- Small-molecule anti-HIV-1 agents based on HIV-1 capsid proteins
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The capsid of human immunodeficiency virus type 1 (HIV-1) is a shell that encloses viral RNA and is highly conserved among many strains of the virus. It forms a conical structure by assembling oligomers of capsid (CA) proteins. CA dysfunction is expected to be an important target of suppression of HIV-1 replication, and it is important to understand a new mechanism that could lead to the CA dysfunction. A drug targeting CA however, has not been developed to date. Hydrophobic interactions between two CA molecules via Trp184/Met185 in CA were recently reported to be important for stabilization of the multimeric structure of CA. In the present study, a small molecule designed by in silico screening as a dipeptide mimic of Trp184 and Met185 in the interaction site, was synthesized and its significant anti-HIV-1 activity was confirmed. Structure activity relationship (SAR) studies of its derivatives were performed and provided results that are expected to be useful in the future design and development of novel anti-HIV agents targeting CA.
- Kobayakawa, Takuya,Yokoyama, Masaru,Tsuji, Kohei,Fujino, Masayuki,Kurakami, Masaki,Boku, Sayaka,Nakayama, Miyuki,Kaneko, Moemi,Ohashi, Nami,Kotani, Osamu,Murakami, Tsutomu,Sato, Hironori,Tamamura, Hirokazu
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- Benzoxaborole Catalyst for Site-Selective Modification of Polyols
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The site-selective modification of polyols bearing several hydroxyl groups without the use of protecting groups remains a significant challenge in synthetic chemistry. To address this problem, novel benzoxaborole derivatives were designed as efficient catalysts for the highly site-selective and protecting-group-free modification of polyols. To identify the effective substituent groups enhancing the catalytic activity and selectivity, a series of benzoxaborole catalysts 1a–k were synthesized. In-depth analysis for the substituent effect revealed that 1i–k, bearing multiple electron-withdrawing fluoro- and trifluoromethyl groups, exhibited the greatest catalytic activity and selectivity. Moreover, 1i-catalyzed benzoylation, tosylation, benzylation, and glycosylation of various cis-1,2-diol derivatives proceeded with good yield and site-selective manner.
- Kusano, Shuhei,Miyamoto, Shoto,Matsuoka, Aki,Yamada, Yuji,Ishikawa, Ryuta,Hayashida, Osamu
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supporting information
p. 1598 - 1602
(2020/02/11)
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- Regioselective Sulfonylation/Acylation of Carbohydrates Catalyzed by FeCl3 Combined with Benzoyltrifluoroacetone and Its Mechanism Study
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A catalytic amount of FeCl3 combined with benzoyl trifluoroacetone (Hbtfa) (FeCl3/Hbtfa = 1/2) was used to catalyze sulfonylation/acylation of diols and polyols using diisopropylethylamine (DIPEA) or potassium carbonate (K2CO3) as a base. The catalytic system exhibited high catalytic activity, leading to excellent isolated yields of sulfonylation/acylation products with high regioselectivities. Mechanism studies indicated that FeCl3 initially formed [Fe(btfa)3] (btfa = benzoyl trifluoroacetonate) with twice the amount of Hbtfa under basic conditions in the solvent acetonitrile at room temperature. Then, Fe(btfa)3 and two hydroxyl groups of the substrates formed a five- or six-membered ring intermediate in the presence of the base. The subsequent reaction between the cyclic intermediate and a sulfonylation reagent led to the selective sulfonylation of the substrate. All key intermediates were captured in the high-resolution mass spectrometry assay, therefore demonstrating this mechanism for the first time.
- Dong, Hai,Liu, Yu,Lv, Jian,Zhu, Jia-Jia
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p. 3307 - 3319
(2020/03/25)
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- BENZYLAMINE COMPOUND, AND PHARMACEUTICAL COMPOSITION AND ANTI-HIV AGENT THEREOF
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PROBLEM TO BE SOLVED: To provide: a novel benzylamine compound; and a pharmaceutical composition and an anti-HIV agent that are suitable for suppression of HIV activity. SOLUTION: The benzylamine compound is represented by the general formula (1) in the figure. In the general formula (1), R1 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group; A represents an oxygen atom or sulfur atom; R2 represents a substituted or unsubstituted alkyl group; and n represents an integer from 1 to 10. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT
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Paragraph 0070-0071
(2020/05/13)
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- 2-AMINO-QUINOLINE DERIVATIVES
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Described herein are 2-amino-quinoline derivatives that are agonists of toll-like receptors 7 and 8 (TLR7/8), pharmaceutical compositions, and methods of use of the compounds and compositions to treat various diseases, such as viral, cancer, and allergic diseases, in need thereof by administering a therapeutically effective amount of a 2-amino-quinoline derivative.
