- Dual Rh?Ru Catalysts for Reductive Hydroformylation of Olefins to Alcohols
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An active and selective dual catalytic system to promote domino hydroformylation–reduction reactions is described. Apart from terminal, di- and trisubstituted olefins, for the first time the less active internal C?C double bond of tetrasubstituted alkenes can also be utilized. As an example, 2,3-dimethylbut-2-ene is converted into the corresponding n-alcohol with high yield (90 %) as well as regio- and chemoselectivity (>97 %). Key for this development is the use of a combination of Rh complexes with bulky monophosphite ligands and the Ru-based Shvo's complex. A variety of aromatic and aliphatic alkenes can be directly used to obtain mainly linear alcohols.
- Rodrigues, Fábio M. S.,Kucmierczyk, Peter K.,Pineiro, Marta,Jackstell, Ralf,Franke, Robert,Pereira, Mariette M.,Beller, Matthias
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p. 2310 - 2314
(2018/07/31)
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- Davis-Beirut reaction: Route to thiazolo-, thiazino-, and thiazepino-2 h -indazoles
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Methods for the construction of thiazolo-, thiazino-, and thiazepino-2H-indazoles from o-nitrobenzaldehydes or o-nitrobenzyl bromides and S-trityl-protected 1°-aminothioalkanes are reported. The process consists of formation of the requisite N-(2-nitroben
- Farber, Kelli M.,Haddadin, Makhluf J.,Kurth, Mark J.
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p. 6939 - 6945
(2014/08/18)
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- Synthesis and toxicopharmacological evaluation of m-Hydroxymexiletine, the first metabolite of mexiletine more potent than the parent compound on voltage-gated sodium channels
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The first synthesis of m-hydroxymexiletine (MHM) has been accomplished. MHM displayed hNav1.5 sodium channel blocking activity, and tests indicate it to be ～2-fold more potent than the parent mexiletine and to have more favorable toxicological properties than mexiletine. Thus, MHM and possible related prodrugs might be studied as agents for the treatment of arrhythmias, neuropathic pain, and myotonias in substitution of mexiletine (metabolite switch), which has turned out to be tainted with common toxicity.
- Catalano, Alessia,Desaphy, Jean-Fran?ois,Lentini, Giovanni,Carocci, Alessia,Di Mola, Antonia,Bruno, Claudio,Carbonara, Roberta,De Palma, Annalisa,Budriesi, Roberta,Ghelardini, Carla,Perrone, Maria Grazia,Colabufo, Nicola Antonio,Conte Camerino, Diana,Franchini, Carlo
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scheme or table
p. 1418 - 1422
(2012/04/18)
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- Novel diamide insecticides: Sulfoximines, sulfonimidamides and other new sulfonimidoyl derivatives
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Novel insecticidal anthranilamides with elaborated sulfur-containing groups are described. The synthesis of compounds with functional groups such as sulfoximines and scarcely reported groups such as sulfonimidoyl hydrazides and hydroxylamides, their in vitro and in vivo biological activity as well as their physical properties are reported.
- Gnamm, Christian,Jeanguenat, Andre,Dutton, Ana C.,Grimm, Christoph,Kloer, Daniel P.,Crossthwaite, Andrew J.
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scheme or table
p. 3800 - 3806
(2012/07/17)
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- Design, synthesis, and pharmacological effects of structurally simple ligands for MT1 and MT2 melatonin receptors
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A series of phenoxyalkyl and phenylthioalkyl amides were prepared as melatoninergic ligands. Modulation of affinity of the newly synthesized compound by applying SARs around the terminal amide moiety, the alkyl chain, and the methoxy group on the aromatic ring provides compounds with nanomolar affinity for both melatonin receptor subtypes. Affinity towards MT1 and MT2 receptors were modulated also exploiting chirality. The investigation of intrinsic activity revealed that all the tested compounds behave as full or partial agonists.
- Carocci, Alessia,Catalano, Alessia,Lovece, Angelo,Lentini, Giovanni,Duranti, Andrea,Lucini, Valeria,Pannacci, Marilou,Scaglione, Francesco,Franchini, Carlo
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scheme or table
p. 6496 - 6511
(2010/10/02)
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- Chiral aryloxyalkylamines: Selective 5-HT1B/1D activation and analgesic activity
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A series of chiral 2,3-dichlorophenoxy and 1-naphthyloxy alkylamines were synthesized, and their binding affinities towards 5-HT1D and h5-HT1B receptors were evaluated. In the naphthyloxy series, the (R)-prolinol derivative was the most selective 5-HT1D ligand, while (S)-N-methyl-2-(1-naphthyloxy)propan-1-amine showed the highest selectivity for h5-HT1B. Both compounds performed as 5-HT1D agonists in the isolated guinea pig assay and showed higher analgesic activity than both sumatriptan and the achiral analogue 20b in the mouse hotplate test. Neither ligand displayed any affinity for nicotinic ACh receptors present in mouse brain membranes, thus indicating that their analgesic activity does not arise through interaction with these receptors.
