DK3074400T3 - Octahydro-cyclobuta[1,2-c;3,4-c']dipyrrol derivater som autotaxin inhibitorer - Google Patents

Octahydro-cyclobuta[1,2-c;3,4-c']dipyrrol derivater som autotaxin inhibitorer Download PDF

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DK3074400T3
DK3074400T3 DK14805527.0T DK14805527T DK3074400T3 DK 3074400 T3 DK3074400 T3 DK 3074400T3 DK 14805527 T DK14805527 T DK 14805527T DK 3074400 T3 DK3074400 T3 DK 3074400T3
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carbonyl
cyclobuta
octahydro
substituted
methanone
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Daniel Hunziker
Giorgio Patrick Di
Markus Rudolph
Patrizio Mattei
Lisha Wang
Jérôme Hert
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Hoffmann La Roche
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Claims (15)

1. Forbindelser med formlen (I)
hvor R1 er substitueret quinolinyl, substitueret 1,2,3,4-tetrahydroquinolinyl, substitueret isoquinolinyl, substitueret 1,2,3,4-tetrahydroisoquinolinyl, substitueret 9H-carbazolyl, substitueret chromanyl, substitueret indolyl, substitueret naphthyl, substitueret oxazolyl, substitueret phenyl, substitueret phenyl-(Ci-C7)-alkyl, substitueret phenyl-(C3-C8)-cycloalkyl, substitueret phenoxy-(Ci-C7)-alkyl, substitueret phenyl-(Ci-C7)-alkoxy, substitueret phenyl-(C2-C7)-alkenyl, substitueret phenylalkynyl, substitueret pyridazinyl, substitueret pyridazinyl-(Ci-C7)-alkyl, substitueret pyridazinyl-(C2-C7)-alkenyl, substitueret pyridazinlalkynyl, substitueret pyridinyl, substitueret pyridinyl-(Ci-C7)-alkyl, substitueret pyridinyl-(C2-C7)-alkenyl, substitueret pyridinylalkynyl, substitueret pyridinonyl, substitueret pyridinonyl-(Ci-C7)-alkyl, substitueret pyridinonyl-(C2-C7)-alkenyl, substitueret pyridinonylalkynyl, substitueret thiophenyl, substitueret thiophenyl-(Ci-C7)-alkyl substitueret thiophenyl-(C2-C7)-alkenyl, substitueret thiophenylalkynyl, substitueret tetralinyl eller substitueret tetralinonyl, hvor substitueret quinolinyl, substitueret 1,2,3,4-tetrahydroquinolinyl, substitueret isoquinolinyl, substitueret 1,2,3,4-tetrahydroisoquinolinyl, substitueret 9H-carbazolyl, substitueret chromanyl, substitueret indolyl, substitueret naphthyl, substitueret oxazolyl, substitueret phenyl, substitueret phenyl-(Ci-C7)-alkyl, substitueret phenyl-(C3-C8)-cycloalkyl, substitueret phenoxy-(Ci-C7)-alkyl, substitueret phenyl-(Ci-C7)-alkoxy, substitueret phenyl-(C2-C7)-alkenyl, substitueret phenylalkynyl, substitueret pyridazinyl, substitueret pyridazinyl-(Ci-C7)-alkyl, substitueret pyridazinyl-(C2-C7)-alkenyl, substitueret pyridazinylalkynyl, substitueret pyridinyl, substitueret pyridinyl-(Ci-C7)-alkyl, substitueret pyridinyl-(C2-C7)-alkenyl, substitueret pyridinylalkynyl, substitueret pyridinonyl, substitueret pyridinonyl-(Ci-C7)-alkyl, substitueret pyridinonyl-(C2-C7)-alkenyl, substitueret pyridinonylalkynyl, substituerett hiophenyl, substitueret thiophenyl-(Ci-C7)-alkyl, substitueret thiophenyl-(C2-C7)-alkenyl, substitueret thiophenylalkynyl, substitueret tetralinyl og substitueret tetralinonyl er substitueret med R6, R7 og R8 Y er -C(O)- eller -S(0)2-; R2 er substitueret pyridinyl, substitueret phenyl eller er valgt blandt ringsystemerne A, B og C, hvor substitueret pyridinyl og substitueret phenyl er substitueret med én substitueret aminosulfonyl, hvor substitueret aminosulfonyl er substitueret på nitrogenatomet med en eller to substituenter, der er uafhængigt valgt blandt H, (Ci-C7)-alkyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(Ci-C7)-alkyl, hydroxy-(Ci-C7)-alkyl og (Ci-C7)-alkoxy-(Ci-C7)-alkyl;
R3, R4 og R5 er uafhængigt valgt blandt H, (Ci-C7)-alkyl, halogen, halogen-(Ci-C7)-alkyl og (Ci-C7)-alkoxy; R6, R7 og R8 er uafhængigt valgt blandt H, halogen, cyano, cyano-(Ci-C7)-alkyl, (Ci-C7)-alkyl, hydroxy-(Ci-C7)-alkyl, halogenalkyl, hydroxyhalogen-(Ci-C7)-alkyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(Ci-C7)-alkyl, (C3-C8)-cycloalkyl-(Ci-C7)-alkoxy, (C3-C8)-cycloalkoxy, (C3-C8)-cycloalkoxy-(Ci-C7)-alkyl, (C3-C8)-cycloalkyl-(Ci-C7)-alkoxy-(Ci-C7)-alkyl, (Ci-C7)-alkoxy, (Ci-C7)-alkoxy-(Ci-C7)-alkyl, halogen-(Ci-C7)-alkoxy, (Ci-C7)-alkoxyhalogen-(Ci-C7)-alkyl, (Ci-C7)-alkoxy-(Ci-C7)-alkoxy, (Ci-C7)-alkoxy-(Ci-C7)-alkoxy-(Ci-C7)-alkyl, (Ci-C7)-alkylsulfonyl, furanyl, tetrahydropyranyl, phenyl, substitueret phenyl, phenyl-(Ci-C7)-alkoxy, substitueret phenyl-(Ci-C7)-alkoxy, pyridinyl, substitueret pyridinyl, pyrrolyl, substitueret pyrrolyl, pyrrolydinyl og substitueret pyrrolydinyl, hvor substitueret phenyl, substitueret phenylalkoxy, substitueret pyridinyl, substitueret pyrrolyl og substitueret pyrrolydinyl er substitueret med et til tre halogenatomer; eller farmaceutisk acceptable salte.
