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Multifunctional isoquinoline-oxazolines (MIQOXs) were conceived and synthesized from commercially available chiral amino acids. The multifunctional role of MIQOXs was demonstrated by Pd-catalyzed highly enantioselective addition of arylboronic acids to nitrostyrenes, and by the discovery of novel antifungal candidates.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H1731N – PubChem

 

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Substitution reactions of four Pt(II) complexes, namely; N-(2-picolyl)picolinamide-platinum(II) chloride (Pt3), N-(8-quinolyl)pyridine-2-carboxamide platinum(II) chloride (Pt4), N-(8-quinolyl)-3-isoquinolinecarboxamide platinum(II) chloride (Pt5) and N-(8-quinolinyl)-1-isoquinolinecarboxamide platinum(II) chloride (Pt6), were studied with biorelevant nucleophiles, viz. thiourea (TU), N,N?-dimethylthiourea (DMTU) and N,N,N?,N?-tetramethylthiourea (TMTU) under pseudo first order conditions as a function of concentration and temperature using the stopped flow spectrophotometer. The observed pseudo first order rate constants for the substitution reactions obey the rate law kobs = k2[Nu]. The reactivity of the studied complexes depends on strength of pi-backbonding of the attached ligands, which is enhanced by the strong electron withdrawing nature of the carboxamide group on the non-leaving ligands of Pt(II) complexes. Quinoline moieties of Pt5 and Pt6 lie out-of-the square plane, resulting in enhanced reactivity due to the aided entrapment of the nucleophile by the non-planar groups of the ligand. Negative activation entropies and positive enthalpies of activation support an associative mode of activation.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1740N – PubChem

 

Extracurricular laboratory:new discovery of Isoquinoline-3-carboxylic acid

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A number of quinolines and isoquinolines connected in various ways to a substituted benzimidazol-2-yl system were synthesized and evaluated as novel antagonists of adenosine receptors (ARs) by competition experiments using human A1, A2A, and A3 ARs. The new compounds were designed based on derivatives of 2-(benzimidazol-2-yl)quinoxaline, previously reported as potent and selective antagonists of A1 and A3 ARs. Among these, 3-[4-(ethylthio)-1H-benzimidazol-2-yl]isoquinoline 4b exhibited the best combination of potency toward the A1 AR (Ki=1.4nM) and selectivity against the A2A (Ki>10mum), A2B (Ki>10mum), and A3 ARs (Ki>1muM). Functional experiments in circular smooth muscle preparations of isolated human colon showed that 4b behaves as a potent and selective antagonist of the A1 AR in the neuromuscular compartment of this intestinal region. Biological and pharmacological data suggest that 4b is a suitable starting point for the development of novel agents endowed with stimulant properties on colonic activity.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1704N – PubChem

 

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The structures, spectroscopy, and cytotoxicity of four novel nominally square-planar gold(III) chelates 1-4 with the general formula cis-AuCl 2(X), where the ligand X is an anionic bidentate pyridyl- or isoquinolylamido chelating agent, are described. The Au-Namido, Au-Npyridyl, and Au-Nisoquinolyl distances are 2.002(9)-2.016(3), 2.01(1)-2.037(3), and 2.037(3) A, respectively. Density functional theory simulations afforded accurate gold(III) coordination geometries for 1-4 (bond distances and angles to within 5% of the X-ray values), while accurate transition energies were limited to those calculated in the UV spectral region. The complexes had variable stability in dimethyl sulfoxide: compound 3 (relatively rigid) was indefinitely stable, compounds 1 and 2 (conformationally flexible) slowly demetalated over 30 days, and 4 (extensively aromatic) formed an insoluble precipitate after 10 days (72 h in an aqueous buffer). The isoquinolylamido derivative 4 was sufficiently cytotoxic in the NCI-60 screen to undergo full five-dose testing. Notably low GI50 (1.8, 2.3, and 3.2 muM) and IC50 (4.0, 9.8, and 15 muM) values were recorded for the OVCAR-3, IGROV1, and SW-620 cell lines, respectively. Hierarchical cluster analysis employing the National Cancer Institute (NCI) data for known anticancer drugs and 4 revealed that compound 4 is mechanistically identical with the topoisomerase IIalpha (Top2) poison zorubicin and statistically similar to the topoisomerase IB (Top1) poisons camptothecin and 9-methoxycamptothecin. The Top2-catalyzed decatenation reaction of kinetoplast DNA was studied as a function of the concentration of 4: the compound acts as an interfacial poison of Top2 at low concentrations (<1 muM) and a catalytic inhibitor of the enzyme above 5 muM. Gel mobility shift assays (plasmid DNA substrate) showed that the catalytic inhibition of Top2 likely correlates with DNA binding by 4 at concentrations >5 muM. Compound 4 is also a catalytic inhibitor of Top1 at higher concentrations, consistent with DNA binding by the complex.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1762N – PubChem

 

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Reference of 6624-49-3, Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Article, and a compound is mentioned, 6624-49-3, Isoquinoline-3-carboxylic acid, introducing its new discovery.

