- Asymmetric alkynylation/lactamization cascade: An expeditious entry to enantiomerically enriched isoindolinones
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An unprecedented CuI-pybox-diPh-catalyzed highly enantioselective (up to >99% ee) alkynylation/lactamization cascade has been developed as a general catalytic system for the synthesis of diversely substituted isoindolinones of immense biologica
- Bisai, Vishnumaya,Suneja, Arun,Singh, Vinod K.
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- Matrix Studies of the Photolysis of o-Carbomethoxyphenyldiazomethane. Direct Observation of Carbonyl Ylide and Its Photoinduced Valence Tautomerization
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Photoreactions of o-carbomethoxyphenyldiazomethane (1), in Ar matrix at 10 K are studied by means of infrared spectroscopy.Irradiation (>350 nm) of 1 generates the carbonyl ylide, which undergoes the reversible photo-isomerization to the corresponding oxi
- Murata, Shigeru,Ohtawa, Yasuki,Tomioka, Hideo
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- Structural Characterization of the Hydratase-Aldolases, NahE and PhdJ: Implications for the Specificity, Catalysis, and N-Acetylneuraminate Lyase Subgroup of the Aldolase Superfamily
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NahE and PhdJ are bifunctional hydratase-aldolases in bacterial catabolic pathways for naphthalene and phenanthrene, respectively. Bacterial species with these pathways can use polycyclic aromatic hydrocarbons (PAHs) as sole sources of carbon and energy.
- Levieux, Jake A.,Medellin, Brenda,Johnson, William H.,Erwin, Kaci,Li, Wenzong,Johnson, Ingrid A.,Zhang, Yan Jessie,Whitman, Christian P.
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- Ruthenium water oxidation catalysts containing the non-planar tetradentate ligand, biisoquinoline dicarboxylic acid (biqaH2)
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Two ruthenium complexes containing the tetradentate ligand [1,1′-biisoquinoline]-3,3′-dicarboxylic acid, and 4-picoline or 6-bromoisoquinoline as axial ligands have been prepared. The complexes have been fully characterised and initial studies on their potential to function as molecular water oxidation catalysts have been performed. Both complexes catalyse the oxidation of water in acidic media with CeIV as a stoichiometric chemical oxidant, although turnover numbers and turnover frequencies are modest when compared with the closely related Ru-bda and Ru-pda analogues. Barriers for the water nucleophilic attack and intermolecular coupling pathways were obtained from density functional theory calculations and the crucial influence of the ligand framework in determining the most favourable reaction pathway was elucidated from a combined analysis of the theoretical and experimental results.
- Scherrer, Dominik,Schilling, Mauro,Luber, Sandra,Fox, Thomas,Spingler, Bernhard,Alberto, Roger,Richmond, Craig J.
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Read Online
- Studies on isocyanides: synthesis of tetrazolyl-isoindolinones via tandem Ugi four-component condensation/intramolecular amidation
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The Ugi four-component condensation between methyl o-formylbenzoates 1, anilines 2a-c, isocyanides 3, and trimethylsilyl azide (4) afforded the expected Ugi adducts 5a-d, which were cyclized to the title compounds 6a-d upon treatment with sodium ethoxide
- Marcos, Carlos F.,Marcaccini, Stefano,Menchi, Gloria,Pepino, Roberto,Torroba, Tomás
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- Alkyne Aminopalladation/Heck and Suzuki Cascades: An Approach to Tetrasubstituted Enamines
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Alkyne aminopalladation reactions starting from tosylamides are reported. The emerging vinylic Pd species are converted either in an intramolecular Heck reaction with olefinic units or in an intermolecular Suzuki reaction by using boronic acids exhibiting broad functional group tolerance. Tetra(hetero)substituted tosylated enamines are obtained in a simple one-pot process.
- Geffers, Finn J.,Jones, Peter G.,Kurth, Florens R.,Werz, Daniel B.
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supporting information
p. 14846 - 14850
(2021/10/19)
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- Influence of the proton relay spacer on hydrogen electrocatalysis by cobalt hangman porphyrins
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A cobalt hangman porphyrin system with a phenyl spacer between the porphyrin ring and an internal carboxylic acid group as well as its non-hangman analogue were synthesized and utilized for the study of the proton-coupled electron transfer (PCET) kinetics
- Roubelakis, Manolis M.,Bediako, D. Kwabena,Dogutan, Dilek K.,Nocera, Daniel G.
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p. 714 - 723
(2021/06/21)
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- PhIO-Mediated oxidative dethioacetalization/dethioketalization under water-free conditions
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Treatment of thioacetals and thioketals with iodosobenzene in anhydrous DCM conveniently afforded the corresponding carbonyl compounds in high yields under water-free conditions. The mechanistic studies indicate that this dethioacetalization/dethioketalization process does not need water and the oxygen of the carbonyl products comes from the hypervalent iodine reagent.
