Crystal form B of ABT-888, preparation method and applications thereof

Abstract

The present invention relates to a crystal form B of ABT-888, a preparation method and applications thereof, wherein the characteristic peaks exist in the X-ray powder diffraction spectrum (CuK[alpha] radiation) of the crystal form B when the 2[theta] value is 9.4+/-0.2 DEG, 17.3+/-0.2 DEG, and 22.8+/-0.2 DEG. The preparation method comprises: dissolving ABT-888 free alkali in methanol, and naturally volatilizing at a room temperature to obtain the crystal form B. Compared with the existing crystal form, the crystal form B has characteristics of high solubility, simple preparation process and good stability, and provides important significance for improvement of treatment effects of metastatic breast cancer, colon cancer, metastatic melanoma and brain tumor and reduction of drug loading.

Description

technical field [0001] The present invention relates to crystal form B of 2-[(2R)-2-methyl-2-pyrrolidinyl]-1H-benzimidazole-7-carboxamide and a preparation method thereof. Background technique [0002] 2-[(2R)-2-methyl-2-pyrrolidinyl]-1H-benzimidazole-7-carboxamide (compound shown in formula I), also known as ABT-888 (veliparib), is manufactured by Abbott ( A new type of highly selective PARP inhibitor developed by Abbvie). In vivo and in vitro experiments have shown that ABT-888 has a significant inhibitory effect on PARP activity, and has achieved remarkable effects in the treatment of metastatic breast cancer, colon cancer, metastatic melanoma and brain tumors. At present, the combined application of ABT-888 and whole brain radiotherapy for the treatment of metastatic brain tumors has entered the phase I clinical stage, and the treatment of metastatic breast cancer, colon cancer and metastatic melanoma has also entered the phase II clinical stage, and it is used in combi...

AI Technical Summary

Problems solved by technology

Among the two crystal forms, the solubility of crystal form 1 is relatively good, but crystal form 1 needs to react with the acid or diacid salt of ABT-888 with a base, and the crystal form 1 mixed with one or more than one solvent can be made by deprotonation reaction. ABT-888 is obtained by crystallization or recrystallization in the form of solid, semi-solid, wax or oil. The preparation process is relatively complicated and the requirements for operation are also high.

Although the preparation of crystal form 2 is relatively simple, it can be obtained by completely dissolving ABT-888 in methanol, then concentrating at 35°C, and drying to constant weight, but its solubility is poor

Images