Benzyl and pyridinyl derivatives as modulators of the hedgehog signaling pathway
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Abstract
The present disclosure relates to compounds relating to the diagnosis and treatment of pathologies relating to the Hedgehog pathway, including but not limited to tumor formation, cancer, neoplasia, and non-malignant hyperproliferative disorders; specifically relating to compounds of formula I:
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Citations
5 Claims
- 1. A compound of Formula I:
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5. A compound selected from:
- 6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-nicotinonitrile;
1-Benzyl-4-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-phthalazine;
1-Benzyl-4-[4-(5-trifluoromethyl-pyridin-2-yl)-[1,4]diazepan-1-yl]-phthalazine;
6-[4-(4-Pyridin-4-ylmethyl-phthalazin-1-yl)-piperazin-1-yl]-nicotinonitrile;
4-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-benzoic acid ethyl ester;
1-(4-Phenyl-piperazin-1-yl)-4-pyridin-4-ylmethyl-phthalazine;
1-Benzyl-4-[4-(4-tert-butyl-phenyl)-piperazin-1-yl]-phthalazine;
1-[4-(4-tert-Butyl-phenyl)-piperazin-1-yl]-4-pyridin-4-ylmethyl-phthalazine;
1-[4-(4-tert-Butyl-phenyl)-piperazin-1-yl]-4-(3,5-dichloro-benzyl)-phthalazine;
4-[4-(4-tert-Butyl-phenyl)-piperazin-1-yl]-6-methyl-1-pyridin-4-ylmethyl-phthalazine;
1-(2-Methyl-pyridin-4-ylmethyl)-4-(4-phenyl-piperazin-1-yl)-phthalazine;
1-Benzyl-4-(4-phenyl-piperidin-1-yl)-phthalazine;
1-(4-Phenyl-piperidin-1-yl)-4-pyridin-4-ylmethyl-phthalazine;
1-(2-Methyl-pyridin-4-ylmethyl)-4-(4-phenyl-piperidin-1-yl)-phthalazine;
1-Pyridin-4-ylmethyl-4-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-phthalazine;
4-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-benzoic acid;
1-Benzyl-4-[4-(3-chloro-5-trifluoromethyl-pyridin-2-yl)-[1,4]diazepan-1-yl]-phthalazine;
1-Benzyl-4-(4-quinolin-2-yl-piperazin-1-yl)-phthalazine;
6-[4-(4-Benzyl-phthalazin-1-yl)-[1,4]diazepan-1-yl]-nicotinonitrile;
4-(4-Pyridin-4-ylmethyl-phthalazin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2′
]bipyrazinyl;
4-(4-Benzyl-phthalazin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2′
]bipyrazinyl;
1-(2-Methyl-pyridin-4-ylmethyl)-4-(4-pyridin-2-yl-piperazin-1-yl)-phthalazine;
1-Pyridin-4-ylmethyl-4-(4-pyridin-2-yl-piperazin-1-yl)-phthalazine;
1-Benzyl-4-(4-pyridin-2-yl-piperazin-1-yl)-phthalazine;
1-Benzyl-4-(4-pyrimidin-2-yl-piperazin-1-yl)-phthalazine;
1-Pyridin-4-ylmethyl-4-(4-pyridin-4-yl-piperazin-1-yl)-phthalazine;
1-Benzyl-4-(3-methyl-4-p-tolyl-piperazin-1-yl)-phthalazine;
1-(3-Methyl-4-p-tolyl-piperazin-1-yl)-4-pyridin-4-ylmethyl-phthalazine;
1-(2-Methyl-pyridin-4-ylmethyl)-4-(3-methyl-4-p-tolyl-piperazin-1-yl)-Phthalazine;
1-Benzyl-4-[4-(3,4-dichloro-phenyl)-piperazin-1-yl]-phthalazine;
1-Benzyl-4-(4-naphthalen-2-yl-piperazin-1-yl)-phthalazine;
1-(4-Naphthalen-2-yl-piperazin-1-yl)-4-pyridin-4-ylmethyl-phthalazine;
1-(2-Methyl-pyridin-4-ylmethyl)-4-(4-naphthalen-2-yl-piperazin-1-yl)-phthalazine;
1-Benzyl-4-(4-naphthalen-1-yl-piperazin-1-yl)-phthalazine;
1-(2-Methyl-pyridin-4-ylmethyl)-4-(4-naphthalen-1-yl-piperazin-1-yl)-phthalazine;
1-(4-Naphthalen-1-yl-piperazin-1-yl)-4-pyridin-4-ylmethyl-phthalazine;
1-Benzyl-4-(4-pyridin-4-yl-piperazin-1-yl)-phthalazine;
1-Benzyl-4-(4-o-tolyl-piperazin-1-yl)-phthalazine;
2-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyrimidine-5-carbonitrile;
1-Benzyl-4-(4-pyrimidin-2-yl-[1,4]diazepan-1-yl)-phthalazine;
1-Benzyl-4-[4-(4-methyl-pyrimidin-2-yl)-[1,4]diazepan-1-yl]-phthalazine;
1-Benzyl-4-[4-(5-propyl-pyrimidin-2-yl)-piperazin-1-yl]-phthalazine;
1-Benzyl-4-[4-(5-ethyl-pyrimidin-2-yl)-piperazin-1-yl]-phthalazine;
