- Synthesis and biological evaluation of 9-oxo-9hindeno[1,2-b]pyrazine-2,3- dicarbonitrile analogues as potential inhibitors of deubiquitinating enzymes
-
High-throughput screening highlighted 9-oxo-9H-indeno[1,2-b]pyrazine-2,3- dicarbonitrile (1) as an active inhibitor of ubiquitin-specific proteases (USPs), a family of hydrolytic enzymes involved in the removal of ubiquitin from protein substrates. The chemical behavior of compound 1 was examined. Moreover, the synthesis and in vitro evaluation of new compounds, analogues of 1, led to the identification of potent and selective inhibitors of the deubiquitinating enzyme USP8.
- Colombo, Matteo,Vallese, Stefania,Peretto, Ilaria,Jacq, Xavier,Rain, Jean-Christophe,Colland, Frederic,Guedat, Philippe
-
-
Read Online
- Kinetic resolution of racemic benzofused alcohols catalysed by HMFO variants in presence of natural deep eutectic solvents
-
5-Hydroxymethylfurfural oxidase (HMFO) has demonstrated to be a useful biocatalyst for the selective oxidation of alcohols employing oxygen as mild oxidant with no requirement of expensive organic cofactors. This wild-type HMFO biocatalyst and an engineered thermostable variant have been tested in the kinetic resolution of different benzofused alcohols. The use of natural deep eutectic solvents was also explored in HMFO-catalysed oxidation of alcohols. The oxidation of racemic 1-indanol showed a higher conversion and selectivity in presence of 60% v/v of different NADES, especially for those containing carbohydrates. By choosing properly the biocatalyst and the NADES, good enantioselectivity values can be obtained, demonstrating the advantages of employing these neoteric solvents in biocatalysed processes.
- Fraaije, Marco,Lon?ar, Nikola,de Gonzalo, Gonzalo
-
-
- Synthesis and anticancer activity of some 1H-inden-1-one substituted (Heteroaryl)acetamide derivatives
-
Background: The synthesis of 2-[3/4-((6-substituted-1-oxo-2,3-dihydro-1H-inden-2-ylidene)methyl)phenoxy]-N-(heteroaryl)acetamide derivatives and the investigation of their anticancer activity were studied. Methods: 2-(3/4-Hydroxybenzylidene)-6-substituted-2,3-dihydro-1H-inden-1-ones were reacted with suitable 2-chloroacetamides to give 2-[3/4-((6-substituted-1-oxo-2,3-dihydro-1H-inden-2-ylidene) methyl)phenoxy]-N-(heteroaryl)acetamide derivatives. Results: The structure elucidation of the newly synthesised 16 compounds was performed by IR, 1H-NMR, mass spectroscopic data and elemental analyses. The anticancer screening was carried out in National Cancer Institute (NCI), USA. Conclusion: Compound 3e (2-(3-((6-chloro-1-oxo-2,3-dihydro-1H-inden-2-ylidene)methyl)phenoxy)-N-(thiazol-2-yl)acetamide), exhibited highest growth inhibition against the leukaemia (61.47%), non-small cell lung cancer (79.31%) and breast cancer (62.82%) cell lines.
- Karaburun, Ahmet Cagri,Gundogdu-Karaburun, Nalan,Yurttas, Leyla,Kayagil, Ismail,Demirayak, Seref
-
p. 111 - 118
(2019/01/04)
-
- Benzo cyclic ketone compound preparation method
-
The invention discloses a benzo cyclic ketone compound preparation method, which specifically comprises: adding a phenyl acyl chloride compound into a solvent hexafluoroisopropanol in a dropwise manner, and under the catalytic effect of a catalyst Lewis acid (aluminum trichloride or iron trichloride), carrying out a reaction at a temperature of 0-59 DEG C until the acyl chloride is completely converted so as to obtain the benzo cyclic ketone compound. According to the present invention, the benzo cyclic ketone compound is prepared through the cyclization reaction by using the hexafluoroisopropanol as the solvent, such that the use of a large amount of Lewis acid or strong protic acid is avoided so as to substantially reduce the generation of three wastes and provide the less corrosivenessto the equipment; and the method of the present invention is environmentally friendly and safe, and has good economical benefits.
- -
-
Paragraph 0023; 0024
(2018/03/26)
-
- CARBAMATE DERIVATIVE COMPOUNDS, PROCESSES FOR PREPARING THEM AND THEIR USES
-
The present invention relates to a pharmaceutical composition for treating or preventing CNS disorders containing a carbamate derivative compound and/or pharmaceutically acceptable salt thereof as an active ingredient. Furthermore, the present invention relates to a method for treatment or prevention CNS disorders comprising administering a carbamate derivative compound in a pharmaceutically effective amount to a subject in need of treatment or prevention of CNS disorders.
