Mild and convenient one-pot synthesis of 1,3,4-oxadiazoles

Stabile, Paolo; Lamonica, Alessandro; Ribecai, Arianna; Castoldi, Damiano; Guercio, Giuseppe; Curcuruto, Ornella

doi:10.1016/j.tetlet.2010.06.139

Cited by 65 publications

(25 citation statements)

References 29 publications

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“…The two‐step one‐pot synthesis of 1,2,4‐oxadiazoles 45 – 50 was accomplished in good yields (55–60 %) by treating acid precursor 4 with the corresponding amidoxime derivatives 44 in the presence of EDC⋅HCl in diglyme, followed by heating to 110 °C for the cyclodehydration step . Similarly, 1,3,4‐oxadiazoles 52 – 58 were obtained in 58–80 % yields by treatment of 4 with benzoylhydrazides 51 in the presence of N,N,N’,N’ ‐tetramethyl‐ O‐ (1 H ‐benzotriazol‐1‐yl)uronium hexafluorophosphate (HBTU) and subsequent ring closure mediated by 4‐methylbenzenesulfonyl chloride (TsCl) and diisopropylethylamine (DIPEA) …”

Section: Resultsmentioning

confidence: 99%

“…[25] Similarly,1 ,3,4-oxadiazoles 52-58 were obtainedi n5 8-80% yields by treatment of 4 with benzoylhydrazides 51 in the presence of N,N,N',N'-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) and subsequentr ing closure mediated by 4-methylbenzenesulfonyl chloride (TsCl) and diisopropylethylamine (DIPEA). [26] K D value determinationf or these heterocyclesr evealed that none of these isosteres reached the potency of the guiding amides (Table 3). However,w ewere able to co-crystallize the 1,3,4-oxadiazole 52 in complex with PDEd (2.1 resolution, Figure 3a and c).…”

Section: Determination Of K D Values In Fluorescencep Olarization Assaysmentioning

confidence: 99%

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Development of Pyridazinone Chemotypes Targeting the PDEδ Prenyl Binding Site

Murarka

Martín‐Gago

Schultz‐Fademrecht

et al. 2016

Chemistry A European J

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The K-Ras GTPase is a major target in anticancer drug discovery. However, direct interference with signaling by K-Ras has not led to clinically useful drugs yet. Correct localization and signaling by farnesylated K-Ras is regulated by the prenyl binding protein PDEδ. Interfering with binding of PDEδ to K-Ras by means of small molecules provides a novel opportunity to suppress oncogenic signaling. Here we describe the identification and structure-guided development of novel K-Ras-PDEδ inhibitor chemotypes based on pyrrolopyridazinones and pyrazolopyridazinones that bind to the farnesyl binding pocket of PDEδ with low nanomolar affinity. We delineate the structure-property relationship and in vivo pharmacokinetic (PK) and toxicokinetic (Tox) studies for pyrazolopyridazinone-based K-Ras-PDEδ inhibitors. These findings may inspire novel drug discovery efforts aimed at the development of drugs targeting oncogenic Ras.

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Section: Resultsmentioning

confidence: 99%

Section: Determination Of K D Values In Fluorescencep Olarization Assaysmentioning

confidence: 99%

Development of Pyridazinone Chemotypes Targeting the PDEδ Prenyl Binding Site

Murarka

Martín‐Gago

Schultz‐Fademrecht

et al. 2016

Chemistry A European J

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“…Finally, treatment of hydrazides 6 with p -toluenesulfonyl chloride in the presence of triethylamine in CH 2 Cl 2 under ambient temperature gave cyclodehydration products 7. Compounds 7m-v were conveniently prepared using a one-pot synthesis, as described in the literature 37 (Scheme). The synthesized compounds are listed in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis and characterization of novel 1,2-benzisothiazol-3(2H)-one and 1,3,4-oxadiazole hybrid derivatives: Potent inhibitors of Dengue and West Nile virus NS2B/NS3 proteases

