RU2003106193A

RU2003106193A - METHOD FOR TREATING ALLERGIES USING SUBSTITUTED PYRAZOLES

Info

Publication number: RU2003106193A
Application number: RU2003106193/15A
Authority: RU
Inventors: Кристофер Р. Батлер; Хьюи КАЙ; Джеймс П. Эдвардс; Черил А. Грайс; Йин ГУ; Дарин Дж. ГАСТИН; Ларс Карлссон; Харипада КХАТУЯ; Стивен П. Медуна; Барбара А. ПАЙО; Кларк А. Сехон; Сикван СУН; Кевин Л. ТЭЙС; Робин Л. ТЁРМОНД; Джианмей ВЕЙ
Original assignee: Орто-Макнейл Фармасьютикал, Инк.
Priority date: 2000-09-06
Filing date: 2001-09-05
Publication date: 2004-07-27

Claims

1. A method of treating an allergic condition of a patient, comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising a compound of formula (I)

where Ar ₂ represents a monocyclic or bicyclic ring system, unsaturated, saturated or aromatic, optionally condensed, optionally including 1 to 5 heteroatomic moieties in the ring, independently selected from O, S, N, SO ₂ and C = O, wherein said ring system Ar _{2 is} optionally substituted with 1-4 substituents;

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 _2-5 alkenyl, C _1-5 alkoxy, C _1-5 alkylthio, halogen or 4-7 membered carbocyclyl or heterocyclyl, in alternative in the case, R ⁷ and R ⁸ may together form an optionally substituted 5-7 membered carbocyclic or heterocyclic ring, which may be unsaturated or aromatic and may optionally be substituted with one to three substituents independently selected from halogen, cyano, amino, hydroxy, nitro, R ⁴ , R ⁴ O-, R ⁴ S-, R ⁴ O (C _1-5 alkylene) -, R ⁴ O (C = O) -, R ⁴ (C = O) -, R ⁴ (C = S) -, R ⁴ (C = O) O-, R ⁴ O (C = O) (C = O) -, R ⁴ S O ₂ , NHR ⁴⁴ (C = NH) -, NHR ⁴⁴ SO ₂ - and NHR ⁴⁴ (C = O) -;

R ⁴ is H, C _1-5 alkyl, C _2-5 alkenyl, C _1-5 heterocyclyl, (C _1-5 heterocyclyl) C _1-6 alkylene, phenyl, benzyl, phenethyl, NH ₂ mono- or di (C _1-6 -alkyl) N-, (C _1-6 -alkoxy) carbonyl- or R ⁴² OR ⁴³ -, where R ⁴² represents H, C _1-5 -alkyl, C _2-5 alkenyl, phenyl, benzyl, phenethyl, C _1-5 heterocyclyl or (C _1-6 heterocyclyl) C _1-6 alkylene and R ⁴³ is C _1-5 alkylene, phenylene or divalent C _1-5 - heterocyclyl;

R ⁴⁴ may be H in addition to the values for R ⁴ ;

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 alkoxy, C _1-5 alkyl, oxo, hydroxyimino, CO ₂ R ^k , R ^k R ¹ N , R ^k R ¹ NCO ₂ , (L) -C _1-4 alkylene, (L) -C _1-5 alkoxy, N ₃ or [(L) -C _1-5 alkylene] amino;

each of R ^k and R ¹ is independently hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl, phenethyl or C _1-5 heterocyclyl; alternatively, R ^k and R ¹ may be taken together with the formation of an optionally substituted 4-7 membered heterocyclic ring, which may be saturated, unsaturated or aromatic;

L is amino, mono- or di C _1-5 alkylamino, pyrrolidinyl, morpholinyl, piperidinyl, homopiperidinyl or piperazinyl, where the 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 represents 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 ²⁴ SO ₂ , R ²⁴ S, R ²⁴ SO, R ²⁴ 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, phenethyl, benzyl or C _1-5 heterocyclyl, C _2-8 acyl, aroyl, R ³⁸ OC = O, R ²⁵ R ²⁶ NC = O, R ³⁸ SO, R ³⁸ SO ₂ , R ³⁸ S or R ²⁵ R ²⁶ NSO ₂ ;