- -
-
Paragraph 402-404
(2017/09/15)
-
- Recyclable Hypervalent-Iodine-Mediated Dehydrogenative α,β′-Bifunctionalization of β-Keto Esters under Metal-Free Conditions
-
We have developed a method for recyclable hypervalent-iodine-mediated direct dehydrogenative α,β′- bifunctionalization of β-ketoesters and β-diketones under metal-free conditions, which affords a straightforward way to synthesize benzo-fused 2,3-dihydrofurans. This efficient, mild method, which has a wide substrate scope and good functional-group tolerance, was used for the multistep synthesis of the protected aglycone of a naturally occurring phenolic glycoside. A mechanism involving Michael addition to an enone intermediate and subsequent oxidative cyclization is proposed.
- Duan, Ya-Nan,Cui, Li-Qian,Zuo, Lin-Hong,Zhang, Chi
-
supporting information
p. 13052 - 13057
(2015/09/07)
-
- Non-conventional methodologies in the synthesis of 1-indanones
-
1-Indanones have been successfully prepared by means of three different non-conventional techniques, namely microwaves, high-intensity ultrasound and a Q-tube reactor. A library of differently substituted 1-indanones has been prepared via one-pot intramolecular Friedel-Crafts acylation and their efficiency and "greenness" have been compared.
- Oliverio, Manuela,Nardi, Monica,Costanzo, Paola,Cariati, Luca,Cravotto, Giancarlo,Giofre, Salvatore Vincenzo,Procopio, Antonio
-
p. 5599 - 5610
(2014/06/10)
-
- Synthesis and anticancer activity of some 2-[3/4-(2-substituted phenyl-2-oxoethoxy)benzylidene]-6-substituted-2,3-dihydro-1H-inden-1-one derivatives
-
The synthesis of 2-[3/4-(2-substituted phenyl-2-oxoethoxy)benzylidene]-6- substituted-2,3-dihydro-1H-inden-1-one derivatives and the investigation of their anticancer activity were studied. 2-(3- or 4-Hydroxybenzylidene)-6- substituted-2,3-dihydro-1H-inden-1-ones were reacted with suitable 2-bromoacetophenones to give 2-[3/4-(2-substituted phenyl-2-oxoethoxy) benzylidene]-6-substituted-2,3-dihydro-1H-inden-1-one derivatives. The structure elucidation of the synthesised compounds was performed by IR, 1H-NMR, mass spectroscopic data and elemental analyses. The anticancer screening was carried out in National Cancer Institute (NCI), USA. Notable activity was obtained for some compounds.
- Gundogdu-Karaburun, Nalan,Karaburun, Ahmet Cagri,Demirayak, Seref,Kayagil, Ismail,Yurttas, Leyla
-
p. 578 - 585
(2014/05/20)
-
- Catalytic asymmetric cross-dehydrogenative coupling: Activation of C-H bonds by a cooperative bimetallic catalyst system
-
A cooperative bimetallic catalyst system was applied in the catalytic asymmetric cross-dehydrogenative coupling of β-ketoesters and xanthene. Various optically active xanthene derivatives bearing a quaternary stereogenic carbon center were obtained in moderate to good yields (up to 90%) with excellent enantioselectivities (up to 99% ee). Meanwhile, a transition-state model was proposed to explain the origin of the asymmetric induction.
- Cao, Weidi,Liu, Xiaohua,Peng, Ruixue,He, Peng,Lin, Lili,Feng, Xiaoming
-
supporting information
p. 3470 - 3472
(2013/05/23)
-
- Identification and optimization of tetrahydro-2H-3-benzazepin-2-ones as squalene synthase inhibitors
-
Novel squalene synthase inhibitors are disclosed. SAR and pharmacological profile of selected compounds are discussed.
- Griebenow, Nils,Flessner, Timo,Buchmueller, Anja,Raabe, Martin,Bischoff, Hilmar,Kolkhof, Peter
-
scheme or table
p. 2554 - 2558
(2011/05/15)
-
- Inter- and intramolecular hydroacylation of alkenes employing a bifunctional catalyst system
-
Based on a conceptually innovative bifunctional P,N ligand, an efficient protocol for the rhodium-catalyzed inter- and intramolecular hydroacylation of alkenes has been developed.
- Vautravers, Nicolas R.,Regent, Damien D.,Breit, Bernhard
-
p. 6635 - 6637
(2011/06/27)
-
- SUBSTITUTED FLUOROETHYL UREAS AS ALPHA 2 ADRENERGIC AGENTS
-
Therapeutic compounds, and methods, compositions, and medicaments related thereto are disclosed herein.
- -
-
Page/Page column 20
(2008/12/04)
-
- THERAPEUTIC FLUOROETHYLCYANO GUANIDINES
-
Disclosed herein is compound having a formula as described herein. Therapeutic methods, compositions, and medicaments related thereto are also disclosed.
