cas 4160-80-9, Glutaric anhydride | Articles data

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Prochiral Recognition in the Reaction of 3-Substituted Glutaric Anhydrides with Chiral Secondary Alcohols
The scope of a previously-reported process for the desymmetrization 3-substituted glutaric anhydrides has been investigated.Thus, prochiral anhydrides 5-9 react with 1-(1'-naphthyl)ethanol (2) to give glutaric acid half-esters, which are esterified by treatment with diazomethane to obtaine the corresponding diesters 16-20.The degree of prochiral recognition is inversely related to the steric bulk of the stereodifferentiating group, which the series TBDMSO, Me, Et, Ph, i-Pr, and t-Bu giving ratios of 40:1, 16:1, 14:1, 8:1, 7:1, and 1:3, respectively.The absolute sense of the prochiral recognition was established by conversion of two of the diesters, 16a and 18a, into 3-substituted valerolactones (22a, 22c) of known absolute configuration.
Theisen, Peter D.,Heathcock, Clayton H.
p. 142 - 146
(1993)
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An NMR method for determination of configuration of β-substituted carboxylic acids
The absolute configuration of the stereogenic center at the β-position of a carboxylic acid can be determined via derivatization with chiral benzylic amines [PhCH(Me)NH2 or 1-NpCH(Me)NH2]. Acids of known configuration and with a variety of β-substituents were subjected to derivatization. Analysis of the signs of the chemical shift differences of substituent protons permits determination of the absolute configuration. (C) 2000 Elsevier Science Ltd.
Hoye, Thomas R.,Hamad, Abdel-Sattar S.,Koltun, Dmitry O.,Tennakoon, Manomi A.
p. 2289 - 2293
(2000)
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Novel amide derivatives of 3-phenylglutaric acid as potent soluble epoxide hydrolase inhibitors
Abstract: Soluble epoxide hydrolase (sEH) enzyme plays an important role in the metabolism of endogenous chemical mediators, epoxyeicosatrienoic acids, which are involved in the regulation of blood pressure and inflammation. According to the pharmacophoric model suggested for sEH inhibitors, some new amide-based derivatives of 3-phenylglutaric acid were designed, synthesized and biologically evaluated. Docking study illustrated that the amide group as a primary pharmacophore had a suitable distance from the three amino acids of Tyr383, Tyr466 and Asp335 for effective hydrogen binding. Most of the compounds showed moderate to high sEH inhibitory activities in in vitro test in comparison with 12-(3-Adamantan-1-yl-ureido)-dodecanoic acid, as a potent urea-based sEH inhibitor. Compound 6o with phenethyl in R position exhibited the highest activity with IC50 value of 0.5?nM. Graphic abstract: In this study, some new amide-based derivatives of 3-phenylglutaric acid were designed, synthesized and biologically evaluated. Most of the synthesized compounds provided nanomolar range inhibition against sEH enzyme. The best observed IC50 value was 0.5?nM. Incorporating a carboxylic moiety into these structures by forming carboxylate salts would increase the solubility and improving physicochemical properties.[Figure not available: see fulltext.]
Rezaee, Elham,Amrolah, Somayeh Minaei,Nazari, Maryam,Tabatabai, Sayyed Abbas
p. 45 - 53
(2020/01/03)

Glycinamide derivative as well as preparation method and application thereof
The invention discloses a glycinamide derivative as well as a preparation method and application thereof. The derivative with a structural formula as shown in the following formula (I) is provided; and in the formula, R1 is selected from Cl and H, R2 is one selected from H, CH3 and CH2CH3; and X is one selected from NHCH3, NHCH2CH3, N (CH2CH3) 2, a pyrrolyl group and a piperidyl group. During preparation, different phenyl glutaric acid compounds are selected as raw materials and are respectively subjected to amidation reaction twice with an aminoindane hydrochloride derivative and an ethylenediamine derivative to obtain a target derivative. The prepared derivative or the pharmaceutically acceptable salt thereof, or the pharmaceutical composition thereof can be used as an S-adenosyl homocysteine hydrolase inhibitor for the development of antitumor drugs .
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Paragraph 0013; 0053-0056; 0057-0058; 0059-0060; 0061; ...