2. Forbindelse ifølge krav 1, hvor R1 er substitueret quinolinyl, substitueret 1,2,3,4-tetrahydroquinolinyl, substitueret isoquinolinyl, substitueret 1,2,3,4-tetrahydroisoquinolinyl, substitueret 9H-carbazolyl, substitueret chromanyl, substitueret indolyl, substitueret naphthyl, substitueret oxazolyl, substitueret phenyl, substitueret phenyl(Ci-C7)-alkyl, substitueret phenoxy-(Ci-C7)-alkyl, substitueret phenyl-(Ci-C7)-alkoxy, substitueret phenyl-(C2-C7)-alkenyl, substitueret pyridazinyl, substitueret pyridinyl, substitueret pyridinonyl, substitueret tetralinyl eller substitueret tetralinonyl, hvor substitueret quinolinyl, substitueret 1,2,3,4-tetrahydroquinolinyl, substitueret isoquinolinyl, substitueret 1,2,3,4-tetrahydroisoquinolinyl, substitueret 9H-carbazolyl, substitueret chromanyl, substitueret indolyl, substitueret naphthyl, substitueret oxazolyl, substitueret phenyl, substitueret phenyl-(Ci-C7)-alkyl, substitueret phenoxy-(Ci-C7)-alkyl, substitueret phenyl-(Ci-C7)-alkoxy, substitueret phenyl-(C2-C7)-alkenyl, substitueret pyridazinyl, substitueret pyridinyl, substitueret pyridinonyl, substitueret tetralinyl og substitueret tetralinonyl er substitueret med R6, R7 og R8.
3. Forbindelse ifølge et hvilket som helst af kravene 1 til 2, hvor R2 er valgt blandt ringsystemerne A og C.
4. Forbindelse ifølge et hvilket som helst af kravene 1 til 3, hvor R2 er ringsystemet A.
5. Forbindelse ifølge et hvilket som helst af kravene 1 til 4, hvor Y er -C(O)-.
6. Forbindelse ifølge et hvilket som helst af kravene 1 til 5, hvor R3, R4 og R5 er uafhængigt valgt blandt Fl og halogen.
7. Forbindelse ifølge et hvilket som helst af kravene 1 til 6, hvor R6 er H, halogen, cyano, cyano(Ci-C7)-alkyl, (Ci-C7)-alkyl, halogen-(Ci-C7)-alkyl, (C3-Cs)-cycloalkyl-(Ci-C7)-alkoxy, (Ci-C7)-alkoxy, (Ci-C7)-alkoxy-(Ci-C7)-alkyl, halogen-(Ci-C7)-alkoxy, (Ci-C7)-alkoxy-(Ci-C7)-alkoxy, phenyl, phenyl-(Ci-C7)-alkoxy eller phenyl substitueret med et til tre halogenatomer.
8. Forbindelse ifølge et hvilket som helst af kravene 1 til 7, hvor R7 er H, halogen, (Ci-C7)-alkyl, (C3-C8)-cycloalkyl, (Ci-C7)-alkoxy, halogen-(Ci-C7)-alkoxy, (Ci-C7)-alkylsulfonyl, furanyl eller tetrahydropyranyl.
9. Forbindelse ifølge et hvilket som helst af kravene 1 til 8, hvor R8 er Fl eller (Ci-C7)-alkyl.
10. Forbindelse ifølge et hvilket som helst af kravene 1 til 9, der er valgt blandt [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-(6-chlor-naphthalen-2-yl)-methanon; l-[(3aS,3bR,6aS,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-3-(4-trifluormethoxy-phenyl)-propan-l-on; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4'-fluor-biphenyl-4-yl)-methanon; (E)-l-[(3aS,3bR,6aS,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro- cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-3-(4-trifluormethoxy-phenyl)-propenon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(6-brom-naphthalen-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(6-methoxy-naphthalen-2-yl)-methanon; (E)-l-[(3aS,3bS,6aR,6bR)-5-((R)-4,5,6,7-tetrahydro-lH-benzotriazol-5- carbonyl)octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-3-(4-trifluormethoxy-phenyl)- propenon; 6-[(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-carbonyl]-naphthalen-2-carbonitril l-[(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-2-(4-trifluormethoxy-phenoxy)-ethanon; l-[(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-2-(2-isopropyl-phenoxy)-ethanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(5-trifluormethoxy-lH-indol-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(6-trifluormethoxy-lH-indol-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-naphthalen-2-yl-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(6-methyl-naphthalen-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(7-methyl-naphthalen-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(6-phenyl-naphthalen-2-yl)-methanon; (6-brom-naphthalen-2-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahydro-lH- benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4'-chlor-biphenyl-4-yl)-methanon; (4'-chlor-biphenyl-4-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahydro-lH- benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-methanon; [(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahydro-lH-benzotriazol-5-carbonyl)- octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-(5-trifluormethoxy-lH-indol-2-yl)- methanon; [(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahydro-lH-benzotriazol-5-carbonyl)- octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-(6-trifluormethoxy-lH-indol-2-yl)- methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(3-methoxy-naphthalen-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(l-methoxy-naphthalen-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(lH-indol-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(l-methyl-lH-indol-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-cyclopropylmethoxy-naphthalen-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-methoxy-naphthalen-2-yl)-methanon; 2-[(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-carbonyl]-lH-indol-5-carbonitril; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(3-methoxy-phenyl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-methoxy-quinolin-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-[2-(4-chlor-phenyl)-5-methyl-oxazol-4-yl]-methanon; [(3aS,3bR,6aS,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(l,2,3,4-tetrahydro-naphthalen-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(l-methyl-5-trifluormethoxy-lH-indol-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(6-chlor-lH-indol-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(6-chlor-l-methyl-lH-indol-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(6-methyl-lH-indol-2-yl)-methanon; {2-[(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro- cyclobuta[l,2-c;3,4-c']dipyrrol-2-carbonyl]-indol-l-yl>-acetonitril; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(l-isobutyl-lH-indol-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-quinolin-2-yl-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-isoquinolin-3-yl-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(lH-indol-6-yl)-methanon; 