1038924-00-3

Basic information

• Product Name: 7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylic acid, 13-cyclohexyl-3-methoxy-, 10-(1,1-dimethylethyl) ester
• Synonyms: 7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylic acid, 13-cyclohexyl-3-methoxy-, 10-(1,1-dimethylethyl) ester
• CAS NO: 1038924-00-3
• Molecular Weight: 487.596
• Mol File: 1038924-00-3.mol
• Article Data: 6

Chemical Properties

• CAS DataBase Reference: 7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylic acid, 13-cyclohexyl-3-methoxy-, 10-(1,1-dimethylethyl) ester(CAS DataBase Reference)
• NIST Chemistry Reference: 7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylic acid, 13-cyclohexyl-3-methoxy-, 10-(1,1-dimethylethyl) ester(1038924-00-3)
• EPA Substance Registry System: 7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylic acid, 13-cyclohexyl-3-methoxy-, 10-(1,1-dimethylethyl) ester(1038924-00-3)

Safety Data

• Hazardous Substances Data: 1038924-00-3(Hazardous Substances Data)

Upstream product

• 928844-30-8 13-cyclohexyl-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylic acid 10-(1,1-dimethylethyl) ester 6-methyl ester 
• 108-94-1 cyclohexanone 
• 50820-65-0 indole-6-carboxylic acid methyl ester 
• 1670-82-2 Indole-6-carboxylic acid 
• 494799-76-7 2-bromo-3-cyclohexyl-1H-indole-6-carboxylic acid 
• 494799-19-8 methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate 
• 494799-16-5 3-(cyclohex-1-en-1-yl)-1H-indole-6-carboxylic acid 
• 494799-17-6 3-cyclohexyl-1-methyl-1H-indole-6-carboxylic acid 
• 494799-18-7 methyl 3-cyclohexyl-1H-indole-6-carboxylate 
• 139962-95-1 2-formyl-4-methoxyphenylboronic acid 
• 879498-90-5 1H-indole-6-carboxylic acid, 2-bromo-3-cyclohexyl-, 1,1-dimethylethyl ester 
• 958002-18-1 1H-indole-6-carboxylic acid, 3-cyclohexyl-2-(2-formyl-4-methoxyphenyl)-, 1,1-dimethylethyl ester 

Downstream Products

• 1204416-97-6 2,19-methano-3,7:4,1-dimetheno-1H,11H-14,10,2,9,11,17-benzoxathiatetraazacyclodocosine-8,18(9H,15H)-dione, 27-cyclohexyl-12,13,16,17-tetrahydro-22-methoxy-11,17-dimethyl-, 10,10-dioxide 
• 1204417-13-9 11H-2,18-methano-3,7:4,1-dimetheno-10,2,9,11,16-benzothiatetraazacycloheneicosine-8,17(9H,12H)-dione, 26-cyclohexyl-13,14,15,16-tetrahydro-21-methoxy-11,16-dimethyl-, 10,10-dioxide 
• 1384259-02-2 C₃₆H₄₇N₃O₄ 
• 1485522-43-7 1,1-dimethylethyl 13-cyclohexyl-3-methoxy-6-[[(methylsulfonyl)oxy]methyl]-7H-indolo[2,1-a] [2]-benzazepine-10-carboxylate 
• 1485522-40-4 1,1-dimethylethyl 13-cyclohexyl-6-hydroxymethyl-3-methoxy-7H-indolo[2,1-a][2]benzazepine-10-carboxylate 
• 1204417-29-7 C₄₁H₅₄N₄O₆ 
• 1384259-03-3 C₃₅H₄₅N₃O₄ 
• 1384259-01-1 C₃₈H₅₁N₃O₄ 
• 1384259-04-4 C₃₅H₄₆N₄O₄ 
• 1204417-01-5 C₃₂H₃₇N₅O₅S 
• 1204416-99-8 (19R)-2,19-methano-3,7:4,1-dimetheno-1H,11H-14,10,2,9,11,17-benzoxathiatetraazacyclodocosine-8,18(9H,15H)-dione 27-cyclohexyl-12,13,16,17,19,20-hexahydro-22-methoxy-11,17-dimethyl-10,10-dioxide 
• 1204417-00-4 (19S)-2,19-methano-3,7:4,1-dimetheno-1H,11H-14,10,2,9,11,17-benzoxathiatetraazacyclodocosine-8,18-(9H,15H)-dione 27-cyclohexyl-12,13,16,17,19,20-hexahydro-22-methoxy-11,17-dimethyl-10,10-dioxide 
• 1204417-02-6 C₃₂H₃₉N₅O₅S 
• 1204417-21-9 C₃₂H₃₈N₄O₅S 

Relevant articles and documents

Discovery and early development of TMC647055, a non-nucleoside inhibitor of the hepatitis C virus NS5B polymerase

Structure-based macrocyclization of a 6-carboxylic acid indole chemotype has yielded potent and selective finger-loop inhibitors of the hepatitis C virus (HCV) NS5B polymerase. Lead optimization in conjunction with in vivo evaluation in rats identified several compounds showing (i) nanomolar potency in HCV replicon cells, (ii) limited toxicity and off-target activities, and (iii) encouraging preclinical pharmacokinetic profiles characterized by high liver distribution. This effort culminated in the identification of TMC647055 (10a), a nonzwitterionic 17-membered-ring macrocycle characterized by high affinity, long polymerase residence time, and broad genotypic coverage. In vitro results of the combination of 10a with the HCV protease inhibitor TMC435 (simeprevir) supported an evaluation of this combination in patients with regard to virus suppression and resistance emergence. In a phase 1b trial with HCV genotype 1-infected patients, 10a was considered to be safe and well-tolerated and demonstrated potent antiviral activity, which was further enhanced in a combination study with TMC435.

MACROCYCLIC INDOLE DERIVATIVES USEFUL AS HEPATITIS C VIRUS INHIBITORS

Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein R1, R2, R4, R5, R6 and R7 have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in HCV therapy.

COMPOUNDS FOR THE TREATMENT OF HEPATITIS C

The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.