JPWO2021026180A5 - - Google Patents

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JPWO2021026180A5
JPWO2021026180A5 JP2022507441A JP2022507441A JPWO2021026180A5 JP WO2021026180 A5 JPWO2021026180 A5 JP WO2021026180A5 JP 2022507441 A JP2022507441 A JP 2022507441A JP 2022507441 A JP2022507441 A JP 2022507441A JP WO2021026180 A5 JPWO2021026180 A5 JP WO2021026180A5
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Prior art keywords
salt
solid form
pyrrolidin
methoxyphenyl
pyrimidine
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JP2022507441A
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JP2022543155A (en
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Priority claimed from PCT/US2020/044919 external-priority patent/WO2021026180A1/en
Publication of JP2022543155A publication Critical patent/JP2022543155A/en
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本明細書に記載するものに加えて、本発明の様々な修正が、前述の説明から当業者には明白となろう。そのような修正はまた、添付の特許請求の範囲の範囲内に入ることが意図される。本出願に引用される全ての特許、特許出願、及び刊行物を含むそれぞれの参考文献は、参照によりその全体が本明細書に組み込まれる。
また、本願は下記の態様も包含する。
［態様１］
以下の式を有する化合物１の固体形態であって、
前記固体形態が、結晶形態Ｉを有する、前記固体形態。
［態様２］
約６．７、約９．９、約１３．４、及び約１５．５度の２θから選択される少なくとも１つの特徴的なＸ線粉末回折（「ＸＲＰＤ」）ピークを有する、請求項１に記載の固体形態。
［態様３］
約６．７、約９．９、約１３．４、約１４．１、約１５．５、約１８．３、約１９．９、及び約２０．４度の２θから選択される少なくとも１つの特徴的なＸＲＰＤピークを有する、請求項１に記載の固体形態。
［態様４］
図１に実質的に示される特徴的ピークを有するＸＲＰＤパターンを有する、請求項１に記載の固体形態。
［態様５］
約８６℃及び約１８３℃の温度で吸熱ピークを有するＤＳＣサーモグラムを示す、請求項１～４のいずれか１項に記載の固体形態。
［態様６］
実質的に図２に示されるようなＤＳＣサーモグラムを有する、請求項１～４のいずれか１項に記載の固体形態。
［態様７］
実質的に図３に示されるようなＴＧＡサーモグラムを有する、請求項１～６のいずれか１項に記載の固体形態。
［態様８］
以下の構造を有する、Ｎ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドの酸性塩である塩であって、
前記酸がリン酸、塩酸、Ｌ－（＋）－酒石酸、リンゴ酸、カンファースルホン酸、マンデル酸、及びクエン酸から選択される、前記塩。
［態様９］
前記塩が結晶性である、請求項８に記載の塩。
［態様１０］
前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドリン酸塩である、請求項８または９に記載の塩。
［態様１１］
前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミド塩酸塩である、請求項８または９に記載の塩。
［態様１２］
前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドＬ－酒石酸塩である、請求項８または９に記載の塩。
［態様１３］
前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドリンゴ酸塩である、請求項８または９に記載の塩。
［態様１４］
前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドカンシル酸塩である、請求項８または９に記載の塩。
［態様１５］
前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドマンデル酸塩である、請求項８または９に記載の塩。
［態様１６］
前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドクエン酸塩である、請求項８または９に記載の塩。
［態様１７］
実質的に図４に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１０に記載の塩。
［態様１８］
実質的に図７に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１１に記載の塩。
［態様１９］
実質的に図１０に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１２に記載の塩。
［態様２０］
実質的に図１３に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１３に記載の塩。
［態様２１］
実質的に図１６に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１４に記載の塩。
［態様２２］
実質的に図１９に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１５に記載の塩。
［態様２３］
実質的に図２２に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１６に記載の塩。
［態様２４］
以下の構造を有する、Ｎ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－４－（４－シアノピリジン－３－イル）フェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドの酸性塩である塩であって、
前記酸がリン酸及び塩酸から選択される、前記塩。
［態様２５］
前記塩が結晶性である、請求項２４に記載の塩。
［態様２６］
前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－４－（４－シアノピリジン－３－イル）フェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドリン酸塩である、請求項２４または２５に記載の塩。
［態様２７］
前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－４－（４－シアノピリジン－３－イル）フェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミド塩酸塩である、請求項２４または２５に記載の塩。
［態様２８］
実質的に図２５に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項２６に記載の塩。
［態様２９］
実質的に図２８に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項２７に記載の塩。
［態様３０］
請求項１～７のいずれか１項に記載の固体形態または請求項８～２９のいずれか１項に記載の塩と、薬学的に許容される担体または賦形剤と、を含む、医薬組成物。
［態様３１］
ＨＰＫ１活性の阻害方法であって、前記方法が、請求項１～７のいずれか１項に記載の固体形態、または、請求項８～２９のいずれか１項に記載の塩を、ＨＰＫ１と接触させることを含む、前記方法。
［態様３２］
前記接触させることが、前記化合物を患者に投与することを含む、請求項３１に記載の方法。
［態様３３］
ＨＰＫ１相互作用の阻害に関連する疾患または障害の治療方法であって、前記方法が、前記治療を必要とする患者に、治療有効量の、請求項１～７のいずれか１項に記載の固体形態、または請求項８～２９のいずれか１項に記載の塩を投与することを含む、前記方法。
［態様３４］