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Paragraph 0174; 0209-0210
(2018/11/22)
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- Ionic liquid brush as an efficient and reusable heterogeneous catalytic assembly for the tosylation of phenols and alcohols in neat water
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A very efficient and reusable heterogeneous ionic liquid brush assembly was developed. The catalyst exhibits high catalytic activity for the tosylation of phenols and alcohols in neat water. Moreover, the catalyst shows outstanding stability and reusability, and it can be simply and effectively recovered and reused five times without noticeable loss of catalytic activity.
- Feng, Simin,Li, Jing,Wei, Junfa
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supporting information
p. 4743 - 4746
(2017/07/12)
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- Isolation, Structure Elucidation, and (Bio)Synthesis of Haprolid, a Cell-Type-Specific Myxobacterial Cytotoxin
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Myxobacteria are well-established sources for novel natural products exhibiting intriguing bioactivities. We here report on haprolid (1) isolated from Byssovorax cruenta Har1. The compound exhibits an unprecedented macrolactone comprising four modified amino acids and a polyketide fragment. As configurational assignment proved difficult, a bioinformatic analysis of the biosynthetic gene cluster was chosen to predict the configuration of each stereocenter. In-depth analysis of the corresponding biosynthetic proteins established a hybrid polyketide synthase/nonribosomal peptide synthetase origin of haprolid and allowed for stereochemical assignments. A subsequent total synthesis yielded haprolid and corroborated all predictions made. Intriguingly, haprolid showed cytotoxicity against several cell lines in the nanomolar range whereas other cells were almost unaffected by treatment with the compound.
- Steinmetz, Heinrich,Li, Jun,Fu, Chengzhang,Zaburannyi, Nestor,Kunze, Birgitte,Harmrolfs, Kirsten,Schmitt, Viktoria,Herrmann, Jennifer,Reichenbach, Hans,H?fle, Gerhard,Kalesse, Markus,Müller, Rolf
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supporting information
p. 10113 - 10117
(2016/08/16)
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- METHOD FOR PRODUCING 3-BUTENE-2-OL
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PROBLEM TO BE SOLVED: To provide a method for efficiently producing racemic 3-butene-2-ol having an (S)- or (R)-configuration. SOLUTION: There is provided a method for producing racemic 3-butene-2-ol, wherein an ammonium salt compound represented by the following general formula (1) (wherein, R1, R2 or R3 represents an alkyl group, an aryl group or an aralkyl group; X- represents OH-, HCO3-, CO32-, R4O-, R5CO2-, R6SO3- (R4, R5 or R6 represents an alkyl group, an aryl group or an aralkyl group) and a halide ion; n represents 0.5 when X- is CO32- and n represents 1 when X- is other than CO32-; the carbon atom marked with * is an asymmetric carbon atom) is subjected to Hofmann elimination. COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 0031; 0032
(2016/11/07)
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- SUBSTITUTED XANTHINES AND METHODS OF USE THEREOF
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Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.
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Page/Page column 394
(2014/09/29)
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- Regioselective, borinic acid-catalyzed monoacylation, sulfonylation and alkylation of diols and carbohydrates: Expansion of substrate scope and mechanistic studies
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Synthetic and mechanistic aspects of the diarylborinic acid-catalyzed regioselective monofunctionalization of 1,2- and 1,3-diols are presented. Diarylborinic acid catalysis is shown to be an efficient and general method for monotosylation of pyranoside derivatives bearing three secondary hydroxyl groups (7 examples, 88% average yield). In addition, the scope of the selective acylation, sulfonylation, and alkylation is extended to 1,2- and 1,3-diols not derived from carbohydrates (28 examples); the efficiency, generality, and operational simplicity of this method are competitive with those of state-of-the-art protocols including the broadly applied organotin-catalyzed or -mediated reactions. Mechanistic details of the organoboron-catalyzed processes are explored using competition experiments, kinetics, and catalyst structure-activity relationships. These experiments are consistent with a mechanism in which a tetracoordinate borinate complex reacts with the electrophilic species in the turnover-limiting step of the catalytic cycle.
- Lee, Doris,Williamson, Caitlin L.,Chan, Lina,Taylor, Mark S.