- Carocci, Alessia,Lentini, Giovanni,Catalano, Alessia,Cavalluzzi, Maria Maddalena,Bruno, Claudio,Muraglia, Marilena,Colabufo, Nicola Antonio,Galeotti, Nicoletta,Corbo, Filomena,Matucci, Rosanna,Ghelardini, Carla,Franchini, Carlo
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scheme or table
p. 696 - 704
(2011/02/22)
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- Hydroxylated analogs of mexiletine as tools for structural-requirements investigation of the sodium channel blocking activity
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[2-(2-Aminopropoxy)-1,3-phenylene]dimethanol 1 and 4-(2-aminopropoxy)-3- (hydroxymethyl)-5-methylphenol 2, two dihydroxylated analogs of mexiletine - a well known class IB anti-arrhythmic drug - were synthesized and used as pharmacological tools to investigate the blockingactivity requirements of human skeletal muscle, voltage-gated sodium channel. The very low blocking activity shown by newly synthesized compounds corroborates the hypothesis that the presence of a phenolic group in the para-position to the aromatic moiety and/or benzylic hydroxyl groups on the aromatic moiety of local anesthetic-like drugs impairs either the transport to or the interaction with the binding site in the pore of Na+ channels.
- Catalano, Alessia,Carocci, Alessia,Cavalluzzi, Maria M.,Di Mola, Antonia,Lentini, Giovanni,Lovece, Angelo,Dipalma, Antonella,Costanza, Teresa,Desaphy, Jean-Francois,Camerino, Diana Conte,Franchini, Carlo
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scheme or table
p. 325 - 332
(2011/07/29)
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- Structure-based design, parallel synthesis, structure - Activity relationship, and molecular modeling studies of thiocarbamates, new potent non-nucleoside HIV-1 reverse transcriptase inhibitor isosteres of phenethylthiazolylthiourea derivatives
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In this paper we describe our structure-based ligand design, synthetic strategy, and structure-activity relationship (SAR) studies that led to the identification of thiocarbamates (TCs), a novel class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), isosteres of phenethylthiazolylthiourea (PETT) derivatives. Assuming as a lead compound O-[2-(phthalimido)ethyl] phenylthiocarbamate 12, one of the precursors of the previously described acylthiocarbamates (Ranise, A.; et al. J. Med. Chem. 2003, 46, 768-781), two targeted solution-phase TC libraries were prepared by parallel synthesis. The lead optimization strategy led to para-substituted TCs 31, 33, 34, 39, 40, 41, 44, 45, and 50, which were active against wild-type HIV-1 in MT-4-based assays at nanomolar concentrations (EC50 range: 0.04-0.01 μM). The most potent congener 50 (EC50 = 0.01 μM) bears a methyl group at position 4 of the phthalimide moiety and a nitro group at the para position of the N-phenyl ring. Most of the TCs showed good selectivity indices, since no cytotoxic effect was detected at concentrations as high as 100 μM. TCs 31, 37, 39, 40, and 44 significantly reduced the multiplication of the Y181C mutant, but they were inactive against K103R and K103N + Y181C mutants. Nevertheless, the fold increase in resistance of 41 was not greater than that of efavirenz against the K103R mutant in enzyme assays. The docking model predictions were consistent with in vitro biological assays of the anti-HIV-1 activity of the TCs and related compounds synthesized.
- Ranise, Angelo,Spallarossa, Andrea,Cesarini, Sara,Bondavalli, Francesco,Schenone, Silvia,Bruno, Olga,Menozzi, Giulia,Fossa, Paola,Mosti, Luisa,La Colla, Massimiliano,Sanna, Giuseppina,Murreddu, Marta,Collu, Gabriella,Busonera, Bernardetta,Marongiu, Maria Elena,Pani, Alessandra,La Colla, Paolo,Loddo, Roberta
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p. 3858 - 3873
(2007/10/03)
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- Acid-mediated intramolecular cationic cyclization using an oxygen atom as internal nucleophile: Synthesis of substituted oxazolo-, oxazino- and oxazepinoisoindolinones
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Efficient assembly of substituted oxazolo-, oxazino-, and oxazepinoisoindolinones (5-7, 12-15 and 19) is described in three steps according to an acidic α-oxoamidoalkylation reaction from ready available phthalic anhydride by successive imidation, sodium borohydride reduction and intramolecular cationic cyclization involving N-acyliminium species. The relative stereochemistry accompanying these reactions was also discussed.
- Sikoraiová, Jana,Marchalín, ?tefan,Da?ch, Adam,Decroix, Bernard
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p. 4747 - 4751
(2007/10/03)
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- Stereospecific synthesis of mexiletine and related compounds: Mitsunobu versus Williamson reaction
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Mexiletine [1-(2,6-dimethylphenoxy)-2-propanamine], a chiral, orally effective antiarrhythmic agent, and several analogues substituted on either the stereogenic centre or the xylyloxy moiety, were prepared in both, highly enriched, optically active forms. According to the 'chiral pool' approach, the appropriate amino alcohols, protected as the corresponding phthalimide derivatives, were condensed with the desired phenols under either Mitsunobu (method A) or Williamson (method B) conditions. Generally, method A provided the most efficient route, both in terms of yields and number of steps necessary. Only when an isopropyl group was present on the stereogenic centre, i.e. when 2-amino-3-methylbutanol was used as the starting alcohol, method B proved to be the only available route, method A giving no product other than the starting phthalimide derivative. Regardless of the method used, enantiomeric excesses ranged from 91 to 99%. Given the availability of both variously substituted phenols and optically active amino alcohols, the two methods described herein, taken together, may serve as a versatile approach, useful to meet the needs of new chiral, optically active mexiletine analogues, possibly endowed with higher potency in exerting a use-dependent block on sodium channels and/or more resistant to biotransformations. Copyright (C) 2000 Elsevier Science Ltd.
- Carocci, Alessia,Catalano, Alessia,Corbo, Filomena,Duranti, Andrea,Amoroso, Rosa,Franchini, Carlo,Lentini, Giovanni,Tortorella, Vincenzo
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p. 3619 - 3634
(2007/10/03)
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