ChemInform Abstract: Oxidation of Alcohols with o‐Iodoxybenzoic Acid (IBX) in DMSO: A New Insight into an Old Hypervalent Iodine Reagent.

Frigerio, M.; Santagostino, Marco; Sputore, Simona; Palmisano, Giovanni

doi:10.1002/chin.199612058

Cited by 5 publications

(9 citation statements)

References 1 publication

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“…Solution of 16 (460 mg, 0.64 mmol) and IBX 56 (896 mg, 3.2 mmol) was dissolved in DMSO. CF 3 CO 2 H (104.4 μL) was added, and the mixture was stirred at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria

et al. 2014

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Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ) based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were synthesized. Introducing an amino group at the C(3) position of the cholate component markedly increased potency (IC50 values for such derivatives ranged from 0.81 to 2.27 μM). Two additional subclasses were prepared: bis(steroidal)-4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided inhibitors with nanomolar-range potencies (e.g., the Ki of compound 67 is 0.10 μM). During BoNT/A challenge using primary neurons, select derivatives protected SNAP-25 by up to 89%. Docking simulations were performed to rationalize the compounds’ in vitro potencies. In addition to specific residue contacts, coordination of the enzyme’s catalytic zinc and expulsion of the enzyme’s catalytic water were a consistent theme. With respect to antimalarial activity, the compounds provided better IC90 activities against chloroquine resistant (CQR) malaria than CQ, and seven compounds were more active than mefloquine against CQR strain W2.

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“…Solution of 16 (460 mg, 0.64 mmol) and IBX 56 (896 mg, 3.2 mmol) was dissolved in DMSO. CF 3 CO 2 H (104.4 μL) was added, and the mixture was stirred at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria

et al. 2014

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“…Subsequent coupling of tripeptide 10 with warhead 8 provided intermediate 11 (Scheme 2). The tetrapeptide scaffold 11 was then oxidized with 2-iodoxybenzoic acid (IBX), 29 followed by final acidolysis of protective groups with HF. Compounds were generally obtained as a 8:2 mixtures of epimers, 25 which were separated by reverse-phase preparative high-performance liquid chromatography (HPLC).…”

mentioning

confidence: 99%

Design and Synthesis of Potent, Selective Inhibitors of Matriptase

Colombo

Désilets

Duchêne

et al. 2012

ACS Med. Chem. Lett.

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Matriptase is a member of the type II transmembrane serine protease family. Several studies have reported deregulated matriptase expression in several types of epithelial cancers, suggesting that matriptase constitutes a potential target for cancer therapy. We report herein a new series of slow, tightbinding inhibitors of matriptase, which mimic the P1−P4 substrate recognition sequence of the enzyme. Preliminary structure−activity relationships indicate that this benzothiazole-containing RQAR-peptidomimetic is a very potent inhibitor and possesses a good selectivity for matriptase versus other serine proteases. A molecular model was generated to elucidate the key contacts between inhibitor 1 and matriptase.

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“…Ester cleavage and coupling of acid 7 with cyclopropylamine yielded hydroxyamide 8. Final oxidation using either Pfitzner− Moffat conditions 12 or, in the case of alkoxy-substituted amides, 2-iodobenzoic acid 13 gave ketoamides 9−32 as racemic mixtures. 14,15 Detailed experimental procedures for the preparation of key compounds 15 and 23 are given in the Supporting Information.…”

Section: Acs Medicinal Chemistry Lettersmentioning

confidence: 99%

Mitigating the Metabolic Liability of Carbonyl Reduction: Novel Calpain Inhibitors with P1′ Extension

Kling

Jantos

Mack

et al. 2018

ACS Med. Chem. Lett.

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Dysregulation of calpains 1 and 2 has been implicated in a variety of pathological disorders including ischemia/reperfusion injuries, kidney diseases, cataract formation, and neurodegenerative diseases such as Alzheimer's disease (AD). 2-(3-Phenyl-1)-pyrazol-1-yl)nicotinamides represent a series of novel and potent calpain inhibitors with high selectivity and efficacy. However, carbonyl reduction leading to the formation of the inactive hydroxyamide was identified as major metabolic liability in monkey and human, a pathway not reflected by routine absorption, distribution, metabolism, and excretion (ADME) assays. Using cytosolic clearance as a tailored ADME assay coupled with hepatocyte metabolism enabled the identification of analogues with enhanced stability against carbonyl reduction. These efforts led to the identification of P1' modified calpain inhibitors with significantly improved pharmacokinetic profile including P1'-methoxyamide as potential candidate compound for non-central nervous system indications.

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ChemInform Abstract: Oxidation of Alcohols with o‐Iodoxybenzoic Acid (IBX) in DMSO: A New Insight into an Old Hypervalent Iodine Reagent.

Abstract: The title reaction with the mild and chemoselective reagent IBX is reported for a variety of alcohols like (I), (VII), (XI). -(FRIGERIO, M.; SANTAGOSTINO, M.; SPUTORE, S.; PALMISANO, G.; J.

Cited by 5 publications

References 1 publication

Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria

Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria

Design and Synthesis of Potent, Selective Inhibitors of Matriptase

Mitigating the Metabolic Liability of Carbonyl Reduction: Novel Calpain Inhibitors with P1′ Extension

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