Search

US-12617786-B2 - Dihydro-cyclopenta-isoquinoline sulfonamides derivatives

US12617786B2US 12617786 B2US12617786 B2US 12617786B2US-12617786-B2

Abstract

The present invention relates to dihydro-cyclopenta-isoquinoline derivatives of formula (I): processes for preparing them, pharmaceutical compositions containing them and their use in treating disorders caused by IgE (such as allergic responses, non-allergic mast cell responses or certain autoimmune responses), and in particular, disorders caused by the interaction of IgE with the FcεRI receptor.

Inventors

  • Timothy John Norman
  • GREGORY WILLIAM HASLETT
  • Benedicte Lallemand
  • Nathaniel Julius Thomas Monck
  • Julian Hugh Rowley
  • Giancarlo Trani
  • Zhaoning Zhu
  • Selvaratnam SUGANTHAN
  • Konstantinos RAMPALAKO
  • James Madden
  • Jag Paul Heer
  • Richard Jeremy Franklin
  • RICKKI LEE CONNELLY
  • Thierry Demaude

Assignees

  • UCB Biopharma SRL

Dates

Publication Date
20260505
Application Date
20201222
Priority Date
20191223

Claims (19)

  1. 1 . A compound of general formula (I) or a pharmaceutically acceptable salt thereof, Wherein: X is C or N, Y is C or O, When Y is O, R1 is hydrogen or hydroxy, R1′ is hydrogen and R2 and R2′ are absent; R1 represents Hydrogen; Hydroxy; An oxo group; Amino; C1-6-alkyl; C1-6-alkylamino; C(O)OH; C(O)NH-Heteroaryl; —NH—C1-6-alkyl-C3-6-cycloalkyl; —NH—C1-6-alkyl-C(O)OH optionally substituted with an amino group; —NH-cycloalkyl optionally substituted with one or more groups which are independently halogen; oxo; C1-6-alkyl; C1-6-alkylamino; C1-6-alkyl-C1-4-alkylamino; C3-8-cycloalkyl-C1-6-alkylamino; heteroaryl; or heteroarylamino optionally substituted with one or more C1-6-alkyl; Heteroaryl optionally substituted with one or more groups which are independently Halogen; hydroxy; oxo; amino; cyano; —C(O)—C1-6-alkyl; C1-6-alkyl; C1-6-alkylamino; C1-6-alkoxy; —NH—(C1-6-alkyl)-heterocycloalkyl; —NH—(C1-6-alkyl)-heteroaryl optionally substituted with one or more C1-6-alkyl; —NH—C1-6-alkyl-cycloalkyl; —NH—C(O)-cycloalkyl; —NH-heteroaryl substituted with one or more C1-6-alkyl; or —NH—C1-6-alkyl-C(O)OH; Heteroaryl substituted with heteroarylamino optionally substituted with C1-6-alkyl; C1-6-alkoxy; C3-6-cycloalkyl; C1-6-haloalkoxy, C1-6-haloalkyl; CN, halogen; C(O)OH, or —C(O)O—C1-6-alkyl; —NH—C(S)—NH—Ra 1 ; —NH—SO2-Rb 1 ; —NH-heteroaryl optionally substituted with one or more groups which are independently oxo; C1-6-alkyl; C1-6-alkylamino; heteroaryl optionally substituted with one or more oxo; C1-6-alkyl; —C(O)—NHNH—C(O)CH3; aryl; heteroarylamino; C1-6-alkoxy; C3-6-cycloalkyl; C1-6-haloalkoxy, C1-6-haloalkyl; CN, halogen; C(O)OH, or —C(O)O—C1-6-alkyl; —NH-heterocycloalkyl optionally substituted with one or more groups which are independently Halogen; C1-6-alkyl; oxo; heteroaryl; C(O)ORb 1 ; C1-6-alkyl-NRb 1 Rb 1 ; NHC(O)-aryl; or NHC(O)-heteroaryl; —NH—C1-6-Alkyl substituted with one heteroaryl group optionally substituted with one or more groups which are independently C1-6-alkyl or amino; —NH—C(O)O—Rb 1 ; NH—C(NCN)—NH—Ra 1 ; —NH—C(NCN)—NH-Heteroaryl; —NH—C(O)—C3-8-heterocycloalkyl-C(O)O—Rb 1 ; —C(O)NH—C1-6-alkyl; —NH—C(O)NH—C1-6-alkyl optionally substituted with one or more C3-8-heterocyclolakyl; —NH—C(O)NH-heterocycloalkyl-C1-6-alkyl; —NH—C1-6-alkyl-C(O)—C1-6-alkylamino; Heteroaryloxy; —NH—C(O)-aryl; —NH—C(O)-heteroaryl; —NH—C(O)-heterocycloalkyl; —NH—C(O)—C1-6-alkyl optionally substituted with one or more amino group; —NH—C(O)—C1-6-alkyl-C(O)ORb 1 optionally substituted with amino; —NH—C(O)ORb 1 Heterocycloalkyl optionally substituted with one or more groups which are independently amino; —C(O)NH—Rb 1 ; —C(O)ORb 1 ; —NHC(O)-heteroaryl optionally substituted with one or more C1-6-alkyl; —NHC(O)—C1-6-alkyl optionally substituted with an amino group; or —NHC(O)O—C1-6-alkyl; —NH—C(O)Rb 1 ; or —C2-6-alkene group optionally substituted with one or more groups which are halogen; or ═NH group; Ra 1 represents C1-6-alkyl; Aryl optionally substituted with one or more C1-6-alkyl; or Heteroaryl optionally substituted with one or more C1-6-alkyl; Rb 1 represents Hydrogen; C1-6-alkyl; or Aryl optionally substituted with one or more halogen; C1-6-alkyl; or hydroxy; R1′ represents hydrogen; or hydroxy; R2 