- Pyrazolo [3, 4 - c] pyridine - 7 - ketone compound and use thereof
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Belonging to the technical field of medicine, the invention relates to a 4, 5-dihydro-1H-pyrazolo[3, 4-c]pyridine-7-one containing derivative shown as general formula I, and pharmaceutically acceptable salt, hydrate or prodrug thereof, wherein the substituents A, R1 and R2 have meanings given in the specification. The preparation also relates to a preparation method of the general formula I compound and its pharmaceutically acceptable salt or prodrug, medicinal compositions containing the compound and application of the compound as an Xa factor inhibitor, especially application in preparation of drugs for treatment and/or prevention of thromboembolic diseases. (formula I).
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Paragraph 0197; 0238; 0243; 0244
(2017/09/01)
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- Apixaban derivatives as well as preparation method and application thereof
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The invention belongs to the technical field of medicines and discloses apixaban derivatives and analogues as well as a preparation method and application thereof. The structure of the compounds is shown as the following formula. Cheap and readily available paranitroaniline serves as an initial raw material. The preparation method comprises the following steps: performing amidation-cyclization, chlorination, condensation-elimination, cyclization-elimination, reduction, amidation-cyclization so as to obtain a key intermediate; and dehydrating, performing ammonolysis or chlorination, and condensing to synthesize the target compound. The method is simple in operation, convenient in after-treatment and high in yield. The in-vitro anti-coagulant activity of the target compound is investigated by determining the activated partial thromboplastin time (APTT) and thromboplastin time (PT). The EC2X(APTT) of result compounds APX-02, APX-15 and APX-16 is respectively 2.15mug/L, 3.65mug/L and 2.35mug/L, the EC2X(PT) of the result compounds is respectively 0.12mug/L, 3.57mug/L and 1.57mug/L, which are higher than the EC2X(APTT) value of 3.78mug/L and the EC2X(PT) value of 1.59mug/L of a positive control agent Apixaban. The compounds have high anti-coagulant activities. The EC2X(APTT) value of the rest compounds is between 5mug/L and 65mug/L, and the EC2X(PT) value is between 3mug/L and 18mug/L. The structural formula is as shown in the specification.
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Paragraph 0026; 0031; 0042-0044
(2017/12/27)
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- Design, synthesis, and biological activity of novel tetrahydropyrazolopyridone derivatives as FXa inhibitors with potent anticoagulant activity
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A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant potency, and compounds 15b, 15c, 20b, 20c, and 22b were further examined for their inhibitory activity against human FXa in vitro. While compounds 15c and 22b were tested for rat venous thrombosis in vivo. The most promising compound 15c, with an IC50 (FXa) value of 0.14?μM and 98% inhibition rate, warranted further investigation as an FXa inhibitor.
- Sun, Xiaoqing,Hong, Zexin,Liu, Moyi,Guo, Su,Yang, Di,Wang, Yong,Lan, Tian,Gao, Linyu,Qi, Hongxia,Gong, Ping,Liu, Yajing
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p. 2800 - 2810
(2017/04/18)
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- Design, synthesis and structure-activity relationships of novel 4-phenoxyquinoline derivatives containing 1,2,4-triazolone moiety as c-Met kinase inhibitors
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A series of novel 4-phenoxyquinoline derivatives containing 1,2,4-triazolone moiety were synthesized and evaluated for their in?vitro cytotoxic activity against four cancer cell lines (HT-29, H460, A549 and MKN-45). Most of the compounds exhibited moderate-to-significant cytotoxicity. Compounds 33, 37, 39, 44, 46, 47, 53, 55, 61, 64 and 66 were further examined for their inhibitory activity against c-Met kinase. The most promising compound 47 (with c-Met IC50value of 1.57?nM) showed remarkable cytotoxicity against HT-29, H460, A549 and MKN-45?cell lines with IC50values of 0.08?μM, 0.14?μM, 0.11?μM and 0.031?μM, respectively, and thus it was 1.1- to 2.3- fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity.
- Liu, Ju,Nie, Minhua,Wang, Yanjing,Hu, Jinxing,Zhang, Feng,Gao, Yanlin,Liu, Yajing,Gong, Ping
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p. 431 - 446
(2016/08/04)
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- Pyrazolo[3,4-c]pyridine derivative
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The invention relates to a pyrazolo[3,4-c]pyridine derivative. The invention relates to a compound represented by a formula (I), a tautomer thereof, an optical isomer thereof or a pharmaceutically acceptable salt thereof, wherein the formula (I) is shown in the description, and Z, X, RNc, RNd, RNe and RNf are defined according to the claim 1. The invention further relates to the pharmaceutical composition contain the compound. The invention further relates to use of the compound or the pharmaceutical composition in preparing a drug for preventing and/or treating a disease which inhibits positive influence of an Xa factor, particularly use in preparing the drug for preventing and/or treating the disease which inhibits positive influence of the Xa factor under the condition of low hemorrhage risk.
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Paragraph 0391; 0392; 0393
(2016/10/08)
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- 4,5-dihydropyrazolo [3,4-c] pyridine-2-one spiro derivatives, its preparation method and application
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Disclosed are a spirocyclic derivative of 4,5-dihydropyrazolo[3,4-c]pyridine-2-one as represented by general formula (I), preparation method and use thereof, the definition of each substituent in the compound of general formula (I) being the same as the definition in the description.
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Paragraph 0396; 0451-0455; 0501; 0502-0506
(2016/10/08)
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- NOVEL PROCESS FOR THE PREPARATION OF A LACTAM-CONTAINING COMPOUND
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Provided herein is a novel, commercially viable and industrially advantageous process for the preparation of 1-(4-Methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazole-[3,4-c]pyridine-3-carboxamide, in high yield and with high purity, using a novel intermediate 3-chloro-1-(4-iodophenyl)-5,6-dihydropyridin-2(1H)-one.
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Page/Page column 25; 26
(2015/12/08)
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- DIHYDROPYRAZOLE GPR40 MODULATORS
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The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are GPR40 G protein-coupled receptor modulators which may be used as medicaments.
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Paragraph 00230
(2014/06/11)
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- APIXABAN PREPARATION PROCESS
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Process for the preparation of apixaban and intermediates useful for the preparation thereof.
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Page/Page column 16-17
(2013/02/27)
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- A new method for the synthesis of 1-aryl-1,2,4-triazole derivatives
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A new and convenient one-step recyclization method for the synthesis of ethyl 1-aryl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxylates is reported. Various ethyl chloro(2-arylhydrazinylidene)ethanoates react with thiazolidine-2,4-dione in the presence of potassium hydroxide to produce the 1-aryl-1,2,4-triazole derivatives in moderate to good yields. The procedure is economical, environmentally friendly and simple to perform. Georg Thieme Verlag Stuttgart - New York.
- Matiychuk, Vasyl S.,Potopnyk, Mykhaylo A.,Luboradzki, Roman,Obushak, Mykola D.
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experimental part
p. 1799 - 1803
(2011/07/08)
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- Process for preparing 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones
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A novel process and intermediates thereof for making 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones of the type shown below from appropriate phenyl hydrazines is described. These compounds can be useful as factor Xa inhibitors.
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Page/Page column 11-12
(2010/10/20)
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