Application of Ullmann and Ullmann–Finkelstein reactions for the synthesis of N-aryl-N-(1H-pyrazol-3-yl) acetamide or N-(1-aryl-1H-pyrazol-3-yl) acetamide derivatives and pharmacological evaluation

Deprez-Poulain, Rébecca; Cousaert, Nicolas; Toto, Patrick; Willand, Nicolas; Déprez, Benoît

doi:10.1016/j.ejmech.2011.05.056

Cited by 14 publications

(9 citation statements)

References 30 publications

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“…The synthetic molecule 2 (Scheme 2) bears a bioisosteric replacement of the CH 2 bridge between the biphenyl system and the nitrogen heterocyle by an NH moiety [50].…”

Section: Resultsmentioning

confidence: 99%

Rational Drug Design and Synthesis of Molecules Targeting the Angiotensin II Type 1 and Type 2 Receptors

2015

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Abstract:The angiotensin II (Ang II) type 1 and type 2 receptors (AT1R and AT2R) orchestrate an array of biological processes that regulate human health. Aberrant function of these receptors triggers pathophysiological responses that can ultimately lead to death. Therefore, it is important to design and synthesize compounds that affect beneficially these two receptors. Cardiovascular disease, which is attributed to the overactivation of the vasoactive peptide hormone Αng II, can now be treated with commercial AT1R antagonists. Herein, recent achievements in rational drug design and synthesis of molecules acting on the two AT receptors are reviewed. Quantitative structure activity relationships (QSAR) and molecular modeling on the two receptors aim to assist the search for new active compounds. As AT1R and AT2R are GPCRs and drug action is localized in the transmembrane region the role of membrane bilayers is exploited. The future perspectives in this field are outlined. Tremendous progress in the field is expected if the two receptors are crystallized, as this will assist the structure based screening of the chemical space and lead to new potent therapeutic agents in cardiovascular and other diseases.

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“…The synthetic molecule 2 (Scheme 2) bears a bioisosteric replacement of the CH 2 bridge between the biphenyl system and the nitrogen heterocyle by an NH moiety [50].…”

Section: Resultsmentioning

confidence: 99%

Rational Drug Design and Synthesis of Molecules Targeting the Angiotensin II Type 1 and Type 2 Receptors

2015

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“…Then the primary amide function was converted to cyano group using trifluoroacetic acid in pyridine. Then the nitrile function was converted to the tetrazole using NaN 3 to give 32 (Scheme 6) [26]. …”

Section: Chemistrymentioning

confidence: 99%

Structure–activity relationships of imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, dual binders of human insulin-degrading enzyme

Charton

Gauriot

Totobenazara

et al. 2015

European Journal of Medicinal Chemistry

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Insulin degrading enzyme (IDE) is a zinc metalloprotease that degrades small amyloid peptides such as amyloid-β and insulin. So far the dearth of IDE-specific pharmacological inhibitors impacts the understanding of its role in the physiopathology of Alzheimer’s disease, amyloid-β clearance, and its validation as a potential therapeutic target. Hit 1 was previously discovered by high-throughput screening. Here we describe the structure-activity study, that required the synthesis of 48 analogues. We found that while the carboxylic acid, the imidazole and the tertiary amine were critical for activity, the methyl ester was successfully optimized to an amide or a 1,2,4-oxadiazole. Along with improving their activity, compounds were optimized for solubility, lipophilicity and stability in plasma and microsomes. The docking or co-crystallization of some compounds at the exosite or the catalytic site of IDE provided the structural basis for IDE inhibition. The pharmacokinetic properties of best compounds 44 and 46 were measured in vivo. As a result, 44 (BDM43079) and its methyl ester precursor 48 (BDM43124) are useful chemical probes for the exploration of IDE’s role.

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“…To list a few pyrazole derivatives that are already booming in the market, some of them are as follows: celecoxib ( 5 , COX‐2 selective non‐steroidal anti‐inflammatory drug [NSAID]), antipyrine/phenazone ( 6 , analgesic, NSAID and an antipyretic drug), analgin/metamizole ( 7 , analgesic, antispasmodic (spasm reliever) and antipyretic), allopurinol/zyloprim ( 8 , hyperuricemia and xanthine oxidase inhibitor), phenylbutazone ( 9 , analgesic, NSAID and an antipyretic drug), oxyphenbutazone ( 10 , NSAID) , pirazole ( 11 , NSAID) , pyrazofurin ( 12 , adenosine kinase) , ramifenazone ( 13 , analgesic, antipyretic and anti‐inflammatory agent) , indisteron ( 14 ) , apixaban ( 15 , anticoagulant), fipronil ( 16 , insecticide), rimonabant ( 17 , anorectic antiobesity drug) and many more are already in market (Fig. ).…”

Section: Introductionmentioning

confidence: 99%

Recent Progress on Pyrazole Scaffold‐Based Antimycobacterial Agents

Keri

Chand

Ramakrishnappa

et al. 2015

Archiv der Pharmazie

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New and reemerging infectious diseases will continue to pose serious global health threats well into the 21st century and according to the World Health Organization report, these are still the leading cause of death among humans worldwide. Among infectious diseases, tuberculosis claims approximately 2 million deaths per year worldwide. Also, agents that reduce the duration and complexity of the current therapy would have a major impact on the overall cure rate. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat Mycobacterium tuberculosis. Subsequently, there is an urgent need for the development of new drug candidates with newer targets and alternative mechanism of action. In this perspective, pyrazole, one of the most important classes of heterocycles, has been the topic of research for thousands of researchers all over the world because of its wide spectrum of biological activities. To pave the way for future research, there is a need to collect the latest information in this promising area. In the present review, we have collated published reports on the pyrazole core to provide an insight so that its full therapeutic potential can be utilized for the treatment of tuberculosis. In this article, the possible structure-activity relationship of pyrazole analogs for designing better antituberculosis (anti-TB) agents has been discussed and is also helpful for new thoughts in the quest for rational designs of more active and less toxic pyrazole-based anti-TB drugs.

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Application of Ullmann and Ullmann–Finkelstein reactions for the synthesis of N-aryl-N-(1H-pyrazol-3-yl) acetamide or N-(1-aryl-1H-pyrazol-3-yl) acetamide derivatives and pharmacological evaluation

Cited by 14 publications

References 30 publications

Rational Drug Design and Synthesis of Molecules Targeting the Angiotensin II Type 1 and Type 2 Receptors

Rational Drug Design and Synthesis of Molecules Targeting the Angiotensin II Type 1 and Type 2 Receptors

Structure–activity relationships of imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, dual binders of human insulin-degrading enzyme

Recent Progress on Pyrazole Scaffold‐Based Antimycobacterial Agents

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