R ²³ represents hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl or C _1-5 heterocyclyl; alternatively, R ²² and R ²³ may together form an optionally substituted 4-7 membered heterocyclic ring which may be saturated, unsaturated or aromatic;

each of R ²⁴ is C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl or C _1-5 heterocyclyl;

R ²⁵ and R ²⁶ independently represent hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl or C _1-5 heterocyclyl or, alternatively, R ²⁵ and R ²⁶ may optionally form together a substituted 4-7 membered heterocyclic ring which may be saturated, unsaturated or aromatic;

W represents O, S, NR ²⁷ , C = O, (C = O) NH, NH (C = O), CHR ²⁸ or a covalent bond;

R ^z represents H or OH and the dashed line is absent or R ^{z is} absent when the dashed line represents the sp ² bond;

R ²⁷ represents hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, naphthyl, benzyl, phenethyl, C _1-5 heterocyclyl, C _2-8 acyl, aroyl, R ²⁹ OC = O, R ³⁰ R ³¹ NC = O, R ²⁹ SO, R ²⁹ S, R ²⁹ SO ₂ or R ³⁰ R ³¹ NSO ₂ or, alternatively, R ²⁷ and part of Ar ₂ may together form an optionally substituted 5- or 6-membered heterocyclic a ring with optional 1-3 additional heteroatomic moieties in the ring selected from O, NR ⁹ , NR ¹⁰ , N, SO ₂ , C = O and S, the ring may be saturated, unsaturated or aromatic; R ⁹ and R ¹⁰ are independently selected from H, C _1-3 alkyl and —CH ₂ CO ₂ (C _1-4 alkyl);

R ²⁸ represents hydrogen, C _1-5 alkyl, C _3-5 alkenyl, hydroxy, phenyl, benzyl, C _1-5 heterocyclyl, R ²⁹ O, R ³⁰ R ³¹ NC = O, R ²⁹ S, R ²⁹ SO, R ²⁹ SO ₂ or R ³⁰ R ³¹ NSO ₂ ;

R ²⁹ is C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl or C _1-5 heterocyclyl;

R ³⁰ and R ^{31 are} independently selected from hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl, phenethyl, naphthyl and C _1-5 heteroaryl; alternatively, R ³⁰ and R ³¹ may together form optionally substituted 4-7 membered carbocyclic or heterocyclic ring, which may be saturated, unsaturated or aromatic,

where each of the above hydrocarbon or heterohydrocarbon groups, unless otherwise indicated, is optionally and independently substituted, along with any of the indicated substituents, 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 Ar ₂ selected from 2,5-di (C _1-6 -alkyl) aminopyrrolyl and groups of the following 6 formulas:

where each dashed line may be a sp ² bond or absent;

X _c represents O, S or N and X _d represents O or S;

R ¹ represents hydrogen, halogen, C _1-5 alkoxy, hydroxy, C _1-5 alkyl, C _2-5 alkenyl, cyano, nitro, R ^a R ^b N, C _2-8 acyl, C _{1- 5-} heterocyclyl, (C _1-5- heterocyclyl) C _1-5 -alkylene, R ¹¹ S, R ¹¹ SO, R ¹¹ SO ₂ , R ^c OC = O, R ^c R ^d NC = O or R ^c R ^d NSO ₂ or R ¹ can be taken together with R ²⁷ , as described below;

R ² represents hydrogen, halogen, C _1-5 alkoxy, hydroxy, C _1-5 alkyl, C _2-5 alkenyl, cyano, nitro, R ^e R ^f N, C _1-5 heterocyclyl or C _{2- 8-} acyl;

