171596-42-2

Basic information

• Product Name: (1S,3R)-Methyl-1,2,3,4-tetrahydro-1-(3,4-Methylenedioxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate
• Synonyms: (1S,3R)-Methyl-1,2,3,4-tetrahydro-1-(3,4-Methylenedioxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate;(1S,3R)-1-(1,3-Benzodioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic Acid Methyl Ester;Tadalafil Impuirty Ⅵ
• CAS NO: 171596-42-2
• Molecular Formula: C₂₀H₁₈N₂O₄
• Molecular Weight: 350
• Product Categories: Chiral Reagents
• Mol File: 171596-42-2.mol

Chemical Properties

• Melting Point: 83-85°C
• Boiling Point: 531.0±50.0 °C(Predicted)
• Appearance: /
• Density: 1.359±0.06 g/cm3(Predicted)
• Storage Temp.: Refrigerator
• Solubility: Acetone (Slightly), Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (S
• PKA: 16.87±0.60(Predicted)
• CAS DataBase Reference: (1S,3R)-Methyl-1,2,3,4-tetrahydro-1-(3,4-Methylenedioxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: (1S,3R)-Methyl-1,2,3,4-tetrahydro-1-(3,4-Methylenedioxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate(171596-42-2)
• EPA Substance Registry System: (1S,3R)-Methyl-1,2,3,4-tetrahydro-1-(3,4-Methylenedioxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate(171596-42-2)

Safety Data

• Hazardous Substances Data: 171596-42-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(1S,3R)-Methyl-1,2,3,4-tetrahydro-1-(3,4-Methylenedioxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate is used as an intermediate in the synthesis of Tadalafil (T004500) for the treatment of erectile dysfunction. Tadalafil is a phosphodiesterase 5 inhibitor that helps improve blood flow to the penis, allowing for a stronger and more sustained erection in response to sexual stimulation.
As an intermediate in the synthesis of Tadalafil, this compound is essential for the development of medications that address erectile dysfunction, a common condition affecting many men worldwide. Its role in the pharmaceutical industry highlights the importance of its chemical properties and the potential for further research and development in this area.

Upstream product

• 120-57-0 piperonal 
• 14907-27-8 (R)-(+)-tryptophan methyl ester hydrochloride 
• 1039484-71-3 (3R)-1-(3,4-methylenedioxyphenyl)-2,3,4,9-tetrahidro-9H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester 
• 171752-68-4 (1R,3R)-1-benzo[1,3]dioxol-5-yl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester hydrochloride 
• 17680-04-5 (3,4-methylenedioxy)phenylmagnesium bromide 
• 153-94-6 D-tryptophan 
• 497182-99-7 (S)-1-benzo[1,3]dioxol-5-yl-2-benzyl-2,3,4,9-tetrahydro-1H-β-carboline-(R)-3-carboxylic acid methyl ester 
• 1453864-08-8 (1S,3R)-methyl 1-(benzo[d][1,3]dioxol-5-yl)-2-(naphthalen-1-yl-methyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate 
• 1453863-95-0 (1S,3S)-methyl 1-(benzo[d][1,3]dioxol-5-yl)-2-(naphthalen-1-yl-methyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate 
• 171596-43-3 (1S,3S)-1-(3,4-methylenedioxyphenyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid methyl ester 
• 1453863-96-1 (1S,3S)-methyl 1-(benzo[d][1,3]dioxol-5-yl)-2-benzyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate 
• 4299-70-1 L-tryptophan methyl ester 
• 67-56-1 methanol 
• 474668-76-3 (1R,3R)-1,2,3,4-tetrahydro-1-(3,4-methylenedioxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylic acid hydrochloride 

