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A gene delivery system (by machine translation)

The invention discloses gene nano liposome carrier Isoquinoline – 3 – acyl – RGDV (IRV) and IRV/STAT3 – siRNA preparation method of gene delivery system, in the present invention IRV/STAT3 – siRNA gene delivery system consists of a liposome carrier with IRV STAT3 – siRNA, protamines, calf Thymus DNA according to proportion, with slow release and targeting; the invention to lung cancer A549 cell strain is model to evaluate the complex cell transfection efficiency, in vitro anti-tumor activity, and mRNA level and protein at the level of gene silencing efficiency and cell mechanism, result display IRV/STAT3 – siRNA gene delivery system than every group has more excellent anti-tumor activity and gene silencing efficiency. Under the invention to S180 shui liu the abdomen of the mouse as a model to evaluate the IRV/STAT3 – siRNA gene delivery system of the anti-tumor activity, the result shows that 100% IRV/STAT3 – siRNA group has anti-tumor effect. (by machine translation)

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Reference：
Isoquinoline – Wikipedia,
Isoquinoline | C9H1667N – PubChem

 

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ISOQUINOLINE-3-CARBOXYLIC ACID AMIDES AND PHARMACEUTICAL USES THEREOF

The present invention relates to novel isoquinoline-3-carboxylic acid amides having alpha7 nicotinic acetylcholine receptor agonistic activity, their preparation, their use as pharmaceuticals and pharmaceutical compositions containing them.

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Isoquinoline – Wikipedia,
Isoquinoline | C9H1684N – PubChem

 

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Synthesis and pharmacological evaluation of potent and highly selective D3 receptor ligands: Inhibition of cocaine-seeking behavior and the role of dopamine D3/D2 receptors

The synthesis, pharmacological evaluation, and structure – activity relationships (SARs) of a series of novel arylalkylpiperazines structurally related to BP897 (3) are described. In binding studies, the new derivatives were tested against a panel of dopamine, serotonin, and noradrenaline receptor subtypes. Focusing mainly on dopamine D3 receptors, SAR studies brought to light a number of structural features required for high receptor affinity and selectivity. Several heteroaromatic systems were explored for their dopamine receptor affinities, and combinations of synthesis, biology, and molecular modeling, were used to identify novel structural leads for the development of potent and selective D3 receptor ligands. Introduction of an indole ring linked to a dichlorophenylpiperazine system provided two of the most potent and selective ligands known to date (D 3 receptor affinity in the picomolar range). The intrinsic pharmacological properties of a subset of potent D3 receptor ligands were also assessed in [35S]-GTPgammaS binding assays. Evidence from animal studies, in particular, has highlighted the dopaminergic system’s role in how environmental stimuli induce drug-seeking behavior. We therefore tested two novel D3 receptor partial agonists and a potent D 3-selective antagonist in vivo for their effect in the cocaine-seeking behavior induced by reintroduction of cocaine-associated stimuli after a long period of abstinence, and without any further cocaine. Compound 5g, a nonselective partial D3 receptor agonist with a pharmacological profile similar to 3, and 5p, a potent and selective D 3 antagonist, reduced the number of active lever presses induced by reintroduction of cocaine-associated stimuli. However, 5q, a highly potent and selective D3 partial agonist, did not have any effect on cocaine-seeking behavior. Although brain uptake studies are needed to establish whether the compounds achieve brain concentrations comparable to those active in vitro on the D3 receptor, our experiments suggest that antagonism at D2 receptors might significantly contribute to the reduction of cocaine craving by partial D3 agonists.

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Reference：
Isoquinoline – Wikipedia,
Isoquinoline | C9H1701N – PubChem

 

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Solid-phase synthesis of libraries of ethynylated aminosteroid derivatives as potential antileukemic agents

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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Reference：
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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New use of glutamate antagonists for the treatment of cancer

New therapies can be devised based upon a demonstration of the role of glutamate in the pathogenesis of cancer. Inhibitors of the interaction of glutamate with the AMPA, kainate, or NMDA receptor complexes are likely to be useful in treating cancer and can be formulated as pharmaceutical compositions. They can be identified by appropriate screens.

