- Xylochemical synthesis and biological evaluation of shancigusin c and bletistrin g
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The biological activities of shancigusin C (1) and bletistrin G (2), natural products isolated from orchids, are reported along with their first total syntheses. The total synthesis of shancigusin C (1) was conducted by employing the Perkin reaction to forge the central stilbene core, whereas the synthesis of bletistrin G (2) was achieved by the Wittig olefination followed by several regiose-lective aromatic substitution reactions. Both syntheses were completed by applying only renewable starting materials according to the principles of xylochemistry. The cytotoxic properties of shancigusin C (1) and bletistrin G (2) against tumor cells suggest suitability as a starting point for further structural variation.
- Efferth, Thomas,Geske, Leander,Kauhl, Ulrich,Opatz, Till,Saeed, Mohamed E. M.,Schüffler, Anja,Thines, Eckhard
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- Yicathins B and C and Analogues: Total Synthesis, Lipophilicity and Biological Activities
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Natural products have always been an important source of new hits and leads in drug discovery, with the marine environment being regarded as a significant source of novel and exquisite bioactive compounds. Yicathins B and C are two marine-derived xanthones that have shown antibacterial and antifungal activity. Herein, the total synthesis of these yicathins and six novel analogues is reported for the first time. As marine natural products tend to have very lipophilic scaffolds, the lipophilicity of yicathins and their analogues was evaluated in the classical octanol/water system and a biomimetic model-based system. As the xanthonic nucleus is a “privileged structure”, other biological activities were evaluated, namely antitumor and anti-inflammatory activities. An interesting anti-inflammatory activity was identified for yicathin analogues that paves the way for the design of dual activity (anti-infective and anti-inflammatory) marine-inspired xanthone derivatives.
- Afonso, Carlos M. M.,Azevedo, Carlos M. G.,Bousbaa, Hassan,Ferreira, Helena,Henriques, Ana,Loureiro, Daniela R. P.,Magalh?es, álvaro F.,Neves, Nuno,Pinto, Joana,Pinto, Madalena M. M.,Reis, Salette,Soares, José X.,Vieira, Sara
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supporting information
(2020/04/17)
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- Chain substituted cannabilactones with selectivity for the CB2 cannabinoid receptor
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In earlier work, we reported a novel class of CB2 selective ligands namely cannabilactones. These compounds carry a dimethylheptyl substituent at C3, which is typical for synthetic cannabinoids. In the current study with the focus on the pharmacophoric side chain at C3 we explored the effect of replacing the C1′-gem-dimethyl group with the bulkier cyclopentyl ring, and, we also probed the chain's length and terminal carbon substitution with bromo or cyano groups. One of the analogs synthesized namely 6-[1-(1,9-dihydroxy-6-oxo-6H-benzo[c]chromen-3-yl) cyclopentyl] hexanenitrile (AM4346) has very high affinity (Ki = 4.9 nM) for the mouse CB2 receptor (mCB2) and 131-fold selectivity for that target over the rat CB1 (rCB1). The species difference in the affinities of AM4346 between the mouse (m) and the human (h) CB2 receptors is reduced when compared to our first-generation cannabilactones. In the cyclase assay, our lead compound was found to be a highly potent and efficacious hCB2 receptor agonist (EC50 = 3.7 ± 1.5 nM, E(max) = 89%). We have also extended our structure-activity relationship (SAR) studies to include biphenyl synthetic intermediates that mimic the structure of the phytocannabinoid cannabinodiol.
- Alapafuja, Shakiru O.,Nikas, Spyros P.,Ho, Thanh C.,Tong, Fei,Benchama, Othman,Makriyannis, Alexandros
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- INTEGRIN ANTAGONISTS
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The present disclosure provides therapeutic agents including those of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such therapeutic agents. Methods of using the therapeutic agents are also provided.
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Page/Page column 58
(2018/05/24)
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- Aryl-Allene Cyclization via a Hg(OTf)2-Catalytic Pathway
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Hg(OTf)2-catalyzed aryl-allene cyclization accompanied by formation of a quaternary carbon center has been realized. Deuterium-labeling experiments and computational modeling were used to propose a novel catalytic pathway involving direct H-transfer from the aromatic ring to the vinyl mercury moiety followed by mercury 1,2-migration.
