- New four-component Ugi-type reaction. Synthesis of 3-methyl-1-oxo-1,3,4,6, 11,11a-hexahydro-2H-pyrazino[1,2-b]isoquinoline-3-carboxamides
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A small-sized library of novel 3,4,11,11a-tetrahydro-2H-pyrazino[1,2-b] isoquinolin-1(6H)-ones is synthesized. Key synthetic step is based on a new variant of Ugi four component reaction using bifunctional keto acids, amine and isocyanide as starting mate
- Ilyn, Alexey P.,Trifilenkov, Andrey S.,Kovrigin, Denis I.,Yudin, Michail V.,Ivachtchenko, Alexandre V.
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- USP30 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of USP30, and the treatment of USP30-mediated disorders.
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Paragraph 00315; 00373-00374
(2021/03/19)
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- NATURAL KILLER CELLS
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This invention relates to Natural Killer (NK) cell populations, to methods of producing the same and therapeutic applications thereof. More specifically, the invention relates to the expansion of IMK cells by increasing the expression of specific transcription factors associated with NK cell production.
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Page/Page column 91-92; 98
(2020/01/24)
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- Gene delivery system
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The invention discloses a preparation method of a gene nano-liposome carrier Isoquinoline-3-acyl-RGDV(IRV) and an IRV/STAT3-siRNA gene delivery system. The IRV/STAT3-siRNA gene delivery system is composed of liposome carriers IRV and STAT3-siRNA, protamine and calf thymus DNA in a proportion, and has slow release and targeting effects. The cell transfection efficiency, the in-vitro anti-tumor activity, and the gene silencing efficiency and a cell action mechanism on the mRNA level and the protein level of a compound are evaluated with the lung cancer A549 cell strain as a model, and the result shows the IRV/STAT3-siRNA gene delivery system has more excellent anti-tumor activity and gene silencing efficiency compared with control groups. According to the system, the anti-tumor activity of the IRV/STAT3-siRNA gene delivery system is evaluated with an S180 ascites tumor mouse as a model, and the result shows that a 100% IRV/STAT3-siRNA group has an anti-tumor effect.
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- Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox
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Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.
- Hermant, Paul,Bosc, Damien,Piveteau, Catherine,Gealageas, Ronan,Lam, Baovy,Ronco, Cyril,Roignant, Matthieu,Tolojanahary, Hasina,Jean, Ludovic,Renard, Pierre-Yves,Lemdani, Mohamed,Bourotte, Marilyne,Herledan, Adrien,Bedart, Corentin,Biela, Alexandre,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
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p. 9067 - 9089
(2017/11/14)
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- Synthesis and assay of isoquinoline derivatives as HIV-1 Tat-TAR interaction inhibitors
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Four new isoquinoline derivatives bearing guanidinium group or amino group-terminated side chain were synthesized to target the HIV-1 TAR element. Their abilities to bind TAR RNA and inhibit Tat-TAR RNA interaction were determined by CE analysis, a Tat-dependent HIV-1 LTR-driven CAT assay and SIV-induced syncytium evaluation.
- He, Meizi,Yuan, Dekai,Lin, Wei,Pang, Ruifang,Yu, Xiaolin,Yang, Ming
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p. 3978 - 3981
(2007/10/03)
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- META-SUBSTITUTED PHENYLALANINE DERIVATIVES
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D,L-, L-and D-phenyl alanine derivatives of formula (I) defined in claim 1 in which R 1 is an amidino-, guanidino-, oxamidino-, aminomethyl-or amino group have been discovered which effectively prevent blood coagulation or thrombosis. The antithrombotically active compounds have low toxicity and may be administered by mouth, subcutaneously or intravenously.
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- Angiotensin converting enzyme inhibitors: N-substituted monocyclic and bicyclic amino acid derivatives
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The synthesis of N-(3-mercaptopropionyl)-N-arylglycines (14a-x), -N-arylalanines (15a,b), -N-cycloalkylglycines (16a-k), and -1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids (17a-d), -1,2,3,4-tetrahydroquinoline-2-carboxylic acids (18a-f), and -indoline-2-carboxylic acids (19a-k) is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound, and the structure-activity relationship for each series is discussed. The in vivo inhibition of ACE and antihypertensive effects of representative compounds from each series are discussed. The most potent compound, 19d, had an in vitro ACE IC50 of 2.6 x 10-9 M and lowered blood pressure in spontaneous hypertensive rats 85 mm at a dose of 10 mg/kg po.
- Stanton,Gruenfeld,Babiarz,Ackerman,Friedmann,Yuan,Macchia
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p. 1267 - 1277
(2007/10/02)
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- β-Carbolines: Synthesis and neurochemical and pharmacological actions on brain benzodiazepine receptors
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The authors have prepared a series of tetrahydro-β-carbolines (THβC), β-carbolines (β-C), and other nitrogen heterocycles and evaluated them in vitro with respect to their ability to bind to benzodiazepine receptors. The fully aromatic β-C's were more pot
- Cain,Weber,Guzman,Cook,Barker,Rice,Crawley,Paul,Skolnick
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p. 1081 - 1091
(2007/10/02)
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