“…Other strategies involve the reaction between isatoic anhydride and thiourea derivatives to affect ring closure , and the use of orthoformates to react with both nitrogen atoms . Other groups have also utilized the quinazolinone scaffold in combinatorial synthesis. , …”
I. Introduction 893 A. The Drug Discovery Process 895 B. Characteristics of Privileged Substructures 896 C. Scope of the Review 897 II. Phenyl-Substituted Monocycles 898 A. Biphenyls 898 B. Arylpiperidines 899 C. Arylpiperazines 901 D. 1,4-Dihydropyridines 901 E. Dihydropyrimidones 902 III. Fused [7−6] Ring Systems 904 A. 1,4-Benzodiazepin-2-ones 904 B. 1,5-Benzodiazepin-2-ones 905 C. 1,4-Benzodiazepin-2,5-diones and Pyrrolo-[2,1-c][1,4]benzodiazepin-5,11-diones 906 D. 1,4-Benzothiazepin-5-ones 907 E. 5,11-Dihydro-benzo[e]pyrido[3,2-b][1,4]diazepin-6-ones 907 IV. Fused [6−6] Ring Systems 908 A. Benzopyrans, Chromones, Coumarins, and Pyranocoumarins 908 1. Benzopyrans 908 2. Chromones 909 3. Coumarins 911 4. Pyranocoumarins 911 B. Quinoxalines/Quinazolines 913 1. 3,4-Dihydroquinoxalin-2-ones (Benzopiperazinones) 913 2. Quinazolinones 915 3. Quinazolindiones 916 4. Imidazoquinoxalines 917 V. Fused [5−6] Ring Systems 919 A. Indoles 919 B. Benzimidazoles 921 C. Benzofurans 922 D. Benzothiophenes 924 VI. Conclusions 925 VII. Acknowledgments 925 VIII. References 925
“…Other strategies involve the reaction between isatoic anhydride and thiourea derivatives to affect ring closure , and the use of orthoformates to react with both nitrogen atoms . Other groups have also utilized the quinazolinone scaffold in combinatorial synthesis. , …”
I. Introduction 893 A. The Drug Discovery Process 895 B. Characteristics of Privileged Substructures 896 C. Scope of the Review 897 II. Phenyl-Substituted Monocycles 898 A. Biphenyls 898 B. Arylpiperidines 899 C. Arylpiperazines 901 D. 1,4-Dihydropyridines 901 E. Dihydropyrimidones 902 III. Fused [7−6] Ring Systems 904 A. 1,4-Benzodiazepin-2-ones 904 B. 1,5-Benzodiazepin-2-ones 905 C. 1,4-Benzodiazepin-2,5-diones and Pyrrolo-[2,1-c][1,4]benzodiazepin-5,11-diones 906 D. 1,4-Benzothiazepin-5-ones 907 E. 5,11-Dihydro-benzo[e]pyrido[3,2-b][1,4]diazepin-6-ones 907 IV. Fused [6−6] Ring Systems 908 A. Benzopyrans, Chromones, Coumarins, and Pyranocoumarins 908 1. Benzopyrans 908 2. Chromones 909 3. Coumarins 911 4. Pyranocoumarins 911 B. Quinoxalines/Quinazolines 913 1. 3,4-Dihydroquinoxalin-2-ones (Benzopiperazinones) 913 2. Quinazolinones 915 3. Quinazolindiones 916 4. Imidazoquinoxalines 917 V. Fused [5−6] Ring Systems 919 A. Indoles 919 B. Benzimidazoles 921 C. Benzofurans 922 D. Benzothiophenes 924 VI. Conclusions 925 VII. Acknowledgments 925 VIII. References 925
“…For example, aryl hydrazine urea-based antibacterial agents were identified from a 10,000 semi-carbazone library [34]. Those agents act specifically against Gram-positive bacteria via disruption of the bacterial cell wall biosynthesis pathway.…”
Section: Strategies Toward the Development Of Antimicrobial Peptides mentioning
Antibiotic resistant bacterial strains represent a global health problem with a strong social and economic impact. Thus, there is an urgent need for the development of antibiotics with novel mechanisms of action. There is currently an extensive effort to understand the mode of action of antimicrobial peptides which are considered as one alternative to classical antibiotics. The main advantage of this class of substances, when considering bacterial resistance, is that they rapidly, within minutes, kill bacteria. Antimicrobial peptides can be found in every organism and display a wide spectrum of activity. Hence, the goal is to engineer peptides with an improved therapeutic index, i.e. high efficacy and target specificity. For the rational design of such novel antibiotics it is essential to elucidate the molecular mechanism of action. Biophysical studies have been performed using to a large extent membrane model systems demonstrating that there are distinctive different mechanisms of bacterial killing by antimicrobial peptides. One can distinguish between peptides that permeabilize and/or disrupt the bacterial cell membrane and peptides that translocate through the cell membrane and interact with a cytosolic target. Lantibiotics exhibit specific mechanisms, e.g. binding to lipid II, a precursor of the peptidoglycan layer, either resulting in membrane rupture by pore formation or preventing cell wall biosynthesis. The classical models of membrane perturbation, pore formation and carpet mechanism, are discussed and related to other mechanisms that may lead to membrane dysfunction such as formation of lipid-peptide domains or membrane disruption by formation of non-lamellar phases. Emphasis is on the role of membrane lipid composition in these processes and in the translocation of antimicrobial peptides.
“…Urea-Based Antibacterials. A second example of the isolation and identification of a biologically active byproduct from a library was reported by Wilson (Figure ) . A 10 000 member mixture-library of semicarbazones ( 96 ; library 5.9) was synthesized in solution as shown in Figure .…”
Section: Biologically Active Libraries (Tables −5)mentioning
confidence: 99%
“… 9 Inhibitors of influenza virus fusion 10 Hydrazinyl-urea byproduct identified as potent antibacterial agent 11 Disulfide library 5.11 based on psammaplin A. , 12 Natural products as library templates in 2001. 13 Advances in REM resin methodology. , 14 Substituted hydroxylamines from REM resin …”
An exhaustive compilation of biologically active libraries covering the years 1992-1997 was presented in a previous review [1a]. In that review, libraries were divided among 4 major categories, including those active against proteases, non-proteolytic enzymes, Gprotein coupled receptors, and non-G-protein coupled receptors. A generic structure for each library was provided as well as the structure of the most active member. The number of biologically active libraries reported in the literature during this time period (86 total) represents <25% of the total number of published library constructs. Disclosure of library synthesis without accompanying screening data is a more common occurrence. Because these types of libraries are equally important to the practicing combinatorial chemist, it was thought that a comprehensive listing of such libraries spanning the years 1992-1997 would be a useful supplement to the previous review [1a,b].Library constructs [2-248] listed herein are relegated to one of five tables. Table 1 is entitled 'Scaffold derivatization' and includes all constructs in which a multi-functional scaffold is modified in some fashion to create a library. An example of a construct found in Table 1 would be the sequential addition of three nucleophiles to trichloropyrimidine. Table 2, entitled 'Acyclic synthesis', lists all linear constructs such as those derived from multi-component Ugi condensations.
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