- Du, Yunfei,Ouyang, Yaxin,Wang, Xi,Wang, Xiaofan,Yu, Zhenyang,Zhao, Bingyue,Zhao, Kang
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- Strategies towards potent trypanocidal drugs: Application of Rh-catalyzed [2?+?2?+?2] cycloadditions, sulfonyl phthalide annulation and nitroalkene reactions for the synthesis of substituted quinones and their evaluation against Trypanosoma cruzi
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Rhodium-catalyzed [2 + 2 + 2] cycloadditions, sulfonyl phthalide annulations and nitroalkene reactions have been employed for the synthesis of 56 quinone-based compounds. These were evaluated against Trypanosoma cruzi, the parasite that causes Chagas disease. The reactions described here are part of a program that aims to utilize modern, versatile and efficient synthetic methods for the one or two step preparation of trypanocidal compounds. We have identified 9 compounds with potent activity against the parasite; 3 of these were 30-fold more potent than benznidazole (Bz), a drug used for the treatment of Chagas disease. This article provides a comprehensive outline of reactions involving over 120 compounds aimed at the discovery of new quinone-based frameworks with activity against T. cruzi.
- Wood, James M.,Satam, Nishikant S.,Almeida, Renata G.,Cristani, Vinicius S.,de Lima, Dênis P.,Dantas-Pereira, Luiza,Salom?o, Kelly,Menna-Barreto, Rubem F.S.,Namboothiri, Irishi N.N.,Bower, John F.,da Silva Júnior, Eufranio N.
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- Cobalt Corroles as Electrocatalysts for Water Oxidation: Strong Effect of Substituents on Catalytic Activity
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Two Co(III) complexes (1Py2 and 2Py2) of new corrole ligands H3L1 (5,15-bis(p-methylcarboxyphenyl)-10-(o-methylcarboxyphenyl)corrole) and H3L2 (5,15-bis(p-nitrophenyl)-10-(o-methylcarboxyphenyl)corrole) with two apical pyridine ligands have been synthesized and thoroughly characterized by cyclic voltammetry, UV-vis-NIR, and EPR spectroscopy, spectroelectrochemistry, single-crystal X-ray diffraction studies, and DFT methods. Complexes 1Py2 and 2Py2 possess much lower oxidation potentials than cobalt(III)-tris-pentafluorophenylcorrole (Co(tpfc)) and similar corroles containing pentafluorophenyl (C6F5) substituents, thus allowing access to high oxidation states of the former metallocorroles using mild chemical oxidants. The spectroscopic (UV-vis-NIR and EPR) and electronic properties of several oxidation states of these complexes have been determined by a combination of the mentioned methods. Complexes 1Py2 and 2Py2 undergo three oxidations within 1.3 V vs FcH+/FcH in MeCN, and we show that both complexes catalyze water oxidation in an MeCN/H2O mixture upon the third oxidation, with kobs (TOF) values of 1.86 s-1 at 1.29 V (1Py2) and 1.67 s-1 at 1.37 V (2Py2). These values are five times higher than previously reported TOF values for C6F5-substituted cobalt(III) corroles, a finding we ascribe to the additional charge in the corrole macrocycle due to the increased oxidation state. This work opens up new possibilities in the study of metallocorrole water oxidation catalysts, particularly by allowing spectroscopic probing of high-oxidation states and showing strong substituent-effects on catalytic activity of the corrole complexes.
- Neuman, Nicolás I.,Albold, Uta,Ferretti, Eleonora,Chandra, Shubhadeep,Steinhauer, Simon,R?ner, Paul,Meyer, Franc,Doctorovich, Fabio,Vaillard, Santiago E.,Sarkar, Biprajit
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supporting information
p. 16622 - 16634
(2020/12/02)
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- New preparation method of 4-aminoindan compound
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The invention relates to a new preparation method of a 4-aminoindan compound. 4-Aminoindan is an important medical intermediate. With carboxybenzaldehyde as an initial raw material, through esterification, condensation, cyclization, reduction elimination, Curtius rearrangement, an amidogen deprotection reaction and a hydrogenation reaction in sequence, the 4-aminoindan is prepared. According to the method, the problems of difficult generation of isomers, difficult separation of substitution products and the like in a traditional method are solved, the whole preparation method is convenient toimplement, the yield is high, and the method has great industrial prospects.
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Paragraph 0011; 0021-0023
(2019/10/01)
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- Chained cyclic dipeptide derivative containing sulfonyl groups and preparation method thereof
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The invention relates to a chained cyclic dipeptide derivative containing sulfonyl groups and a preparation method thereof. A structural formula of the chained cyclic dipeptide derivative containing the sulfonyl groups is shown as follows (please see the
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Paragraph 0037-0039; 0046-0048
(2019/11/12)
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- A General Way to Construct Arene-Fused Seven-Membered Nitrogen Heterocycles
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Imines react with seven-membered cyclic anhydrides (prepared from the corresponding dicarboxylic acids by a recently discovered in-situ cyclodehydration protocol) by the Castagnoli–Cushman reaction pathway to give privileged seven-membered arene-fused nitrogen-heterocyclic compounds with reagent-controlled diversity of the skeleton and peripheral groups.
