Crystalline form of SHP2 inhibitor, and composition thereof, preparation method therefor, and use thereof
The present application relates to a compound 1 ((S)-1′-(8-((2-amino-3-chloropyridin-4-yl)thio)imidazo[1,2-c]pyrimidin-5-yl)-5,7-dihydrospiro[cyclopenta[b]pyridine-6,4′-piperidine]-5-amine) represented by formula (I), a novel crystalline form of a hydrate or a solvate thereof, and a pharmaceutical composition comprising the novel crystalline form. The present application further relates to a preparation method for the novel crystalline form and a use of the novel crystalline form.
1 . A crystalline form of a compound represented by formula (I):
wherein the crystalline form is selected from a group consisting of:
a crystalline form A, which has an XRPD pattern with all peaks selected from the following group expressed in values of degrees 2θ at:
°2θ
6.46
11.70
12.64
12.93
13.27
13.50
14.60
16.49
17.30
17.66
18.27
18.69
19.30
20.06
21.71
22.34
23.04
23.61
24.36
25.42
25.79
26.52
27.41
27.83
28.23
28.90
29.45
30.75
32.67
34.98;
a crystalline form B of a hydrate of the compound, which has an XRPD pattern with all peaks selected from the following group expressed in values of degrees 2θ at:
°2θ
7.36
10.82
11.10
11.51
14.70
15.25
15.99
17.13
18.42
18.81
19.80
20.96
21.73
23.35
23.78
25.15
27.20
28.38
29.07;
a crystalline form C of a hydrate of the compound, which has an XRPD pattern with all peaks selected from the following group expressed in values of degrees 2θ at:
°2θ
7.33
11.08
14.70
15.20
16.23
17.33
17.60
18.85
20.05
21.20
22.03
23.70
24.33
25.09
25.73
27.07
27.51
28.35
29.13
29.63
30.72
32.51
33.61
35.08
37.61;
a crystalline form D of a solvate of the compound, which has an XRPD pattern with all the peaks selected from the following group expressed in values of degrees 2θ at:
°2θ
8.24
9.13
12.89
13.46
15.32
15.90
16.84
18.45
20.26
21.83
23.08
23.80
25.59;
wherein the solvate is dichloromethane; and
a crystalline form E of a solvate of the compound, which has an XRPD pattern with all peaks selected from the following group expressed in values of degrees 2θ at:
°2θ
5.85
8.00
9.10
11.69
13.03
13.49
14.75
15.30
16.35
17.56
18.24
20.13
20.60
21.05
22.63
23.35
24.12
25.06
25.52
27.51
29.46
30.90
34.20
35.51
36.24
36.93;
wherein the solvate is isopropanol.
2 . The crystalline form according to claim 1 , wherein the crystalline form is a substantively pure crystalline form, wherein said substantively pure crystalline form has a purity of more than 90 wt %.
3 . A pharmaceutical composition comprising a compound represented by formula (I) and a pharmaceutically acceptable carrier, wherein the compound has a crystalline form as defined in claim 1 .
4 . The pharmaceutical composition according to claim 3 , which further comprises other therapeutic agents.
5 . A method of inhibiting of SHP2 activity or preventing or treating a disease disorder associated with abnormal activity of SHP2, comprising the following steps: administering an effective amount of the crystalline form according to claim 1 or a pharmaceutical composition comprising the crystalline form to a subject having such a need.
6 . The method according to claim 5 , wherein the disease disorder associated with abnormal activity of SHP2 is a cancer selected from a group consisting of Noonan syndrome, Leopard syndrome, adolescent myelomonocytic leukemia, neuroblastoma, melanoma, acute myeloid leukemia, breast cancer, esophageal cancer, lung cancer, colon cancer, head cancer, squamous cell carcinoma of the head and neck, gastric cancer, anaplastic large cell lymphoma, glioblastoma, hepatocellular carcinoma (HCC), acute lymphoblastic leukemia, adrenal cortex carcinoma, anal cancer, appendix cancer, astrocytomas, atypical malformations/tumoroids, basal cell carcinoma, cholangiocarcinoma, bladder cancer, bone cancer (osteosarcoma and malignant fibrous histiocytoma), brainstem glioma, brain tumor, brain and spinal cord tumor, bronchial tumor, Burkitt lymphoma, cervical cancer, chronic lymphocytic leukemia, chronic myelogenous leukemia, colorectal cancer, craniopharyngioma, embryonic tumor, endometrial cancer, epithelial cell tumors, ependymomas, Ewing sarcoma family tumors, eye cancer, retinoblastoma, gallbladder carcinoma, gastrointestinal carcinoid, gastrointestinal stromal tumors (GIST), gastrointestinal stromal cell tumors, germ cell tumors, gliomas, hair cell leukemia, head and neck cancer, Hodgkin lymphoma, hypopharyngeal cancer, islet cell tumor (endocrine pancreas), Kapozi sarcoma, kidney cancer, Langerhans cell histiocytosis, laryngeal cancer, leukemia, hair cell leukemia, liver cancer, non-small cell lung cancer, small cell lung cancer, lymphoma, medulloblastoma, medullary epithelioma, mesothelioma, oral cancer, multiple myeloma, nasopharyngeal cancer, neuroblastoma, non-Hodgkin lymphoma, oropharyngeal cancer, osteosarcoma, malignant bone fibrous histiocytoma, ovarian cancer, ovarian epithelial carcinoma, ovarian germ cell tumor, ovarian low malignant potential tumor, pancreatic cancer, papillomatosis, parathyroid carcinoma, penile cancer, pharyngeal cancer, pineal intermediate differentiation tumor, osteoblastoma and supratentorial primitive neuroectodermal tumor, pituitary tumor, plasma cell tumor/multiple myeloma, pleural pneumocytoma, primary central nervous system lymphoma, prostate cancer, rectal cancer, kidney cell (kidney) cancer, retinoblastoma, rhabdomyosarcoma, salivary adenocarcinoma, sarcoma, Ewing sarcoma family tumors, sarcoma, Kaposi disease, Sezary syndrome, skin cancer, small intestinal carcinoma, soft tissue sarcoma, squamous cell carcinoma, supratentorial primitive neuroectodermal tumor, T-cell lymphoma, testicular cancer, laryngeal cancer, thymoma and thymus cancer, thyroid cancer, urethral cancer, uterine cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Waldenstrom macroglobulinemia and Wilms tumors.