5491-18-9Relevant articles and documents
Design and synthesis of novel symmetric fluorene-2,7-diamine derivatives as potent hepatitis C virus inhibitors
Mousa, Mai H. A.,Ahmed, Nermin S.,Schwedtmann, Kai,Frakolaki, Efseveia,Vassilaki, Niki,Zoidis, Grigoris,Weigand, Jan J.,Abadi, Ashraf H.
, (2021/04/16)
Hepatitis C virus (HCV) is an international challenge. Since the discovery of NS5A direct-acting antivirals, researchers turned their attention to pursue novel NS5A inhibitors with optimized design and structure. Herein we explore highly potent hepatitis C virus (HCV) NS5A inhibitors; the novel analogs share a common symmetrical prolinamide 2,7-diaminofluorene scaffold. Modification of the 2,7-diaminofluorene backbone included the use of (S)-prolinamide or its isostere (S,R)-piperidine-3-caboxamide, both bearing different amino acid residues with terminal carbamate groups. Compound 26 exhibited potent inhibitory activity against HCV genotype (GT) 1b (effective concentration (EC50) = 36 pM and a selectivity index of >2.78 × 106). Compound 26 showed high selectivity on GT 1b versus GT 4a. Interestingly, it showed a significant antiviral effect against GT 3a (EC50 = 1.2 nM). The structure-activity relationship (SAR) analysis revealed that picomolar inhibitory activity was attained with the use of S-prolinamide capped with R- isoleucine or R-phenylglycine residues bearing a terminal alkyl carbamate group.
Symmetric benzidine derivatives as anti-HCV agents: Insight into the nature, stereochemistry of the capping amino acid and the size of the terminal capping carbamates
Abadi, Ashraf H.,Abdel Karim, Shereen E.,Abdel-Halim, Mohammad,Ahmed, Nermin S.,Frakolaki, Efseveia,Vassilaki, Niki,Youssef, Youssef H.,Zoidis, Grigoris
, (2020/07/27)
Novel symmetric molecules, bearing a benzidine prolinamide core, two terminal carbamate caps of variable sizes and nature, including natural and unnatural amino acids were developed. Several terminal N-carbamate substituents of the core structure, ranging from linear methyl, ethyl and butyl groups to branching isobutyl group; and an aromatic substituent were also synthesized. Series 1 has hydrophobic AA residues, namely S and R phenylglycine and a terminal carbamate capping group, whereas Series 2 bears sulphur containing amino acids, specifically S and R methionine and the natural R methylcysteine. The novel compounds were tested for their inhibitory activity (EC50) and their cytotoxicity (CC50), using an HCV 1b (Con1) reporter replicon cell line. Compound 4 with the unnatural capping residue, bearing D-Phenylglycine amino acid residue and N-isobutyloxycarbonyl capping group, was the most active within the two series, with EC50 = 0.0067 nM. Moreover, it showed high SI50 > 14788524 and was not cytotoxic at the highest tested concentration (100 μΜ), indicating its safety profile. Compound 4 also inhibited HCV genotypes 2a, 3a and 4a. Compared to the clinically approved NS5A inhibitor Daclatasvir, compound 4 shows higher activity against genotypes 1b and 3a, as well as improved safety profile.
THERAPEUTIC USE OF LEVOROTATORY ?-LACTAMS IN HEMATOPOIESIS, IMMUNO-ONCOLOGY THERAPY, AND REGULATION OF LIPOPROTEIN AND APOLIPOPROTEIN LEVELS
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Page/Page column 29-30, (2018/08/20)
A method for increasing the number of CD4+ T-lymphocytes in the serum of a subject in need of such treatment comprising administering to the subject a pharmaceutical composition comprising an amount of an L-isomer of β-lactam effective to increase the number of CD4+ T-lymphocytes in said patient's serum.
Montmorillonite K10 catalyzed highly regioselective azidolysis of epoxides: A short and efficient synthesis of phenylglycine
Ch Ghosh, Keshab,Banerjee, Isita,Sinha, Surajit
, p. 2923 - 2934 (2018/12/04)
A series of β‐hydroxyazides were effectively synthesized from the regioselective ring opening of epoxides by sodium azide using montmorillonite K10 as a novel heterogeneous catalyst in aqueous acetonitrile in good to excellent yields. The utility of this method has been demonstrated by achieving a short synthesis of phenylglycine in 33.5% overall yield.
