Methods to Access 2-aminobenzimidazoles of Medicinal Importance

: Benzimidazole (BI) and derivatives are interesting because several of these compounds have been found to have a diversity of biological activities with clinical applications. In view of their importance, the synthesis of BI and its derivatives is still considered as a challenge for synthetic chemists. Examples of compounds used in medicinal chemistry containing BI, as important nucleus, are Astemizole (antihistaminic), Omeprazole (antiulcerative) and Rabendazole (fungicide), some of these compounds have the 2- aminobenzimidazole (2ABI) as base nucleus. The structure of 2ABI derivatives contains a cyclic guanidine moiety, which is interesting because of its free lone pairs, labile hydrogen atoms and planar delocalized structure. The delocalized 10-π electron system and the extension of the electron conjugation with the exocyclic amino group, in 2ABI, making these heterocycles to have amphoteric character. The 2ABI has been used as building blocks for the synthesis of several BI derivatives as medicinally important molecules. On these bases, herein, we present a bibliographic review concerning the recent methodologies used in the synthesis of 2ABIs, including the substituted ones.

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The Generated Databases (GDBs) as a Source of 3D-shaped Building Blocks for Use in Medicinal Chemistry and Drug Discovery

CHIMIA International Journal for Chemistry ◽

10.2533/chimia.2020.241 ◽

2020 ◽

Vol 74 (4) ◽

pp. 241-246 ◽

Cited By ~ 2

Author(s):

Kris Meier ◽

Sven Bühlmann ◽

Josep Arús-Pous ◽

Jean-Louis Reymond

Keyword(s):

Drug Discovery ◽

Medicinal Chemistry ◽

Organic Molecules ◽

Chemical Space ◽

Building Blocks ◽

Chiral Molecules ◽

Hydrogen Atoms ◽

Quaternary Centers ◽

Medical Needs ◽

Unmet Medical Needs

Drug discovery is in constant need of new molecules to develop drugs addressing unmet medical needs. To assess the chemical space available for drug design, our group investigates the generated databases (GDBs) listing all possible organic molecules up to a defined size, the largest of which is GDB-17 featuring 166.4 billion molecules up to 17 non-hydrogen atoms. While known drugs and bioactive compounds are mostly aromatic and planar, the GDBs contain a plethora of non-aromatic 3D-shaped molecules, which are very useful for drug discovery since they generally have more desirable absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. Here we review GDB enumeration methods and the selection and synthesis of GDB molecules as modulators of ion channels. We summarize the constitution of GDB subsets focusing on fragments (FDB17), medicinal chemistry (GDBMedChem) and ChEMBL-like molecules (GDBChEMBL), and the ring system database GDB4c as a rich source of novel 3D-shaped chiral molecules containing quaternary centers, such as the recently reported trinorbornane.

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Pyrazole Carboxylic Acid and Derivatives: Synthesis and Biological Applications

Mini-Reviews in Organic Chemistry ◽

10.2174/1570193x17999200507094857 ◽

2020 ◽

Vol 17 ◽

Author(s):

Adnan Cetin

Keyword(s):

Organic Chemistry ◽

Biological Activity ◽

Carboxylic Acid ◽

Heterocyclic Compounds ◽

Medicinal Chemistry ◽

Biological Activities ◽

Building Blocks ◽

Literature Survey ◽

Synthetic Methods ◽

Biological Applications

: The heterocyclic compounds are the building blocks for synthesis of the different biological active compounds in the organic chemistry. Heterocyclic compounds have versatile synthetic applicability and biological activity. Pyrazole carboxylic acid derivatives are significant scaffold structures in heterocyclic compounds due to biologic activities such as antimicrobial, anticancer, inflammatory, antidepressant, antifungal anti-tubercular and antiviral etc. The aim of this mini-review is an overview synthesis of pyrazole carboxylic acid derivatives and their biologic applications. The summarized literature survey presents in detail biological activities of pyrazole carboxylic acid derivatives and their various synthetic methods. This mini-review can be guide to many scientists in medicinal chemistry.

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Cascade CuH-Catalyzed Conversion of Alkynes to Enantioenriched 1,1-Disubstituted Products

10.26434/chemrxiv.7961633.v1 ◽

2019 ◽

Author(s):

De-Wei Gao ◽

Yang Gao ◽

Huiling Shao ◽

Tian-Zhang Qiao ◽

Xin Wang ◽

...

