- Synthesis and biological evaluation of cyclopentyl-triazolol-pyrimidine (CPTP) based P2Y12 antagonists
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In this Letter we describe SAR investigation on the cyclopentyl-triazolol- pyrimidine scaffold in pursuit of new oral P2Y12 inhibitors. Different synthetic routes were developed for variations at the cyclopentyl core. Optimization finally led t
- Tu, Wangyang,Fan, Jiang,Zhang, Haitang,Xu, Guoji,Liu, Zhiwei,Qu, Jian,Yang, Fanglong,Zhang, Lei,Luan, Tianyu,Yuan, Jijun,Gong, Aishen,Feng, Jun,Sun, Piaoyang,Dong, Qing
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- Synthesis and anticancer activities of novel 8-azapurine carbocyclic nucleoside hydrazones
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A series of novel 8-azapurine carbocyclic nucleoside hydrazones were synthesized through a useful procedure starting from amino alcohol and pyrimido dichloride. All the products were characterized by 1H NMR, 13C NMR and HRMS spectral analysis and the stereochemical structure of key intermediate was also confirmed by a single crystal X-ray diffraction crystallographic analysis. Moreover, the anticancer activities were evaluated in vitro against human liver cancer Huh-7 cell line and human breast cancer A549 cell line.
- Wang, Yeming,Yan, Hong,Ma, Chao,Lu, Dan
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- Synthesis and biological evaluation of: N 6derivatives of 8-azapurine as novel antiplatelet agents
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Two series of novel N6 derivatives of 8-azapurine I and II were designed as antiplatelet agents. Series I and II were N6 amino derivatives and N6 hydrazone derivatives of 8-azapurine, respectively. The compounds were synthesized in acceptable yields via conventional procedures, including nucleophilic substitution, diazotization, and amination or hydrazonation with amino alcohol and 4,6-dichloropyrimidine as starting materials. To assess the ability of the synthesized compounds as antiplatelet agents, the ADP-induced platelet aggregation assay of Born was performed both in vitro and in vivo using ticagrelor as a reference control substance. The analysis of the structure-activity relationship and molecular docking were also discussed in detail. The results demonstrated that series I and II compounds exhibited antiplatelet activity in vitro and IIh was the most active compound (IC50 = 0.20 μM) among the target compounds, being almost 4-fold better than ticagrelor (IC50 = 0.74 μM). For a preliminary assessment of the safety profile, a bleeding test (mouse tail) and a single-dose toxicity test were conducted. The use of compound IIh resulted in a shorter bleeding time, less blood loss and lower acute toxicity compared to ticagrelor. In addition, a molecular docking study was performed to investigate the binding capacity and binding mode between IIh and P2Y12. This journal is
- Tian, Nana,Wang, Juan,Wang, Yeming,Yan, Hong,Zhao, Zhichang
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p. 1414 - 1427
(2021/11/09)
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- NEW PYRIMIDINE DERIVATIVES FOR PREVENTION AND TREATMENT OF GRAM-NEGATIVE BACTERIAL INFECTION, CONTAMINATION AND FOULING
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New pyrimidine derivatives together with a membrane penetrating agent, optionally with a detectable isotope and pharmaceutical composition for use in treatment or prevention of Gram-negative bacterial infection in a host mammal in need of such treatment or prevention and use as inhibitors of Gram-negative biofilm formation on a surface of biomaterial or medical device, particularly of cardiovascular device such as prosthetic heart valve or pacemakers. New pyrimidine derivatives together with a membrane penetrating agent; for use as radiotracer in diagnosing or prognosing Gram-negative bacterial infection in a host mammal.
