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Preparation of 2-alkyl- and 2-acylpropenals from 5-(trifluoromethanesulfonyloxy)-4H-1,3-dioxin: A versatile acrolein alpha-cation synthon

5-(Trifluoromethanesulfonyloxy)-4H-1,3-dioxin (3) participates in a variety of nucleophilic substitution reactions with cuprate reagents or in palladium catalyzed cross-coupling reactions to provide 5-substituted-4H-1,3-dioxins 5. Upon thermolysis, these compounds undergo facile retrocycloaddition reactions to generate the corresponding 2-substituted acroleins which, if necessary, can be trapped in situ with dienes or heterodienophiles. In particular, the heretofore unknown 2-acylacroleins can be generated using this methodology and trapped with enol ethers to afford 5-acyl-3,4-dihydro-2H-pyrans (6g,h), a substructural unit common to many natural products. (C) 2000 Elsevier Science Ltd.

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Isoquinoline | C9H7N – PubChem

 

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Ir(iii)-catalyzed: Ortho C-H alkylations of (hetero)aromatic aldehydes using alkyl boron reagents

Transition-metal-catalyzed C-H alkylation reactions directed by aldehydes or ketones have been largely restricted to electronically activated alkenes. Herein, we report a general protocol for the Ir(iii)-catalyzed ortho C-H alkylations of (hetero)aromatic aldehydes using alkyl boron reagents as the coupling partner. Featuring aniline as an inexpensive catalytic ligand, the method was compatible with a wide variety of benzaldehydes, heterocyclic aldehydes, potassium alkyltrifluoroborates as well as a few alpha,beta-unsaturated aldehydes. An X-ray crystal structure of a benzaldehyde ortho C-H iridation intermediate was also successfully obtained.

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Isoquinoline | C9H7N – PubChem

 

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Bioavailability Studies and in vitro Profiling of the Selective Excitatory Amino Acid Transporter Subtype 1 (EAAT1) Inhibitor UCPH-102

Although the selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor UCPH-101 has become a standard pharmacological tool compound for in vitro and ex vivo studies in the EAAT research field, its inability to penetrate the blood-brain barrier makes it unsuitable for in vivo studies. In the present study, per os (p.o.) administration (40 mg kg-1) of the closely related analogue UCPH-102 in rats yielded respective plasma and brain concentrations of 10.5 and 6.67 mum after 1 h. Three analogue series were designed and synthesized to improve the bioavailability profile of UCPH-102, but none displayed substantially improved properties in this respect. In vitro profiling of UCPH-102 (10 mum) at 51 central nervous system targets in radioligand binding assays strongly suggests that the compound is completely selective for EAAT1. Finally, in a rodent locomotor model, p.o. administration of UCPH-102 (20 mg kg-1) did not induce acute effects or any visible changes in behavior. EAAT1 inhibition beyond the BBB: In the present study, oral administration (40 mg kg-1) of the selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor UCPH-102 in rats yielded respective plasma and brain concentrations of 10.5 and 6.67 mum after 1 h. In vitro profiling of UCPH-102 (10 mum) at 51 central nervous system targets in radioligand binding assays strongly suggests that the compound is fully selective for EAAT1.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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Synthesis of Enantiomerically Pure Ring-Substituted l -Pyridylalanines by Biocatalytic Hydroamination

Current routes to nitrogen-containing heteroarylalanines involve complex multistep synthesis and are often reliant on protection/deprotection steps and wasteful chromatographic purifications. In order to complement existing methodologies, a convenient telescopic strategy was developed for the synthesis of l-pyridylalanine analogues (12 examples) and other l-heteroarylalanines (5 examples) starting from the corresponding aldehydes. A phenylalanine ammonia lyase (PAL) from Anabaena variabilis was used as the biocatalyst to give conversions ranging between 88 and 95%, isolated yields of 32-60%, and perfect enantiopurity (>99% ee) by employing an additional deracemization cascade where necessary.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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Azastilbenes. 1. Synthesis, Characterization, and Structure

The synthesis of several symmetric and asymmetric azastilbenes is described, and their spectral characteristics (NMR, mass, UV, IR) are given.Four of them are new compounds, namely, 1,2-di(4-isoquinolyl)ethylene, 1-(3-pyridyl)-2-(2-pyrazinyl)ethylene, 1-(3-pyridyl)-2-(4-isoquinolyl)ethylene, and 1-(2-pyrazinyl)-2-(4-isoquinolyl)ethylene.The molecular structure and crystalline stacking of some of these azastilbenes and of the quaternary salts of 1,2-di(2-pyridyl)ethylene and 1,2-di(4-pyridyl)ethylene have been determined by X-ray diffraction on a single crystal and their characteristic parameters indicated.