- Bakulina, Olga,Chizhova, Maria,Dar'in, Dmitry,Krasavin, Mikhail
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supporting information
p. 362 - 371
(2018/01/27)
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- Sterically Shielded, Stabilized Nitrile Imine for Rapid Bioorthogonal Protein Labeling in Live Cells
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In pursuit of fast bioorthogonal reactions, reactive moieties have been increasingly employed for selective labeling of biomolecules in living systems, posing a challenge in attaining reactivity without sacrificing selectivity. To address this challenge, here we report a bioinspired strategy in which molecular shape controls the selectivity of a transient, highly reactive nitrile imine dipole. By tuning the shape of structural pendants attached to the ortho position of the N-aryl ring of diaryltetrazoles-precursors of nitrile imines, we discovered a sterically shielded nitrile imine that favors the 1,3-dipolar cycloaddition over the competing nucleophilic addition. The photogenerated nitrile imine exhibits an extraordinarily long half-life of 102 s in aqueous medium, owing to its unique molecular shape that hinders the approach of a nucleophile as shown by DFT calculations. The utility of this sterically shielded nitrile imine in rapid (~1 min) bioorthogonal labeling of glucagon receptor in live mammalian cells was demonstrated.
- An, Peng,Lewandowski, Tracey M.,Erbay, Tug?e G.,Liu, Peng,Lin, Qing
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supporting information
p. 4860 - 4868
(2018/04/16)
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- Synthesis of chiral isoindolinones via asymmetric propargylation/lactamization cascade
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A Zn-mediated propargylation/lactamization cascade reaction with chiral 2-formylbenzoate derived N-tert-butanesulfinyl imines was realized, which provided a practical and efficient method for the synthesis of chiral isoindolinones. High diastereoselectivities (up to 97:3 dr) and good reaction yields were observed for most examined cases.
- Meng, Jiao-Long,Jiao, Tang-Qian,Chen, Ya-Heng,Fu, Rui,Zhang, Shu-Sheng,Zhao, Qian,Feng, Chen-Guo,Lin, Guo-Qiang
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p. 1564 - 1567
(2018/03/23)
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- An Easy-to-Machine Electrochemical Flow Microreactor: Efficient Synthesis of Isoindolinone and Flow Functionalization
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Flow electrochemistry is an efficient methodology to generate radical intermediates. An electrochemical flow microreactor has been designed and manufactured to improve the efficiency of electrochemical flow reactions. With this device only little or no supporting electrolytes are needed, making processes less costly and enabling easier purification. This is demonstrated by the facile synthesis of amidyl radicals used in intramolecular hydroaminations to produce isoindolinones. The combination with inline mass spectrometry facilitates a much easier combination of chemical steps in a single flow process.
- Folgueiras-Amador, Ana A.,Philipps, Kai,Guilbaud, Sébastien,Poelakker, Jarno,Wirth, Thomas
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supporting information
p. 15446 - 15450
(2017/11/10)
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- Dioxygenation of flavonol catalyzed by Copper(II)complexes supported by carboxylate-containing ligands: Structural and functional models of quercetin 2,4-dioxygenase
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To obtain insights into the role of the carboxylate group of Glu73 in the active site of quercetin 2,4-dioxygenase (2,4-QD), the copper(Icomplexes [CuIILn(AcO)] [1 (Ln = L1), 2 (Ln = L2), 3 (Ln = L3), and 4 (Ln = L4)] supported by a series of carboxylate-containing ligands [L1H = 2-{[bis(pyridin-2-ylmethyl)amino]methyl}benzoic acid L2H = 3-{[bis(pyridin-2-ylmethyl)amino]methyl}benzoic acid, L3H = 2-({bis[2-(pyridin-2-yl)ethyl]amino}methyl)benzoic acid L4H = 3-({bis[2-(pyridin-2-yl)ethyl]amino}methyl)benzoic acid] as well as the ternary CuII flavonolate (fla-) complexes [CuIILn(fla)] [5 (Ln = L1), 6 (Ln = L2), 7 (Ln = L3), and 8 (Ln = L4)] were synthesized and characterized as structural and functional models for the active site of 2,4-QD. The ternary complexes [CuIILn(fla)] showed different reactivities in the dioxygenation of bound flavonolate to benzoic acid, salicylic acid, and N,N-dimethylbenzamide at 75-90 °C (single-turnover reactioin the order 5 >> 7 > 8 ≈ 6. A similar reactivity tendency was found in the catalytic dioxygenation of the substrate flavonol (multiturnover reactioby the binary complexes. The different reactivities of the copper complexes could be attributed to the different Lewis acidities of the copper(Iions induced by the different coordination environments of the ligands. The results will provide important insights into the pivotal catalytic role of the carboxylate group of Glu73 in 2,4-QD.