R ³ represents hydrogen, halogen, C _1-5 alkoxy, hydroxy, C _1-5 alkyl, C _2-5 alkenyl, cyano, nitro, R ^g R ^h N, C _2-8 acyl, C _{1- 5-} heterocyclyl, R ^h OC = O, R ^g R ^h NC = O or R ^g R ^h NSO ₂ ;

R ^{a is} selected from hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl, phenethyl, C _1-5 heterocyclyl, C _2-8 acyl, aroyl, R ^j OC = O, R ⁱ R ^j NC = O, R ¹² SO, R ¹² SO ₂ , R ¹² S and R ⁱ R ^j NSO ₂ ;

R ^{e is} selected from hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl, phenethyl, C _1-5 heterocyclyl, C _2-8 acyl, aroyl, R ³² OC = O, R ³² R ³³ NC = O, R ¹³ SO, R ¹³ SO ₂ , R ¹³ S and R ³² R ³³ NSO ₂ ;

R ^{m is} selected from hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl, phenethyl, C _1-5 heterocyclyl, C _2-8 acyl, aroyl, R ³⁴ OC = O, R ³⁴ R ³⁵ NC = O, R ¹⁵ SO, R ¹⁵ SO ₂ , R ¹⁵ S and R ³⁴ R ³⁵ NSO ₂ ;

R ° is selected from hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl, phenethyl, C _1-5 heterocyclyl, C _2-8 acyl, aroyl, R ³⁶ OC = O, R ³⁶ R ³⁷ NC = O, R ¹⁹ SO, R ¹⁹ SO ₂ , R ¹⁹ S and R ³⁶ R ³⁷ NSO ₂ ;

each of R ^b , R ^f , R ⁿ , R ^p , R ³² , R ³³ , R ³⁴ , R ³⁵ , R ³⁶ , R ³⁷ , R ³⁹ and R ⁴⁰ is independently selected from hydrogen, C _1-5 alkyl C _3-5 alkenyl, phenyl, benzyl, phenethyl and C _1-5 heteroaryl, alternatively R ^a and R ^b , R ^e and R ^f , R ^m and R ⁿ and R ° and R ^p , independently, may together form an optionally substituted 4-7 membered heterocyclic ring, which may be saturated, unsaturated or aromatic;

each of R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁹ , R ³⁸ and R ⁴¹ is independently C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl, phenethyl or C _1-5 heterocyclyl;

each of R ^c and R ^d and R ⁱ and R ^j is independently hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl, phenethyl or C _1-5 heteroaryl, alternatively R ^c and R ^d and R ⁱ and R ^j , independently, may together form an optionally substituted 4-7 membered heterocyclic ring, which may be saturated, unsaturated or aromatic;

R ^g represents hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl, phenethyl or C _1-5 heterocyclyl, C _2-8 acyl, aroyl, R ¹⁷ OC = O, R ¹⁷ R ¹⁸ NC = O, R ¹⁶ S, R ¹⁶ SO, R ¹⁶ SO ₂ or R ¹⁷ R ¹⁸ NSO ₂ ;

R ^h is hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl, phenethyl or C _1-5 heterocyclyl; alternatively, R ^g and R ^h may together form an optionally substituted 4-7 membered a heterocyclic ring which may be saturated, unsaturated or aromatic;

R ¹⁷ and R ¹⁸ independently represent hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, benzyl or C _1-5 heterocyclyl; alternatively, R ¹⁷ and R ¹⁸ may together form optionally substituted 4 A 7 membered heterocyclic ring which may be saturated, unsaturated or aromatic;

Y _e represents nitrogen or R ²⁰ C;

Z _e represents nitrogen or R ²¹ C;

R ²⁰ represents hydrogen, halogen, C _1-5 alkoxy, C _1-5 alkyl, C _2-5 alkenyl, cyano, nitro, R ^m R ⁿ N, C _2-8 acyl, R ^m OC = O R ¹⁴ S, R ¹⁴ SO or R ¹⁴ SO ₂ ;