Keyword(s):

Organic Synthesis ◽

Medicinal Chemistry ◽

Proteasome Inhibitors ◽

Building Blocks ◽

Unique Role ◽

Efficient Strategy ◽

Carbon Centers ◽

Rapid Access ◽

Cascade Catalysis ◽

Privileged Scaffolds

Enantioenriched α-aminoboronic acids play a unique role in medicinal chemistry and have emerged as privileged pharmacophores in proteasome inhibitors. Additionally, they represent synthetically useful chiral building blocks in organic synthesis. Recently, CuH-catalyzed asymmetric alkene hydrofunctionalization has become a powerful tool to construct stereogenic carbon centers. In contrast, applying CuH cascade catalysis to achieve reductive 1,1-difunctionalization of alkynes remains an important, but largely unaddressed, synthetic challenge. Herein, we report an efficient strategy to synthesize α-aminoboronates via CuH-catalyzed hydroboration/hydroamination cascade of readily available alkynes. Notably, this transformation selectively delivers the desired 1,1-heterodifunctionalized product in favor of alternative homodifunctionalized, 1,2-heterodifunctionalized, or reductively monofunctionalized byproducts, thereby offering rapid access to these privileged scaffolds with high chemo-, regio- and enantioselectivity.

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Potential Triazole-based Molecules for the Treatment of Neglected Diseases

Current Medicinal Chemistry ◽

10.2174/0929867324666170727103901 ◽

2019 ◽

Vol 26 (23) ◽

pp. 4403-4434 ◽

Cited By ~ 5

Author(s):

Susimaire Pedersoli Mantoani ◽

Peterson de Andrade ◽

Talita Perez Cantuaria Chierrito ◽

Andreza Silva Figueredo ◽

Ivone Carvalho

Keyword(s):

Effective Treatment ◽

Chagas Disease ◽

Medicinal Chemistry ◽

Biological Activities ◽

Neglected Diseases ◽

Triazole Derivatives ◽

Wide Range ◽

The World ◽

Great Relevance ◽

The Moment

Neglected Diseases (NDs) affect million of people, especially the poorest population around the world. Several efforts to an effective treatment have proved insufficient at the moment. In this context, triazole derivatives have shown great relevance in medicinal chemistry due to a wide range of biological activities. This review aims to describe some of the most relevant and recent research focused on 1,2,3- and 1,2,4-triazolebased molecules targeting four expressive NDs: Chagas disease, Malaria, Tuberculosis and Leishmaniasis.

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Synthesis and Biological Activity of Hydrazones and Derivatives: A Review

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666191014142448 ◽

2020 ◽

Vol 20 (5) ◽

pp. 342-368 ◽

Cited By ~ 5

Author(s):

Juliana de Oliveira Carneiro Brum ◽

Tanos Celmar Costa França ◽

Steven R. LaPlante ◽

José Daniel Figueroa Villar

Keyword(s):

Biological Activity ◽

Medicinal Chemistry ◽

Biological Activities ◽

New Drugs ◽

New Drug ◽

Cancer Inflammation

Hydrazones and their derivatives are very important compounds in medicinal chemistry due to their reported biological activity for the treatment of several diseases, like Alzheimer’s, cancer, inflammation, and leishmaniasis. However, most of the investigations on hydrazones available in literature today are directed to the synthesis of these molecules with little discussion available on their biological activities. With the purpose of bringing lights into this issue, we performed a revision of the literature and wrote this review based on some of the most current research reports of hydrazones and derivatives, making it clear that the synthesis of these molecules can lead to new drug prototypes. Our goal is to encourage more studies focused on the synthesis and evaluation of new hydrazones, as a contribution to the development of potential new drugs for the treatment of various diseases.

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Janus All‐Cis 2,3,4,5,6‐Pentafluorocyclohexyl Building Blocks Applied to Medicinal Chemistry and Bioactives Discovery Chemistry

Chemistry - A European Journal ◽

10.1002/chem.202102819 ◽

2021 ◽

Author(s):

Joshua L. Clark ◽

Rifahath M. Neyyappadath ◽

Cihang Yu ◽

Alexandra M. Z. Slawin ◽

David B. Cordes ◽

...

Keyword(s):

Medicinal Chemistry ◽

Building Blocks

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Semisynthetic triazoles as an approach in the discovery of Novel Lead Compounds

Current Organic Chemistry ◽

10.2174/1385272825666210126100227 ◽

2021 ◽

Vol 25 ◽

Author(s):

Pedro Alves Bezerra Morais ◽

Carla Santana Francisco ◽

Heberth de Paula ◽

Rayssa Ribeiro ◽

Mariana Alves Eloy ◽

...

