Basic information Safety Supplier Related

ACIVICIN

Basic information Safety Supplier Related

ACIVICIN Basic information

Product Name:
ACIVICIN
Synonyms:
  • (alpha-s,5s)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleaceticacid
  • (s-(r*,r*))-4,5-dihydro-alpha-amino-3-chloro-5-isoxazoleaceticacid
  • 4,5-dihydro-alpha-amino-3-chloro-,(s-(r*,r*))-5-isoxazoleaceticaci
  • acivicine
  • antibioticat125
  • nsc-163501
  • AT-125
  • (2S)-2-Amino-2-[(5S)-3-chloro-4,5-dihydroisoxazol-5-Yl]acetic acid
CAS:
42228-92-2
MF:
C5H7ClN2O3
MW:
178.57
Product Categories:
  • Amines
  • Chiral Reagents
  • Heterocycles
  • Inhibitors
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
Mol File:
42228-92-2.mol
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ACIVICIN Chemical Properties

Melting point:
>200°C (dec.)
Boiling point:
341.6±48.0 °C(Predicted)
Density 
1.85±0.1 g/cm3(Predicted)
storage temp. 
2-8°C
solubility 
H2O: soluble10mg/mL (warmed)
pka
2.02±0.10(Predicted)
form 
White solid.
color 
white to beige
Water Solubility 
Soluble in water at 10mg/ml with warming
Stability:
Hygroscopic
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Safety Information

Hazard Codes 
Xn
Risk Statements 
20/21/22
Safety Statements 
36
RIDADR 
3172
WGK Germany 
3
RTECS 
NY2103000
HazardClass 
6.1(b)
PackingGroup 
III

MSDS

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ACIVICIN Usage And Synthesis

Chemical Properties

Off-White Solid

Originator

Acivicin ,ZYF Pharm Chemical

Uses

Inhibits glutamine amidotransferases in purine and pyrimidine synthetic pathways. Tumor growth inhibitor

Uses

Azaserine and Acivicin are classical and irreversible inhibitors of γ-Glutamyltranspeptidase

Definition

ChEBI: An L-alpha-amino acid that is L-alanine in which the methyl group is replaced by a (5S)-3-chloro-4,5-dihydro-1,2-oxazol-5-yl group. A glutamine analogue antimetabolite, it interferes with lutamate metabolism and several glutamate-dependent synthetic enzymes. It is obtained as a fermentation product of Streptomyces sviceus bacteria.

Manufacturing Process

Starting from commercial, cis-2-buten-1,4-diol, the monotrichloroacetimidate was obtained as a colorless liquid (60%, b.p. 88°-102°C/0.2 mm Hg) by treatment with trichloroacetonitrile (1 equivalent) in tetrahydrofuran at -23°C in the presence of catalytic amount of sodium. Monotrichloroacetimidate upon refluxing in tert-butyl benzene for about 1 hour underwent, smoothly,rearrangement to afford the vinylglycine synton (84%, MP: 30°C). The treatment of the last compound with bromonitrile oxide (3 equiv.) generated in situ from dibromoformaldoxime in ethyl acetate containing excess of KHCO3 and trace amounts of water afforded 3:2 mixture of cycloadducts threo- and erythro-N-[1-(3-bromo-4,5-dihydroisoxazol-5-yl)-2-hydroxyethyl]-2,2,2- trichloroacetamide. The undesired threo- isomer (MP: 164°-165°C) was quantitatively removed from the mixture by fractional crystallization from chloroform. The erythro-isomer (oil) was refluxed with methanolic-HCl for 1 hour to give the chloro-alchohol (50%, syrup), which upon Jones oxidation (with H2Cr2O7/acetone) followed by deprotection of trichloroacetyl group (Ba(OH)2/H2O, H3+O) afforded racemic acivicin (66 %). The synthetic, racemic antibiotic was spectrally (UV, 1H NMR) indistinguishable from

Therapeutic Function

Antineoplastic

Enzyme inhibitor

This cytotoxic isoxazole and copper chelator (FW = 178.57 g/mol; CAS 42228-92-2; Source: Streptomyces sviceus), also known as L-(aS,5S)-aamino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, AT-125, and NSC165301, strongly inhibitsγ-glutamyl transpeptidase. Its clinical application in cancer treatment failed as a consequence of unacceptable toxicity, and the cause(s) of the desired and undesired biological effects have never been elucidated and only limited information about acivicin-specific targets is available. Target deconvolution by quantitative mass spectrometry (MS) has now revealed acivicin’s preference for the specific aldehyde dehydrogenase known as ALDH4A1 by binding to the catalytic site. Moreover, siRNA-mediated downregulation of ALDH4A1 results in a severe inhibition of cell growth, a finding that may explain acivicin’s cytotoxicity. Targets: Acivicin is thought to be a glutamine analogue, an assumption that is amply supported by its ability to inhibit the following enzymes that possess essential amidohydrolase activities that generate nascent ammonia: asparagine synthetase; carbamoyl-phosphate synthetase; anthranilate synthase; glutamate synthase; CTP symthetase; amidophospho-ribosyltransferase; glutamin(asparagin)ase, or glutaminase-asparaginase; GMP synthase, glutamine-dependent; phosphoribosyl-formylglycinamidine synthetase (formylglycinamidine ribonucleotide synthetase; thiol oxidase; γ-glutamyl hydrolase; imidazole-glycerol phosphate synthetase.

ACIVICINSupplier

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