- Pyrimido triazole compound and medical application thereof (by machine translation)
-
The present invention relates to a compound of general (I) or a hydrate thereof or a pharmaceutically acceptable salt, thereof, a hydrate thereof or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the same or a pharmaceutically acceptable salt thereof, and use, of the compound or a pharmaceutically acceptable salt thereof in the manufacture of a medicament . The medicament is for anti-platelet aggregation and treatment of related diseases such as antithrombotic . (by machine translation)
- -
-
Paragraph 0043; 0072-0075
(2020/05/30)
-
- METHOD FOR PREPARATION OF CHLORINATED S-PROPYLTHIOBARBITURIC ACID
-
The invention discloses a method for preparation of 4,6-dichloro-5-nitro-2- (propylthio)pyrimidine by conversion of 5-nitro-2-propylthiopyrimidine-4,6-diol with phosgene in the presence of DMF.
- -
-
Page/Page column 10
(2019/02/06)
-
- Method for preparing 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine
-
The invention discloses a method for preparing 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine. The method comprises the following steps: dissolving 6-hydroxy-5-nitro-2-(propylmercapto)-4-(3H)-pyrimidone into toluene, performing cooling, slowly dropping pyrophosphoryl chloride, performing heating, adding a catalyst, performing a reaction for 10-40 hours, performing cooling after the reaction is ended, pouring the reaction system into ice water, performing stirring and layering, adding neutral silica gel of 60-120 meshes into the upper toluene layer, performing stirring, performing filtration, and performing rotary evaporation on the filtrate to recycle the toluene so as to obtain the oily 4,6-dichloro-5-nitro-2-(propylmercapto)-pyrimidine. The method is mild in reaction condition, high in reaction yield and small in environment pollution.
- -
-
Paragraph 0020-0026
(2019/10/04)
-
- Design, synthesis and in vitro biological evaluation of novel [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing a thiosemicarbazide moiety
-
A series of hybrid molecules containing [1,2,3]triazolo[4,5-d]pyrimidine and thiosemicarbazide moieties were designed, synthesized and evaluated for their antiproliferative activities against MGC-803, NCI-H1650 and PC-3 human cancer cells. Some of the synthesized compounds showed moderate to good activity against three selected cancer cell lines. Among these compounds, compound 29 displayed the most potent antiproliferative activity as well as good selectivity between cancer cells and normal cells. Further mechanism studies revealed that compound 29 could obviously inhibit the colony formation and migration of MGC-803 as well as induced apoptosis.
- Geng, Peng-Fei,Liu, Xue-Qi,Zhao, Tao-Qian,Wang, Cong-Cong,Li, Zhong-Hua,Zhang, Ji,Wei, Hao-Ming,Hu, Biao,Ma, Li-Ying,Liu, Hong-Min
-
p. 147 - 156
(2018/02/10)
-
- For the improvement of the [...] intermediates preparation method
-
The invention relates to an improved preparation method for the intermediate 4, 6-dihalogen-2-(propythio)pyrimidine-5-amine used for preparing the anticoagulation drug ticagrelor, and application of the intermediate in preparation of ticagrelor. By use of a phase transfer reagent, the method reduces the halogenating reagent consumption and emission and treatment of toxic substances. Also, the obtained product has high yield and good purity. Thus, the method is a greener and more economical preparation method more suitable for industrial application.
- -
-
Paragraph 0250-0252
(2018/02/04)
-
- Synthesis, Antiplatelet Aggregation Activity Evaluation and 3D-QSAR of a Series of Novel 6-Alkylamino(Alkoxyl)-2-Propylthio-8-Azapurine Nucleosides
-
A series of novel 6-alkylamino(alkoxyl)-2-propylthio-8-azapurine nucleosides were synthesized by an improved route, and the human antiplatelet aggregation activities of these new compounds were evaluated. A self-organizing molecular field analysis method was used to study the three-dimensional quantitative structure–activity relationship of these novel nucleosides. The results of the antiplatelet aggregation activity evaluation and analysis of the self-organizing molecular field analysis models through shape and electrostatic grids may provide a basis for the development of new and potent antiplatelet agents.