COMPOUNDS USEFUL AS CSF1 MODULATORS
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Paragraph 00423; 00428; 00429, (2016/04/26)
This invention relates to novel compounds and to pharmaceutical compositions comprising the novel compounds. More specifically, the invention relates to compounds useful as Colony Stimulating Factor 1 Receptor (cFMS) modulators (e.g. cFMS inhibitors). This invention also relates to processes for preparing the compounds, uses of the compounds in treatment and methods of treatment employing the compounds. Specifically, the invention relates to the use of the compounds for the treatment of cancer and autoimmune diseases.
N-METHYL-N-(1-PHENYL-2-(1-PYRROLIDINYL)ETHYL)-2-AMINOPHENYLACETAMIDE DERIVATIVES AGONISTS FOR THE KAPPA OPIOID RECEPTOR
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Paragraph 00158-00159, (2016/07/27)
Compounds and pharmaceutically acceptable salts and solvates thereof are described. The compounds relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology and organic chemistry.
KAPPA OPIOID AGONISTS AND USES THEREOF
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Paragraph 00520; 00521, (2015/01/16)
Provided are compounds of Formula I; and pharmaceutically acceptable salts and solvates thereof. The compounds of Formula I described herein relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology, organic chemistry and polymer chemistry.
METHOD FOR PRODUCING CARBOXYLIC ACID AND ALCOHOL BY HYDROLYSIS OF ESTER
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Paragraph 0069; 0070, (2014/11/13)
As shown by the following formula (1), after methyl laurate (2 mmol) and water (8 mL) are added to an ammonium pyrosulfate catalyst (5 mol%), a hydrolysis reaction of methyl laurate is carried out by heating for 24 hours at 60°C while stirring is performed, so that lauric acid can be obtained with a yield of 86%.
SUBSTITUTED HETEROCYCLIC ACETAMIDES AS KAPPA OPIOID RECEPTOR (KOR) AGONISTS
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Page/Page column 122, (2013/09/26)
The present invention relates to a series of substituted compounds having the general formula (I), including their ste reoisomers and/or their pharmaceutically acceptable salts, wherein R1, R2, R3. R4, R5, and R6 are as defined herein. This invention also relates to methods of making these compounds including intermediates. The compounds of this invention are effective at the kappa (κ) opioid receptor (KOR) site. Therefore, the compounds of this invention are useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of central nervous system disorders (CNS), including but not limited to acute and chronic pain, and associated disorders, particularly functioning peripherally at the CNS.
One-step synthesis of racemic α-amino acids from aldehydes, amine components, and gaseous CO2 by the aid of a bismetal reagent
Mita, Tsuyoshi,Higuchi, Yuki,Sato, Yoshihiro
, p. 1123 - 1128 (2013/02/23)
α-Amino acids are essential resources for human life and are highly useful as building blocks for organic synthesis. The core framework of an α-amino acid can be divided into three basic components: an aldehyde, an amine, and carbon dioxide (CO2). We report herein that a one-step synthesis of α-amino acids has been successfully achieved from these three basic and inexpensive chemicals with a single operation, in which the mixture of an aldehyde, a sulfonamide, and gaseous CO2 was heated at 100 °C in the presence of Bu3Sn-SnBu3 and CsF. In this one-pot sequential protocol, two important intermediates (imine and α-amino stannane) are involved and the stannyl anion generated in situ plays a crucial role, particularly for the efficient stannylation of the imine in the presence of proton sources and for promoting retrostannylation of the undesired α-alkoxy stannane owing to its high stability and tolerance of the presence of proton sources. This methodology enabled the synthesis of a wide range of racemic arylglycine derivatives in high yields. Go retro! α-Amino acids are essential resources for human life and are highly useful as building blocks for organic synthesis. The core framework of an α-amino acid is retrosynthesized to an aldehyde, an amine, and carbon dioxide. A one-step synthesis of α-amin Copyright