- -
-
Page/Page column 15
(2008/12/04)
-
- Synthesis and biological evaluation of novel 2,4-diaminoquinazoline derivatives as SMN2 promoter activators for the potential treatment of spinal muscular atrophy
-
Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord that is caused by deletion and/or mutation of the survival motor neuron gene (SMN1). Adjacent to SMN1 are a variable number of copies of the SMN2 gene. The two genes essentially differ by a single nucleotide, which causes the majority of the RNA transcripts from SMN2 to lack exon 7. Although both SMN1 and SMN2 encode the same Smn protein amino acid sequence, the loss of SMN1 and incorrect splicing of SMN2 have the consequence that Smn protein levels are insufficient for the survival of motor neurons. The therapeutic goal of our medicinal chemistry effort was to identify small-molecule activators of the SMN2 promoter that, by up-regulating gene transcription, would produce greater quantities of full-length Smn protein. Our initial medicinal chemistry effort explored a series of C5 substituted benzyl ether based 2,4-diaminoquinazoline derivatives that were found to be potent activators of the SMN2 promoter; however, inhibition of DHFR was shown to be an off-target activity that was linked to ATP depletion. We used a structure-guided approach to overcome DHFR inhibition while retaining SMN2 promoter activation. A lead compound 11a was identified as having high potency (EC50 = 4 nM) and 2.3-fold induction of the SMN2 promoter. Compound 11a possessed desirable pharmaceutical properties, including excellent brain exposure and long brain half-life following oral dosing to mice. The piperidine compound 11a up-regulated expression of the mouse SMN gene in NSC-34 cells, a mouse motor neuron hybrid cell line. In type 1 SMA patient fibroblasts, compound 11a induced Smn in a dose-dependent manner when analyzed by immunoblotting and increased the number of intranuclear particles called gems. The compound restored gems numbers in type I SMA patient fibroblasts to levels near unaffected genetic carriers of SMA.
- Thurmond, John,Butchbach, Matthew E. R.,Palomo, Marty,Pease, Brian,Rao, Munagala,Bedell, Louis,Keyvan, Monica,Pai, Grace,Mishra, Rama,Haraldsson, Magnus,Andresson, Thorkell,Bragason, Gisli,Thosteinsdottir, Margret,Bjornsson, Jon Mar,Coovert, Daniel D.,Burghes, Arthur H. M.,Gurney, Mark E.,Singh, Jasbir
-
p. 449 - 469
(2008/09/18)
-
- Synthesis of 1-indanones via intramolecular cyclodehydration of 3-arylpropionic acids catalyzed by heteropoly acid as heterogeneous catalyst
-
Intramolecular cyclodehydration of 3-arylpropionic acids catalyzed by heteropoly acids was investigated for the first time. Several 3-arylpropionic acids were refluxed and dehydrated in chlorobenzene in the presence of 0.2 equivalent of heteropoly acids, and 1-indanones were obtained in good yield. At the same time, intermolecular Friedel-Crafts acylation were observed in this experiment. Copyright Taylor & Francis Group, LLC.
- Lan, Kun,Shan, Zi-Xing
-
p. 2171 - 2177
(2008/02/05)
-
- The discovery and synthesis of novel adenosine receptor (A2A) antagonists
-
In high throughput screening of our file compounds, a novel structure 1 was identified as a potent A2A receptor antagonist with no selectivity over the A1 adenosine receptor. The structure-activity relationship investigation using 1 as a template lead to identification of a novel class of compounds as potent and selective antagonists of A2A adenosine receptor. Compound 26 was identified to be the most potent A2A receptor antagonist (Ki = 0.8 nM) with 100-fold selectivity over the A1 adenosine receptor.
- Matasi, Julius J.,Caldwell, John P.,Hao, Jinsong,Neustadt, Bernard,Arik, Leyla,Foster, Carolyn J.,Lachowicz, Jean,Tulshian, Deen B.
-
p. 1333 - 1336
(2007/10/03)
-
- 2,4-DIAMINOQUINAZOLINES FOR SPINAL MUSCULAR ATROPHY
-
2,4-Diaminoquinazolines of formulae I-IV and VI (I, II, III, IV and VI) are useful for treating spinal muscular atrophy (SMA).
- -
-
-
- TETRAHYDROBENZO[D]AZEPIN-2- ONE DERIVATIVES AND THE USE THEREOF FOR TREATING CARDIOVASCULAR DISEASES
-
The invention concerns novel tetrahydrobenzo[d]azepin-2-one derivatives, a method for the production thereof, their use for treating and/or preventing diseases, and their use for producing medicaments for treating and/or preventing diseases, preferably for treating and/or preventing cardiovascular diseases, particularly dyslipidemias, arteriosclerosis, restenosis and ischemias.