represents hydrogen; Halogen; A hydroxy group; An oxo group; C1-6-alkyl; C3-8-heterocycloalkyl optionally substituted with one or more hydroxy; Halogen; amino; amino-C-1-6-alkyl; C1-6-alkyl; C(O)O—C1-6-alkyl; or C(O)NH2; Heteroaryl optionally substituted with one or more groups which are independently C1-6-alkylamino; heteroaryl optionally substituted with one or more C1-6-alkyl; halogen; Heteroaryl optionally substituted with —NH-heteroaryl optionally substituted with one or more C1-6-alkyl; halogen; cyano; —C(O)OH; —C(O)O—C1-6-alkyl, C1-6-haloalkyl; C1-6-alkoxy; C1-6-haloalkoxy; or C3-6-cycloalkyl; —NH-cycloalkyl optionally substituted with one or more groups which are independently halogen; oxo; C1-6-alkyl; C1-6-alkylamino; C1-6-alkyl-C1-4-alkylamino; C3-8-cycloalkyl-C1-6-alkylamino; aryl; heteroaryl; or heteroarylamino optionally substituted with one or more C1-6-alkyl; —NH-heteroaryl optionally substituted with one or more groups which are independently hydroxy; halogen; oxo; C1-6-alkyl; C1-6-alkoxy; heteroaryl optionally substituted with one or more hydroxy; Halogen; oxo; C1-6-alkyl; C(O)O—C1-6-alkyl; C(O)OH; C1-6-haloalkyl; C1-6-alkoxy; C1-6-haloalkoxy; C3-6-cycloalkyl; C1-6-alkylamino; cyano; or heterocycloalkyl substituted with one or more hydroxy Halogen; oxo group; —NH—C1-6-Alkyl substituted with one heteroaryl group optionally substituted with one or more independently selected C1-6-alkyl groups; —NH—SO2-Heteroaryl optionally substituted with one or more halogen; —NHC(O)—C1-6-alkyl optionally substituted with one or more halogen; C1-6-alkoxy; amino; C3-8-cycloalkyl; C3-8-heterocycloalkyl; or heteroaryl; —NHC(O)-heteroaryl optionally substituted with one or more groups which are independently halogen; hydroxy; oxo; C1-6-alkyl; heteroaryl; C1-6-alkylamino; S(O)2-C1-3-alkyl; or —NHC(O)—C1-6-alkyl; —NHC(O)—C3-8-heterocycloalkyl optionally substituted with one or more oxo; or C1-6-alkyl; —NHC(O)O—C1-6-alkyl; —NHC(O)O—C1-6-alkyl-Ra 2 ; —NHC(O)O-aryl; —NHC(O)NH—Ra 2 ; —NHC(O)NH—C1-6-alkyl-Ra 2 ; —NH—C(NCN)—NH—Ra 1 ; —NHC(O)—C3-8-cycloalkyl; —NH—SO 2 —Rb 2 ; —NH—C(S)—NH—Rb 2 ; —NH—C3-8-heterocycloalkyl optionally substituted with one or more groups which are independently oxo; or C1-6-alkyl; An Aryloxy group; or Heteroaryloxy group; Ra 2 represents Hydrogen; Aryl optionally substituted with one or more groups which are independently halogen; hydroxy; oxo; or C1-6-alkyl; Heteroaryl optionally substituted with one or more groups which are independently halogen; hydroxy; oxo; or C1-6-alkyl; Rb 2 represents C1-6-alkyl; or Heteroaryl; R2′ represents hydrogen; or hydroxy; R3 represents C1-6-alkyl optionally substituted with one or more independently selected R3 a groups; C1-3-alkanediyl-C3-6-cycloalkyl optionally substituted with one or more independently selected R3 a groups; C1-3-alkanediyl-C3-6-heterocycloalkyl optionally substituted with one or more independently selected R3 a groups; C3-6-heterocycloalkyl optionally substituted with one or more independently selected R3 a groups; or C3-6-cycloalkyl optionally substituted with one or more independently selected R3 a groups; R3 a represents hydrogen; Halogen; C1-2-alkyl; hydroxy; or C1-2-alkoxy; R4 represents: C3-6-cycloalkyl optionally substituted with one or more R4 a group; or C1-6-alkanediyl-C3-6-cycloalkyl optionally substituted with one or more R4 a group; or C1-6-alkanediyl-C3-6-heterocycloalkyl optionally substituted with one or more R4 a group; R4 a represents a group which are independently hydroxy; Halogen; or C1-2-alkyl; and R5 represents Hydrogen, methyl or halogen; With the proviso that: when R1′ is hydroxy, then R1 is pyridyl or C1-6-alkyl; when R2′ is hydroxy, then R2 is pyridyl or C1-6-alkyl; when R1 is different than hydrogen, then R2 and R2′ are hydrogen; when R2 is different than hydrogen, then R1 and R1′ are hydrogen; when R1 is oxo, R1′ is absent; and when R2 is oxo, R2′ is absent.
  2. 2 . A compound of general formula (I) according to claim 1 , wherein R4 represents cyclopropyl or spiro[2.2]pentanyl; each of which is optionally substituted with one or more groups which are independently hydroxy; chloro, fluoro, bromo; or methyl.
  3. 3 . A compound of general formula (I) according to claim 1 , wherein R4 represents cyclopropyl.