3-[(3aS,3bR,6aS,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-carbonyl]-3,4-dihydro-2H-naphthalen-l-on; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-chroman-2-yl-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(lH-indol-5-yl)-methanon; (4-methoxy-naphthalen-2-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahydro- lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-[6-(4-chlor-phenyl)-pyridin-3-yl]-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(l-methoxy-isoquinolin-3-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-methyl-quinolin-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(5-chlor-lH-indol-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-[4-(2-methoxy-ethoxy)-naphthalen-2-yl]-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(7-phenyl-naphthalen-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-ethoxy-naphthalen-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-isopropoxy-naphthalen-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-benzyloxy-lH-indol-6-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(5,6,7,8-tetrahydro-naphthalen-2-yl)-methanon; [(3aS,3bR,6aS,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4,4-dimethyl-l,2,3,4-tetrahydro-naphthalen-2-yl)-methanon; [(3aS,3bR,6aS,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-[l-(3-methoxy-propyl)-1,2,3,4-tetrahydro-quinolin-3-yl]-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-[l-(2-methoxy-ethoxy)-isoquinolin-3-yl]-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(l-cyclopropylmethoxy-isoquinolin-3-yl)-methanon; (4-isopropoxy-naphthalen-2-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahydro- lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-[l-(2,2,2-trifluor-ethoxy)-isoquinolin-3-yl]-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-isopropoxy-lH-indol-6-yl)-methanon; 4-[(3aS,3bS,6aR,6bR)-5-(4-isopropoxy-naphthalen-2-carbonyl)-octahydro- cyclobuta[l,2-c;3,4-c']dipyrrol-2-carbonyl]-benzensulfonamid; [6-(4-chlor-phenyl)-pyridin-3-yl]-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahydro- lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-methanon; (l-cyclopropylmethoxy-isoquinolin-3-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7- tetrahydro-lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2- yl]-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-isopropoxy-l-methyl-lH-indol-6-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-ethoxy-quinolin-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-isopropoxy-quinolin-2-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(6-chlor-9H-carbazol-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-[4-(2-methoxy-ethoxy)-quinolin-2-yl]-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-isopropoxy-7-trifluormethyl-quinolin-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-cyclopropylmethoxy-quinolin-2-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-[5-(4-chlor-phenyl)-pyridin-2-yl]-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(l-ethoxy-isoquinolin-3-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(l-ethyl-4-isopropoxy-lH-indol-6-yl)-methanon; 6-[(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-carbonyl]-3-(4-chlor-phenyl)-lH-pyridin-2-on; l-[(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(7-chlor-4-ethoxy-quinolin-2-yl)-methanon; (7-chlor-4-ethoxy-quinolin-2-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahydro- lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-isopropoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-methanon; (lH-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[4-(2-methoxy-ethoxy)-7- trifluormethyl-quinolin-2-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>- methanon; (lH-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(4-ethoxy-6-trifluormethyl- quinolin-2-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotnazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-ethoxy-l-ethyl-lH-indol-5-yl)-methanon; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-[l-ethyl-4-(2,2,2-trifluor-ethoxy)-lH-indol-5-yl]-methanon; 5-[(3aS,3bR,6aS,6bR)-5-(4-ethoxy-quinolin-2-carbonyl)-octahydro- cyclobuta[l,2-c;3,4-c']dipyrrol-2-carbonyl]-pyridin-2-sulfonsyreamid; (lH-benzotnazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[4-(2,2,2-tnfluor-ethoxy)- quinolin-2-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>-methanon; (lH-benzotnazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[4-ethoxy-l-(2,2,2-tnfluor-ethyl)- lH-indol-6-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>-methanon; (lH-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(5-chlor-4-cyclopropylmethoxy- pyridin-2-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-methanon; (lH-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(5-cyclopropyl-6- cyclopropylmethoxy-pyridin-2-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2- yl]-methanon; (3,4-dimethyl-phenyl)-[(3aS,3bR,6aS,6bR)-5-(4-ethoxy-5,6,7,8-tetrahydro- quinolin-2-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-methanon; (lH-benzotriazol-5-yl)-[(3aS,3bS,6aR,6bR)-5-(4'-chlor-biphenyl-3-carbonyl)- octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-methanon; (lH-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(4-ethoxy-7-methoxy-quinolin-2- carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c,]dipyrrol-2-yl]-methanon; [(3aS,3bS,6aR,6bR)-5-(4-ethoxy-6-trifluormethyl-quinolin-2-carbonyl)- octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-(lH-[l,2,3]tnazolo[4,5-b]pyridin-5-yl)- methanon; [(3aS,3bS,6aR,6bR)-5-(l-ethoxy-isoquinolin-3-carbonyl)-octahydro- cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-(lH-[l,2,3]triazolo[4,5-b]pyndin-5-yl)-methanon; (lH-benzotnazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(6-cyclopropylmethoxy-5- trifluormethyl-pyridin-2-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c,]dipyrrol-2-yl]- methanon; (lH-benzotriazol-5-yl)-<(3aS,3bR,6aS,6bR)-5-[5-cyclopropyl-4-(2,2,2-trifluor- ethoxy)-pyridin-2-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>-methanon; (lH-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[6-cyclopropyl-5-(2,2,2-trifluor- ethoxy)-pyridazin-3-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>- methanon]dipyrrol-2-yl>-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(6-chlor-4-ethoxy-quinolin-2-yl)-methanon; (lH-benzotnazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[6-(2,2,2-tnfluor-ethoxy)-5- trifluormethyl-pyridin-2-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>- methanon; (lH-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[6-(2,2,2-trifluor-ethoxy)-pyndin- 2- carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>-methanon; (lH-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[6-(2/2/2-trifluor-ethoxy)-pyridin- 3- carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>-methanon; (lH-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-brom-6-(2,2,2-trifluor-ethoxy)- pyridin-3-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c,]dipyrrol-2-yl>-methanon; (lH-benzotriazol-5-yl)-{(3aS,3bR,6aS,6bR)-5-[5-(2/2/2-trifluor-ethoxy)-pyridin- 2-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>-methanon; [(3aS,3bR,6aS,6bR)-5-(6-cyclopropylmethoxy-pyridazin-3-carbonyl)-octahydro- cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-(3,4-dimethyl-phenyl)-methanon; (lH-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-brom-2-methyl-6-(2,2,2- trifluor-ethoxy)-pyridin-3-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>- methanon; (lH-benzotnazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-cyclopropyl-6-(2,2,2-trifluor- ethoxy)-pyridin-3-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>-methanon; (lH-benzotnazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[6-(2,2,2-trifluor-ethoxy)-5- trifluormethyl-pyridin-3-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl)- methanon; (lH-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-(tetrahydro-pyran-4-yl)-6- (2,2,2-trifluor-ethoxy)-pyridin-3-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2- yl}-methanon; (lH-benzotriazol-5-yl)-<(3aS,3bR,6aS,6bR)-5-[4-(4-chlor-phenyl)-5-(2,2,2- trifluor-ethoxy)-pyridin-2-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c,]dipyrrol-2-yl>- methanon; (lH-benzotriazol-5-yl)-<(3aS,3bS,6aR,6bR)-5-[5-furan-2-yl-6-(2,2,2-trifluor- ethoxy)-pyridin-3-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c,]dipyrrol-2-yl>-methanon; (lH-benzotriazol-5-yl)-<(3aS,3bS,6aR,6bR)-5-[5-chlor-6-(2,2,2-trifluor-ethoxy)- pyridin-3-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c,]dipyrrol-2-yl>-methanon; [(3aS,3bR,6aS,6bR)-5-(4-ethoxy-quinolin-2-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-yl]-(4-fluor-lH-benzotriazol-5-yl)-methanon; {(3aS,3bS,6aR,6bR)-5-[5-methansulfonyl-6-(2,2,2-trifluor-ethoxy)-pyridin-3- carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>-phenyl-methanon; (3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-carboxylsyre-4-trifluormethoxy-benzylester; (3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c']dipyrrol-2-carboxylsyre-3,5-dichlor-benzylester; (lH-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(4'-fluor-biphenyl-4-sulfonyl)- octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-methanon; (lH-benzotriazol-5-yl)-[(3aS,3bR,6aS,6bR)-5-(6-chlor-naphthalen-2-sulfonyl)- octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-(6-trifluormethyl-3,4-dihydro-lH-isoquinolin-2-yl)-methanon; og farmaceutisk acceptable salte deraf.
11. Forbindelse ifølge et hvilket som helst af kravene 1 til 10, der er valgt blandt (E)-l-[(3aS,3bR,6aS,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro- cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl]-3-(4-trifluormethoxy-phenyl)-propenon; (4-isopropoxy-naphthalen-2-yl)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahydro- lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c,]dipyrrol-2-yl]-methanon; 4-[(3aS,3bS,6aR,6bR)-5-(4-isopropoxy-naphthalen-2-carbonyl)-octahydro- cyclobuta[l,2-c;3,4-c']dipyrrol-2-carbonyl]-benzensulfonamid; [(3aS,3bS,6aR,6bR)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c,]dipyrrol-2-yl]-(4-isopropoxy-l-methyl-lH-indol-6-yl)-methanon; [(3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2- c;3,4-c,]dipyrrol-2-yl]-[4-(2-methoxy-ethoxy)-quinolin-2-yl]-methanon; (lH-benzotriazol-5-yl)-{(3aS,3bS,6aR,6bR)-5-[5-brom-6-(2,2,2-trifluor-ethoxy)- pyridin-3-carbonyl]-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-yl>-methanon; (3aR,3bS,6aR,6bS)-5-(lH-benzotriazol-5-carbonyl)-octahydro-cyclobuta[l,2-c;3,4-c']dipyrrol-2-carboxylsyre-4-trifluormethoxy-benzylester; og farmaceutisk acceptable salte deraf.
12. Fremgangsmåde til fremstilling af en forbindelse ifølge et hvilket som helst af kravene 1 til 11, hvilken fremgangsmåde omfatter reaktionen afen forbindelse med formlen (II) i nærvær af en forbindelse med formlen (III), hvor R1, R2, A og Y er som defineret ovenfor.
13. Forbindelse ifølge et hvilket som helst af kravene 1 til 11 til anvendelse som terapeutisk aktivt stof.
14. Farmaceutisk sammensætning, der omfatter en forbindelse ifølge et hvilket som helst af kravene 1 til 11 og en terapeutisk inert bærer.
15. Forbindelse ifølge et hvilket som helst af kravene 1 til 11 til anvendelse i behandlingen eller forebyggelsen af nyrelidelser, leverlidelser, inflammatoriske lidelser, lidelser af nervesystemet, lidelser i åndedrætssystemet, vaskulære og cardiovaskulære lidelser, fibrotiske sygdomme, cancer, okulære lidelser, stofskiftelidelser, cholestatisk og andre former for kronisk pruritus og akut og kronisk organtransplantatafstødning.
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Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI633087B (zh) 2012-06-13 2018-08-21 赫孚孟拉羅股份公司 新穎二氮雜螺環烷及氮雜螺環烷
EP3590940B1 (en) 2012-09-25 2021-06-09 F. Hoffmann-La Roche AG Hexahydropyrrolo[3,4-c]pyrrole derivatives and related compounds as autotaxin (atx) inhibitors and as inhibitors of the lysophosphatidic acid (lpa) production for treating e.g. renal diseases
AR095079A1 (es) 2013-03-12 2015-09-16 Hoffmann La Roche Derivados de octahidro-pirrolo[3,4-c]-pirrol y piridina-fenilo
NO3074400T3 (da) 2013-11-26 2018-04-14
MA39792B1 (fr) 2014-03-26 2019-12-31 Hoffmann La Roche Composés bicycliques en tant qu'inhibiteurs de production d'autotaxine (atx) et d'acide lysophosphatidique (lpa)
EP3122751B1 (en) 2014-03-26 2019-10-30 F.Hoffmann-La Roche Ag Condensed [1,4]diazepine compounds as autotaxin (atx) and lysophosphatidic acid (lpa) production inhibitors
MA41898A (fr) 2015-04-10 2018-02-13 Hoffmann La Roche Dérivés de quinazolinone bicyclique
MX387736B (es) 2015-09-04 2025-03-18 Hoffmann La Roche Derivados de fenoximetilo.