R ²¹ represents hydrogen, halogen, C _1-5 alkoxy, C _1-5 alkyl, C _2-5 alkenyl, cyano, nitro, R ° R ^p N, C _2-8 acyl, R ¹⁶ OC = O , R ^ll S, R ⁿ SO or R ¹¹ SO ₂ , alternatively R ³ and R ²⁰ or R ³ and R ²¹ may together form an optionally substituted 5 or 6 membered carbocyclic or heterocyclic ring, which may be saturated, unsaturated or aromatic, wherein said ring may optionally be substituted with halogen, di- (C _1-5 alkyl) amino, C _2-5 acyl and C _1-5 alkoxy;

R ²⁷ represents hydrogen, C _1-5 alkyl, C _3-5 alkenyl, phenyl, naphthyl, benzyl, phenethyl, C _1-5 heterocyclyl, C _2-8 acyl, aroyl, R ²⁹ OC = O, R ³⁰ R ³¹ NC = O, R ²⁹ SO, R ²⁹ S, R ²⁹ SO ₂ or R ³⁰ R ³¹ NSO ₂ ; or, alternatively, R ²⁷ and R ¹ may together form an optionally substituted 5- or 6-membered heterocyclic ring with optional 1-3 additional heteroatomic moieties in the ring selected from O, NR ⁹ , NR ¹⁰ , N, SO ₂ , C = O and S, wherein the ring may be saturated, unsaturated or aromatic;

R ⁹ and R ^{10 are} independently selected from H, C _1-3 alkyl and —CH ₂ CO ₂ (C _1-4 alkyl);

X _f represents CHR ^1f , = N-, NH, C = O, SO ₂ , CHSR ^1f , where in the formula (f) R ^1f represents hydrogen, halogen, C _1-5 alkoxy, hydroxy, C _1-5 alkyl , C _3-5 alkenyl, cyano, nitro, R ³⁹ R ⁴⁰ N, C _2-8 acyl, C _1-5 heterocyclyl, (C _1-5 heterocyclyl) C _1-5 alkylene, R ⁴¹ S, R ⁴¹ SO, R ⁴¹ SO ₂ , R ³⁹ OC = O, R ³⁹ R ⁴⁰ NC = O, R ³⁹ R ⁴⁰ NSO ₂ , R ⁴¹ SO ₃ - or R ³⁹ (C = O) O-;

Y _f represents CH ₂ , CHR ^2f , = CR ^2f , O or NR ^2f , where R ^2f represents H, C _1-7 alkyl, C _3-5 alkenyl, C _2-8 acyl, C _1-5 - heterocyclyl, (C _1-5 -heterocyclyl) -C _1-5 -alkylene, phenyl, (phenyl) -C _1-5 -alkylene, (C _3-7 -cycloalkyl) -C _1-5 -alkylene, (H ₂ NCO) -C _1-5 -alkylene, C _1-5 -haloalkyl, C _1-5 -cyanoalkyl, (C _1-5 -alkoxycarbonyl) -C _1-5 -alkylene and (phenylcarbonyl) NH-;

m is 0 or 1;

p = 0 or 1,

where each of the above hydrocarbon or heterohydrocarbon groups, unless otherwise indicated, is optionally and independently substituted, along with any of the indicated substituents, 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.

