- Synthesis and biophysical testing of a novel pyrrole-containing polyamide-benzamidine hybrid
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This communication details the rationale for the design of a novel polyamide molecule, 1, in which the standard dimethylamino C-terminus functionality has been replaced with a benzamidine moiety. The synthesis of this molecule and the subsequent DNA binding properties, determined from surface plasmon resonance and DNA melts are reported. The benzamidine moiety was shown to significantly increase the binding affinity of the polyamide to its cognate AATTT sequence compared to the parent C-terminus compound 2.
- Turlington, Mark,Mackay, Hilary,Rutledge, Caleb,Taherbhai, Zarmeen,Nguyen, Binh,Wilson, David,Lee, Moses
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Read Online
- α-Amino acid-derived 2-phenylimidazoles with potential antimycobacterial activity
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α-Amino acid-derived 2-phenylimidazole derivatives were designed, synthesized, and further investigated as potential antimycobacterial agents. The synthesis of target imidazole derivatives involved the transformation of Cbz-protected α-amino acids (Ala, Val, Phe, Leu, iLe, and Pro) into α-diazoketones and α-bromoketones, respectively. Subsequent treatment of α-bromoketones with (4-nitro) benzamidine afforded imidazole derivatives bearing α-amino acid residue appended to the imidazole C4 and (4-nitro)phenyl ring in the position C2. Antimycobacterial activities of both series of compounds against M. tuberculosis, M. avium, and M. kansasii were screened and basic structure-activity relationships were further evaluated.
- Cvejn, Daniel,Bures, Filip,Klimesova, Vera
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Read Online
- Design, synthesis and biological evaluation of novel 2-phenyl pyrimidine derivatives as potent Bruton's tyrosine kinase (BTK) inhibitors
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BTK is an effective target for the treatment of B-cell malignant tumors and autoimmune diseases. In this work, a series of 2-phenyl pyrimidine derivatives were prepared and their preliminary in vitro activities on B-cell leukemia cells as well as the BTK enzyme were determined. The results showed that compound 11g displayed the best inhibitory activity on BTK with an inhibition rate of 82.76% at 100 nM and excellent anti-proliferation activity on three B-cell leukemia lines (IC50 = 3.66 μM, 6.98 μM, and 5.39 μM against HL60, Raji and Ramos, respectively). Besides, the flow cytometry analysis results indicated that 11g inhibited the proliferation of the Raji cells in a dose- and time-dependent manner, and blocked the Ramos cells at the G0/G1 phase, which is in accordance with the positive control ibrutinib. The mechanism investigation demonstrated that 11g could inhibit the phosphorylation of BTK and its downstream substrate phospholipase γ2 (PLCγ2). All these results showed that 11g was a promising lead compound that merited further optimization as a novel class of BTK inhibitor for the treatment of B-cell lymphoblastic leukemia.
- Li, Xinyu,Shi, Binyu,Teng, Yu,Cheng, Yu,Yang, Huizhu,Li, Jiurong,Wang, Lianjian,He, Siying,You, Qidong,Xiang, Hua
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supporting information
p. 294 - 299
(2019/03/02)
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- 2-phenylpyrimidine compounds, preparation method and medical application
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The invention belongs to the field of medicines and particularly relates to 2-phenylpyrimidine compounds and pharmacologically-acceptable salts thereof and an isotope marker. The invention also discloses a pharmaceutical composition containing the substances and application of the pharmaceutical composition for treating diseases related with protein kinase activity, such as cancer and inflammation. (The formula is shown in the description).
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Paragraph 0046; 0047; 0048
(2018/06/15)
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- Bispyrimidine diamine and preparation method thereof
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The invention discloses bispyrimidine diamine and a preparation method thereof. According to the preparation method, the bispyrimidine diamine is prepared through a five-step reaction by taking nitrobenzonitrile as a raw material. The bispyrimidine diamine disclosed by the invention can also be used as a raw material for synthesising high-performance polymers, such as polyimide and polyamide, and has a wide application prospect in the aspect of high-performance fibres.