- Du,Yu,Deng,Lu,Li
-
p. 436 - 449
(2017/02/05)
-
- Preparation method for ticagrelor intermediate
-
The invention discloses a preparation method for a cagrelor intermediate. The preparation method comprises the following steps; step 1, reacting 2-nitro-1,3-malonic acid diester with sodium sulfocyanate and ammonium acetate in an aqueous solution of acetic acid so as to obtain a compound as shown in a formula II which is described in the specification; step 2, subjecting the compound as shown in the formula II to reflux in ethanol under the action of sodium alkoxide so as to obtain a compound as shown in a formula III which is described in the specification; step 3, subjecting the compound as shown in the formula III and 1-bromopropane to a contact reaction in 1,4-dioxane in the presence of alkali under the catalysis of zinc chloride; and step 4, subjecting a product of the step 3 and a chlorination reagent to a chlorination reaction in acetonitrile so as to obtain the ticagrelor intermediate 4,6-dichloro-5-nitro-2-(propylthio)pyridine. The preparation method provided by the invention has the advantages of few by-products, easy purification and high yield of the ticagrelor intermediate, usage of cheap and easily available raw materials and suitable for industrial production.
- -
-
Paragraph 0052; 0053
(2017/08/03)
-
- Pyrimidine and triazole containing LSD1 inhibitor and preparation method and application thereof
-
The invention belongs to the field of medicinal chemistry, and discloses a pyrimidine and triazole containing compound and a preparation method and application thereof in preparation of anti-cancer medicine with lysine specific demethylase 1 (LSD1) being a target. The general formula of the compound is shown in the drawing I. In-vitro LSD1 enzyme inhibition activity experiments prove that by inhibiting LSD1 activity, the compound has obvious inhibiting and killing effects on kinds of cancer cells and can be applied to preparation of the anti-cancer medicine as a further developed lead compound.
- -
-
Paragraph 0084; 0085
(2017/04/03)
-
- Design, synthesis and antiproliferative activity of thiazolo[5,4-d]pyrimidine derivatives through the atom replacement strategy
-
A series of thiazolo[5,4-d]pyrimidine derivatives were designed through the atom replacement strategy based on biologically validated scaffolds and then evaluated for their antiproliferative activities on cancer cell lines. The structure-activity relationship studies were conducted, leading to the identification of compound 22, which exhibited good antiproliferative activity against HGC-27 with an IC50 value of 1.22 μM and low toxicity against GES-1 cells. Mechanistic studies showed that compound 22 inhibited the colony formation and migration of HGC-27 as well as induced apoptosis. The western blot experiments proved that compound 22 up-regulated expression of Bax, down-regulated expression levels of Bcl-2 and cleaved caspased-3/9. These findings indicate that compound 22 may serve as a template for designing new agents for the treatment of human gastric cancers. The atom replacement strategy could be viable strategy for designing new anticancer drugs and may find its applications in drug design.
- Li, Zhong-Hua,Liu, Xue-Qi,Geng, Peng-Fei,Zhang, Ji,Ma, Jin-Lian,Wang, Bo,Zhao, Tao-Qian,Zhao, Bing,Zhang, Xin-Hui,Yu, Bin,Liu, Hong-Min
-
p. 1034 - 1041
(2017/08/02)
-
- Design, synthesis, and biological evaluation of new thiazolo[5,4-: D] pyrimidine derivatives as potent antiproliferative agents
-
A series of thiazolo[5,4-d]pyrimidine derivatives were synthesized and evaluated for their antiproliferative activities against several human cancer cell lines. Structure-activity relationship studies were carried out, showing that most of the target compounds had good inhibition against the tested cell lines. Among them, compound 7i exhibited potent inhibition against human gastric cancer cells MGC-803 and HGC-27 with IC50 values of 4.64 and 5.07 μM, respectively and around 12-fold selectivity between MGC-803 and GES-1, indicating a relatively low toxicity to normal cells. The potency and low toxicity of compound 7i make the thiazolo[5,4-d]pyrimidine an attractive scaffold for designing new derivatives selectively targeting MGC-803 cells.
