- Structure-based linker optimization of 6-(2-cyclohexyl-1-alkyl)-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors
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In continuation of our efforts toward the discovery of potent HIV-1 NNRTIs with diverse structures, a series of novel S-DACO analogues of 6-(2-cyclohexyl-1-alkyl)-2-(2-oxo-2-phenyl-ethylsulfanyl)pyrimidin-4(3H)-ones were designed, synthesized and evaluated for their antiviral activities in MT-4 cells. Most of these new compounds showed moderate to good activities against wild type HIV-1 with IC50 values ranging from 7.55 μmol/L to 0.018 μmol/L. Among them, compound 5c was identified as the most promising inhibitor against HIV-1 replication with an IC50 = 0.018 μmol/L, CC50 = 194 μmol/L, and SI = 12791, which was much more potent than the reference drugs NVP and DLV and comparable to AZT and EFV. In addition, 5c also exhibited improved activity against double mutant HIV-1 strain RES056 compared to that of the reference drugs NVP/DLV and DB02. The preliminary structure-activity relationship (SAR) and molecular modeling studies were also discussed, which provides some useful indications for guiding the further rational design of new S-DACO analogues.
- Li, Daxiong,Zhang, Chunsheng,Ding, Wei,Huang, Siming,Yu, Le,Lu, Nan,Pan, Wenkai,Li, Yiming,De Clercq, Erik,Pannecouque, Christophe,Zhang, Hongbing,Wang, Yueping,He, Yanping,Chen, Fener
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supporting information
p. 1020 - 1024
(2020/10/12)
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- Carbonylative Transformation of Allylarenes with CO Surrogates: Tunable Synthesis of 4-Arylbutanoic Acids, 2-Arylbutanoic Acids, and 4-Arylbutanals
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In this Communication, procedures for the selective synthesis of 4-arylbutanoic acids, 2-arylbutanoic acids, and 4-arylbutanals from the same allylbenzenes have been developed. With formic acid or TFBen as the CO surrogate, reactions proceed selectively and effectively under carbon monoxide gas-free conditions.
- Wu, Fu-Peng,Li, Da,Peng, Jin-Bao,Wu, Xiao-Feng
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supporting information
p. 5699 - 5703
(2019/08/01)
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- 1-Aminopyridinium Ylides as Monodentate Directing Groups for sp3 C-H Bond Functionalization
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1-Aminopyridinium ylides are efficient directing groups for palladium-catalyzed β-arylation and alkylation of sp3 C-H bonds in carboxylic acid derivatives. The efficiency of these directing groups depends on the substitution at the pyridine moiety. The unsubstituted pyridine-derived ylides allow functionalization of primary C-H bonds, while methylene groups are unreactive in the absence of external ligands. 4-Pyrrolidinopyridine-containing ylides are capable of C-H functionalization in acyclic methylene groups in the absence of external ligands, thus rivaling the efficiency of the aminoquinoline directing group. Preliminary mechanistic studies have been performed. A cyclopalladated intermediate has been isolated and characterized by X-ray crystallography, and its reactivity was studied.
- Le, Ky Khac Anh,Nguyen, Hanh,Daugulis, Olafs
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supporting information
p. 14728 - 14735
(2019/10/11)
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- Site-Selective Catalytic Carboxylation of Unsaturated Hydrocarbons with CO2 and Water
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A catalytic protocol that reliably predicts and controls the site-selective incorporation of CO2 to a wide range of unsaturated hydrocarbons utilizing water as formal hydride source is described. This platform unlocks an opportunity to catalytically repurpose three abundant, orthogonal feedstocks under mild conditions.
- Gaydou, Morgane,Moragas, Toni,Juliá-Hernández, Francisco,Martin, Ruben
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p. 12161 - 12164
(2017/09/12)
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- COMPOUNDS USEFUL AS MODULATORS OF TRPM8
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The present invention includes compounds useful as modulators of TRPM8, such as compounds of Formulae (Ia), (Ib) and (Ic), and the subgenus and species thereof; personal products containing those compounds; and the use of those compounds and the personal products, particularly the use of increasing or inducing chemesthetic sensations, such as cooling or cold sensations.
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Paragraph 0890
(2016/03/29)
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- Facile palladium-catalyzed hydrocarboxylation of olefins without external CO gas
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An effective Pd-catalyzed hydrocarboxylation of olefins with phenyl formate and formic acid is described. A variety of carboxylic acids are obtained in good yields with high regioselectivities under operationally simple conditions without the use of toxic CO gas.
