阅读说明：本技术 一种用作iap抑制剂的smac模拟物的结晶及其制备方法 (Crystals of SMAC mimetics useful as IAP inhibitors and methods of making the same ) 是由 刘迎春 徐招兵 胡利红 丁照中 朱兴训 陈曙辉 于 2020-05-09 设计创作，主要内容包括：一种用作IAP抑制剂的SMAC模拟物的结晶及其制备方法,还包括所述结晶在制备治疗受益于cIAP1抑制的癌症的药物中的用途。本申请所述式(I)化合物的结晶稳定性高、吸湿性小,在物理性质、安全性和代谢稳定性方面具有优势,有较高的成药价值。(Crystals of a SMAC mimetic for use as an IAP inhibitor and methods of making the same, further comprising use of the crystals in the manufacture of a medicament for treating a cancer that benefits from cIAP1 inhibition. The compound of formula (I) has the advantages of high crystallization stability, low hygroscopicity, physical property, safety and metabolic stability, and high pharmaceutical value.)

Crystals of the compound of formula (I)

The crystal of claim 1, which is a crystal a of the compound of formula (I) having characteristic diffraction peaks at the following 2 Θ angles using the X-ray powder diffraction pattern of Cu ka radiation: 12.1 ° ± 0.200 °, 16.1 ° ± 0.200 °, 18.5 ° ± 0.200 °, 20.2 ° ± 0.200 °, 21.3 ° ± 0.200 ° and 23.0 ° ± 0.200 °.

Crystalline a of a compound of formula (I) according to claim 2 having characteristic diffraction peaks at the following 2 Θ angles using the X-ray powder diffraction pattern of Cu ka radiation: 12.1 ° ± 0.200 °, 16.1 ° ± 0.200 °, 18.5 ° ± 0.200 °, 18.8 ° ± 0.200 °, 19.2 ° ± 0.200 °, 19.8 ° ± 0.200 °, 20.2 ° ± 0.200 °, 21.3 ° ± 0.200 °, 23.0 ° ± 0.200 °, 26.6 ° ± 0.200 ° and 27.4 ° ± 0.200 °.

Crystalline a of a compound of formula (I) according to claim 3 having characteristic diffraction peaks at the following 2 Θ angles using the X-ray powder diffraction pattern of Cu ka radiation: 7.0 ° ± 0.200 °, 8.7 ° ± 0.200 °, 12.1 ° ± 0.200 °, 13.2 ° ± 0.200 °, 13.9 ° ± 0.200 °, 16.1 ° ± 0.200 °, 16.7 ° ± 0.200 °, 18.5 ° ± 0.200 °, 18.8 ° ± 0.200 °, 19.2 ° ± 0.200 °, 19.8 ° ± 0.200 °, 20.2 ° ± 0.200 °, 21.0 ° ± 0.200 °, 21.3 ° ± 0.200 °, 23.0 ° ± 0.200 °, 24.3 ° ± 0.200 °, 25.3 ° ± 0.200 °, 26.6 ° ± 0.200 ° and 27.4 ° ± 0.200 °.

Crystalline a of a compound of formula (I) according to claim 4 having characteristic diffraction peaks at the following 2 Θ angles using the X-ray powder diffraction pattern of Cu ka radiation: 7.0 ° ± 0.200 °, 8.7 ° ± 0.200 °, 12.1 ° ± 0.200 °, 13.2 ° ± 0.200 °, 13.9 ° ± 0.200 °, 16.1 ° ± 0.200 °, 16.5 ° ± 0.200 °, 16.7 ° ± 0.200 °, 18.5 ° ± 0.200 °, 18.8 ° ± 0.200 °, 19.2 ° ± 0.200 °, 19.8 ° ± 0.200 °, 20.2 ° ± 0.200 °, 21.0 ° ± 0.200 °, 21.3 ° ± 0.200 °, 23.0 ° ± 0.200 °, 23.2 ° ± 0.200 °, 24.3 ° ± 0.200 °, 25.3 ° ± 0.200 °, 26.6 ° ± 0.200 °, 26.9 ° ± 0.200 °, 27.4 ° ± 0.200 ° and 29.4 ° ± 0.200 °.

