- HERBICIDAL PYRIDINIUM COMPOUNDS
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Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially as herbicides.
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Page/Page column 70
(2020/08/22)
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- Synthesis and evaluation of 2-pyridinylpyrimidines as inhibitors of HIV-1 structural protein assembly
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In an effort to identify an HIV-1 capsid assembly inhibitor with improved solubility and potency, we synthesized two series of pyrimidine analogues based on our earlier lead compound N-(4-(ethoxycarbonyl)phenyl)-2-(pyridine-4-yl)quinazoline-4-amine. In vitro binding experiments showed that our series of 2-pyridine-4-ylpyrimidines had IC50values higher than 28 μM. Our series of 2-pyridine-3-ylpyrimidines exhibited IC50values ranging from 3 to 60 μM. The congeners with a fluoro substituent introduced at the 4-N-phenyl moiety, along with a methyl at C-6, represent potent HIV capsid assembly inhibitors binding to the C-terminal domain of the capsid protein.
- Ko?í?ek, Milan,?těpánek, Ond?ej,Parkan, Kamil,Berenguer Albi?ana, Carlos,Pávová, Marcela,Weber, Jan,Kr?usslich, Hans-Georg,Konvalinka, Jan,Machara, Ale?
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supporting information
p. 3487 - 3490
(2016/07/21)
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- Geometrically restricted intermediates in the self-assembly of an M12L24 cuboctahedral complex
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The self-assembly of a cuboctahedral M12L24 complex is traced by time-dependent NMR spectroscopy and mass spectrometry. The metastable intermediate structures that exist during the self-assembly process are not a chaotic mixture of numerous species, but instead are geometrically restricted. Short-lived M8L16 (D4d) and relatively long-lived M9L18 (D3h) are fully characterized as major intermediates. Employing a ligand with a smaller bend angle (112°) allows these two species to be kinetically trapped and more clearly observed by NMR spectroscopy. X-ray crystallography shows that M9L18 has the framework topology predicted by geometric discussion.
- Fujita, Daishi,Yokoyama, Hiroyuki,Ueda, Yoshihiro,Sato, Sota,Fujita, Makoto
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p. 155 - 158
(2015/05/19)
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- Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors
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Sant-75 is a newly identified potent inhibitor of the hedgehog pathway. We designed a diversity-oriented synthesis program, and synthesized a series of Sant-75 analogues, which lays the foundation for further investigation of the structure-activity relationship of this important class of hedgehog-pathway inhibitors.
- Che, Chao,Li, Song,Yang, Bo,Xin, Shengchang,Yu, Zhixiong,Shao, Taofeng,Tao, Chuanye,Lin, Shuo,Yang, Zhen
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scheme or table
p. 841 - 849
(2012/07/28)
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- Preparation of amidines from amidoximes via transfer hydrogenation
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Amidoximes are reduced into amidine using triethyl silane and PdCl 2 in acetic acid. Copyright
- Mahajan, Umesh S.,Godinde, Rupesh R.,Mandhare
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experimental part
p. 2195 - 2199
(2011/06/27)
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- SAR studies of 4-pyridyl heterocyclic anilines that selectively induce autophagic cell death in von Hippel-Lindau-deficient renal cell carcinoma cells
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We recently identified a class of pyridyl aniline thiazoles (PAT) that displayed selective cytotoxicity for von Hippel-Lindau (VHL) deficient renal cell carcinoma (RCC) cells in vitro and in vivo. Structure-activity relationship (SAR) studies were used to develop a comparative molecular field analysis (CoMFA) model that related VHL-selective potency to the three-dimensional arrangement of chemical features of the chemotype. We now report the further molecular alignment-guided exploration of the chemotype to discover potent and selective PAT analogues. The contribution of the central thiazole ring was explored using a series of five- and six-membered ring heterocyclic replacements to vary the electronic and steric interactions in the central unit. We also explored a positive steric CoMFA contour adjacent to the pyridyl ring using Pd-catalysed cross-coupling Suzuki-Miyaura, Sonogashira and nucleophilic displacement reactions to prepare of a series of aryl-, alkynyl-, alkoxy- and alkylamino-substituted pyridines, respectively. In vitro potency and selectivity were determined using paired RCC cell lines: the VHL-null cell line RCC4 and the VHL-positive cell line RCC4-VHL. Active analogues selectively induced autophagy in RCC4 cells. We have used the new SAR data to further develop the CoMFA model, and compared this to a 2D-QSAR method. Our progress towards realising the therapeutic potential of this chemotype as a targeted cytotoxic therapy for the treatment of RCC by exploiting the absence of the VHL tumour suppressor gene is reported.
- Bonnet, Muriel,Flanagan, Jack U.,Chan, Denise A.,Lai, Edwin W.,Nguyen, Phuong,Giaccia, Amato J.,Hay, Michael P.