(2021/06/12)

Carboxylative Cyclization of 2-Butenoates with Carbon Dioxide: Access to Glutaconic Anhydrides
Cyclic anhydrides are versatile synthons and functional comonomers. Herein, we reported an organic base-promoted carboxylative cyclization of 2-butenoates with carbon dioxide to produce important glutaconic anhydrides in good yields. This metal-free react
Zhang, Ke,Zhang, Wen-Zhen,Tao, Xue-Yan,Zhang, Min,Ren, Wei-Min,Lu, Xiao-Bing
p. 11579 - 11588
(2020/10/12)

TRICYCLIC MODULATORS OF TNF SIGNALING
The invention provides tricyclic heterocyclic compounds, pharmaceutically acceptable salts, prodrugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variables are defined herein. The compounds of the invention may be useful for treating immunological and oncological conditions.
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(2016/11/02)

Enantioselective Desymmetrization of Glutarimides Catalyzed by Oxazaborolidines Derived from cis-1-Amino-indan-2-ol
Enantioselective reductive desymmetrization of glutarimides has been achieved employing an oxazaborolidine catalyst derived from cis-1-amino-indan-2-ol. The reaction was found to proceed through a stereoablative process that upgraded the enantioselectivity of an intermediate hydroxy-lactam. The reaction was generally tolerant of a number of substituents in the 4-position, giving enantiomeric excesses of greater than 82%.
Kutama, Ibrahim U.,Jones, Simon
p. 11468 - 11479
(2015/12/04)

Synthesis and biological evaluation of pentanedioic acid derivatives as farnesyltransferase inhibitors
Structure-based virtual screening of a commercial library identified pentanedioic acid derivatives (6 and 13b) as a kind of novel scaffold farnesyltransferase inhibitors (FTIs). Chemical modifications of the lead compounds, biological assays and analysis of the structure-activity relationships (SAR) were conducted to discover more potent FTIs. Some of them displayed excellent inhibition against FTase, and among them, the most active compound 13n with an IC50 value of 0.0029 μM and SAR analysis might be helpful to the discovery of more potent FTIs. This journal is
Yang, Liuqing,Liu, Wei,Mei, Hanbing,Zhang, Yuan,Yu, Xiaojuan,Xu, Yufang,Li, Honglin,Huang, Jin,Zhao, Zhenjiang
supporting information
p. 671 - 676
(2015/04/27)

ALLOSTERIC PROTEIN KINASE MODULATORS
The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.
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(2012/03/10)

METHOD FOR PRODUCING CARBOXYLIC ANHYDRIDE AND ARYLBORONIC ACID COMPOUND
When phthalic acid is heated in heptane under azeotropic reflux conditions in the presence of a catalytic amount of an arylboronic acid compound (such as 2,6-(diisopropylaminomethyl)phenylboronic acid or 2,6-bis(diisopropylaminomethyl)phenylboronic acid), phthalic anhydride is obtained in high yield.
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(2012/01/13)

Bronsted base-assisted boronic acid catalysis for the dehydrative intramolecular condensation of dicarboxylic acids
Bronsted base-assisted boronic acid catalysis for the dehydrative self-condensation of carboxylic acids is described. Arylboronic acid bearing bulky (N,N-dialkylamino)methyl groups at the 2,6-positions can catalyze the intramolecular dehydrative condensation of di-and tetracarboxylic acids. This is the first successful method for the catalytic dehydrative self-condensation of carboxylic acids.(Figure Presented)
Sakakura, Akira,Ohkubo, Takuro,Yamashita, Risa,Akakura, Matsujiro,Ishihara, Kazuaki
scheme or table
p. 892 - 895
(2011/05/02)

