- Synthesis and Studies of Potential Inhibitors of CD73 Based on a Triazole Scaffold
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The ecto-5′-nucleotidase CD73 is involved in the production of immunosuppressive adenosine in the tumoral microenvironment and recently became a validated target in immuno-oncology. To avoid formation of CD73-produced adenosine, several series of potential inhibitors of the target enzyme based on a triazole scaffold were synthetized and evaluated on recombinant purified hCD73 and in cell-based assays.
- Braka, Abdenour,Chaloin, Laurent,Cros-Perrial, Emeline,Grosjean, Félix,Jordheim, Lars Petter,Mathé, Christophe,Peyrottes, Suzanne,Uttaro, Jean-Pierre
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supporting information
(2021/12/14)
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- Synthesis of Functionalized Indolines and Dihydrobenzofurans by Iron and Copper Catalyzed Aryl C-N and C-O Bond Formation
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A simple and effective one-pot, two-step intramolecular aryl C-N and C-O bond forming process for the preparation of a wide range of benzo-fused heterocyclic scaffolds using iron and copper catalysis is described. Activated aryl rings were subjected to a highly regioselective, iron(III) triflimide-catalyzed iodination, followed by a copper(I)-catalyzed intramolecular N-or O-arylation step leading to indolines, dihydrobenzofurans, and six-membered analogues. The general applicability and functional group tolerance of this method were exemplified by the total synthesis of the neolignan natural product, (+)-obtusafuran. DFT calculations using Fukui functions were also performed, providing a molecular orbital rationale for the highly regioselective arene iodination process.
- Henry, Martyn C.,Senn, Hans Martin,Sutherland, Andrew
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p. 346 - 364
(2019/01/08)
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- PIPECOLIC ESTERS FOR INHIBITION OF THE PROTEASOME
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The present disclosure relates to chemical compounds that modulate proteasome activity, pharmaceutical compositions containing such compounds, and use of these compounds and compositions for the treatment of disorders of uncontrolled cellular proliferation such as, for example, a cancer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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Paragraph 00274
(2019/08/26)
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- Synthesis, in vitro and in silico evaluation of diaryl heptanones as potential 5LOX enzyme inhibitors
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A new series of diaryl heptanones (12a-q) were synthesized and their structures were confirmed by its 1H, 13C NMR and Mass spectral data. These analogs were evaluated for their anti-oxidant activity and potential to inhibit 5-lipoxygenase. Compounds 12k and 12o showed potent in vitro 5-lipoxygenase enzyme inhibitory activity with IC50 values of 22.2, 21.5 μM, which are comparable to curcumin (24.4 μM). Further they also have shown significant antioxidant activity. Molecular docking studies clearly showed correlation between binding energy and potency of these compounds.
- Meka, Bharani,Ravada, Suryachandra Rao,Muthyala, Murali Krishna Kumar,Kurre, Purna Nagasree,Golakoti, Trimurtulu
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p. 408 - 421
(2018/07/13)
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- NOVEL ALLOSTERIC INHIBITORS OF PROTEASOME AND METHODS OF USE THEREOF
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The present invention relates generally to novel allosteric regulators of proteasome activity, methods for preparation and use, and pharmaceutical compositions thereof. Specifically piperidine-2-carboxylic acid derivatives containing 1-oxo-aroyl group and
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Page/Page column 45-46
(2015/01/09)
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- A natural product inspired tetrahydropyran collection yields mitosis modulators that synergistically target CSE1L and tubulin
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A Prins cyclization between a polymerbound aldehyde and a homoallylic alcohol served as the key step in the synthesis of tetrahydropyran derivatives. A phenotypic screen led to the identification of compounds that inhibit mitosis (as seen by the accumulation of round cells with condensed DNA and membrane blebs; see picture). These compounds were termed tubulexins as they target the CSE1L protein and the vinca alkaloid binding site of tubulin.
- Voigt, Tobias,Gerding-Reimers, Claas,Tran, Tuyen Thi Ngoc,Bergmann, Sabrina,Lachance, Hugo,Sch?lermann, Beate,Brockmeyer, Andreas,Janning, Petra,Ziegler, Slava,Waldmann, Herbert
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supporting information
p. 410 - 414
(2013/02/23)
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- Synthesis of salidroside analogues and their ability of DPPH radical scavenging activity
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Salidroside is a phenylpropanoid glycoside isolated from Rhodiolarosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this paper, about 22 novel glycosides have been synthesized and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenge activity of each glycoside has been evaluated. 2-(3,4,5-Trihydroxyphenyl)ethyl β-D-galactopyranoside and 3-(3,4,5-trihydroxyphenyl)propyl β-D-glucopyranoside exhibit significant activity prior to salidroside and Vitamin C with EC50 values of 35.85 μM and 36.71 μM, respectively. The results indicate that the phenolic hydroxyl group of these compounds is important for radical scavenging activity and phenyl ring substitution by electron-donating substituents lead to increased antioxidant activity.
