DK1957461T3 - Bisamidhæmmere af hedgehog-signalering - Google Patents

Bisamidhæmmere af hedgehog-signalering Download PDF

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Publication number
DK1957461T3
DK1957461T3 DK06844364.7T DK06844364T DK1957461T3 DK 1957461 T3 DK1957461 T3 DK 1957461T3 DK 06844364 T DK06844364 T DK 06844364T DK 1957461 T3 DK1957461 T3 DK 1957461T3
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Prior art keywords
chloro
phenyl
nicotinamide
methyl
alkyl
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DK06844364.7T
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English (en)
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Richard A Goldsmith
Daniel P Sutherlin
Kirk D Robarge
Alan G Olivero
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Genentech Inc
Curis Inc
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    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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Claims (17)

1. Forbindelse med formlen I til anvendelse ved behandling af angiogenese-medierede sygdomme valgt blandt en solid tumor, makulade-generation og en inflammatorisk sygdom eller en immunsygdom, hvor den inflammatoriske sygdom eller immunsygdommen er Crohns sygdom, inflammatorisk tarmsygdom, Sjogrens syndrom, astma, organtransplantat-afstødning, systemisk lupus erythematosus, reumatoid arthritis, psoriasis-arthritis, psoriasis eller multipel sklerose:
Ϊ hvor ringen A er benzen; ringen B er pyridin; carbocyklen er en mono-, bi- eller tricyklisk alifatisk ring med 3 til 14 carbonatomer, som er mættet eller umættet, aromatisk eller ikke-aromatisk; heterocyklen er en mono-, bi- eller tricyklisk, mættet eller umættet, aromatisk eller ikke-aromatisk ring med fra 5 til ca. 14 ringatomer, hvor ringatomerne er 1 til 4 nitrogen-, svovl- eller oxygenheteroatomer, og resten er carbonatomer; Ri er hydroxy, halogen, amino, nitro, cyano, alkyl, acyl, sulfonyl, sulfinyl, alkoxy, carbamoyl, acylamin, sulfamoyl eller sulfonamid; hvor amino-, alkyl-, acyl-, sulfonyl-, sulfinyl-, alkoxy-, carbamoyl-, acylamin-, sulfamoyl-og sulfonamidsubstituenten eventuelt er substitueret med amino, halogen, hydroxy, oxo eller er substitueret med en carbocykel eller en heterocykel som defineret ovenfor, der eventuelt er substitueret med hydroxy, amino, halogen, halogenalkyl, alkyl, alkoxy eller acyl; eller Ri er en carbocykel eller en heterocykel som defineret ovenfor, der eventuelt er substitueret med hydroxy, halogen, amino, nitro, cyano, alkyl, acyl, sulfonyl, sulfinyl, alkoxy, carbamoyl, acylamin, sulfamoyl, sulfonamid, en carbocykel eller en heterocykel som defineret ovenfor; hvor amino-, alkyl-, acyl-, sulfonyl-, sulfinyl-, alkoxy-, carbamoyl-, acylamin-, sulfamoyl-, sulfonamid-, carbocykel- og heterocykelsubstituenten eventuelt er substitueret med amino, halogen, hydroxy, oxo eller er substitueret med en carbocykel eller en heterocykel som defineret ovenfor, der eventuelt er substitueret med hydroxy, amino, halogen, halogenalkyl, alkyl, alkoxy eller acyl; R2 er hydrogen; R3 er halogen, hydroxy, carboxy, alkyl, acyl, alkoxy, alkoxycarbonyl, carbamoyl, sulfid, sulfinyl, sulfonyl, en carbocykel eller en heterocykel som defineret ovenfor, hvor hver(t) alkyl, acyl, alkoxy, alkoxycarbonyl, carbamoyl, sulfid, sulfinyl, sulfonyl, carbocykel og heterocykel eventuelt er substitueret med hydroxy, halogen, amino, nitro, alkyl, acyl, sulfonyl eller alkoxy; hvert R4 uafhængigt er H eller alkyl; R5 er chlor; m er 0 til 3; n er 0 til 4; eller et salt eller solvat deraf.
