101-98-4Relevant academic research and scientific papers
Biquaternary ammonium compound and preparation method and application thereof
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Paragraph 0142-0145, (2021/06/02)
The invention provides a biquaternary ammonium compound and a preparation method and application thereof. The biquaternary ammonium compound is shown as a formula (I). The compound disclosed by the invention has quick-acting and ultra-short-acting non-depolarized muscle relaxation molecular activity, is quick in acting and can generate a complete muscle relaxation effect under the condition of low administration dosage, and the time required for complete recovery of muscle strength is short and is obviously shorter than that of a positive drug cisatracurium and a depolarized muscle relaxation drug succinylcholine; the problems of non-depolarized muscle relaxant in the prior art are effectively solved, and the compound can be used for preparing the non-depolarized muscle relaxant with an excellent effect and has a good prospect.
CRYSTAL FORM OF MONOMETHANESULFONATE OF DEUTERATED 3-(4,5-SUBSTITUTED AMINOPYRIMIDINE)PHENYL COMPOUND AND PREPARATION METHOD THEREFOR
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Paragraph 0047, (2021/02/26)
Disclosed in the present invention are a crystal form of monomethanesulfonate of a deuterated 3-(4,5-substituted aminopyrimidine)phenyl compound as represented by formula I, and a preparation method therefor. The crystal form is highly stable, can be used for treatment or prevention of diseases or conditions by means of epidermal growth factor receptors (EGFRs) in some mutation forms, can effectively inhibit the growth of a variety of tumor cells, and have an inhibiting effect on other proteases of EGFR and Her families, and thus can be used for preparing antitumor drugs.
A Universal Labeling Strategy for Nucleic Acids in Expansion Microscopy
Hofkens, Johan,Leen, Volker,Rohand, Taoufik,Vandereyken, Katy,Vanheusden, Marisa,Voet, Thierry,Wen, Gang
supporting information, p. 13782 - 13789 (2021/09/11)
Expansion microscopy (ExM) enables the nanoscale imaging of ribonucleic acids (RNAs) on a conventional fluorescence microscope, providing information on the intricate patterns of gene expression at (sub)cellular resolution and within spatial context. To extend the use of such strategies, we examined a series of multivalent reagents that allow the labeling and grafting of deoxyribonucleic acid (DNA) oligonucleotide probes in a unified approach. We show that the reagents are directly compatible with third-generation in situ hybridization chain reaction RNA FISH (fluorescence in situ hybridization) techniques while displaying complete retention of the targeted transcripts. Furthermore, we validate and demonstrate that our labeling method is compatible with multicolor staining. Through oligonucleotide-conjugated antibodies, we demonstrate excellent performance in ×4 ExM and ×10 ExM, achieving a resolution of ～50 nm in ×10 ExM for both pre- and postexpansion labeling strategies. Our results indicate that our multivalent molecules enable the rapid functionalization of DNA oligonucleotides for ExM.
Ru-Catalyzed Switchable N-Hydroxyethylation and N-Acetonylation with Crude Glycerol
Xin, Zhuo,Jia, Le,Huang, Yuxing,Du, Chen-Xia,Li, Yuehui
, p. 2007 - 2011 (2020/03/19)
Highly efficient Ru-catalyzed selective C?C or C?O bond cleavage of polyols (e.g., crude glycerol) for N-hydroxyethylation or N-acetonylation of amines was achieved through the hydrogen-borrowing approach. A variety of amines were transformed to the desired amino alcohols/ketones in moderate-to-excellent yields, opening up new avenues for generation of oxygenated pharmaceuticals and fine chemicals from renewable raw materials. The use of new redox-active catalysts containing bisphosphine/thienylmethylamine ligands allows this hydrogen-borrowing system to be operated selectively under both basic and acidic conditions.
DEUTERATED 3-(4,5-SUBSTITUTED PYRIMIDINAMINE) PHENYL DERIVATIVES AND APPLICATIONS THEREOF
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Paragraph 0025-0028; 0079-0082, (2019/06/27)
The present invention discloses a type of deuterated 3-(4,5-substituted aminopyrimidine)phenyl derivatives and use thereof. The derivatives are compounds of Formula (I) or pharmaceutically acceptable salts thereof. These compounds or salts thereof can be used for treatment or prevention of diseases or illnesses through certain mutant forms of epidermal growth factor receptors, inhibit the growth of various tumor cells effectively, and inhibit other proteases of EGFR and Her families, they can be used for preparing anti-tumor drugs.
