OCTAHYDRO-CYCLOBUTA [1,2-c;3,4-c']DIPYRROL-2-YL

• US 20160264586A1
• Filed: 05/25/2016
• Published: 09/15/2016
• Est. Priority Date: 11/26/2013
• Status: Abandoned Application

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Di Giorgio, Patrick, Mattei, Patrizio, Hunziker, Daniel, Hert, Jerome, Rudolph, Markus, Wang, Lisha
• Application Number:
  US15/164,122
• Publication Number:
  US 20160264586A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 209/56 Ring systems containing three or more rings
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The invention provides novel compounds having the general formula (I)

wherein R¹, Y and R² are as described herein, compositions including the compounds and methods of using the compounds.

Claims

1. A compound of formula (I)

2. The compound according to claim 1, wherein R¹ is substituted quinolinyl, substituted 1,2,3,4-tetrahydroquinolinyl, substituted isoquinolinyl, substituted 1,2,3,4-tetrahydroisoquinolinyl, substituted 9H-carbazolyl, substituted chromanyl, substituted indolyl, substituted naphthyl, substituted oxazolyl, substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylalkoxy, substituted phenylalkenyl, substituted pyridazinyl, substituted pyridinyl, substituted pyridinonyl, substituted tetralinyl or substituted tetralinonyl, wherein substituted quinolinyl, substituted 1,2,3,4-tetrahydroquinolinyl, substituted isoquinolinyl, substituted 1,2,3,4-tetrahydroisoquinolinyl, substituted 9H-carbazolyl, substituted chromanyl, substituted indolyl, substituted naphthyl, substituted oxazolyl, substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylalkoxy, substituted phenylalkenyl, substituted pyridazinyl, substituted pyridinyl, substituted pyridinonyl, substituted tetralinyl and substituted tetralinonyl are substituted with R⁶, R⁷ and R⁸.

3. The A compound of claim 1, wherein R¹ is substituted quinolinyl, substituted indolyl, substituted naphthyl, substituted phenylalkoxy, substituted phenylalkenyl or substituted pyridinyl, wherein substituted quinolinyl, substituted indolyl, substituted naphthyl, substituted phenylalkoxy, substituted phenylalkenyl and substituted pyridinyl are substituted with R⁶, R⁷ and R⁸.

4. The A compound of claim 1, wherein R¹ is substituted quinolinyl, substituted indolyl, substituted naphthyl or substituted pyridinyl, wherein substituted quinolinyl, substituted indolyl, substituted naphthyl and substituted pyridinyl are substituted with R⁶, R⁷ and R⁸.

5. The A compound of claim 1, wherein R² is selected from the ring systems A and C.

6. The A compound of claim 1, wherein R² is the ring system A.

7. The A compound of claim 1, wherein Y is —

C(O)—

.

8. The A compound of claim 1, wherein R³, R⁴ and R⁵ are independently selected from H and halogen.

9. The A compound of claim 1, wherein R³, R⁴ and R⁵ are H.

10. The A compound of claim 1, wherein R⁶ is H, halogen, cyano, cyanoalkyl, alkyl, haloalkyl, cycloalkylalkoxy, alkoxy, alkoxyalkyl, haloalkoxy, alkoxyalkoxy, phenyl, phenylalkoxy or phenyl substituted with one to three halogen.

11. The A compound of claim 1, wherein R⁶ is alkoxy, haloalkoxy or alkoxyalkoxy.

12. The A compound of claim 1, wherein R⁷ is H, halogen, alkyl, cycloalkyl, alkoxy, haloalkoxy, alkylsulfonyl, furanyl or tetrahydropyranyl.

13. The A compound of claim 1, wherein R⁷ is H or halogen.

14. The A compound of claim 1, wherein R⁸ is H or alkyl.

15. The A compound of claim 1, wherein R⁸ is H.

16. The A compound of claim 1, selected from

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-chloro-naphthalen-2-yl)-methanone;

1-[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-3-(4-trifluoromethoxy-phenyl)-propan-1-one;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4′

-fluoro-biphenyl-4-yl)-methanone;

(E)-1-[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-3-(4-trifluoromethoxy-phenyl)-propenone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-bromo-naphthalen-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-methoxy-naphthalen-2-yl)-methanone;

(E)-1-[(3aS,3bS,6aR,6bR)-5-((R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-3-(4-trifluoromethoxy-phenyl)-propenone;

6-[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrole-2-carbonyl]-naphthalene-2-carbonitrile;

1-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-2-(4-trifluoromethoxy-phenoxy)-ethanone;

1-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-2-(2-isopropyl-phenoxy)-ethanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(5-trifluoromethoxy-1H-indol-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-trifluoromethoxy-1H-indol-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-naphthalen-2-yl-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-methyl-naphthalen-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(7-methyl-naphthalen-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-phenyl-naphthalen-2-yl)-methanone;

