- Enantioselective Sequential-Flow Synthesis of Baclofen Precursor via Asymmetric 1,4-Addition and Chemoselective Hydrogenation on Platinum/Carbon/Calcium Phosphate Composites
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Continuous-flow synthesis of baclofen precursor (2) was achieved using achiral and chiral heterogeneous catalysts in high yield with high enantioselectivity. The key steps are chiral calcium-catalyzed asymmetric 1,4-addition of a malonate to a nitroalkene and chemoselective reduction of a nitro compound to the corresponding amino compound by using molecular hydrogen. A dimethylpolysilane (DMPS)-modified platinum catalyst supported on activated carbon (AC) and calcium phosphate (CP) has been developed that has remarkable activity for the selective hydrogenation of nitro compounds.
- Furiya, Yuichi,Ishitani, Haruro,Kobayashi, Shu
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supporting information
(2020/05/05)
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- Tacrine-O-protected phenolics heterodimers as multitarget-directed ligands against Alzheimer's disease: Selective subnanomolar BuChE inhibitors
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Concerned by the devastating effects of Alzheimer's disease, and the lack of effective drugs, we have carried out the design of a series of tacrine-phenolic heterodimers in order to tackle the multifactorial nature of the disease. Hybridization of both pharmacophores involved the modification of the nature (imino, amino, ether) and the length of the tether, together with the type (hydroxy, methoxy, benzyloxy), number and position of the substituents on the aromatic residue. Title compounds were found to be strong and selective inhibitors of human BuChE (from low nanomolar to subnanomolar range), an enzyme that becomes crucial in the more advanced stages of the disease. The lead compound, bearing an ether-type tether, had an IC50 value of 0.52 nM against human BuChE, and a selectivity index of 323, with an 85-fold increase of activity compared to parent tacrine; key interactions were analysed using molecular modelling. Moreover, it also inhibited the self-aggregation of Aβ42, lacking neurotoxicity up to 5 μM concentration, and showed neuroprotective activity in primary rat neurons in a serum and K+ deprivation model, widely employed for reproducing neuronal injury and senescence. Moreover, low hepatoxicity effects and complete stability under physiological conditions were found for that compound. So, overall, our lead compound can be considered as a promising multitarget-directed ligand against Alzheimer's disease, and a good candidate for developing new drugs.
- Roldán-Pe?a, Jesús M.,Romero-Real,Hicke, Javier,Maya, Inés,Franconetti, Antonio,Lagunes,Padrón, José M.,Petralla, Sabrina,Poeta, Eleonora,Naldi, Marina,Bartolini, Manuela,Monti, Barbara,Bolognesi, Maria L.,López, óscar,Fernández-Bola?os, José G.
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- SYNTHESIS OF POLYCYCLIC ALKALOIDS
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Disclosed embodiments concern polycyclic alkaloid compounds and methods for their use and synthesis. Particular embodiments concern polycyclic alkaloids having a fused, six-membered ring, while other embodiments concern polycyclic alkaloids having a fused
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- PTERIDINES AND THEIR USE AS AGROCHEMICALS
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The present disclosure relates to 1- or 2-(4-(aryloxy)-phenyl)ethylamino-, oxy- or sulfanyl)pteridines and 1- or 2-(4-(heteroaryloxy)-phenyl)ethylamino-, oxy- or sulfanyl)pteridines and their use as agrochemicals and animal health products.
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- PTERIDINES AND THEIR USE AS AGROCHEMICALS
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The present disclosure relates to 1- or 2-(4-(aryloxy)-phenyl)ethylamino-, oxy- or sulfanyl)pteridines and 1- or 2-(4-(heteroaryloxy)-phenyl)ethylamino-, oxy- or sulfanyl)pteridines and their use as agrochemicals and animal health products.
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- The total synthesis of cannabisin G
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A convenient method for the synthesis of lignanamide cannabisin G, starting from vanillin, was developed. The convergent synthesis was based on the Stobbe reaction as C-C bond-forming steps to give the skeleton of lignan, which was condensed with a deriva
- Yamu, Xia,Yinglan, Guo,Yanling, Wen
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p. 1617 - 1623
(2011/09/20)
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- S1P RECEPTORS MODULATORS
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The invention relates to novel compounds that have S1P receptor modulating activity and, preferably, apoptotic activity and/or anti proliferative activity against cancer cells and other cell types. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, cancer. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as cancer.