PE20180451A1 (es) 2015-09-24 2018-03-05 Hoffmann La Roche Nuevos compuestos biciclicos como inhibidores de atx
CN107635995B (zh) * 2015-09-24 2022-08-19 豪夫迈·罗氏有限公司 作为atx抑制剂的二环化合物
KR20180054634A (ko) 2015-09-24 2018-05-24 에프. 호프만-라 로슈 아게 이중 오토탁신(atx)/탄산 무수화효소(ca) 억제제로서 신규한 이환형 화합물
MX2017015034A (es) 2015-09-24 2018-04-13 Hoffmann La Roche Nuevos compuestos biciclicos como inhibidores duales de autotaxina (atx)/anhidrasa carbonica (ca).
CN108456208B (zh) * 2017-02-22 2021-04-16 广州市恒诺康医药科技有限公司 氮杂螺环类化合物及其制备方法和应用
MA49879A (fr) 2017-03-16 2020-06-24 Hoffmann La Roche Composés hétérocycliques utiles en tant qu'inhibiteurs doubles d'atx/ca
CN110382484B (zh) 2017-03-16 2022-12-06 豪夫迈·罗氏有限公司 新的作为atx抑制剂的二环化合物
FR3079742B1 (fr) 2018-04-06 2023-01-13 Keranova Appareil de traitement d’un tissu incluant des systemes optiques originaux de deviation et de focalisation d’un faisceau l.a.s.e.r.

Family Cites Families (138)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1252898B (de) 1965-06-12 1967-10-26 Bayer Ag Verfahren zur Herstellung von Copolymerisaten des Trioxans
US5240928A (en) 1989-07-03 1993-08-31 Merck & Co., Inc. Substituted quinazolinones as angiotensin II antagonists
DE3930262A1 (de) 1989-09-11 1991-03-21 Thomae Gmbh Dr K Kondensierte diazepinone, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
KR910009330B1 (ko) 1989-10-23 1991-11-11 재단법인 한국화학연구소 항균작용을 갖는 퀴놀린계 화합물과 그의 제조방법
CA2037630C (en) 1990-03-07 2001-07-03 Akira Morimoto Nitrogen-containing heterocylic compounds, their production and use
US5470975A (en) 1990-10-16 1995-11-28 E.R. Squibb & Sons, Inc. Dihydropyrimidine derivatives
US5290780A (en) 1991-01-30 1994-03-01 American Cyanamid Co. Angiotensin II receptor blocking 2,3,6 substituted quinazolinones
US5238942A (en) 1991-05-10 1993-08-24 Merck & Co., Inc. Substituted quinazolinones bearing acidic functional groups as angiotensin ii antagonists
DE4121214A1 (de) 1991-06-27 1993-01-14 Bayer Ag 7-azaisoindolinyl-chinolon- und -naphthyridoncarbonsaeure-derivate
US5202322A (en) 1991-09-25 1993-04-13 Merck & Co., Inc. Quinazolinone and pyridopyrimidine a-II antagonists
US5532243A (en) 1992-02-14 1996-07-02 The Dupont Merck Pharmaceutical Company Antipsychotic nitrogen-containing bicyclic compounds
US5358951A (en) 1993-04-23 1994-10-25 American Cyanamid Company Angiotensin II receptor blocking 2, 3, 6 substituted quinazolinones
DE4407047A1 (de) 1994-03-03 1995-09-07 Merck Patent Gmbh Acetamide
US20010016657A1 (en) 1997-03-18 2001-08-23 Smithkline Beecham P.L.C. Substituted isoquinoline derivatives and their use as anticonvulsants
SK11402000A3 (sk) 1998-02-04 2001-03-12 Banyu Pharmaceutical Co., Ltd Cyklické n-acylaminoderiváty
JP2001039950A (ja) 1999-07-30 2001-02-13 Banyu Pharmaceut Co Ltd Ｎ−アシル環状アミン誘導体
DE60005545D1 (de) 1999-10-27 2003-10-30 Millennium Pharm Inc Pyridyl enthaltende spirocyclische verbindungen als inhibitoren der fibrinogen-abhängigen blutplättchen aggregation
MXPA03008109A (es) 2001-03-07 2003-12-12 Pfizer Prod Inc Moduladores de la actividad de receptores de quimiocinas.
JP4459629B2 (ja) 2002-04-12 2010-04-28 メルク エンド カムパニー インコーポレーテッド 二環式アミド
GB0303852D0 (en) 2003-02-19 2003-03-26 Pfizer Ltd Triazole compounds useful in therapy
WO2005023762A1 (en) 2003-09-04 2005-03-17 Abbott Laboratories Pyrrolidine-2-carbonitrile derivatives and their use as inhibitors of dipeptidyl peptidase-iv (dpp-iv)
SE0302811D0 (sv) 2003-10-23 2003-10-23 Astrazeneca Ab Novel compounds
GB0324790D0 (en) 2003-10-24 2003-11-26 Astrazeneca Ab Amide derivatives
US7226951B2 (en) 2003-12-17 2007-06-05 Allergan, Inc. Compounds having selective cytochrome P450RAI-1 or selective cytochrome P450RAI-2 inhibitory activity and methods of obtaining the same
KR100610731B1 (ko) 2004-02-24 2006-08-09 한국과학기술연구원 Ｔ-형 칼슘 채널 차단제로서 유용한 ３,４-디히드로퀴나졸린유도체 및 그의 제조 방법
CN1950082B (zh) 2004-03-03 2013-02-06 凯莫森特里克斯股份有限公司 双环和桥连的含氮杂环化物
DK1761542T3 (da) 2004-06-09 2008-04-28 Hoffmann La Roche Octahydropyrrolo[3,4-C] pyrrolderivater og anvendelsen deraf som antivirusmidler
RU2401833C2 (ru) 2004-08-10 2010-10-20 Янссен Фармацевтика Н.В. Производные 1, 2, 4-триазин-6-она, ингибирующие вич
US7410949B2 (en) 2005-01-18 2008-08-12 Hoffmann-La Roche Inc. Neuropeptide-2 receptor (Y-2R) agonists and uses thereof
GB0504019D0 (en) 2005-02-26 2005-04-06 Astrazeneca Ab Amide derivatives
MX2007013469A (es) 2005-04-28 2008-01-22 Wyeth Corp Forma ii polimorfa de tanaproget.