(6-bromo-naphthalen-2-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4, 5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4′

-chloro-biphenyl-4-yl)-methanone;

(4′

-chloro-biphenyl-4-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4, 5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

[(3aR,3bS,6aR,6bS)-5-((R)-4, 5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(5-trifluoromethoxy-1H-indol-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-((R)-4, 5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-trifluoromethoxy-1H-indol-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(3-methoxy-naphthalen-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1-methoxy-naphthalen-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1H-indol-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1-methyl-1H-indol-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-cyclopropylmethoxy-naphthalen-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-methoxy-naphthalen-2-yl)-methanone;

2-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrole-2-carbonyl]-1H-indole-5-carbonitrile;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(3-methoxy-phenyl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-methoxy-quinolin-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-[2-(4-chloro-phenyl)-5-methyl-oxazol-4-yl]-methanone;

[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1,2,3,4-tetrahydro-naphthalen-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1-methyl-5-trifluoromethoxy-1H-indol-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-chloro-1H-indol-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-chloro-1-methyl-1H-indol-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-methyl-1H-indol-2-yl)-methanone;

{2-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrole-2-carbonyl]-indol-1-yl}-acetonitrile;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1-isobutyl-1H-indol-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-quinolin-2-yl-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-isoquinolin-3-yl-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1H-indol-6-yl)-methanone;

3-[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrole-2-carbonyl]-3,4-dihydro-2H-naphthalen-1-one;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-chroman-2-yl-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1H-indol-5-yl)-methanone;

(4-methoxy-naphthalen-2-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4, 5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-[6-(4-chloro-phenyl)-pyridin-3-yl]-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1-methoxy-isoquinolin-3-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-methyl-quinolin-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(5-chloro-1H-indol-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-[4-(2-methoxy-ethoxy)-naphthalen-2-yl]-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(7-phenyl-naphthalen-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-ethoxy-naphthalen-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-isopropoxy-naphthalen-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-benzyloxy-1H-indol-6-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(5,6,7, 8-tetrahydro-naphthalen-2-yl)-methanone;

[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4,4-dimethyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-methanone;

[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-[1-(3-methoxy-propyl)-1,2,3,4-tetrahydro-quinolin-3-yl]-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-[1-(2-methoxy-ethoxy)-isoquinolin-3-yl]-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1-cyclopropylmethoxy-isoquinolin-3-yl)-methanone;

(4-isopropoxy-naphthalen-2-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4, 5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-[1-(2,2,2-trifluoro-ethoxy)-isoquinolin-3-yl]-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-isopropoxy-1H-indol-6-yl)-methanone;

4-[(3aS,3bS,6aR,6bR)-5-(4-isopropoxy-naphthalene-2-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrole-2-carbonyl]-benzenesulfonamide;

[6-(4-chloro-phenyl)-pyridin-3-yl]-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

(1-cyclopropylmethoxy-isoquinolin-3-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-isopropoxy-1-methyl-1H-indol-6-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-ethoxy-quinolin-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-isopropoxy-quinolin-2-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-chloro-9H-carbazol-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-[4-(2-methoxy-ethoxy)-quinolin-2-yl]-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-isopropoxy-7-trifluoromethyl-quinolin-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-cyclopropylmethoxy-quinolin-2-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-[5-(4-chloro-phenyl)-pyridin-2-yl]-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1-ethoxy-isoquinolin-3-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1-ethyl-4-isopropoxy-1H-indol-6-yl)-methanone;

6-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrole-2-carbonyl]-3-(4-chloro-phenyl)-1H-pyridin-2-one;

1-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(7-chloro-4-ethoxy-quinolin-2-yl)-methanone;

(7-chloro-4-ethoxy-quinolin-2-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4, 5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-isopropoxy-5,6,7, 8-tetrahydro-naphthalen-2-yl)-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[4-(2-methoxy-ethoxy)-7-trifluoromethyl-quinoline-2-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

(1H-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(4-ethoxy-6-trifluoromethyl-quinoline-2-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-ethoxy-1-ethyl-1H-indol-5-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-[1-ethyl-4-(2,2,2-trifluoro-ethoxy)-1H-indol-5-yl]-methanone;

5-[(3aS,3bR,6aS,6bR)-5-(4-ethoxy-quinoline-2-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrole-2-carbonyl]-pyridine-2-sulfonic acid amide;

(1H-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[4-(2,2,2-trifluoro-ethoxy)-quinoline-2-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

(1H-benzotriazol-5-yl)-(3aS,3bS,6aR,6bR)-5-[4-ethoxy-1-(2,2,2-trifluoro-ethyl)-1H-indole-6-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

(1H-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(5-chloro-4-cyclopropylmethoxy-pyridine-2-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

(1H-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(5-cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

(3,4-dimethyl-phenyl)-[(3aS,3bR,6aS,6bR)-5-(4-ethoxy-5,6,7, 8-tetrahydro-quinoline-2-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