- Wang, Yang,Ren, Wenlong,Li, Jingfu,Wang, Haining,Shi, Yian
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supporting information
p. 5960 - 5963
(2015/02/19)
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- Nickel-catalyzed direct arylation of C(sp3)-H bonds in aliphatic amides via bidentate-chelation assistance
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The Ni-catalyzed, direct arylation of C(sp3)-H (methyl and methylene) bonds in aliphatic amides containing an 8-aminoquinoline moiety as a bidentate directing group with aryl halides is described. Deuterium-labeling experiments indicate that the C-H bond cleavage step is fast and reversible. Various nickel complexes including both Ni(II) and Ni(0) show a high catalytic activity. The results of a series of mechanistic experiments indicate that the catalytic reaction does not proceed through a Ni(0)/Ni(II) catalytic cycle, but probably through a Ni(II)/Ni(IV) catalytic cycle.
- Aihara, Yoshinori,Chatani, Naoto
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p. 898 - 901
(2014/02/14)
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- SUBSTITUTED HETEROCYCLIC COMPOUNDS
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The present invention relates to substituted heterocyclic compounds of Formula I or XI: or pharmaceutically acceptable salts or N-oxides or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are histamine II4 receptor inhibitors useful in the treatment of histamine II4 receptor-associated conditions or diseases or disorders including, for example, inflammatory diseases or disorders, pruritus, and pain.
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Page/Page column 92-93
(2010/10/03)
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- Acylguanidines as bioisosteres of guanidines: NG-acylated imidazolylpropylguanidines, a new class of histamine h2 receptor agonists
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N1-Aryl(heteroaryl)alkyl-N2-[3-(1H-imidazol-4-yl) propyl]guanidines are potent histamine H2-receptor (H2R) agonists, but their applicability is compromised by the lack of oral bioavailability and CNS penetration. To improve pharmacokinetics, we introduced carbonyl instead of methylene adjacent to the guanidine moiety, decreasing the basicity of the novel H2R agonists by 4-5 orders of magnitude. Some acylguanidines with one phenyl ring were even more potent than their diaryl analogues. As demonstrated by HPLC-MS, the acylguanidines (bioisosteres of the alkylguanidines) were absorbed from the gut of mice and detected in brain. In GTPase assays using recombinant receptors, acylguanidines were more potent at the guinea pig than at the human H2R. At the hH1R and hH3R, the compounds were weak to moderate antagonists or partial agonists. Moreover, potent partial hH4R agonists were identified. Receptor subtype selectivity depends on the imidazolylpropylguanidine moiety (privileged structure), opening an avenue to distinct pharmacological tools including potent H4R agonists.
- Ghorai, Prasanta,Kraus, Anja,Keller, Max,G?tte, Carsten,Igel, Patrick,Schneider, Erich,Schnell, David,Bernhardt, Günther,Dove, Stefan,Zabel, Manfred,Elz, Sigurd,Seifert, Roland,Buschauer, Armin
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supporting information; experimental part
p. 7193 - 7204
(2009/10/02)
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- Palladium-catalyzed asymmetric reduction of racemic allylic esters with formic acid: Effects of phosphine ligands on isomerization of π- allylpalladium intermediates and enantioselectivity
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A new MOP ligand (lb), (R)-(+)-2-(bis(3- trifluoromethylphenyl)phosphino)-2'-methoxy-1,1'-binaphthyl, was found to be more enantioselective than other MOP ligands for the palladium-catalyzed asymmetric reduction of α,α-disubstituted allylic esters with formic acid. The reduction of DL-2-(1-naphthyl)-3-buten-2-yl benzoate gave 3-(1-naphthyl)- 1-butene of 90% ee. The higher enantioselectivity of lb is ascribed to fast syn-anti isomerization of π-allylpalladium intermediates formed by oxidative addition of allylic ester to a palladium(0) species. The rate of syn-anti isomerization was measured by the magnetization saturation transfer in 1H NMR. (C) 2000 Elsevier Science Ltd.
- Kawatsura, Motoi,Uozumi, Yasuhiro,Ogasawara, Masamichi,Hayashi, Tamio
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p. 2247 - 2257
(2007/10/03)
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- Effiziente Synthese neuer 2-Cycloalk(en)yl-propansaeure-Derivate - mittlere und grosse Ringe als Bioisostere von Alkylphenylresten?