- Li, Zhong-Hua,Liu, Xue-Qi,Geng, Peng-Fei,Ma, Jin-Lian,Zhao, Tao-Qian,Wei, Hao-Ming,Yu, Bin,Liu, Hong-Min
-
p. 1655 - 1658
(2017/08/22)
-
- Pyrimidotriazole-containing LSD1 inhibitor, preparation method and application
-
Belonging to the field of pharmaceutical chemistry, the invention discloses a pyrimidotriazole compound, a preparation method and application of the compound with lysine specific demethylase 1 (LSD1) as the target in preparation of antitumor drugs. The general formula of the compound is shown as I in the specification. In vitro LSD1 enzyme inhibitory activity experiments prove that by inhibiting the activity of LSD1, the compound has obvious inhibition and killing effects on multiple tumor cells, can be applied as a lead compound for further development in preparation of antitumor drugs.
- -
-
Paragraph 0056; 0057
(2017/08/31)
-
- Inhibitor with pyrimido-triazole-tetrazole-thione LSD1 (lysine specific demethylase 1), preparation method of inhibitor and application
-
The invention belongs to the field of medicinal chemistry, and discloses a compound with pyrimido-triazole-tetrazole-thione structures, a preparation method of the compound and an application of the compound to preparation of anti-tumor medicines by taking lysine specific demethylase 1 (hereinafter referred to as LSD1) as a target. The general formula of the compound is as shown in the specification. In-vitro LSD1 inhibitory activity tests show that the compound has obvious inhibiting and killing functions on various tumor cells by inhibiting activity of the LSD1, can serve as a further developed lead and is applied to preparation of anti-tumor medicines.
- -
-
Paragraph 0058; 0059
(2017/09/05)
-
- Preparing method for ticagrelor intermediate 4,6-dichloro-2-tri-sulfydryl-5-aminopyrimidine
-
The invention relates to a preparing method of a ticagrelor intermediate 4,6-dichloro-2-tri-sulfydryl-5-aminopyrimidine and belongs to the field of medicine preparation. The preparing method for 4,6-dichloro-2-tri-sulfydryl-5-aminopyrimidine comprises the following reaction steps that malonic acid bis-alkane ester serves as a raw material, 2-nitro malonic acid bis-alkane ester is obtained through nitration and then is subjected to cyclization with thiourea to generate 5-mitro-2-thiobarbituric acid, 5-mitro-2-thiobarbituric acid and halogenated n-propane are subjected to a thio-alkylation reaction to obtain 4,6-dyhydroxyl-5-nitro-2-tri-sulfydryl pyrimidine, then 4,6-dyhydroxyl-5-amono-2-tri-sulfydryl pyrimidine is obtained under catalytic hydrogenation, and finally 4,6-dyhydroxyl-5-amono-2-tri-sulfydryl pyrimidine and phosphorus oxychloride are subjected to a chlorination reaction to obtain the target compound 4,6-dichloro-2-tri-sulfydryl-5-aminopyrimidine. The method has the advantages that few reaction steps are needed, the reaction conditions are mild, and industrialization is easy to achieve.
- -
-
Paragraph 0018; 0044; 0045
(2018/02/04)
-
- PROCESSES FOR PREPARING TICAGRELOR INTERMEDIATE, 4,6-DICHLORO-5-NITRO-2-(PROPYLTHIO)PYRIMIDINE
-
Provided herein are improved, commercially viable and industrially advantageous processes for the preparation of a substantially pure ticagrelor intermediate, 4,6-dichloro-5-nitro-2-(propylthio)pyrimidine, Formula (II). The intermediate is useful for preparing ticagrelor, or a pharmaceutically acceptable salt thereof in high yield and purity.