US7737279B2 (en) 2005-05-10 2010-06-15 Bristol-Myers Squibb Company 1,6-dihydro-1,3,5,6-tetraaza-as-indacene based tricyclic compounds and pharmaceutical compositions comprising same
TW200800999A (en) 2005-09-06 2008-01-01 Astrazeneca Ab Novel compounds
EP1942108B1 (en) 2005-10-28 2013-09-04 Ono Pharmaceutical Co., Ltd. Compound containing basic group and use thereof
EP1961744B1 (en) 2005-11-18 2013-04-17 Ono Pharmaceutical Co., Ltd. Basic group-containing compound and use thereof
JP2007176809A (ja) 2005-12-27 2007-07-12 Hideaki Natsukari 複素環置換アミド化合物、その製造法および医薬組成物
WO2007103719A2 (en) 2006-03-03 2007-09-13 Incyte Corporation MODULATORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME
JP2008031064A (ja) 2006-07-27 2008-02-14 Astellas Pharma Inc ジアシルピペラジン誘導体
CN101600698B (zh) 2006-09-11 2012-01-11 欧加农股份有限公司;药典有限责任公司 喹唑啉酮和异喹啉酮乙酰胺衍生物
CA2663500A1 (en) 2006-09-15 2008-03-20 Schering Corporation Spiro-condensed azetidine derivatives useful in treating pain, diabetes and disorders of lipid metabolism
US8735411B2 (en) 2006-10-02 2014-05-27 Abbvie Inc. Macrocyclic benzofused pyrimidine derivatives
TWI454262B (zh) 2006-11-02 2014-10-01 Targacept Inc 菸鹼乙醯膽鹼受體亞型選擇性之二氮雜雙環烷類醯胺
EP2097388B1 (en) 2006-11-15 2011-09-07 High Point Pharmaceuticals, LLC Novel 2-(2-hydroxyphenyl)benzimidazoles useful for treating obesity and diabetes
TW200831085A (en) 2006-12-13 2008-08-01 Merck & Co Inc Non-nucleoside reverse transcriptase inhibitors
EP1975165A1 (de) 2007-03-27 2008-10-01 Boehringer Ingelheim Pharma GmbH & Co. KG Substituierte Pyrrolidinamide, deren Herstellung und deren Verwendung als Arzneimittel
KR20090127178A (ko) 2007-03-29 2009-12-09 에프. 호프만-라 로슈 아게 비뉴클레오시드 역전사 효소 억제제
CL2008001002A1 (es) 2007-04-11 2008-10-17 Actelion Pharmaceuticals Ltd Compuestos derivados de oxazolidinona; composicion farmaceutica que comprende a dichos compuestos; y su uso para preparar un medicamento para tratar una infeccion bacteriana.
JP2010524987A (ja) 2007-04-27 2010-07-22 サノフィ−アベンティス ２−ヘテロアリール−ピロロ［３，４−ｃ］ピロール誘導体及びｓｃｄ阻害剤としてのそれらの使用
KR20100039300A (ko) 2007-08-07 2010-04-15 애보트 게엠베하 운트 콤파니 카게 세로토닌 5-ｈｔ6 수용체의 조절에 반응하는 장애를 치료하는데 적합한 퀴놀린 화합물
DE102007047737A1 (de) 2007-10-05 2009-04-30 Merck Patent Gmbh Piperidin- und Piperazinderivate
MX2010004281A (es) 2007-10-19 2010-09-10 Sarcode Corp Composiciones y metodos para el tratamiento de la retinopatia diabetica.
PA8802501A1 (es) 2007-10-31 2009-06-23 Janssen Pharmaceutica Nv Diaminas en puente o fusionadas sustituidas con arilo como moduladores de leucotrieno, hidrolasa
JP2009161449A (ja) 2007-12-28 2009-07-23 Lion Corp Ｐｐａｒ活性促進剤並びに美容用飲食品、皮膚外用剤及び医薬
JPWO2009154132A1 (ja) 2008-06-19 2011-12-01 Ｍｓｄ株式会社 スピロジアミン−ジアリールケトオキシム誘導体
WO2010028761A1 (de) 2008-09-09 2010-03-18 Sanofi-Aventis 2-heteroaryl-pyrrolo[3, 4-c]pyrrol-derivate und ihre verwendung als scd inhibitoren
TW201020247A (en) 2008-11-06 2010-06-01 Gruenenthal Gmbh Substituierte disulfonamide
US8188090B2 (en) 2008-11-17 2012-05-29 Hoffman-La Roche Inc. Naphthylacetic acids
DE102008059578A1 (de) 2008-11-28 2010-06-10 Merck Patent Gmbh Benzo-Naphtyridin Verbindungen
EA201100879A1 (ru) 2008-12-01 2012-01-30 Мерк Патент Гмбх Производные пиридопиримидина в качестве ингибиторов аутотаксина
TW201035102A (en) 2009-03-04 2010-10-01 Gruenethal Gmbh Sulfonylated tetrahydroazolopyrazines and their use as medicinal products
BRPI1006113A2 (pt) 2009-03-05 2016-02-16 Daiichi Sankyo Co Ltd "derivado de piridina".