- Sun, Ying-Ji,Li, Pei,Huang, Qian-Qian,Zhang, Jian-Jun,Itoh, Shinobu
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supporting information
p. 1845 - 1854
(2017/12/06)
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- 6,5-BICYCLIC OCTAHYDROPYRROLOPYRIDINE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to 6,5-bicyclic octahydropyrrolopyridine compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 43; 44
(2016/07/05)
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- METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 34
(2016/06/28)
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- ETHYLDIAMINE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to ethyldiamne compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 44
(2016/07/05)
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- FUSED HETEROARYL DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
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Fused heteroaryl derivative compounds which are antagonists of orexin receptors are provided. The compounds can be used in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. Also provided is a composition which comprises the compound can be use to prevent or treat such diseases in which orexin receptors are involved.
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Page/Page column 35
(2016/07/27)
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- BRIDGED DIAZEPANE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to bridged diazepane compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 41
(2016/06/14)
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- Hauser–Kraus Annulation of Phthalides with Nitroalkenes for the Synthesis of Fused and Spiro Heterocycles
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Hauser–Kraus annulation of sulfonylphthalides with simple conjugated nitroalkenes follows the expected pathway to furnish naphthoquinones in moderate yields. However, a strategic variation of this reaction by employing nitroalkenes bearing an additional nucleophilic site results in [4+4] annulation leading to complex fused and spiro heterocycles in high yields with high selectivity through a cascade process involving Michael addition, Dieckmann cyclization, and a series of eliminations and rearrangements.
- Kumar, Tarun,Satam, Nishikant,Namboothiri, Irishi N. N.
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supporting information
p. 3316 - 3321
(2016/07/26)
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- Five-membered azole heterocyclic compound and its preparation method, pharmaceutical composition and use thereof
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The present invention relates to a five-membered azole heterocycle compound represented by the following general formula (I), a preparation method of the five-membered azole heterocycle compound, a drug composition of the five-membered azole heterocycle compound, and a use of the five-membered azole heterocycle compound in preparation of drugs for prevention or treatment of TGR5-mediated diseases. The formula (I) is represented by the instruction.
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Paragraph 0524; 0525
(2017/02/28)
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- Design, synthesis, and biological evaluation of benzoselenazole-stilbene hybrids as multi-target-directed anti-cancer agents
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To identify novel multi-target-directed drug candidates for the treatment of cancer, a series of benzoselenazole-stilbene hybrids were synthesised by combining the pharmacophores of resveratrol and ebselen. The biological assay indicated that all of the h
- Yan, Jun,Guo, Yueyan,Wang, Yali,Mao, Fei,Huang, Ling,Li, Xingshu
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p. 220 - 229
(2015/03/31)
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- Design, syntheses, and pharmacological characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan analogues as opioid receptor ligands
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A series of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan (NAQ) analogues were synthesized and pharmacologically characterized to study their structure-activity relationship at the mu opioid receptor (MOR). The competition binding assay showed two-atom spacer and aromatic side chain were optimal for MOR selectivity. Meanwhile, substitutions at the 1′- and/or 4′-position of the isoquinoline ring retained or improved MOR selectivity over the kappa opioid receptor while still possessing above 20-fold MOR selectivity over the delta opioid receptor. In contrast, substitutions at the 6′- and/or 7′-position of the isoquinoline ring reduced MOR selectivity as well as MOR efficacy. Among this series of ligands, compound 11 acted as an antagonist when challenged with morphine in warm-water tail immersion assay and produced less significant withdrawal symptoms compared to naltrexone in morphine-pelleted mice. Compound 11 also antagonized the intracellular Ca2+ increase induced by DAMGO. Molecular dynamics simulation studies of 11 in three opioid receptors indicated orientation of the 6′-nitro group varied significantly in the different 'address' domains of the receptors and played a crucial role in the observed binding affinities and selectivity. Collectively, the current findings provide valuable insights for future development of NAQ-based MOR selective ligands.
- Yuan, Yunyun,Zaidi, Saheem A.,Stevens, David L.,Scoggins, Krista L.,Mosier, Philip D.,Kellogg, Glen E.,Dewey, William L.,Selley, Dana E.,Zhang, Yan
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supporting information
p. 1701 - 1715
(2015/03/30)
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- Carboxylic acid compound, and the basic photobase generator containing a photosensitive resin composition
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PROBLEM TO BE SOLVED: To provide a carboxylic acid compound which has excellent reaction efficiency without generating carbon dioxide when generating a base, a base generator and a photosensitive resin composition containing the base generator. SOLU
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Paragraph 0123-0125
(2016/12/16)
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- Enantioselective addition of arylboronic acids to methyl 2-formylbenzoates by using a ruthenium/Me-BIPAM catalyst for synthesis of chiral 3-aryl-isobenzofuranones
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Ruthenium/Me-BIPAM-catalyzed asymmetric addition of arylboronic acids to methyl 2-formylbenzoates afforded chiral 3-aryl-isobenzofuranones. [RuCl2(p-cymene)]2/Me-BIPAM and RuCl2(PPh3)3/Me-BIPAM catalyst systems tolerate a variety of functional groups and give high yields with high enantioselectivities.