3. The method according to claim 2, where Ar ₂ selected from formula (f).

4. The method according to claim 2, where Ar ₂ has the formula (e) and R ¹ represents halogen, C _1-5 alkoxy, hydroxy, C _1-5 alkyl, cyano, nitro and R ^a R ^b N or R ¹ can be taken together with R ²⁷ as follows, R ² represents hydrogen, halogen, C _1-5 alkoxy, C _1-5 alkyl or R ^e R ^f N, R ³ represents hydrogen, halogen, C _1-5 alkoxy, hydroxy, C _1-5 alkyl, cyano, R ^g R ^h N, R ⁵ and R ^{6 are} independently selected from hydrogen and C _1-3 alkyl, R ⁷ and R ⁸ independently together form optionally substituted 5-7 a membered carbocyclic or heterocyclic ring which may be saturated, unsaturated or aromatic, each of R ^a , R ^e , R ^m and R ° is independently selected from hydrogen, C _1-5 alkyl, C _2-8 acyl and the corresponding groups ROC = O, RRNC = O, RS, RSO, RSO ₂ and RRNSO ₂ , each of R ^b , R ^f , R ⁿ and R ^{p is} independently selected from hydrogen and C _1-5 alkyl, each of R ¹¹ , R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁹ and R ³⁸ independently represents C _1-5 alkyl, each of R ^c and R ^d , R ⁱ and R ^j , R ^k and R ^l , R ³² and R ³³ , R ³⁴ and R ³⁵ , R ³⁶ and R ³⁷ independently represents hydrogen or C _1-5 alkyl or together form an optionally substituted 4-7 membered heterocyclic ring,

R ^g represents hydrogen, C _1-5 alkyl, C _2-8 acyl, R ¹⁷ OC = O, R ¹⁷ R ¹⁸ NC = O, R ¹⁶ S, R ¹⁶ SO, R ¹⁶ SO ₂ or R ¹⁷ R ¹⁸ NSO ₂ , R ^h represents hydrogen or C _1-5 alkyl; alternatively, R ^g and R ^h may together form an optionally substituted 4-7 membered heterocyclic ring, R ¹⁷ and R ¹⁸ independently represent hydrogen or C _1-5 alkyl, n = 0 or 1, G represents C _3-4 alkenediyl or C _3-4 alkanediyl optionally substituted with hydroxy, halogen, C _1-5 alkyloxy, (L) -C _1-5 alkyloxy, N ₃ or [(L) -C _1-5 alkylene] amino, L is amino, mono- or di-C _1-5 alkylamino, pyrrolidinyl, morpholinyl, piperidinyl, homopiperidinyl or piperazinyl, where available nitrogen atoms may be optionally substituted by C _1-5 -alkyl, benzyl, _2-5 -alkilkarbonilom or C _1-5 -alkiloksikarbonilom, Y _e is nitrogen or R ²⁰ C, Z _e is nitrogen or R ²¹ C, R ²⁰ and R ²¹ are independently selected from hydrogen, halogen, C _1-5 alkoxy, C _1-5 alkyl, cyano, nitro and R ^m R ⁿ N or R ° R ^p N, respectively; alternatively, R ³ and R ²⁰ or R ³ and R ²¹ may together form an optionally substituted 5- or 6-membered carbocyclic or heterocyclic ring, Ar is a monocyclic or bicyclic aryl or heteroaryl ring, optionally substituted with 1 to 3 substituents independently selected from halogen, C _1-5 alkoxy, C _1-5 alkyl, cyano, azido, nitro, R ²² R ²³ N, R ²⁴ SO ₂ , R ²⁴ OC = O, R ²⁵ R ²⁶ NC = O, CF ₃ , OCF ₃ , CF ₃ S and C _1-5 alkylthio, R ²² represents hydrogen, C _1-5 alkyl, phenyl, benzyl, phenethyl, C _1-5 heterocyclyl, C _2-8 acyl, aroyl, R ²⁴ OC = 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 together form an optionally substituted 4-7 membered heterocyclic ring, 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 together form an optionally substituted 4-7 membered heterocycle, W represents NR ²⁷ or CHR ²⁸ , R ²⁷ represents hydrogen, C _1-5 alkyl, R ²⁹ OC = O, R ³⁰ R ³¹ NC = O, R ²⁹ SO, R ²⁹ SO ₂ or R ³⁰ R ³¹ NSO ₂ or, alternatively, R ²⁷ and R ¹ may together obrazovyvat optionally substituted 5- or 6-membered heterocyclic ring which may be saturated, unsaturated or aromatic, R ²⁸ represents hydrogen, hydroxy, C _1-5 -heterocyclyl, phenyl or C _1-5 -alkyl, R ²⁹ represents C _1-5 -alkyl and R ³⁰ and R ^{31 are} independently selected from hydrogen, C _1-5 alkyl, alternatively R ³⁰ and R ³¹ may together form an optionally substituted 4-7 membered heterocycle.