Highly enantioselective hydrogenative desymmetrization of bicyclic imides leading to multiply functionalized chiral cyclic compounds
Highly enantioselective hydrogenative desymmetrization of bicyclic imides has been developed with chiral CpRu(PN) catalysts. The present hydrogenation directly provides stereochemically well-defined cyclic compounds with excellent enantiomeric exessses, which might otherwise require a detour to reach.
Ito, Masato,Kobayashi, Chika,Himizu, Akio,Ikariya, Takao
supporting information; experimental part
p. 11414 - 11415
(2010/10/03)

ALLOSTERIC PROTEIN KINASE MODULATORS
The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.
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Page/Page column 53-54

(2010/04/30)

Highly enantioselective desymmetrizations of meso-anhydrides
Readily available, low molecular cyclohexane-based organocatalysts promote highly enantioselective desymmetrizations of cyclic meso-anhydrides applying alcohols and benzyl mercaptan as nucleophiles. Both succinic and glutaric anhydrides furnished the corresponding products with up to 96% ee in mostly quantitative yields.
Schmitt, Ellen,Schiffers, Ingo,Bolm, Carsten
experimental part
p. 6349 - 6357
(2010/10/03)

Enantioselective alcoholysis of meso-glutaric anhydrides catalyzed by Cinchona-based sulfonamide catalysts
The bifunctional Cinchona-based sulfonamide catalysts showed the highest levels of enantioselectivity reported to date in the alcoholytic desymmetrization of meioglutaric anhydrides. Density functional theory (DFT) computational studies provide detailed insight into the observed sense of enantioselectivity. Moreover, detailed experimental studies and single crystal X-ray analysis confirmed that these bifunctional organocatalysts 3 do not form Hbonded self-aggregates in both solution and solid state. The synthetic utility of this methodology was also demonstrated in the synthesis of pharmaceutically important γ-amino acids, such as (S)-pregabalin. Of the many asymmetric syntheses of enantiomerically pure (S)-pregabalin reported to date, our synthesis requires the least number of and the simplest steps.
Park, Sang Eun,Nam, Eun Hye,Jang, Hyeong Bin,Oh, Joong Suk,Some, Surajit,Lee, Yong Seop,Song, Choong Eui
supporting information; experimental part
p. 2211 - 2217
(2010/11/19)

A polymer-supported Cinchona-based bifunctional sulfonamide catalyst: A highly enantioselective, recyclable heterogeneous organocatalyst
The design, synthesis, and catalytic application of a highly enantioselective and indefinitely stable polymer-supported Cinchona-based bifunctional sulfonamide is reported.
Youk, Sung Hun,Oh, Sang Ho,Rho, Ho Sik,Lee, Je Eun,Lee, Ji Woong,Song, Choong Eui
supporting information; experimental part
p. 2220 - 2222
(2009/09/06)

A one-pot synthesis of 3-arylglutaric anhydrides by reaction of ketene with aromatic aldehydes and ketones
Aromatic aldehydes and ketones react with ketene under Lewis acid catalysis to produce β-lactones, which in situ react with another molecule of ketene to produce 3-arylglutaric anhydrides. The mechanism, scope, and limitation of this one-pot synthesis of 3-substituted glutaric anhydrides are discussed.
Matsunaga, Hirokazu,Ikeda, Kiyoshi,Iwamoto, Ken-ichi,Suzuki, Yumiko,Sato, Masayuki
experimental part
p. 2334 - 2336
(2009/09/06)

Highly enantioselective desymmetrization of meso anhydrides by a bifunctional thiourea-based organocatalyst at low catalyst loadings and room temperature
(Chemical Equation Presented) Bifunctional (thio)urea-based cinchona alkaloid derivatives have been shown to promote highly efficient enantioselective desymmetrization reactions of meso anhydrides. The most selective of these catalysts is capable of the enantioselective methanolysis of succinic and glutaric anhydride derivatives to form hemiester products with >90% yield and enantiomeric excess at 1 mol % loading and ambient temperature.
Peschiulli, Aldo,Gun'ko, Yurii,Connon, Stephen J.
p. 2454 - 2457
(2008/09/19)

