- Synthesis and in vitro antimicrobial activity of new 2-[p-substituted-benzyl]-5-[substituted-carbonylamino]benzoxazoles
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Some new 2-(benzyl/p-chlorobenzyl)-5-[(substituted-thienyl/phenyl/phenylthiomethyl/benzyl)carbonylamino]benzoxazole derivatives have been synthesized by reacting 5-amino-2-(benzyl/p-chlorobenzyl)benzoxazoles with appropriate carboxylic acid chlorides. The structures of the synthesized compounds were confirmed by IR, 1H NMR and MASS spectral data. In vitro antimicrobial activities of the compounds were investigated using twofold serial dilution technique against different two Gram-positive, two Gram-negative bacteria and three Candida spp. in comparison with standard drugs. Microbiological results indicated that the newly synthesized 2-(benzyl/p-chlorobenzyl)-5-[(substituted-thienyl/phenyl/phenylthiomethyl/benzyl)carbonylamino]benzoxazole derivatives (3-12) possessed a broad spectrum of activity having MIC values of 6.25-100 μg/ml against the tested microorganisms. Especially, with an MIC value of 6.25 μg/ml, 2-(p-chlorophenyl)-5-[(2,5-dimethylphenyl)carbonylamino]benzoxazole 4 displayed the same activity against Candida albicans as the standard drug clotrimazole.
- Tekiner-Gulbas, Betul,Temiz-Arpaci, Ozlem,Yildiz, Ilkay,Altanlar, Nurten
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Read Online
- Cu(II)-Catalyzed 6π-Photocyclization of Non-6πSubstrates
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This research successfully achieved a Cu(II)-catalyzed 6π-photocyclization of non-6πsubstrates. The photoenolization converts ortho-alkylphenyl alkynl ketones into a triene-type intermediate which undergoes the subsequent 6π-photocyclization to give napht
- Zhang, Yanbin,Jin, Ruiwen,Kang, Wenjie,Guo, Hao
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supporting information
p. 5502 - 5505
(2020/07/08)
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- N-Heterocyclic Carbene Catalyzed Photoenolization/Diels–Alder Reaction of Acid Fluorides
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The combination of light activation and N-heterocyclic carbene (NHC) organocatalysis has enabled the use of acid fluorides as substrates in a UVA-light-mediated photochemical transformation previously observed only with aromatic aldehydes and ketones. Stoichiometric studies and TD-DFT calculations support a mechanism involving the photoactivation of an ortho-toluoyl azolium intermediate, which exhibits “ketone-like” photochemical reactivity under UVA irradiation. Using this photo-NHC catalysis approach, a novel photoenolization/Diels–Alder (PEDA) process was developed that leads to diverse isochroman-1-one derivatives.
- Agrawal, Arush,G?tze, Jan P.,Golz, Paul,Hopkinson, Matthew N.,Mavroskoufis, Andreas,Rajes, Keerthana,Ru?, Vincent
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supporting information
p. 3190 - 3194
(2020/01/24)
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- Rhodium-Catalyzed Alkylation of C?H Bonds in Aromatic Amides with Non-activated 1-Alkenes: The Possible Generation of Carbene Intermediates from Alkenes
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The alkylation of C?H bonds (hydroarylation) in aromatic amides with non-activated 1-alkenes using a rhodium catalyst and assisted by an 8-aminoquinoline directing group is reported. The addition of a carboxylic acid is crucial for the success of this reaction. The results of deuterium-labeling experiments indicate that one of deuterium atoms in the alkene is missing, suggesting that the reaction does not proceed through the commonly accepted mechanism for C?H alkylation reactions. Instead the reaction is proposed to proceed through a carbene mechanism. The carbene mechanism is also supported by preliminary DFT calculations.
- Yamaguchi, Takuma,Natsui, Satoko,Shibata, Kaname,Yamazaki, Ken,Rej, Supriya,Ano, Yusuke,Chatani, Naoto
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supporting information
p. 6915 - 6919
(2019/05/10)
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- C?O Activation by a Rhodium Bis(N-Heterocyclic Carbene) Catalyst: Aryl Carbamates as Arylating Reagents in Directed C?H Arylation
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Despite recent progress in the catalytic transformation of inert phenol derivatives as alternatives to aryl halides and triflates, attempts at the cross-coupling of inert phenol derivatives with the C?H bonds of arenes have met with limited success. Herein, we report the rhodium-catalyzed cross-coupling of aryl carbamates with arenes bearing a convertible directing group. The key to success is the use of an in situ generated rhodium bis(N-heterocyclic carbene) species as the catalyst, which can promote activation of the inert C(sp2)?O bond in aryl carbamates.
