Creating chemical diversity space by scaffold decoration of dihydropyrimidines

2005 ◽  
Vol 77 (1) ◽  
pp. 155-161 ◽  
Author(s):  
Doris Dallinger ◽  
C. Oliver Kappe
Keyword(s):  
Drug Discovery ◽  
Driving Force ◽  
New Technologies ◽  
Materials Science ◽  
Building Blocks ◽  
Chemical Diversity ◽  
Combinatorial Synthesis ◽  
Biologically Active ◽  
Compound Libraries

The demand for diverse compound libraries for screening in drug discovery and materials science is the driving force behind the development of new technologies for rapid parallel and combinatorial synthesis. The focus of this article will be on the scaffold decoration of biologically active dihydropyrimidines (DHPMs) of the Biginelli type, exploring the diversity on all six positions around the scaffold. This opens up the generation of a very large number of analogs given the commercial availability of the building blocks that are used in the functionalization process.

Oxazole-Based Compounds As Anticancer Agents

2020 ◽  
Vol 26 (41) ◽  
pp. 7337-7371 ◽  
Author(s):  
Maria A. Chiacchio ◽  
Giuseppe Lanza ◽  
Ugo Chiacchio ◽  
Salvatore V. Giofrè ◽  
Roberto Romeo ◽  
...  
Keyword(s):  
Cancer Research ◽  
Drug Discovery ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Chemical Diversity ◽  
Biologically Active ◽  
New Drugs ◽  
The Core ◽  
Anti Cancer ◽  
Biologically Active Derivatives

: Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

ChemInform Abstract: Combinatorial Synthesis - The Design of Compound Libraries and Their Application to Drug Discovery

ChemInform ◽  
2010 ◽  
Vol 26 (43) ◽  
pp. no-no
Author(s):  
N. K. TERRETT ◽  
M. GARDNER ◽  
D. W. GORDON ◽  
R. J. KOBYLECKI ◽  
J. STEELE
Keyword(s):  
Drug Discovery ◽  
Combinatorial Synthesis ◽  
Compound Libraries

ChemInform Abstract: Combinatorial Synthesis - The Design of Compound Libraries and Their Application to Drug Discovery

ChemInform ◽  
2010 ◽  
Vol 26 (47) ◽  
pp. no-no
Author(s):  
N. K. TERRETT ◽  
M. GARDNER ◽  
D. W. GORDON ◽  
R. J. KOBYLECKI ◽  
J. STEELE
Keyword(s):  
Drug Discovery ◽  
Combinatorial Synthesis ◽  
Compound Libraries

Combinatorial synthesis — the design of compound libraries and their application to drug discovery

Tetrahedron ◽  
1995 ◽  
Vol 51 (30) ◽  
pp. 8135-8173 ◽  
Author(s):  
Nicholas K. Terrett ◽  
Mark Gardner ◽  
David W. Gordon ◽  
Ryszard J. Kobylecki ◽  
John Steele
Keyword(s):  
Drug Discovery ◽  
Combinatorial Synthesis ◽  
Compound Libraries

scholarly journals Open Innovation for Phenotypic Drug Discovery: The PD2 Assay Panel

2011 ◽  
Vol 16 (6) ◽  
pp. 588-602 ◽  
Author(s):  
Jonathan A. Lee ◽  
Shaoyou Chu ◽  
Francis S. Willard ◽  
Karen L. Cox ◽  
Rachelle J. Sells Galvin ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Open Source ◽  
Open Innovation ◽  
Chemical Diversity ◽  
Statistical Validation ◽  
Innovation Potential ◽  
Compound Libraries ◽  
Therapeutic Value ◽  
Lead Generation ◽  
Internal Sources

Phenotypic lead generation strategies seek to identify compounds that modulate complex, physiologically relevant systems, an approach that is complementary to traditional, target-directed strategies. Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target “agnostic” fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD2), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD2 assay panel. Analysis of PD2 submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD2 have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD2, may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery.