  4. 4 . A compound of general formula (I) according to claim 1 , wherein R1 represents: Hydrogen; methoxyimidazopyridinyl; carboxy group; cyclopropyl-methyl-carbamoyl-amino; pyridine-carbonylamino; hydroxy(pyridyl); [(fluorocarbonimidoyl)propenyl]; [(cyclopropylmethylamino)imidazolyl]; [[(cyclopropylmethyl)imidazolyl]amino]; [(dimethylpyrazolyl)carbamothioylamino]; [[(dimethylpyrazolyl)-triazolyl]amino]; (pyridylamino); (tert-butoxycarbonylamino); Amino; [(cyclopropylmethylamino)-triazolyl]; pyridylcarbamoyl; [(cyclopropanecarbonylamino)pyrazolyl]; (aminotetrazolyl); [[(methyltetrazolyl)pyridyl]amino]; [(methylpyrazolopyridinyl)amino]; [[(methyl-oxadiazolyl)-pyridyl]amino]; Oxo; hydroxy(methyl); ethylcarbamothioylamino); [(ethylamino)-triazolyl]; [[(ethylamino)-dioxo-cyclobutenyl]amino]; [[(ethylamino)-dioxo-thiadiazolyl]amino]; [[N′-cyano-N-(p-tolyl)carbamimidoyl]amino]; [(tert-butoxycarbonylazetidine-carbonyl)amino]; [aminopiperidyl]; [(methylcarbamoyl)pyrrolidinyl]; [[(dimethylpyrazole-arbonyl)amino]azetidinyl]; [(dimethyl-oxo-cyclobutenyl)amino]; (indolylmethylamino); Methanesulfonamido; [[dioxo(pyridylamino)cyclobutenyl]amino]; ethylcarbamoylamino; [[(dimethylpyrazolyl)amino]-triazolyl]; [[(methyl-pyridyl)amino]-triazolyl]; [[(pyridyl)-triazolyl]amino]; [(pyridylamino)-triazolyl]; (benzimidazolylamino); pyridyloxy; (pyridylcarbamothioylamino).
  5. 5 . A compound of general formula (I) according to claim 1 , wherein R2 represents: Hydrogen; [(methylbenzotriazolyl)-triazolyl]methyl; [[(methylpyrazolyl)-triazolyl]amino]; [[(methylpyrazolyl)amino]-triazolyl]; [[(fluoro-pyridyl)-triazolyl]amino]; [[(fluoro-pyridyl)amino]-triazolyl]; (pyridylmethylamino); (pyridylsulfonylamino); [(fluoro-indolecarbonyl)amino]; [(methylbenzimidazolyl)amino]; [(methoxycarbonyl-pyridyl)amino]; [(carboxypyridyl)amino]; [(methyl-pyrazole-carbonyl)amino]; (pyridine-carbonylamino); [(methylcyclopropanecarbonyl)amino]; (pyrimidinylamino); [(oxoindolinyl)amino]; [(methoxypyridyl)amino]; (pyridylamino); [(methylpyrazolopyridinyl)amino]; Benzyloxycarbonylamino; [(bromophenyl)carbamoylamino]; [(dimethylpyrazolyl)methylcarbamoylamino]; Hydroxy; Oxo; Methyl; Fluorine; [[(ethylamino)-dioxo-thiadiazolyl]amino]; [(cyanomethyl-pyrazolyl)amino]; (isoquinolylamino); [[N′-cyano-N-(p-tolyl)carbamimidoyl]amino]; Methanesulfonamido; Ethylcarbamothioylamino; [(ethylamino)-triazolyl]; [(ethyl-triazolyl)amino]; (pyridylcarbamothioylamino); [[(pyridyl)-triazolyl]amino]; [[(methyltetrazolyl)-pyridyl]amino]; [[dioxo-(pyridylamino)cyclobutenyl]amino]; [[(ethylamino)-dioxo-cyclobutenyl]amino]; (benzimidazolylamino); pyridyloxy.
  6. 6 . A compound of formula (I) according to claim 1 wherein R1 represents Hydrogen; (7-methoxyimidazo[4,5-b]pyridin-3-yl); Carboxy group; cyclopropyl-methyl-carbamoyl-amino; pyridine-3-carbonylamino; hydroxy(3-pyridyl); [1-(fluorocarbonimidoyl)prop-1-enyl]; [2-(cyclopropylmethylamino)imidazol-1-yl]; [[1-(cyclopropylmethyl)imidazol-2-yl]amino]; [(2,5-dimethylpyrazol-3-yl)carbamothioylamino]; [[4-(2,5-dimethylpyrazol-3-yl)-1,2,4-triazol-3-yl]amino]; (3-pyridylamino); (tert-butoxycarbonylamino); Amino; [3-(cyclopropylmethylamino)-1,2,4-triazol-4-yl]; 3-pyridylcarbamoyl; [5-(cyclopropanecarbonylamino)pyrazol-1-yl]; (5-aminotetrazol-1-yl); [[6-(2-methyltetrazol-5-yl)-3-pyridyl]amino]; [(1-methylpyrazolo[3,4-c]pyridin-4-yl)amino]; [[6-(5-methyl-1,3,4-oxadiazol-2-yl)-3-pyridyl]amino]; oxo; hydroxy(methyl); (ethylcarbamothioylamino); [3-(ethylamino)-1,2,4-triazol-4-yl]; [[2-(ethylamino)-3,4-dioxo-cyclobuten-1-yl]amino]; [[4-(ethylamino)-1,1-dioxo-1,2,5-thiadiazol-3-yl]amino]; [[N′-cyano-N-(p-tolyl)carbamimidoyl]amino]; [(1-tert-butoxycarbonylazetidine-3-carbonyl)amino]; [3-amino-1-piperidyl]; [(2R)-2-(methylcarbamoyl)pyrrolidin-1-yl]; [3-[(2,5-dimethylpyrazole-3-carbonyl)amino]azetidin-1-yl]; [(4,4-dimethyl-3-oxo-cyclobuten-1-yl)amino]; (1H-indol-2-ylmethylamino); Methanesulfonamido; [[3,4-dioxo-2-(3-pyridylamino)cyclobuten-1-yl]amino]; ethylcarbamoylamino; [3-[(2,5-dimethylpyrazol-3-yl)amino]-1,2,4-triazol-4-yl]; [3-[(5-methyl-3-pyridyl)amino]-1,2,4-triazol-4-yl]; [[4-(3-pyridyl)-1,2,4-triazol-3-yl]amino]; [3-(3-pyridylamino)-1,2,4-triazol-4-yl]; (1H-benzimidazol-2-ylamino); 3-pyridyloxy; (3-pyridylcarbamothioylamino).