患者におけるがんの治療方法であって、前記方法が、前記患者に、治療有効量の、請求項１～７のいずれか１項に記載の固体形態、または請求項８～２９のいずれか１項に記載の塩を投与することを含む、前記方法。
［態様３５］
前記がんが乳癌、大腸癌、肺癌、卵巣癌、及び膵臓癌から選択される、請求項３４に記載の方法。 Various modifications of the invention, in addition to those described herein, will become apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. Each reference, including all patents, patent applications, and publications cited in this application are hereby incorporated by reference in their entirety.
Moreover, this application also includes the following aspects.
[Aspect 1]
A solid form of Compound 1 having the formula:
The solid form, wherein the solid form has crystalline form I.
[Aspect 2]
2. The method of claim 1, having at least one characteristic X-ray powder diffraction ("XRPD") peak selected from about 6.7, about 9.9, about 13.4, and about 15.5 degrees 2-theta. Solid form as described.
[Aspect 3]
at least one selected from about 6.7, about 9.9, about 13.4, about 14.1, about 15.5, about 18.3, about 19.9, and about 20.4 degrees 2-theta; 2. The solid form of claim 1, having characteristic XRPD peaks.
[Aspect 4]
2. The solid form of claim 1, having an XRPD pattern with characteristic peaks substantially as shown in FIG.
[Aspect 5]
5. The solid form of any one of claims 1-4, which exhibits a DSC thermogram with endothermic peaks at temperatures of about 86°C and about 183°C.
[Aspect 6]
5. The solid form of any one of claims 1-4 having a DSC thermogram substantially as shown in FIG.
[Aspect 7]
7. The solid form of any one of claims 1-6, having a TGA thermogram substantially as shown in FIG.
[Aspect 8]
N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6- A salt that is an acid salt of methoxyphenyl)pyrimidine-4-carboxamide,
Said salt, wherein said acid is selected from phosphoric acid, hydrochloric acid, L-(+)-tartaric acid, malic acid, camphorsulfonic acid, mandelic acid, and citric acid.
[Aspect 9]
9. The salt of claim 8, wherein said salt is crystalline.
[Aspect 10]
The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide phosphate.
[Aspect 11]
The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide hydrochloride.
[Aspect 12]
The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide L-tartrate.
[Aspect 13]
The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide malate.
[Aspect 14]
The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamidecansylate.
[Aspect 15]
The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide mandelate.
[Aspect 16]
The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide citrate.
[Aspect 17]
11. The salt of claim 10, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG.
[Aspect 18]
12. The salt of claim 11 having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG.
[Aspect 19]
13. The salt of claim 12, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG.
[Aspect 20]
14. The salt of claim 13, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG.
[Aspect 21]
15. The salt of claim 14, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG.
[Aspect 22]
16. The salt of claim 15, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG.
[Aspect 23]
17. The salt of claim 16, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG.
[Aspect 24]
N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-, having the structure A salt that is an acid salt of 2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide,
Said salt, wherein said acid is selected from phosphoric acid and hydrochloric acid.
[Aspect 25]
25. The salt of claim 24, wherein said salt is crystalline.
[Aspect 26]
The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-( 26. A salt according to claim 24 or 25 which is 2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide phosphate.
[Aspect 27]
The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-( 26. A salt according to claim 24 or 25 which is 2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide hydrochloride.
