- A Highly Efficient NHC-Catalyzed Aerobic Oxidation of Aldehydes to Carboxylic Acids
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An N-heterocyclic carbene (NHC) organocatalytic aerobic oxidation of aldehydes to the corresponding carboxylic acids is explored. Remarkably, this method allows for efficient conversion of different classes of aldehydes including highly challenging electron-rich aryl aldehydes, ortho -substituted aryl aldehydes, various heteroaromatic aldehydes and α,β-unsaturated aldehydes under mild reaction conditions. These substrates, under previously reported NHC-catalyzed methods, are typically unreactive or give poor yields, require high reaction temperatures and reaction times of several days.
- Khatana, Anil Kumar,Singh, Vikram,Gupta, Manoj Kumar,Tiwari, Bhoopendra
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p. 4290 - 4294
(2018/11/23)
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- Design, synthesis and structure–activity relationship studies of novel free fatty acid receptor 1 agonists bearing amide linker
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The free fatty acid receptor 1 (FFA1/GPR40) has attracted extensive attention as a novel antidiabetic target. Aiming to explore the chemical space of FFA1 agonists, a new series of lead compounds with amide linker were designed and synthesized by combining the scaffolds of NIH screened lead compound 1 and GW9508. Among them, the optimal lead compound 17 exhibited a considerable agonistic activity (45.78%) compared to the NIH screened compound 1 (15.32%). During OGTT in normal mice, the compound 17 revealed a significant glucose-lowering effect (?23.7%) at the dose of 50?mg/kg, proximity to the hypoglycemic effect (?27.8%) of Metformin (200?mg/kg). In addition, the compound 17 (100?mg/kg) also exhibited a significant improvement in glucose tolerance with a 29.1% reduction of glucose AUC0–2?h in type 2 diabetic mice. All of these results indicated that compound 17 was considered to be a promising lead structure suitable for further optimization.
- Yang, Jianyong,Li, Zheng,Li, Huilan,Liu, Chunxia,Wang, Nasi,Shi, Wei,Liao, Chen,Cai, Xingguang,Huang, Wenlong,Qian, Hai
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supporting information
p. 2445 - 2450
(2017/04/03)
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- Pd-Catalyzed β-C(sp3)?H Arylation of Propionic Acid and Related Aliphatic Acids
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A generally applicable Pd-catalyzed protocol for the β-C(sp3)?H arylation of propionic acid and related α-branched aliphatic acids is reported. Enabled by the use of N-acetyl-β-alanine as ligand our protocol delivers a broad range of arylation products. Notably, the highly challenging substrate, propionic acid, which lacks any acceleration through the Thorpe–Ingold effect, can be employed as substrate with synthetically useful yields. Furthermore, the scalability and synthetic applicability of the protocol are demonstrated.
- Ghosh, Kiron K.,van Gemmeren, Manuel
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supporting information
p. 17697 - 17700
(2017/12/07)
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- Synthesis of isomeric (3,3,3-trifluoropropyl)anilines
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Ortho-, meta- and para-isomers of (3,3,3-trifluoropropyl)aniline have been prepared in 60-70 g amount from the corresponding nitrobenzaldehydes in three steps. The key synthesis step was a transformation of the carboxylic group of 3-(nitrophenyl)propanoic acids into the trifluoromethyl group by SF4.
- Trofymchuk, Sergii,Bezdudny, Andrii,Pustovit, Yurii,Mykhailiuk, Pavel K.
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p. 174 - 176
(2015/03/04)
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- Synthesis of tetrahydronaphthalene lignan esters by intramolecular cyclization of ethyl p-azidophenyl-2-phenylalkanoates and evaluation of the growth inhibition of human tumor cell lines
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Figure Presented. Intramolecular cyclization via nitrenium ion of 2-phenylpentanoic/2-phenylbutanoic acid esters with a terminal p-azidophenyl group gives direct access to tetrahydronaphthalene lignan esters. The p-azidophenyl-substituted butanoate led to
- Pinto, Orlando,Sardinha, Jo?o,Vaz, Pedro D.,Piedade, Fátima,Calhorda, Maria J.,Abramovitch, Rudolph,Nazareth, Nair,Pinto, Madalena,Nascimento, Maria S. J.,Rauter, Amélia P.