- Tobisu, Mamoru,Yasui, Kosuke,Aihara, Yoshinori,Chatani, Naoto
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supporting information
p. 1877 - 1880
(2017/02/05)
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- Synthesis of 12-oxobenzo[c]phenanthridinones and 4-substituted 3-arylisoquinolones via Vilsmeier-Haack reaction
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Vilsmeier-Haack reaction on 3-arylisoquinolones resulted in versatile 4-formylated 3-arylisoquinolones that were further derivatized into 12-oxobenzo[c]phenanthridinones, 4-alkoxymethyl-3-arylisoquinolones, 3-aryl-4-phenoxymethylisoquinolones, 4-aminometh
- Khadka, Daulat Bikram,Yang, Su Hui,Cho, Suk Hee,Zhao, Chao,Cho, Won-Jea
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experimental part
p. 250 - 261
(2012/01/05)
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- Toward optimization of the second aryl substructure common to transthyretin amyloidogenesis inhibitors using biochemical and structural studies
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Transthyretin (TTR) amyloidogenesis inhibitors are typically composed of two aromatic rings and a linker. We have previously established optimal structures for one aromatic ring and the linker. Herein, we employ a suboptimal linker and an optimal aryl-X substructure to rank order the desirability of aryl-Z substructures-using a library of 56 N-(3,5-dibromo-4-hydroxyphenyl) benzamides. Coconsideration of amyloid inhibition potency and ex vivo plasma TTR binding selectivity data reveal that 2,6, 2,5, 2, 3,4,5, and 3,5 substituted aryls bearing small substituents generate the most potent and selective inhibitors, in descending order. These benzamides generally lack undesirable thyroid hormone receptor binding and COX-1 inhibition activity. Three high-resolution TTR ? inhibitor crystal structures (1.31-1.35 ?) provide insight into why these inhibitors are potent and selective, enabling future structure-based design of TTR kinetic stabilizers.
- Johnson, Steven M.,Connelly, Stephen,Wilson, Ian A.,Kelly, Jeffery W.
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supporting information; experimental part
p. 1115 - 1125
(2009/12/24)
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- Total synthesis of 8-oxypseudopalmatine and 8-oxypseudoberberine via ring-closing metathesis
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Concise synthesis of 8-oxypseudopalmatine and 8-oxypseudoberberine has been achieved using ruthenium-catalyzed ring-closing metathesis (RCM) as the key step, in which the RCM substrates, 3-arylisoquinolinones, were prepared by lithiated cycloaddition reac
- Van, Hue Thi My,Yang, Su Hui,Khadka, Daulat Bikram,Kim, Yong-Chul,Cho, Won-Jea
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experimental part
p. 10142 - 10148
(2010/02/27)
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- Novel potent and efficacious nonpeptidic urotensin II receptor agonists
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Six different series of nonpeptidic urotensin II receptor agonists have been synthesized and evaluated for their agonistic activity in a cell-based assay (R-SAT). The compounds are ring-opened analogues of the isochromanone-based agonist AC-7954 with different functionalities constituting the linker between the two aromatic ring moieties. Several of the compounds are highly potent and efficacious, with N-[1-(4-chlorophenyl)-3-(dimethylamino)- propyl]-4-phenylbenzamide oxalate (5d) being the most potent. The pure enantiomers of 5d were obtained from the corresponding diastereomeric amides. It was shown by a combination of X-ray crystallography and chemical correlation that the activity resides in the S-enantiomer of 5d (pEC50 7.49).
- Lehmann, Fredrik,Pettersen, Anna,Currier, Erika A.,Sherbukhin, Vladimir,Olsson, Roger,Hacksell, Uli,Luthman, Kristina
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p. 2232 - 2240
(2007/10/03)
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- Isochromanone-based urotensin-II receptor agonists
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A series of analogues of the selective non-peptide urotensin II (UII) receptor agonist 3-(4-chlorophenyl)-3-(2-dimethylaminoethyl)-isochroman-1-one (AC-7954, 1) was synthesized and evaluated for UII agonist activity using a functional cell-based assay. The introduction of a methyl group in the 4-position resulted in a complete loss of activity, whereas substituents in the aromatic rings were beneficial. Sterically demanding amino groups were also detrimental to the activity. Several potent agonists were identified, six compounds being equally or more potent than 1. The most potent compound in the series was the 6,7-dimethyl analogue of 1 (16, pEC50 6.87). The racemate of 16 was resolved into the pure enantiomers using preparative straight phase HPLC. It was shown that the potency resides in the (+)-enantiomer (pEC50 7.11). The synthesized compounds seem to be selective for the UII receptor as no activities were observed at the closely related SSTR3 and 5 receptors.