(1H-benzotriazol-5-yl)-[(3aS,3bS,6aR,6bR)-5-(4′

-chloro-biphenyl-3-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

(1H-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(4-ethoxy-7-methoxy-quinoline-2-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

[(3aS,3bS,6aR,6bR)-5-(4-Ethoxy-6-trifluoromethyl-quinoline-2-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-methanone;

[(3aS,3bS,6aR,6bR)-5-(1-ethoxy-isoquinoline-3-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(1H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-methanone;

(1H-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(6-cyclopropylmethoxy-5-trifluoromethyl-pyridine-2-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[5-cyclopropyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[6-cyclopropyl-5-(2,2,2-trifluoro-ethoxy)-pyridazine-3-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone′

]dipyrrol-2-yl}-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-chloro-4-ethoxy-quinolin-2-yl)-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[6-(2,2,2-trifluoro-ethoxy)-5-trifluoromethyl-pyridine-2-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[6-(2,2,2-trifluoro-ethoxy)-pyridine-2-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

(1H-benzotriazol-5-yl)-(3aS,3bS,6aR,6bR)-5-[6-(2,2,2-trifluoro-ethoxy)-pyridine-3-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl})-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-bromo-6-(2,2,2-trifluoro-ethoxy)-pyridine-3-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[5-(2,2,2-trifluoro-ethoxy)-pyridine-2-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl})-methanone;

[(3aS,3bR,6aS,6bR)-5-(6-cyclopropylmethoxy-pyridazine-3-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(3,4-dimethyl-phenyl)-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-bromo-2-methyl-6-(2,2,2-trifluoro-ethoxy)-pyridine-3-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-cyclopropyl-6-(2,2,2-trifluoro-ethoxy)-pyridine-3-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[6-(2,2,2-trifluoro-ethoxy)-5-trifluoromethyl-pyridine-3-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-(tetrahydro-pyran-4-yl)-6-(2,2,2-trifluoro-ethoxy)-pyridine-3-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl)}-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[4-(4-chloro-phenyl)-5-(2, 2,2-trifluoro-ethoxy)-pyridine-2-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-furan-2-yl-6-(2,2,2-tri fluoro-ethoxy)-pyridine-3-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl})-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-chloro-6-(2,2,2-trifluoro-ethoxy)-pyridine-3-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-methanone;

[(3aS,3bR,6aS,6bR)-5-(4-ethoxy-quinoline-2-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-fluoro-1H-benzotriazol-5-yl)-methanone;

{(3aS,3bS,6aR,6bR)-5-[5-methanesulfonyl-6-(2,2,2-trifluoro-ethoxy)-pyridine-3-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl}-phenyl-methanone;

(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrole-2-carboxylicacid 4-trifluoromethoxy-benzyl ester;

(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrole-2-carboxylic acid 3,5-dichloro-benzyl ester;

(1H-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(4′

-fluoro-biphenyl-4-sulfonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

(1H-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(6-chloro-naphthalene-2-sulfonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(6-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-methanone;

and pharmaceutically acceptable salts thereof.

17. The A compound of claim 16, selected from

(E)-1-[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-3-(4-trifluoromethoxy-phenyl)-propenone;

(4-isopropoxy-naphthalen-2-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4, 5,6,7-tetrahydro-1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-methanone;

4-[(3aS,3bS,6aR,6bR)-5-(4-isopropoxy-naphthalene-2-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrole-2-carbonyl]-benzenesulfonamide;

[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-(4-isopropoxy-1-methyl-1H-indol-6-yl)-methanone;

[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl]-[4-(2-methoxy-ethoxy)-quinolin-2-yl]-methanone;

(1H-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-bromo-6-(2,2,2-trifluoro-ethoxy)-pyridine-3-carbonyl]-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrol-2-yl})-methanone;

(3aR,3bS,6aR,6bS)-5-(1H-benzotriazole-5-carbonyl)-octahydro-cyclobuta[1,2-c;

3,4-c′

]dipyrrole-2-carboxylicacid 4-trifluoromethoxy-benzyl ester;

and pharmaceutically acceptable salts thereof.

18. A process to prepare a compound of claim 1 comprising the reaction of a compound of formula (II) in the presence of a compound of formula (III), wherein R¹, R², A and Y are as defined above.

20. A pharmaceutical composition comprising a compound of claim 1 and a therapeutically inert carrier.

24. A method for the treatment or prophylaxis a condition selected from the group consisting of renal conditions, liver conditions, inflammatory conditions, conditions of the nervous system, conditions of the respiratory system, vascular and cardiovascular conditions, fibrotic diseases, cancer, ocular conditions, metabolic conditions, cholestatic and other forms of chronic pruritus and acute and chronic organ transplant rejection, which method comprises administering an effective amount of a compound of claim 1.

19. (canceled)

21-23. -23. (canceled)

25-26. -26. (canceled)