4439-22-9Relevant academic research and scientific papers
Torii-Type Electrosynthesis of α,β-Unsaturated Esters from Furfurylated Ethylene Glycols and Amino Alcohols
Darzina, Madara,Lielpetere, Anna,Jirgensons, Aigars
supporting information, p. 4224 - 4228 (2021/08/24)
Electrosynthesis of unsaturated esters from furan derivatives, reported by Torii et al. in 1976, is an attractive method for the valorization of furanoic platform chemicals. Nevertheless, it has received practically no attention, presumably due to specific reaction conditions including the use of expensive Pt electrodes. With the aim of expanding the application of Torii-type ester electrosynthesis, we explored the electrochemical transformation of O-furfuryl ethylene glycols and N-furfuryl amino alcohols to esters 5. These can be obtained in two consecutive electrochemical steps: bis-alkoxylation of the furan derived substrates 3 to give spirocycles 4, followed by ring-opening involving oxidative fragmentation of the C?C bond. Both steps can be carried out at ambient conditions, using inexpensive graphite electrodes; however, each step required a different supporting electrolyte and acidic additive to achieve good yields of the product. Additionally, conditions were found for efficient one-pot transformation of N-furfuryl amino alcohols to esters 5 while O-furfuryl ethylene glycols under the same conditions gave esters 5 in moderate yields.
Zinc-Catalyzed Esterification of N-β-Hydroxyethylamides: Removal of Directing Groups under Mild Conditions
Nishii, Yuji,Hirai, Takahiro,Fernandez, Sarah,Knochel, Paul,Mashima, Kazushi
supporting information, p. 5010 - 5014 (2017/09/21)
Amide transformations involving C–N bond cleavage are recognized as difficult reactions owing to the inert nature of amides resulting from resonance. Accordingly, a strong inductive effect and geometrical distortion reasonably decrease the resonance stabilization to attenuate the C–N linkage. Although the conversion of such activated amides has been studied intensively, reaction systems for “unactivated” amides are underdeveloped. We herein report that a zinc(II) trifluoromethanesulfonate [Zn(OTf)2] catalyst achieves the esterification of a wide range of unactivated tertiary amides with the assistance of intramolecular acyl rearrangement. The reaction was applied to the one-pot removal of various amide-based directing groups under mild reaction conditions to afford the corresponding esters in high yields.
Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy
Papeo, Gianluca,Posteri, Helena,Borghi, Daniela,Busel, Alina A.,Caprera, Francesco,Casale, Elena,Ciomei, Marina,Cirla, Alessandra,Corti, Emiliana,D'Anello, Matteo,Fasolini, Marina,Forte, Barbara,Galvani, Arturo,Isacchi, Antonella,Khvat, Alexander,Krasavin, Mikhail Y.,Lupi, Rosita,Orsini, Paolo,Perego, Rita,Pesenti, Enrico,Pezzetta, Daniele,Rainoldi, Sonia,Riccardi-Sirtori, Federico,Scolaro, Alessandra,Sola, Francesco,Zuccotto, Fabio,Felder, Eduard R.,Donati, Daniele,Montagnoli, Alessia
, p. 6875 - 6898 (2015/09/22)
The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectively. Cocrystal structures of 20by with both PARP-1 and PARP-2 catalytic domain proteins allowed rationalization of the observed selectivity.
Synthesis and antibacterial activity of aromatic and heteroaromatic amino alcohols
de Almeida, Camila G.,Reis, Samira G.,de Almeida, Angelina M.,Diniz, Claudio G.,da Silva, Vania L.,Le Hyaric, Mireille
, p. 876 - 880 (2012/06/18)
Two series of aromatic and heteroaromatic amino alcohols were synthesized from alcohols and aldehydes and evaluated for their antibacterial activities. All the octylated compounds displayed a better activity against the four bacteria tested when evaluated by the agar diffusion method and were selected for the evaluation of minimal inhibitory concentration. The best results were obtained for p-octyloxybenzyl derivatives against Staphylococcus epidermidis (minimal inhibitory concentrations = 32μm).
HSP90 FAMILY PROTEIN INHIBITORS
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Page/Page column 111-112, (2008/06/13)
The present invention provides Hsp90 family protein inhibitors comprising, as an active ingredient, a benzoyl compound represented by general formula (I): (wherein n represents an integer of 0 to 10; R1 represents substituted or unsubstituted lower alkoxy, substituted or unsubstituted lower alkoxycarbonyl, CONR7R8 or the like; R2 represents substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group or the like; R3 and R5, which may be the same or different, each represent a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl or the like; and R4 and R6, which may be the same or different, each represent a hydrogen atom, halogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl or the like) or a prodrug thereof, or a pharmaceutically acceptable salt of said benzoyl compound or said prodrug.
Chemokine receptor binding heterocyclic compounds
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Page column 65, (2008/06/13)
This invention relates to a novel class of heterocyclic compounds that bind chemokine receptors, inhibiting the binding of their natural ligands thereby. These compounds result in protective effects against infection by HIV through binding to chemokine receptors, including CXCR4 and CCR5, thus inhibiting the subsequent binding by these chemokines. The present invention provides a compound of Formula I wherein, W is a nitrogen atom and Y is absent or, W is a carbon atom and Y═H; R1to R7may be the same or different and are independently selected from hydrogen or straight, branched or cyclic C1-6alkyl; R8is a substituted heterocyclic group or a substituted aromatic group Ar is an aromatic or heteroaromatic ring each optionally substituted at single or multiple, non-linking positions with electron-donating or withdrawing groups; n and n′ are independently, 0-2; X is a group of the formula: Wherein, Ring A is an optionally substituted, saturated or unsaturated 5 or 6-membered ring, and P is an optionally substituted carbon atom, an optionally substituted nitrogen atom, sulfur or oxygen atom. Ring B is an optionally substituted 5 to 7-membered ring. Ring A and Ring B in the above formula can be connected to the group W from any position via the group V, wherein V is a chemical bond, a (CH2)n″group (where n″=0-2) or a C═O group. Z is, (1) a hydrogen atom, (2) an optionally substituted C1-6alkyl group, (3) a C0-6alkyl group substituted with an optionally substituted aromatic or heterocyclic group, (4) an optionally substituted C0-6alkylamino or C3-7cycloalkylamino group, (5) an optionally substituted carbonyl group or sulfonyl. These compounds further include any pharmaceutically acceptable acid addition salts and metal complexes thereof and any stereoisomeric forms and mixtures of stereoisomeric forms thereof.