  7. 7 . A compound of general formula (I) according claim 1 wherein R2 represents Hydrogen; [4-(1-methylbenzotriazol-4-yl)-1,2,4-triazol-3-yl]methyl; [[4-(2-methylpyrazol-3-yl)-1,2,4-triazol-3-yl]amino]; [3-[(2-methylpyrazol-3-yl)amino]-1,2,4-triazol-4-yl]; [[4-(5-fluoro-3-pyridyl)-1,2,4-triazol-3-yl]amino]; [3-[(5-fluoro-3-pyridyl)amino]-1,2,4-triazol-4-yl]; (3-pyridylmethylamino); (3-pyridylsulfonylamino); [(6-fluoro-1H-indole-3-carbonyl)amino]; [(1-methylbenzimidazol-2-yl)amino]; [(6-methoxycarbonyl-3-pyridyl)amino]; [(6-carboxy-3-pyridyl)amino]; [(5-methyl-1H-pyrazole-3-carbonyl)amino]; (pyridine-3-carbonylamino); [(2-methylcyclopropanecarbonyl)amino]; (pyrimidin-5-ylamino); (2-oxoindolin-5-yl)amino; [(5-methoxy-3-pyridyl)amino]; (3-pyridylamino); [(1-methylpyrazolo[3,4-c]pyridin-4-yl)amino]; Benzyloxycarbonylamino; [(4-bromophenyl)carbamoylamino]; [(2,5-dimethylpyrazol-3-yl)methylcarbamoylamino]; Hydroxy oxo; Methyl; fluorine; [[4-(ethylamino)-1,1-dioxo-1,2,5-thiadiazol-3-yl]amino]; [(4-cyano-1-methyl-pyrazol-3-yl)amino]; (4-isoquinolylamino); [[N′-cyano-N-(p-tolyl)carbamimidoyl]amino]; Methanesulfonamido; Ethylcarbamothioylamino; [3-(ethylamino)-1,2,4-triazol-4-yl]; [(4-ethyl-1,2,4-triazol-3-yl)amino]; (3-pyridylcarbamothioylamino); [[4-(3-pyridyl)-1,2,4-triazol-3-yl]amino]; [[6-(2-methyltetrazol-5-yl)-3-pyridyl]amino]; [[3,4-dioxo-2-(3-pyridylamino)cyclobuten-1-yl]amino]; [[2-(ethylamino)-3,4-dioxo-cyclobuten-1-yl]amino]; (1H-benzimidazol-2-ylamino); 3-pyridyloxy.
  8. 8 . A compound of general formula (I) according to claim 1 which is 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-7-(7-methoxyimidazo[4,5-b]pyridin-3-yl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-isobutyl-9-[[4-(1-methylbenzotriazol-4-yl)-1,2,4-triazol-3-yl]amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-isobutyl-9-[[4-(2-methylpyrazol-3-yl)-1,2,4-triazol-3-yl]amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-isobutyl-9-[3-[(2-methylpyrazol-3-yl)amino]-1,2,4-triazol-4-yl]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-9-[[4-(5-fluoro-3-pyridyl)-1,2,4-triazol-3-yl]amino]-N-isobutyl-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-9-[3-[(5-fluoro-3-pyridyl)amino]-1,2,4-triazol-4-yl]-N-isobutyl-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-5-[(2-fluoro-2-methylpropyl)sulfamoyl]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-7-carboxylic acid; 1-(cyclopropylmethyl)-3-[(7R*)-3-cyclopropyl-5-[(2-fluoro-2-methylpropyl)sulfamoyl]-8,9-dihydro-7H-cyclopenta[h]isoquinolin-7-yl]urea [* or S]; N-[(7R*)-3-cyclopropyl-5-[(2-fluoro-2-methylpropyl)sulfamoyl]-8,9-dihydro-7H-cyclopenta[h]isoquinolin-7-yl]pyridine-3-carboxamide [* or S]; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-7-hydroxy-7-pyridin-3-yl-8,9-dihydrocyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-7-(2-fluoropyridin-3-yl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; (7R*)-3-cyclopropyl-7-[2-(cyclopropylmethylamino)imidazol-1-yl]-N-(2-fluoro-2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide [* or S]; (7R*)-3-cyclopropyl-7-[[1-(cyclopropylmethyl)imidazol-2-yl]amino]-N-(2-fluoro-2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide [* or S]; 3-cyclopropyl-N-(2-methylpropyl)-9-(pyridin-3-ylmethylamino)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-methylpropyl)-9-(pyridin-3-ylsulfonylamino)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 6-fluoro-N-[(9R*)-3-cyclopropyl-5-[(2-fluoro-2-methylpropyl)sulfamoyl]-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]-1H-indole-3-carboxamide [* or S]; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-9-[(1-methylbenzimidazol-2-yl)amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; methyl 5-[[3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]amino]pyridine-2-carboxylate; 5-[[3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]amino]pyridine-2-carboxylic acid; 5-methyl-N-[(9R*)-3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]-1H-pyrazole-3-carboxamide [* or S]; N-[(9R*)-3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]pyridine-3-carboxamide [* or S]; 3-cyclopropyl-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]cinnoline-5-sulfonamide; 1-[3-cyclopropyl-5-[(2-fluoro-2-methylpropyl)sulfamoyl]-8,9-dihydro-7H-cyclopenta[h]cinnolin-7-yl]-3-(2,5-dimethylpyrazol-3-yl)thiourea; 3-cyclopropyl-7-[[4-(2,5-dimethylpyrazol-3-yl)-1,2,4-triazol-3-yl]amino]-N-(2-fluoro-2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]cinnoline-5-sulfonamide; (7R*)-3-cyclopropyl-7-[3-[(25-dimethylpyrazol-3-yl)amino]-1,2,4-triazol-4-yl]-N-(2-fluoro-2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]cinnoline-5-sulfonamide [* or S]; N-[3-cyclopropyl-5-[(2-fluoro-2-methylpropyl)sulfamoyl]-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]-2-methylcyclopropane-1-carboxamide; 3-cyclopropyl-4-fluoro-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-9-(pyrimidin-5-ylamino)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-9-[(2-oxo-1,3-dihydroindol-5-yl)amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-9-[(5-methoxypyridin-3-yl)amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-7-(pyridin-3-ylamino)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-9-(pyridin-3-ylamino)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; tert-butyl N-[3-cyclopropyl-5-[(1,1-dideuterio-2-methylpropyl)sulfamoyl]-8,9-dihydro-7H-cyclopenta[h]isoquinolin-7-yl]carbamate; 7-amino-3-cyclopropyl-N-(1,1-dideuterio-2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-7-[3-(cyclopropylmethylamino)-1,2,4-triazol-4-yl]-N-(1,1-dideuterio-2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 7-cyclopropyl-N-(2-fluoro-2-methylpropyl)-3-hydroxy-2,3-dihydrofuro[3,2-h]isoquinoline-5-sulfonamide; (7R*)-3-cyclopropyl-5-[(2-fluoro-2-methylpropyl)sulfamoyl]-N-pyridin-3-yl-8,9-dihydro-7H-cyclopenta[h]isoquinoline-7-carboxamide [* or S]; N-[2-[3-cyclopropyl-5-[(2-fluoro-2-methylpropyl)sulfamoyl]-8,9-dihydro-7H-cyclopenta[h]isoquinolin-7-yl]pyrazol-3-yl]cyclopropanecarboxamide; 