公开(公告)号：US20160137654A1

公开(公告)日：2016-05-19

申请号：US14943014

申请日：2015-11-16

Applicant: Array BioPharma, Inc.

Inventor： Alisha B. Arrigo ,  Derrick Juengst ,  Khalid Shah

IPC: C07D487/04

Abstract: A novel crystalline form of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.

Abstract translation: （S）-N-（5 - （（R）-2-（2,5-二氟苯基）吡咯烷-1-基） - 吡唑并[1,5-a]嘧啶-3-基） - 3-羟基吡咯烷-1-甲酰胺，含有所述结晶形式的药物组合物和所述结晶形式用于治疗疼痛，癌症，炎症，神经变性疾病或克氏锥虫感染的用途。 在一些实施方案中，新的结晶形式包含（S）-N-（5 - （（R）-2-（2,5-二氟苯基）吡咯烷-1-基） - 吡唑并[1,5-a ]嘧啶-3-基）-3-羟基吡咯烷-1-甲酰胺硫酸氢盐。 本发明进一步涉及制备新型结晶形式的方法。

公开(公告)号：US20170165267A1

公开(公告)日：2017-06-15

申请号：US15399207

申请日：2017-01-05

Applicant: Array BioPharma, Inc.

Inventor： Alisha B. Arrigo ,  Derrick Juengst ,  Khalid Shah

IPC: A61K31/519 ,  C12Q1/48

CPC classification number: A61K31/519 ,  C07D487/04 ,  C12Q1/485 ,  C12Y207/10001 ,  G01N2333/91205 ,  G01N2800/52

Abstract: A novel crystalline form of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.

公开(公告)号：US10813936B2

公开(公告)日：2020-10-27

申请号：US16366368

申请日：2019-03-27

Applicant: Array BioPharma, Inc.

Inventor： Alisha B. Arrigo ,  Derrick Juengst ,  Khalid Shah

IPC: A61K31/519 ,  C07D487/04 ,  C12Q1/48

Abstract: A novel crystalline form of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.

公开(公告)号：US20180021342A1

公开(公告)日：2018-01-25

申请号：US15706062

申请日：2017-09-15

Applicant: Array BioPharma, Inc.

Inventor： Alisha B. Arrigo ,  Derrick Juengst ,  Khalid Shah

IPC: A61K31/519 ,  C12Q1/48

CPC classification number: A61K31/519 ,  C07D487/04 ,  C12Q1/485 ,  C12Y207/10001 ,  G01N2333/91205 ,  G01N2800/52 ,  Y02A50/414

Abstract: A novel crystalline form of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.

公开(公告)号：US20200000807A1

公开(公告)日：2020-01-02

申请号：US16366368

申请日：2019-03-27

Applicant: Array BioPharma, Inc.

Inventor： Alisha B. Arrigo ,  Derrick Juengst ,  Khalid Shah

IPC: A61K31/519 ,  C07D487/04 ,  C12Q1/48

Abstract: A novel crystalline form of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.

公开(公告)号：US09782414B2

公开(公告)日：2017-10-10

申请号：US15399207

申请日：2017-01-05

Applicant: Array BioPharma, Inc.

Inventor： Alisha B. Arrigo ,  Derrick Juengst ,  Khalid Shah

IPC: A01N43/90 ,  A61K31/519 ,  C07D487/00 ,  C12Q1/48

CPC classification number: A61K31/519 ,  C07D487/04 ,  C12Q1/485 ,  C12Y207/10001 ,  G01N2333/91205 ,  G01N2800/52

Abstract: A novel crystalline form of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.

公开(公告)号：US09278936B2

公开(公告)日：2016-03-08

申请号：US14382178

申请日：2013-02-27

Applicant: Array BioPharma Inc.

Inventor： Alisha B. Arrigo ,  Donald T. Corson ,  Coralee G. Mannila

IPC: C07D231/56 ,  A61K31/4155

CPC classification number: C07D231/56 ,  A61K31/4155 ,  Y02A50/411 ,  Y02A50/463

Abstract: Provided herein is a hydrogen chloride salt of 1-(3-/t?r/-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzyl)urea, crystalline forms of 1-(3-½^butyl-1^-tolyl-1H-pyrazol-5-yl)-3-(5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzyl)urea hydrochloride, processes for the preparation of said crystalline forms, pharmaceutical compositions containing a crystalline form of 1-(3-r

Abstract translation: 本文提供的是1-（3-叔丁基-1-叔丁基-1-对甲苯基-1H-吡唑-5-基）-3-（5-氟-2-（1-（2 - 羟基乙基）-1H-吲唑-5-基氧基）苄基）脲，1-（3 - 1/2丁基-1'-甲苯基-1H-吡唑-5-基）-3-（5-氟-2 - （1-（2-羟乙基）-1H-吲唑-5-基氧基）苄基）脲盐酸盐，制备所述结晶形式的方法，含有1-（3-r 丁基-1-对甲苯基-1H-吡唑-5-基）-3-（5-氟-2-（1-（2-羟乙基）-1H-吲唑-5-基氧基）苄基）脲盐酸盐形式B ，所述组合物的制备方法，通过所述方法制备的药物组合物，以及所述组合物在治疗各种疾病和病症中的用途。

公开(公告)号：US10799505B2

公开(公告)日：2020-10-13

申请号：US14943014

申请日：2015-11-16

Applicant: Array BioPharma, Inc.

Inventor： Alisha B. Arrigo ,  Derrick Juengst ,  Khalid Shah

IPC: C07D487/04 ,  A61K31/519 ,  C12Q1/48

Abstract: A novel crystalline form of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.

公开(公告)号：US10285993B2

公开(公告)日：2019-05-14

申请号：US15706062

申请日：2017-09-15

Applicant: Array BioPharma, Inc.

Inventor： Alisha B. Arrigo ,  Derrick Juengst ,  Khalid Shah

IPC: A61K31/519 ,  C07D487/04 ,  C12Q1/48

Abstract: A novel crystalline form of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.

公开(公告)号：US10172861B2

公开(公告)日：2019-01-08

申请号：US15872769

申请日：2018-01-16

Applicant: Array BioPharma, Inc.

Inventor： Alisha B. Arrigo ,  Derrick Juengst ,  Khalid Shah

IPC: A61K31/519 ,  C07D487/04 ,  C12Q1/48

Abstract: A novel crystalline form of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.