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Isoquinoline – Wikipedia,
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DERIVATIVES OF PIPERLONGUMINE AND USES THEREOF

The present invention relates to a group of 1-[(E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoyl]-2,3- dihydropyridin-6-one (piperlongumine) derivatives, analogs and pharmaceutically acceptable salts thereof. The present invention also relates to processes for preparing the same; a pharmaceutical composition and formulation containing a derivative of piperlogumine; and use of the derivatives and analogs for treating cancer.

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Structure Guided Lead Generation toward Nonchiral M. tuberculosis Thymidylate Kinase Inhibitors

In recent years, thymidylate kinase (TMPK), an enzyme indispensable for bacterial DNA biosynthesis, has been pursued for the development of new antibacterial agents including against Mycobacterium tuberculosis, the causative agent for the widespread infectious disease tuberculosis (TB). In response to a growing need for more effective anti-TB drugs, we have built upon our previous efforts toward the exploration of novel and potent Mycobacterium tuberculosis TMPK (MtTMPK) inhibitors, and reported here the design of a novel series of non-nucleoside inhibitors of MtTMPK. The inhibitors display hitherto unexplored interactions in the active site of MtTMPK, offering new insights into structure-activity relationships. To investigate the discrepancy between enzyme inhibitory activity and the whole-cell activity, experiments with efflux pump inhibitors and efflux pump knockout mutants were performed. The minimum inhibitory concentrations of particular inhibitors increased significantly when determined for the efflux pump mmr knockout mutant, which partly explains the observed dissonance.

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Highly selective recognition of a-chiral primary organoammonium ions by C3-symmetric peptide receptors

A straightforward synthesis of C3-symmet:ric, imidazole-containing, macrocyclic peptides with different binding arms is presented, The chirality of the backbone and the selection of adequate receptor arms make these systems highly selective receptors for alpha-chiral primary organoammonium ions. Furthermore, the receptors have the ability to discriminate between enantiomeric guests with selectivity ratios of up to 87:13, The binding constants and the selectivity ratios were estimated by standard 1H NMR titration techniques in CDCl3.

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Reactions of Allenylic Tin Reagents to N-Alkoxycarbonyl-isoquinolinium and -quinolinium Salts. Effective Introduction of 2-Alkynylic Groups to Isoquinoline and Quinoline Systems

Reaction of allenylic tin reagents with isoquinoline in the presence of chloroformate esters as acylating agents give 2-alkoxycarbonyl-1-(2-alkynyl)-1,2-dihydroisoquinolines in good to excellent yields.Similarly, the reactions with quinoline give 1- alkoxycarbonyl-2-(2-alkynyl)-1,2-dihydroquinolines exclusively.

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Isoquinoline aldehydes

Isoquinoline-4-aldehydes of the formula STR1 in which X denotes bromine or chlorine, R1 is phenyl optionally mono- or disubstituted by halogen, hydroxy, nitro, amino, or amino substituted by one or two aliphatic, cycloaliphatic or aromatic hydrocarbon radicals having from 2 to 18 carbon atoms, the nitrogen atom possibly being included in a heterocyclic ring, acyl amino, alkyl or alkoxy each having from 1 to 6 carbon atoms, benzoyloxy, or trifluoromethyl, or is pyridyl or thienyl; R2 is hydrogen, halogen, hydroxy, alkyl or alkoxy having from 1 to 6 carbon atoms, nitro, amino, benzyloxy, methylene dioxy or ethylene dioxy and m is 1 or 2; which are effective in the treatment of spasms and as tranquilizers.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem