【结 构 式】 |
【药物名称】 【化学名称】N,2-Bis[2-(dimethylamino)ethyl]-9-nitro-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxamide dihydrochloride 【CA登记号】220249-88-7 【 分 子 式 】C22H29Cl2N7O3 【 分 子 量 】510.42753 |
【开发单位】Università degli Studi di Camerino (Originator) 【药理作用】Oncolytic Drugs, DNA-Intercalating Drugs |
合成路线1
The Ullmann condensation between 2-chloro-5-nitrobenzoic acid (I) and 2-amino-4-chlorobenzoic acid (II) afforded the diaryl amine (III). Cyclization of (III) by treatment with POCl3 in refluxing xylene yielded a mixture of the desired acridine (IV) and minor amounts of its regioisomer (V). The isomeric mixture of acids (IV) and (V) was activated as the respective mixed anhydrides with ethyl chloroformate and subsequently condensed with N,N-dimethylethylenediamine (VI) to produce the corresponding amides. The required isomer (VII) was easily isolated from the mixture owing to its insolubility in the reaction solvent. Finally, the title pyrazoloacridine compound was prepared by condensation of (VII) with 2-(dimethylamino)ethyl hydrazine in 2-ethoxyethanol at 120 C.
【1】 Antonini, I.; et al.; Synthesis, antitumor cytotoxicity, and DNA-binding of novel N-5,2-Di(omega-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl) acridine-5-carboxamides. J Med Chem 2001, 44, 20, 3329. |
【2】 Matelli, S.; Polucci, P.; Antonini, I. (Università degli Studi di Camerino); Pyrazolo-acridine derivs. having antitumour activity. WO 9906405 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 10188 | 2-Chloro-5-nitrobenzoic acid | 2516-96-3 | C7H4ClNO4 | 详情 | 详情 |
(II) | 52504 | 4-Chloro-2-aminobenzoic acid; 2-Amino-4-chlorobenzoic acid; 2-Carboxy-5-chloroaniline; 3-Amino-4-carboxy-1-chlorobenzene; 4-Chloroanthranilic acid | 89-77-0 | C7H6ClNO2 | 详情 | 详情 |
(III) | 52505 | C14H9ClN2O6 | 详情 | 详情 | ||
(IV) | 52506 | 1-chloro-7-nitro-9-oxo-9,10-dihydro-4-acridinecarboxylic acid | C14H7ClN2O5 | 详情 | 详情 | |
(V) | 52507 | 6-chloro-2-nitro-9-oxo-9,10-dihydro-4-acridinecarboxylic acid | C14H7ClN2O5 | 详情 | 详情 | |
(VI) | 14881 | N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine | 108-00-9 | C4H12N2 | 详情 | 详情 |
(VII) | 52508 | 1-chloro-N-[2-(dimethylamino)ethyl]-7-nitro-9-oxo-9,10-dihydro-4-acridinecarboxamide | C18H17ClN4O4 | 详情 | 详情 | |
(VIII) | 41186 | N-(2-hydrazinoethyl)-N,N-dimethylamine; 2-hydrazino-N,N-dimethyl-1-ethanamine | C4H13N3 | 详情 | 详情 |