4316-93-2Relevant academic research and scientific papers
CYCLOALKYLIDENE CARBOXYLIC ACIDS AND DERIVATIVES AS BTK INHIBITORS
-
Page/Page column 129, (2021/03/05)
The present invention relates to novel cycloalkylidene carboxylic acids and derivatives thereof useful as Bruton tyrosine kinase (BTK) inhibitors. The present disclosure also relates to processes for their preparation, pharmaceutical compositions containing one or more such compounds, and to the use of such compounds and pharmaceutical compositions for the treatment of disorders involving mediation of BTK in humans (Formula I).
Discovery of 5-Nitro-6-thiocyanatopyrimidines as Inhibitors of Cryptococcus neoformans and Cryptococcus gattii
Donlin, Maureen J.,Lane, Thomas R.,Riabova, Olga,Lepioshkin, Alexander,Xu, Evan,Lin, Jeffrey,Makarov, Vadim,Ekins, Sean
, p. 774 - 781 (2021/05/04)
Opportunistic infections from pathogenic fungi present a major challenge to healthcare because of a very limited arsenal of antifungal drugs, an increasing population of immunosuppressed patients, and increased prevalence of resistant clinical strains due to overuse of the few available antifungals. Cryptococcal meningitis is a life-threatening opportunistic fungal infection caused by one of two species in the Cryptococcus genus, Cryptococcus neoformans and Cryptococcus gattii. Eighty percent of cryptococcosis diseases are caused by C. neoformans that is endemic in the environment. The standard of care is limited to old antifungals, and under a high standard of care, mortality remains between 10 and 30%. We have identified a series of 5-nitro-6-thiocyanatopyrimidine antifungal drug candidates using in vitro and computational machine learning approaches. These compounds can inhibit C. neoformans growth at submicromolar levels, are effective against fluconazole-resistant C. neoformans and a clinical strain of C. gattii, and are not antagonistic with currently approved antifungals.
Efficient Phosphorus-Free Chlorination of Hydroxy Aza-Arenes and Their Application in One-Pot Pharmaceutical Synthesis
Wang, Jian,Li, Yan-Hui,Pan, Song-Cheng,Li, Ming-Fang,Du, Wenting,Yin, Hong,Li, Jing-Hua
supporting information, p. 146 - 153 (2020/03/10)
The chlorination of hydroxy aza-arenes with bis(trichloromethyl) carbonate (BTC) and SOCl2 has been effectively performed by refluxing with 5 wt % 4-dimethylaminopyridine (DMAP) as a catalyst. Various substrates are chlorinated with high yields. The obtained chlorinated aza-arenes can be used directly with simple workup for succedent one-pot synthesis on a large scale.
Synthesis method of 4,5,6-triaminopyrimidine
-
Paragraph 0022-0024; 0027-0029; 0032-0034; 0037-0039, (2019/11/14)
The invention discloses a synthesis method of 4,5,6-triaminopyrimidine. The synthesis method includes the following steps that an intermediate product of 4,6-dichloro-5-nitropyrimidine is prepared by5-nitro-4,6-dihydroxypyrimidine, phosphorus oxychloride and organic alkali; ethyl alcohol is added into a product prepared by the 4,6-dichloro-5-nitropyrimidine and ammonium hydroxide to obtain a product; and the 4,5,6-triaminopyrimidine is prepared by the product, hydrazine hydrate, and raney nickel. According to the synthesis method, targeted objects can be obtained just through three steps, total yield is high, synthesis routes are short, reaction is mild, time is short, operation is easy and safe, at the same time, the 4,6-dichloro-5-nitropyrimidine is taken as a starting material, due tothe fact that the starting material has a large amount of commercial supplies, and is cheap and easy to obtain, an auxiliary material can be recycled and reused, and the cost can be significantly reduced; and due to the fact that appropriate raw material and auxiliary material are selected, the pollution of toxic substances to environments in the production process is avoided, the yield and purityof prepared pyrimidine are high, and the pyrimidine has good industrial application prospects.