1-Benzyl-4-[4-(5-propyl-pyrimidin-2-yl)-[1,4]diazepan-1-yl]-phthalazine;
1-Benzyl-4-[4-(5-ethyl-pyrimidin-2-yl)-[1,4]diazepan-1-yl]-phthalazine;
2-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-6-methoxy-3H-pyrimidin-4-one;
1-Benzyl-4-[4-(4-methyl-pyrimidin-2-yl)-piperazin-1-yl]-phthalazine;
1-Benzyl-4-[4-(4,6-dimethyl-pyrimidin-2-yl)-piperazin-1-yl]-phthalazine;
1-Benzyl-4-[4-(5-chloro-3-fluoro-pyridin-2-yl)-piperazin-1-yl]-phthalazine;
1-Benzyl-4-[4-(4-trifluoromethyl-pyrimidin-2-yl)-piperazin-1-yl]-phthalazine;
1-Benzyl-4-[4-(2,5-difluoro-pyridin-3-yl)-piperazin-1-yl]-phthalazine;
1-Benzyl-4-[4-(3,5-difluoro-pyridin-2-yl)-piperazin-1-yl]-phthalazine;
6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-nicotinamide;
6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-nicotinic acid ethyl ester;
2-{6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridin-3-yl}-propan-2-ol;
6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-nicotinic acid;
6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-N-(2-hydroxy-ethyl)-N-methyl-nicotinamide;
6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-N-ethyl-N-(2-hydroxy-ethyl)-nicotinamide;
6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-N-(2-hydroxy-ethyl)-nicotinamide;
6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-N-(2-methoxy-ethyl)-nicotinamide;
6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-N-(2-methoxy-ethyl)-N-methyl-nicotinamide;
6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-N-(2-dimethylamino-ethyl)-nicotinamide;
{6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridin-3-yl}-(4-methyl-piperazin-1-yl)-methanone;
{6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridin-3-yl}-piperazin-1-yl-methanone;
{6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridin-3-yl}-morpholin-4-yl-methanone;
N-Benzyl-6-[4-(4-benzyl-phthalazin-1-yl)-piperazin-1-yl]-nicotinamide;
6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-N-cyclohexylmethyl-nicotinamide;
6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-N-propyl-nicotinamide;
{6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridin-3-yl}-(3-hydroxy-pyrrolidin-1-yl)-methanone;
{6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridin-3-yl}-thiazolidin-3-yl-methanone;
{6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridin-3-yl}-(1-oxo-1lambda*4*-thiazolidin-3-yl)-methanone;
({6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridine-3-carbonyl}-amino)-acetic acid methyl ester;
1-Benzyl-4-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-phthalazine;
6-{4-[4-(3-Trifluoromethyl-benzyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[4-(4-Cyano-benzyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[4-(3,4-Dimethoxy-benzyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotino-nitrile;
6-{4-[4-(4-Chloro-benzyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[4-(3-Chloro-benzyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
6-[4-(4-Phenethyl-phthalazin-1-yl)-piperazin-1-yl]-nicotinonitrile;
6-[4-(4-Naphthalen-2-ylmethyl-phthalazin-1-yl)-piperazin-1-yl]-nicotino-nitrile;
6-{4-[4-(4-Trifluoromethyl-benzyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[4-(4-Methoxy-benzyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[4-(3-Cyano-benzyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[4-(4-Bromo-benzyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[4-(3-Bromo-benzyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[4-(1-Phenyl-ethyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[4-(4-Methyl-benzyl)-phthalazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
N-{6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridin-3-ylmethyl}-acetamide;