2. Forbindelse til anvendelse ved behandling af angiogenesemedierede sygdomme ifølge krav 1, hvor sygdommen med solid tumor er en colon-, lunge-, pankreas-, ovarie-, bryst- eller gliomsygdom med solid tumor, og makuladegenerationssygdommen er våd aldersrelateret makuladegeneration.
3. Anvendelse af en forbindelse med formlen I til fremstilling af et lægemiddel til anvendelse ved behandling af angiogenesemedierede sygdomme valgt blandt en solid tumor, makuladegeneration og en inflammatorisk sygdom/immunsygdom, hvor den inflammatoriske sygdom/immunsygdommen er Crohns sygdom, inflammatorisk tarmsygdom, Sjogrens syndrom, astma, organtransplantatafstødning, systemisk lupus erythematosus, reumatoid arthritis, psoriasisarthritis, psoriasis eller multipel sklerose:
I hvor ringen A er benzen; ringen B er pyridin; carbocyklen er en mono-, bi- eller tricyklisk alifatisk ring med 3 til 14 carbonatomer, som er mættet eller umættet, aromatisk eller ikke-aromatisk; heterocyklen er en mono-, bi- eller tricyklisk, mættet eller umættet, aromatisk eller ikke-aromatisk ring med fra 5 til ca. 14 ringatomer, hvor ringatomerne er 1 til 4 nitrogen-, svovl- eller oxygenheteroatomer, og resten er carbonatomer; Ri er hydroxy, halogen, amino, nitro, cyano, alkyl, acyl, sulfonyl, sulfinyl, alkoxy, carbamoyl, acylamin, sulfamoyl eller sulfonamid; hvor amino-, alkyl-, acyl-, sulfonyl-, sulfinyl-, alkoxy-, carbamoyl-, acylamin-, sulfamoyl-og sulfonamidsubstituenten eventuelt er substitueret med amino, halogen, hydroxy, oxo eller er substitueret med en carbocykel eller en heterocykel som defineret ovenfor, der eventuelt er substitueret med hydroxy, amino, halogen, halogenalkyl, alkyl, alkoxy eller acyl; eller Ri er en carbocykel eller en heterocykel som defineret ovenfor, der eventuelt er substitueret med hydroxy, halogen, amino, nitro, cyano, alkyl, acyl, sulfonyl, sulfinyl, alkoxy, carbamoyl, acylamin, sulfamoyl, sulfonamid, en carbocykel eller en heterocykel som defineret ovenfor; hvor amino-, alkyl-, acyl-, sulfonyl-, sulfinyl-, alkoxy-, carbamoyl-, acylamin-, sulfamoyl-, sulfonamid-, carbocykel- og heterocykelsubstituenten eventuelt er substitueret med amino, halogen, hydroxy, oxo eller er substitueret med en carbocykel eller en heterocykel som defineret ovenfor, der eventuelt er substitueret med hydroxy, amino, halogen, halogenalkyl, alkyl, alkoxy eller acyl; Fb er hydrogen; Fb er halogen, hydroxy, carboxy, alkyl, acyl, alkoxy, alkoxycarbonyl, carbamoyl, sulfid, sulfinyl, sulfonyl, en carbocykel eller en heterocykel som defineret ovenfor, hvor hver(t) alkyl, acyl, alkoxy, alkoxycarbonyl, carbamoyl, sulfid, sulfinyl, sulfonyl, carbocykel og heterocykel eventuelt er substitueret med hydroxy, halogen, amino, nitro, alkyl, acyl, sulfonyl eller alkoxy; hvert FU uafhængigt er H eller alkyl; R5 er chlor; m er 0 til 3; n er 0 til 4; eller et salt eller solvat deraf.
4. Anvendelse af en forbindelse med formlen I ifølge krav 3, hvor sygdommen med solid tumor er en colon-, lunge-, pankreas-, ovarie-, bryst- eller gliomsygdom med solid tumor, og makuladegenerationssygdommen er våd aldersrelateret makuladegeneration.
