- 2-amino-4-oxo-quinazoline dithioformate derivative and pharmaceutical composition and application thereof
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The invention discloses a 2-amino-4-oxo-quinazoline dithioformate derivative and a pharmaceutical composition and application thereof. The 2-amino-4-oxo-quinazoline dithioformate derivative is a compound shown as a formula A in the specification. The derivative disclosed by the invention has a broad-spectrum anti-tumor effect, and particularly has inhibitory activity on paclitaxel drug-resistant tumors.
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Paragraph 0027-0029
(2022/01/12)
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- Synthesis of 2-Aminoquinazolinones via Carbonylative Coupling of ortho-Iodoanilines and Cyanamide
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Herein, we describe a convenient and efficient synthesis of 2-aminoquinazolin-4(3H)-ones and N1-substituted 2-aminoquinazolin-4(1H)-ones by a domino carbonylation/cyclization process. The reaction proceeds via carbonylative coupling of readily available ortho-iodoanilines with cyanamide followed by in situ ring closure of an N-cyanobenzamide intermediate. The products were easily isolated by precipitation in moderate to excellent yields for a wide range of substrates, making this a highly attractive method for the synthesis of 2-aminoquinazolinones.
- ?kerbladh, Linda,Odell, Luke R.
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p. 2966 - 2973
(2016/04/26)
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- QUINAZOLINE DERIVATIVES FOR THE TREATMENT OF VIRAL INFECTIONS AND FURTHER DISEASES
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This invention relates to quinazoline derivatives, processes for their preparation, pharmaceutical compositions, and their use in therapy of disorders in which the modulation of toll-like-receptors is involved.
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Paragraph 0055; 0070
(2014/03/25)
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- QUINAZOLINE DERIVATIVES FOR THE TREATMENT OF VIRAL INFECTIONS AND FURTHER DISEASES
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This invention relates to quinazoline derivatives, processes for their preparation, pharmaceutical compositions, and their use in therapy of disorders in which the modulation of toll - like - receptors is involved.
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Page/Page column 12; 13
(2012/12/13)
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- 2-Pivalamido-3H-pyrimidin-4-one derivatives: Convenient pivalamide hydrolysis using Fe(NO3)3 in MeOH
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A simple methodology for pivalamide (trimethylacetamide, pivaloylamino) hydrolysis has been discovered using Fe(NO3)3 in MeOH at room temperature. The pivalamido group of 2-pivalamido-3H-pyrimidin-4-ones or fused 2-pivalamido-3H-pyrimidin-4-ones such as 2-pivalamido-3H-quinazolin-4-ones and 2-pivalamido-3H-pteridines have been hydrolysed under these conditions to afford the corresponding amine.
- Bavetsias,Henderson,McDonald
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p. 5643 - 5644
(2007/10/03)
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- Potent inhibition of thymidylate synthase by two series of nonclassical quinazolines
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The synthesis and biological activity of two series of nonclassical thymidylate synthase (TS) inhibitors are described. The first is a series of 10-propargyl-5.8-dideazafolic acid derivatives (10a-j) and the second is a series of the analogous 2-desamino
- McNamara,Berman,Fry,Werbel
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p. 2045 - 2051
(2007/10/02)
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- Synthesis and biological properties of 3-methyl-10-propargyl-5,8-dideazafolic acid
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The synthesis of N3-methyl-10-propargyl-5,8-dideazafolic acid (1b) is described. Ring closure of methyl-5-methylanthranilate with chloroformamidine hydrochloride gave a high yield of pure 2-amino-4-hydroxy-6-methylquinazoline treatment of which with indomethane/sodium hydroxide provided the corresponding 3-methylquinazoline (6) which was converted to its 2-pivaloylamino derivative. This synthetic approach, next involving functionalisation of the 6-methyl group, was not further pursued because of difficulty encountered in removing the pivaloyl group. Methyl 5-methylanthranilate was treated with p-toluenesulfonyl chloride and the product then N-methylated. The tosyl group was cleaved with hydrogen bromide/phenol and the resulting methylamine ring-closed with chloroformamidine hydrochloride to provide 2-amino-1,4-dihydro-1,6-dimethyl-4-oxoquinazoline (11). The 2-pivaloylamino derivative of 11 was prone to hydrolytic deamination when attempts were made to remove the pivaloyl group and further elaboration of this heterocycle, with the intention of obtaining N1-methyl-10-propargyl-5,8-dideazafolic acid was, too, not attempted. Di-t-butyl N-(4-propargylamino)benzoyl)-L-glutamate was therefore prepared and coupled with 2-amino-6-bromomethyl-4-hydroxyquinazoline hydrobromide. The resulting antifolate diester was N-monomethylated. Removal of the t-butyl groups with trifluoracetic acid afforded the target compound 1b and its structure was proved by degradation to the quinazoline 6. Its IC50 for L1210 thymidylate synthase (TS) was 26 μM; the control value for 10-propargyl-5,8-dideazafolic acid (1a) was 0.02 μM. Thus the substitution of the lactam hydrogen in 1a by a methyl group reduced the TS inhibition by 1300-fold. Compound 1b was poorly cytotoxic to L1210 cells in culture (ID50 > 100 μM). An unperturbed lactam group in this class of antifolate is important for binding to TS.
- Jones,Betteridge,Newell,Jackman
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p. 1501 - 1507
(2007/10/02)
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