330600-85-6 Usage
Description
(1S,2R,3R,4R)-3-(1-acetamido-2-ethyl-butyl)-4-(diaminomethylideneamino)-2-hydroxy-cyclopentane-1-carboxylic acid, also known as Peramivir, is a neuraminidase (NA) inhibitor that was approved in Japan in 2010 for the treatment of patients with influenza. It is the only NA inhibitor available for intravenous (IV) use and is the first of two NA inhibitors approved in 2010, the second being the inhaled drug laninamivir octanoate. Peramivir was discovered using structure-based drug design and is synthesized in six steps from Boc-protected methyl (1S,4R)-4-amino-cyclopent-2-enecarboxylate, which is prepared from 2-azabicyclo[2.2.1]hept-5-en-3-one. It is a potent inhibitor of influenza virus A and B NA, with a low enzymatic off-rate, suggesting that it could inhibit NA activity for a prolonged period and allow a lower frequency of dosing.
Uses
Used in Influenza Treatment:
Peramivir is used as a neuraminidase inhibitor for treating human and avian influenza. It is selective for influenza neuraminidase over bacterial, mammalian, and other viral neuraminidases. It inhibits neuraminidase activity in H1N1, H2N2, H3N2, and H6N2 influenza strains and reduces lysis of MDCK cells infected with influenza. Pretreatment with peramivir protects mice against lethal influenza infections and increases survival in ferrets infected intranasally with avian influenza type A H5N1 when injected intramuscularly after infection.
Used in Pharmaceutical Industry:
Peramivir is used in the pharmaceutical industry for the development of antiviral drugs targeting influenza viruses. Its unique structure and potent inhibitory activity against neuraminidase make it a valuable compound for the treatment of influenza infections, particularly in seriously ill patients who require intravenous administration. Formulations containing peramivir have been used to treat influenza, providing an effective therapeutic option for patients suffering from this viral infection.
Originator
BioCryst Pharmaceuticals Inc. (United States)
Synthesis
Several syntheses of this drug have been reported and the improved route disclosed in a recent
patent is described in the scheme. Ring opening of commercially available (±)-2-
azabicyclo[2.2.1]hept-5-en-3-one (117) with methanolic HCl followed by classical resolution with Ltartaric
acid gave the (1S,4R)-methyl ester 118 in 85% yield. Protection of 118 with Boc anhydride and
TEA in CH2Cl2 afforded carbamate 119 in 90% yield. Alkene 119 was then subject to nitrone dipolar
cycloaddition conditions involving 2-ethyl-N-hydroxybutanimidoyl chloride 120 and triethylamine,
followed by the basic workup and then treatment with methanolic HCl, ultimately resulting in
dihydroisoxazole 121. Interestingly, the nitrone generated from 120 approached alkene 119 from the
less hindered face and proceeded with remarkable regioselectivity to provide azacycle 121 in 76% yield
for the three step sequence. Treatment of 121 with 1.5 eq. lithium aluminum hydride resulted in
rupture of the N-O bond within this system, which afforded the amino alcohol 122 in 81% yield. It
should be noted that neither the Boc group or the methyl ester were reduced under these reaction
conditions. Then, a one-pot three step sequence involving acetylation of the amino group, removal of
the Boc group, and hydrolysis of the carboxylic ester followed by guanylation with
pyrazolecarboxamidine hydrochloride (123) provided peramivir (X) in 82% yield over the final four
steps.
Check Digit Verification of cas no
The CAS Registry Mumber 330600-85-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,3,0,6,0 and 0 respectively; the second part has 2 digits, 8 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 330600-85:
(8*3)+(7*3)+(6*0)+(5*6)+(4*0)+(3*0)+(2*8)+(1*5)=96
96 % 10 = 6
So 330600-85-6 is a valid CAS Registry Number.
InChI:InChI=1/C15H28N4O4/c1-4-8(5-2)12(18-7(3)20)11-10(19-15(16)17)6-9(13(11)21)14(22)23/h8-13,21H,4-6H2,1-3H3,(H,18,20)(H,22,23)(H4,16,17,19)/t9-,10+,11+,12-,13+/m0/s1