- Yamamoto, Hirofumi,Ueda, Maho,Yamasaki, Naoto,Fujii, Akiyoshi,Sasaki, Ikuo,Igawa, Kazunobu,Kasai, Yusuke,Imagawa, Hiroshi,Nishizawa, Mugio
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supporting information
p. 2864 - 2867
(2016/07/06)
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- SULFONAMIDE DERIVATIVES AND PHARMACEUTICAL APPLICATIONS THEREOF
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PROBLEM TO BE SOLVED: To provide novel compounds having excellent α4 integrin inhibitory action. SOLUTION: The invention relates to sulfonamide derivatives represented by the general formula (I) in the figure, or pharmaceutically acceptable salts thereof, or prodrugs thereof. (In the formula, a, b, c, d, D, E, R11, B, e, f, g, h and W are as defined herein.) SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 0060
(2016/10/08)
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- Total synthesis of (±)-kuwanol e
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The total synthesis of the Diels-Alder-type adducts (±)-kuwanol E and the heptamethyl ether derivative of (±)-kuwanon Y has been accomplished via a convergent strategy involving 2′-hydroxychalcone 6 or 9 and dehydroprenylstilbene 7, in nine steps. The syn
- Iovine, Valentina,Benni, Irene,Sabia, Rocchina,D'Acquarica, Ilaria,Fabrizi, Giancarlo,Botta, Bruno,Calcaterra, Andrea
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p. 2495 - 2503
(2016/11/09)
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- Total synthesis of achlisocoumarins I-II from Achlys triphylla
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A concise and efficient total synthesis of achlisocoumarin I-II has been completed featuring a construction of the isocoumarin skeleton in a single step and the geranyl coupling with bromoarene ring at -10 C exclusive of any chelating ligand.
- Saeed, Aamer,Mahesar, Parvez Ali
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p. 1401 - 1407
(2014/02/14)
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- Concise total synthesis of permethylated anigopreissin a, a new benzofuryl resveratrol dimer
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The versatile preparation of permethylated anigopreissin A (1) has been accomplished from methyl 3,5-dihydroxybenzoate. The key steps of the synthesis are sequential Sonogashira and Suzuki cross-couplings for the construction of the 2,3-diarylbenzo[b]furan moiety and Wittig olefination for the introduction of the styryl group.
- Chiummiento, Lucia,Funicello, Maria,Lopardo, Maria Teresa,Lupattelli, Paolo,Choppin, Sabine,Colobert, Francoise
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scheme or table
p. 188 - 192
(2012/01/15)
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- PYRAZOLOTHIAZOLE COMPOUND
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A compound represented by the formula (I) or pharmacologically acceptable salt thereof exhibits an excellent CRF receptor antagonism wherein X is a nitrogen atom or CH; R1 is -A11-A12; A11 is a single bond or a C1-6 alkylene group; A12 is a hydrogen atom, a C1-6 alkyl group or a C3-6 cycloalkyl group, etc.; R2 is -A21-A22; A21 is a single bond or a C1-6 alkylene group; A22 is a hydrogen atom, a C1-6 alkyl group, a C3-6 cycloalkyl group, a non-aromatic heterocyclic group, or a heteroaryl group, etc.; R3 is a C 1-6 alkyl group, a C3-6 cycloalkyl group, a C1-6 alkoxy group, a C3-6 cycloalkoxy C1-6 alkyl group, di-C1-6 alkyl amino group, a halogen atom, a cyano group, a formyl group, or a carboxyl group, etc; R4 is a hydrogen atom or a C1-6 alkoxy group; R5 is a halogen atom, a C1-6 alkyl group, or a C1-6 alkoxy group; R6 is a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a C1-6 alkylthio group, or a C1-6 alkyl sulfinyl group etc.; and R7 is a C1-6 alkyl group, a C1-6 alkoxy group, or a C1-6 alkylthio group
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Page/Page column 28; 29
(2011/04/25)
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- 3-PHENYLPYRAZOLO[5,1-b]THIAZOLE COMPOUNDS
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A compound represented by the following formula (I), or salt thereof exhibits excellent CRF receptor antagonism, and sufficient pharmacological activity, safety and pharmacokinetic properties as a drug. wherein R1 represents the formula -A11-A12; R2 represents tetrahydrofurylmethyl, tetrahydropyranylmethyl or tetrahydropyranyl; A11 represents a single bond, methylene or 1,2-ethylene; A12 represents C1-6 alkyl, C3-6 cycloalkyl or C3-6 cycloalkyl having methyl; R3 represents methoxy, cyano, cyclobutyloxymethyl, methoxymethyl or ethoxymethyl; and R4 represents methoxy or chlorine.
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Page/Page column 31
(2009/10/21)
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- Process for production of pyrazole-fused ring derivatives
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An object of the invention is to find out intermediates usful for the synthesis of pyrazol-fused ring derivatives (such as 7-phenylpyrazolo[1,5-a]pyridine derivatives) and a method for producing the same. A method for producing compound represented by the general formula (II), wherein Z1 and Z2 each independently represents a methine group or a nitrogen atom; R1 represents an ethyl group or the like; R5 represents a hydrogen atom or the like; R2 and R3 each independently represents a C1-6 alkyl group or the like, salts thereof, or solvates of both, comprising the step of: reacting a compound represented by the general formula (I), wherein Z1, Z2, R5, R1, R2 and R3 each has the same definition as described above, with an organometallic reagent; and then reacting the resulting product with pentafluoroiodobenzene. [image]
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Page/Page column 12
(2010/11/28)
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- Total synthesis of topopyrones B and D
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(Chemical Equation Presented) We describe a straightforward synthesis of topopyrones B and D, which are potent and selective inhibitors of topoisomerase I. The chemistry should be suitable for additional structure-activity relationship (SAR) work.