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experimental part
p. 3175 - 3187
(2011/07/30)
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- 2,4,5-TRISUBSTITUTED THIAZOLE COMPOUNDS,PREPARATION METHODS, PHARMACEUTICAL COMPOSITIONS AND MEDICAL USES THEREOF
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The present invention relates to 2,4,5-trisubstituted thiazole compounds of formula (I) or all possible isomers, prodrugs, pharmaceutically acceptable salts, solvates or hydrates thereof for the inhibition of plasma PLTP activity and/or plasma CETP activity, wherein the substituents are as defined in the specification; a process for the preparation of the compounds of formula (I); a pharmaceutical composition comprising the compound of formula (I) and its use for the preparation of a medicament for treatment and/or prevention of diseases associated with the increased plasma PLTP activity and/or the increased plasma CETP activity in a mammal, such as atherosclerosis, cardiovascular diseases and peripheral vascular diseases, etc.
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Page/Page column 22
(2009/04/23)
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- TRISUBSTITUTED THIAZOLE COMPOUNDS, PREPARATIONS METHODS, PHARMACEUTICAL COMPOSITIONS AND MEDICALS USES THEREOF
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The present invention relates to 2,4,5-trisubstituted thiazole compounds of formula (I) or all possible isomers, prodrugs, pharmaceutically acceptable salts, solvates or hydrates thereof for the inhibition of plasma PLTP activity and/or plasma CETP activity, wherein the substituents are as defined in the specification; a process for the preparation of the compounds of formula (I); a pharmaceutical composition comprising the compound of formula (I) and its use for the preparation of a medicament for treatment and/or prevention of diseases associated with the increased plasma PLTP activity and/or the increased plasma CETP activity in a mammal, such as atherosclerosis, cardiovascular diseases and peripheral vascular diseases, etc.
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Page/Page column 15-16
(2009/12/23)
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- INDANYLAMINO URACILS AND THEIR USE AS ANTIOXIDANTS AND NEUROPROTECTANTS
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Disclosed are compounds having the structure (I) wherein, R1 is H, NH2, NH-(C1-C4) alkyl, or N-[(C1-C4)alkyl]2; R2 and R3 are each independently H, (C1-C4) alkyl, or structure (II), wherein R4 is H, (C1-C4) alkyl, halogen, hydroxy, (C1-C10)alkoxy, cyano, nitro, -NR5R6, or -OCONR7R8; wherein R5 and R6 are each independently H, or a substituted or unsubstituted (C1-C4) alkyl; and wherein R7 and R8 are each independently H, or substituted or unsubstituted (C1-C4) alkyl or (C1-C10)aryl; and wherein only one of R2 and R3 is H, enantiomers, tautomers, and pharmaceutically acceptable salts of the compounds, pharmaceutical compositions containing such compounds or salts, and processes for their preparation. The subject invention also provides methods of alleviating symptoms of neurologic and inflammatory disorders, methods of preventing oxidation of lipids, proteins, or deoxyribonucleic acids on a cellular level, and methods of protecting human red blood cells from lysis by O2 radicals.
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Page/Page column 50
(2008/06/13)
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- A chemoselective hydrogenation of the olefinic bond of α,β- unsaturated carbonyl compounds in aqueous medium under microwave irradiation
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A microwave-assisted mild and ecofriendly catalytic transfer hydrogenation process was developed to reduce various α,β-unsaturated carbonyl compounds into the corresponding saturated carbonyl compounds in the presence of silica-supported palladium chloride as catalyst and a combination of MeOH/HCOOH/H2O (1:2:3) as hydrogen source within 22-55 minutes in moderate to excellent yields with 100% chemoselectivity.
- Sharma, Anuj,Kumar, Vinod,Sinha, Arun K.
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p. 354 - 360
(2007/10/03)
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- Linker arms for nanocrystals and compounds thereof
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A nanocrystal compound comprising: a nanocrystal, and attached thereto a compound of the following formula: n is 0 or an integer from 1 to 48; X and Z are independently O, NH, N—R, S, CH2, CO, COHN, NHCO, SO, SO2NH, NHSO2, carbamate and thio carbamate; R is alkyl or aryl; r is 0 or an integer from 1 to 15; and wherein S is the attachment point to a nanocrystal compound. The nanocrystal compounds of the present invention are useful fluorescent labels.