- -
-
Paragraph 0117
(2013/03/26)
-
- NOVEL PROCESSES FOR PREPARING TRIAZOLO[4,5-D]PYRIMIDINE DERIVATIVES AND INTERMEDIATES THEREOF
-
Provided herein is a novel process for the preparation of triazolo[4,5-d]pyrimidine derivatives. Provided particularly herein is a novel, commercially viable and industrially advantageous process for the preparation of highly pure ticagrelor or a pharmaceutically acceptable salt thereof. Provided further herein is a novel process for the preparation of substituted cyclopentanamine derivatives, which are useful intermediates in the preparation of triazolo[4,5-d]pyrimidine compounds. Provided particularly herein is a novel, commercially viable and industrially advantageous process for the preparation of a ticagrelor intermediate, 2-[[(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d] [1,3]- dioxol-4-yl]oxy]- 1 -ethanol.
- -
-
Page/Page column 45-46
(2012/07/13)
-
- CYCLOPROPYL MODULATORS OF P2Y12 RECEPTOR
-
The present invention relates to new cyclopropyl modulators of P2Y12 receptor activity, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Page/Page column 40-41
(2011/02/24)
-
- IMPROVED PROCESSES FOR PREPARING TICAGRELOR INTERMEDIATE, 4,6-DICHLORO-5-NITRO-2-(PROPYLTHIO)PYRIMIDINE
-
Provided herein are improved, commercially viable and industrially advantageous processes for the preparation of a substantially pure ticagrelor intermediate, 4,6-dichloro-5-nitro-2- (propylthio)pyrimidine, Formula (II). The intermediate is useful for preparing ticagrelor, or a pharmaceutically acceptable salt thereof, in high yield and purity.
- -
-
Page/Page column 20
(2011/09/19)
-
- Triazolo[4,5-D]pyrimidinyl derivatives and their use as medicaments
-
The invention relates to triazolo[4,5-d]pyrimidin-3-yl derivatives which are useful in the treatment of platelet aggregation disorders.
- -
-
-
- Triazolo [4,5-d]pyrimidine compounds, their use as medicaments, compositions containing them and processes for their preparation
-
PCT No. PCT/SE98/01392 Sec. 371 Date Sep. 30, 1998 Sec. 102(e) Date Sep. 30, 1998 PCT Filed Jul. 15, 1998 PCT Pub. No. WO99/05142 PCT Pub. Date Feb. 4, 1999The invention provides new triazolo[4,5-d]pyrimidine compounds, their use as medicaments, compositions containing them and processes for their preparation.
- -
-
-
- Inhibitors of platelet aggregation
-
Compounds of the formula (I) STR1 wherein B is O or CH2 ; X is selected from NR1 R2, SR1, and C1 -C7 alkyl; Y is selected SR1, NR1 R2, and C1 -C7 alkyl; R1 and R2 is each and independently selected from H, or C1 -C7 alkyl optionally substituted upon or within the alkyl chain by one or more of O, S, N or halogen; R3 and R4 are both H, or R3 and R4 together form a bond; A is COOH, C(O)NH(CH2)p COOH, C(O)N?(CH2)q COOH!2, C(O)NHCH(COOH)(CH2)r COOH, or 5-tetrazolyl, wherein p, q and r is each and independently 1, 2 or 3; as well as pharmaceutically acceptable salts and prodrugs thereof, pharmaceutical compositions comprising the novel compounds and use of the compounds in therapy. Also within the scope of the invention are novel intermediates to the novel compounds. The novel compounds are in particular useful in the prevention of platelet aggregation.
- -
-
-