Development of dichloroacetamide pyrimidines as pyruvate dehydrogenase kinase inhibitors to reduce cancer cell growth: Synthesis and biological evaluation
Zhang, Shao-Lin,Zhang, Wen,Xiao, Qingpin,Yang, Zheng,Hu, Xiaohui,Wei, Zhiyi,Tam, Kin Yip
, p. 78762 - 78767 (2016/09/09)
Pyruvate dehydrogenases kinases (PDKs) have recently emerged as an attractive target for anticancer treatment. Herein, we report the synthesis and biological evaluation of novel PDK1 inhibitors as anticancer agents. Of the newly synthesized compounds, N-(4,6-bis(4-(2-hydroxyacetyl)piperazin-1-yl)-2-methylpyrimidin-5-yl)-2,2-dichloroacetamide (40) is found to inhibit the growth of SF188 cancer cells with an IC50 value of 8.21 M. Isothermal titration calorimetry (ITC) experiments reveal that compound 40 directly binds to PDK1 with a Kd value of 14.7 M. Compound 40 inhibits PDK1 activity by 72.5% at a concentration of 40 , meaning it could be a useful compound to explore the pharmacology of PDK1.
Synthesis of [14C]-, [13C4]-, and [ 13C4, 15N2]-5-amino-4-iodopyrimidine
Latli, Bachir,Jones, Paul-James,Krishnamurthy, Dhileepkumar,Senanayake, Chris H.
, p. 54 - 58 (2008/09/18)
5-Amino-4-iodopyrimidine labeled with either carbon-14 or with the stable isotopes carbon-13 and nitrogen-15 was prepared starting from commercially available labeled diethylmalonate and formamide. This compound is a useful intermediate for carbon-nitrogen and carbon-carbon bond formations. Copyright
Compounds containing a N-heteroaryl moiety linked to fused ring moieties for the inhibition of NAD(P)H oxidases and platelet activation
-
Page/Page column 90, (2008/06/13)
The invention relates to compounds containing a N-heteroaryl moiety, which is linked via oxygen, sulfur or nitrogen, or via a methylene bridge and oxygen, sulfur or nitrogen to a fused ring moiety, in particular to the 1,2,3-triazolo[4,5-d]pyrimidine-7-yl radical. The invention also relates to a process for the preparation of said compounds and the use thereof in drugs for the treatment of NAD(P)H oxidases-related diseases and disorders and inhibition of platelet activation.
Structure-activity relationships of a series of pyrrolo[3,2-d]pyrimidine derivatives and related compounds as neuropeptide Y5 receptor antagonists
Norman,Chen,Chen,Fotsch,Hale,Han,Hurt,Jenkins,Kincaid,Liu,Lu,Moreno,Santora,Sonnenberg,Karbon
, p. 4288 - 4312 (2007/10/03)
Neuropeptide Y (NPY) has been shown to play an important role in the regulation of food intake and energy balance. Pharmacological data suggests that the Y5 receptor subtype contributes to the effects of NPY on appetite, and therefore a Y5 antagonist might be a useful therapeutic agent for the treatment of obesity. In attempts to identify potential Y5 antagonists, a series of pyrrolo[3,2-d]pyrimidine derivatives was prepared and evaluated for their ability to bind to Y5 receptors in vitro. We report here the synthesis and initial structure-activity relationship investigations for this class of compounds. The target compounds were prepared by a variety of synthetic routes designed to modify both the substitution and the heterocyclic core of the pyrrolo[3,2-d]pyrimidine lead 1. In addition to identifying several potent Y5 antagonists for evaluation as potential antiobesity agents, a pharmacophore model for the human Y5 receptor is presented.
Dinucleotide-analogous tetrapeptides. Specific triplex formation with complementary polynucleotides
Yamazaki, Takahisa,Komatsu, Kazunori,Umemiya, Hiroki,Hashimoto, Yuichi,Shudo, Koichi,Kagechika, Hiroyuki
, p. 8363 - 8366 (2007/10/03)
Several tetrapeptides (1-4) having two adenyl moieties at the side chains interacted complementary base-specifically with poly (dT) or poly (U). The hypochromic effects and CD spectra of the complexes suggested the formation of triplexes, which are more stable than those between natural ApA and the polynucleotides.
