- Design, synthesis and biological evaluation of 3-benzyloxy-linked pyrimidinylphenylamine derivatives as potent HIV-1 NNRTIs
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A novel series of 3-benzyloxy-linked pyrimidinylphenylamine derivatives (8a-8s) was designed, synthesized and evaluated for their in vitro anti-HIV activity in MT-4 cell cultures. Most of the compounds inhibited wild-type (wt) HIV-1 replication in the lower micromolar concentration range (EC50 = 0.05-35 μM) with high selectivity index (SI) values (ranged from 10 to >4870). In particular, 8h and 8g displayed excellent antiretroviral activity against wt HIV-1 with low cytotoxicity (EC50 = 0.07 μM, CC 50 >347 μM, SI >4870; EC50 = 0.05 μM, CC 50 = 42 μM, SI = 777, respectively), comparable to that of the marked drug nevirapine (EC50 = 0.113 μM, CC50 >15 μM, SI >133). In order to confirm the binding target, 8h was selected to perform the anti-HIV-1 RT assay. Additionally, preliminary structure activity relationship (SAR) analysis and molecular docking studies of newly synthesized compounds were also discussed, as well as the predicted physicochemical properties.
- Rai, Diwakar,Chen, Wenmin,Tian, Ye,Chen, Xuwang,Zhan, Peng,De Clercq, Erik,Pannecouque, Christophe,Balzarini, Jan,Liu, Xinyong
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- BENZOAZEPINE ANALOGS AS INHIBITING AGENTS FOR BRUTON'S TYROSINE KINASE
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Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, and methods for their production and compounds of formula (I) for use in treating a disease responsive to the inhibition of Bruton's tyrosine.
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Page/Page column 56; 60; 61
(2018/11/10)
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- Pyrimidine heterocyclic compounds, pyrimidine heterocyclic compound salts, and preparation method and application thereof
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The invention provides pyrimidine heterocyclic compounds, pyrimidine heterocyclic compound salts, and a preparation method and application thereof. According to the pyrimidine heterocyclic compounds provided by the invention, specific Rq is selected, so that the obtained compounds have favorable drug resistance and long half life when being used as the medicine for treating or preventing HIV. The compounds have the advantages of high activity, low toxicity and high stability.
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Paragraph 0123; 0124; 0125; 0126
(2017/07/26)
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- BIARYL COMPOUNDS USEFUL FOR THE TREATMENT OF HUMAN DISEASES IN ONCOLOGY, NEUROLOGY AND IMMUNOLOGY
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The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.
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Paragraph 0170
(2015/06/25)
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- PROCESS FOR RILPIVIRINE
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The present invention provides a novel process for the preparation of 4-(4-hydroxypyrimidin-2-ylamino)benzonitrile. The present invention also provides a novel process for the preparation of 4-iodo-2,6-dimethyl benzenamine. The present invention further provides an improved process for the preparation of rilpivirine. The present invention further provides a tosylate salt of rilpivirine, process for its preparation and pharmaceutical compositions comprising it.
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Paragraph 0079
(2014/08/19)
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- RILPIVIRINE HYDROCHLORIDE
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The present invention provides a novel process for the preparation of rilpivirine. The present invention also provides a novel process for the preparation of rilpivirine hydrochloride. The present invention further provides a rilpivirine hydrochloride monohydrate, process for its preparation and pharmaceutical compositions comprising it.
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Paragraph 0082
(2014/12/09)
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- Structural tuning of ancillary chelate in tri-carboxyterpyridine Ru(ii) sensitizers for dye sensitized solar cells
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Three distinct classes of ancillary chelates, namely: 2-(3- trifluoromethylpyrazol-5-yl)-6-(3-trifluoromethylphenyl)pyridine (L3, H 2pzppy), 4-(3-trifluoromethylpyrazol-5-yl)-2-(3-trifluoromethyl) phenylpyrimidine (L5, H2pzppm) and 4-(6-(3-trifluoromethylpyrazol-5- yl)pyridin-2-yl)-2-trifluoromethylpyrimidine (L6, H2pzpypm), which showed an identical skeletal topology, but with the more electronegative nitrogen atom replacing the isoelectronic methine group at the selected skeletal position, were obtained to investigate the photophysical and electrochemical properties and hence the associated Ru(ii) sensitizers based DSCs. To increase the optical absorptivity we also strategically added thiophene (thienyl) or 3,4-ethylenedioxythiophene (EDOT) appendages to L6, for boosting the short-circuit photocurrent (JSC) and the overall efficiency (η) of the fabricated DSC devices. Under AM 1.5G illumination, the best sensitizer showed performance data of JSC = 18.11 mA cm-2, V OC = 0.66 V, FF = 0.729 and η = 8.72%, and a good cell stability at 60 °C for 1000 hours, being only decreased by ～5% in the η value.