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Paragraph 0070; 0071; 0072
(2017/08/29)
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- Transition-metal-free approach to 4-ethynylpyrimidines via alkenynones
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A practical approach to the synthesis of 4-ethynylpyrimidines by the condensation of arylamidines with 2-aryl-1-ethoxy-5-(trimethylsilyl)pent-1-en-4- yn-3-ones has been developed. As these latter ketones are easily accessible from bis(trimethylsilyl)acetylene and arylacetyl chlorides, the regioselective condensation reported herein provides a facile access to both TMS-protected and unprotected 4-ethynylpyrimidines in yields of up to 85%. Copyright
- Golubev, Pavel R.,Pankova, Alena S.,Kuznetsov, Mikhail A.
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p. 3614 - 3621
(2014/06/23)
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- Synthesis and structure of aroylamidines and N-arylbenzamidines hydrochlorides
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Aroylamidines can be obtained as salts in a reaction of the corresponding arylcarbonitriles with anhydrous ethanol in the presence of dry HCl followed by treating intermediate imidoesters with alcoholic solution of ammonia. N-Arylbenzamidines are obtained by reacting benzonitrile with arylamines in the presence of AlCl3. The structure of arylamines and the reaction conditions signifi cantly affect the yield of the target product, and sometimes the very possibility of its preparation. Pleiades Publishing, Ltd., 2012.
- Kuvaeva,Fedorova,Zaitsev,Yakovlev,Zakharov,Semakova
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p. 209 - 213
(2012/06/01)
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- PYRIMIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES
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The invention relates to pyrimidine compounds of the Formula I: or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
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Page/Page column 51; 77-78
(2010/11/04)
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- SUBSTITUTED IMIDAZOTRIAZINES
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The invention relates to novel substituted imidazotriazines, to methods for the production thereof, and to their use for producing medicaments for the treatment and/or prophylaxis of cancer and neurodegenerative diseases, particularly Parkinson's disease and schizophrenia.
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Page/Page column 43-44
(2010/02/06)
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- IMIDAZOLE DERIVATIVES FOR TREATMENT OF ALLERGIC AND HYPERPROLIFERATIVE DISORDERS
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The preferred embodiments are directed to small molecule inhibitors of the IgE response to allergens, which are useful in the treatment of allergy and/or asthma or any diseases where IgE is pathogenic. The preferred embodiments also relate to imidazole molecules that are cellular proliferation inhibitors and thus are useful as anticancer agents. The preferred embodiments further relate to small molecules which suppress cytokines and leukocytes.
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Page/Page column 46; 52; 63; 69
(2010/02/09)
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- Novel heterocycles 3
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The invention relates to 7-(4-tert butyl-cyclohexyl)-imidazotriazinones, processes for their preparation and their use in medicaments, esp. for the treatment and/or prophylaxis of inflammatory processes and/or immune diseases.
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- 5-ETHYLIMIDAROTRIAZONES
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The invention relates to novel 5-ethyl-imidazotriazinones, processes for their preparation and their use in medicaments, esp. for the treatment and/or prophylaxis of inflammatory processes and/or immune diseases.