Animal African trypanosomiasis (AAT) is a significant socioeconomic burden for sub-Saharan Africa because of its huge impact on livestock health. Existing therapies including those based on minor groove binders (MGBs), such as the diamidines, which have been used for decades, have now lost efficacy in some places because of the emergence of resistant parasites. Consequently, the need for new chemotherapies is urgent. Here, we describe a structurally distinct class of MGBs, Strathclyde MGBs (S-MGBs), which display excellent in vitro activities against the principal causative organisms of AAT: Trypanosoma congolense, and Trypanosoma vivax. We also show the cure of T. congolense-infected mice by a number of these compounds. In particular, we identify S-MGB-234, compound 7, as curative by using two applications of 50 mg/kg intraperitoneally. Crucially, we demonstrate that S-MGBs do not show cross-resistance with the current diamidine drugs and are not internalized via the transporters used by diamidines. This study demonstrates that S-MGBs have significant potential as novel therapeutic agents for AAT.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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On the basis of a mu opioid receptor (MOR) homology model and the isosterism concept, three generations of 14-heteroaromatically substituted naltrexone derivatives were designed, synthesized, and evaluated as potential MOR-selective ligands. The first-generation ligands appeared to be MOR-selective, whereas the second and the third generation ones showed MOR/kappa opioid receptor (KOR) dual selectivity. Docking of ligands 2 (MOR selective) and 10 (MOR/KOR dual selective) to the three opioid receptor crystal structures revealed a nonconserved-residue-facilitated hydrogen-bonding network that could be responsible for their distinctive selectivity profiles. The MOR/KOR dual-selective ligand 10 showed no agonism and acted as a potent antagonist in the tail-flick assay. It also produced less severe opioid withdrawal symptoms than naloxone in morphine-dependent mice. In conclusion, ligand 10 may serve as a novel lead compound to develop MOR/KOR dual-selective ligands, which might possess unique therapeutic value for opioid addiction treatment.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1769N – PubChem

 

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Previously obtained benzylamides of isoquinoline-3-carboxylic acids and isoquinoline-1-carboxylic acids exhibited anticonvulsant activity. In search for more effective anticonvulsants, a series of amides of isoquinoline-3- and isoquinoline-1-carboxylic acids have been synthesized (1-9). The obtained compounds were evaluated qualitatively for their anticonvulsant activity in the maximal electroshock seizure test (MES test), minimal clonic seizure test (6Hz test) and subcutaneous metrazol seizure threshold test (sc MET test) as well as in the rotorod neurotoxicity test (Tox test). One selected compound was tested quantitatively in 6Hz-test in mice after intraperitoneal administration and showed activity ED50 = 385.69 mg/kg and TD50 > 600 mg/kg (1).

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

Discovery of Isoquinoline-3-carboxylic acid

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Ghrelin receptor ligands based on a trisubstituted 1,2,4-triazole scaffold were recently synthesized and evaluated for their in vitro affinity for the GHS-R1a receptor and their biological activity. In this study, replacement of the alpha-aminoisobutyryl (Aib) moiety (a common feature present in numerous growth hormone secretagogues described in the literature) by aromatic and heteroaromatic groups was explored. We found potent antagonists incorporating the picolinic moiety in place of the Aib moiety. In an attempt to increase affinity and activity of our lead compound 2, we explored the modulation of the pyridine ring. Herein we report the design and the structure-activity relationships study of these new ghrelin receptor ligands.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1694N – PubChem

 

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Steroids possessing an ethynyl group at position 17alpha (tertiary alcohols) are well known to be more stable than their non-ethynyl analogs (secondary alcohols). To facilitate the development of new drugs with better metabolic stability, we developed a new diethylsilyl acetylenic linker allowing us to rapidly synthesize libraries of ethynylated steroid derivatives using a solid-phase strategy. To illustrate its usefulness, this linker was used to expand the molecular diversity of a lead compound having a hydroxy acetylenic pattern and to potentially find new compounds with interesting cytotoxic activity against leukemia cell lines. Herein, we report the chemical synthesis and the characterization of three libraries of ethynylated aminosteroid derivatives using the diethylacetylenic linker. We discuss their antiproliferative activities obtained in 2 leukemia cell lines (HL-60 and Jurkat), which results provided new structure-activity relationships. We also identified a new promising aminosteroid derivative with an azetidine moiety (compound B1) inhibiting 60% and 75% of HL-60 and Jurkat cell proliferation, respectively, at 1 muM. More generally, these results validate the use of a diethylsilyl acetylenic linker for researchers interested in generating libraries of alcohol derivatives with better stability and drug profile.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H1756N – PubChem

 

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Nowadays, the inhibition of acetylcholinesterase is one of the main pharmacological strategies for the treatment of Alzheimer’s disease. Therefore, a set of thirty-four derivatives of the diterpenoid dehydroabietylamine has been synthesized and screened in colorimetric Ellman’s assays to determine their ability to inhibit the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). A systematic variation of the substitution of dehydroabietylamides enabled an approach to analogs showing a remarkable inhibition potency for AChE. Particularly N-benzoyldehydroabietylamines 11, 12 and 13 were excellent inhibitors for AChE, showing inhibition rates comparable to standard galantamine hydrobromide.

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Reference:
Isoquinoline – Wikipedia,
Isoquinoline | C9H1760N – PubChem