7-(5-aminotetrazol-1-yl)-3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-7-[[6-(2-methyltetrazol-5-yl)pyridin-3-yl]amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-7-[(1-methylpyrazolo[3,4-c]pyridin-4-yl)amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-7-[[6-(5-methyl-1,3,4-oxadiazol-2-yl)pyridin-3-yl]amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-9-[(1-methylpyrazolo[3,4-c]pyridin-4-yl)amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; benzyl N-[3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]carbamate; 1-(4-bromophenyl)-3-[3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]urea; 1-[3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]-3-[(2,5-dimethylpyrazol-3-yl)methyl]urea; 3-cyclopropyl-7-hydroxy-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-methylpropyl)-7-oxo-8,9-dihydrocyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-7-hydroxy-7-methyl-N-(2-methylpropyl)-8,9-dihydrocyclopenta[h]isoquinoline-5-sulfonamide; 7-amino-3-cyclopropyl-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 1-[3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-7-yl]-3-ethylthiourea; (7R*)-3-cyclopropyl-7-[3-(ethylamino)-1,2,4-triazol-4-yl]-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide (* or S); (7R*)-3-cyclopropyl-7-[[2-(ethylamino)-3,4-dioxocyclobuten-1-yl]amino]-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide (* or S); 3-cyclopropyl-7-[[4-(ethylamino)-1,1-dioxo-1,2,5-thiadiazol-3-yl]amino]-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 2-cyano-1-[3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-7-yl]-3-(4-methylphenyl)guanidine; tert-butyl 3-[[(7R*)-3-cyclopropyl-5-[(2-fluoro-2-methylpropyl)sulfamoyl]-8,9-dihydro-7H-cyclopenta[h]isoquinolin-7-yl]carbamoyl]azetidine-1-carboxylate [* or S]; 7-[(3R)-3-aminopiperidin-1-yl]-3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; (2R)-1-[(7R*)-3-cyclopropyl-5-[(2-fluoro-2-methylpropyl)sulfamoyl]-8,9-dihydro-7H-cyclopenta[h]isoquinolin-7-yl]-N-methylpyrrolidine-2-carboxamide [* or S]; N-[1-[3-cyclopropyl-5-[(2-fluoro-2-methylpropyl)sulfamoyl]-8,9-dihydro-7H-cyclopenta[h]isoquinolin-7-yl]azetidin-3-yl]-2,5-dimethylpyrazole-3-carboxamide; 3-cyclopropyl-7-[(4,4-dimethyl-3-oxocyclobuten-1-yl)amino]-N-(2-fluoro-2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-7-(1H-indol-2-ylmethylamino)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-9-hydroxy-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-methylpropyl)-9-oxo-7,8-dihydrocyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-9-hydroxy-9-methyl-N-(2-methylpropyl)-7,8-dihydrocyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-9-fluoro-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-9-[[4-(ethylamino)-1,1-dioxo-1,2,5-thiadiazol-3-yl]amino]-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 9-[(4-cyano-1-methylpyrazol-3-yl)amino]-3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-9-(isoquinolin-4-ylamino)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 2-cyano-1-[3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]-3-(4-methylphenyl)guanidine; 3-cyclopropyl-9-(methanesulfonamido)-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 1-[3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]-3-ethylthiourea; 3-cyclopropyl-9-[3-(ethylamino)-1,2,4-triazol-4-yl]-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; (9R*)-3-cyclopropyl-9-[(4-ethyl-1,2,4-triazol-3-yl)amino]-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide [* or S]; 1-[3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-9-yl]-3-pyridin-3-ylthiourea; 3-cyclopropyl-N-(2-methylpropyl)-9-[(4-pyridin-3-yl-1,2,4-triazol-3-yl)amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-9-[[6-(5-methyl-1,3,4-oxadiazol-2-yl)pyridin-3-yl]amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-9-[[6-(2-methyltetrazol-5-yl)pyridin-3-yl]amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-9-[[3,4-dioxo-2-(pyridin-3-ylamino)cyclobuten-1-yl]amino]-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; (9R*)-3-cyclopropyl-9-[[2-(ethylamino)-3,4-dioxocyclobuten-1-yl]amino]-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide [* or S]; (9R*)-9-(1H-benzimidazol-2-ylamino)-3-cyclopropyl-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide [* or S]; 3-cyclopropyl-7-[3-(cyclopropylmethylamino)-1,2,4-triazol-4-yl]-N-(3,3-difluorocyclobutyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-7-[3-(cyclopropylmethylamino)-1,2,4-triazol-4-yl]-N-(3-fluorocyclobutyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-7-(methanesulfonamido)-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-7-[[3,4-dioxo-2-(pyridin-3-ylamino)cyclobuten-1-yl]amino]-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 1-ethyl-3-[(7R*)-3-cyclopropyl-5-(2-methylpropylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-7-yl]urea [* or S]; (7R*)-3-cyclopropyl-7-[3-[(25-dimethylpyrazol-3-yl)amino]-1,2,4-triazol-4-yl]-N-(2-fluoro-2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide [* or S]; (7R*)-3-cyclopropyl-7-[3-[(25-dimethylpyrazol-3-yl)amino]-1,2,4-triazol-4-yl]-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide [* or S]; 3-cyclopropyl-7-[[4-(2,5-dimethylpyrazol-3-yl)-1,2,4-triazol-3-yl]amino]-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; (7R*)-3-cyclopropyl-N-(2-methylpropyl)-7-[3-[(5-methyl pyridin-3-yl)amino]-12,4-triazol-4-yl]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide [* or S]; 3-cyclopropyl-N-(2-methylpropyl)-7-[(4-pyridin-3-yl-1,2,4-triazol-3-yl)amino]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-methylpropyl)-7-[3-(pyridin-3-ylamino)-1,2,4-triazol-4-yl]-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 7-(1H-benzimidazol-2-ylamino)-3-cyclopropyl-N-(2-methylpropyl)-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-9-pyridin-3-yloxy-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; 3-cyclopropyl-N-(2-fluoro-2-methylpropyl)-7-pyridin-3-yloxy-8,9-dihydro-7H-cyclopenta[h]isoquinoline-5-sulfonamide; or 1-[3-cyclopropyl-5-(isobutylsulfamoyl)-8,9-dihydro-7H-cyclopenta[h]isoquinolin-7-yl]-3-(3-pyridyl)thiourea.
