1,721,043 research outputs found
Polycondensed heterocycles. IV. Synthesis of 1,4-Dioxo-2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzothiazine
No full textA method for the synthesis of the title compound 3 consisted of an intramolecular cyclization in a stannic chloride catalyzed Friedel‐Crafts reaction of N‐(2‐methylthiophenyl)‐5‐oxoproline chloride 10, prepared by chlorination of the corresponding acid 9 obtained by hydrolysis of its ethyl ester 8. Condensation of 2‐methylthioaniline 4 with diethyl bromomalonate 5 afforded diethyl 2‐methylthioanilinomalonate 6 which gave 8 either directly by reaction with ethyl acrylate or by alkylation with ethyl β‐bromopropionate or ethyl acrylate and cyclization of resulting triethyl 2‐(2‐methylthio)anilino‐2‐carboxyglutarate 7. This method was not convenient because of the poor yield of 3 (14%). On the other hand, cyclization of N‐(2‐mercaptophenyl)‐5‐oxoproline 14 with DCC and DMAP provided 3 in 45% yield. Oxidation with m‐CPBA of the esters 11 and 8, demethylation via the Pummerer rearrangement of the respective sulphoxides 12 and 17 with TFAA and oxidation with iodine of resulting N‐(2‐mercap‐tophenyl)‐5‐oxoproline esters 13 and 18 gave the corresponding disulphides 16 and 19. Hydrolysis of these latter compounds and reduction of the resulting bis[2‐[2‐(hydroxycarbonyl)‐5‐oxo‐1‐pyrrolidinyl]phenyl] disulphide 15 with sodium dithionite afforded the required 14. Deprotection of t‐butyl ester 13 with TFA at 55° to obtain 14 led to 3 in 42% yield. Finally the Pummerer rearrangement of N‐(2‐methylsulphinylphenyl)‐5‐oxo‐proline 20 yielded the mixture of 14 and 15. Copyright © 1990 Journal of Heterocyclic Chemistry
Polycondensed heterocycles. VI. A new efficient synthesis of 4H-pyrrolo[2,1-c][1,4]benzothiazines
No full textA novel and efficient method to obtain 4H-pyrrolo [2,1-c][1,4] benzothiazine and its 4-alkyl and 4-aryl derivatives via an intramolecular nucleophilic aromatic fluoride displacement has been developed. © 1990, Taylor & Francis Group, LLC. All rights reserved
Benzothiazine and Benzothiazepine derivatives: synthesis and preliminary biological evaluation
No full textSeveral tricyclic benzothiazines and benzothiazepines have been synthesized by different intramolecular cyclization reactions. Their functionalization led to biologically active compounds. Some stereochemical aspects as well as biological responses have been outlined
Polycondensed heterocycles. VII. A convenient synthesis of pyrrolo[1,2-a]quinoxaline derivatives by intramolecular aromatic nucleophilic displacement
No full text4-(4-Methyl-1-piperazinyl)-7-trifluoromethylpyrrolo[1,2-a]quinoxaline (CGS 12066B) and related analogs were prepared in good overall yield through a reaction sequence involving as a key step the intramolecular substitution of aromatic fluoride or nitro groups by a carboxamide moiety. © 1991, Taylor & Francis Group, LLC. All rights reserved
The stereoselective targeting of a specific enzyme-substrate complex is the molecular mechanism for the synergic inhibition of HIV-1 reverse transcriptase by (R)-(-)-PPO464. A novel generation of nonnucleoside inhibitors.
No full textThe human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitor pyrrolopyridooxazepinone (PPO) derivative, (+/-)-PPO294, was shown to be active toward wild type and mutated HIV-1 RT and to act synergistically in combination with 3'-azido-3'-deoxythymidine (Campiani, G., Morelli, E., Fabbrini, M., Nacci, V., Greco, G., Novellino, E., Ramunno, A., Maga, G., Spadari, S., Caliendo, G., Bergamini, A., Faggioli, E., Uccella, I., Bolacchi, F., Marini, S., (1999) J. Med. Chant. 42, 4462-4470). The (+/-)-PPO294 racemate was resolved into its pure enantiomers, and the absolute configuration was determined by x-ray analysis. Only one enantiomer, (R)-(-)-PPO464, displayed antiviral activity against both the wild type and the K103N mutant HIV-1 RT and was found to interact exclusively with the reaction intermediate formed by RT complexed with both the DNA and the nucleotide substrates. Being the first compound of its class to display this behavior, (R)-(-)-PPO464 is the representative of a novel generation of nonnucleoside inhibitors. (R)(-)-PPO464 showed significant synergism when tested in combination with other RT inhibitors and efficiently inhibited viral replication when tested against the laboratory strain HIV-1 IIIB or against either wild type or multidrug-resistant clinical isolates. Pharmacokinetic studies in mice and rats showed a more favorable profile for (R)-(-)-PPO464 than for the corresponding racemate. (R)-(-)-PPO464 was also found to easily cross the blood-brain barrier. The coadministration of the HIV-1 protease inhibitor ritonavir increased the bioavailability of (R)-(-)-PPO464, having little effect on its plasma and brain elimination rates
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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