US20120010186A1 (en) 2009-03-23 2012-01-12 Merck Frosst Canada Ltd. Heterocyclic compounds as inhibitors of stearoyl-coenzyme a delta-9 desaturase
TW201038572A (en) 2009-03-25 2010-11-01 Gruenenthal Gmbh Substituted spiro-amide compounds
CA2757415C (en) * 2009-04-02 2018-02-06 Merck Patent Gmbh Autotaxin inhibitors
EP2623101B1 (en) * 2009-04-02 2021-04-21 Merck Patent GmbH Piperidine and piperazine derivatives as autotaxin inhibitors
JP5767205B2 (ja) 2009-04-02 2015-08-19 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ オートタキシン阻害剤としての複素環式化合物
FR2945534B1 (fr) 2009-05-12 2012-11-16 Sanofi Aventis DERIVES DE CYCLOPENTAL[c]PYRROLE-2-CARBOXYLATES, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE
EP2432779A1 (en) 2009-05-22 2012-03-28 Exelixis, Inc. Benzoxazepines based p13k/mt0r inhibitors against proliferative diseases
US20120083476A1 (en) 2009-06-05 2012-04-05 Janssen Pharmaceutica Nv Heteroaryl-substituted spirocyclic diamine urea modulators of fatty acid amide hydrolase
DE102009033392A1 (de) 2009-07-16 2011-01-20 Merck Patent Gmbh Heterocyclische Verbindungen als Autotaxin-Inhibitoren II
CN102574822A (zh) 2009-08-04 2012-07-11 阿米拉制药公司 作为溶血磷脂酸受体拮抗剂的化合物
UA107360C2 (en) 2009-08-05 2014-12-25 Biogen Idec Inc Bicyclic aryl sphingosine 1-phosphate analogs
AR079022A1 (es) 2009-11-02 2011-12-21 Sanofi Aventis Derivados de acido carboxilico ciclico sustituidos con acilamino, su uso como productos farmaceuticos, composicion farmaceutica y metodo de preparacion
ES2534516T3 (es) 2010-01-07 2015-04-23 E.I. Du Pont De Nemours And Company Compuestos heterocíclicos fungicidas
WO2011115813A1 (en) 2010-03-18 2011-09-22 Abbott Laboratories Lactam acetamides as calcium channel blockers
PL2547679T3 (pl) 2010-03-19 2016-02-29 Pfizer Pochodne 2,3-dihydro-1H-inden-1-ylo-2,7-diazaspiro[3.5]nonanu i ich zastosowanie jako antagonistów lub odwrotnych agonistów receptora greliny
WO2011116867A1 (de) 2010-03-26 2011-09-29 Merck Patent Gmbh Benzonaphthyridinamine als autotaxin-inhibitoren
GB201008005D0 (en) 2010-05-13 2010-06-30 Sentinel Oncology Ltd Pharmaceutical compounds
EP2575794A2 (en) 2010-06-04 2013-04-10 B.S.R.C. "Alexander Fleming" Autotaxin pathway modulation and uses thereof
JP5781071B2 (ja) 2010-06-29 2015-09-16 オリンパス株式会社 光学素子の製造方法および光学素子の製造装置
ES2646834T3 (es) 2010-08-20 2017-12-18 Amira Pharmaceuticals, Inc. Inhibidores de autotaxina y usos de los mismos
EP2611808B1 (en) 2010-09-02 2014-11-12 Merck Patent GmbH Pyrazolopyridinone derivatives as lpa receptor antagonists
JP5699223B2 (ja) 2010-12-02 2015-04-08 シャンハイ デュァ ノボ ファルマテック カンパニー リミテッド 複素環誘導体、その合成法および医療用途
US20140031547A1 (en) 2010-12-14 2014-01-30 Electrophoretics Limited CASEIN KINASE 1delta (CK 1delta) INHIBITORS AND THEIR USE IN THE TREATMENT OF NEURODE-GENERATIVE DISEASES SUCH AS TAUOPATHIES
US9260416B2 (en) 2011-05-27 2016-02-16 Amira Pharmaceuticals, Inc. Heterocyclic autotaxin inhibitors and uses thereof
US8664213B2 (en) 2011-08-29 2014-03-04 Bristol-Myers Squibb Company Spiro bicyclic diamine derivatives as HIV attachment inhibitors
WO2013054185A1 (en) * 2011-10-13 2013-04-18 Pfizer, Inc. Pyrimidine and pyridine derivatives useful in therapy
JPWO2013065712A1 (ja) 2011-10-31 2015-04-02 東レ株式会社 ジアザスピロウレア誘導体及びその医薬用途
US8809552B2 (en) 2011-11-01 2014-08-19 Hoffmann-La Roche Inc. Azetidine compounds, compositions and methods of use
US9815851B2 (en) 2011-12-02 2017-11-14 Phenex Pharmaceuticals Ag Pyrrolo carboxamides as modulators of orphan nuclear receptor RAR-related orphan receptor-gamma (RORγ, NR1F3) activity and for the treatment of chronic inflammatory and autoimmune diseases
TWI638802B (zh) 2012-05-24 2018-10-21 芬蘭商奧利安公司 兒茶酚ｏ－甲基轉移酶活性抑制化合物
TWI633087B (zh) * 2012-06-13 2018-08-21 赫孚孟拉羅股份公司 新穎二氮雜螺環烷及氮雜螺環烷
LT3495367T (lt) 2012-06-13 2021-02-25 Incyte Holdings Corporation Pakeistieji tricikliniai junginiai, kaip fgfr inhibitoriai
CA2871388A1 (en) 2012-06-27 2014-01-03 F. Hoffmann-La Roche Ag 5-azaindazole compounds and methods of use
WO2014018881A1 (en) 2012-07-27 2014-01-30 Biogen Idec Ma Inc. Atx modulating agents
TWI631097B (zh) 2012-07-27 2018-08-01 百健Ｍａ公司 作爲ｓ１ｐ調節劑及／或ａｔｘ調節劑之化合物
AR092211A1 (es) 2012-09-24 2015-04-08 Merck Patent Ges Mit Beschränkter Haftung Derivados de hidropirrolopirrol
EP3590940B1 (en) 2012-09-25 2021-06-09 F. Hoffmann-La Roche AG Hexahydropyrrolo[3,4-c]pyrrole derivatives and related compounds as autotaxin (atx) inhibitors and as inhibitors of the lysophosphatidic acid (lpa) production for treating e.g. renal diseases