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supporting information; experimental part
p. 3347 - 3356
(2011/07/09)
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- 2,4-Diaryl-4,6,7,8-tetrahydroquinazolin-5(1H)-one derivatives as anti-HBV agents targeting at capsid assembly
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A series of novel 2,4-diaryl-4,6,7,8-tetrahydroquinazolin-5(1H)-one derivatives were designed and synthesized as potent inhibitors of HBV capsid assembly. These compounds arose from efforts to rigidify an earlier series of heteroaryldihydropyrimidines (HA
- Zhu, Xuejun,Zhao, Guoming,Zhou, Xiaoping,Xu, Xiaoqian,Xia, Guangqiang,Zheng, Zhibing,Wang, Lili,Yang, Xiaohong,Li, Song
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scheme or table
p. 299 - 301
(2010/04/05)
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- Synthesis and SAR of 6-chloro-4-fluoroalkylamino-2-heteroaryl-5-(substituted)phenylpyrimidines as anti-cancer agents
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The synthesis and SAR of a series of 6-chloro-4-fluoroalkylamino-2-heteroaryl-5-(substituted)phenylpyrimidines as anti-cancer agents are described. This series of 2-heteroarylpyrimidines was developed by modifying a series of anti-tumor [1,2,4]triazolo[1,5-a]pyrimidines and 2-cyanoaminopyrimidines we reported earlier. For the 2-heteroaryl group, the best activity is obtained when the heteroaryl group has a nitrogen atom at the ortho-position to the pyrimidyl core. The structure-activity relationship for the rest of the molecule in this 2-heteroarylpyrimidine series mimics that of the [1,2,4]triazolo[1,5-a]pyrimidine series. Like triazolopyrimidines and 2-cyanoaminopyrimidines, the 2-heteroarylpyrimidines retain the capability to overcome multidrug resistance due to Pgp. Mechanism of action studies showed that the lead compounds behaved in the same manner as triazolopyrimidines and 2-cyanoaminopyrimidines. The lead compounds in this series are more potent than the corresponding triazolopyrimidines in vitro and in vivo. Compound 21 (PTI-868) showed tumor growth inhibition in several nude mouse xenograft models, and was selected to advance to preclinical development.
- Zhang, Nan,Ayral-Kaloustian, Semiramis,Nguyen, Thai,Hernandez, Richard,Lucas, Judy,Discafani, Carolyn,Beyer, Carl
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experimental part
p. 111 - 118
(2011/02/25)
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- Therapeutic quinazoline derivatives
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A compound of formula (I) or a salt, ester, amide or prodrug thereof; where X is O, or S, S(O), S(O)2 or NR6 where R6 is hydrogen of C1-6alkyl; R5 is an optionally substituted 6-membered aromatic ring containing at least one nitrogen atom, and R1, R2, R3, R4 are independently selected from halogeno, cyano, nitro, C1-3alkylsulphanyl, —N(OH)R7— (wherein R7 is hydrogen, or C1-3alkyl), or R9X1— (wherein X1 represents a direct bond, —O—, —CH2—, —OC(O), —C(O)—, —S—, —SO—, —SO2—, —NR10C(O)—, —C(O)NR11—, —SO2NR12—, —NR13SO2— or NR14— (wherein R10, R11, R12, R13 and R14 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl), and R9 is hydrogen, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or optionally substituted alkoxy; provided that at least one of R2 or R3 is other than hydrogen. These compounds inhibit aurora 2 kinase and are useful in the preparation of medicaments for the treatment of proliferative disease such as cancer.
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- New piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives as selective 5-HT1A receptor agonists with highly potent anti-ischemic effects
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A series of new piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives were synthesized. Among these compounds, 4-methyl-2-(1,2,3,6- tetrahydropyridin-4-yl)pyrimidine derivative 23 (SUN N5147) exhibited sub-nanomolar affinity for 5-HT1A receptor with 1000-fold selectivity over both dopamine D2 and α1-adrenergic receptors and remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model.
- Kamei, Katsuhide,Maeda, Noriko,Katsuragi-Ogino, Ryoko,Koyama, Makoto,Nakajima, Mika,Tatsuoka, Toshio,Ohno, Tomochika,Inoue, Teruyoshi
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p. 2990 - 2993
(2007/10/03)
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- Arylalkane-sulfonamides having endothelin-antagonist activity
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The invention relates to novel aryl-alkane-sulfonamides and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.
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- PROLINE DERIVATIVES AND USE THEREOF AS DRUGS
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The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.
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- Butyne diol derivatives
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The present invention relates to novel butyne diol derivatives of the general formula I and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of the general formula I and especially their use as endothelin receptor antagonists.