- Tan, Jason Samuel,Ciufolini, Marco A.
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p. 4771 - 4774
(2007/10/03)
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- Anti-inflammatory and psoriasis treatment and protein kinase inhibition by hydroxy stilbenes and novel stilbene derivatives and analogues
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The present invention provides novel diphenyl ethene compounds and pharmaceutically-acceptable salts thereof. Also provided are methods for making the compounds of the invention as well as methods for the use thereof in the treatment of immune, inflammatory, and auto-immune diseases.
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- 7-phenylpyrazolopyridine compounds
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A compound represented by the formula: [wherein R1 is methoxy, methylthio, ethyl, etc.; R5 and R6 are each independently cyclopropylmethyl, (4-tetrahydropyranyl)methyl, etc.; and two of R40, R41 and R42 are C1-6 alkoxy while the remaining one is methoxymethyl, etc.], a salt thereof, or a hydrate of the foregoing. This compound has excellent antagonism against corticotropin-releasing factor receptor.
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- A PROCESS FOR PREPARING A PHENYLALANINE DERIVATIVE AND INTERMEDIATES THEREOF
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The present invention provides a process for preparing a novel phenylalanine derivative of the formula (I): wherein X1 is a halogen atom, X2 is a halogen atom, Q is a group of the formula -CH2- or -(CH2)2- and Y is a lower alkyl group, or a pharmaceutically acceptable salt thereof, which has excellent inhibitory effects on α4 integrin-mediated cell adhesion, and an intermediate useful in the process.
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Page/Page column 26-27
(2008/06/13)
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- A facile route to Aryl-substituted 1,10-phenanthrolines by means of Suzuki coupling reactions between substituted areneboronic acids and halogeno-1,10-phenanthrolines
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Twelve new mono- or diaryl-substituted 1,10-phenanthrolines (17 and 18) have been synthesized. The key step is a Suzuki coupling reaction between the substituted areneboronic acids 6, 11, and 15 and the mono- and dihalo-1,10-phenanthrolines 16. The syntheses of bis-ortho-substituted boronic acids 6, 11, and 15 from substituted arenes 5 or substituted bromoarenes 10 and 14 by lithiation and subsequent treatment with trimethyl borate is described. Not only 2,9-diiodo- (16c) but also 2,9-dichloro-1,10-phenanthroline (16b) can be used with good yields (65-92%) in the described Suzuki coupling. For the syntheses of unsymmetrically substituted 1,10-phenanthrolines 18b, 18i, and 18j, the use of 2- chloro-9-iodo-1,10-phenanthroline is not necessary; two different bis-ortho-substituted arene rings can be introduced stepwise in 46 to 64% total yield. ( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002).
- Luening, Ulrich,Abbass, Michael,Fahrenkrug, Frank
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p. 3294 - 3303
(2007/10/03)
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- Regioselectivity in the Lithiation of 1,3-Disubstituted Arenes
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The regioselectivity of the lithiation of 1,4,5,8-tetramethoxynaphthalene-2-carbaldehyde (7) with butyllithium or phenyllithium in the presence of N,N,N′-trimethylethylenediamine and the subsequent bromination of the lithiated species so generated with 1,2-dibromotetrafluoroethane were investigated. Similar investigations with butyllithium as base in the presence of N,N,N′,N′-tetramethylethylenediamine or potassium t-butoxide were carried out on 1,4,5,8-tetramethoxynaphthalene-2-methanol (14). These studies were extended to 1,5,8-trirnethoxynaphthalene-3-methanol (25), 3-methoxybenzenemethanol (29) and 3,5-dimethoxybenzenemethanol (32). The X-ray crystal structure of 6-bromo-1,4,5,8-tetramethoxynaphthalene-2-methanol (17) is described.
- Baker, Robert W.,Liu, Song,Sargent, Melvyn V.,Skelton, Brian W.,White, Allan H.
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p. 831 - 840
(2007/10/03)
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- Lipophilicity and serotonin agonist activity in a series of 4 substituted mescaline analogues
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Replacement of the 4 methoxy of mescaline with higher alkyl homologues or with bromine led to increased activity at serotonin receptors in a sheep umbilical artery preparation. This activity appears correlated with lipophilicity, as measured by 1 octanol water partition coefficients, but drops off when the 4 substituent is about five atoms in length. It is suggested that 3,4,5 trisubstitution may give compounds which are as active as those with the 2,4 5 substitution pattern.
- Nichols,Dyer
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p. 299 - 301
(2007/10/06)
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