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Page/Page column 98
(2010/04/30)
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- Non-urea functionality as the primary pharmacophore in soluble epoxide hydrolase inhibitors
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Inhibition of soluble epoxide hydrolase has been proposed as a promising new pharmaceutical target for diseases involving hypertension and vascular inflammation. The most potent sEH inhibitors reported to date contain a urea or amide moiety as the central or 'primary' pharmacophore. We evaluated replacing the urea pharmacophore with other functional groups such as thiourea, sulfonamide, sulfonylurea, aminomethylene amide, hydroxyamide, and ketoamide to identify novel and potent inhibitors. The hydroxyamide moiety was identified as a novel pharmacophore affording potency comparable to urea.
- Anandan, Sampath-Kumar,Do, Zung N.,Webb, Heather K.,Patel, Dinesh V.,Gless, Richard D.
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body text
p. 1066 - 1070
(2009/09/04)
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- Structure-based approach to falcipain-2 inhibitors: Synthesis and biological evaluation of 1,6,7-Trisubstituted dihydroisoquinolines and isoquinolines
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1,4,7-Trisubstituted isoquinolines were designed, synthesized and evaluated for their inhibition against Plasmodium falciparum cysteine protease falcipain-2. The 1-benzyloxyphenyl-dihydroisoquinoline and -isoquinoline derivatives were found to exhibit better activity against falcipain-2 than their corresponding 1-hydroxyphenyl or 1-methoxyphenyl analogues. The docking scores correlate with the IC50 values of compounds and give a high coefficient correlation of 0.94.
- Batra, Sanjay,Sabnis, Yogesh A.,Rosenthal, Philip J.,Avery, Mitchell A.
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p. 2293 - 2299
(2007/10/03)
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- Compounds and pharmaceutical use thereof
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PCT No. PCT/JP97/00291 Sec. 371 Date Aug. 6, 1998 Sec. 102(e) Date Aug. 6, 1998 PCT Filed Feb. 6, 1997 PCT Pub. No. WO97/29079 PCT Pub. Date Aug. 14, 1997The compounds of the formula (I) wherein each symbol is as defined in the specification, pharmaceutically acceptable salts thereof and pharmaceutical use thereof. The Compound (I) and pharmaceutically acceptable salts thereof of the present invention selectively act on cannabinoid receptors, particularly peripheral receptors, cause less side effects on the central system, and have superior immunoregulating action, antiinflammatory action, antiallergic action and therapeutic effect on nephritis. Therefore, they are useful as cannabinoid receptor, particularly peripheral cannabinoid receptor activators and antagonists, immunoregulators, therapeutic agents for autoimmune diseases, antiinflammatory agents, antiallergic agents and therapeutic agents for nephritis.
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- Biologically compatible linear block copolymers of polyalkylene oxide and peptide units
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A linear block copolymer comprising units of an alkylene oxide, linked to units of peptide via a linking group comprising a --CH2 CHOHCH2 N(R)-- moiety, is useful as an imaging agent, drug, prodrug or as a delivery system for imaging agents, drugs or prodrugs.
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- Diazaestrones and analogs. I. Pharmacological study and synthesis of heterosteroid analogs to establish structure-analgesic activity relationships
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With the intention of showing the effect, about pharmacological properties, in replacing two estron asymetric carbon by nitrogen atoms and removal of angular methyl from steroid, stereospecific synthesis of 8,13-diazaestron and several substituted similar compounds was realized from β-1-(succinimidoethyl)-dihydroisoquinolines, precursors of a C open ring synthesis. The splitting of the 2-methoxydiazaestron methyl ester was carried out by mean of binaphthylphosphoric acid, and synthesis of several modified analogs of heterosteroid, was carried out to determine the effect of aromatic ring reduction, lactamic carbonyl reduction, and distance between 8 and 13 nitrogen atoms, about pharmacological activity. Hormonal, spasmolytic and analgesic activities were studied, good results were observed in analgesic activity.
- Hocquaux,Marcot,Redeuilh,et al.
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p. 319 - 329
(2007/10/02)
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