5. Forbindelse til anvendelsen ifølge et hvilket som helst af kravene 1 til 4, hvor Ri er alkyl, halogenalkyl, aryl, en heterocykel eller heterocycloalkyl, hvor aryl-, heterocykel- og heterocycloalkylgruppen eventuelt er substitueret med hydroxy, halogen, alkyl, alkanoyl eller hydroxyalkyl.
6. Forbindelse til anvendelsen ifølge krav 5, hvor Ri er Me, CF3, Ph, 4-F-phenyl, piperazin-1-yl, 4-methylpiperazin-1-yl, 4-ethylpiperazin-1-yl, 4-acetylpiperazin-1 -yl, 3,5-dimethylpiperazin-1 -yl, 4-(2-hydroxyethyl)-piperazin-1 -yl, (4-methylpiperazin-1 -yl)methyl, (4-ethylpiperazin-1 -yl)methyl, (4-acetylpiperazin-1 -yl)methyl, (3,5-dimethylpiperazin-1 -yl)methyl, 4-hydroxypiperidin-1 -yl, (piperidin-1 -yl)methyl, (1 -methylpiperidin-4-ylamino)methyl, morpholino, (3,5-dimethyl)morpholino, morpholinomethyl eller 1/-/-1,2,4-triazol-1-yl.
7. Forbindelse til anvendelsen ifølge et hvilket som helst af kravene 1 til 3 eller 5 til 6, hvor R3 er halogen, alkyl, alkylsulfonyl, alkylsulfonylalkyl eller en heterocykel.
8. Forbindelse til anvendelsen ifølge krav 7, hvor R3 er Me, F, Cl, -CH2-S02-Me, -SC>2-Me, 1H-1,2,4-triazol-1-yl, 1 /-/-imidazol-1 -yl, morpholino, thiomorpholino-methyl (hvor S er i den oxiderede form SO2), 1,2,3-thiadiazol-4-yl eller N-methyl-piperizinyl.
9. Forbindelse til anvendelsen ifølge et hvilket som helst af kravene 1 til 3 eller 5 til 8, hvor begge R4-grupper er H.
10. Forbindelse til anvendelsen ifølge et hvilket som helst af kravene 1 til 3 eller 5 til 9, hvor sygdommen er cancer, hvor canceren er en cancer med solid tumor.
11. Forbindelse til anvendelsen ifølge krav 10, hvor sygdommen er basalcellekarcinom, medullablastom, meningiom, hæmangiom, glioblastom, pancreas-adenokarcinom, pianocellulært lungekarcinom, småcellet lungekarcinom, ikke-småcellet lungekarcinom, chondrosarkom, mammakarcinom, rhabdomyosarkom, øsofaguscancer, mavecancer, galdevejscancer, nyrekarcinom eller thyroideakarcinom.