5. The method according to claim 1, where one of R ⁵ and R ⁶ represents H, R ⁷ and R ⁸ together form an optionally substituted 6-membered carbocyclic or heterocyclic ring and

Ar represents a monocyclic ring optionally substituted with 1 or 2 substituents selected from halogen, C _1-5 alkyl, cyano, azido, nitro, R ²² R ²³ N, CF ₃ and OCF ₃ .

6. The method according to claim 5, where both R ⁵ and R ⁶ each represent H and Ar represents a six-membered ring substituted with 1 or 2 substituents independently selected from halogen, methyl, CF ₃ and OCF ₃ , wherein said substituent or substituents are in the 4-position or in the 3- and 4-positions.

7. The method according to claim 2, where R ²⁰ and R ³ taken together represent a six-membered carbocyclic or heterocyclic ring optionally substituted with 1-3 substituents independently selected from halogen, C _1-3 alkoxy, di- (C _{1- 3-} alkyl) amino and C _2-5 acyl.

8. The method according to claim 1, where the specified compound is selected from 1- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4, 3-c] pyridin-1-yl] propyl} piperidin-4-yl) -1,3-dihydrobenzoimidazol-2-one;

1- (1- {3- [3- (3,4-dichlorophenyl) -5-methanesulfonyl-4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidin-4 -yl) -1,3-dihydrobenzoimidazol-2-one;

amide 3- (3,4-dichlorophenyl) -1- {3- [4- (2-oxo-2,3-dihydrobenzimidazol-1-yl) piperidin-1-yl] propyl} -1,4,6,7 Tetrahydropyrazolo [4,3-c] pyridine-5-carboxylic acid;

6-chloro-1- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidine -4-yl) -1,3-dihydrobenzoimidazol-2-one;

amide 3- (3,4-dichlorophenyl) -1- {3- [4- (3-methyl-2-oxo-2,3-dihydrobenzoimidazol-1-yl) piperidin-1-yl] propyl} -1,4 6,7-tetrahydropyrazolo [4,3-c] pyridine-5-carboxylic acid;

[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) -2-oxo-2,3-dihydrobenzoimidazol-1-yl] acetonitrile;

[3- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl ethyl ester ] propyl} piperidin-4-yl) -2-oxo-2,3-dihydrobenzoimidazol-1-yl] acetic acid;

5-chloro-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) -1-methyl-1,3-dihydrobenzoimidazol-2-one;

amide 1- {3- [4- (6-chloro-3-methyl-2-oxo-2,3-dihydrobenzimidazol-1-yl) piperidin-1-yl] propyl} -3- (3,4-dichlorophenyl) -1,4,6,7-tetrahydropyrazolo [4,3-c] pyridine-5-carboxylic acid;

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) -1,5-dimethyl-1,3-dihydrobenzoimidazol-2-one;

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) -1,3-dihydroimidazo [4,5-b] pyridin-2-one;

3- (1- {3- [3- (4-bromophenyl) -5-methanesulfonyl-4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -2-hydroxypropyl} piperidin- 4-yl) -5-methoxy-1,3-dihydroimidazo [4,5-b] pyridin-2-one;

amide 3- (4-bromophenyl) -1- {2-hydroxy-3- [4- (5-methoxy-2-oxo-1,2-dihydroimidazo [4,5-b] pyridin-3-yl) piperidin- 1-yl] propyl} -1,4,6,7-tetrahydropyrazolo [4,3-c] pyridine-5-carboxylic acid;