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Stichworte: Cycloalkanone, Cyclooxygenase-Inhibitoren, Mittlere Ringe, Zinkverbindungen
- Greve, Bjoern,Imming, Peter,Laufer, Stefan
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p. 1312 - 1314
(2007/10/03)
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- Stereoselective addition of organometallic reagents to N-(tosyl)vinylsulfoximines
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Treatment of N-(toluene-p-sulfonyl)vinylsulfoximines 3 with methyllithium at -78°C, followed by addition of chlorotrimethylsilane, results in the efficient formation of α-silyl vinylsulfoximines 6 in good to excellent yield. Nucleophilic addition of a range of simple alkyl and aryl organometallics (lithium, copper-lithium and Grignard reagents) occurs in variable yield to give the Michael adducts 8 with organolithium reagents most effective. The degree of stereoselectivity of each of the addition reactions was determined by 1H NMR of the desilylated products 9, and proved to be synthetically useful for compounds in which the starting α-silylvinylsulfoximines were branched at the γ-position, and also when phenylhthium was used as the nucleophile. The sense of stereoselectivity was determined in two cases by X-ray crystal structure analyses (of 9e and 9i). A one-pot process for the conversion of α-silylvinylsulfoximines 6 to α-substituted carboxylic acids 11 was developed, using an in situ phenylselenation-oxidation process following the initial conjugate addition. Use of enantiomerically pure starting materials allowed the assignment of configuration of two carboxylic acids (13e and 13h) by comparison with literature data, and hence indirectly of the relative stereochemistry of the initial Michael adducts 9e and 9h.
- Jackson, Richard F. W.,Briggs, Andrew D.,Brown, Paul A.,Clegg, William,Elsegood, Mark R. J.,Frampton, Christopher
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p. 1673 - 1682
(2007/10/03)
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- Perfumery composition comprising 2-cyclohexylpropionic acid or its derivative
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Disclosed is a perfumery composition comprising a 2-cyclohexylpropionic acid or its derivative represented by the following formula (I): STR1 wherein R is a hydrogen atom, an alkyl group having 1-4 carbon atoms, or an alkenyl group having 2-4 carbon atoms. The compounds have a wide variety of odors and a wide application as perfumery compositions such as high-grade perfumery compositions, perfumes, soaps, shampoos, rinses, detergents, cosmetics, sprays, room fragrances, and the like.
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- 2,5,6,7-tetranor-4,8-inter-m-phenylene PGI2 derivatives
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Disclosed herein are novel prostaglandin I2 (PGI2) derivatives exhibiting excellent in vivo duration and activities, said derivatives being represented by the general formula: STR1 wherein R1, X, R2 and R3 are as defined herein.
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- The Regiospecific Palladium Catalysed Hydrocarboxylation of Alkenes under Mild Conditions
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Alkenes react with carbon monoxide, water, oxygen, hydrochloric acid, and palladium and copper chlorides, to give branched chain acids in good yields.
- Alper, Howard,Woell, James B.,Despeyroux, Bertrand,Smith, David J. H.
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p. 1270 - 1271
(2007/10/02)
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- New Methods and Reagents in Organic Synthesis. 26. Reductive Desulfonylation of α-Sulfonylacetates
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α-Acyl-benzylsulfonyldiazomethanes (2a-d) have been converted to α-benzylsulfonyl-α-substituted-acetic acids (7a-d) by means of the Wolff rearrangement.Reductive removal of the benzylsulfonyl group of 7b-d can be achieved by the use of sodium-ethanol in tetrahydrofuran. α-Benzylsulfonyl-α-substituted-propionic acids (9a-d), prepared from benzyl α-benzylsulfonyl-α-substituted-acetates (3a-d), were also debenzylsulfonylated under similar reductive conditions.The overall process, in combination with the Arndt-Eistert synthesis of α-sulfonylacetates from acyl chlorides and benzylsulfonyldiazomethane (1), provides a new, safe method for the homologation of carboxylic acids.Keywords-reductive desulfonylation; Wolff rearrangement; sodium amalgam reduction; catalytic debenzylation; sodium-ethanol reduction; methylation; α-substituted propionic acid; α-sulfonylacetate
- Kuo, Ying-Che,Aoyama, Toyohiko,Shioiri, Takayuki
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p. 2787 - 2792
(2007/10/02)
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