WO2014048881A1 (en) 2012-09-25 2014-04-03 Bayer Pharma Aktiengesellschaft Combination of regorafenib and acetylsalicylic acid for treating cancer
AR092742A1 (es) 2012-10-02 2015-04-29 Intermune Inc Piridinonas antifibroticas
PL2912019T3 (pl) 2012-10-25 2021-11-02 Tetra Discovery Partners Llc Heteroarylowe inhibitory pde4
DK2938598T3 (da) 2012-12-31 2017-02-13 Cadila Healthcare Ltd Substitueret phthalazin-1(2H)-on-derivater som selektive hæmmere af poly-(adp-ribose-)polymerase-1
JPWO2014133112A1 (ja) 2013-03-01 2017-02-02 国立大学法人 東京大学 オートタキシン阻害活性を有する８−置換イミダゾピリミジノン誘導体
CN105026403B (zh) 2013-03-12 2018-05-18 艾伯维公司 四环布罗莫结构域抑制剂
TWI593692B (zh) 2013-03-12 2017-08-01 美國禮來大藥廠 四氫吡咯并噻嗪化合物
JP2016512528A (ja) 2013-03-12 2016-04-28 アクセラ インコーポレイテッド 眼疾患及び眼障害を治療するための置換された３−フェニルプロピルアミン誘導体
AR095079A1 (es) 2013-03-12 2015-09-16 Hoffmann La Roche Derivados de octahidro-pirrolo[3,4-c]-pirrol y piridina-fenilo
EP2970302A1 (en) 2013-03-15 2016-01-20 Biogen MA Inc. S1p and/or atx modulating agents
PT3022202T (pt) 2013-07-18 2019-09-03 Novartis Ag Inibidores da autotaxina compreendendo um núcleo beteroaromático anel-benzilo-amida-ciclo
SI3057959T1 (en) 2013-10-17 2018-07-31 Vertex Pharmaceuticals Incorporated DNA-PK INHIBITORS
KR102367876B1 (ko) 2013-11-22 2022-02-24 사브레 테라퓨틱스 엘엘씨 오토탁신 억제제 화합물
AR098475A1 (es) 2013-11-26 2016-06-01 Bayer Cropscience Ag Compuestos pesticidas y usos
NO3074400T3 (da) 2013-11-26 2018-04-14
EP3122751B1 (en) 2014-03-26 2019-10-30 F.Hoffmann-La Roche Ag Condensed [1,4]diazepine compounds as autotaxin (atx) and lysophosphatidic acid (lpa) production inhibitors
JO3512B1 (ar) 2014-03-26 2020-07-05 Astex Therapeutics Ltd مشتقات كينوكسالين مفيدة كمعدلات لإنزيم fgfr كيناز
MA39792B1 (fr) 2014-03-26 2019-12-31 Hoffmann La Roche Composés bicycliques en tant qu'inhibiteurs de production d'autotaxine (atx) et d'acide lysophosphatidique (lpa)
BR112016020117B1 (pt) 2014-03-26 2020-03-17 Basf Se “compostos, composição e método para o combate dos fungos fitopatogênicos
CR20160496A (es) 2014-04-04 2017-01-02 X-Rx Inc Inhibidores espirocíclicos sustituidos de la autotaxina
JP6632532B2 (ja) 2014-08-29 2020-01-22 国立大学法人 東京大学 オートタキシン阻害活性を有するピリミジノン誘導体
TWI675032B (zh) 2014-10-14 2019-10-21 美商維它藥物公司 ＲＯＲ-γ之二氫吡咯并吡啶抑制劑
WO2016128529A1 (en) 2015-02-15 2016-08-18 F. Hoffmann-La Roche Ag 1-(het)arylsulfonyl-(pyrrolidine or piperidine)-2-carboxamide derivatives and their use as trpa1 antagonists
MA41898A (fr) 2015-04-10 2018-02-13 Hoffmann La Roche Dérivés de quinazolinone bicyclique
CN104927727B (zh) 2015-07-06 2017-01-11 香山红叶建设有限公司 一种玻璃幕墙用结构密封胶及其制备方法
PL415078A1 (pl) 2015-09-04 2017-03-13 Oncoarendi Therapeutics Spółka Z Ograniczoną Odpowiedzialnością Podstawione aminotriazole przydatne jako inhibitory kwaśnej chitynazy ssaków
MX387736B (es) 2015-09-04 2025-03-18 Hoffmann La Roche Derivados de fenoximetilo.
KR20180054634A (ko) 2015-09-24 2018-05-24 에프. 호프만-라 로슈 아게 이중 오토탁신(atx)/탄산 무수화효소(ca) 억제제로서 신규한 이환형 화합물
HK1255699A1 (zh) 2015-09-24 2019-08-23 Ionis Pharmaceuticals, Inc. Kras表达的调节剂
MX2017015034A (es) 2015-09-24 2018-04-13 Hoffmann La Roche Nuevos compuestos biciclicos como inhibidores duales de autotaxina (atx)/anhidrasa carbonica (ca).
PE20180451A1 (es) 2015-09-24 2018-03-05 Hoffmann La Roche Nuevos compuestos biciclicos como inhibidores de atx
CN107635995B (zh) 2015-09-24 2022-08-19 豪夫迈·罗氏有限公司 作为atx抑制剂的二环化合物
WO2017087858A1 (en) 2015-11-20 2017-05-26 Abide Therapeutics, Inc. Pyrazole compounds and methods of making and using same
WO2017087863A1 (en) 2015-11-20 2017-05-26 Abide Therapeutics, Inc. Pyrazole compounds and methods of making and using same
CA3003288A1 (en) 2015-11-25 2017-06-01 Dana-Farber Cancer Institute, Inc. Bivalent bromodomain inhibitors and uses thereof
CA3006029C (en) 2015-12-01 2020-08-04 Nihon Nohyaku Co., Ltd. 3h-pyrrolopyridine compound, n-oxide thereof or salt thereof, agricultural and horticultural insecticide comprising the compound and method for using the same
WO2017139978A1 (zh) 2016-02-19 2017-08-24 吴伟东 手机app更新方法及系统
MA49879A (fr) 2017-03-16 2020-06-24 Hoffmann La Roche Composés hétérocycliques utiles en tant qu'inhibiteurs doubles d'atx/ca
CN110382484B (zh) 2017-03-16 2022-12-06 豪夫迈·罗氏有限公司 新的作为atx抑制剂的二环化合物
EP3680241A1 (en) 2017-03-20 2020-07-15 Forma Therapeutics, Inc. Pyrrolopyrrole compositions as pyruvate kinase (pkr) activators

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