903575-56-4

Upstream product

• 153-94-6 D-tryptophan 
• 104-88-1 4-chlorobenzaldehyde 
• 4299-70-1 D-Tryptophan methyl ester 

Downstream Products

• 1286256-49-2 (6R,12aR)-2-ethyl-6-(4-chlorophenyl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione 
• 1286256-57-2 (6R,12aR)-2-tert-butyl-6-(4-chlorophenyl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione 
• 1286256-42-5 (5R,11aR)-2,5-bis(4-chlorophenyl)-5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione 
• 1027590-60-8 methyl (1R,3R)-1-(4-chlorophenyl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate 
• 1286256-38-9 (5R,11aR)-2-tert-butyl-5-(4-chlorophenyl)-5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione 

Relevant academic research and scientific papers

Synthesis of tadalafil analogues

Five novel compounds as potential phosphodiesterase type 5 (PDE-5) inhibitors were synthesized from D-tryptophan methyl ester via the Pictet-Spengler reaction and cyclization reaction. The structures of those compounds were confirmed by elemental analyses

Extending the use of tadalafil scaffold: Development of novel selective phosphodiesterase 5 inhibitors and histone deacetylase inhibitors

Herein we present the synthesis and characterization of a novel chemical series of tadalafil analogues that display different pharmacological profiles. Compounds that have the 6R, 12aR configuration and terminal carboxylic acid group at the side chain arising from the piperazinedione nitrogen were potent PDE5 inhibitors, with compound 11 having almost equal potency to tadalafil and superior selectivity over PDE11, the most common off–target for tadalafil. Modifying the stereochemistry into 6S, 12aS configuration and adopting the hydroxamic acid moiety as a terminal group gave rise to compounds that only inhibited HDAC. Dual PDE5/HDAC inhibition could be achieved with compounds having 6R, 12aR configuration and hydroxamic acid moiety as a terminal group. The anticancer activity of the synthesized compounds was evaluated against a diverse number of cell lines of different origin. The compounds elicited anticancer activity against cell lines belonging to lymphoproliferative cancer as well as solid tumors. Despite the previous reports suggesting anticancer activity of PDE5 inhibitors, the growth inhibitory activity of the compounds seemed to be solely dependent on HDAC inhibition. Compound 26 (pan HDAC IC50 = 14 nM, PDE5 IC50 = 46 nM) displayed the most potent anticancer activity in the present series and was shown to induce apoptosis in Molt-4 cells. HDAC isoform selectivity testing for compound 26 showed that it is more selective for HDAC6 and 8 over HDAC1 by more than 20-fold.

Design, synthesis and structure-activity relationship of functionalized tetrahydro-β-carboline derivatives as novel PDE5 inhibitors

Starting from tadalafil as a template, a series of functionalized tetrahydro-β-carboline derivatives have been prepared and identified as novel potent and selective PDE5 inhibitors. Replacing the 3,4- methylenedioxyphenyl at position 6 of tadalafil, together with elongation of the N2-methyl substituent and manipulation of the stereochemical aspects of the two chiral carbons led to the identification of compound XXI, a highly potent PDE5 inhibitor (IC50 = 3 nM). Compound XXI was also highly selective for PDE5 versus PDE3B, PDE4B, and PDE11A, with a selectivity index of 52 and 235 towards PDE5 rather than PDE11 with both cAMP and cGMP as substrate, respectively.

Pictet-Spengler cyclization in room temperature ionic liquid: A convenient access to tetrahydro β-carbolines

1,2,3,4-Tetrahydro-β-carbolines have been synthesized in moderate to good yields in short reaction time using the ionic liquid [bbim] BF4 as reaction medium and promoter. There was no need for the use of an additional catalyst normally employed