Lai

Dou

Aravapalli

et al. 2013

Bioorganic & Medicinal Chemistry

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1,2-Benzisothiazol-3(2H)-ones and 1,3,4-oxadiazoles individually have recently attracted considerable interest in drug discovery, including as antibacterial and antifungal agents. In this study, a series of functionalized 1,2-benzisothiazol-3(2H)-one - 1,3,4-oxadiazole hybrid derivatives were synthesized and subsequently screened against Dengue and West Nile virus proteases. Ten out of twenty-four compounds showed greater than 50% inhibition against DENV2 and WNV proteases ([I] = 10 μM). The IC50 values of compound 7n against DENV2 and WNV NS2B/NS3 were found to be 3.75 ± 0.06 and 4.22 ± 0.07 μM, respectively. The kinetics data support a competitive mode of inhibition by compound 7n. Molecular modeling studies were performed to delineate the putative binding mode of this series of compounds. This study reveals that the hybrid series arising from the linking of the two scaffolds provides a suitable platform for conducting a hit-to-lead optimization campaign via iterative structure-activity relationship studies, in vitro screening and X-ray crystallography.

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“…Stabile and co‐workers described one example of 1,3,4‐oxadiazoles 55.2 synthesis from phenylacetic acids and benzohydrazide (Eq. 55‐1).…”

Section: Electrophilic Acidsmentioning

confidence: 99%

Arylacetic Acids in Organic Synthesis

et al. 2019

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Arylacetic acids are widely used in organic reactions and their recent advances are summarized in six categories according to their triggered pathways: (1) the acid as directing group in ortho-or meta-CÀ H activation; (2) decarboxylation; (3) deprotonation; (4) nucleophilic methylenes; (5) nucleophilic acids; (6) electrophilic acids. Reactions with alkenes, alkynes, aldehydes, amines, water, Grignard reagents, silanes and so forth are discussed. We hope this Minireview will promote future research in this area. Recently, the Zeng group [3g] reported a weakly coordinationassisted alkynylation of arylacetic acids with iridium catalysis under air atmosphere (Eq. 2-2). It was supported the sixmembered ring cycloiridiated 2.5 acted as the key intermediate. The alkynylation of indole, thiophene, pyrrole, and benzo[b] thiophene afforded better yields than phenylacetic acids. The acid moiety could also participated in the intramolecular ortho-CÀ H activation, which was developed by the Shi group to obtain lactonization 2.6 (Eq. 2-3) (Scheme 2). Meta-CÀ H ArylationThe study of Yu group [3e] in 2017 revealed a successful control of meta selectivity 3.1 of arylation from aryl iodides (Eq. 3-1). The use of mono-protected 3-amino-2-hydroxypyridine (as ligand) and 2-carbomethoxynorbornene (NBE-CO 2 Me) were crucial. In the absence of NBE-CO 2 Me, only ortho-arylated product was obtained. This method was still efficient in a gramsale (Scheme 3). Decarboxylation Decarboxylative CouplingAs shown in Scheme 4, the decarboxylation could generate benzyl radicals 4.1. Then, direct couplings of 4.1 with diverse [ + ] These authors contributed equally. Scheme 1. Six categories based on triggered mechanism. 2 3 4 5 6 7 8 . Passerini Three-Component ReactionThe Passerini reaction was the oldest multicomponent reaction (MCR) [37d] in which isocyanides, carboxylic acids and aldehydes were used. It was powerful for the rapid construction of complex molecules. The tactic to expand the scope of Passerini reaction was to use surrogates of the carbonyl partners. As described in Scheme 51, syn-chlorooximes, [37b] diazoketones, [37c] alcohols, [37d,e] azirines [37f] and isatins [37g] could be employed instead of aryl or alkyl aldehydes [37a] (Scheme 51). Besides, in 2018, Zhang and co-workers [37] have firstly reported asymmetric phosphoric acid-catalyzed four-component Ugi reaction, which Scheme 45. BTM-catalyzed cycloaddition. Scheme 46. HBTM-catalyzed cycloaddition. Scheme 47. TFA-catalyzed reaction. Scheme 48. Friedel-Crafts triggered tandem reactions. Scheme 49. C-acylation of 1,3-diones. Scheme 50. C-acylation of 1,3-indandiones.

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Mild and convenient one-pot synthesis of 1,3,4-oxadiazoles

Cited by 65 publications

References 29 publications

Development of Pyridazinone Chemotypes Targeting the PDEδ Prenyl Binding Site

Development of Pyridazinone Chemotypes Targeting the PDEδ Prenyl Binding Site

Design, synthesis and characterization of novel 1,2-benzisothiazol-3(2H)-one and 1,3,4-oxadiazole hybrid derivatives: Potent inhibitors of Dengue and West Nile virus NS2B/NS3 proteases

Arylacetic Acids in Organic Synthesis

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