C-{6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridin-3-yl}-methyl-amine;
4-[4-(4-Pyridin-4-ylmethyl-phthalazin-1-yl)-piperazin-1-yl]-benzylamine;
4-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-benzylamine;
4-[5-({6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-pyridin-3-ylmethyl}-carbamoyl)-pentyl]-8-ethyl-3,8,9,10-tetrahydro-2H-1,6,11-trioxa-8,13-diaza-4-azonia-pentacene;
N-{4-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-benzyl}-acetamide;
N-{4-[4-(4-Pyridin-4-ylmethyl-phthalazin-1-yl)-piperazin-1-yl]-benzyl}-acetamide;
{4-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-benzyl}-carbamic acid benzyl ester;
{4-[4-(4-Pyridin-4-ylmethyl-phthalazin-1-yl)-piperazin-1-yl]-benzyl}-carbamic acid benzyl ester;
N-{4-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-benzyl}-propionamide;
N-{4-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-benzyl}-2-methoxy-acetamide;
N-{4-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-benzyl}-3-methyl-butyramide;
6-[4-(1-Benzyl-isoquinolin-4-yl)-piperazin-1-yl]-nicotinonitrile;
6-{4-[1-(3-Cyano-benzyl)-isoquinolin-4-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[1-(3-Chloro-benzyl)-isoquinolin-4-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[1-(3-Trifluormethyl-benzyl)-isoquinolin-4-yl]-piperazin-1-yl}-nicotinonitrile;
6-[4-(4-Benzyl-isoquinolin-1-yl)-piperazin-1-yl]-nicotinonitrile;
4-{4-[6-(4-Fluoro-benzyl)-4-methyl-pyridazin-3-yl]-piperazin-1-yl}-benzo-nitrile;
4-{4-[6-(4-Fluoro-benzyl)-5-methyl-pyridazin-3-yl]-piperazin-1-yl}-benzo-nitrile;
4-{4-[6-(4-Benzyl)-4-methyl-pyridazin-3-yl]-piperazin-1-yl}-nicotinonitrile;
4-{4-[6-(4-Benzyl)-5-methyl-pyridazin-3-yl]-piperazin-1-yl}-nicotinonitrile;
6-Benzyl-4-methyl-3-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyridazine;
6-Benzyl-5-methyl-3-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyridazine;
6-(4-Fluoro-benzyl)-4-methyl-3-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyridazine;
6-(4-Fluoro-benzyl)-5-methyl-3-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-pyridazine;
4-{4-[6-(4-chloro-benzyl)-4-methyl-pyridazin-3-yl]-piperazin-1-yl}-nicotinonitrile;
4-{4-[6-(4-chloro-benzyl)-5-methyl-pyridazin-3-yl]-piperazin-1-yl}-nicotinonitrile;
4-{4-[6-(4-Fluoro-benzyl)-4,5-dimethyl-pyridazin-3-yl]-piperazin-1-yl}-nicotinonitrile;
4-{4-[4-(4-fluoro-benzyl)-5,6,7,8-tetrahydro-phthalzin-1-yl]-piperazin-1-yl}-nicotinonitrile;
6-{4-[4-(4-Fluoro-benzyl)-6,7-dihydro-5H-cyclopenta[d]pyridazin-1-yl]-piperazin-1-yl}-nicotinonitrile;
3-{4-[1-(4-Fluoro-benzyl)-1H-indol-3-yl]-piperidine-1-carbonyl}-benzo-nitrile;
4-[1-(4-Fluoro-benzyl)-1H-indol-3-yl)-5′
-trifluoromethyl-3,4,5,6-tetra-hydro-2H-[1,2]-bipyridinyl;
4-[3-(5′
-Trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-4-yl)-indol-1-ylmethyl]-benzonitrile;
4-[1-Benzyl-1H-indol-3-yl)-5′
-trifluoromethyl-3,4,5,6-tetra-hydro-2H-[1,2]-bipyridinyl;
4-[1-(4-Fluoro-benzyl)-1H-indol-3-yl]-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-5′
-carbonitrile;
4-[1-(4-Bromo-benzyl)-1H-indol-3-yl)-5′
-trifluoromethyl-3,4,5,6-tetra-hydro-2H-[1,2]-bipyridinyl;
4-(1-Benzyl-1H-indol-3-yl)-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-5′
-carbonitrile;
{4-[1-(4-Fluoro-benzyl)-1H-indol-3-yl]-piperidin-1-yl}-(3-fluoro-phenyl)-methanone;
4-{4-[1-(4-Fluoro-benzyl)-1H-indol-3-yl]-piperidine-1-carbonyl}-benzonitrile;
3-{4-[1-(4-Fluoro-benzyl)-1H-indol-3-yl]-piperidine-1-carbonyl}-benzonitrile;
{4-[1-(4-Fluoro-benzyl)-1H-indol-3-yl]-piperidin-1-yl}-(4-trifluoromethyl-phenyl)-methanone;
or {4-[1-Benzyl-1H-indol-3-yl]-piperidin-1-yl}-(4-trifluoromethyl-phenyl)-methanone.
- 6-[4-(4-Benzyl-phthalazin-1-yl)-piperazin-1-yl]-nicotinonitrile;
Specification