  9. 9 . A method for the treatment or prevention of disorders caused by IgE comprising administration to a patient in need thereof a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
  10. 10 . A method for the treatment or prevention of allergy, non-allergic mast cell responses, type 1 hypersensitivity, urticaria, or familiar sinus inflammation comprising administration to a patient in need thereof a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
  11. 11 . A method for the treatment or prevention of airway constriction in asthma, local inflammation in eczema, increased mucus secretion in allergic rhinitis, urticaria, or increased vascular permeability comprising administration to a patient in need thereof a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
  12. 12 . A method for the treatment or prevention of eosinophilic granulomatosis with polyangiitis, aspirin exacerbated respiratory disease, or cutaneous T-cell lymphoma comprising administration to a patient in need thereof a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
  13. 13 . A pharmaceutical composition comprising a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
  14. 14 . A method for the treatment or prevention of allergy, non-allergic mast cell responses, type 1 hypersensitivity, urticaria, familiar sinus inflammation, eosinophilic granulomatosis with polyangiitis, aspirin exacerbated respiratory disease, or cutaneous T-cell lymphoma, which comprises the administration of a compound according to claim 1 or a pharmaceutically acceptable salt thereof in a therapeutically effective amount to a patient.
  15. 15 . A compound of general formula (I) according to claim 1 , wherein R4 represents cyclopropyl.
  16. 16 . A compound of general formula (I) according to claim 1 , wherein R1 represents: Hydrogen; methoxyimidazopyridinyl; carboxy group; cyclopropyl-methyl-carbamoyl-amino; pyridine-carbonylamino; hydroxy(pyridyl); [(fluorocarbonimidoyl)propenyl]; [(cyclopropylmethylamino)imidazolyl]; [[(cyclopropylmethyl)imidazolyl]amino]; [(dimethylpyrazolyl)carbamothioylamino]; [[(dimethylpyrazolyl)-triazolyl]amino]; (pyridylamino); (tert-butoxycarbonylamino); Amino; [(cyclopropylmethylamino)-triazolyl]; pyridylcarbamoyl; [(cyclopropanecarbonylamino)pyrazolyl]; (aminotetrazolyl); [[(methyltetrazolyl)pyridyl]amino]; [(methylpyrazolopyridinyl)amino]; [[(methyl-oxadiazolyl)-pyridyl]amino]; Oxo; hydroxy(methyl); ethylcarbamothioylamino); [(ethylamino)-triazolyl]; [[(ethylamino)-dioxo-cyclobutenyl]amino]; [[(ethylamino)-dioxo-thiadiazolyl]amino]; [[N′-cyano-N-(p-tolyl)carbamimidoyl]amino]; [(tert-butoxycarbonylazetidine-carbonyl)amino]; [aminopiperidyl]; [(methylcarbamoyl)pyrrolidinyl]; [[(dimethylpyrazole-arbonyl)amino]azetidinyl]; [(dimethyl-oxo-cyclobutenyl)amino]; (indolylmethylamino); Methanesulfonamido; [[dioxo(pyridylamino)cyclobutenyl]amino]; ethylcarbamoylamino; [[(dimethylpyrazolyl)amino]-triazolyl]; [[(methyl-pyridyl)amino]-triazolyl]; [[(pyridyl)-triazolyl]amino]; [(pyridylamino)-triazolyl]; (benzimidazolylamino); pyridyloxy; (pyridylcarbamothioylamino).