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- Nitric acid in the presence of P2O5 supported on silica gel - A useful reagent for nitration of aromatic compounds under solvent-free conditions
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A variety of aromatic compounds are nitrated to parent nitro aromatic compounds under solvent-free conditions using 65% nitric acid in the presence of P2O5 supported on silica gel is described. This methodology is useful for nitration of activated and deactivated aromatic rings.
- Hajipour, Abdol Reza,Ruoho, Arnold E.
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p. 8307 - 8310
(2007/10/03)
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- Direct synthesis of 3-arylpropionic acids by tetraphosphine/palladium catalysed Heck reactions of aryl halides with acrolein ethylene acetal
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Through the use of [PdCl(C3H5)]2/Cis,cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of aryl bromides undergoes Heck reaction with acrolein ethylene acetal. With this acetal, the selective formation of 3-arylpropionic acids/esters was observed. The functional group tolerance on the aryl halide is remarkable; substituents such as fluoro, methyl, methoxy, acetyl, formyl, benzoyl, nitro or nitrile are tolerated. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl bromides. Graphical Abstract.
- Lemhadri, Mhamed,Doucet, Henri,Santelli, Maurice
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p. 11533 - 11540
(2007/10/03)
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- A fast and mild method for nitration of aromatic rings
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The use of benzyltriphenylphosphonium nitrate (PhCH2Ph 3P+NO3-) (BTPPN) as a useful reagent for nitration aromatic compounds in the presence of methanesulfonic anhydride under solvent-free conditions is described. This methodology is useful for nitration of activated aromatic rings.
- Hajipour, Abdol R.,Ruoho, Arnold E.
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p. 221 - 226
(2007/10/03)
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- Ring expansion-annulation strategy for the synthesis of substituted azulenes and oligoazulenes. 2. Synthesis of azulenyl halides, sulfonates, and azulenylmetal compounds and their application in transition-metal-mediated coupling reactions
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A "ring expansion-annulation strategy" for the synthesis of substituted azulenes is described based on the reaction of β'-bromo- α-diazo ketones with rhodium carboxylates. The key transformation involves an intramolecular Buechner reaction followed by β-elimination of bromide, tautomerization, and in situ trapping of the resulting 1-hydroxyazulene as a carboxylate or triflate ester. Further synthetic elaboration of the azulenyl halide and sulfonate annulation products can be achieved by employing Heck, Negishi, Stille, and Suzuki coupling reactions. Reaction of the azulenyl triflate 84 with pinacolborane provides access to the azulenylboronate 91, which participates in Suzuki coupling reactions with alkenyl and aryl iodides. The application of these coupling reactions to the synthesis of biazulenes, terazulene 101, and related oligoazulenes is described, as well as the preparation of the azulenyl amino acid derivative 110.
- Crombie, Aimee L.,Kane Jr., John L.,Shea, Kevin M.,Danheiser, Rick L.
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p. 8652 - 8667
(2007/10/03)
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- Synthesis and Cu1+ assisted radiosynthesis of 2-radioiodo phloretinic acid, a potential glut tracer
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2-Bromo-phloretinic acid (2-Br-PLA): 2-bromo-4-(3-oxo-3(2,4,6-trihydroxyphenyl)propyl)benzoic acid, the precursor molecule for the radiosynthesis of 2-radioiodo-phloretinic acid (2-*I-PLA): 2-radioiodo-4-(3-oxo-3(2,4,6-trihydroxyphenyl)propyl)benzoic acid, was prepared by a twelve step synthesis starting from hydrocinnamic acid. The radiosynthesis was carried out by applying the Cu(I)-assisted nucleophilic non-isotopic exchange reaction in acidic reducing medium.
- Mertens, J.,Boumon, R.,Steegmans, P.