- Lehmann, Fredrik,Currier, Erika A.,Olsson, Roger,Hacksell, Uli,Luthman, Kristina
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p. 3057 - 3068
(2007/10/03)
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- Asymmetric synthesis of 3-substituted dihydro-2H-isoquinolin-1-ones, dihydro- and tetrahydroisoquinolines via 1,2-addition/ring closure
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The asymmetric synthesis of 3-substituted dihydro-2H-isoquinolin-1-ones, dihydro- and tetrahydroisoquinolines is described. The key operation is a tandem 1,2-addition/ring closure sequence employing lithiated ortho-toluamides and aldehyde SAMP- or RAMP-hydrazones as substrates, followed by N-N bond cleavage to remove the auxiliary. Moderate to good yields and high enantiomeric excesses (ee = 85-99%) are reached.
- Enders, Dieter,Braig, Volker,Boudou, Marine,Raabe, Gerhard
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p. 2980 - 2990
(2007/10/03)
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- CCR8 INHIBITORS
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Disclosed is an inhibitor of CCR8 that is represented by Structural Formula (I). Also disclosed are pharmaceutical compositions comprising a pharmaceutically acceptable carrier or diluent and a CCR8 inhibitor represented by Structural Formula (I). Also disclosed is a method of treating inflammatory disorders in a subject by administering a CCR8 inhibitor to the subject.
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- CCR8 INHIBITORS
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Disclosed are CCR8 inhibitors represented by Structural Formulas (I). The variables in Structural Formula (I) are described herein. Also disclosed are methods of treating a subject with a CCR8 mediated condition, especially asthma, by administering one of the disclosed CCR8 inhibitors to the subject.
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- Synthesis and microbiological activity of some N-(2-hydroxy-4-substitutedphenyl)benzamides, phenylacetamides and furamides as the possible metabolites of antimicrobial active benzoxazoles
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The synthesis of some N-(2-hydroxy-4-substitutedphenyl)benzamides, phenylacetamides and furamides as the possible metabolites of benzoxazoles ( II(1-15)) was performed in order to determine their in vitro antimicrobial activity against three Gram-positive bacteria, two Gram-negative bacteria and the fungus Candida albicans and their activities were compared with several control drugs. The compounds II(11), II(12), and II(13) were found active at a MIC value of 12.5 μg/ml against the Gram-negative microorganism Pseudomonas aeruginosa. Most of the compounds show antibacterial activity at MIC a value of 25 μg/ml against the Gram-positive bacteria Staphylococcus aureus. For the antifungal activity against C. albicans, compound II(10) was found more active than the other derivatives. The antimicrobial activity of some of these benzamides, phenylacetamides (II(1) and II(10)) which are the possible metabolites of benzoxazoles, was also compared to their corresponding cyclic analogues III-IV. Compound II(10) possesses two dilutions better antifungal activity than its cyclic analogue, benzoxazole IV, against C. albicans.
- Aki-Sener, Esin,Bingoel, Kamuran K.,Temiz-Arpaci, Oezlem,Yalcin, Ismail,Altanlar, Nurten
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p. 451 - 456
(2007/10/03)
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- Novel sparteine-mediated enantio-dichotomic formal synthesis of (R)-(-)- and (S)-(+)-curcuphenol
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High and opposite enantiodiscriminations were observed between tertiary amides and secondary amides in the sparteine-mediated lateral metalation-allylation of 2-ethyl-m-toluamide derivatives (2a, 2e). The results described above have been applied for the formal synthesis of both enantiomers of curcuphenol. The brief mechanistic studies suggested that stereoinformation was introduced after the deprotonation step.