- Chou, Chun-Cheng,Chen, Pei-Hua,Hu, Fa-Chun,Chi, Yun,Ho, Shu-Te,Kai, Ji-Jung,Liu, Shih-Hung,Chou, Pi-Tai
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p. 5418 - 5426
(2014/04/03)
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- RILPIVIRINE HYDROCHLORIDE
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As used herein the term "room temperature" refers to a temperature of about 25°C to about 35°C. According to one aspect of the present invention, there IS provided a novel process for the preparation of rilpivirine, which comprises: a) condensing the (E)-3-( 4-amino-3,5-dimethylphenyl)acrylonitrile hydrochloride with 4-( 4-chloropyrimidin-2-ylamino )benzonitrile m the presence of Nmethylpyrrolidone; b) heating the contents obtained in step (a) at about 75 to 95°C to obtain a solution; c) cooling the solution obtained in step (b) at below 35°C; d) adding water to the reaction mass; and e) isolating rilpivirine. The reaction in step (b) may preferably be heated to 100 to 110°C. Step (c) may preferably be carried out at room temperature. Rilpivirine may be isolated in step (e) by the methods known such as Filtration or centrifugation.
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Page/Page column 8
(2013/03/28)
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- PROCESS FOR RILPIVIRINE
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The present invention provides a novel process for the preparation of 4-(4-hydroxypyrimidin-2-ylamino)benzonitrile. The present invention also provides a novel process for the preparation of 4-iodo-2,6-dimethyl benzenamine. The present invention further provides an improved process for the preparation of rilpivirine. The present invention further provides a tosylate salt of rilpivirine, process for its preparation and pharmaceutical compositions comprising it.
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Page/Page column 8-9
(2012/11/13)
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- 10A-AZALIDE COMPOUND HAVING 4-MEMBERED RING STRUCTURE
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A 10a-azalide compound having a 4-membered ring structure crosslinked at the 10a- and 12-positions, which is represented by the formula (I), and is effective on even Haemophilus influenzae, or erythromycin resistant bacteria (e.g., resistant pneumococci and streptococci).
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Page/Page column 58
(2011/04/14)
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- (3-HYDROXY-4-AMINO-BUTAN-2-YL) -3- (2-THIAZOL-2-YL-PYRROLIDINE-1-CARBONYL) BENZAMIDE DERIVATIVES AND RELATED COMPOUNDS AS BETA-SECRETASE INHIBITORS FOR TREATING
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The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease. (Formula)
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Page/Page column 82-83
(2009/05/29)
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- Synthesis and biological evaluation of 10,11-methylenedioxy-14- azacamptothecin
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10,11-Methylenedioxy-14-azacamptothecin, a potent analogue of the antitumor agent camptothecin (CPT), has been prepared via a key condensation between AB and DE ring precursors. The biological testing of this compound validated a strategy for modulation of the off-rate of camptothecin analogues from the topoisomerase-DNA-CPT ternary complex via structural modification.
- Elban, Mark A.,Sun, Wenyue,Eisenhauer, Brian M.,Gao, Rong,Hecht, Sidney M.