Highly efficient nickel-catalyzed cross-coupling of succinic and glutaric anhydrides with organozinc reagents
A nickel-catalyzed alkylation of succinic and glutaric anhydrides with alkyl- and arylzinc reagents has been developed. A dramatic olefin effect has been investigated resulting in the identification of several styrene-based promoters which show pronounced enhancements in reaction rate. The substrate scope with respect to electrophilic and nucleophilic coupling partners has been examined and found to be remarkably broad, allowing for rapid introduction of molecular complexity through the use of functionalized coupling partners. Regioselective alkylation of an unsymmetrical succinic anhydride and a profound effect of pendent coordinating olefins on reaction rate suggest a mechanism involving discrete oxidative addition of the nickel complex into the cyclic anhydride followed by a transmetalation event.
Bercot, Eric A.,Rovis, Tomislav
p. 247 - 254
(2007/10/03)

Enzymatic desymmetrization of 3-arylglutaric acid anhydrides
Optically active (R)- and (S)-3-arylglutaric acid monoesters 3 were synthesized in quantitative yields and good stereoselectivities by lipase-catalyzed desymmetrization of the corresponding 3-arylglutaric anhydrides 2 with alcohols. It was observed that the stereochemical outcome of the reaction was influenced by the substituents present on the aromatic ring. The influence of the enzyme, alcohol, and solvent was systematically examined. Absolute configurations of the monoesters 3 were assigned by chemical correlation to corresponding lactones 4.
Fryszkowska, Anna,Komar, Marta,Koszelewski, Dominik,Ostaszewski, Ryszard
p. 2475 - 2485
(2007/10/03)

BENZO-FUSED 5-MEMBERED HETROCYCLE COMPOUNDS,PROCESS FOR PREPARATION OF THE SAME, AND USE THEREOF
A compound represented by the formula: (wherein, R1 and R2 are the same or different and each represents a hydrogen atom, hydrocarbon group or heterocyclic group, or R1 and R2 may form, together with the adjacent carbon atom, a 3-8 membered iso- or heterocyclic group, R3 represents a cyclic group, a hydroxy group, a mercapto group that may have oxo, or an amino group, R4 represents a hydrogen atom, a hydrocarbon group, a hydroxy group, a mercapto group which may have oxo, or an amino group, or R2 and R4 may link together to form a double bond, X represents a bond or a linear hydrocarbon group, W represents an oxygen atom or a sulfur atom, ring B represents a 5-8 membered nitrogen-containing heterocyclic group, ring C represents a benzene ring, and --- represents a single bond or a double bond), or a salt or a prodrug thereof that has excellent neurodegenerative inhibitory activity and brain penetrability, and is useful as an agent for preventing/treating neurodegenerative diseases.
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(2010/02/06)

Discovery of Novel 2,8-Diazaspiro[4.5]decanes as Orally Active Glycoprotein IIb-IIIa Antagonists
In our efforts to develop orally active GPIIb-IIIa antagonists with improved pharmaceutical properties, we have utilized a novel 2,8-diazaspiro[4.5]decane scaffold as a template. We describe here our investigation of a variety of templates including spiropiperidinyl-γ -lactams, spiropiperidinylimide, spiropiperidinylureas, and spiropiperidinylhydantoins. With the appropriate acidic and basic pharmacophores in place, each template yielded analogues with potent GPIIb-IIIa inhibitory activity. One of the compounds, 59 (CT50787), was also used to demonstrate for the first time the use of a pharmacological agent which is αIIbβ3 specific to display biological activity in a lower species such as mouse and to extend bleeding times. Evaluation of the pharmacokinetic properties of selected compounds from each series in rat, dog, and cynomolgus monkey has led to the identification of 22 (CT51464), a double prodrug, with excellent pharmacokinetic properties. It exhibited good pharmacokinetic profile across species (F% = 33 (Cyno), 73 (dog), 22 (rat); t1/2β = 14. 2 h (Cyno), 8.97 h (dog), 1.81 h (rat)). The biologically active form, 23 (CT50728), displayed inhibition of platelet aggregation in platelet rich plasma (PRP) with an IC50 value of 53 nM in citrate buffer, 110 nM in PPACK anticoagulated PRP, and 4 nM in solid-phase GPIIb-IIIa competition binding assay (ELISA). Both 23 and 22 were stable in human liver microsomes, did not inhibit the P450 3A4 isozyme, and had low protein binding (18.22% for 23) and a desirable log P (0.45 ± 0.06 for 22, and -0.91 ± 0.32 for 23). It is predicted that the high oral bioavailability for these compounds in multiple species should translate into lower intra- and intersubject variability in man. The long plasma half-life of the lead is consistent with once or twice daily administration for chronic therapy. Analogue 22 (CT51464) thus appears to be a promising oral GPIIb-IIIa inhibitor with significantly improved pharmacokinetic properties over the previously described clinical candidates and may be found useful in the treatment of arterial occlusive disorders.
Mehrotra, Mukund M.,Heath, Julie A.,Smyth, Mark S.,Pandey, Anjali,Rose, Jack W.,Seroogy, Joseph M.,Volkots, Deborah L.,Nannizzi-Alaimo, Lisa,Park, Gary L.,Lambing, Joseph L.,Hollenbach, Stanley J.,Scarborough, Robert M.
p. 2037 - 2061
(2007/10/03)

