106585-70-0

Basic information

• Product Name: 2-Desamino-5,8-dideazafolic acid
• Synonyms: 2-Desamino-5,8-dideazafolic acid;N-[4-[[[(1,4-Dihydro-4-oxoquinazolin)-6-yl]methyl]amino]benzoyl]-L-glutamic acid
• CAS NO: 106585-70-0
• Molecular Formula: C₂₁H₂₀N₄O₆
• Molecular Weight: 0
• Mol File: 106585-70-0.mol

Chemical Properties

• Boiling Point: 822.2°Cat760mmHg
• Flash Point: 451.1°C
• Appearance: /
• Density: 1.47g/cm³
• Vapor Pressure: 1.3E-28mmHg at 25°C
• Refractive Index: 1.683
• CAS DataBase Reference: 2-Desamino-5,8-dideazafolic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Desamino-5,8-dideazafolic acid(106585-70-0)
• EPA Substance Registry System: 2-Desamino-5,8-dideazafolic acid(106585-70-0)

Safety Data

• Hazardous Substances Data: 106585-70-0(Hazardous Substances Data)

Usage

InChI:InChI=1/C21H20N4O6/c26-18(27)8-7-17(21(30)31)25-19(28)13-2-4-14(5-3-13)22-10-12-1-6-16-15(9-12)20(29)24-11-23-16/h1-6,9,11,17,22H,7-8,10H2,(H,25,28)(H,26,27)(H,30,31)(H,23,24,29)/t17-/m0/s1

Upstream product

• 106585-62-0 Diethyl N-(4-(((3,4-dihydro-4-oxo-3-((pivaloyl)oxy) methyl-6-quinazolinyl)methyl)amino)benzoyl)-L-glutamate 
• 2941-78-8 2-Amino-5-methylbenzoic acid 
• 19181-53-4 6-methyl-3H-quinazolin-4-one 
• 106585-53-9 <6-(bromomethyl)-4-oxo-3(4H)-quinazolinyl>methyl 2,2-dimethylpropanoate 
• 106585-52-8 3,4-dihydro-6-methyl-4-oxo-3-<(pivaloyloxy)methyl>quinazoline 

Relevant articles and documents

Anti-cancer quinazoline derivatives

A compound of formula I: STR1 wherein R is hydrogen; oran alkyl, alkenyl or alkynyl group of up to 6 carbon atoms; nis O; 1 or 2; Z represents --CH=CH-- or --S--; each X independently represents halogeno, C1 -C4 alkyl, C1 -C4 alkoxy, nitro or trifluoromethyl; and Y represents a group of formula: STR2 or a pharmaceutically acceptable salt or ester thereof.

Quinazoline antifolates inhibiting thymidylate synthase: 2-Desamino derivatives with enhanced solubility and potency

The poor solubility of the thymidylate synthase (TS) inhibiting antifolate 10-propargyl-5,8-dideazafolic acid has posed problems for its clinical use and is probably responsible for its renal toxicity. The insolubility is caused by the 2-amino-3,4-dihydro-4-oxopyridimine moiety of the drug which stabilizes the solid state by intermolecular hydrogen bonding. In examining this moiety we have removed the 2-amino group and now report on 2-desamino-10-propargyl-5,8-dideazafolic acid (8e) and four analogues with H, Me, Et, and allyl at N10. 3,4-Dihydro-4-oxo-6-methylquinazoline was solubilized by alkylating the lactam nitrogen with chloromethyl pivalate. Reaction with N-bromosuccinimide gave the corresponding 6-bromomethyl compound, which was coupled with diethyl N-(4-aminobenzoyl)-L-glutamate or the appropriate N-substituted derivative thereof. The quinazoline N3 nitrogen and carboxyl groups in the product were simultaneously deprotected by cold alkali in the final step to give the desired five antifolates. These were tested against L1210 TS and its was found that removal of the 2-amino group caused a slight (3-9-fold) loss of TS inhibition. 8e was only 8-fold a lesser TS inhibitor than the parent drug. Inhibition of rat liver dihydrofolate reductase was reduced by over 1 order of magnitude for three compounds tested. All five analogues were more cytotoxic to L1210 cells in culture than their 2-amino counterparts; 8e was 8.5-fold more active with an ID50 of 0.4 μM. This remarkable result probably owes to increased cellular penetration. 8e was 5-fold more soluble than 1 at pH 5.0 and > 340-fold more soluble at pH 7.4.