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p. S951 - S953
(2007/10/03)
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- A ring expansion-annulation strategy for the synthesis of substituted azulenes. Preparation and suzuki coupling reactions of 1-azulenyl triflates
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(matrix presented) A new strategy for the synthesis of substituted azulenes is reported, based on the reaction of β′-bromo-α-diazo ketones with rhodium carboxylates The key transformation involves intramolecular addition of a rhodium carbenoid to an arene π-bond, electrocyclic ring opening, β-elimination, tautomerization, and trapping to produce 1-hydroxyazulene derivatives. The synthetic utility of the method is enhanced by the ability of the triflate derivatives to participate in Suzuki coupling reactions, as illustrated in a synthesis of the antiulcer drug egualen sodium (KT1-32).
- John L Jr., Kane,Shea, Kevin M.,Crombie, Aimee L.,Danheiser, Rick L.
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p. 1081 - 1084
(2007/10/03)
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- Synthesis and serotonergic activity of substituted 2,N- benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N,N-dimethyltryptamine derivatives: Novel antagonists for the vascular 5-HT(1B)-like receptor
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The synthesis and vascular 5-HT(1B)-like receptor activity of a novel series of substituted 2,N-benzylcarboxamido-5-(2-ethyl-1- dioxoimidazolidinyl)-N,N-dimethyltryptamine derivatives are described. Modifications to the 5-ethylene-linked heterocycle and to substituents on the 2-benzylamide side chain have been explored. Several compounds were identified which exhibited affinity at the vascular 5-HT(1B)-like receptor of pK(B) > 7.0, up to 100-fold selectivity over α1-adrenoceptor affinity and 5-HT(2A) receptor affinity, and which exhibited a favorable pharmacokinetic profile. N-Benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(4,4-dimethyl-2,5-dioxo-1- imidazolidinyl)ethyl]-1H-indole-2-carboxamide (23) was identified as a highly potent, silent (as judged by the inability of angiotensin II to unmask 5- HT(1B)-like receptor-mediated agonist activity in the rabbit femoral artery), and competitive vascular 5-HT(1B)-like receptor antagonist with a plasma elimination half-life of ~4 h in dog plasma and with good oral bioavailability. The selectivity of compounds from this series for the vascular 5-HT(1B)-like receptors over other receptor subtypes is discussed as well as a proposed mode of binding to the receptor pharmacophore. It has been proposed that the aromatic ring of the 2,N-benzylcarboxamide group can occupy an aromatic binding site rather than the indole ring. The resulting conformation allows an amine-binding site to be occupied by the ethylamine nitrogen and a hydrogen-bonding site to be occupied by one of the hydantoin carbonyls. The electronic nature of the 2,N-benzylcarboxamide aromatic group as well as the size of substituents on this aromatic group is crucial for producing potent and selective antagonists. The structural requirement on the 3-ethylamine side chain incorporating the protonatable nitrogen is achieved by the bulky 2,N-benzylcarboxamide group and its close proximity to the 3- side chain.
- Moloney, Gerard P.,Martin, Graeme R.,Mathews, Neil,Milne, Aynsley,Hobbs, Heather,Dodsworth, Susan,Sang, Pang Yih,Knight, Cameron,Williams, Marnie,Maxwell, Miles,Glen, Robert C.
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p. 2504 - 2526
(2007/10/03)
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- Experiments on the Chaperon effect in the nitration of aromatics
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A nitro group may be effectively delivered to the ortho position of alkylbenzenes, provided that a suitable chaperon function is located in α- position and a dilute of HNO3 in CH2Cl2 is used. The carbonyl function of an aldehyde or ketone is the best choice, but a carboxyl, alkoxycarbonyl, and amide groups all work well. The ether function showed a less pronounced ortho orientation effect, whereas the hydroxyl group was too prone to oxidation. Side reactions were minimal under the conditions employed. A para chaperon effect was seemingly at work in the CH2Cl2 nitration of benzenepropanenitrile. All the results were compared with the corresponding classical nitration in H2SO4.
- Strazzolini, Paolo,Giumanini, Angelo G.,Runcio, Antonio,Scuccato, Massimo
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p. 952 - 958
(2007/10/03)
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- Reduction of olefins on solid support using diimide
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The reduction of solid supported olefinic substrate using diimide is described. The diimide, prepared from sulfonylhydrazide, was found to efficiently reduce the olefinic substrates. Typically, the reaction proceeds in over 90% yield to afford the reduction product cleanly after cleavage from the Wang resin.