12. Forbindelse med formlen II:
11 hvor: X er CRi; Yer CRi; Ri er hydroxy, halogen, amino, nitro, cyano, alkyl, acyl, sulfonyl, sulfinyl, alkoxy, carbamoyl, acylamin, sulfamoyl eller sulfonamid; hvor amino-, alkyl-, acyl-, sulfonyl-, sulfinyl-, alkoxy-, carbamoyl-, acylamin-, sulfamoyl-og sulfonamidsubstituenten eventuelt er substitueret med amino, halogen, hydroxy, oxo eller er substitueret med en carbocykel eller en heterocykel, der eventuelt er substitueret med hydroxy, amino, halogen, halogenalkyl, alkyl, alkoxy eller acyl; eller Ri er en carbocykel eller en heterocykel, der eventuelt er substitueret med hydroxy, halogen, amino, nitro, cyano, alkyl, acyl, sulfonyl, sulfinyl, alkoxy, carbamoyl, acylamin, sulfamoyl, sulfonamid, en carbocykel eller en heterocykel; hvor amino-, alkyl-, acyl-, sulfonyl-, sulfinyl-, alkoxy-, carbamoyl-, acylamin-, sulfamoyl-, sulfonamid-, carbocykel- og heterocykelsubstituenten eventuelt er substitueret med amino, halogen, hydroxy, oxo eller er substitueret med en carbocykel eller en heterocykel, der eventuelt er substitueret med hydroxy, amino, halogen, halogenalkyl, alkyl, alkoxy eller acyl; carbocyklen er en mono-, bi- eller tricyklisk alifatisk ring med 3 til 14 carbonatomer, som er mættet eller umættet, aromatisk eller ikke-aromatisk; heterocyklen er en mono-, bi- eller tricyklisk, mættet eller umættet, aromatisk eller ikke-aromatisk ring med fra 5 til ca. 14 ringatomer, hvor ringatomerne er 1 til 4 nitrogen-, svovl- eller oxygenheteroatomer, og resten er carbonatomer; R2 er hydrogen; R3 er halogen, hydroxy, carboxy, alkyl, acyl, alkoxy, alkoxycarbonyl, carbamoyl, sulfid, sulfinyl, sulfonyl, en carbocykel eller en heterocykel som defineret ovenfor, hvor hver(t) alkyl, acyl, alkoxy, alkoxycarbonyl, carbamoyl, sulfid, sulfinyl, sulfonyl, carbocykel og heterocykel eventuelt er substitueret med hydroxy, halogen, amino, nitro, alkyl, acyl, sulfonyl eller alkoxy; R4 er H eller alkyl; R5 er chlor; m er 0 til 3; n er 0 til 4; eller et salt eller solvat deraf.
13. Forbindelse ifølge krav 12 til anvendelse ved behandling af cancer hos et pattedyr, hvor canceren er en cancer med solid tumor.
14. Forbindelse til anvendelse ifølge krav 13, hvor canceren er basalcellekarcinom, medullablastom, pancreas-adenokarcinom, småcellet lungekarcinom, mammakarcinom, rhabdomyosarkom, øsofaguscancer, mavecancer, galdevejscancer.
15. Forbindelse ifølge krav 12 til anvendelse ved behandling af angiogenesemedierede sygdomme valgt blandt en solid tumor, makuladegeneration, og følgende inflammatoriske sygdomme eller immunsygdomme: Crohns sygdom, inflammatorisk tarmsygdom, Sjogrens syndrom, astma, organtransplantatafstødning, systemisk lupus erythematosus, reumatoid arthritis, psoriasisarthritis, psoriasis eller multipel sklerose hos et pattedyr.
16. Anvendelse af forbindelsen ifølge krav 12 til fremstilling af et lægemiddel til behandling af angiogenesemedierede sygdomme valgt blandt en solid tumor, makuladegeneration, og følgende inflammatoriske sygdomme eller immunsygdomme: Crohns sygdom, inflammatorisk tarmsygdom, Sjogrens syndrom, astma, organtransplantatafstødning, systemisk lupus erythematosus, reumatoid arthritis, psoriasisarthritis, psoriasis eller multipel sklerose.