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) -5-methoxy-1-methyl-1,3-dihydroimidazo [4,5-b] pyridin-2-one;

5-dimethylamino-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) -1,3-dihydroimidazo [4,5-b] pyridin-2-one;

6-chloro-1- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidine -4-yl) -1,3-dihydroindol-2-one;

1- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidine -4-yl) -3,4-dihydro-1H-quinolin-2-one;

4- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidin-4-yl ) -4H-benzo [1,4] oxazin-3-one;

4- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidine -4-yl) -4H-benzo [1,4] oxazin-3-one and

1- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidin-4-yl ) -3,4-dihydro-1H-quinazolin-2-one.

9. The method according to claim 1, where the specified compound is selected from

[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) -2-oxo-2,3-dihydrobenzoimidazol-1-yl] acetonitrile and 4- (1- {2-Hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4, 5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidin-4-yl) -4H-benzo [1,4] oxazin-3-one.

10. The method according to claim 1, where the specified compound is selected from

2- (1- {3- [5-acetyl-3- (4-chlorophenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -2-hydroxypropyl} piperidin- 4-ylamino) benzonitrile;

1- (1- {3- [5-acetyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -2-hydroxypropyl} piperidin- 4-yl) -1,3-dihydrobenzoimidazol-2-one;

3- (1- {3- [5-acetyl-3- (4-bromophenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -2-hydroxypropyl} piperidin- 4-yl) -3H-benzooxazol-2-one;

1- (3- (4-chloro-3-methylphenyl) -1- {3- [4- (3,4-dichlorophenoxy) piperidin-1-yl] propyl} -1,4,6,7-tetrahydropyrazolo [4 3-c] pyridin-5-yl) ethanone;

1- (3- (4-chloro-3-methylphenyl) -1- {3- [4- (2,3-dihydroindol-1-yl) piperidin-1-yl] -2-hydroxypropyl} -1,4, 6,7-tetrahydropyrazolo [4,3-c] pyridin-5-yl) ethanone;

(S) -1- (1- {3- [5-acetyl-3- (4-chloro-3-methylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl ] -2-hydroxypropyl} piperidin-4-yl) -6-chloro-1,3-dihydrobenzoimidazol-2-one;

1- (1- {3- [5-acetyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -2-hydroxypropyl} piperidin- 4-yl) -3- (2-morpholin-4-yl-ethyl) -1,3-dihydrobenzoimidazol-2-one;

3- (1- {3- [3- (4-bromophenyl) -5-methanesulfonyl-4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -2-hydroxypropyl} piperidin- 4-yl) -6-chloro-1,3-dihydrobenzoimidazol-2-one;

[3- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidin-4- il) -2-oxo-2,3-dihydrobenzoimidazol-1-yl] acetonitrile;

5-chloro-3- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidine -4-yl) -1-methyl-1,3-dihydrobenzoimidazol-2-one;

1- (1- {3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidin-4-yl ) -1,3-dihydroindol-2-one;

1- [3- (4-chloro-3-methylphenyl) -1- (3- {4- [3- (4-chlorophenyl) - [1,2,4] oxadiazol-5-yl] piperidin-1-yl } -2-hydroxypropyl) -1,4,6,7-tetrahydropyrazolo [4,3-c] pyridin-5-yl] ethanone;

1- [1- {2-hydroxy-3- [4- (5-trifluoromethylbenzotriazol-2-yl) piperidin-1-yl] propyl} -3- (4-trifluoromethylphenyl) -1,4,6,7-tetrahydropyrazolo [4,3-c] pyridin-5-yl] ethanone;

1- [1- {3- [4- (benzo [d] isoxazol-3-yloxy) piperidin-1-yl] -2-hydroxypropyl} -3- (4-trifluoromethylphenyl) -1,4,6,7- tetrahydropyrazolo [4,3-c] pyridin-5-yl] ethanone;

