M-dihydroxybenzene derivative crystal and salt, and manufacturing method thereof

Patent metadata

Field	Value
Publication number	US-10851071-B2
Application number	US-201716318606-A
Country	US
Kind code	B2
Filing date	Jul 20, 2017
Priority date	Jul 21, 2016
Publication date	Dec 1, 2020
Grant date	Dec 1, 2020

Abstract

Provided are a crystal and salt of an m-dihydroxybenzene derivative represented by formula (I), a manufacturing method thereof, and an application of the crystal in preparing a pharmaceutical product for treating a HSP90-mediated disease.

First claim

What is claimed is:

1. A compound of formula (I) in crystalline form,

or a salt of the compound of formula (I), wherein the salt of the compound of formula (I) is selected from: trifluoroacetate, methanesulfonate, ρ-toluenesulfonate, citrate, maleate, fumarate, hydrobromide, phosphate or sulfate, or a compound of formula (II),

wherein HA is selected from trifluoroacetic acid, methanesulfonic acid, ρ-toluenesulfonic acid, citric add, maleic acid, fumaric acid, hydrochloric acid, hydrobromic acid, phosphoric acid, and sulfuric acid
wherein HA is selected from trifluoroacetic acid, methanesulfonic acid, ρ-toluenesulfonic acid, citric acid, maleic acid, fumaric acid, hydrochloric acid, hydrobromic acid, phosphoric acid, and sulfuric acid±characterized in that the X-ray powder diffraction pattern of the compound of formula (I) in crystalline form has diffraction peaks at the following 2θ angles: 10.66±0.2°, 15.09±0.2°, 19.17±0.2°.

2. The compound of formula ( 1 ) in crystalline form or the salt of the compound of formula (I) according to claim 1 , characterized in that the X-ray powder diffraction pattern of the compound of formula (I) in crystalline form has diffraction peaks at the following 2θ angles: 10.66±0.2°, 11.41±0.2°, 15.09±0.2°, 19.17±0.2°, 20.43±0.2 °, 22.19±0.2°, 25.76±0.2°.

3. The compound of formula. ( 1 ) in crystalline form or the salt of the compound of formula (I) according to claim 1 , characterized in that a X-ray powder diffraction pattern of the compound of formula (I) in crystalline form has diffraction peaks at the following 2θ angles: 7.34±0.2°, 12.23±0.2°, 12.53±0.2°, 14.69±0.2°, 18.72±0.2°, 19.03±0.2°, 0.2°, 20.67±0.2°, 22.15±0.2°.

4. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 1 , characterized in that a X-ray powder diffraction pattern of the compound of formula (I) in crystalline form has diffraction peaks at the following 2θ angles: 6.45±0.2°, 7.68±0.2°, 10.56±0.2°, 12.91±0.2°, 13.58±0.2°, 15.40±0.2°, 21.14±0.2°, 26.32±0.2°.

5. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 1 , characterized in that a X-ray powder diffraction pattern of the compound of formula (I) in crystalline form has diffraction peaks at the following 2θ angles: 5.96±0.2°, 9.53±0.2°, 9.65±0.2°, 11.94±0.2°, 16.42±0.2°, 19.43±0.2°, 22.01±0.2°, 25.49±0.2°.

6. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 1 , which is presented as a crystalline composition, wherein weight of the compound of formula (I) in crystalline form is 50% or more with respect to weight of the composition.

7. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 1 , wherein the salt is selected from a compound represented by formula (II-1) or a compound represented by formula (II-2):

8. A pharmaceutical composition comprising the compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 1 .

9. A method for treating a HSP90-mediated disease selected from cancer and neurodegenerative disorder, wherein the cancer includes: bladder cancer, breast cancer, colon cancer, kidney cancer, liver cancer, lung cancer including small cell lung cancer, esophageal cancer, gallbladder cancer, ovarian cancer, pancreatic cancer, gastric cancer, cervical cancer, thyroid cancer, prostate cancer, and skin cancer including squamous cell carcinoma; lymphatic hematopoietic tumors, including leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma, and Burkitt's lymphoma; myeloid hematopoietic carcinomas, including acute and chronic myelogenous leukemia, myelodysplastic syndrome and promyelocytic leukemia; mesenchyme-derived cancer including fibrosarcoma and rhabdomyosarcoma; cancers of central and peripheral nervous system, including astrocytoma, neurocytoma, glioma, and neurilemmoma, melanoma, seminoma, teratocarcinoma, osteosarcoma, xeroderma pigmentosum, keratoxanthoma, thyroid follicular carcinoma, and Kaposi's sarcoma; and the neurodegenerative disorder includes: Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and spinal and bulbar muscular atrophy, comprising administering the compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 1 to a subject in need thereof.

10. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 2 , characterized in that the X-ray powder diffraction pattern of the compound of formula (I) in crystalline form has diffraction peaks at the following 2θ angles: 10.66±0.2°, 11.41±0.2°, 15.09±0.2°, 17.85±0.2°, 19.17±0.2°, 19.60±0.2°, 20.43±0.2°, 21.81±0.2°, 22.19±0.2°, 25.76±0.2°.

11. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 10 , characterized in that the X-ray powder diffraction pattern of the compound of formula (I) in crystalline form has diffraction peaks at the following 2θ angles: 10.66±0.2°, 11.41±0.2°, 15.09±0.2°, 15.84±0.2°, 17.85±0.2 °, 18.22±0.2°, 19.17 ±0.2°, 19.60±0.2°, 20.19±0.2°, 20.43±0.2°, 21.81±0.2°, 22.19±0.2°, 22.86±0.2°, 24.57±0.2°, 25.76±0.2°, 26.05±0.2°, 27.75±0.2°.

12. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 1 , characterized in that a differential scanning calorimetry curve of the compound of formula (I) has a starting point of endothermic peaks at 198 ±5° C.

13. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 1 , characterized in that a differential scanning calorimetry curve of the compound of formula ( 1 ) has a starting point of endothermic peaks at 55 ±5° C.

14. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 1 , characterized in that a differential scanning calorimetry curve of the compound of formula (I) has a starting point of endothermic peaks at 108 ±5° C.

15. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 1 , characterized in that a differential scanning calorimetry curve of the compound of formula W has a starting point of endothermic peaks at 141 ±5° C.

16. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 6 , wherein weight of the compound of formula (I) in crystalline form is 70% or more with respect to weight of the composition.

17. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 16 , wherein weight of the compound of formula ( 1 ) in crystalline form is 90% or more with respect to weight of the composition.

18. The compound of formula (I) in crystalline form or the salt of the compound of formula (I) according to claim 17 , wherein weight of the compound of formula (I) in crystalline form is 95% or more with respect to weight of the composition.

Assignees

• Chia Tai Tianqing Pharmaceutical Group Co Ltd

Inventors

• Yan Xiaobing
• Huang Wei
• Li Dan
• Ding Charles Z
• Liu Fei
• Zhang Xiquan

Classifications

• A61K31/422

  not condensed and containing further heterocyclic rings · CPC title

• C07D261/08

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D413/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D261/18 Primary

  Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen · CPC title

• A61P35/00

  Antineoplastic agents · CPC title