- Zheng, Cheng,Guo, Yibing,Meng, Ying,Dou, Sufeng,Shao, Jian,Yang, Yumin
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p. 654 - 664
(2013/07/11)
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- Synthesis of gingerol and diarylheptanoids
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The synthesis of gingerol 1 and related compounds 2-5 along with diarylheptanoids 6-8 has been accomplished using a Keck allylation, Crimmins' aldol reaction, aldehyde coupling with acetylene, and chelation controlled reductions as the key reactions. The absolute configuration of these molecules was confirmed by preparing their acetonide derivatives and by comparison of the NMR data with natural compounds.
- Sabitha, Gowravaram,Srinivas, Chitti,Reddy, Teega Rammohan,Yadagiri, Kurra,Yadav, Jhillu Singh
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p. 2124 - 2133
(2012/03/27)
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- New two-step sequence involving a hetero-Diels-Alder and a nonphenolic oxidative coupling reaction: A convergent access to analogs of steganacin
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A new family of analogs of steganacin, an important antimitotic compound, was accessed. It takes advantage of a completely stereoselective sequence of two key steps. The central dihydropyrane core is built by a highly diastereoselective and facially controlled hetero-Diels-Alder reaction. It is followed by a nonphenolic biaryl oxidative coupling with a complete atropo-stereoselectivity. It leads to a quick way to form cyclic biaryl lignans.
- Laurent, Mathieu Y.,Stocker, Vivien,Temgoua, Valéry Momo,Dujardin, Gilles,Dhal, Robert
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supporting information; experimental part
p. 1608 - 1611
(2011/04/26)
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- A new shortcut synthesis route for (±)raphidecursinol
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The new shortcut synthesis route of (±)raphidecursinol 1, a racemic 8,4′-oxyneolignan compound, can be more easily achieved by the synthesis route, starting from readily available inexpensive 3,4,5-trimethoxy-benzaldehyde and 1,2,3-trihydroxybenzene. All structures were confirmed by 1H NMR, IR and MS.
- Yuan, Hua Jie,Cheng, Yao Yao,Qian, Shan,Xiao, Xiang,Wu, Yong
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body text
p. 127 - 130
(2010/11/18)
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- Synthesis of (S)-(-)-N-acetylcolchinol using intramolecular biaryl oxidative coupling
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An asymmetric synthesis of the tubulin polymerisation inhibitor (S)-(-)-N-acetylcolchinol is reported based on an intramolecular biaryl oxidative coupling of a 1,3-diarylpropyl acetamide intermediate using phenyliodonium bis(trifluoroacetate) as the final
- Besong, Gilbert,Jarowicki, Krzysztof,Kocienski, Philip J.,Sliwinski, Eric,Boyle, F. Thomas
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p. 2193 - 2207
(2008/02/09)
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- Caulerpenyne-colchicine hybrid: Synthesis and biological evaluation
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The synthesis of an analog of caulerpenyne having a trimethoxyaryl moiety was achieved in 11% overall yield over 11 steps. Its biological activity has been evaluated as inhibitor of in vitro tubulin polymerization or angiogenesis.
- Bourdron, Julien,Commeiras, Laurent,Barbier, Pascale,Bourgarel-Rey, Veronique,Pasquier, Eddy,Vanthuyne, Nicolas,Hubaud, Jean-Claude,Peyrot, Vincent,Parrain, Jean-Luc
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p. 5540 - 5548
(2007/10/03)
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- Unsymmetrical cyclic diamine compound
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A cyclic diamine compound of formula (1): wherein A is (CH2)n, (CH2)n—CH═CH, CO—(CH2)n or CO—(CH2)n—CH═CH, in which n is a number of 0 to 3; Z represents a formula (2) or (3): in which R1, R2, R4, R5 and R6 are individually a hydrogen atom, alkyl group, alkoxy group, halogen atom or nitro group; R3 is a hydrogen atom, alkyl group, alkoxy group, halogen atom, nitro group, naphthyl group, or phenyl group which may be substituted by 1 to 3 substituents selected from the group consisting of alkyl groups, alkoxy groups, halogen atoms, a nitro group and a phenyl group; and X and Y are individually CH or a nitrogen atom; and m is 1 or 2; an acid-addition salt thereof, or a hydrate thereof, and a medicine containing such a compound.