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supporting information; experimental part
p. 8260 - 8267
(2012/07/14)
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- Synthesis and biological evaluation of (phenylpiperazinyl-propyl)arylsulfonamides as selective 5-HT2A receptor antagonists
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A novel series of 5-HT2A ligands that contain a (phenylpiperazinyl-propyl)arylsulfonamides skeleton was synthesized. Thirty-seven N-(cycloalkylmethyl)-4-methoxy-N-(3-(4-arylpiperazin-1-yl)propyl)-arylsulfonamide and N-(4-(4-arylpiperazin-1-yl)b
- Yoo, Euna,Yoon, Juhee,Pae, Ae Nim,Rhim, Hyewhon,Park, Woo-Kyu,Kong, Jae Yang,Park Choo, Hea-Young
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experimental part
p. 1665 - 1675
(2010/05/02)
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- Fluorinated isatin derivatives. Part 1: Synthesis of new N-substituted (S)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatins as potent caspase-3 and -7 inhibitors
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A series of new N-substituted (S)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin derivatives has been synthesized and tested as inhibitors of caspases-3 and -7, which are known to be downstream enzymes critical in the execution of apoptosis. N-Propyl-
- Podichetty, Anil Kumar,Faust, Andreas,Kopka, Klaus,Wagner, Stefan,Schober, Otmar,Schaefers, Michael,Haufe, Guenter
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body text
p. 2680 - 2688
(2009/08/15)
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- Tandem alkylation - Michael addition to vinylogous carbonates for the stereoselective construction of 2,3,3,6-tetrasubstituted tetrahydropyrans
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A stereoselective method for the synthesis of substituted tetrahydropyran derivatives employing a tandem SN2-Michael addition sequence to vinylogous carbonates is developed. The method is extended to the synthesis of bicyclic ether motifs present in polyether ladder toxins.
- Gharpure, Santosh J.,Reddy, S. Raja Bhushan
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supporting information; scheme or table
p. 2519 - 2522
(2009/10/18)
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- Preparation of piperazine derivatives as 5-HT7 receptor antagonists
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Twenty-four compounds of 4-methoxy-N-[3-(4-substituted phenyl-piperazine-1-yl)propyl] benzene sulfonamides and N-[3-(4-substituted phenyl-piperazine-1-yl)propyl] naphthyl sulfonamides were prepared and evaluated as 5-HT7 receptor antagonists. Most of the compounds showed the IC50 values of 12-580 nM. Four methyl branched analogues were also obtained, but the activity for methyl branched analogues was almost same as its straight chain congeners. Among the synthesized compounds, 3c showed a good activity on 5-HT7 receptors and a good selectivity on 5-HT1a, 5-HT2a, 5-HT2c, and 5-HT6 receptors.
- Yoon, Juhee,Yoo, Eun A,Kim, Ji-Yeon,Pae, Ae Nim,Rhim, Hyewhon,Park, Woo-Kyu,Kong, Jae Yang,Park Choo, Hea-Young
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p. 5405 - 5412
(2008/12/21)
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- COMPOUND, COMPOSITION, RETARDATION PLATE, ELLIPTICALLY-POLARIZING PLATE AND LIQUID-CRYSTAL DISPLAY DEVICE
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A compound useful for fabrication of retardation plates, which is represented by the formula (DI): wherein Y11 to Y13 represent methine or nitrogen; R11 to R13 represent a group of the formula (DI-A) below or ot
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Page/Page column 65-66
(2008/06/13)
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- KAPPA-OPIOID RECEPTOR AGONIST COMPRISING 2-PHENYLBENZOTHIAZOLINE DERIVATIVE
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The present invention provides κ opioid receptor agonists comprising 2-phenylbenzothiazoline derivatives. The present invention relates to κ opioid receptor agonists comprising compounds or salts thereof having the chemical structure represented by the ge
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- SULFONAMIDE DERIVATIVES AS 5HT7 RECEPTOR ANTAGONISTS
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The present invention discloses a compound of formula (I): - wherein A is an aromatic moiety or selected from benzyl, C1-C16 alkyl dialkylamino, dialkylaminoalkyl, alkoxyalkyl, cyano, and mono-, di-, or tri-hydroxyalkyl and/or aryl,
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Page/Page column 14
(2008/06/13)
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- Diastereoselective Manipulations of Bicyclo[m.1.0]alkane Derivatives. 6. Stereocontrolled Synthesis of Tricyclo[m.n.0.0]alkenones
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Enolates derived from bicyclo[m.1.0]alkan-2-ones possessing 5-, 6-, and 7-membered rings were sequentially alkylated with iodomethane and with precursors to 2-oxopropyl or 3-oxobutyl substituents. High diastereoselectivities were observed. Product yields for more active electrophiles were generally good to very good and were fair for less active electrophiles. Following unmasking of the 2-oxopropyl or 3-oxobutyl substituents, ring closure and dehydration under basic conditions provided the corresponding tricyclic γ,δ-cyclopropyl-α,β-enones. Reversal of the order of alkylation switched the configuration of the angular methyl substituent relative to the stereogenic cyclopropane in the tricyclo[m.n.0.0]alkenone product.
- Mash, Eugene A.,Baron, James A.