- Yohda, Masaaki,Yamamoto, Yasunori
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p. 10874 - 10880
(2015/11/17)
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- Diphosphino-functionalised MCM-41-supported palladium complex: An efficient and recyclable catalyst for the formylation of aryl halides
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The heterogeneous formylation of aryl halides with HCO2Na at atmospheric pressure by carbon monoxide was readily achieved in the presence of the diphosphino-functionalised MCM-41-supported palladium complex in DMF to afford the corresponding aromatic aldehydes in good to excellent yields. This heterogeneous palladium catalyst can be recovered by simple filtration and reused 10 times without any loss of activity.
- Jiang, Jianwen,Wang, Pingping,Cai, Mingzhong
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p. 218 - 222
(2014/05/06)
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- A phosphine-free heterogeneous formylation of aryl halides catalyzed by a thioether-functionalized MCM-41-immobilized palladium complex
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Thioether-functionalized MCM-41-immobilized palladium(II) complex [MCM-41-S-PdCl2] was found to be a highly efficient catalyst for the formylation of aryl iodides or bromides with CO (1 atm) using HCO2Na as a hydrogen source. This phosphine-free heterogeneous palladium complex can be easily recovered by simple filtration and reused for at least 10 consecutive trials without any decreases in activity.
- Hao, Wenyan,Ding, Guodong,Cai, Mingzhong
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- A general catalytic route to isoindolinones and tetrahydroisoquinolines: Application in the synthesis of (±)-crispine A
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An unprecedented highly efficient Lewis acid catalyzed one-pot cascade has been demonstrated as a general catalytic system for the synthesis of diversely substituted isoindolinones and tetrahydroisoquinolines. The cascade effects one C-C and two C-N bond-
- Dhanasekaran, Sivasankaran,Bisai, Vishnumaya,Unhale, Rajshekhar A.,Suneja, Arun,Singh, Vinod K.
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supporting information
p. 6068 - 6071
(2015/01/09)
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- Highly enantioselective synthesis of 2,3-dihydro-1 H-imidazo[2,1-a isoindol-5(9b H)-ones via catalytic asymmetric intramolecular cascade imidization-nucleophilic addition-lactamization
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Highly enantioselective catalytic asymmetric intramolecular cascade imidization-nucleophilic addition-lactamization of N1-alkylethane-1,2-diamine with methyl 2-formylbenzoate catalyzed by a chiral phosphoric acid represents the first efficient method for the preparation of medicinally interesting chiral 2,3-dihydro-1H-imidazo[2,1-a]isoindol-5(9bH)-ones with high yields and excellent enantioselectivities. This strategy has been shown to be quite general toward various methyl 2-formylbenzoates.
- He, Yuwei,Cheng, Chuyu,Chen, Bin,Duan, Kun,Zhuang, Yue,Yuan, Bo,Zhang, Meisan,Zhou, Yougui,Zhou, Zihong,Su, Yu-Jun,Cao, Rihui,Qiu, Liqin
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p. 6366 - 6369
(2015/01/16)
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- Structure activity relationship studies of 17-cyclopropylmethyl-3,14β- dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido) morphinan (NAQ) analogues as potent opioid receptor ligands: Preliminary results on the role of electronic characteristics for affinity and function
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17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α- (isoquinoline-3′-carboxamido)morphinan (NAQ) was previously designed following the 'message-address' concept and was identified as a potent and highly selective mu opioid receptor (MOR) ligand based on its pharmacological profile. We here report the preliminary structure activity relationship (SAR) studies of this novel lead compound. For the new ligands synthesized as NAQ analogues, their binding assay results showed that a longer spacer and a saturated ring system of the side chain were unfavorable for their MOR selectivity over the kappa and delta opioid receptors. In contrast, substitutions with different electronic properties at either 1′- or 4′-position of the isoquinoline ring of the side chain were generally acceptable for reasonable MOR selectivity. The majority of NAQ analogues retained low efficacy at the MOR compared to NAQ in the 35S- GTP[γS] binding assays while electron-withdrawing groups at 1′-position of the isoquinoline ring induced higher MOR stimulation than electron-donating groups did. In summary, the electronic characteristics of substituents at 1′- or 4′-position of the isoquinoline ring in NAQ seem to be critical and need to be further tuned up to achieve higher MOR selectivity and lower MOR stimulation.
- Yuan, Yunyun,Elbegdorj, Orgil,Beletskaya, Irina O.,Selley, Dana E.,Zhang, Yan
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supporting information
p. 5045 - 5048
(2013/09/12)
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- A synthetic route to chiral C(3)-functionalized phthalides via a Ag(I)-catalyzed allylation/transesterification sequence
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A Ag(I)-catalyzed synthesis of chiral C(3)-substituted phthalides (8a-f) via a Sakurai-Hosomi allylation/transesterification reaction is described (ee ≤86%). A notable feature of this reaction is that it utilizes ortho-substituted aldehydes, which are a class of compounds that generally afford poor levels of stereoinduction when applying most known catalytic asymmetric allylation approaches. It was also found that elongation of the n-alkyl chain length (R1, up to n=6; R2=H) of the starting alkyl 2-formylbenzoates (7g-i) improved the enantiomeric excess (ee) of the product.