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- Synthesis of new 2,4-Diaminopyrido[2,3-d]pyrimidine and 2,4-Diaminopyrrolo[2,3-d]pyrimidine inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductase
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A concise new route allowing easy access to five previously unreported 2,4-diamino-6-(substituted benzyl)pyrido[2,3-d]pyrimidines (2a-e) was developed, involving condensation of 2,4-dipivaloylamino-5-bromopyrido[2,3-d]pyrimidine (6) with an organozinc halide in the presence of a catalytic amount of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)·CH 2Cl2, followed by removal of the pivaloyl groups with base. Also prepared via a scheme based on the Taylor ring expansion/ring annulation synthesis were three heretofore undescribed 2,4-diamino-5-(substituted benzyl)-7H-pyrrolo[2,3-d]pyrimidines (3b-c). Standard spectrophotometric assays were used to compare the ability of 2a-e and 3b-c to inhibit dihydrofolate reductase (DHFR) from Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium, three examples of opportunistic pathogens to which AIDS patients are highly vulnerable because of their immunocompromised state. For comparison, 13 previously untested 2,4-diamino-6-(substituted benzyl)quinazolines (17a-m) were also evaluated as inhibitors of these enzymes, as well as the enzyme from rat liver. None of the quinazolines or pyridopyrimidines tested was more potent against the P. carinii enzyme than the structurally related reference compound piritrexim (1), and none showed selectivity for the P. carinii enzyme over the rat enzyme. One of the pyridopyrimidines (2c) showed 10-fold selectivity for T. gondii versus rat DHFR, and two of them (2b, 2c) showed selectivity for the M. avium enzyme. However, this gain in species selectivity was achieved at the cost of decreased in potency, as has been noted with many other lipophilic DHFR inhibitors.
- Rosowsky, Andre,Chen, Han,Fu, Hongning,Queener, Sherry F.
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- Synthesis of highly functionalized arene systems. Novel selectivities of intra- and intermolecular Friedel-Crafts reactions
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The intermolecular Friedel-Crafts acylation of electron-rich aromatic rings can be difficult in the presence of easily ionized groups. During these studies directed toward the synthesis of colchicine, it was observed that the stability of the cation is ke
- McMills, Mark,Wright, Dennis,Weekly, R. Matt
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p. 2417 - 2425
(2007/10/03)
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- Hypervalent iodine(III)-induced intramolecular cyclization reaction of substituted phenol ethers with an alkyl azido side-chain: A novel and efficient synthesis of quinone imine derivatives
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Novel and efficient syntheses of quinone imine ketals (2aj) and quinone imines (4ah) from substituted phenol ethers (1ak) bearing an alkyl azido side-chain using the combination of hypervalent iodine(III) reagent, phenyliodine(III) bis(trifluoroacetate) (PIFA) and trimethylsilyl trifluoromethanesulfonate (TMSOTf), have been developed.
- Kita, Yasuyuki,Egi, Masahiro,Ohtsubo, Makoto,Saiki, Toyokazu,Okajima, Akiko,Takada, Takeshi,Tohma, Hirofumi
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p. 241 - 245
(2007/10/03)
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- Development of novel reactions using hypervalent iodine(III) reagents: Total synthesis of sulfur-containing pyrroloiminoquinone marine product, (±)-makaluvamine F
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Novel and efficient intramolecular nucleophilic substitution reactions of phenol ethers using activated hypervalent iodine species have been developed and their application to the total synthesis of strongly cytotoxic makaluvamine F (1), a member of sulfur-containing pyrroloiminoquinone marine products, is described.
- Kita, Yasuyuki,Egi, Masahiro,Takada, Takeshi,Tohma, Hirofumi
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p. 885 - 897
(2007/10/03)
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- 2,4-diamino-6,7-dihydro-5?-cyclopentacf|pyrimidine analogues of trimethoprim as inhibitors of pneumocystis carinii and toxoplasma gondii dihydrofolate reductase
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Three previously unreported (R,S)-2,4-diamino-5-[(3,4,5-trimethoxyphenyl)alkyl]-6,7-dihydro5.ff- cyclopenta[rf]pyrimidines 15a-c were synthesized as analogues of trimethoprim (TMP) and were tested as inhibitors of Pneumocystis carinii, Toxoplasma gondii,
- Rosowsky, Andre,Papoulis, Andrew T.,Queener, Sherry F.
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p. 913 - 918
(2007/10/03)
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- LEWIS X DERIVATIVE AND PROCESS FOR PRODUCING THE SAME
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A novel oligosaccharide derivative having a cell adhesion inhibitory activity and represented by structural formula (I).
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- Process for the preparation of polycyclic compounds using ferric perchlorate and acid trifluoroacidic
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Polycyclic compounds (I) can be prepared in accordance with the following reaction formula: STR1 wherein R1 -R8 each represents a hydrogen atom, a hydroxyl group, an alkoxyl group or a substituted or unsubstituted benzyloxy group or
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- Polycyclic compounds, their preparation and their use as phosphodiesterases inhibitors
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Polycyclic compounds (I) can be prepared in accordance with the following reaction formula: wherein R1-R8 each represents a hydrogen atom, a hydroxyl group, an alkoxyl group or a substituted or unsubstituted benzyloxy group or neighb
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