Downstream Products

• 171596-41-1 (1R,3R)-methyl 1,2,3,4-tetrahydro-1-(3,4-methylenedioxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate 
• 171489-59-1 methyl (1R,3R)-1-(3,4-methylenedioxyphenyl)-2-chloroacetyl-2,3,4,9-tetrahydro-9H-pyrido[3,4-b]indol-3-carboxylate 
• 1018814-78-2 (6S,12aR)-6-(benzo[d][1,3]dioxol-5-yl)-2-((R)-1-benzylpyrrolidin-3-yl)-2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione 
• 171596-28-4 (6S,12aR)-6-(benzo[d][1,3]dioxol-5-yl)-2-methyl-2,3,12,12a tetrahydropyrazino [1',2':1,6] pyrido[3,4b] indole1,4(6H,7H)-dione 
• 629652-72-8 (6R,12aR)-6-(1,3-benzodioxol-5-yl)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1′,2’:1,6]-pyrido[3,4-b]indole-1,4-dione 
• 531500-48-8 11-benzo[1,3]dioxol-5-yl-3-methyl-2,3,4a,11-tetrahydro-10H-3,10,11a-triaza-benzo[b]fluorene-1,4,5-trione 
• 531500-48-8 11-benzo[1,3]dioxol-5-yl-3-methyl-2,3,4a,11-tetrahydro-10H-3,10,11a-triaza-benzo[b]fluorene-1,4,5-trione 
• 497182-99-7 (S)-1-benzo[1,3]dioxol-5-yl-2-benzyl-2,3,4,9-tetrahydro-1H-β-carboline-(R)-3-carboxylic acid methyl ester 

Relevant articles and documents

Preparation method of tadalafil intermediate impurity

A preparation method of a tadalafil intermediate impurity comprises the following steps: firstly, fully dissolving raw materials in an isomerization solvent, sequentially carrying out a heating reflux reaction and vacuum concentration to obtain a residue I, adding an alkaline solution and an extraction solvent into the residue I, sequentially carrying out room temperature stirring and standing, then taking an organic phase, and carrying out vacuum evaporation to dryness to obtain a residue II; and adding a resolving solvent into the residue II, sequentially carrying out heating reflux reaction, natural stirring crystallization and filtration to obtain filtrate and a filter cake, and finally drying the filter cake to obtain an intermediate impurity, wherein the temperature of natural stirring crystallization is 30-60 DEG C. According to the preparation method, the principle that the intermediates and the reaction byproducts have different solubilities in the resolving solvents at different temperatures is utilized, the intermediates and the reaction byproducts are resolved, the preparation efficiency is high, the cost is low, and the purity of the prepared intermediates is high.

NOVEL DUAL MODE OF ACTION SOLUBLE GUANYLATE CYCLASE ACTIVATORS AND PHOSPHODIESTERASE INHIBITORS AND USES THEREOF

The present invention relates to compounds of formula (I), or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein said compound of formula (I) comprises at least one covalently bound -ONO2 or -ONO moiety and at most four covalently bound -ONO2 or -ONO moieties, and wherein AR, R1, X, R3 and R4 are as defined in claim 1; and pharmaceutical compositions thereof, and their use in methods of treating or preventing a disease alleviated by inhibition of PDE5 in a human or in a non-human mammal.

3,4-methylenedioxyphenyl substituted tetrahydro-beta-carboline piperazine dione derivative and uses thereof

The present invention relates to a 3,4-methylenedioxyphenyl substituted tetrahydro-beta-carboline piperazine dione derivative and uses thereof, and specifically discloses a compound represented by a formula I, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein each group is defined in the specification. According to the present invention, the compound has dual inhibitory activity on acetylcholinesterase and phosphodiesterase 5, and has good blood-brain barrier permeability, such that the compound can be used for preparing drugs for treatment and/or prevention ofAlzheimer's diseases. The formula I is defined in the specification.

Design, Synthesis, and Biological Evaluation of Orally Available First-Generation Dual-Target Selective Inhibitors of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) for the Treatment of Alzheimer's Disease

Through drug discovery strategies of repurposing and redeveloping existing drugs, a series of novel tadalafil derivatives were rationally designed, synthesized, and evaluated to seek dual-target AChE/PDE5 inhibitors as good candidate drugs for Alzheimer's disease (AD). Among these derivatives, 1p and 1w exhibited excellent selective dual-target AChE/PDE5 inhibitory activities and improved blood-brain barrier (BBB) penetrability. Importantly, 1w·Cit (citrate of 1w) could reverse the cognitive dysfunction of scopolamine-induced AD mice and exhibited an excellent effect on enhancing cAMP response element-binding protein (CREB) phosphorylation in vivo, a crucial factor in memory formation and synaptic plasticity. Moreover, the molecular docking simulations of 1w with hAChE and hPDE5A confirmed that our design strategy was rational. In summary, our research provides a potential selective dual-target AChE/PDE5 inhibitor as a good candidate drug for the treatment of AD, and it could also be regarded as a small molecule probe to validate the novel AD therapeutic approach in vivo.