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Page/Page column 49
(2010/02/07)
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- SRN1 Reactions of Arylhalodiazirines with Azide Ion
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(m-(Trifluoromethyl)phenyl)bromodiazirine, 10, reacts with 15N terminally labeled sodium azide in dimethyl sulfoxide to give m-(trifluoromethyl)benzonitrile which, in all cases, contains 15N incorporation.The largest amount of label incorporation (42 percent) and the fastest rate, is observed when the reaction is carried out in room light.The smallest amount of label incorporation (11 percent), and the slowest reaction, is observed when the reaction is carried out in the dark and a trace of the free radical, galvinoxyl, is added.The reaction in the light is proposed to occur mainly via the SRN1 chain process.The intermediate C-azidodiazirine substitution product is not observed, but presumably rapidly loses 2 mol of nitrogen to give the nitrile product. (p-Nitrophenyl)bromodiazirine, 20, can also react with azide ion via an analogous SRN1 process, and the reaction is more facile than that of 10.Label incorporation from 15N-labeled sodium azide is substantial (47.3 percent) and is in agreement with the proposed SRN1 process.A variety of arylchlorodiazirines, substituted with electron-deficient aromatic groups, also react with azide ion in room light, to give nitriles via C-azidodiazirines, which lose molecular nitrogen.Evidence for the proposed SRN1 process includes initiation of the reaction by exposure to room light, initiation by the addition of the sodium salt of 2-nitropropane or sodium thiophenoxide, and inhibition of the reaction by the addition of galvinoxyl.In the case of these arylchlorodiazirines, reaction with 15N terminally labeled sodium azide led to 15N label incorporation approaching the maximum amount possible for a reaction proceeding exclusively via C-azidodiazirines.These studies show the propensity for arylhalodiazirines to undergo reaction initiated by electron-transfer processes.
- Creary, Xavier,Sky, Anthony F.,Phillips, Gillian
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p. 2005 - 2011
(2007/10/02)
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- Preparation of N,N,N'-tris(trimethylsilyl)amidines; a convenient route to unsubstituted amidines
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The tris(trimethylsilyl)amidines RC(NSiMe3)N(SiMe3)2 (R = C6H5, p-CH3C6H4, p-ClC6H4, p-MeOC6H4, p-Me2NC6H4, p-CF3C6H4, p-C6H5C6H4 and CF3) are prepared by the reaction of the respective nitriles with (Me3Si)2NLI.OEt2 in ether to give intermediates RC(NLi)N(SiMe3)2.Heating these intermediates with ClSiMe3 in toluene affords the products, which are isolated by vacuum distillation, in high yield.With 1,4-dicyanobenzene, two equivalents of reagents affords the per(trimethylsilyl)-1,4-diamidine.Hydrolysis of the intermediates with 6N ethanolic HCl affords the unsubstituted amidine hydrochlorides RC(NH)NH2.HCl (R = C6H5, p-MeOC6H4, p-ClC65H4, p-O2NC6H4) in high yield.
- Boere, Rene T.,Onkley, Richard T.,Reed, Robert W.
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p. 161 - 168
(2007/10/02)
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- A Substituent Chemical Shift (SCS) Effect Study by 13C and 19F NMR of para-Substituted Phenylhalodiazirines
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A range of 3-(para-substituted-phenyl)-3-halodiazirines have been prepared and their 13C and 19F NMR spectra measured.Calculated with these data were the susceptibility coefficients ρ1 and ρR of the inductive (?1) and resonance (?R0) effects, respectively, to substituent-induced chemical shift differences at the diazirine carbon (13C NMR) and the 3-fluorine(19F NMR of the 3-fluorodiazirine series).An inverse relationship was found between the suceptibility parameters and the electronegativity of the halo substituent at the diazirine carbon. KET WORDS - 13C NMR 19F NMR substituent induced chemical shifts p-substituted phenylhalodiazirines
- Terpinski, Jacek,Denney, Dorothy Z.,Beveridge, Richard,Cox, Phillip D.,Moss, Robert A.
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p. 923 - 927
(2007/10/02)
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- Styrylamidines
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Styrylamidines are prepared by treating styrylsulfonylamidines with base. The styrylamidines are effective in the prevention of aggregation of blood platelets and as analgesics. Compounds of the invention are also useful as anticonvulsants, diuretics and antihypertensive agents. The styrylsulfonylamidines of the invention which serve as precursors to the styrylamidines also have analgesic properties. Illustrative of the styrylamidines of the present invention are 4-amino-N-(4-aminostyryl)benzamidine and N-(3,4-dichlorostyryl)acetamidine. An example of a styrylsulfonylamidine is N-(styrylsulfonyl)acetamidine.
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