- Lacombe, Patrick,Castagner, Bastien,Gareau, Yves,Ruel, Rejean
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p. 6785 - 6786
(2007/10/03)
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- Simple, safe, large scale synthesis of 5-arylmethyl-2,2-dimethyl-1,3-dioxane-4,6-diones and 3-aryl-propanoic acids
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Reaction of aryl aldehydes with Meldrum's acid 2 in the presence of formic acid and triethylamine with 5-arylmethyl Meldrum's acid derivatives 4 at room temperature, whereas at 80-100°C 3-arylpropanoic acids 5 are formed.
- Toth,Kover
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p. 3067 - 3074
(2007/10/03)
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- Process for the preparation of carboxylic acids and derivatives of them
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The subject matter of the invention is a process for the preparation of carboxylic acids and derivatives of them of the general formula STR1 wherein R means hydrogen, or a C1-4 alkyl or a (C1-5 alkoxy)carbonyl group, R1 is as defined in claim 1, R7 stands for hydrogen or a C1-7 alkyl group and R8 means hydrogen or a carboxyl group, by reacting a 1,3-dioxane-4,6-dione derivative of the general formula STR2 wherein R9 stands for a C1-4 alkyl group or a phenyl group, optionally monosubstituted by halogen and R10 stands for hydrogen or a C1-5 alkyl group or R9 and R10 together form a pentamethylene group, and an aldehyde or ketone of the general formula STR3 in the presence of formic acid.
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- Process for the preparation of carboxylic acids and derivatives of them
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The subject matter of the invention is a process for the preparation of carboxylic acids and derivatives of them of the general formula wherein Rmeans hydrogen, or a C1 4alkyl or a (C1 5alkoxy)carbonyl group, R1is as defined in claim 1, R7stands for hydrogen or a C1 7alkyl group and R8means hydrogen or a carboxyl group, by reacting a 1,3-dioxane-4,6-dione derivative of the general formula wherein R9stands for a C1 4alkyl group or a phenyl group, optionally monosubstituted by halogen and R10stands for hydrogen or a C1 5alkyl group or R9 and R10together form a pentamethylene group, and an aldehyde or ketone of the general formula in the presence of formic acid and of [a] amine(s) and, if desired, of an alcohol of the general formula, , R7 - OH VI,, , wherein R7is a C1 7alkyl group, at a temperature of 20 to 140°C, and/or, reducing an unsaturated 1,3-dioxane-4,6-dione derivative of the general formula and/or, a 1,3-dioxane-4,6-dione derivative of the general formula with formic acid in the presence of [a] amine(s) and, if desired, of an alcohol as above defined.
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- Electron Spin Resonance Studies. Part 71. Side-chain Oxidation Pathways in the Reactions of .OH and SO4-. with Some Phenyl-substituted Carboxylic Acids, their Anions, and Some related Compounds
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A series of arene radical-cations has been generated in situ by the reactions of methylbenzene, phenylethanoic acid, and some derivatives and cyclic analogues with both SO4-. and .OH (the latter in acid solution).The results are interpreted in terms of a variety of subsequent rapid reactions including hydration, deprotonation (to give benzylic radicals), and fragmentation (decarboxylation: for a series of radical-zwitterions +.Ar(CH2)nCO2- (n=1-3) decarboxylation (k >/= 1E9 dm3 mol-1 s-1) appears to proceed via direct intramolecular elecron-transfer, though in some cases formation of a discrete ?-bonded intermediate cannot be ruled out.
- Gilbert, Bruce C.,Scarratt, Cathryn J.,Thomas, C. Barry,Young, John
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p. 371 - 380
(2007/10/02)
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- Phenylmercaptotetrazolo- and nitroindazolo masked development/image modifiers
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Novel nitrobenzyl compounds are incorporated into a photographic emulsion or developer for controlled release of development/image modifier compounds. This occurs imagewise only after developer oxidation products have been formed in the course of the development process. For example, nitrobenzyl-masked phenylmercaptotetrazole (PMT), incorporated into a silver halide emulsion, reacts with developer oxidation products via an electron transfer mechanism to release the potent development restrainer PMT.
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