Shanghai Pharmaceuticals Holding Co., Ltd.

Jiansheng Han

Guangxin Xia

Liang Zhao

Toru Iijima

Yanjun Liu

Di Li

Naoko Ueda

Jianshu Xie

Ning Zhou

Guohui Jia

Ao Chen

A salt of a quinazoline derivative (N-[4-(3-chlorine-4-fluoroanilino)]-7-(3-morpholinepropanol)-6-(2-fluoroacrylamide)-quinazoline, the structure thereof is as represented by formula I). Compared with a known quinazoline derivative, the salt of the quinazoline derivative has one or more improved properties and at least has better water solubility, wherein a citrate, a benzene sulfonate, and an ethanedisulphonate thereof further have better crystallinity and are not easy to absorb moisture. 

Salt of quinazoline derivative, preparation method therefor and application thereof

The present invention provides novel pharmaceutically acceptable salts of a morpholine derivative, including a malate, a tartrate, a hydrochloride, an acetate, and a naphthalene disulfonate thereof, wherein the tartrate has 3 crystal salt forms: crystal form A, crystal form B and dihydrate; the malate, the hydrochloride, and the acetate each have one crystal salt form; the naphthalene disulfonate is amorphous. When compared to the known morpholine derivative free base, the present invention has one or more improved properties, e.g., a better crystalline state, greatly improved water solubility, light stability and thermal stability, etc. The present invention further provides preparation methods for the salts of morpholine derivative and the crystal forms thereof, pharmaceutical compositions and use thereof.

Salts of morpholine derivative, crystal forms thereof, processes for producing the same, pharmaceutical compositions including the same, and use thereof

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Shanghai, China

Jiansheng Han