DELAVIRDINE, MESYLATE Struktur

DELAVIRDINE, MESYLATE

Bezeichnung:DELAVIRDINE, MESYLATE

CAS-Nr147221-93-0

Englisch Name:DELAVIRDINE, MESYLATE

CBNumberCB1292152

SummenformelC23H32N6O6S2

Molgewicht552.67

MOL-Datei147221-93-0.mol

DELAVIRDINE, MESYLATE physikalisch-chemischer Eigenschaften

Schmelzpunkt	118-120°C
storage temp.	Inert atmosphere,Room Temperature
Löslichkeit	DMSO: >5mg/mL
Aggregatzustand	powder
Farbe	white to tan
CAS Datenbank	147221-93-0

Sicherheit

WGK Germany	3
Giftige Stoffe Daten	147221-93-0(Hazardous Substances Data)

Gefahreninformationscode (GHS)

DELAVIRDINE, MESYLATE Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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.
Chemische Eigenschaften
Light Brown Solid
Originator
Pharmacia ＆ Upjohn (US)
Verwenden
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.
Trademarks
Rescriptor (Agouron).
Therapeutic Function
Antiviral, Anti-HIV virus agent

DELAVIRDINE, MESYLATE Upstream-Materialien And Downstream Produkte

DELAVIRDINE, MESYLATE Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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