  17. 17 . A compound of general formula (I) according to claim 1 , wherein R2 represents: Hydrogen; [(methylbenzotriazolyl)-triazolyl]methyl; [[(methylpyrazolyl)-triazolyl]amino]; [[(methylpyrazolyl)amino]-triazolyl]; [[(fluoro-pyridyl)-triazolyl]amino]; [[(fluoro-pyridyl)amino]-triazolyl]; (pyridylmethylamino); (pyridylsulfonylamino); [(fluoro-indolecarbonyl)amino]; [(methylbenzimidazolyl)amino]; [(methoxycarbonyl-pyridyl)amino]; [(carboxypyridyl)amino]; [(methyl-pyrazole-carbonyl)amino]; (pyridine-carbonylamino); [(methylcyclopropanecarbonyl)amino]; (pyrimidinylamino); [(oxoindolinyl)amino]; [(methoxypyridyl)amino]; (pyridylamino); [(methylpyrazolopyridinyl)amino]; Benzyloxycarbonylamino; [(bromophenyl)carbamoylamino]; [(dimethylpyrazolyl)methylcarbamoylamino]; Hydroxy; Oxo; Methyl; Fluorine; [[(ethylamino)-dioxo-thiadiazolyl]amino]; [(cyanomethyl-pyrazolyl)amino]; (isoquinolylamino); [[N′-cyano-N-(p-tolyl)carbamimidoyl]amino]; Methanesulfonamido; Ethylcarbamothioylamino; [(ethylamino)-triazolyl]; [(ethyl-triazolyl)amino]; (pyridylcarbamothioylamino); [[(pyridyl)-triazolyl]amino]; [[(methyltetrazolyl)-pyridyl]amino]; [[dioxo-(pyridylamino)cyclobutenyl]amino]; [[(ethylamino)-dioxo-cyclobutenyl]amino]; (benzimidazolylamino); pyridyloxy.
  18. 18 . A compound of formula (I) according to claim 1 wherein R1 represents Hydrogen; (7-methoxyimidazo[4,5-b]pyridin-3-yl); Carboxy group; cyclopropyl-methyl-carbamoyl-amino; pyridine-3-carbonylamino; hydroxy(3-pyridyl); [1-(fluorocarbonimidoyl)prop-1-enyl]; [2-(cyclopropylmethylamino)imidazol-1-yl]; [[1-(cyclopropylmethyl)imidazol-2-yl]amino]; [(2,5-dimethylpyrazol-3-yl)carbamothioylamino]; [[4-(2,5-dimethylpyrazol-3-yl)-1,2,4-triazol-3-yl]amino]; (3-pyridylamino); (tert-butoxycarbonylamino); Amino; [3-(cyclopropylmethylamino)-1,2,4-triazol-4-yl]; 3-pyridylcarbamoyl; [5-(cyclopropanecarbonylamino)pyrazol-1-yl]; (5-aminotetrazol-1-yl); [[6-(2-methyltetrazol-5-yl)-3-pyridyl]amino]; [(1-methylpyrazolo[3,4-c]pyridin-4-yl)amino]; [[6-(5-methyl-1,3,4-oxadiazol-2-yl)-3-pyridyl]amino]; oxo; hydroxy(methyl); (ethylcarbamothioylamino); [3-(ethylamino)-1,2,4-triazol-4-yl]; [[2-(ethylamino)-3,4-dioxo-cyclobuten-1-yl]amino]; [[4-(ethylamino)-1,1-dioxo-1,2,5-thiadiazol-3-yl]amino]; [[N′-cyano-N-(p-tolyl)carbamimidoyl]amino]; [(1-tert-butoxycarbonylazetidine-3-carbonyl)amino]; [3-amino-1-piperidyl]; [(2R)-2-(methylcarbamoyl)pyrrolidin-1-yl]; [3-[(2,5-dimethylpyrazole-3-carbonyl)amino]azetidin-1-yl]; [(4,4-dimethyl-3-oxo-cyclobuten-1-yl)amino]; (1H-indol-2-ylmethylamino); Methanesulfonamido; [[3,4-dioxo-2-(3-pyridylamino)cyclobuten-1-yl]amino]; ethylcarbamoylamino; [3-[(2,5-dimethylpyrazol-3-yl)amino]-1,2,4-triazol-4-yl]; [3-[(5-methyl-3-pyridyl)amino]-1,2,4-triazol-4-yl]; [[4-(3-pyridyl)-1,2,4-triazol-3-yl]amino]; [3-(3-pyridylamino)-1,2,4-triazol-4-yl]; (1H-benzimidazol-2-ylamino); 3-pyridyloxy; (3-pyridylcarbamothioylamino).
  19. 19 . A compound of general formula (I) according claim 1 wherein R2 represents Hydrogen; [4-(1-methylbenzotriazol-4-yl)-1,2,4-triazol-3-yl]methyl; [[4-(2-methylpyrazol-3-yl)-1,2,4-triazol-3-yl]amino]; [3-[(2-methylpyrazol-3-yl)amino]-1,2,4-triazol-4-yl]; [[4-(5-fluoro-3-pyridyl)-1,2,4-triazol-3-yl]amino]; [3-[(5-fluoro-3-pyridyl)amino]-1,2,4-triazol-4-yl]; (3-pyridylmethylamino); (3-pyridylsulfonylamino); [(6-fluoro-1H-indole-3-carbonyl)amino]; [(1-methylbenzimidazol-2-yl)amino]; [(6-methoxycarbonyl-3-pyridyl)amino]; [(6-carboxy-3-pyridyl)amino]; [(5-methyl-1H-pyrazole-3-carbonyl)amino]; (pyridine-3-carbonylamino); [(2-methylcyclopropanecarbonyl)amino]; (pyrimidin-5-ylamino); (2-oxoindolin-5-yl)amino; [(5-methoxy-3-pyridyl)amino]; (3-pyridylamino); [(1-methylpyrazolo[3,4-c]pyridin-4-yl)amino]; Benzyloxycarbonylamino; [(4-bromophenyl)carbamoylamino]; [(2,5-dimethylpyrazol-3-yl)methylcarbamoylamino]; Hydroxy oxo; Methyl; fluorine; [[4-(ethylamino)-1,1-dioxo-1,2,5-thiadiazol-3-yl]amino]; [(4-cyano-1-methyl-pyrazol-3-yl)amino]; (4-isoquinolylamino); [[N′-cyano-N-(p-tolyl)carbamimidoyl]amino]; Methanesulfonamido; Ethylcarbamothioylamino; [3-(ethylamino)-1,2,4-triazol-4-yl]; [(4-ethyl-1,2,4-triazol-3-yl)amino]; (3-pyridylcarbamothioylamino); [[4-(3-pyridyl)-1,2,4-triazol-3-yl]amino]; [[6-(2-methyltetrazol-5-yl)-3-pyridyl]amino]; [[3,4-dioxo-2-(3-pyridylamino)cyclobuten-1-yl]amino]; [[2-(ethylamino)-3,4-dioxo-cyclobuten-1-yl]amino]; (1H-benzimidazol-2-ylamino); 3-pyridyloxy.