[Aspect 28]
27. The salt of claim 26, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG.
[Aspect 29]
28. The salt of claim 27, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG.
[Aspect 30]
A pharmaceutical composition comprising a solid form according to any one of claims 1-7 or a salt according to any one of claims 8-29 and a pharmaceutically acceptable carrier or excipient. thing.
[Aspect 31]
A method of inhibiting HPK1 activity, said method comprising contacting a solid form according to any one of claims 1-7 or a salt according to any one of claims 8-29 with HPK1. The method as described above, comprising causing
[Aspect 32]
32. The method of claim 31, wherein said contacting comprises administering said compound to a patient.
[Aspect 33]
A method of treating a disease or disorder associated with inhibition of HPK1 interaction, said method administering to a patient in need of said treatment a therapeutically effective amount of the solid of any one of claims 1-7. form, or a salt according to any one of claims 8-29.
[Aspect 34]
A method of treating cancer in a patient, said method administering to said patient a therapeutically effective amount of the solid form of any one of claims 1-7, or any one of claims 8-29. The above method comprising administering a salt according to clause.
[Aspect 35]
35. The method of claim 34, wherein said cancer is selected from breast cancer, colon cancer, lung cancer, ovarian cancer, and pancreatic cancer.

Claims (35)

以下の式を有する化合物１の固体形態であって、
前記固体形態が、結晶形態Ｉを有する、前記固体形態。 A solid form of Compound 1 having the formula:
The solid form, wherein the solid form has crystalline form I. 約６．７、約９．９、約１３．４、及び約１５．５度の２θから選択される少なくとも１つの特徴的なＸ線粉末回折（「ＸＲＰＤ」）ピークを有する、請求項１に記載の固体形態。 2. The method of claim 1, having at least one characteristic X-ray powder diffraction ("XRPD") peak selected from about 6.7, about 9.9, about 13.4, and about 15.5 degrees 2-theta. Solid form as described. 約６．７、約９．９、約１３．４、約１４．１、約１５．５、約１８．３、約１９．９、及び約２０．４度の２θから選択される少なくとも１つの特徴的なＸＲＰＤピークを有する、請求項１に記載の固体形態。 at least one selected from about 6.7, about 9.9, about 13.4, about 14.1, about 15.5, about 18.3, about 19.9, and about 20.4 degrees 2-theta; 2. The solid form of claim 1, having characteristic XRPD peaks. 図１に実質的に示される特徴的ピークを有するＸＲＰＤパターンを有する、請求項１に記載の固体形態。 2. The solid form of claim 1, having an XRPD pattern with characteristic peaks substantially as shown in FIG. 約８６℃及び約１８３℃の温度で吸熱ピークを有するＤＳＣサーモグラムを示す、請求項１～４のいずれか１項に記載の固体形態。 5. The solid form of any one of claims 1-4, which exhibits a DSC thermogram with endothermic peaks at temperatures of about 86°C and about 183°C. 実質的に図２に示されるようなＤＳＣサーモグラムを有する、請求項１～４のいずれか１項に記載の固体形態。 5. The solid form of any one of claims 1-4 having a DSC thermogram substantially as shown in FIG. 実質的に図３に示されるようなＴＧＡサーモグラムを有する、請求項１～６のいずれか１項に記載の固体形態。 7. The solid form of any one of claims 1-6, having a TGA thermogram substantially as shown in FIG. 以下の構造を有する、Ｎ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドの酸性塩である塩であって、
前記酸がリン酸、塩酸、Ｌ－（＋）－酒石酸、リンゴ酸、カンファースルホン酸、マンデル酸、及びクエン酸から選択される、前記塩。 N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6- A salt that is an acid salt of methoxyphenyl)pyrimidine-4-carboxamide,
Said salt, wherein said acid is selected from phosphoric acid, hydrochloric acid, L-(+)-tartaric acid, malic acid, camphorsulfonic acid, mandelic acid, and citric acid. 前記塩が結晶性である、請求項８に記載の塩。 9. The salt of claim 8, wherein said salt is crystalline. 前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドリン酸塩である、請求項８または９に記載の塩。 The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide phosphate. 前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミド塩酸塩である、請求項８または９に記載の塩。 The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide hydrochloride. 前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドＬ－酒石酸塩である、請求項８または９に記載の塩。 The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide L-tartrate. 前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドリンゴ酸塩である、請求項８または９に記載の塩。 The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide malate. 前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドカンシル酸塩である、請求項８または９に記載の塩。 The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamidecansylate. 前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドマンデル酸塩である、請求項８または９に記載の塩。 The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide mandelate. 