公开(公告)号：US11174237B2

公开(公告)日：2021-11-16

申请号：US16623297

申请日：2018-05-31

Applicant: SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES ,  FUKANG (SHANGHAI) HEALTH TECHNOLOGY CO., LTD.

Inventor： Chunhao Yang ,  Zehong Miao ,  Cun Tan ,  Xiajuan Huan ,  Jian Ding ,  Yi Chen

IPC: C07D307/84

Abstract: Disclosed are a 2-[4-(methylaminomethyl)phenyl]-5-fluoro-benzofuran-7-carboxamide hydrochloride polymorph, a preparation method therefor and an application thereof. Specifically, disclosed are three crystalline forms, i.e., crystalline forms A, B, and C, of 2-[4-(methylaminomethyl)phenyl]-5-fluoro-benzofuran-7-carboxamide hydrochloride (formula I), preparation methods for the three crystalline forms, and use of the three crystalline forms in preparation of drugs.

公开(公告)号：US20170000800A1

公开(公告)日：2017-01-05

申请号：US15269069

申请日：2016-09-19

Applicant: Shanghai Institute of Materia Medica, Chinese Academy of Sciences ,  Shanghai Haihe Pharmaceutical Co., Ltd.

Inventor： CHUNHAO YANG ,  Linghua Meng ,  Yanhong Chen ,  Xiang Wang ,  Cun Tan ,  Jiapeng Li ,  Jian Ding ,  Yi Chen

IPC: A61K31/5377 ,  A61K31/5386

CPC classification number: A61K31/5377 ,  A61K31/53 ,  A61K31/5386 ,  C07D419/04 ,  C07D419/14

Abstract: The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.

Abstract translation: 本发明涉及吡咯并[2,1-f] [1,2,4]三嗪化合物，其异构体或其药学上可接受的盐，酯或水合物及其制备方法和应用。 吡咯并[2,1-f] [1,2,4]三嗪化合物具有通式（I）表示的结构。 由通式（I）表示的吡咯并[2,1-f] [1,2,4]三嗪化合物可抑制磷脂酰肌醇-3激酶（PI3K）信号通路，从而用于制备治疗磷脂酰肌醇-3激酶 相关疾病如癌症。

公开(公告)号：US11214572B2

公开(公告)日：2022-01-04

申请号：US16626254

申请日：2018-06-22

Applicant: SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES

Inventor： Chunhao Yang ,  Linghua Meng ,  Haoyue Xiang ,  Jing Li ,  Xi Zhang ,  Xiang Wang ,  Cun Tan ,  Qian He ,  Jian Ding ,  Yi Chen

IPC: C07D487/04 ,  C07D519/00

Abstract: The present disclosure relates to 7-substituted pyrrolo[2,1-f][1,2,4]triazine compounds or pharmaceutically acceptable salts thereof, and preparation methods and uses thereof. These compounds show good PI3K inhibitory activity, can effectively inhibit the activity of PI3K kinase, and has significant enhancement and improvement of pharmacokinetic properties, such as bioavailability, due to the introduction of the 7-position group; furthermore, the compounds of the present disclosure exhibit an unpredictable high selectivity and strong inhibitory activity on PI3Kδ, and thus these compounds can be used for treating diseases related to PI3K pathway, especially for anti-cancer or for the treatment of tumors, leukemias and autoimmune diseases. After further optimizing and screening, the compounds are expected to be developed into a new type of anti-tumor drugs.

公开(公告)号：US20150018542A1

公开(公告)日：2015-01-15

申请号：US14375742

申请日：2013-01-14

Applicant: SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES ,  CISEN PHARMACEUTICAL CO., LTD.

Inventor： Chunhao Yang ,  Zehong Miao ,  Jian Ding ,  Meng Wang ,  Jinxue He ,  Cun Tan ,  Yi Chen

IPC: C07D307/81 ,  C07C67/307 ,  C07C67/08 ,  C07D405/04 ,  C07D407/12

CPC classification number: C07D307/81 ,  C07C67/08 ,  C07C67/307 ,  C07D405/04 ,  C07D405/12 ,  C07D407/12

Abstract: Provided in the present invention are a 2-arylbenzofuran-7-formamide compound as shown in general formula I or a pharmacologically or physiologically acceptable salt thereof, a preparation method thereof and use thereof in preparing anti-tumour drugs, wherein R1 and R2 are each independently hydrogen, straight or branched chained C1-C4 alkyl, C3-C4 cycloalkyl or saturated 5- or 6-membered heterocyclyl containing oxygen or nitrogen; or R1 and R2 together with N form an unsubstituted or substituted saturated 5- or 6-membered heterocyclyl containing at least one heteroatom, wherein the heteroatom is O, N and S, the substituent is a methyl on N; R3 is a hydrogen atom or a chlorine atom; R4 is a hydrogen atom or a fluorine atom; X is CH, CF or N; and Y is CH, CF or N.

Abstract translation: 本发明提供了通式Ⅰ所示的2-芳基苯并呋喃-7-甲酰胺化合物或其药理学或生理学上可接受的盐，其制备方法及其在制备抗肿瘤药物中的用途，其中R1和R2分别为 独立的氢，直链或支链C 1 -C 4烷基，C 3 -C 4环烷基或饱和的含有氧或氮的5-或6-元杂环基; 或R 1和R 2与N一起形成含有至少一个杂原子的未取代或取代的饱和的5-或6-元杂环基，其中杂原子是O，N和S，取代基是N上的甲基; R3是氢原子或氯原子; R4是氢原子或氟原子; X是CH，CF或N; Y为CH，CF或N.

公开(公告)号：US09533965B2

公开(公告)日：2017-01-03

申请号：US14375742

申请日：2013-01-14

Applicant: SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACADEMY OF SCIENCES ,  CISEN PHARMACEUTICAL CO., LTD.

Inventor： Chunhao Yang ,  Zehong Miao ,  Jian Ding ,  Meng Wang ,  Jinxue He ,  Cun Tan ,  Yi Chen

IPC: A61K31/343 ,  A61K31/4025 ,  A61K31/443 ,  A61K31/496 ,  A61K31/501 ,  A61K31/5355 ,  A61K31/541 ,  A61K31/551 ,  C07D307/79 ,  C07D405/04 ,  C07D405/10 ,  C07D405/14 ,  C07D413/10 ,  C07D413/14 ,  C07D417/10 ,  C07D417/14 ,  C07D307/81 ,  C07D405/12 ,  C07C67/08 ,  C07C67/307 ,  C07D407/12

CPC classification number: C07D307/81 ,  C07C67/08 ,  C07C67/307 ,  C07D405/04 ,  C07D405/12 ,  C07D407/12

Abstract: Provided in the present invention are a 2-arylbenzofuran-7-formamide compound as shown in general formula I or a pharmacologically or physiologically acceptable salt thereof, a preparation method thereof and use thereof in preparing anti-tumour drugs, wherein R1 and R2 are each independently hydrogen, straight or branched chained C1-C4 alkyl, C3-C4 cycloalkyl or saturated 5- or 6-membered heterocyclyl containing oxygen or nitrogen; or R1 and R2 together with N form an unsubstituted or substituted saturated 5- or 6-membered heterocyclyl containing at least one heteroatom, wherein the heteroatom is O, N and S, the substituent is a methyl on N; R3 is a hydrogen atom or a chlorine atom; R4 is a hydrogen atom or a fluorine atom; X is CH, CF or N; and Y is CH, CF or N.