1- [1- {3- [4- (5-chlorobenzooxazol-2-yl) piperidin-1-yl] -2-hydroxypropyl} -3- (4-trifluoromethylphenyl) -1,4,6,7-tetrahydropyrazolo [ 4,3-c] pyridin-5-yl] ethanone;

1- [1- {3- [4-benzothiazol-2-ylamino) piperidin-1-yl] -2-hydroxypropyl} -3- (4-trifluoromethylphenyl) -1,4,6,7-tetrahydropyrazolo [4,3 -c] pyridin-5-yl] ethanone;

1- [1- {3- [4- (3,5-dichloropyridin-4-yloxy) piperidin-1-yl] -2-hydroxypropyl} -3- (4-trifluoromethylphenyl) -1,4,6,7- tetrahydropyrazolo [4,3-c] pyridin-5-yl] ethanone;

1- [1- {3- [4- (1H-benzoimidazol-2-yl) piperidin-1-yl] -2-hydroxypropyl} -3- (4-trifluoromethylphenyl) -1,4,6,7-tetrahydropyrazolo [ 4,3-c] pyridin-5-yl] ethanone;

6-chloro-4- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl ] propyl} piperidin-4-yl) -4H-benzo [1,4] oxazin-3-one;

6-chloro-1- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl ] propyl} piperidin-4-yl) -3,4-dihydro-1H-quinolin-2-one;

6-chloro-1- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl ] propyl} piperidin-4-yl) -3,4-dihydro-1H-quinazolin-2-one;

1- [4- (6-chloro-2,2-dioxo-3,4-dihydro-2H-2λ ^6- benzo [1,2,6] thiadiazin-1-yl) piperidin-1-yl] -3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propan-2-ol;

4- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidine -4-yl) -4H-pyrido [3,2-b] [1,4] oxazin-3-one;

5-chloro-1- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl ] propyl} piperidin-4-yl) -1,3-dihydroindol-2-one;

1- [4- (6-chloroindol-1-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- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] propyl} piperidin-4-yl ) -1H-benzotriazole;

amide 1- {3- [4- (3-methyl-2-oxo-2,3-dihydrobenzoimidazol-1-yl) piperidin-1-yl] propyl} -3- (4-trifluoromethylphenyl) -1,4,6 , 7-tetrahydropyrazolo [4,3-c] pyridin-5-sulfonic acid;

5-chloro-3- (1- {2-hydroxy-3- [4-pyridin-4-yl-3- (4-trifluoromethylphenyl) pyrazolyl-1-yl] propyl} piperidin-4-yl) -1-methyl -1,3-dihydrobenzoimidazol-2-one;

4- (1- {2-hydroxy-3- [4-pyrazin-2-yl-3- (4-trifluoromethylphenyl) pyrazolyl-1-yl] propyl) piperidin-4-yl) -4H-benzo [1,4 ] oxazin-3-one;

(S) -1- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl ] propyl} piperidin-4-yl) -3-methyl-1,3-dihydrobenzoimidazol-2-one and

(S) -5-dimethylamino-3- (1- {2-hydroxy-3- [5-methanesulfonyl-3- (4-trifluoromethylphenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridine -1-yl] propyl} piperidin-4-yl) -1-methyl-1,3-dihydroimidazo [4,5-b] pyridin-2-one.

11. The method according to claim 1, where the specified compound is selected from

1- (1- {3- [5-acetyl-3- (4-bromophenyl) -4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl] -2-hydroxypropyl} piperidin- 4-yl) -5-methoxy-1,3-dihydrobenzoimidazol-2-one;

6-chloro-1- (1- {3- [3- (4-chloro-3-methylphenyl) -5-methanesulfonyl-4,5,6,7-tetrahydropyrazolo [4,3-c] pyridin-1-yl ] -2-hydroxypropyl} piperidin-4-yl) -1,3-dihydrobenzoimidazol-2-one.

12. The method according to claim 1, where the specified pharmaceutical composition is made in a dosage amount suitable for the treatment of an allergic condition.