Description

TECHNICAL FIELD The present invention relates to dihydro-cyclopenta-isoquinoline derivatives of formula (I), processes for preparing them, pharmaceutical compositions containing them and their use in treating disorders caused by IgE (such as allergic responses, non-allergic mast cell responses or certain autoimmune responses), and in particular disorders caused by the interaction of IgE with the FcεRI receptor. BACKGROUND OF THE INVENTION IgE (immunoglobulin E) is a member of the immunoglobulin family and mediates allergic responses such as asthma, food allergies, type 1 hypersensitivity and the familiar sinus inflammation. IgE is secreted by, and expressed on the surface of, B-cells. IgE synthesized by B-cells is anchored in the B-cell membrane by a transmembrane domain linked to the mature IgE sequence by a short membrane binding region. IgE also is bound to B-cells (and monocytes, eosinophils and platelets) through its Fc region to a low affinity IgE receptor (FcεRII). Upon exposure of a mammal to an allergen, B-cells are clonally amplified which synthesize IgE that binds the allergen. This IgE in turn is released into the circulation by the B-cells where it is bound by B-cells (through FcεRII) and by mast cells and basophils through the so-called high affinity receptor (FcεRI) found on the surface of the mast cells and basophils. Such mast cells and basophils are thereby sensitized for allergen. The next exposure to the allergen cross-links the FcεRI on these cells and thus activate their release of histamine and other factors which are responsible for clinical hypersensitivity and anaphylaxis. Currently, allergic diseases, urticaria, and asthma are usually treated with one or more of the following drugs: (1) antihistamines and antileukotrienes which antagonize the inflammatory mediators histamine and leukotrienes, (2) local or systemic (oral or injectable) corticosteroids or immunosuppressants which suppress a broad spectrum of inflammatory mechanisms, (3) short or long-acting bronchodilators which relax smooth muscle of constricted airway in asthma, or (4) mast cell stabilizers which inhibit the degranulation of mast cells that is normally triggered by IgE-binding at FcεRI, (5) biologicals which prevent the binding of IgE at FcεRI. There has been also attempts to use peptides that modulate IgE binding to FcεRI. As an example, WO96/01643 describes peptides that consist of 4-50 amino to treat immediate allergic responses. However, there is still a need to identify compounds which have therapeutic utility in the treatment or prevention of disorders caused by IgE, particularly disorders caused by the interaction of IgE with the FcεRI receptor. SUMMARY OF THE INVENTION It has been found that compounds of formula (I) and their pharmaceutically acceptable salts can be used for this purpose. DETAILED DESCRIPTION The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof: Wherein:X is C or N,Y is C or O,When Y is O, R1 is hydrogen or hydroxy, R1′ is hydrogen and R2, R2′ is absent;R1 representsHydrogen,Hydroxy;An oxo group;Amino;C1-6-alkyl;C1-6-alkylamino;C(O)OH;C(O)NH-Heteroaryl;NH—C1-6-alkyl-C3-6-cycloalkyl;NH—C1-6-alkyl-C(O)OH optionally substituted with an amino group—NH-cycloalkyl optionally substituted with one or more group chosen amongst halogen; oxo; C1-6-alkyl; C1-6-alkylamino; C1-6-alkyl-C1-4-alkylamino; C3-8-cycloalkyl-C1-6-alkylamino; heteroaryl; heteroarylamino optionally substituted with one or more C1-6-alkyl;Heteroaryl optionally substituted with one or more groups chosen amongst Halogen; hydroxy; oxo; amino; cyano; —C(O)—C1-6-alkyl; C1-6-alkyl; C1-6-alkylamino; C1-6-alkoxy; —NH—(C1-6-alkyl)-heterocycloalkyl; —NH—(C1-6-alkyl)-heteroaryl optionally substituted with one or more C1-6-alkyl; —NH—C1-6-alkyl-cycloalkyl; —NH—C(O)-cycloalkyl; —NH-heteroaryl substituted with one or more C1-6-alkyl; —NH—C1-6-alkyl-C(O)OH;Heteroaryl substituted with heteroarylamino optionally substituted with C1-6-alkyl; C1-6-alkoxy; C3-6-cycloalkyl; C1-6-haloalkoxy, C1-6-haloalkyl; CN, halogen; C(O)OH, —C(O)O—C1-6-alkyl;—NH—C(S)—NH—Ra1;NH—SO2-Rb1;—NH-heteroaryl optionally substituted with one or more groups chosen amongst oxo; C1-6-alkyl; C1-6-alkylamino; heteroaryl optionally substituted with one or more oxo; C1-6-alkyl; —C(O)—NHNH—C(O)CH3; aryl; heteroarylamino; C1-6-alkoxy; C3-6-cycloalkyl; C1-6-haloalkoxy, C1-6-haloalkyl; CN, halogen; C(O)OH, —C(O)O—C1-6-alkyl;—NH-heterocycloalkyl optionally substituted with one or more groups chosen amongst Halogen; C1-6-alkyl; oxo; heteroaryl; C(O)ORb1; C1-6-alkyl-NRb1Rb1; NHC(O)-aryl; NHC(O)-heteroaryl;—NH—C1-6-Alkyl substituted with one heteroaryl group optionally substituted with one or more groups chosen amongst C1-6-alkyl; amino;—NH—C(O)O—Rb1;—NH—C(NCN)—NH—Ra1;—NH—C(NCN)—NH-Heteroaryl;—NH—C(O)—C3-8-heterocycloalkyl-C(O)O—Rb1;—C(O)NH—C1-6-alkyl;—NH—C(O)NH—C1-6-alkyl optionally substituted with one or more C3-8-heterocycloalkyl;—NH—C(O)