Crystalline a of a compound of formula (I) according to claim 5 having characteristic diffraction peaks at the following 2 Θ angles using the X-ray powder diffraction pattern of Cu ka radiation: 0.200 degree of 7.0 +/-0.200 degree, 8.7 +/-0.200 degree, 9.7 +/-0.200 degree, 10.6 +/-0.200 degree, 11.4 +/-0.200 degree, 12.1 +/-0.200 degree, 13.2 +/-0.200 degree, 13.9 +/-0.200 degree, 16.1 +/-0.200 degree, 16.5 +/-0.200 degree, 16.7 +/-0.200 degree, 17.5 +/-0.200 degree, 18.5 +/-0.200 degree, 18.8 +/-0.200 degree, 19.2 +/-0.200 degree, 19.8 +/-0.200 degree, 20.2 +/-0.200 degree, 21.0 +/-0.200 degree, 21.3 +/-0.200 degree, 22.5 +/-0.200 degree, 23.0 degree, 23.2 +/-0.200 degree, 0.0.0 degree, 0.200 degree, 0.0.200 degree, 0.0 degree, 0.200 degree, 3 +/-0.200 degree, 2 +/-0.200 degree, 3 +/-0.200 degree, 22.200 degree, 30.200 degree, 30 degree, 30.0 degree, 30 degree, 30.30 degree, 30 degree, 30.1.9 +/-0.1.9 +/-0 degree, 30 +/-0.200 degree, 30 degree, 30.1.1.1.200 degree, 30 degree, 30.1.1.200 degree, 30 degree, 0.200 degree, 13.200 degree, 0.200 degree, 0 degree, 0.200 degree, 13.200 degree, 13.1.1.200 degree, 13.200 degree, 30 degree, 13.200 degree, 0 degree, 13 degree, 30 degree, 0.1.1.200 degree, 13.200 degree, 30 degree, 13 degree, 0 degree, 0.200 degree, 0 degree, 13.200 degree, 0 degree, 0.200 degree, 13 degree, 0.200 degree, 0 degree, 30 degree, 13.200 degree, 13.1.200 degree, 30 degree, 13.200 degree, 30 degree, 0.9 degree, 30 degree, 30.200 degree, 30 degree, 30.200 degree, 0.200 degree, 30 degree, 30.200 degree, 30 degree, 30.200 degree, 30 degree, 30.200 degree, 30 degree, 30.200 degree, 30 degree, 34.8 ° ± 0.200 °, 35.5 ° ± 0.200 °, 36.6 ° ± 0.200 °, 37.6 ° ± 0.200 °, 38.6 ° ± 0.200 ° and 39.6 ° ± 0.200 °.

Crystalline a of the compound of formula (I) as claimed in any one of claims 2 to 6 having a peak of absorption peak in a differential scanning calorimetry trace at 202.5 ℃.

Crystalline a of the compound of formula (I) as claimed in any one of claims 2 to 6 having a differential scanning calorimetry measurement pattern in which the onset of the absorption peak is at about 200.8 ℃.

A crystalline composition wherein more than 50%, preferably more than 75%, more preferably more than 90%, most preferably more than 95% by weight of the crystalline composition of the compound of formula (I) as defined in claim 1 is crystallised.

A pharmaceutical composition comprising a crystalline compound of formula (I) according to claim 1 or a crystalline composition according to claim 9.

Use of a crystalline compound of formula (I) as defined in claim 1, a crystalline composition as defined in claim 9, or a pharmaceutical composition as defined in claim 10, for the manufacture of a medicament for the treatment of a cancer benefiting from the inhibition of cIAP 1.