Crystal form of compound represented by formula I, and preparation therefor and application thereof
A crystal form of a compound represented by formula (I), and a preparation therefor and an application thereof are provided. Also disclosed are a variety of crystal forms of the compound represented by formula (I) (especially crystal form A). The crystal forms have the advantages of excellent stability, hygroscopicity and purity, etc., and has great significance for promoting later-stage drug development of the compound represented by formula (I).
1 . A crystal form of a compound of formula I:
selected from the group consisting of:
i) crystal form A, wherein the X-ray powder diffraction (XRPD) pattern of crystal form A, expressed as ±0.2° 2θ, has 6 or more peaks selected from the group consisting of: 11.764±0.2° 2θ, 12.414±0.2° 2θ, 14.924±0.2° 2θ, 16.423±0.2° 2θ, 17.352±0.2° 2θ, 17.967±0.2° 2θ, 18.269±0.2° 2θ, 19.160±0.2° 2θ, 22.670±0.2° 2θ, 24.052±0.2° 2θ, 24.399±0.2° 2θ, 26.578±0.2° 2θ and 32.318±0.2° 2θ;
ii) crystal form B, wherein the XRPD pattern of crystal form B, expressed as ±0.2° 2θ, has 6 or more peaks selected from the group consisting of: 4.645±0.2° 2θ, 8.812±0.2° 2θ, 10.066±0.2° 2θ, 15.861±0.2° 2θ, 17.109±0.2° 2θ, 18.738±0.2° 2θ, 23.947±0.2° 2θ and 32.151±0.2° 2θ;
iii) crystal form D, wherein the XRPD pattern of crystal form D, expressed as ±0.2° 2θ, has 6 or more peaks selected from the group consisting of: 13.234±0.2° 2θ, 13.446±0.2° 2θ, 16.018±0.2° 2θ, 17.783±0.2° 2θ, 19.383±0.2° 2θ, 20.400±0.2° 2θ, 21.737±0.2° 2θ, 24.324±0.2° 2θ, 26.505±0.2° 2θ and 27.214±0.2° 2θ;
iv) crystal form E, wherein the XRPD pattern of crystal form E, expressed as ±0.2° 2θ, has 6 or more peaks selected from the group consisting of: 9.132±0.2° 2θ, 10.002±0.2° 2θ, 11.745±0.2° 2θ, 12.538±0.2° 2θ, 16.607±0.2° 2θ, 18.287±0.2° 2θ, 18.969±0.2° 2θ, 20.115±0.2° 2θ, 23.626±0.2° 2θ, 24.022±0.2° 2θ, 25.243±0.2° 2θ and 28.238±0.2° 2θ;
v) crystal form F, wherein the XRPD pattern of crystal form F, expressed as ±0.2° 2θ, has 6 or more peaks selected from the group consisting of: 9.246±0.2° 2θ, 10.153±0.2° 2θ, 10.749±0.2° 2θ, 11.228±0.2° 2θ, 11.851±0.2° 2θ, 12.692±0.2° 2θ, 16.050±0.2° 2θ, 16.737±0.2° 2θ, 17.255±0.2° 2θ, 18.503±0.2° 2θ, 19.210±0.2° 2θ, 20.331±0.2° 2θ, 20.687±0.2° 2θ, 21.753±0.2° 2θ and 22.536±0.2° 2θ; and
vi) crystal form G, wherein the XRPD pattern of crystal form G, expressed as ±0.2° 2θ, has 6 or more peaks selected from the group consisting of: 12.411±0.2.2θ, 14.045±0.2° 2θ, 15.905±0.2° 2θ, 18.452±0.2° 2θ, 18.872±0.2° 2θ, 20.186±0.2° 2θ, 20.847±0.2° 2θ, 22.004±0.2° 2θ, 23.682±0.2° 2θ, 23.922±0.2° 2θ, 24.202±0.2° 2θ, 26.664±0.2° 2θ, 28.137±0.2° 2θ, 29.075±0.2° 2θ, 30.333±0.2° 2θ and 32.077±0.2° 2θ.
2 . The crystal form according to claim 1 , wherein crystal form A has 10 or more peaks selected from the group consisting of: 11.764±0.2.2θ, 12.414±0.2° 2θ, 14.924±0.2° 2θ, 16.423±0.2° 2θ, 17.352±0.2° 2θ, 17.967±0.2° 2θ, 18.269±0.2° 2θ, 19.160±0.2° 2θ, 22.670±0.2° 2θ, 24.052±0.2° 2θ, 24.399±0.2° 2θ, 26.578±0.2° 2θ and 32.318±0.2° 2θ.
3 . The crystal form according to claim 1 , wherein crystal form B has 7 or more peaks selected from the group consisting of: 4.645±0.2° 2θ, 8.812±0.2° 2θ, 10.066±0.2° 2θ, 15.861±0.2° 2θ, 17.109±0.2.2θ, 18.738±0.2° 2θ, 23.947±0.2° 2θ and 32.151±0.2° 2θ.
4 . The crystal form according to claim 1 , wherein crystal form D has 9 or more peaks selected from the group consisting of: 13.234±0.2.2θ, 13.446±0.2° 2θ, 16.018±0.2° 2θ, 17.783±0.2° 2θ, 19.383±0.2° 2θ, 20.400±0.2° 2θ, 21.737±0.2° 2θ, 24.324±0.2° 2θ, 26.505±0.2° 2θ and 27.214±0.2° 2θ.
5 . The crystal form according to claim 1 , wherein crystal form E has 10 or more peaks selected from the group consisting of: 9.132±0.2° 2θ, 10.002±0.2° 2θ, 11.745±0.2° 2θ, 12.538±0.2° 2θ, 16.607±0.2° 2θ, 18.287±0.2.2θ, 18.969±0.2° 2θ, 20.115±0.2° 2θ, 23.626±0.2° 2θ, 24.022±0.2° 2θ, 25.243±0.2° 2θ and 28.238±0.2° 2θ.
6 . The crystal form according to claim 1 , wherein crystal form F has 10 or more peaks selected from the group consisting of: 9.246±0.2.2θ, 10.153±0.2.2θ, 10.749±0.2° 2θ, 11.228±0.2° 2θ, 11.851±0.2° 2θ, 12.692±0.2° 2θ, 16.050±0.2° 2θ, 16.737±0.2° 2θ, 17.255±0.2° 2θ, 18.503±0.2° 2θ, 19.210±0.2° 2θ, 20.331±0.2° 2θ, 20.687±0.2° 2θ, 21.753±0.2° 2θ and 22.536±0.2° 2θ.
7 . The crystal form according to claim 1 , wherein crystal form G has 10 or more peaks selected from the group consisting of: 12.411±0.2° 2θ, 14.045±0.2° 2θ, 15.905±0.2° 2θ, 18.452±0.2° 2θ, 18.872±0.2° 2θ, 20.186±0.2° 2θ, 20.847±0.2° 2θ, 22.004±0.2° 2θ, 23.682±0.2° 2θ, 23.922±0.2° 2θ, 24.202±0.2° 2θ, 26.664±0.2.2θ, 28.137±0.2° 2θ, 29.075±0.2° 2θ, 30.333±0.2° 2θ and 32.077±0.2° 2θ.
8 . A pharmaceutical composition comprising one or more crystal forms according to claim 1 and one or more pharmaceutically acceptable carriers or excipients.
9 . A method of treating hepatitis B virus infection in a subject in need thereof, comprising administering to the subject, a pharmaceutical composition according to claim 8 .
10 . The method of claim 9 , wherein the subject is a mammal.