前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－５－フルオロフェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドクエン酸塩である、請求項８または９に記載の塩。 The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-5-fluorophenyl)-2-(2-fluoro-6-methoxyphenyl) A salt according to claim 8 or 9, which is pyrimidine-4-carboxamide citrate. 実質的に図４に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１０に記載の塩。 11. The salt of claim 10, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG. 実質的に図７に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１１に記載の塩。 12. The salt of claim 11 having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG. 実質的に図１０に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１２に記載の塩。 13. The salt of claim 12, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG. 実質的に図１３に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１３に記載の塩。 14. The salt of claim 13, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG. 実質的に図１６に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１４に記載の塩。 15. The salt of claim 14, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG. 実質的に図１９に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１５に記載の塩。 16. The salt of claim 15, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG. 実質的に図２２に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項１６に記載の塩。 17. The salt of claim 16, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG. 以下の構造を有する、Ｎ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－４－（４－シアノピリジン－３－イル）フェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドの酸性塩である塩であって、
前記酸がリン酸及び塩酸から選択される、前記塩。 N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-, having the structure A salt that is an acid salt of 2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide,
Said salt, wherein said acid is selected from phosphoric acid and hydrochloric acid. 前記塩が結晶性である、請求項２４に記載の塩。 25. The salt of claim 24, wherein said salt is crystalline. 前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－４－（４－シアノピリジン－３－イル）フェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミドリン酸塩である、請求項２４または２５に記載の塩。 The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-( 26. A salt according to claim 24 or 25 which is 2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide phosphate. 前記塩がＮ－（２－（（２Ｓ，４Ｓ）－４－アミノ－２－（ヒドロキシメチル）ピロリジン－１－イル）－４－（４－シアノピリジン－３－イル）フェニル）－２－（２－フルオロ－６－メトキシフェニル）ピリミジン－４－カルボキサミド塩酸塩である、請求項２４または２５に記載の塩。 The salt is N-(2-((2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl)-4-(4-cyanopyridin-3-yl)phenyl)-2-( 26. A salt according to claim 24 or 25 which is 2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide hydrochloride. 実質的に図２５に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項２６に記載の塩。 27. The salt of claim 26, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG. 実質的に図２８に示すような特徴的ピークを有するＸ線粉末回折パターンを有する、請求項２７に記載の塩。 28. The salt of claim 27, having an X-ray powder diffraction pattern with characteristic peaks substantially as shown in FIG. 請求項１～７のいずれか１項に記載の固体形態または請求項８～２９のいずれか１項に記載の塩と、薬学的に許容される担体または賦形剤と、を含む、医薬組成物。 A pharmaceutical composition comprising a solid form according to any one of claims 1-7 or a salt according to any one of claims 8-29 and a pharmaceutically acceptable carrier or excipient. thing. ＨＰＫ１活性のインビトロでの阻害方法であって、前記方法が、請求項１～７のいずれか１項に記載の固体形態または請求項８～２９のいずれか１項に記載の塩を、ＨＰＫ１とインビトロで接触させることを含む、前記方法。 A method of inhibiting HPK1 activity in vitro , said method comprising a solid form according to any one of claims 1-7 or a salt according to any one of claims 8-29. in vitro with HPK1. 請求項１～７のいずれか１項に記載の固体形態または請求項８～２９のいずれか１項に記載の塩を含む、ＨＰＫ１活性を阻害するための医薬。 A medicament for inhibiting HPK1 activity, comprising a solid form according to any one of claims 1-7 or a salt according to any one of claims 8-29. ＨＰＫ１相互作用の阻害に関連する疾患または障害の治療用医薬であって、請求項１～７のいずれか１項に記載の固体形態または請求項８～２９のいずれか１項に記載の塩を含む、前記医薬。 A medicament for the treatment of a disease or disorder associated with inhibition of HPK1 interaction, wherein the solid form of any one of claims 1-7 or any one of claims 8-29. Said medicament , comprising a salt of 患者におけるがんの治療用医薬であって、請求項１～７のいずれか１項に記載の固体形態または請求項８～２９のいずれか１項に記載の塩を含む、前記医薬。 A medicament for the treatment of cancer in a patient, said Medicine . 前記がんが乳癌、大腸癌、肺癌、卵巣癌、及び膵臓癌から選択される、請求項３４に記載の医薬。 35. A medicament according to claim 34, wherein said cancer is selected from breast cancer, colon cancer, lung cancer, ovarian cancer and pancreatic cancer.
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