- -
-
Page/Page column 19; 36-37
(2008/06/13)
-
- Tricyclic pyrazoles. Part 1: synthesis and biological evaluation of novel 1,4-dihydroindeno[1,2-c]pyrazol-based ligands for CB1and CB2 cannabinoid receptors.
-
Cannabinoids receptors, cellular elements of the endocannabinoid system, have been the focus of extensive studies because of their potential functional role in several important physiological and pathological processes. To further evaluate the properties of CB receptors, especially CB(1) and CB(2) subtypes, we have designed, using SR141716A as a benchmark, a new series of rigid 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides. Compounds 1 were synthesized from substituted 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxylic acids and requisite amines. The various analogues were assayed for binding both to the brain and peripheral cannabinoid receptors (CB(1) and CB(2)). Seven of the new compounds displayed very high in vitro CB(2) binding affinities, especially 1a, 1b, 1c, 1e, 1g, 1h and 1j which showed K(i) values of 0.34, 0.225, 0.27, 0.23, 0.385, 0.037 and 0.9 nM, respectively. Compounds 1a, 1b, 1c and 1h showed the highest selectivity for CB(2) receptor with K(i)(CB(1)) to K(i)(CB(2)) ratios of 6029, 5635, 5814 and 9810, respectively. Noticeably, 1h exhibited the highest affinity and selectivity for CB(2) receptors.
- Mussinu, Jean Mario,Ruiu, Stefania,Mule, Antonio C,Pau, Amedeo,Carai, Mauro A M,Loriga, Giovanni,Murineddu, Gabriele,Pinna, Gerard A
-
p. 251 - 263
(2007/10/03)
-
- Indanylidenes. 1. Design and synthesis of (E)-2-(4,6-difluoro-1-indanylidene)acetamide, a potent, centrally acting muscle relaxant with antiinflammatory and analgesic activity
-
The design of rigid cyclic analogues derived from cinnamamide 1, (E)-N-cyclopropyl-3-(3-fluorophenyl)prop-2-enamide, and β-methylcinnamamide 2, (E)-N-cyclopropyl-3-(3-fluorophenyl)but-2-enamide, has led to the discovery of the potent, centrally acting muscle relaxant (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 17. Compound 17 also possesses potent antiinflammatory and analgesic activity. This paper describes the synthesis and the muscle relaxant, antiinflammatory, and analgesic structure-activity relationships of 17 and 67 of its analogues. Compound 17 has been taken into phase I clinical trials.
- Musso, David L.,Cochran, Felicia R.,Kelley, James L.,McLean, Ed W.,Selph, Jeffrey L.,Rigdon, Greg C.,Orr, G. Faye,Davis, Ronda G.,Cooper, Barrett R.,Styles, Virgil L.,Thompson, James B.,Hall, William R.
-
p. 399 - 408
(2007/10/03)
-
- Synthesis and Na+/H+ exchange inhibitory activity of indanylideneacetylguanidines
-
Synthesis of indanylideneacetylguadines 7a-i and their corresponding reduced compounds 8a-e has been achieved and their Na+/H+ exchange inhibitory activity evaluated. All the compounds studied exhibit significant inhibition of Na+/H+ exchanger activity. Promising activity is shown by compounds 7g, 8b and 8d. From the structure activity analysis, it appears that reduction of exocyclic double bond is associated with a marked increase in inhibitory activity.
- Ramakrishna,Jain,Ghate,Gupte,Vadlamudi
-
p. 407 - 412
(2007/10/03)
-
- Rhodium Complex-Catalyzed Desilylative Cyclocarbonylation of 1-Aryl-2-(trimethylsilyl)acetylenes: A New Route to 2,3-Dihydro-1H-inden-1-ones
-
Under water gas shift reaction conditions, 1-aryl-2-(trimethylsilyl)acetylenes undergo Rh-catalyzed desilylative cyclocarbonylation to give 2,3-dihydro-1H-inden-1-ones and trimethylsilanol.A wide variety of functional groups, such as methoxy, chloro, acetyl, ethoxycarbonyl, cyano, and trifluoromethyl, are tolerated on the aromatic ring under the reaction conditions.The products were obtained in good to excellent yield whether the substituent on the aromatic ring was electron-donating or electron-withdrawing.The cyclizations of substrates bearing a meta substituent onthe aromatic ring regiospecifically gave 5-substituted-2,3-dihydro-1H-inden-1-ones except when the meta substituent was a methoxy group.The desilylative cyclocarbonylation is an alternative to the conventional preparation of 2,3-dihydro-1H-inden-1-ones, an intramolecular Friedel-Crafts acylation.A possible mechanism for the process is described.
- Takeuchi, Ryo,Yasue, Hiroyuki
-
p. 5386 - 5392
(2007/10/02)
-