Diacylhydrazine derivatives
Diacylhydrazine derivatives of general formula (I) wherein X, Y, Z, R1,2and R3are as defined herein, and their physiologically acceptable salts or solvates thereof, are integrin inhibitors and can be used to combat thromboses, myocardial infarcts, coronary cardiac diseases, arteriosclerosis, inflammations, tumors, osteoporosis, infections, and restenosis following angioplasty or during pathological processes that are maintained or propagated by angiogenesis.
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(2008/06/13)

Solid-phase synthesis of a nonpeptide RGD mimetic library: New selective αvβ3 integrin antagonists
The solid-phase synthesis of a low molecular weight RGD mimetic library is described. Activities of the compounds in inhibiting the interaction of ligands, vitronectin and fibrinogen, with isolated immobilized integrins αvβ3 and αIIbβ3 were determined in a screening assay. Highly active and selective nonpeptide αvβ3 integrin antagonists with regard to orally bioavailability were developed, based on the aza-glycine containing lead compound 1. An important variation is the substitution of the aspartic amide of 1 by an aromatic residue. Furthermore, different guanidine mimetics have been incorporated to improve the pharmacokinetic profile. Exchange of the β-amino acid NH by a methylene moiety in one set of RGD mimetics leads to the azacarba analogue compounds representing a novel peptidomimetic approach, which should increase the metabolic stability.
Sulyok,Gibson,Goodman,H?lzemann,Wiesner,Kessler
p. 1938 - 1950
(2007/10/03)

Asymmetric syntheses of trans-3,4-disubstituted 2-piperidinones and piperidines
A convenient and practical method for the preparation of chiral 4-aryl-2-piperidinone from 3-arylglutaric anhydride and (S)-methylbenzylamine is described. Acylation or alkylation at the α-carbon of the chiral 4-aryl-2-piperidinone product afforded chiral trans-3,4-disubstituted 2-piperidinone derivatives and reduction of the chiral 2-piperidinones with lithium aluminum hydride provided the corresponding enantiomerically pure trans-3,4-disubstituted piperidines. This methodology has been successfully applied to the synthesis of the anti-depressant paroxetine.
Liu, Lee Tai,Hong, Pao-Chiung,Huang, Hsiang-Ling,Chen, Shyh-Fong,Wang, Chia-Lin Jeff,Wen, Yuh-Sheng
p. 419 - 426
(2007/10/03)

