- Facile synthesis of 4-substituted 1,2,4,5-tetrahydro-1,4-benzodiazepin-3-ones by reductive cyclization of 2-chloro-N-(2-nitrobenzyl)acetamides
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A facile and efficient method was developed for the synthesis of 1,2,4,5-tetrahydro-1,4-benzodiazepine-3-ones from 2-chloro-N-(2-nitrobenzyl)acetamides through a reductive cyclization using iron-ammonium chloride in ethanol–water in good yields. This method provides a simple approach to these benzodiazepine-3-ones which are of high value in the field of medicinal chemistry research.
- Sasiambarrena, Leandro D.,Barri, Ivan A.,Fraga, Guido G.,Bravo, Rodolfo D.,Ponzinibbio, Agustín
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p. 264 - 267
(2019/01/04)
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- Structure-activity relationship of the cinnamamide family of antibiotic potentiators for methicillin-resistant: Staphylococcus aureus (MRSA)
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Methicillin-resistant Staphylococcus aureus (MRSA) is a global public health threat. MRSA has evolved a complex set of biochemical processes that mobilize the organism for inducible resistance on challenge by β-lactam antibiotics. Interfering pharmacologi
- Speri, Enrico,Fishovitz, Jennifer,Mobashery, Shahriar
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p. 2008 - 2016
(2019/01/04)
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- GLUCURONIDE PRODRUGS OF TOFACITINIB
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The invention relates to glucuronide prodrug compounds of the Janus kinase (JAK) inhibitor tofacitinib having formula (I): (Formula (I)) where A1 and R1 are as defined. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds to treat gastrointestinal inflammatory diseases; and processes and intermediates for preparing such compounds.
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Page/Page column 76
(2018/09/28)
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- GLUCURONIDE PRODRUGS OF JANUS KINASE INHIBITORS
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The invention relates to glucuronide prodrug compounds of Janus kinase (JAK) inhibitors having formula I: where W1, R1 and A1 are as defined. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds to treat gastrointestinal inflammatory diseases; and processes and intermediates for preparing such compounds.
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Paragraph 0416; 0417
(2018/12/11)
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- Stable and Rapid Thiol Bioconjugation by Light-Triggered Thiomaleimide Ring Hydrolysis
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Maleimide-mediated thiol-specific derivatization of biomolecules is one of the most efficacious bioconjugation approaches currently available. Alarmingly, however, recent work demonstrates that the resulting thiomaleimide conjugates are susceptible to breakdown via thiol exchange reactions. Herein, we report a new class of maleimides, namely o-CH2NHiPr phenyl maleimides, that undergo unprecedentedly rapid ring hydrolysis after thiol conjugation to form stable thiol exchange-resistant conjugates. Furthermore, we overcome the problem of low shelf lives of maleimide reagents owing to their propensity to undergo ring hydrolysis prior to bioconjugation by developing a photocaged version of this scaffold that resists ring hydrolysis. UV irradiation of thiol bioconjugates formed with this photocaged maleimide unleashes rapid thiomaleimide ring hydrolysis to yield the desired stable conjugates within 1 h under gentle, ice-cold conditions.
- Kalia, Dimpy,Pawar, Sharad P.,Thopate, Jyoti S.
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supporting information
p. 1885 - 1889
(2017/02/05)
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- Novel chiral bis-phosphoramides as organocatalysts for tetrachlorosilane-mediated reactions
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The formation of novel chiral bidentate phosphoroamides structures able to promote Lewis base-catalyzed Lewis acid-mediated reactions was investigated. Two different classes of phosphoroamides were synthetized: the first class presents a phthalic acid/pri
- Rossi, Sergio,Ziliani, Marco,Annunziata, Rita,Benaglia, Maurizio
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supporting information
(2018/01/12)
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- Quinazolinones, Quinazolinthiones, and Quinazolinimines as Nitric Oxide Synthase Inhibitors: Synthetic Study and Biological Evaluation
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The synthesis of different compounds with a quinazolinone, quinazolinthione, or quinazolinimine skeleton and their in vitro biological evaluation as inhibitors of inducible and neuronal nitric oxide synthase (iNOS and nNOS) isoforms are described. These d
- Camacho, M. Encarnación,Chayah, Mariem,García, M. Esther,Fernández-Sáez, Nerea,Arias, Fabio,Gallo, Miguel A.,Carrión, M. Dora
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p. 638 - 650
(2016/08/27)
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- Sustainable synthesis of diverse privileged heterocycles by palladium-catalyzed aerobic oxidative isocyanide insertion
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Heterocycles containing a guanidine moiety are of great importance in medicinal chemistry (Scheme 1).[1] As a result, several methods for the synthesis of these "privileged scaffolds" have been reported.[2, 3] Classical approaches, such as the addition of diamines to isothiocyanates followed by condensation and the coupling of diamines with cyanogen bromide,[2, 4] have some clear limitations, such as the availability and toxicity of reagents. Moreover, these procedures suffer from poor atom and/or step efficiency, thus making them unattractive from a sustainability point of view.
- Vlaar, Tj?stil,Cioc, Razvan C.,Mampuys, Pieter,Maes, Bert U. W.,Orru, Romano V. A.,Ruijter, Eelco
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supporting information
p. 13058 - 13061
(2013/02/26)
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- Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[ω-(benzylmethylamino)alkoxy]xanthen-9-ones
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In this work, we further investigated a previously introduced class of cholinesterase inhibitors. The removal of the carbamic function from the lead compound xanthostigmine led to a reversible cholinesterase inhibitors 3. Some new 3-[ω-(benzylmethylamino)alkoxy]xanthen-9-one analogs were designed, synthesized, and evaluated for their inhibitory activity against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The length of the alkoxy chain of compound 3 was increased and different substituents were introduced. From the IC50 values, it clearly appears that the carbamic residue is crucial to obtain highly potent AChE inhibitors. On the other hand, peculiarity of these compounds is the high selectivity toward BuChE with respect to AChE, being compound 12 the most selective one (6000-fold). The development of selective BuChE inhibitors may be of great interest to clarify the physiological role of this enzyme and to provide novel therapeutics for various diseases.