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p. 3513 - 3516
(2007/10/03)
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- Piperazine compounds and medicinal use thereof
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The present invention relates to a piperazine compound of the formula wherein R1and R2are each hydrogen, halogen, lower alkyl, lower alkoxy, amino, substituted amino, nitro, hydroxy or cyano, R3, R4and R5are each hydrogen, halogen, lower alkyl, lower alkoxy, nitro, amino, substituted amino or hydroxy, R6and R7are each hydrogen, lower alkyl, lower alkyl substituted by halogen, aralkyl, acyl or lower acyl substituted by halogen, R8and R9are each hydrogen or lower alkyl, Y is lower alkylene and the like, and ring A is phenyl, pyrimidyl, thiazolyl, pyridyl, pyrazyl or imidazolyl, a pharmaceutically acceptable salt thereof and pharmaceutical agents containing these compounds. The compound of the present invention has superior TNF-α production inhibitory effect and/or IL-10 production promoting effect, and, since it is free of or shows only strikingly reduced expression of an effect on the central nervous system, the compound is useful as a highly safe and superior TNF-α production inhibitor an/or IL-10 production promoter and is useful as an agent for the prophylaxis or treatment of various diseases caused by abnormal TNF-α production, diseases curable with IL-10, such as chronic inflammatory diseases, acute inflammatory diseases, inflammatory diseases due to infection, autoimmune diseases, allergic diseases, and TNF-α mediated diseases.
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- Studies on a potentially prebiotic synthesis of RNA
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Current thinking supports an early phase of evolution in which information transfer and catalysis were mediated by evolving RNA. A novel potentially prebiotic synthesis of RNA is proposed involving polymerisation through aldol condensation followed by a retro-Amadori rearrangement and ring closure via a base-paired mesomeric heterocyclic betaine intermediate. The proposed monomer 1 is an achiral mixed phosphodiester and herein we report synthetic routes to 1 containing each of the four RNA bases, The solution phase behaviour of 1 containing adenine and uracil has been investigated and preliminary results of polymerisation experiments are also presented.
- Sutherland, John D.,Whitfield, J. Nicole
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p. 11595 - 11626
(2007/10/03)
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- The Tautomeric Equilibria of Thio Analogues of Nucleic Acid Bases. Part 1. 2-Thiouracil: Background, Preparation of Model Compounds, and Gas-phase Proton Affinities
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The preparation is reported of all four the monoalkyl derivatives of 2-thiouracil and four of the six possible dialkyl derivatives required as models for a study of the tautomeric equilibria by physical methods.Gas-phase proton affinities are determined using ion cyclotron resonance mass spectrometry, and are used to provide quantitative estimates of individual tautomer stabilities in the vapour state.These quantitative results agree well with qualitative deductions of predominant structures for the monoalkyl derivatives from i.r. spectroscopy.
- Katritzky, Alan R.,Baykut, Gokhan,Rachwal, Stanislaw,Szafran, Miroslaw,Caster, Kenneth C.,Eyler, John
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p. 1499 - 1506
(2007/10/02)
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- The anti-H1-histaminic and antimuscarinic effect of 2- and 4-[benzyl-(2-dimethylaminoethyl)amino]pyrimidine compounds
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This paper reports the synthesis of 2- and 4- [benzyl-(2-dimethylaminoethyl)amino]pyrimidine compounds and the evaluation of their inhibitory properties against histamine (H1), acetylcholine and barium chloride, on guinea pig isolated ileum. 4-[p.Methoxybenzyl-(2-dimethylaminoethyl)amino]-2-methoxy-pyrimidine (VIII) is shown to possess H1 receptor antagonist activity, with a potency similar to that observed for Tonzylamine. By contrast, a specific, although weak, antimuscarinic effect is displayed by 4-[benzyl-(2-dimethylaminoethyl)amino]-2-methoxy-5-methylthio-pyrimidine (XII).
- Maggiali,Morini,Mossini,Morini,Barocelli,Impicciatore
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p. 277 - 291
(2007/10/02)
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- Fluorinated Heterocyclic Compounds. 2. 2,4-Difluoro and 4-Amino-2-fluoropyrimidines, Nucleoside Base Analogs
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Nucleoside base analogs in which fluoro substituents replace the enolic hydroxy groups of uracil, thymine and cytosine have been prepared.Improved methods for the preparation and isolation of the known 2,4-difluoropyrimidine, 2,4-difluoro-6-methylpyrimidine and the new 2,4-difluoro-5-methylpyrimidine, 2-fluoro-4-aminopyrimidine, 4-fluoro-2-aminopyrimidine, and other alkylaminofluoropyrimidines are described.
- Svirskaya, Polina I.,Yedidia, Varda,Leznoff, Clifford C.,Miller, Jack M.
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p. 149 - 153
(2007/10/02)
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