- Mirabdolbaghi, Roya,Dudding, Travis
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p. 3287 - 3292
(2013/04/24)
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- Bifunctional building blocks in the Ugi-azide condensation reaction: A general strategy toward exploration of new molecular diversity
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1,5-Disubstituted tetrazoles are an important drug-like scaffold known for their ability to mimic the cis-amide bond conformation. The scaffold is readily accessible via substitution of the carboxylic acid component of the Ugi multi-component reaction (MCR) with TMSN3 in what is herein denoted the Ugi-azide reaction. This full paper presents a concise, novel, general strategy to access a plethora of new heterocylic scaffolds utilizing tethered aldo/keto-acids/esters in the Ugi-azide reaction followed by a ring closing event that generates novel highly complex bis-heterocyclic lactam-tetrazoles. The Royal Society of Chemistry.
- Gunawan, Steven,Hulme, Christopher
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supporting information
p. 6036 - 6046
(2013/09/12)
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- Synthesis and SAR of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin- 5(9bH)-ones as 5-HT2C receptor agonists
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A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones is described, several examples of which exhibit potent 5-HT2C agonism with excellent selectivity over the closely related 5-HT2A and 5-HT2B receptors. Compounds such as 38 and 44 were shown to be effective in reducing food intake in an acute rat feeding model.
- Fevig, John M.,Feng, Jianxin,Rossi, Karen A.,Miller, Keith J.,Wu, Ginger,Hung, Chen-Pin,Ung, Thao,Malmstrom, Sarah E.,Zhang, Ge,Keim, William J.,Cullen, Mary Jane,Rohrbach, Kenneth W.,Qu, Qinling,Gan, Jinping,Pelleymounter, Mary Ann,Robl, Jeffrey A.
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p. 330 - 335
(2013/02/25)
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- Dibenzo[c,h][1,5]naphthyridinediones as topoisomerase i inhibitors: Design, synthesis, and biological evaluation
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Dibenzo[c,h][1,5]naphthyridinediones were prepared via a novel synthetic pathway. The compounds were designed as topoisomerase I (Top1) inhibitors based on the indenoisoquinoline series of drugs. The results of biological evaluation demonstrate that, unlike very closely related dibenzo[c,h][1,6] naphthyridinediones, dibenzo[c,h][1,5]naphthyridinediones retain the Top1 inhibitory activity of similarly substituted indenoisoquinolines.
- Kiselev, Evgeny,Empey, Nicholas,Agama, Keli,Pommier, Yves,Cushman, Mark
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experimental part
p. 5167 - 5172
(2012/07/16)
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- An indium-mediated allylative/transesterification DFT-directed approach to chiral C(3)-functionalized phthalides
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A one-pot synthesis of chiral C(3)-substituted phthalides via an indium-mediated allylation/transesterification reaction is described. The development of this reaction was facilitated through the applied use of DFT calculations to rationalize the stereoselection of a chiral In-mediated process. It was discovered that the enantiomeric excess of this reaction depended upon the steric size, chain length, and substitution of the aldehyde employed.
- Mirabdolbaghi, Roya,Dudding, Travis
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supporting information; experimental part
p. 3748 - 3751
(2012/09/07)
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- Microwave-assisted synthesis of quinoline, isoquinoline, quinoxaline and quinazoline derivatives as CB2 receptor agonists
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Quinoline, isoquinoline, quinoxaline, and quinazoline derivatives were synthesized using microwave-assisted synthesis and their CB1/CB2 receptor activities were determined using the [35S]GTPγS binding assay. Most of the prepared quinoline, isoquinoline, and quinoxalinyl phenyl amines showed low-potency partial CB2 receptor agonists activity. The most potent CB2 ligand was the 4-morpholinylmethanone derivative (compound 40e) (-log EC 50 = 7.8; Emax = 75%). The isoquinolin-1-yl(3- trifluoromethyl-phenyl)amine (compound 26c) was a high efficacy CB2 agonist (-log EC50 = 5.8; Emax = 128%). No significant CB1 receptor activation or inactivation was shown in these studies, except 40e, which showed weak CB1 agonist activity (CB1 -log EC50 = 5.0). These ligands serve as novel templates for the development of selective CB2 receptor agonist.
- Saari, Raimo,T?rm?, Jonna-Carita,Nevalainen, Tapio
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experimental part
p. 939 - 950
(2011/03/19)
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- 3-(Hetero)aryl-4-indolylamino-α-tetralones by diastereoselective internal redox cyclization: An "azaenamine" conjugate addition
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(E)-3-(Hetero)aryl-1-(2-((E)-(indolin-1-ylimino)methyl)phenyl) prop-2-en-1-ones 1 undergo 6-exo-trig cyclization reactions upon treatment with BF3?Me2S in dichloromethane at low temperature to give the tetralones 10 in good yield. Th
- Ghavtadze, Nugzar,Narayan, Rishikesh,Wibbeling, Birgit,Wuerthwein, Ernst-Ulrich
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scheme or table
p. 5185 - 5197
(2011/08/09)
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- Bismuth(III) triflate: A safe and easily handled precursor for triflic acid: Application to the esterification reaction
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A series of carboxylic acids were converted into their corresponding methyl esters using bismuth(III) triflate as a catalyst in methanol. Good to excellent yields were obtained for different aliphatic or aromatic starting materials. In the reaction, bismuth triflate acts as a precursor that, upon hydrolysis, liberates sufficient triflic acid to catalyze the esterification.