- Piazzi, Lorna,Belluti, Federica,Bisi, Alessandra,Gobbi, Silvia,Rizzo, Stefano,Bartolini, Manuela,Andrisano, Vincenza,Recanatini, Maurizio,Rampa, Angela
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p. 575 - 585
(2008/03/12)
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- One-pot synthesis and hydroxylaminolysis of asymmetrical acyclic nitrones
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Aromatic aldehydes 1 were reductively aminated to the corresponding secondary amines 2 using NaBH4 in methanol in good yields. Amines 2 were oxidized with H2O2-WO42- regioselectively to nitrones 3, the structures of which were easily determined by reacting them with hydroxylamine hydrochloride as well as by spectral means. The products of hydroxylaminolysis in ether proved to be the corresponding benzaldehyde oximes 4 and benzyl or methyl hydroxylamine hydrochlorides 5. Copyright Taylor & Francis, Inc.
- Coskun, Necdet,Parlar, Aydin
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p. 2445 - 2451
(2007/10/03)
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- The development of a manufacturing route for the GPIIb/IIIa receptor antagonist SB-214857-A. Part 1: Synthesis of the key intermediate 2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid methyl ester, SB-235349
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The development of an efficient manufacturing route to 2,3,4,5-tetrahydro-4-methyl-3-Oxo-1H-1,4-benzodiazepine-2-acetic acid methyl ester SB-235349, a key intermediate in the synthesis of lotrafiban is described. The synthesis starts with 2-nitrobenzyl alcohol which is mesylated, reacted with methylamine and then dimethylacetylene dicarboxylate followed by reduction of the nitro group. Treatment of the resultant aniline with acid gives an intermediate quinazoline which rearranges on treatment with base to give a 1,4-benzodiazapine. Reduction of the exocyclic double bond affords SB-235349. The process can be run without isolation of any of the intermediates and has been used to prepare several tons of SB-235349.
- Andrews, Ian P.,Atkins, Richard J.,Breen, Gary F.,Carey, John S.,Forth, Michael A.,Morgan, David O.,Shamji, Amin,Share, Andrew C.,Smith, Stephen A. C.,Walsgrove, Timothy C.,Wells, Andrew S.
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p. 655 - 662
(2013/09/05)
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- Highly stereoselective Friedel-Crafts type cyclization. Facile access to enantiopure 1,4-dihydro-4-phenyl isoquinolinones
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The present report describes a stereoselective synthesis of 1,4-dihydro-4-phenyl isoquinolinones 5 based on a stereoselective Friedel-Crafts type cyclization. Cyclization precursors 1 were prepared in two steps, from the readily available (S)-mandelic acid, in 60-80% overall yield. The stereoselective electrophilic cyclization was accomplished in 20-86% yield and with 20-97% ee. In the course of this work, the presence of the amide carbonyl was found to be particularly important to guarantee a stereospecific process during the electrophilic aromatic substitution.
- Philippe, Nicolas,Denivet, Fran?ois,Vasse, Jean-Luc,Sopkova-De Olivera Santos, Jana,Levacher, Vincent,Dupas, Georges
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p. 8049 - 8056
(2007/10/03)
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- A new synthesis of the GPIIb/IIIa receptor antagonist SB-214857-A
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A new synthesis of lotrafiban SB-214857-A is reported. The key steps are the preparation of racemic (4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-2-yl)-acetic acid methyl ester from 2-nitrobenzyl alcohol, a resolution using an immobilised li
- Andrews, Ian P,Atkins, Richard J,Badham, Neil F,Bellingham, Richard K,Breen, Gary F,Carey, John S,Etridge, Stephen K,Hayes, Jerome F,Hussain, Nigel,Morgan, David O,Share, Andrew C,Smith, Stephen A.C,Walsgrove, Timothy C,Wells, Andrew S
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p. 4915 - 4917
(2007/10/03)
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- POTENTIAL CNS ACTIVE 1-ARYL-2-AMINO-1-ETHANOL DERIVATIVES
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New N-(picolyl)-2-(methylamino)-1-aryl-1-ethanols (I) and their O-acyl derivatives (II) were synthesized.Their dopaminomimetic and antidepressant biological activities were examined and compared with the activities of N-(2-aminobenzyl)-2-(methylamino)-1-aryl-1-ethanols (III).It was established that in the reaction of N- methylamine (2) and styryl oxide, the two directions of the splitting of the epoxide ring give rise to two different products that were isolated and identified in the form of their O-acetyl derivatives (13 and 15, respectively).
- Zara-Kaczian, Erzsebet,Deak, Gyula,Gyoergy, Lajos
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p. 441 - 454
(2007/10/02)
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- Oxidations with Cerium(IV) Sulfate: Intramolecular Cyclization of N-Benzyl-&β-aminoketones Yielding 4-Benzoyl-1,2,3,4-tetrahydroisoquinolines
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Preparation and regiospecific cerium(IV) sulfate of the substituted N-benzyl-β-aminoketones 3 are described. 4-Benzoyl-1,2,3,4-tetrahydroisoquinolines 4 so obtained are reduced by sodium borohydride.
- Holzgrabe, Ulrike
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p. 647 - 654
(2007/10/02)
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