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- 6 alkoxy-4-pyrimidinyl bis-sulfonamides
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The present invention relates to novel bis-sulfonamides represented, for example, by formula I below and a pure diastereomer, a mixture of diastereomers, a diastereomeric racemate, a mixture of diastereomeric racemates and meso-forms and a pharmaceutically acceptable salt thereof, wherein R1represents aryl; aryl-lower alkyl; aryl-lower alkenyl; heteroaryl; or heteroaryl-lower alkyl; and R2represents lower alkyl; trifluoromethyl; lower alkoxy-lower alkyl; lower alkenyl; lower alkynyl; aryl; aryl-lower alkyl; aryl-lower alkenyl; heterocyclyl; heterocyclyl-lower alkyl; heteroaryl; heteroaryl-lower alkyl; cycloalkyl; or cycloalkyl-lower alkyl. The present invention also relates to a process for manufacturing those compounds, pharmaceutical compositions containing one or more of those compounds as endothelin antagonists, and a method of treating a subject having a disorder involving endothelin with the compounds of the invention.
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- Pyrimidine derivatives and their salts, useful for making benzoxazepine derivatives
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A benzoxazepine derivative having the general formula (I) and its salts and medicaments containing the same as effective ingredients: wherein, n is an integer of 2 to 5, R1indicates a hydrogen atom, halogen atom, C1to C4lo
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- Carbamoylation process
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The present invention is concerned with a novel process for the carbamoylation of substituted pyridines, especially with a process for the preparation of compounds of formula I wherein R4 to R8 represent hydrogen, lower-alkoxy or halogen; or optionally sa
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- Sulfonamides
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Compounds of the formula: STR1 where A, B, R1 -R8 are as described herein are endothelin inhibitors that can be used in treating diseases associated with endothelin, such as high blood pressure. Chemical synthesis of these compounds and pharmaceutical compositions containing these compounds are also useful.
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- Aromatic, substituted pyrimidine compounds, methods for the preparation thereof, and use thereof
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Aromatic, substituted pyrimidine compounds, methods for the preparation thereof, and use thereof Compounds having a pyrimidine ring, of the formula (I) STR1 are suitable for nonlinear-optical applications, e.g. for fabricating components for frequency-doubling of light. In the formula, AX is STR2 An- is an anion, B is the pyrimidine(1,4) radical, D is --NH2, --NH--NH2, --OR6, --O(CH2)p OH, --OH, --NR5 R6, --NHR6, --N=CH--R4, --HN--N=CH--R4, --NO2, the radicals R1, R2, R3 and R5 are an alkyl radical having from 1 to 22 carbon atoms or a radical CF3 (CF2)m (CH2)n, R4 is a phenyl radical which may be substituted, R6 is an alkyl radical having from 1 to 22 carbon atoms or the radical CF3 (CF2)m (CH2)n, where m is an integer of at least 5, n is an integer of at least zero, and (n+m) is at most 22, or the group (CH2)p OH, where p is an integer from 2 to 5.
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- 6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-ones and compositions and method of use thereof
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Novel 6-heterocyclyl-pyrazolo[3,4-d]pyrimidin-4-ones, useful in treating cardiovascular disease, are prepared by reacting a 5-amino-1H-pyrazole-4-carboxamide with heterocyclylcarboxaldehyde or by reacting a 5-amino-1H-pyrazole-4-carbonitrile with a heterocyclylcarboxamidine, followed by diazotization and hydrolysis of the resulting 4-amino-6-heterocyclyl-pyrazolo[3,4-d]pyrimidine.
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- Preparation of Triazolopyrimidines as Potential Antiasthma Agents
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With the use of the human basophil histamine release assay, 5-aryl-2-aminotriazolopyrimidines were found to be active as mediator release inhibitors.These compounds were prepared by reacting arylamidines with sodium ethyl formylacetate or with ethyl propiolate to give pyrimidinones.Treatment with phosphorus oxychloride gave a chloropyrimidine, which was converted to a hydrazinopyrimidine with hydrazine.Cyclization, using cyanogen bromide, gave the triazolopyrimidines, after a Dimroth rearrangement.Following a structure-activity evaluation, the5--2-amino (8-10), 5-(3-bromophenyl)-2-amino (8-13), 5--2-amino (8-11), and 5-(4-pyridinyl)-2-amino (6-7) compounds were found to have the best activity.They were chosen for further pharmacological and toxicological study.
- Medwid, Jeffrey B.,Paul, Rolf,Baker, Jannie S.,Brockman, John A.,Du, Mila T.,et al.
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p. 1230 - 1241
(2007/10/02)
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- 6-Aryl-4-hydrazinyl-s-triazin-2-ones
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STR1 This invention relates to 6-aryl-4-hydrazinyl-1,2-dihydro-1,3,5-triazin-2-ones and 2-thiones of Formula I, processes for their preparation, intermediates useful in said processes and methods of treating physiological disorders in humans and animals, in particular, cardiovascular disorders, including hypertension.
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