- Kwie, Franciane Ho A.,Baudoin-Dehoux, Cecile,Blonski, Casimir,Lherbet, Christian
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experimental part
p. 1082 - 1087
(2010/05/01)
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- COMPOUNDS FOR INDUCING CELLULAR APOPTOSIS
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The present invention provides isoquinoline, tetrahydroisoquinoline and tetrahydropyridopyrimidine compounds that induce cell death by apoptosis and uses of the compounds in medicine, expecially their use for treating cancer and other diseases.
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Page/Page column 35; 36
(2010/11/17)
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- Selenium-mediated synthesis of biaryls through rearrangement
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"Chemical Equation Presented" A new cyclization of β-keto ester substituted stilbene derivatives using selenium electrophiles in the presence of Lewis acids is described. Substituted naphthols are obtained through cyclization and subsequent 1,2-rearrangement of aryl groups under very mild reaction conditions.
- Shahzad, Sohail A.,Vivant, Clotilde,Wirth, Thomas
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supporting information; experimental part
p. 1364 - 1367
(2010/06/17)
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- Synthesis of chiral 3-substituted phthalides by a sequential organocatalytic enantioselective aldol-lactonization reaction. Three-step synthesis of (S)-(-)-3-butylphthalide
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(Chemical Equation Presented) The development of efficient methods for the facile construction of important molecular frameworks is an important goal in organic synthesis. Chiral 3-substituted phthalides are widely distributed in a large collection of natural products with broad, potent, and potentially path-pointing biological activities. In this investigation, we have uncovered an unprecedented organocatalytic asymmetric aldol-lactonization reaction of 2-formylbenzoic esters with ketones/aldehydes for convenient construction of the enantioenriched "privileged" scaffold. As a result of the sensitive nature of substrate structures of an organocatalytic enantioselective aldol reaction, after extensive optimization of reaction conditions, catalyst L-prolinamide alcohol IV is identified as the best promoter. Interestingly, it is found that in this reaction, addition of an acid additive PhCO2H can significantly enhance reaction efficiency with use of only as low as 2.5 mol % IV for the process. Moreover, due to the sensitivity of reaction conditions toward a sequential aldol-lactonization process without affecting enantioselectivity and racemization, it is essential to remove the catalyst for the subsequent facile lactonization reaction in the presence of K 2CO3. The aldol-lactonization processes serve as a powerful approach to the preparation of synthetically and biologically important 3-substitued phthalides with a high level of enantioselectivities. A 3-step catalytic asymmetric synthesis of the natural product of 3-butylphthalide is reported.
- Zhang, Haoyi,Zhang, Shilei,Liu, Lu,Luo, Guangshun,Duan, Wenhu,Wang, Wei
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supporting information; experimental part
p. 368 - 374
(2010/03/30)
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- 2-Dienylphenacyloxazolones and an intramolecular Diels-Alder approach to the A-B-C ring system of phenanthridone alkaloids
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A general route to the A-B-C ring system of phenanthridone alkaloids is available by acylation of 2-oxa-zolone with a 2-butadienylbenzoic acid derivative, followed by an intramolecular Diels-Alder reaction and hydrolysis.
- Gaenzler, Faith Corbo,Guo, Chen (Lisa),Zhang, Yun-Wei,Azab, Mohammad E.,Salem, Mounir A.I.,Fan, Dong Ping,Smith, Michael B.
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experimental part
p. 8781 - 8785
(2009/12/26)
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- Correlation analysis of reactivity in the oxidation of substituted benzyl alcohols by morpholinium chlorochromate
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Oxidation of benzyl alcohol and some ortho-, meta- andparo-monosubstitutcd derivatives by morpholinium chlorochromate in dimethyl stilphoxide leads to the formation of corresponding benzaldehydcs. The reaction is first order each in both morpholinium chlorochromate and the alcohol. The reaction is promoted by hydrogen ions; the hydrogen-ion dependence has the form kob8 = a + b [H+]. Oxidation of α,α-dideuteriobenzyl alcohol exhibits a substantial primary kinetic isotope effect (kH/kD = 5.86 at 298 K). The reaction has been studied in nineteen organic solvents and the effect of solvent analysed using Taft's and Swain's multi-parametric equations. The rates of oxidation of para- and meta-substituted benzyl alcohols have been correlated in terms of Charton's tripararnetric LDR equation whereas the oxidation of ortho-substituted benzyl alcohols with tetraperametric LDRS equation. The oxidation of para-substituted benzyl alcohols is more susceptible to the derealization effect than that of ortho- and meta- substituted compounds, which display a greater dependence on the field effect. The positive value of η suggests the presence of an electron-deficient reaction centre in the rate-determining step. The reaction is subjected to steric acceleration by the ortho-substituents. A suitable mechanism is also proposed.
