Chinese Academy of Sciences

Zhejiang University

Guangzhou Lixin Pharmaceutical Co., Ltd.

Zhejiang Academy of Traditional Chinese Medicine

Hangzhou Westan Pharmaceutical Technology Co., Ltd

Hangzhou Yirui Pharmaceutical Technology Co., Ltd

Yongzhou Hu

Jia Tao Li

Yubo Zhou

Tao Liu

Xiaowu Dong

Bo Yang

Qiaojun He

Xiaobei Hu

Jia Li

Lei Xu

Anhui Gao

Mingbo Su

Peipei Wang

Lexian Tong

Wenhu Zhan

Qinjie Weng

Mengmeng Zhang

Pinrao Song

Weijuan Kan

Yuji Wang

Fanzhi Kong

Rong Sheng

Jun Wei

Dongyan Gu

Jiankang Zhang

Kaixiang Zhang

Jieyu Liu

Wanping Zhu

Xiaolu Wang

Qing Ye

Xiuai Hu

Xia Liu

Yunfeng Cheng

Provided by the present disclosure are an amino quinazolinone and amino isoquinolone derivatives. It is verified by numerous experiments that the compounds provided by the present disclosure have good inhibiting effects on PI3Kα and PI3Kγ, most of the compounds have prominent inhibiting effect on PI3Kα, and show strong growth inhibiting effect on PIK3CA mutant tumor cells such as human breast cancer cell strain (MCF7). Therefore, the amino quinazolinone and amino isoquinolone derivatives according to the present disclosure can be applied in the preparation of anti-tumor and anti-inflammatory medicines, and can be used as PI3Kα inhibitors in the preparation of medicines for treatment of human or animal cell proliferation related tumors, the medicines comprising the derivatives any one or more of pharmaceutically acceptable salts and solvates thereof as well as pharmaceutically acceptable carriers. Formulas a and b are shown as below:

Aminoquinazolinone and aminoisoquinolinone derivatives and application thereof

Provided in the present invention are a heteroaromatic acetamide derivative and the preparation and the use thereof, wherein the heteroaromatic acetamide derivative is a heteroaromatic acetamide compound as shown in general formula (I), or a pharmaceutically acceptable salt and/or solvate thereof. According to the present invention, experiments have confirmed that the heteroaromatic acetamide derivative of the present invention can specifically bind to transient receptor potential ankyrin 1 (TRPA1) and inhibit or reduce the activity thereof, and can be used for treating diseases mediated by TRPA1. The present invention further provides a method for preparing the heteroaromatic acetamide derivative, and a drug and pharmaceutical composition containing the heteroaromatic acetamide derivative.

Heteroaromatic acetamide derivative, and preparation and use thereof

The invention provides an N-benzyl-N-arylsulfonamide derivative, which is an N-benzyl-N-arylsulfonamide compound represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof. The N-benzyl-N-arylsulfonamide derivative is obtained by condensing a substituted nitrobenzene with 5- or 6-membered nitrogen-containing aliphatic heterocycle (the ring B), reducing the nitro group to an amino group, and subjecting the amino group to reductive amination, sulfonamidation; or by subjecting a substituted nitrobenzene to nitro reduction, reductive amination and sulfonamidation, and condensing the resultant intermediate with 5- or 6-membered nitrogen-containing aliphatic heterocycle (the ring B). It has been experimentally demonstrated that the N-benzyl-N-arylsulfonamide derivative of the invention can specifically bind to Kv1.3 potassium channel and inhibit or decrease its activity, and is useful in the treatment of autoimmune diseases caused by abnormal activation of the Kv1.3 potassium channel in human or animals. The invention further provides a medicament or a pharmaceutical composition comprising the N-benzyl-N-arylsulfonamide derivative.

N-benzyl-N-arylsulfonamide derivative and preparation and use thereof

The present invention provides a 2-polysubstituted aromatic ring-pyrimidine derivative and an optical isomer thereof, or a pharmaceutically acceptable salt or solvate thereof, the compound, and an optical isomer thereof or a pharmaceutically thereof acceptable salts or solvates can be used in the preparation of anti-tumor drugs. The invention designs and synthesizes a series of novel small molecule Chk1 inhibitors by using N-substituted pyridin-2-aminopyrimidine obtained by structure-based virtual screening as a lead compound, and carries out Chk1 kinase inhibitory activity test. The experiment confirmed that said compounds possess potent anticancer activity, Chk1 kinase inhibitory activity, and are promising Chk1 inhibitors, and can be used as new cancer therapeutic drugs, which can be applied to treat solid tumors or hematologic tumors related to proliferative disease of human or animal. The 2-polysubstituted aromatic ring-pyrimidine derivatives provided by the present invention has the structure of the formula I: 

2-polysubstituted aromatic ring-pyrimidine derivatives, preparation and medical application thereof

A polyfluoro-substituted aromatic heterocyclic derivative having the structure as represented by formula I or formula I', wherein at least one of Rand Ris a fluorine atom, and at least two substituents of Rc, Rd, Re, and Rf are fluorine atoms; and an optical isomer of the derivative, or a pharmaceutically acceptable salt or solvate of the same, or a pharmaceutically acceptable salt or solvate of the optical isomer of the same. A composition containing the polyfluoro-substituted aromatic heterocyclic derivative and an application of the composition in preparing an anti-tumour medicament. The compound provides significant inhibitory effects with respect to Akt1 and demonstrates strong proliferation inhibitory activity with respect to tumour cell lines such as an ovarian cancer cell line, a colon cancer cell line, and a prostate cancer cell line. Therefore, the compound may be used as an Akt inhibitor in the medicament for treating a cell proliferation-related solid tumour or blood cancer in the human or animal body.

Polyfluoro-substituted aromatic heterocyclic derivative, pharmaceutical composition containing same, and applications thereof

The present invention discloses a terpinenol compound as well as its preparation method and application. The structure of such terpinenol compound is as shown in Formula (I) or (II). In Formula (I), R is independently selected from C-Calkyl, &#x2014;NRR, &#x2014;SRor &#x2014;OR; R, R, Rand Rare independently selected from C-Calkyl or &#x2014;NO; the C-Calkyl can be substituted by OH; Alternatively, the Rand Rform a five-member ring or six-member ring in together with N used to link up them; the five-member or six-member ring may contain one O or C&#x2550;O. As indicated by results of activity test, such terpinenol compound has satisfactory effect in prevention of asthma, inflammation and pulmonary artery hypertension, which also has high pharmaceutical significance. 

Terpineol and preparation method and application thereof

A 2-substituted aromatic ring-pyrimidine derivative as shown in a general formula I, and an optical isomer or a pharmaceutically acceptable salt or a solvate thereof are provided. The present invention designs and synthesizes a series of novel small molecular Chk1 inhibitors by using N-substituted pyridin-2-aminopyrimidine obtained through structure-based virtual screening as a lead compound, and carries out Chk1 kinase inhibitory activity test. The experiment confirmed that said compounds possess strong anti-cancer effect, Chk1 kinase inhibitory activity and are promising Chk1 inhibitors. The compounds can be used as new cancer therapeutic drugs, which can be applied to treat solid tumors or hematologic tumors related to proliferative disease of human or animal.

2-substituted aromatic ring-pyrimidine derivative and preparation and application thereof

Disclosed are new substituted nitrogen-containing heterocyclic derivatives represented by formula (I) as AKT inhibitors, optical isomers, pharmaceutically acceptable salts or solvates thereof, wherein the definition of R1, R2, R3, R4, R5, R6, ring A, ring C, B, Q, Y, Z and m is shown in the description for details. In addition, medicaments comprising the derivatives as active components are also disclosed, which can be useful for treating proliferative diseases, such as cancer and inflammation, especially diseases relating to AKT kinase.

Substituted nitrogen-containing heterocyclic derivatives, pharmaceutical compositions comprising the same and applications of antitumor thereof

Disclosed are a tripeptide epoxyketone compound, a preparation method thereof, and a use thereof in the preparation of anti-tumor drugs.

Tripeptide epoxyketone compound constructed by heterocycle and preparation method and use thereof

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Zhejiang, China

Yongzhou Hu