- Synthesis, Antiplatelet Aggregation Activity Evaluation and 3D-QSAR of a Series of Novel 6-Alkylamino(Alkoxyl)-2-Propylthio-8-Azapurine Nucleosides
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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
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- Design, synthesis and in vitro biological evaluation of novel [1,2,3]triazolo[4,5-d]pyrimidine derivatives containing a thiosemicarbazide moiety
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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
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- Design, synthesis and antiproliferative activity of thiazolo[5,4-d]pyrimidine derivatives through the atom replacement strategy
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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
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- Design, synthesis, and biological evaluation of new thiazolo[5,4-: D] pyrimidine derivatives as potent antiproliferative agents
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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
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- Pyrimido triazole compound and medical application thereof (by machine translation)
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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)
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Paragraph 0043; 0064-0067
(2020/05/30)
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- A [...] preparation method and intermediate
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The present invention relates to a preparation method and an intermediate of ticagrelor. The preparation method comprises that a compound represented by a formula VIII and a compound represented by a formula VII or a salt thereof as raw materials to carry out a reaction, and the obtained intermediate is subjected to acetonylidene protection group removing, optionally substituted azobenzene protection group removing, and cyclization, and then reacts with a compound represented by a formula II or a salt thereof to prepare the ticagrelor. The preparation method of the present invention has characteristics of short step, high total yield, mild reaction conditions and simple post-treatment, and is suitable for industrial production.
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Paragraph 0052-0054
(2018/04/21)
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- Pyrimidine and triazole containing LSD1 inhibitor and preparation method and application thereof
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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.
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Paragraph 0080; 0081
(2017/04/03)
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- Pyrimidotriazole-containing LSD1 inhibitor, preparation method and application
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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.
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Paragraph 0052; 0053
(2017/08/31)
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- Inhibitor with pyrimido-triazole-tetrazole-thione LSD1 (lysine specific demethylase 1), preparation method of inhibitor and application
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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.
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Paragraph 0054; 0055
(2017/09/05)
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- Preorganization in bistriazolyl anion receptors
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A series of 4,6-bis-(1,2,3-triazolyl)-pyrimidine and 4,6-bis-(1,2,3- triazolyl)-pyridine anion receptors were synthesized and the effect of the pyrimidine and pyridine moieties on their binding properties was examined. We found that intramolecular interactions preorganize the 4,6-bis-(1,2,3-triazolyl) -pyridine receptors resulting in higher anion binding constants in comparison with the nonpreorganized 4,6-bis-(1,2,3-triazolyl)-pyrimidine receptor.
- Merckx, Tamara,Verwilst, Peter,Dehaen, Wim
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supporting information
p. 4237 - 4240
(2013/07/26)
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- PROCESSES FOR PREPARING TICAGRELOR INTERMEDIATE, 4,6-DICHLORO-5-NITRO-2-(PROPYLTHIO)PYRIMIDINE
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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.
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Paragraph 0113
(2013/03/26)
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- NOVEL PROCESSES FOR PREPARING TRIAZOLO[4,5-D]PYRIMIDINE DERIVATIVES AND INTERMEDIATES THEREOF
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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.
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Page/Page column 45
(2012/07/13)
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- Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents
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Ticagrelor (1) is the first reversible P2Y12 receptor antagonist blocking adenine diphosphate (ADP)-induced platelet aggregation with rapid onset and offset of effects. In this study, synthesis of ticagrelor and its derivatives has been accomplished in a convergent way. The compound design was based on modifications of ticagrelor and its major metabolite (33) in order to ameliorate their pharmacokinetic properties and dosing profile. The final compounds (1a-g, 35a-g) were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. The assay results showed that some compounds (e.g., 1b, 1d, 33, 35b, 35f) exhibited comparable potency with that of ticagrelor.
- Zhang, Hao,Liu, Jun,Zhang, Luyong,Kong, Lingyi,Yao, Hequan,Sun, Hongbin
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supporting information; experimental part
p. 3598 - 3602
(2012/07/14)
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- IMPROVED PROCESSES FOR PREPARING TICAGRELOR INTERMEDIATE, 4,6-DICHLORO-5-NITRO-2-(PROPYLTHIO)PYRIMIDINE
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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.
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Page/Page column 18
(2011/09/19)
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- CYCLOPROPYL MODULATORS OF P2Y12 RECEPTOR
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The present invention relates to new cyclopropyl modulators of P2Y12 receptor activity, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 40
(2011/02/24)
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- Novel triazolo pyrimidine compounds
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The present invention relates to a pyrimidine compound (I) useful as a pharmaceutical intermediate, to a process for preparing said pyrimidine compound, to intermediates used in said process, and to the use of said pyrimidine compound in the preparation of pharmaceuticals.
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- Triazolo[4,5-D]pyrimidinyl derivatives and their use as medicaments
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The invention relates to triazolo[4,5-d]pyrimidin-3-yl derivatives which are useful in the treatment of platelet aggregation disorders.
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- Triazolo [4,5-d]pyrimidine compounds, their use as medicaments, compositions containing them and processes for their preparation
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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.
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- ADP and ATP analogues, process for making and administration to inhibit ADP-induced platelet aggregation
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There are disclosed compounds of formula I, STR1 wherein Q represents CR 1 R 2,R represents O or CR 3 R 4,W represents O or CH 2,R 1, R 2, R 3 and R 4 independently represent hydrogen or halogen,X represents S(O) n R 5, alkyl C 1-6 alkoxy C 1-6, acylamino C 1-6, CONR 6 R 7, NR 8 R 9, halogen, a 5- or 6-membered S containing heterocycle, or phenyl optionally substituted by alkyl C 1-6,n represents 0, 1 or 2,R 5 represents aryl or alkyl C 1-6 optionally substituted by one or more substituents selected from hydroxy, alkoxy C 1-6, halogen and aryl;R 6, R 7, R 8 and R 9 independently represent hydrogen or alkyl C 1-6,Y represents NH 2 or alkoxy C 1-6, andZ represents an acidic moiety,in addition, when R represents CR 3 R 4, then --Q--Z may also represent hydroxy or --OP(O)(OH) 2,and pharmaceutically acceptable salts thereof, with certain provisos, for use as pharmaceuticals.
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