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Reference：
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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Synthesis and structure-activity relationships of 4-oxo-1-phenyl- 3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1-hi]indoles: Novel PDE4 inhibitors

A novel series of benzodiazepine derivatives have been discovered as inhibitors of PDE4 enzymes. We have found that our compounds are selective versus other PDE enzymes, and that the activity can be modulated by specific structural modifications. One compound exhibited a strong eosinophilic infiltration inhibiting action on sensitized Brown-Norway rats (compound 9, 5.1 mg/kg p.o.), moreover this compound is not emetic at 3 mg/kg i.v.

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Reference：
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

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Structure-activity relationship of boronic acid derivatives of tyropeptin: Proteasome inhibitors

The structure-activity relationship of the boronic acid derivatives of tyropeptin, a proteasome inhibitor, was studied. Based on the structure of a previously reported boronate analog of tyropeptin (2), 41 derivatives, which have varying substructure at the N-terminal acyl moiety and P2 position, were synthesized. Among them, 3-phenoxyphenylacetamide 6 and 3-fluoro picolinamide 22 displayed the most potent inhibitory activity toward chymotryptic activity of proteasome and cytotoxicity, respectively. The replacement of the isopropyl group in the P2 side chain to H or Me had negligible effects on the biological activities examined in this study.

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Reference£º
Isoquinoline – Wikipedia,
Isoquinoline | C9H1759N – PubChem

 

In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 6624-49-3, name is Isoquinoline-3-carboxylic acid, introducing its new discovery. name: Isoquinoline-3-carboxylic acid

MCH-R1 antagonists based on an arginine scaffold: SAR studies on the amino-terminus

We have identified a novel series of potent MCH-R1 antagonists based on l-arginine. As predicted by computational methods, there was an activity dependence on the pi-electronic character of the aromatic systems corresponding to the amino-terminus of these molecules. These results have enhanced our understanding of the MCH-R1 receptor and the potential for a predictive homology model.

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Reference£º
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 6624-49-3, name is Isoquinoline-3-carboxylic acid, introducing its new discovery. Formula: C10H7NO2

Discovery of a potent class I selective ketone histone deacetylase inhibitor with antitumor activity in vivo and optimized pharmacokinetic properties

The optimization of a potent, class I selective ketone HDAC inhibitor is shown. It possesses optimized pharmacokinetic properties in preclinical species, has a clean off-target profile, and is negative in a microbial mutagenicity (Ames) test. In a mouse xenograft model it shows efficacy comparable to that of vorinostat at a 10-fold reduced dose.

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Reference£º
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

 

Chemistry is traditionally divided into organic and inorganic chemistry. Safety of Isoquinoline-3-carboxylic acid, The former is the study of compounds containing at least one carbon-hydrogen bonds.In a patent£¬Which mentioned a new discovery about 6624-49-3

Non-platinum complexes containing releasable biologically active ligands

Since the discovery of anticancer activity of cisplatin and other transition metal complexes, a lot of compounds have been reported as containing ligand(s) bearing its(their) own biological activity. Nowadays, the complexes containing releasable bioactive ligand(s), for which several terms (e.g., multi-targeted, multi-action or multi-modal) have been introduced, represent one of the hottest topics for the bioinorganic chemists. Herein we focused on rationally designed cytotoxic complexes of platinum-group metals, namely ruthenium, rhodium, palladium, osmium and iridium, which contain releasable bioactive ligand(s). Because a concept of multi-targeted complexes is based on a release and subsequent joint biological effect of multiple species, we concentrate especially on complexes whose fate under the (pseudo)physiological conditions is provably or most likely connected with a release of bioactive ligand(s)/substituent(s) and cytotoxic metal-containing species. Thus, the simultaneous action of the released species ensures various biological profits, such as higher cytotoxic activity, cytotoxicity at different cells (connected with the ability to overcome resistance) or modified processes connected with the mode of action, as compared with the initial complexes without bioactive ligand(s).

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Reference£º
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem