Shanghai Pharmaceuticals Holding Co., Ltd.

Mitsubishi Tanabe Pharma Corporation

Zhejiang University

Shanghai Pharmaceuticals Holdings Co., Ltd.

Shanghai Pharmaceuticals Holding Cd., Ltd.

Guangxin Xia

Jingkang Shen

Toru Iijima

Yanjun Liu

Hiroshi Sugama

Jianshu Xie

Jing Jing Zhang

Takayuki Kawaguchi

Yu Mao

Di Li

Miki Hirai

Qian Wang

Yoichi Takahashi

Hui Ge

Xiong Zhai

Jiansheng Han

Xuemei Liao

Hongjian Zuo

Lingjun Duan

Zhixiong Xiang

Yanan Han

Chen Shi

Guoyong Huo

Liang Zhao

Jia Xu

Hidenori Akatsuka

Yu Hao

Naoko Ueda

Nobumasa Awai

Huixin Wan

Ning Zhou

Xuejun Liu

Yongping Yu

Wenteng Chen

Yuko Togashi

Ao Chen

Chunchun Zhang

Bojun Li

Wenbo Xiao

Guangsheng Wu

Guohui Jia

A nitrogenous heterocyclic compound, a preparation method, an intermediate, a composition, and an application. The present invention provides a nitrogenous heterocyclic compound as represented by formula I, pharmaceutically acceptable salts thereof, enantiomers thereof, diastereoisomers thereof, tautomers thereof, solvates thereof, metabolites thereof, or prodrugs thereof. The compound has high inhibitory activity against ErbB2 tyrosine kinase, has good inhibitory activity against human breast cancer cells BT-474, human gastric cancer cells NCI-N87 and the like with high expression of ErbB2, and in addition has relatively weak inhibitory activity against EGFR kinase, that is, the compound is an EGFR/ErbB2 double target inhibitor that attenuates EGFR kinase inhibitory activity or a small-molecule inhibitor having selectivity for an ErbB2 target. 

Nitrogenous heterocyclic compound, preparation method, intermediate, composition, and application

The present invention discloses a substituted pyridine compound represented by formula I, and a pharmaceutically acceptable salt, stereoisomer and tautomer thereof. The compounds of the present invention are useful in the treatment of cancers. 

Substituted pyrimidines as cyclin-dependent kinase inhibitors

A salt of a quinazoline derivative (N-[4-(3-chlorine-4-fluoroanilino)]-7-(3-morpholinepropanol)-6-(2-fluoroacrylamide)-quinazoline, the structure thereof is as represented by formula I). Compared with a known quinazoline derivative, the salt of the quinazoline derivative has one or more improved properties and at least has better water solubility, wherein a citrate, a benzene sulfonate, and an ethanedisulphonate thereof further have better crystallinity and are not easy to absorb moisture. 

Salt of quinazoline derivative, preparation method therefor and application thereof

Disclosed are a nitrogenous heterocyclic compound, intermediates, a preparation method, a composition and use thereof. The nitrogenous heterocyclic compound in the present invention is as shown in formula I. The compound has a high inhibitory activity towards ErbB2 tyrosine kinase and a relatively good inhibitory activity towards human breast cancer BT-474 and human gastric cancer cell NCI-N87 which express ErbB2 at a high level, and at the same time has a relatively weak inhibitory activity towards EGFR kinase. Namely, the compound is a highly selective small-molecule inhibitor targeted at ErbB2, and hence it has a high degree of safety, and can effectively enlarge the safety window in the process of taking the drug. 

Nitrogenous heterocyclic compound, preparation method, intermediate, composition and use

The present invention discloses a nitrogen-containing fused heterocyclic compound, as well as a preparation method, intermediate, composition and application thereof. The nitrogen-containing fused heterocyclic compound of the present invention as represented by formula (I), as well as the pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, metabolite or drug precursor thereof, exhibit a high selectivity and a high inhibitory activity with respect to CDK4 and CDK6 at a molecular level, an excellent inhibitory activity with respect to breast cancer cells at a cellular level, and significant inhibition of tumor cell proliferation associated with cyclin-dependent kinase activity at an animal level. The invention also exhibits a good stability with respect to human or mouse liver microsomes without significant inhibition of metabolic enzymes, good in vivo absorption in mice and rats, a high bioavailability and good druggability.

The present invention provides novel pharmaceutically acceptable salts of a morpholine derivative, including a malate, a tartrate, a hydrochloride, an acetate, and a naphthalene disulfonate thereof, wherein the tartrate has 3 crystal salt forms: crystal form A, crystal form B and dihydrate; the malate, the hydrochloride, and the acetate each have one crystal salt form; the naphthalene disulfonate is amorphous. When compared to the known morpholine derivative free base, the present invention has one or more improved properties, e.g., a better crystalline state, greatly improved water solubility, light stability and thermal stability, etc. The present invention further provides preparation methods for the salts of morpholine derivative and the crystal forms thereof, pharmaceutical compositions and use thereof.

Salts of morpholine derivative, crystal forms thereof, processes for producing the same, pharmaceutical compositions including the same, and use thereof

The present invention provides a nitrogen-containing saturated heterocyclic compound of the formula [I]: wherein Ris a cycloalkyl group and the like, Ris an optionally substituted aryl and the like, R is a lower alkyl and the like, T is a carbonyl group, Z is &#x2014;O&#x2014; and the like, and Rto Rare the same or different and a hydrogen atom and the like; or a pharmaceutically acceptable salt, that is useful as a renin inhibitor.

Nitrogen-containing saturated heterocyclic compound

The present invention provides a nitrogen-containing saturated heterocyclic compound of the formula [I] which is useful as a renin inhibitor. wherein Ris a cycloalkyl group or an alkyl,

Renin inhibitor

Disclosed are as represented by Formula (I) a quinazoline derivative and a pharmaceutical acceptable salt thereof, or, an enantiomer, a non-enantiomer, a tautomer, a racemate, a solvate, a metabolic precursor, or a prodrug of both. Also disclosed are a preparation method therefor, an intermediate, a pharmaceutical composition having the quinazoline derivative, and an application thereof. The quinazoline derivative of the present invention is provided with improved anti-tumor activity. 

Quinazoline derivative, preparation method therefor, intermediate, composition and application thereof

The present invention provides a nitrogen-containing saturated heterocyclic compound of the formula [I]: wherein Ris a cycloalkyl group and the like, Ris an optionally substituted aryl and the like, R is a lower alkyl and the like, T is a carbonyl group, Z is &#x2014;O&#x2014; and the like, and Rto Rare the same or different and a hydrogen atom and the like;or a pharmaceutically acceptable salt, that is useful as a renin inhibitor.

The present invention provides a morpholine derivative of the formula [I]; wherein Ris a substituted alkyl group, an optionally substituted aryl group, an optionally substituted heterocyclo group, a cycloalkyl group or an alkyl group; Ris a substituted alkyl group, an optionally substituted aryl group, an optionally substituted heterocyclo group, an optionally substituted alkylcarbonyl group, an optionally substituted arylcarbonyl group, an optionally substituted heterocyclo-substituted carbonyl group or a cycloalkylcarbonyl group; T is a methylene group or a carbonyl group; R, R, Rand Rare the same or different and a hydrogen atom, an optionally substituted carbamoyl group or an optionally substituted alkyl group;or pharmaceutically acceptable salts thereof. These compounds are useful as a renin inhibitor.

Morpholine derivative

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Shanghai, China

Guangxin Xia