- Selective 15N-labeling and analysis of 13C- 15N J couplings as an effective tool for studying the structure and azide-tetrazole equilibrium in a series of tetrazolo[1,5- b ][1,2,4]triazines and tetrazolo[1,5-a ]pyrimidines
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Two general methods for the selective incorporation of an 15N-label in the azole ring of tetrazolo[1,5-b][1,2,4]triazines and tetrazolo[1,5-a]pyrimidines were developed. The first approach included treatment of azinylhydrazides with 15/su
- Deev, Sergey L.,Shenkarev, Zakhar O.,Shestakova, Tatyana S.,Chupakhin, Oleg N.,Rusinov, Vladimir L.,Arseniev, Alexander S.
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Read Online
- 1-CYANO-PYRROLIDINE DERIVATIVES AS DUB INHIBITORS
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The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The novel compounds have formula (I): (Formula (I)) or are pharmaceutically acceptable salts thereof, wherein: R1a, R1b, R1c, R1d, R1e and R1f each independently represent hydrogen, optionally substituted C1-C6 alkyl or optionally substituted C3-C4 cycloalkyl, or R1b and R1c together form an optionally substituted C3-C6 cycloalkyl ring, or R1d and R1e together form an optionally substituted C3-C6 cycloalkyl ring; R2 represents hydrogen or optionally substituted C1-C6 alkyl; A represents an optionally further substituted 5 to 10 membered monocyclic or bicyclic heteroaryl, heterocyclyl or aryl ring; L represents a covalent bond or linker; B represents an optionally substituted 3 to 10 membered monocyclic or bicyclic heterocyclyl, heteroaryl, cycloalkyl or aryl ring; and when -A-L-B is at position x attachment to A is via a carbon ring atom of A, and either: A cannot be triazolopyridazinyl, triazolopyridinyl, imidazotriazinyl, imidazopyrazinyl or pyrrolopyrimidinyl; or B cannot be substituted with phenoxyl; or B cannot be cyclopentyl when L is an oxygen atom.
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Paragraph 0883-0884
(2020/11/30)
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- Divergent Conversion of N-Acyl-isoxazol-5(2 H)-ones to Oxazoles and 1,3-Oxazin-6-ones Using Photoredox Catalysis
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The fragmentation of N-acyl-isoxazol-5-ones using visible light photoredox catalysis has been disclosed. The catalyst-controlled divergent mechanisms, namely the oxidative and reductive quenching catalytic cycle, are utilized. Various oxazoles and 1,3-oxazin-6-ones are selectively obtained from the same isoxazol-5-one skeleton under mild conditions.
- Mei, Mingjing,Anand, Devireddy,Zhou, Lei
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supporting information
p. 3548 - 3553
(2019/05/24)
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- Method for highly efficiently synthesizing 2-phenyl-1,3-propylene glycol
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The invention discloses a method for highly efficiently synthesizing 2-phenyl-1,3-propylene glycol. The method includes the following steps that firstly a silicate active agent is prepared; secondly,ethyl benzoacetate, methyl formate and diisopropyl carbodiimide are used as raw materials for condensation reaction; alpha-formyl ethyl phenylacetate is prepared; then sodium borohydride is used as ahydrogenation reductant, the prepared silicate active agent promotes a reduction reaction, and alpha-formyl ethyl phenylacetate is reduced to prepare 2-phenyl-1,3-propylene glycol. The 2-phenyl-1,3-propylene glycol prepared by the method is high in purity, high in yield, short in reaction time and low in cost.
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Paragraph 0021-0025; 0027-0031; 0033-0037; 0039-0049
(2018/04/21)
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- Titanium(IV) Chloride-Mediated Stereoselective α-Alkylidenation to Efficiently Assemble Multisubstituted 1,3-Dienes
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A direct access to multisubstituted 1,3-dienes by α-exclusive alkylidenation of crotonic derivatives has been developed. This protocol, mediated by titanium tetrachloride chelation, features excellent regio- and stereoselectivity, mild reaction conditions, easy operation and wide substrate scope. Conversions of the derived dienes to other useful molecules were also explored. (Figure presented.).