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Page/Page column 78
(2020/10/28)
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- Synthesis of ticagrelor analogues belonging to 1,2,3-triazolo[4,5-d]pyrimidines and study of their antiplatelet and antibacterial activity
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Based on the recent observation that the antiplatelet agent ticagrelor and one of its metabolite exert bactericidal activity against gram-positive bacteria, a series of 1,2,3-triazolo[4,5-d]pyrimidines structurally related to ticagrelor were synthesized and examined as putative antiplatelet and antibacterial agents. The aim was to assess the possibility of dissociating the two biological properties and to find novel 1,2,3-triazolo[4,5-d]pyrimidines expressing antiplatelet activity and devoid of in vitro antibacterial activity. The new compounds synthesized were known metabolites of ticagrelor as well as structurally simplified analogues. Some of them were found to express antiplatelet activity and to lose the antibacterial activity, supporting the view that the two activities were not necessarily linked.
- Goffin, Eric,Jacques, Nicolas,Lancellotti, Patrizio,Musumeci, Lucia,Nchimi, Alain,Pirotte, Bernard,Oury, Cécile
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- PYRIMIDINE DERIVATIVES FOR PREVENTION AND TREATMENT OF BACTERIAL INFECTIONS
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New pyrimidine derivatives of formula (I), optionally with a detectable isotope, pharmaceutical composition and method of preparation thereof. New pyrimidine derivatives for use in treatment or prevention of bacterial infection in a host mammal in need of such treatment or prevention and use as inhibitors of biofilm formation on a surface of biomaterial or medical device, particularly of cardiovascular device such as prosthetic heart valve or pacemakers. New pyrimidine derivatives for use as radiotracer in diagnosing or prognosing bacterial infection in a host mammal.
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Page/Page column 66; 67
(2019/09/04)
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- 6-hydrazone radical-8-aza-purine compound and preparing method and application thereof
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The invention relates to a 6-hydrazone radical-8-aza-purine compound and a preparing method and an application thereof and belongs to the fields of preparation of novel compounds and medicine application. The general molecular formula of the compound is shown in the description, wherein R1 is hydroxide radical, methylol group and hydroxyethoxy, R2 is hydrogen, hydroxide radical, and fluorine, R3 is methyl, ethyl, propyl and 3,3-trifluoropropyl group, and R4 is aryl group, substitutional aryl group, ceteroary, and substitutional ceteroary. A midbody is used as reaction substrate, wherein the formula of the midbody is shown in the description, the midbody and a hydrazine and aldehydes compound are subjected to a condensation reaction, and the 6-hydrazone radical-8-aza-purine compound is obtained. According to the novel 6-hydrazone radical-8-aza-purine compound, the antiplatelet aggregation activity is high, the bleeding side effect is low, and the compound can be used for preparing the antiplatelet aggregation medicine and preventing and treating the related thrombotic disease.
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Paragraph 0021-0023
(2017/09/02)
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- Synthesis of Triazolopyrimidine Compounds
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The present invention relates to the field of organic synthesis and describes the synthesis of specific triazolopyrimidine compounds and intermediates thereof as well as related derivatives.
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- SYNTHESIS OF TRIAZOLOPYRIMIDINE COMPOUNDS
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The present invention relates to the field of organic synthesis and describes the synthesis of specific triazolopyrimidine compounds and intermediates thereof as well as related derivatives.
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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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p. 3598 - 3602
(2012/07/14)
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- Crystalline and amorphous form of a triazolo(4,5-d)pyrimidine compound
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The invention provides new forms of a chemical compound of formula (I). The invention relates to forms fo a chemical compound (I), in particular to crystalline and amorphous forms, more particularly four crystalline forms and an amorphous form. The invention further relates to processes for the preparation of such forms, to pharmaceutical compositions comprising the compound in crystalline and/or amorphous form and to therapeutic use of such forms.
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- Triazolo(4,5-d)pyrimidine compounds
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Triazolo[4,5-d]pyrimidine compounds, their use as medicaments, compositions containing them and processes for their preparation. The compounds of the invention have the formula (I) as follows: wherein R, X and R1through R3are as defined in the specification.
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- 1,2,3-TRIAZOLO[4,5-D]PYRIMIDINES AS P2T RECEPTOR ANTAGONISTS
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Compounds of formula having the following stereochemistrywherein R, R1, R2, R3 and R4 are as defined in the specification. The compounds are useful as P2T receptor antagonists
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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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