Preparation method of tadalafil

The invention discloses a preparation method of tadalafil, starting material D-Tryptophan methyl ester hydrochloride is reacted with oxalyl chloride to obtain an intermediate III, and the final product tadalafil (I) is obtained through cyclization, Grignard reaction, asymmetric reduction, substitution and condensation reaction. The use of national control chemical piperonal is avoided, an intermediate VI can be highly-selectively obtained by the asymmetric reduction, and the method has the advantages of simple postprocessing, short synthesis steps and high product total yield, and is suitable for industrialized production.

Improved synthesis of tadalafil using dimethyl carbonate and ionic liquids

An improved synthesis of tadalafil, a drug for the treatment of male erectile dysfunction, involves the use of safer solvents and reagents as well as a reduced number of steps.

Highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted tetrahydro-β-carbolines into (1S,3R)-trans-1,3-disubstituted tetrahydro-β-carbolines: An improved asymmetric synthesis of tadalafil from l-tryptophan

An efficient and general method for the highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted 1,2,3,4-tetrahydro-β- carbolines (THBCs) into (1S,3R)-trans-1,3-disubstituted THBCs is described. The method contains the following three steps: the enantiomerically pure (1S,3S)-cis-1,3-disubstituted THBCs 1 were first converted into (1S,3S)-cis-1,2,3-trisubstituted THBCs 2 by N-1-naphthylmethylation/benzylation; (1S,3S)-cis-1,2,3-trisubstituted THBCs2 were then converted into (1S,3R)-trans-1,2,3-trisubstituted THBCs 3 in high yields and with high stereoselectivities via a base-catalyzed epimerization at C-3; (1S,3R)-trans-1,2,3-trisubstituted THBCs 3 were subsequently converted into (1S,3R)-trans-1,3-disubstituted THBCs 4 after reductive removal of the 1-naphthylmethyl/benzyl group. In addition, as an application of this method, an improved and highly stereoselective synthesis of the PDE5 inhibitor tadalafil (Cialis) starting from natural and less expensive l-tryptophan was developed.

Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 2. Tadalafil analogs

In this Letter we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). We outline the synthesis and biological evaluation of analogs of tadalafil, a human PDE5 inhibitor currently utilized for treatment of erectile dysfunction, and report that these analogs are weak inhibitors of TbrPDEB1.

Drug to genome to drug: Discovery of new antiplasmodial compounds

Figure Presented. The dominant strategy for discovery of new antimalarial drugs relies on cell-free assays on specific biochemical pathways of Plasmodium falciparum. However, it appears that screening directly on the parasite is a more rewarding approach. The drug to genome to drug approach consists of testing a small set of structural analogues of a drug acting on human proteins that have plasmodial orthologues. Both man and plasmodium possess cyclic nucleotide phosphodiesterases (PDEs) that are key players of cell homeostasis. We synthesized and tested 40 analogues of tadalafil, a human PDE5 inhibitor, on P. falciparum in culture and obtained potent inhibitors of parasite growth. We discuss the structure-activity relationships, which support the hypothesis that our compounds kill the parasite via inhibition of plasmodial PDE activity. We also prove that antiplasmodial derivatives inhibit the hydrolysis of cyclic nucleotides of the parasite, validating the cAMP/cGMP pathways as therapeutic targets against Plasmodium falciparum.

One-pot pictet-spengler reaction and esterification for the preparation of a key tadalafil synthetic intermediate

A new method is reported for the preparation of 2,3,4,9-tetrahydro-1H- β-carboline-3-carboxylic acid methyl ester, a key intermediate in the synthesis of Tadalafil which is used for the treatment of male erectile dysfunction, via one-pot esterification and Pictet-Spengler reaction.