- Sun, Rengwei,Song, Wei,Ma, Chunmei,Zhang, Huiwen,Yu, Xinhong
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supporting information
p. 3977 - 3982
(2016/12/30)
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- Facile synthesis of highly substituted 2-pyrone derivatives via a tandem Knoevenagel condensation/lactonization reaction of β-formyl-esters and 1,3-cyclohexadiones
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A mild and efficient tandem process for the synthesis of new highly substituted 2-pyrones starting from commercially available 2-arylacetic acids has been developed. The synthesis is based on the Knoevenagel condensation of 1,3-cyclohexadiones with various β-formyl-esters, followed by lactonization in the presence of nano ZnO (20 mol %). Moderate to high yields and readily available cheap starting materials are the key features of the present method.
- Moghaddam, Firouz Matloubi,Mirjafary, Zohreh,Javan, Marjan Jebeli,Motamen, Sara,Saeidian, Hamid
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p. 2908 - 2911
(2014/05/06)
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- Synthesis and anticancer evaluation of 3-substituted quinolin-4-ones and 2,3-dihydroquinolin-4-ones
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A series of 3-aryl-5,7-dimethoxyquinolin-4-ones 8 and 3-aryl-5,7-dimethoxy- 2,3-dihydroquinolin-4-ones 13 were synthesized in good yields. Demethylation under a range of conditions afforded the corresponding 5-hydroxy and 5,7-dihydroxy derivatives. Biolog
- Rajput, Santosh,Gardner, Christopher R.,Failes, Timothy W.,Arndt, Greg M.,Black, David Stc.,Kumar, Naresh
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p. 105 - 115
(2014/01/17)
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- Lewis base catalyzed asymmetric hydrosilylation of α-substituted β-enamino esters: Facile access to enantioenriched β2-amino esters via dynamic kinetic resolution
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A chiral Lewis base organocatalyzed asymmetric hydrosilylation of α-substituted β-enamino esters is presented. The reactions proceeded through dynamic kinetic resolution to afford various enantioenriched β2-amino esters with high yields (up to
- Shu, Chang,Hu, Xiao-Yan,Li, Shuai-Shuai,Yuan, Wei-Cheng,Zhang, Xiao-Mei
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supporting information
p. 1879 - 1882
(2014/08/18)
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- Palladium-catalyzed oxidative carbonylation for the synthesis of polycyclic aromatic hydrocarbons (PAHs)
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A direct and facile palladium-catalyzed C-H bond oxidative carbonylation reaction and oxidative cyclization for the synthesis of polycyclic aromatic hydrocarbons (PAHs) is reported herein. The intramolecular cyclocarbonylation, through C-H activation and C-C, C-O bond formations under mild conditions, proceeds smoothly with good functional group tolerance in high to excellent yields. The intramolecular palladium-catalyzed direct oxidative C-H bond functionalization for the C-O bond formation is also demonstrated, which provides an efficient approach for the construction of various PAHs.
- Ji, Fanghua,Li, Xianwei,Wu, Wanqing,Jiang, Huanfeng
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supporting information
p. 11246 - 11253
(2015/01/08)
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- Imidazonaphthyridine systems (part 2): Functionalization of the phenyl ring linked to the pyridine pharmacophore and its replacement by a pyridinone ring produces intriguing differences in cytocidal activity
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We recently discovered that five- and pseudo-five-fused-ring derivatives in an imidazonaphthyridine series were promising hit compounds for the development of new DNA-intercalators. In this study, novel (dihydro)imidazo[1,6] and [1,7]naphthyridi(no)nes were prepared including pseudo-pentacycles. All the compounds synthesized were screened against four tumor cell lines. Compounds 3(b-d) showed significant in vitro cytotoxicity, and DNA intercalation properties were demonstrated at 25 μM. Imidazonaphthyridinones exhibited no DNA binding affinity despite significant growth inhibition activity. Interestingly, when a pyridinone pharmacophore was linked to the imidazo[1,2-a]pyridine scaffold, the geometric orientation of the link had a strong impact on the growth inhibition activity. From these results we conclude that the moderate cytotoxicity observed for these compounds is independent of their DNA-binding and topoisomerase inhibition activities.