Keyword(s):

Natural Products ◽

Medicinal Chemistry ◽

Chemical Space ◽

Biological Activities ◽

Post Translational Modification ◽

Cellular Processes ◽

Modern Drug ◽

New Chemical Entities ◽

Almost All ◽

The 19Th Century

: Historically, the medicinal chemistry is concerned with the approach of organic chemistry to new drug synthesis. Considering the fruitful collections of new molecular entities, the dedicated efforts for medicinal chemistry are rewarding. Planning and search of new and applicable pharmacologic therapies involve the altruistic nature of the scientists. Since the 19th century, notoriously the application of isolated and characterized plant-derived compounds in modern drug discovery and in various stages of clinical development highlight its viability and significance. Natural products influence a broad range of biological processes, covering transcription, translation, and post-translational modification and being effective modulators of almost all basic cellular processes. The research of new chemical entities through “click chemistry” continuously opens up a map for the remarkable exploration of chemical space in towards leading natural products optimization by structure-activity relationship. Finally, here in this review, we expect to gather a broad knowledge involving triazolic natural products derivatives, synthetic routes, structures, and their biological activities.

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The lanthanide-shifted N.M.R. spectra of some cyclopentadienone-cobalt complexes

Australian Journal of Chemistry ◽

10.1071/ch9751681 ◽

1975 ◽

Vol 28 (8) ◽

pp. 1681 ◽

Cited By ~ 7

Author(s):

RS Dickson ◽

SH Johnson ◽

ID Rae

Keyword(s):

Nuclear Magnetic Resonance ◽

Magnetic Resonance ◽

Carbonyl Group ◽

Structure Determination ◽

Cobalt Complexes ◽

Hydrogen Atoms ◽

Pseudocontact Shifts ◽

Lone Pairs ◽

Nuclear Magnetic Resonance Spectra ◽

Lanthanide Shift Reagents

The effect of the lanthanide shift reagents, Eu(fod)3 and Pr(fod)3, on the nuclear magnetic resonance spectra of some (η4-cyclopentadienone)(η- cyclopentadienyl)cobalt complexes has been investigated as an aid to structure determination in this series. The lanthanides complex with the lone pairs of the carbonyl group. Pseudocontact shifts are observed for hydrogens attached to each ring and for hydrogen atoms in substituents on the cyclopentadienone. With Eu(fod)3, contact shifts are also observed for the cyclopentadienone ring hydrogens.

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Substituted Pyrazoles and Their Heteroannulated Analogs—Recent Syntheses and Biological Activities

Molecules ◽

10.3390/molecules26164995 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4995

Author(s):

Mohamed Ramadan ◽

Ashraf A. Aly ◽

Lamiaa E. Abd El-Haleem ◽

Mohammed B. Alshammari ◽

Stefan Bräse

Keyword(s):

Medicinal Chemistry ◽

Biological Activities ◽

Biologically Active ◽

Substituted Pyrazoles ◽

Privileged Scaffolds

Pyrazoles are considered privileged scaffolds in medicinal chemistry. Previous reviews have discussed the importance of pyrazoles and their biological activities; however, few have dealt with the chemistry and the biology of heteroannulated derivatives. Therefore, we focused our attention on recent topics, up until 2020, for the synthesis of pyrazoles, their heteroannulated derivatives, and their applications as biologically active moieties. Moreover, we focused on traditional procedures used in the synthesis of pyrazoles.

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Synthesis and Biological Activities of Some Pyrimidine Derivatives: A Review

Oriental Journal Of Chemistry ◽

10.13005/ojc/360602 ◽

2020 ◽

Vol 36 (6) ◽

pp. 1001-1015

Author(s):

Nadia Ali Ahmed Elkanzi

Keyword(s):

Nitrogen Atom ◽

Medicinal Chemistry ◽

Biological Activities ◽

Heterocyclic Ring ◽

Ring System ◽

Pyrimidine Derivatives ◽

Pharmacological Activities ◽

Cardiovascular Agents ◽

Anti Hiv ◽

Biological And Pharmacological Activities

Nitrogen containing synthetically and biologically important heterocyclic ring system namely pyrimidine possess both biological and pharmacological activities, and defend as aromatic six heterocyclic with 1and 3 nitrogen atom in ring. Preparation of pyrimidine via different methods offer its importance in fields of medicinal chemistry and Chemistry. Pyrimidines and their derivatives act as anti-inflammatory, anti-malaria, anti-tumor, cardiovascular agents, anti-neoplastic, anti-tubercular, anti- HIV, diuretic ,anti-viral, anti-microbial, ,analgesic .This review give light up on biological and pharmacological activities of pyrimidine nucleus.

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