- Soni, Neelam,Tiwari, Vandana,Sharma, Vinita
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scheme or table
p. 669 - 676
(2009/02/08)
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- Correlation analysis of reactivity in the oxidation of substituted benzyl alcohols by 2,2′-bipyridinium chlorochromate
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Oxidation of benzyl alcohol and some ortho-, meta- and para-monosubstituted ones by 2.2′-bipyridinium chlorochromate (BPCC) in DMSO leads to the formation of corresponding benzaldehydes. The reaction is first order in both BPCC and the alcohol. The reaction is promoted by hydrogen ions; the hydrogen-ion dependence has the form : kobs = a + b [H+]. Oxidation of α,α-dideuteriobenzyl alcohol (PhCD2OH) has exhibited a substantial primary kinetic isotope effect (kH/k D = 5.60 at 298 K). The reaction has been studied in nineteen organic solvents and the effect of solvent analysed using Taft's and Swain's multi-parametric equations. The rates of oxidation of para- and meta-substituted benzyl alcohols have been correlated in terms of Charton's triparametric LDR equation whereas the oxidation of ortho-substituted benzyl alcohols with tetraparametric LDRS equation. The oxidation of para-substituted benzyl alcohols is more susceptible to the delocalization effect than that of ortho- and meta-substituted compounds, which display a greater dependence on the field effect. The positive value of η suggests the presence of an electron-deficient reaction centre in the rate-determining step. The reaction is subjected to steric acceleration by the ortho-substituents. A suitable mechanism has been proposed.
- Yajurvedi, Deeksha,Baghmar, Manju,Sharma, Pradeep K.
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body text
p. 496 - 501
(2009/07/18)
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- Synthesis and evaluation in monkey of two sensitive 11C-labeled aryloxyanilide ligands for imaging brain peripheral benzodiazepine receptors in vivo
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We sought to develop 11C-labeled ligands for sensitive imaging of brain peripheral benzodiazepine receptors (PBR) in vivo. Two aryloxyanilides with high affinity for PBR were identified and synthesized, namely, N-acetyl-N-(2-methoxycarbonylbenzyl)-2-phenoxyaniline (3, PBR01) and N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide (10, PBR28). 3 was hydrolyzed to 4, which was esterified with [11C]iodomethane to provide [11C]3. The O-desmethyl analogue of 10 was converted into [11C]10 with [11C]iodomethane. [11C]3 and [11C]10 were each injected into monkey to assess their brain kinetics with positron emission tomography (PET). After administration of either radioligand there was moderately high brain uptake of radioactivity. Receptor blocking and displacement experiments showed that a high proportion of this radioactivity was bound specifically to PBR. In monkey and rat, 3 and 10 were rapidly metabolized by ester hydrolysis and N-debenzylation, respectively, each to a single polar radiometabolite. [11C]3 and [11C]10 are effective for imaging PBR in monkey brain. [11C]10 especially warrants further evaluation in human subjects.
- Briard, Emmanuelle,Zoghbi, Sami S.,Imaizumi, Masao,Gourley, Jonathan P.,Shetty, H. Umesha,Hong, Jinsoo,Cropley, Vanessa,Fujita, Masahiro,Innis, Robert B.,Pike, Victor W.
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- COMPOSITIONS AND METHODS INCLUDING CELL DEATH INDUCERS AND PROCASPASE ACTIVATION
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Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed in connection with modification of procaspases such as procaspase-3. In embodiments, compositions are capable of activation of procaspase-3.
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Page/Page column 77
(2008/12/08)
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- Tandem annulation strategy for the convergent synthesis of benzonaphthopyranones: total synthesis of chartarin and O-methylhayumicinone
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A Hauser-initiated tandem annulation has been developed for the rapid regiospecific synthesis of benzonaphthopyranones via formation of two rings in one-pot operation. This strategy has been generalized with benzonaphthopyranones 26, 29, 32, and 35. It has also been employed in a short synthesis of chartarin (3) and O-methylhayumicinone (67).
- Ray, Sutapa,Patra, Asit,Mal, Dipakranjan
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p. 3253 - 3267
(2008/09/19)
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- Synthesis of nitrogen heterocycles by intramolecular cyclization of alkenyl N-acylaminophthalimides using phenyliodine(III) bis(trifluoroacetate) (PIFA)
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PIFA-mediated intramolecular cyclization of alkenyl N-acylaminophthalimides leads to the formation of a new C-N bond via an N-acyl-N-phthalimidonitrenium ion intermediate. The reaction pathway also results in the introduction of an oxygen function into th
- Tsukamoto, Masato,Murata, Kousuke,Sakamoto, Takeshi,Saito, Setsuo,Kikugawa, Yasuo
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p. 1133 - 1149
(2008/12/20)
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