DELAVIRDINE, MESYLATE Chemical Properties

Melting point:

118-120°C

storage temp. 

Inert atmosphere,Room Temperature

solubility 

DMSO: >5mg/mL

form 

powder

color 

white to tan

CAS DataBase Reference

147221-93-0

Safety Information

WGK Germany 

3

Hazardous Substances Data

147221-93-0(Hazardous Substances Data)

DELAVIRDINE, MESYLATE Usage And Synthesis

Description

Rescriptor was launched in the US for HIV positive individuals. It can be prepared in seven steps from 2-chloro-3-nitropyridine and piperazine. Rescriptor is a member of the bis(heteroaryl)piperazine (BHAP) class of non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) of which it is a second generation drug. It acts exclusively as an allosteric mixed inhibitor of both RNA- and DNA-directed polymerase domains of RT and has a much higher binding affintiy for the enzymesubstrate complex than for the free enzyme. Rescriptor does not inhibit RNase H activity of RT. It prevented the spread of HIV significantly longer than AZT. Development of resistance to Rescriptor can occur, however the mutated strain becomes more vulnerable to other members of the NNRTIs. It is metabolized in the liver by CYP3A.

Chemical Properties

Light Brown Solid

Originator

Pharmacia ＆ Upjohn (US)

Uses

A bisheteroarylpiperazine (BHAP) reverse transcriptase inhibitor.

Definition

ChEBI: The monomethanesulfonic acid salt of delavirdine, a non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. Viral resistance emerges rapidly when delavirdine is used alone, so it is therefore used (as the methanesulfonic acid salt) with other antiretrovirals for combination therapy of HIV infection.

Manufacturing Process

5-Nitroindole-2-carboxylic acid (0.86 g), 1-[3-(N-isopropyl)amino-2- pyridinyl]piperazine (0.43 g), 1-(ethyl)-3-(dimethylaminopropyl)carbodiimide (0.45 g) and THF (4 ml), were stirred at 20-25°C for 3 hr; then the reaction mixture was dissolved in chloroform (50 ml) and extracted with saturated aqueous sodium bicarbonate, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography (200 g silica) eluting with ethyl acetate/hexane (50/50), the appropriate fractions were pooled and concentrated to give 1-[5-nitroindolyl2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, mp 153°- 154°C.
1-[5-Nitroindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2- pyridinyl]piperazine (1.0 g) was dissolved in ethanol (60 ml) and THF (60 ml) and palladium on carbon (10%, 0.15 g) was added. The reaction mixture was hydrogenated at 40 psi for 14 hr, then filtered through celite and concentrated under reduced pressure. Purification by flash chromatography, eluting with ethyl acetate/hexane (50/50) pooling and concentrating the appropriate fractions gave 1-[5-aminoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2- pyridinyl]piperazine, mp 212°-214°C.
1-[5-Aminoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2- pyridinyl]piperazine (0.075 mg) was dissolved in methylene chloride (0.4 ml) and pyridine (0.016 g) was added and the reaction is cooled to 0°C. Then methanesulfonyl chloride (0.023 g) was added. After 2.5 hr of stirring, the reaction was diluted with chloroform and washed with saturated aqueous sodium bicarbonate, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate was dissolved in the minimum amount of chloroform and passed through a small plug of silica gel and then it is recrystallized with ethyl acetate/hexane to provide the 1-[5- methansulfoneamidolyl-2-carbonyl]-4-[3-(1-methylethylenamino)-2- pyridinyl]piperazine, mp 226°-228°C.
The mesylate salt may be formed by dissolving the free base in methanol and methanesulfonic acid (1 eq) is added.

brand name

Rescriptor (Agouron).

Therapeutic Function

Antiviral, Anti-HIV virus agent

DELAVIRDINE, MESYLATE(147221-93-0)Related Product Information

• DELAVIRDINE
• 2-(4-METHYLPIPERAZINO)-3-PYRIDINAMINE
• 3-PYRIDYLAMINE, N-(1-METHYLETHYL)-2-(1-PIPERAZINYL)-,DIHYDROCHLORIDE MONOHYDRATE
• 3-Pyridinamine,2-(1-piperazinyl)-(9CI)
• 3-(Ethylamino)-2-(1-piperazinyl)pyridine
• DELAVIRDINE, MESYLATE