- Masurier, Nicolas,Debiton, Eric,Jacquemet, Alicia,Bussière, Antoine,Chezal, Jean-Michel,Ollivier, Anthony,Tétégan, Daté,Andaloussi, Mounir,Galmier, Marie-Joseph,Lacroix, Jacques,Canitrot, Damien,Teulade, Jean-Claude,Gaudreault, René C.,Chavignon, Olivier,Moreau, Emmanuel
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scheme or table
p. 137 - 150
(2012/07/16)
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- SUBSTITUTED PHENOXYMETHYL DIHYDRO OXAZOLOPYRIMIDINONES, PREPARATION AND USE THEREOF
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The present invention relates to a series of substituted phenoxymethyl dihydro oxazolopyrimidinones of formula (I) defined herein. This invention also relates to methods of making these compounds including novel intermediates. The compounds of this invent
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Page/Page column 36
(2011/04/19)
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- Gold(i) "click" 1,2,3-triazolylidenes: Synthesis, self-assembly and catalysis
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Novel gold(i) "click" carbene(1,2,3-triazolylidene) complexes have been synthesised, characterised and exploited for the self-assembly of a metallomacrocycle and as precatalysts for gold(i)-catalysed reactions.
- Kilpin, Kelly J.,Paul, Ursula S. D.,Lee, Ai-Lan,Crowley, James D.
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supporting information; experimental part
p. 328 - 330
(2011/03/17)
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- Synthesis and pharmacological evaluation of thieno[2,3-b]pyridine derivatives as novel c-Src inhibitors
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Among the recently investigated targets for cancer therapy is the c-Src non-receptor tyrosine kinase. Indeed research around deregulated activity of this enzyme has proven its role in tumor progression, while the beneficial effects of c-Src inhibitors in several pathological models has also been demonstrated. We report here the preparation and pharmacological profile of a novel series of c-Src inhibitors that was elaborated around a 3-amino-thieno[2,3-b]pyridine discovered during an HTS campaign. c-Src enzyme inhibition and c-Src inhibition were investigated in a series of related compounds derived from the initial hit. Molecular modeling as well as X-ray studies on one active compound allowed us to hypothesize on ligand orientation and interactions within the ATP hydrophobic pocket. Design and synthesis of structural analogs then led to new ligands possessing quite efficient enzymatic and c-Src inhibition. The structure-activity elements disclosed in this study shed light on the role played by substituents on the thienopyridine ring as well as the impact of other aromatic moieties in the molecule when interacting with the enzyme.
- Pevet, Isabelle,Brulé, Cédric,Tizot, André,Gohier, Arnaud,Cruzalegui, Francisco,Boutin, Jean A.,Goldstein, Solo
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experimental part
p. 2517 - 2528
(2011/06/11)
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- Synthesis and in vitro evaluation of 3H-pyrrolo[3,2-f]-quinolin-9-one derivatives that show potent and selective anti-leukemic activity
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A series of new substituted 7-phenyl-3H-pyrrolo[3,2-f]quinolin-9-ones were synthesized and evaluated for their antiproliferative activity. The most active derivatives showed high selectivity against human leukemia cell lines and potently inhibited their g
- Ferlin, Maria Grazia,Bortolozzi, Roberta,Brun, Paola,Castagliuolo, Ignazio,Hamel, Ernest,Basso, Giuseppe,Viola, Giampietro
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experimental part
p. 1373 - 1385
(2011/01/12)
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- 1H-Quinolin-4-one compounds, with affinity for the GABA receptor, processes, uses and compositions
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The invention provides new 1 H-quinolin-4-one compounds of formula (I), wherein R1, R2, R3, R4 and R5 have different meanings, and pharmaceutically acceptable salts and hydrates thereof. Compounds of
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Page/Page column 14-15
(2008/06/13)
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- 1,2,3-Thiadiazole substituted pyrazolones as potent KDR/VEGFR-2 kinase inhibitors
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KDR kinase inhibition is considered to play an important role in regulating angiogenesis, which is vital for the survival and proliferation of tumor cells. Recently we disclosed a structure-based kinase inhibitor design strategy which led to the identification of a new class of VEGFR-2/KDR kinase inhibitors bearing heterocyclic substituted pyrazolones as the core template. Instability in a rat S9 preparation and poor iv PK profiles for most of these inhibitors necessitated exploration of new pyrazolones to identify new analogs with improved metabolic stability. Optimization of the heterocyclic moiety led to the identification of the thiadiazole series of pyrazolones (D) as potent VEGFR-2/KDR kinase inhibitors. SAR modifications, kinase selectivity profiling, and structural elements for improved PK properties were explored. Oral bioavailability up to 29% was achieved in the rat. Modeling results based on the Glide XP docking approach supported our postulation regarding the interaction of the lactam segment of the pyrazolones with the hinge region of the KDR kinase.