17. Forbindelse valgt fra gruppen bestående af: N-(3-benzamido-4-chlorphenyl)-4-methyl-6-(trifluormethyl)nicotinamid; N-(4-chlor-3-(2-chlorbenzamido)phenyl)-2-methyl-6-(trifluormethyl)- nicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-2-methyl-6-(trifluormethyl)- nicotinamid; N-(4-chlor-3-(4-chlorbenzamido)phenyl)-2-methyl-6-(trifluormethyl)- nicotinamid; N-(4-chlor-3-(2-fluorbenzamido)phenyl)-2-methyl-6-(trifluormethyl)- nicotinamid; N-(4-chlor-3-(3-fluorbenzamido)phenyl)-2-methyl-6-(trifluormethyl)- nicotinamid; N-(4-chlor-3-(4-fluorbenzamido)phenyl)-2-methyl-6-(trifluormethyl)- nicotinamid; N-(4-chlor-3-(3,4-difluorbenzamido)phenyl)-2-methyl-6-(trifluormethyl)- nicotinamid; N-(4-chlor-3-(3-chlor-4-fluorbenzamido)phenyl)-2-methyl-6- (trifluormethyl)-nicotinamid; N-(4-chlor-3-(2-morpholinobenzamido)phenyl)-2-methyl-6- (trifluormethyl)-nicotinamid; N-(4-chlor-3-(4-(4-methylpiperazin-1-yl)benzamido)phenyl)-2-methyl-6- (trifluormethyl)nicotinamid; N-(4-chlor-3-(4-methoxybenzamido)phenyl)-2-methyl-6-(trifluormethyl)- nicotinamid; N-(3-(4-(1,2,3-thiadiazol-4-yl)benzamido)-4-chlorphenyl)-2-methyl-6- (trifluormethyl)nicotinamid; N-(3-(4-(1H-imidazol-1-yl)benzamido)-4-chlorphenyl)-2-methyl-6- (trifluormethyl)nicotinamid; N-(3-(4-(1 H-1,2,4-triazol-1 -yl)benzamido)-4-chlorphenyl)-2-methyl-6-(trifluormethyl)nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-morpholinonicotinamid; N-(3-benzamido-4-chlorphenyl)-2-methyl-4-phenylpyrimidin-5- carboxamid; N-(3-benzamido-4-chlorphenyl)-1-(4-fluorphenyl)-4-methyl-1H-pyrazol-3- carboxamid; N-(3-benzamido-4-chlorphenyl)-4-methyl-2-phenylpyrimidin-5- carboxamid; N-(3-benzamido-4-chlorphenyl)-6-chlornicotinamid; N-(3-benzamido-4-chlorphenyl)-6-((3S,5R)-3,5-dimethylpiperazin-1-yl)- nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-(4-ethylpiperazin-1-yl)nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-(4-(2-hydroxyethyl)piperazin-1-yl)- nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-(2,6-dimethylmorpholino)nicotinamid; 6-(4-acetylpiperazin-1-yl)-N-(3-benzamido-4-chlorphenyl)nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-(4-hydroxypiperidin-1-yl)nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-(3-methylpiperazin-1-yl)nicotinamid; (R) -N-(3-benzamido-4-chlorphenyl)-6-(3-methylpiperazin-1-yl)nicotinamid; (S) -N-(3-benzamido-4-chlorphenyl)-6-(3-methylpiperazin-1-yl)nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-(piperazin-1-yl)nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-chlor-2-methylnicotinamid; N-(3-benzamido-4-chlorphenyl)-6-((3S,5R)-3,5-dimethylpiperazin-1-yl)-2- methyl-nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-(brommethyl)nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-(morpholinomethyl)nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-(piperidin-1-ylmethyl)nicotinamid; N-(3-benzamido-4-chlorphenyl)-6-((4-methylpiperazin-1-yl)methyl)- nicotinamid; N-(3-benzamido-4-chlorphenyl)-2-phenylthiazol-4-carboxamid; 