629652-72-8

Usage

Uses

Used in Pharmaceutical Industry:
ent-Tadalafil is used as a pharmaceutical compound for its potential therapeutic applications. As an analog of Tadalafil, it may possess similar properties and effects, which can be explored for the development of new drugs or treatments.
Used in Research and Development:
In the field of research and development, ent-Tadalafil serves as a valuable compound for studying the structure-activity relationships of Tadalafil and its derivatives. This can lead to the discovery of new drugs with improved efficacy and safety profiles.
Used in Quality Control and Impurity Profiling:
As a known impurity of Tadalafil, ent-Tadalafil is used in the quality control and impurity profiling of Tadalafil-containing pharmaceutical products. This helps ensure the safety, efficacy, and purity of the final drug product.
Used in Chemical Synthesis:
Due to its unique chemical properties, ent-Tadalafil can be used as a starting material or intermediate in the synthesis of other related compounds. This can be particularly useful in the development of new drugs or materials with specific applications.

Upstream product

• 74-89-5 methylamine 
• 629652-42-2 methyl (1S,3S)-1-(benzo[d][1,3]dioxol-5-yl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate 
• 593-51-1 methylamine hydrochloride 
• 7524-52-9 (S)-tryptophan methyl ester hydrochloride 
• 73-22-3 L-Tryptophan 
• 171596-43-3 (1S,3S)-1-(3,4-methylenedioxyphenyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid methyl ester 
• 4299-70-1 L-tryptophan methyl ester 
• 120-57-0 piperonal 
• 171596-42-2 (1S,3R)-1-(3,4-methylenedioxyphenyl)-2,3,4,9-tetrahidro-9H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester 
• 14907-27-8 (R)-(+)-tryptophan methyl ester hydrochloride 
• 629652-40-0 (1S,3R)-1-benzo[1,3]dioxol-5-yl-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester 

Downstream Products

• 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 
• 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 

Relevant academic research and scientific papers

Diastereospecific Synthesis of Tetrahydroisoquinolines via Radical Cyclization: Application in the Synthesis of ent-Tadalafil

An enantioselective synthesis of 1-substituted tetrahydroisoquinolines from L–Dopa methyl ester through intramolecular aryl radical cyclization is demonstrated. The strategy consists of bromination of (S)-2-amino-3-(2-bromo-4,5-dimethoxyphenyl)propanoate followed by condensation with various aldehydes to afford bromoimidate ester. Aryl radicals generated from bromoimidate ester under the radical generating conditions (nBu3SnH/AIBN) cyclizes via 6-endo mode to afford cis-1-substituted tetrahydroisoquinolines exclusively in 99% ee. The utility of this synthetic protocol is demonstrated in the synthesis of (6S, 12aS) Tadalafil (5 steps, 21%, 99% ee). (Figure presented.).

Preparation method of Tadalafil isomer

The invention discloses a preparation method of a Tadalafil isomer, and belongs to the technical field of drug synthesis. The preparation method comprises the following steps: placing Tadalafil into anon-proton strong polar solvent, and performing partial racemization by using an organic base to obtain an isomer I; performing total synthesis on L-tryptophan serving as a raw material through a four-step reaction to obtain an isomer II; placing the isomer II into the non-proton strong polar solvent, and performing partial racemization by using an organic base to obtain an isomer III; performingstructure confirmation on the three isomers. The preparation method provided by the invention has the advantages of simple procedure, high yield, easiness in post-treatment and easiness in purification.

Synthesis and SAR of tetracyclic pyrroloquinolones as phosphodiesterase 5 inhibitors

The synthesis of the fused tetracyclic pyrroloquinolones 9a-i in four steps is described. The PDE5 inhibitory activities of these compounds, their selectivities against PDE1, PDE2, PDE3, PDE4 and PDE6, the preclinical pharmacokinetic assessments and the in vivo efficacy in increasing intracavernosal pressure are presented and discussed.

The discovery of tadalafil: A novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-Hexahydropyrazino[1′,2′ :1,6]pyrido[3,4-b]indole-1,4-dione analogues

Modification of the hydantoin ring in the previously described lead compound 2a has led to the discovery of compound 12a, tadalafil, a highly potent and highly selective PDE5 inhibitor. The replacement of the hydantoin in compound 2a by a piperazinedione ring led to compound cis-11a which showed similar PDE5 inhibitory potency. Introduction of a 3,4-methylenedioxy substitution on the phenyl ring in position 6 led to a potent PDE5 inhibitor cis-11c with increased cellular potency. Optimization of the chain on the piperazinedione ring led to the identification of the racemic cis-N-methyl derivative 11i. High diastereospecificity for PDE5 inhibition was observed in the piperazinedione series with the cis-(6R,12aR) enantiomer displaying the highest PDE5 inhibitory activity. The piperazinedione 12a, tadalafil (GF196960), has been identified as a highly potent PDE5 inhibitor (IC50 = 5 nM) with high selectivity for PDE5 vs PDE1-4 and PDE6. Compound 12a displays 85-fold greater selectivity vs PDE6 than sildenafil 1. 12a showed profound and long-lasting blood pressure lowering activity (30 mmHg/>7 h) in the spontaneously hypertensive rat model after oral administration (5 mg/kg).