Folding strain stereocontrol in cyclohexane ring formation by means of an intramolecular ester enolate alkylation reaction
Diastereoselectivity in the cyclization of ethyl 7-bromo-2-methylheptanoates with an additional substituent at various positions in the chain, by LDA treatment, was investigated in connection with the concept of folding strain stereocontrol. Cyclization of 3-, 4-, and 6-methyl-substituted substrates revealed high selectivity, which demonstrates the prevalence of folding strain stereocontrol and the usefulness of this approach for stereoselective ring construction. In particular, reactions of the latter two substrates resulted in the stereodivergent preparation of diastereomeric 1,3-dimethylcyclohexanecarboxylates. In the case of the 5-methyl-substituted substrate, the selectivity of ring closure was only moderate. 1H and 13C NMR spectroscopic data were useful for determining the conformation of 1-methylcyclohexanecarboxylate derivatives. The origin of the diastereoselectivity was examined through the qualitative comparison of the strain in the diastereomeric folding in the transition state. Various factors that might affect stereoselectivity were examined in the cyclization of 5-substituted substrates to better understand this concept. As predicted, the selectivity increased as the substituent became bulkier: Ph Me ≈ Et ≤ i-Pr t-Bu. The effects of other factors - solvent, base counter cation, and leaving group - on selectivity agree with results predicted from the reactivity-selectivity relationship.
Tokoroyama, Takashi,Kusaka, Hisashi
p. 2487 - 2502
(2007/10/03)

Synthesis and Use of 3-Amino-4-phenyl-2-piperidones and 4-Amino-2-benzazepin-3-ones as Conformationally Restricted Phenylalanine Isosteres in Renin Inhibitors
The design of P2-P3 conformational restrictions in renin inhibitors by the use of renin computer graphic model led to the synthesis of inhibitors containing N-Boc, N-acetyl, and N-phthalyl derivatives of 3(S)-amino-4(R,S)-2-piperidones and 4(S)-amino-2-benzazepinones in place of phenylalanine in the control compound N-acetyl-L-phenylalanyl-N--1-(S)-(cyclohexylmethyl)-2(S)-hydroxy-5-methylhexyl>-L-norleucinamide (32).The piperidone inhibitors were prepared by utilization of the Evans chiral auxilliary to introduce the amino group with enantioselecivity and also to act as a leaving group in an intramolecular cyclization to the piperidone.The most potent inhibitor, 3(S)-(acetylmino)-α(S)-butyl-N--1(S)-(cyclohexylmethyl)-2(S)-hydroxy-5-methylhexyl>-2-oxo-4(R)-phenyl-1-piperidineacetamide (18, IC50 = 21 nM), was 25-fold less potent than the acyclic control 32.Considerable dependence of potency with the size of the P4 derivative was observed as had been expected based on the presynthetic modeling studies.Attempts to rationalize the observed potencies on the basis of further molecular modeling studies suggested that the loss in inhibitor potency was due to the conformational restrictions distorting the 3S center from the geometry present in the putative extended conformation present when the inhibitor is bound within the renin active site.
Laszlo, S. E. de,Bush, B. L.,Doyle, J. J.,Greenlee, W. J.,Hangauer, D. G.,et al.
p. 833 - 846
(2007/10/02)

β-substituted β-phenylpropionyl chymotrypsins. Structural and stereochemical features in stable acyl enzymes
In order to develop effective alternate substrate inhibitors for serine proteases, we have prepared a series of β-substituted β-phenylpropionic acid esters related to some systems known to form stable acyl enzymes with α-chymotrypsin. Some of these compounds were prepared in enantiomerically pure form by asymmetric synthesis. Acyl enzyme species were generated from chymotrypsin by reaction with the active esters, and the progress of deacylation was monitored by the proflavin displacement assay. In some cases, it was possible to distinguish two different deacylation rates that correspond to the two enantiomers. β-Phenylpropionic acyl enzymes with β-substituents that are nonpolar were not especially stable, but a number of the polar derivatives and particularly the acylamino derivatives showed slow rates of deacylation (k(d) less than 0.005 min-1), with three systems showing deacylation enantioselectivities in the range of 500-1500. These results are consistent with a model in which additional stabilization of the acyl enzyme and enantioselectivity in the deacylation process derives from an additional hydrogen bond between the acyl enzyme species (as an acceptor) and the enzyme (as a donor). A number of active site residues that might be involved in this hydrogen bond are discussed.
Reed,Katzenellenbogen
p. 1162 - 1176
(2007/10/02)