6-chlor-N-(4-chlor-3-(4-fluorbenzamido)phenyl)nicotinamid; N-(4-chlor-3-(4-fluorbenzamido)phenyl)-6-((3S,5R)-3,5- dimethylpiperazin-1-yl)nicotinamid; N-(4-chlor-3-(4-fluorbenzamido)phenyl)-6-(4-hydroxypiperidin-1- yl)nicotinamid; 6-(4-acetylpiperazin-1-yl)-N-(4-chlor-3-(4-fluorbenzamido)- phenyl)nicotinamid; 6-(4-methylsulfonylpiperazin-1-yl-N-(4-chlor-3-(4-fluorbenzamido)phenyl- nicotinamid; N-(3-(4-fluorbenzamido)-4-chlorphenyl)-6-(4-propionylpiperazin-1- yl)pyridin-3-carboxamid; 6-(4-(3-methylbutanoyl)piperazin-1-yl)-N-(3-(4-fluorbenzamido)-4- chlorphenyl)pyridin-3-carboxamid; N-(3-(4-fluorbenzamido)-4-chlorphenyl)-6-(4- cyclopropylcarbonylpiperazin-1-yl)pyridin-3-carboxamid; N-(4-chlor-3-(4-fluorbenzamido)phenyl)-6-(4-ethylpiperazin-1- yl)nicotinamid; N-(4-chlor-3-(4-fluorbenzamido)phenyl)-6-(piperazin-1-yl)nicotinamid; N-(4-chlor-3-(4-fluorbenzamido)phenyl)-6-(3-methylpiperazin-1 -yl)nicotinamid; (R) -N-(4-chlor-3-(4-fluorbenzamido)phenyl)-6-(3-methylpiperazin-1-yl)-nicotinamid; (S) -N-(4-chlor-3-(4-fluorbenzamido)phenyl)-6-(3-methylpiperazin-1-yl)-nicotinamid; 6-chlor-N-(4-chlor-3-(4-fluorbenzamido)phenyl)-2-methylnicotinamid; N-(4-chlor-3-(4-fluorbenzamido)phenyl)-6-(4-hydroxypiperidin-1-yl)-2- methylnicotinamid; N-(4-chlor-3-(4-fluorbenzamido)phenyl)-6-(3,5-dimethylpiperazin-1-yl)-2- methylnicotinamid; 6-(4-acetylpiperazin-1-yl)-N-(4-chlor-3-(4-fluorbenzamido)phenyl)-2- methylnicotinamid; 6-chlor-N-(4-chlor-3-(3-chlorbenzamido)phenyl)nicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-((3S,5R)-3,5- dimethylpjperazin-1-yl)nicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-(4-hydroxypiperidin-1-yl)- nicotinamid; 6-(4-acetylpiperazin-1-yl)-N-(4-chlor-3-(3-chlorbenzamido)phenyl)- nicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-(4-ethylpiperazin-1- yl)nicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-(piperazin-1-yl)nicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-(4-(2-hydroxyethyl)piperazin- 1-yl)-nicotinamid; 6-(brommethyl)-N-(4-chlor-3-(3-chlorbenzamido)phenyl)nicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-((4-ethylpiperazin-1-yl)methyl)- nicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-((4-methylpiperazin-1- yl)methyl)-nicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-((1-methylpiperidin-4- ylamino)methyl)nicotinamid; 6-((4-acetylpiperazin-1-yl)methyl)-N-(4-chlor-3-(3- chlorbenzamido)phenyl)-nicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-(((3S,5R)-3,5- dimethylpiperazin-1-yl)methyl)nicotinamid; 6-chlor-N-(4-chlor-3-(3-chlorbenzamido)phenyl)-2-methylnicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-((3S,5R)-3,5- dimethylpiperazin-1-yl)-2-methylnicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-(4-hydroxypiperidin-1-yl)-2- methylnicotinamid; 