-ol; 6-fluoro-3- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-morpholin-4-yl-ethyl) amide -c] pyridin-1-yl] propyl} piperidin-4-yl) benzo [b] thiophene-2-carboxylic acid; 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (5-hydroxy-1H- pyrrolo [3,2-c] pyridin-3-yl) piperidin-1-yl] propan-2-ol; and 1- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -3- [4- (6-morpholin-4- yl-1H-pyrrolo [3,2-c] pyridin-3-yl) piperidin-1-yl] propan-2-ol. 9. The method according to claim 1, where the specified pharmaceutical composition is prepared with a dose of the active substance suitable for the treatment of allergic diseases.