19F-NMR in Target-based Drug Discovery

2019 ◽  
Vol 26 (26) ◽  
pp. 4964-4983 ◽  
Author(s):  
CongBao Kang
Keyword(s):  
Drug Discovery ◽  
Conformational Changes ◽  
Protein Structures ◽  
19F Nmr ◽  
Binding Affinities ◽  
Protein Ligand Interactions ◽  
Compound Libraries ◽  
Ligand Interactions ◽  
Reference Ligand ◽  
Hit Identification

Solution NMR spectroscopy plays important roles in understanding protein structures, dynamics and protein-protein/ligand interactions. In a target-based drug discovery project, NMR can serve an important function in hit identification and lead optimization. Fluorine is a valuable probe for evaluating protein conformational changes and protein-ligand interactions. Accumulated studies demonstrate that 19F-NMR can play important roles in fragment- based drug discovery (FBDD) and probing protein-ligand interactions. This review summarizes the application of 19F-NMR in understanding protein-ligand interactions and drug discovery. Several examples are included to show the roles of 19F-NMR in confirming identified hits/leads in the drug discovery process. In addition to identifying hits from fluorinecontaining compound libraries, 19F-NMR will play an important role in drug discovery by providing a fast and robust way in novel hit identification. This technique can be used for ranking compounds with different binding affinities and is particularly useful for screening competitive compounds when a reference ligand is available.

Current Approaches to Drug Discovery for Chagas Disease: Methodological Advances

2019 ◽  
Vol 22 (8) ◽  
pp. 509-520
Author(s):  
Cauê B. Scarim ◽  
Chung M. Chin
Keyword(s):  
Drug Discovery ◽  
Chagas Disease ◽  
Drug Candidates ◽  
Lead Compounds ◽  
New Drug ◽  
Compound Libraries ◽  
Screening Assays ◽  
Cruzi Infection

Background: In recent years, there has been an improvement in the in vitro and in vivo methodology for the screening of anti-chagasic compounds. Millions of compounds can now have their activity evaluated (in large compound libraries) by means of high throughput in vitro screening assays. Objective: Current approaches to drug discovery for Chagas disease. Method: This review article examines the contribution of these methodological advances in medicinal chemistry in the last four years, focusing on Trypanosoma cruzi infection, obtained from the PubMed, Web of Science, and Scopus databases. Results: Here, we have shown that the promise is increasing each year for more lead compounds for the development of a new drug against Chagas disease. Conclusion: There is increased optimism among those working with the objective to find new drug candidates for optimal treatments against Chagas disease.

Secondary Metabolites of Plant Origin containing Carbazole as Lead Molecule: A Review

2019 ◽  
Vol 05 ◽  
Author(s):  
Atul Sharma ◽  
Devender Pathak
Keyword(s):  
Drug Discovery ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Chemical Compounds ◽  
Lethal Effect ◽  
Chemical Diversity ◽  
Chemical Transformations ◽  
Pharmacological Effects ◽  
Structural Class ◽  
Biological Targets

Keeping this fact that study of a body is biology but life is all about chemicals and chemical transformations, many medicinal chemist start research in finding new and novel chemical compounds which having pharmacological activities. Most of those chemical compounds which are having active pharmacological effects are heterocyclic compounds. Heterocyclic compounds clutch a particular place among pharmaceutically active natural and synthetic compounds. The ability to serve both as biomimetics and reactive pharmacophores of heterocyclic nuclei is incredible and it has principally contributed to their unique value as traditional key elements of numerous drugs. These heterocyclic nuclei offer a huge area for new lead molecules for drug discovery and for generation of activity relationships with biological targets to enhance pharmacological effects. For these reasons, it is not surprising that this structural class has received special attention in drug discovery. The hydrogen bond acceptors and donors arranged in a manner of a semi-rigid skeleton in heterocyclic rings and therefore they can present a varied display of significant pharmacophores. Lead identification and optimization of drug target probable can be achieved by generation of chemical diversity produced by derivatization of heterocyclic pharmacophores with different groups or substituents. A tricyclic carbazole nucleus is an integral part of naturally occurring alkaloids and synthetic derivatives, possessing various potential biological activities such as anticancer, antimicrobial and antiviral. Binding mechanism of carbazole with target receptor as a molecule or fused molecule exhibits the potential lethal effect.

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