- Kimachi,Takemoto
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p. 2700 - 2704
(2007/10/03)
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- A Selective Receptor for Arginine Derivatives in Aqueous Media. Energetic Consequences of Salt Bridges That Are Highly Exposed to Water
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Quantitative measures of salt-bridge-type interactions in a highly exposed aqueous environment have been obtained by modifying the well-studied cyclophane platform 1 to include carboxylates in close proximity to bound, cationic guests, producing hosts 2 and 3. Many guests show significantly enhanced binding to 2 and 3, but cations of the RNMe3+ type show little or no enhancement. We propose that the latter observations result from the fact that RNMe3+ compounds have very diffuse positive charges. Guests that show enhanced binding have focused regions of large, positive electrostatic potential. The highly charged 3 is able to bind very polar, very well-solvated guests, including a series of arginine-based dipeptides. Neutral, water-soluble host 4 was prepared and found to show a decreased affinity for cationic guests. We propose a novel induced dipole mechanism to rationalize these results.
- Ngola, Sarah M.,Kearney, Patrick C.,Mecozzi, Sandro,Russell, Keith,Dougherty, Dennis A.
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p. 1192 - 1201
(2007/10/03)
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- Bis tertiary amide inhibitors of the HIV-1 protease generated via protein structure-based iterative design
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A series of potent nonpeptide inhibitors of the HIV protease have been identified. Using the structure of compound 3 bound to the HIV protease, his tertiary amide inhibitor 9 was designed and prepared. Compound 9 was found to be about 17 times more potent than 3, and the structure of the protein- ligand complex of 9 revealed the inhibitor binds in an inverted binding mode relative to 3. Examination of the protein-ligand complex of 9 suggested several modifications in the P1 and P1' pockets. Through these modifications it was possible to improve the activity of the inhibitors another 100-fold, highlighting the utility of crystallographic feedback in inhibitor design. These compounds were found to have good antiviral activity in cell culture, were selective for the HIV protease, and were orally available in three animal models.
- Melnick, Michael,Reich, Siegfried H.,Lewis, Kathy K.,Mitchell Jr., Lennert J.,Nguyen, Dzuy,Trippe, Anthony J.,Dawson, Heather,Davies II, Jay F.,Appelt, Krzysztof,Wu, Bor-Wen,Musick, Linda,Gehlhaar, Dan K.,Webber, Stephanie,Shetty, Bhasker,Kosa, Maha,Kahil, Deborah,Andrada, Dominic
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p. 2795 - 2811
(2007/10/03)
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- Aminoalkylindoles: Structure - Activity Relationships of Novel Cannabinoid Mimetics
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Aminoalkylindoles (AAIs) are a novel series of cannabinoid receptor ligands.In this report we disclose the structural features of AAIs which are important for binding to this receptor as measured by inhibition of binding of 3H>Win 55212-2 (5).Functional activity in the mouse vas deferens is also noted and used to distinguish agonists from potential antagonists.The key structural features for potent cannabinoid activity in this series are a bicyclic (naphthyl) substituent at the 3-position, a small (H) substituent at the 2-position, and an aminoethyl (morpholinoethyl) substituent at the 1-position.A 6-bromo analog, Win 54461 (31), has been identified as a potential cannabinoid receptor antagonist.Modeling experiments were done to develop a pharmacophore and also to compare AAI structures with those of classical cannabinoids.The fact that the cannabinoid AAIs arose out of work on a series of cyclooxygenase inhibitors makes sense now that an endogenous cannabinoid ligand has been identified which is a derivative of arachidonic acid.Because of their unique structures and physical properties, AAIs provide useful tools to study the structure and function of the cannabinoid receptor(s).
- Eissenstat, Michael A.,Bell, Malcolm R.,D'Ambra, Thomas E.,Alexander, E. John,Daum, Sol J.,et al.
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p. 3094 - 3105
(2007/10/02)
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- 1(2H)-isoquinolinones and 1-isoquinolineamines as cancer chemotherapeutic agents
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3-(1-Naphthalenyl)-1(2H)-isoquinolinones and 3-(1-naphthalenyl)-1-isoquinolineamines are useful as cancer chemotherapeutic agents.
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- A New Class of Nonhormonal Pregnancy-Terminating Agents. Synthesis and Contragestational Activity of 3,5-Diaryl-s-triazoles
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A series of 3,5-diaryl-s-triazoles were synthesized and evaluated as postimplantation contragestational agents.The introduction of various substituents (e.g., an o-alkyl chain on one phenyl and a m-alkoxy group on the other) was found to increase the potency.Several compounds with very high pregnancy-terminating activity in both hamsters and rats were obtained.One of these, 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-s-triazole, DL 111 (36), was selected for detailed evaluation in various animal species.A synthetic scheme for the preparation of these compounds and preliminary structure-activity relationships are presented.
- Omodei-Sale, Amedeo,Consonni, Pietro,Galliani, Giulio
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p. 1187 - 1192
(2007/10/02)
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