6-chlor-N-(4-chlor-3-(3-chlorbenzamido)phenyl)-2-methylnicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-((3S,5R)-3,5- dimethylpiperazin-1-yl)-2-methylnicotinamid; N-(4-chlor-3-(3-chlorbenzamido)phenyl)-6-(4-hydroxypiperidin-1-yl)-2- methylnicotinamid; 6-(4-acetylpiperazin-1-yl)-N-(4-chlor-3-(3-chlorbenzamido)phenyl)-2- methyl-nicotinamid; 6-(4-acetylpiperazin-1-yl)-N-(4-chlor-3-(2-chlorbenzamido)- phenyl)nicotinamid; 6-(4-acetylpiperazin-1-yl)-N-(4-chlor-3-(2-fluorbenzamido)- phenyl)nicotinamid; 6-chlor-N-(4-chlor-3-(3-fluorbenzamido)phenyl)nicotinamid; N-(4-chlor-3-(3-fluorbenzamido)phenyl)-6-((3S,5R)-3,5- dimethylpiperazin-1-yl)-nicotinamid; N-(4-chlor-3-(3-fluorbenzamido)phenyl)-6-(4-hydroxypiperidin-1-yl)- nicotinamid; 6-(4-acetylpiperazin-1-yl)-N-(4-chlor-3-(3-fluorbenzamido)phenyl)- nicotinamid; 6-chlor-N-(4-chlor-3-(2-fluorbenzamido)phenyl)nicotinamid; N-(4-chlor-3-(2-fluorbenzamido)phenyl)-6-((3S,5R)-3,5- dimethylpiperazin-1-yl)nicotinamid; N-(4-chlor-3-(2-fluorbenzamido)phenyl)-6-(4-hydroxypiperidin-1-yl)- nicotinamid; 6-chlor-N-(4-chlor-3-(4-chlorbenzamido)phenyl)nicotinamid; N-(4-chlor-3-(4-chlorbenzamido)phenyl)-6-((3S,5R)-3,5- dimethylpiperazin-1-yl)nicotinamid; N-(4-chlor-3-(4-chlorbenzamido)phenyl)-6-(4-hydroxypiperidin-1-yl)- nicotinamid; 6-(4-acetylpiperazin-1-yl)-N-(4-chlor-3-(4-chlorbenzamido)phenyl)- nicotinamid; 6-chlor-N-(4-chlor-3-(2-chlorbenzamido)phenyl)nicotinamid; N-(4-chlor-3-(2-chlorbenzamido)phenyl)-6-((3S,5R)-3,5- dimethylpiperazin-1-yl)nicotinamid; N-(4-chlor-3-(2-chlorbenzamido)phenyl)-6-(4-hydroxypiperidin-1-yl)- nicotinamid; 6-chlor-N-(4-chlor-3-(4-methylbenzamido)phenyl)nicotinamid; N-(4-chlor-3-(4-methylbenzamido)phenyl)-6-((3S,5R)-3,5- dimethylpiperazin-1-yl)nicotinamid; N-(4-chlor-3-(4-methylbenzamido)phenyl)-6-(4-hydroxypiperidin-1-yl)- nicotinamid; 6-(4-acetylpiperazin-1-yl)-N-(4-chlor-3-(4-methylbenzamido)phenyl)- nicotinamid; 6-chlor-N-(4-chlor-3-(2-methylbenzamido)phenyl)nicotinamid; N-(4-chlor-3-(2-methylbenzamido)phenyl)-6-((3S,5R)-3,5- dimethylpiperazin-1-yl)nicotinamid; N-(4-chlor-3-(2-methylbenzamido)phenyl)-6-(4-hydroxypiperidin-1-yl)- nicotinamid; 6-(4-acetylpiperazin-1-yl)-N-(4-chlor-3-(2-methylbenzamido)phenyl)- nicotinamid; 6-chlor-N-(4-chlor-3-(3-methylbenzamido)phenyl)nicotinamid; N-(4-chlor-3-(3-methylbenzamido)phenyl)-6-((3S,5R)-3,5- dimethylpiperazin-1-yl)nicotinamid; N-(4-chlor-3-(3-methylbenzamido)phenyl)-6-(4-hydroxypiperidin-1-yl)-nicotinamid; og 6-(4-acetylpiperazin-1-yl)-N-(4-chlor-3-(3-methylbenzamido)phenyl)- nicotinamid.
DK06844364.7T 2005-11-14 2006-11-14 Bisamidhæmmere af hedgehog-signalering DK1957461T3 (da)

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EP1957461A1 (en) 2008-08-20
AU2006315467A1 (en) 2007-05-24
JP2013079283A (ja) 2013-05-02
EP1957461B1 (en) 2016-11-02
ES2604539T3 (es) 2017-03-07
US8101610B2 (en) 2012-01-24
US20080269215A1 (en) 2008-10-30
JP5225857B2 (ja) 2013-07-03
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CA2629814C (en) 2013-12-31

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