- Tripathy, Rabindranath,Ghose, Arup,Singh, Jasbir,Bacon, Edward R.,Angeles, Thelma S.,Yang, Shi X.,Albom, Mark S.,Aimone, Lisa D.,Herman, Joseph L.,Mallamo, John P.
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p. 1793 - 1798
(2007/10/03)
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- New approach to the synthesis of azauracils and azaisocytosines
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A new procedure was developed for the synthesis of 6-phenyltetrazolo[1,5-b] triazin-7-one. Aza analogs of uracil and isocytosine were prepared by the tetrazole ring cleavage. It was demonstrated that these transformations can be used in the synthesis of a
- Shestakova,Deev,Ulomsky,Rusinov,Chupakhin,D'yachenko,Kazheva,Chekhlov,Slepukhin,Kodess
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p. 2071 - 2080
(2007/10/03)
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- Discovery of isoxazolinone antibacterial agents. Nitrogen as a replacement for the stereogenic center found in oxazolidinone antibacterials
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A series of potential antimicrobial derivatives possessing bioisosteric replacements for the central oxazolidinone ring found in oxazolidinone antibacterials have been prepared. The design concept involved replacement of the requisite sp3-hybridized stereogenic center found at the 5-position of the oxazolidinone with a nitrogen atom. The synthesis and antibacterial activity of three such ring systems, the benzisoxazolinones, pyrroles, and isoxazolinones is described.
- Snyder, Lawrence B.,Meng, Zhaoxing,Mate, Robert,D'Andrea, Stanley V.,Marinier, Anne,Quesnelle, Claude A.,Gill, Patrice,Den Bleyker, Kenneth L.,Fung-Tomc, Joan C.,Frosco, MaryBeth,Martel, Alain,Barrett, John F.,Bronson, Joanne J.
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p. 4735 - 4739
(2007/10/03)
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- The synthesis of novel crown ethers, part IX, 3-phenyl chromenone-crown ethers
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3-Phenyl- and 3-(p-methoxyphenyl)-7,8-dihydroxy and -6,7-dihydroxychromenones were prepared from ethyl 3-oxo-2-phenylpropanoate, ethyl 3-oxo-2-(4-methoxyphenyl)-propanoate and the trihydroxy benzenes in H2SO4. 3-Aryl-7,8- and 3-aryl-
- Bulut,Erk
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p. 1291 - 1295
(2007/10/03)
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- The chemistry of 5-oxodihydroisoxazoles. XX: Photolysis of 2,4-diphenylisoxazol-5(2H)-one: Evidence for singlet and triplet pathways
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2,4-Diphenylisoxazol-5(2H)-one (2) has been photolysed in the presence of alcohols, amines and in inert solvents, and the products are shown to arise by two competitive singlet state photolytic processes. The minor pathway involves loss of carbon dioxide to give an imino carbene which is captured by nucleophiles: the major pathway involves isomerization to a ketene which is rapidly decarbonylated, and the resultant carbene captured by solvent. The presence of acetone or other triplet sensitizers induces a third competitive pathway involving triplet states.
- Ang, Kiah H.,Prager, Rolf H.
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p. 483 - 489
(2007/10/03)
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- Synthesis and antiplatelet activity of phenyl quinolones
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In our search for novel antiplatelet agents, seven positional phenyl quinolone isomers were synthesized. Preliminary screening confirmed their inhibitory effects against arachidonic acid (AA)-induced platelet aggregation. Varying the substitutional position of the phenyl group had a profound effect on the antiplatelet activity of these isomers. 3-Phenyl-4-quinolone showed the greatest potency and was superior to indomethacin, although the two structures are quite different. The mechanism and pharmacological action of 3-phenyl-4-quinolone are currently under investigation. Copyright (C) 1998 Elsevier Science Ltd.
- Huang, Li-Jiau,Hsieh, Ming-Chieh,Teng, Che-Ming,Lee, Kuo-Hsiung,Kuo, Sheng-Chu
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p. 1657 - 1662
(2007/10/03)
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