Abstract translation: 本发明提供了通式I所示的2-芳基苯并呋喃-7-甲酰胺化合物或其药理学或生理学上可接受的盐，其制备方法及其在制备抗肿瘤药物中的用途，其中R 1和R 2 各自独立地为氢，直链或支链C 1 -C 4烷基，C 3 -C 4环烷基或含有氧或氮的饱和5-或6-元杂环基; 或R 1和R 2与N一起形成含有至少一个杂原子的未取代或取代的饱和5-或6-元杂环基，其中杂原子是O，N和S，取代基是N上的甲基; R 3为氢原子或氯原子; R 4为氢原子或氟原子; X是CH，CF或N; Y为CH，CF或N.

公开(公告)号：US09447101B2

公开(公告)日：2016-09-20

申请号：US14403014

申请日：2013-04-23

Applicant: Shanghai Institute of Materia Medica, Chinese Academy of Sciences ,  Shanghai Haihe Pharmaceutical Co., Ltd.

Inventor： Chunhao Yang ,  Linghua Meng ,  Yanhong Chen ,  Xiang Wang ,  Cun Tan ,  Jiapeng Li ,  Jian Ding ,  Yi Chen

IPC: C07D419/04 ,  C07D419/14 ,  A61K31/5377 ,  A61K31/5386 ,  A61K31/53 ,  A61P35/00 ,  C07D487/04 ,  C07D519/00 ,  C07D498/08

CPC classification number: C07D487/04 ,  A61K31/5377 ,  A61K31/5386 ,  C07D498/08 ,  C07D519/00

Abstract: The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.

Abstract translation: 本发明涉及吡咯并[2,1-f] [1,2,4]三嗪化合物，其异构体或其药学上可接受的盐，酯或水合物及其制备方法和应用。 吡咯并[2,1-f] [1,2,4]三嗪化合物具有通式（I）表示的结构。 由通式（I）表示的吡咯并[2,1-f] [1,2,4]三嗪化合物可抑制磷脂酰肌醇-3激酶（PI3K）信号通路，从而用于制备治疗磷脂酰肌醇-3激酶 相关疾病如癌症。

公开(公告)号：US09724352B2

公开(公告)日：2017-08-08

申请号：US15269069

申请日：2016-09-19

Applicant: Shanghai Institute of Materia Medica, Chinese Academy of Sciences ,  Shanghai Haihe Pharmaceutical Co., Ltd.

Inventor： Chunhao Yang ,  Linghua Meng ,  Yanhong Chen ,  Xiang Wang ,  Cun Tan ,  Jiapeng Li ,  Jian Ding ,  Yi Chen

IPC: A61K31/53 ,  A61K31/5377 ,  C07D419/04 ,  A61P35/00 ,  A61K31/5386 ,  C07D419/14

CPC classification number: A61K31/5377 ,  A61K31/53 ,  A61K31/5386 ,  C07D419/04 ,  C07D419/14

Abstract: The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.

公开(公告)号：US20150141644A1

公开(公告)日：2015-05-21

申请号：US14403014

申请日：2013-04-23

Applicant: Shanghai Institute of Materia Medica, Chinese Academy of Sciences ,  Shanghai Haihe Pharmaceutical Co., Ltd.

Inventor： Chunhao Yang ,  Linghua Meng ,  Yanhong Chen ,  Xiang Wang ,  Cun Tan ,  Jiapeng Li ,  Jian Ding ,  Yi Chen

IPC: C07D487/04 ,  C07D498/08

CPC classification number: C07D487/04 ,  A61K31/5377 ,  A61K31/5386 ,  C07D498/08 ,  C07D519/00

Abstract: The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.

Abstract translation: 本发明涉及吡咯并[2,1-f] [1,2,4]三嗪化合物，其异构体或其药学上可接受的盐，酯或水合物及其制备方法和应用。 吡咯并[2,1-f] [1,2,4]三嗪化合物具有通式（I）表示的结构。 由通式（I）表示的吡咯并[2,1-f] [1,2,4]三嗪化合物可抑制磷脂酰肌醇-3激酶（PI3K）信号通路，从而用于制备治疗磷脂酰肌醇-3激酶 相关疾病如癌症。