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p. 7412 - 7418
(2007/10/03)
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- SYNTHESIS OF SOME 2'-C-ALKYL DERIVATIVES OF 9-(2-PHOSPHONOMETHOXYETHYL)ADENINE AND RELATED COMPOUNDS
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To study the effect of β-substitution in 2'-alkyl derivatives of 9-(2-phosphonomethoxyethyl)adenine (Ia) on the antiviral activity or group specificity, these derivatives were synthesized. 9-(2-Hydroxyalkyl)adenines VIII were prepared by alkylation of adenine with suitably substituted oxiranes XIII or 2-hydroxyalkyl p-toluenesulfonates IV and VI.After protection of the adenine amino group by benzylation (compounds IX) or amidine formation (compounds X), the intermediates were alkylated with bis(2-propyl) p-toluenesulfonyloxymethanephosphonate (XI) in the presence of sodium hydride.After deprotection, the obtained phosphonate diesters XII were converted into phosphoniuc acids I by transsilylation and hydrolysis.This synthetic scheme was used for the preparation of ethyl (Ie), propyl (If), 2-propyl (Ig), 2-methylpropyl (Ih), cyclopropyl (Ii), cyclohexyl (Ij), benzyl (Ik) and phenyl (Il) derivatives.The 2'-trifluoromethyl derivative XXIIa was prepared analogously from 9-(2-hydroxy-3,3,3-trifluoropropyl)adenine (XXa), obtained by alkylation of adenine sodium salt with 2-hydroxy-3,3,3-trifluoropropyl bromide. 2,6-Diaminopurine derivative XXIIb was obtained analogously. 2'-Trimethylsilyl derivative XIXa was obtained by alkylation of adenine with 2-phosphonylmethoxy-3-(4-toluenesulfonyloxy)propyltrimethylsilane (XVII) followed by transsilylation and hydrolysis of diester XVIIIa. 9-(3-Phosphonomethoxybutyl)adenine (XXVIII) and 9-(2-methyl-2-phosphonomethoxypropyl)adenine (XXXV) were prepared from the corresponding hydroxy derivatives XXVIb and XXXII, respectively, by the same reaction pathway as derivatives I.
- Cvorakova, Hana,Holy, Antonin,Rosenberg, Ivan
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p. 2069 - 2094
(2007/10/02)
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- STUDIEN ZUM VORGANG DER WASSERSTOFFUEBERTRAGUNG.61. Chemische Reaktivitaet und Halbstufenpotential Vergleichende Versuche am Beispiel einiger Arylsulfonsaeurederivate
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In arylsulfonyl halides, the half-wave potentials of the corresponding chlorides and fluorides differ by more than 1000 mV, the fluoride being more negative; the influence of para-substituents is small for the chlorides, large for the fluorides.In agreement with the half-wave potentials, arylsulfonyl chlorides are considerably more reactive chemically than the corresponding fluorides.The O-selectivity found for P(O)F compounds is not observed in arylsulfonyl fluorides.Studies of competitive ester formation using primary and secondary alcohols and various arylsulfonyl chlorides yielded no clear analogy to the half-wave potentials.The primary alcohol is always sulfonated in preference to the secondary alcohol, whether the hydroxy functions are present in different molecules or the same molecule.In the latter case, the secondary hydroxyl function is then attacked in a further step by a second, different, arylsulfonyl chloride, giving the compounds 4-8.The further electroreduction of these diesters may be carried out in high yields, giving selective fission of one ester linkage only (that with the more positive potential) provided the difference in the half-wave potentials of the different ester linkages is sufficiently large.In the electroreductive fission the monosulfinic acid and the corresponding alcohol are liberated (see table II).In the competition reaction between phenol and 1:1 mixtures of tosyl chloride (A) and p-carboxyethyl-benzenesulfonyl chloride (B), the chloride with the more positive potential (B), E1/2=72 mV reacts quicker by a factor of 2.5.In competitive Finkelstein reactions, the selectivity was 1:11 at a difference in half-wave potentials of 760 mV (table IV).Arylsulfonates with free secondary alcohol functions may be oxidized smoothly and in high yield to the corresponding ketone using Na2Cr2O7 (3), without effecting the sulfonate linkage.The alkali hydrolysis of n-hexyl para-substituted arylsulfonates follows the Hammett relation but shows a lesser selectivity than was observed in the electroreductive fission of the same esters at the required potentials.Tables VI, VII and VIII concentrate on the preparative importance of the potential-controlled electroreductive fission of aliphatic and aromatic arylsulfonates.The corresponding hydroxy compounds are liberated in yields of up to over 90percent: N-alkyl- and N-aryl arylsulfonamides give analogous results. (table IX)
- Horner, Leopold,Schmitt, Rolf-Erhard
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p. 189 - 212
(2007/10/02)
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