Nucleophilic Fluorination and Radiofluorination via Aziridinium Intermediates: N-Substituent Influence, Unexpected Regioselectivity, and Differences between Fluorine-19 and Fluorine-18
Médoc, Marie,Sobrio, Franck
, p. 10086 - 10097 (2015/11/03)
The efficient dehydrofluorination and radiofluorination of N,N-disubstituted-β-aminoalcohols through an anchimeric-assisted mechanism was developed. An investigation into the influence of N-substituents on the ring opening of the aziridinium intermediate indicated differences in the isomeric ratio and the yields of fluorinated products obtained from N,N-disubstituted-phenylalaninol. This influence was substantial for 18F-radiofluorination, with yields varying from 0 to 71% at room temperature (RT). Although no significant effects were observed in the fluorine-19 chemistry when the reaction was heated to 90 °C, considerable changes appeared during radiofluorination. In the latter case, the radiochemical yields increased, and degradation of the 2-fluoro-propan-1-amine isomer (b) occurred, leading to a regiospecific reaction in the radiolabeling of [18F]-fluorodeprenyl. This method involving nucleophilic radiofluorination at RT was successfully applied to the radiolabeling of [18F]-2-fluoroethylamines in which the influence of the N-substituent was also observed.
METHOD OF PRODUCING TERTIARY AMINE OR TERTIARY AMINE DERIVATIVE
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Paragraph 0066; 0071, (2018/10/31)
PROBLEM TO BE SOLVED: To provide a method of producing tertiary amine or tertiary amine derivative with high selectivity. SOLUTION: In the method of producing tertiary amine or tertiary amine derivative, a reaction system including: an organic chemical raw material containing at least one kind of group selected from -NH2, -NH2 HCl, >NH and >NH HCl, a nitrogen atom contained in the group bounding to a carbon atom; aliphatic alcohol having 1 to 20 carbon atoms; and a catalyst where a carrier containing titanium oxide carries a silver component (metal silver or silver compound), is irradiated with light, and the group in the organic compound raw material is converted to -NR02 or >NR0, ( R0 is an aliphatic hydrocarbon group having 1 to 20 carbon atoms derived from the aliphatic alcohol). The percentage content of the silver in the catalyst is 0.5 to 10 mass% with respect to the titanium oxide. COPYRIGHT: (C)2015,JPOandINPIT
Benzoxazolone Carboxamides as Potent Acid Ceramidase Inhibitors: Synthesis and Structure-Activity Relationship (SAR) Studies
Bach, Anders,Pizzirani, Daniela,Realini, Natalia,Vozella, Valentina,Russo, Debora,Penna, Ilaria,Melzig, Laurin,Scarpelli, Rita,Piomelli, Daniele
supporting information, p. 9258 - 9272 (2015/12/23)
Ceramides are lipid-derived intracellular messengers involved in the control of senescence, inflammation, and apoptosis. The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphingosine and fatty acid and, by doing so, regulates their signaling activity. AC inhibitors may be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity-stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic administration. The results expand our arsenal of AC inhibitors, thereby facilitating the use of these compounds as pharmacological tools and their potential development as drug leads.
C-F bond substitution via aziridinium ion intermediates
Tr?ff,Janjetovic,Hilmersson
, p. 13260 - 13263 (2015/08/24)
Aliphatic 1,2-aminofluorides undergo extremely fast substitution reactions under the influence of lanthanum tris(hexamethyldisilazide). The substitution proceeds via an in situ generated aziridinium ion intermediate, which subsequently undergoes ring opening by addition of a nucleophile, yielding various β-substituted amines.
Comprehensive evaluation of the physicochemical properties of Ln III complexes of aminoethyl-DO3A as pH-responsive T1-MRI contrast agents
Baranyai, Zsolt,Rolla, Gabriele A.,Negri, Roberto,Forgacs, Attila,Giovenzana, Giovanni B.,Tei, Lorenzo
supporting information, p. 2933 - 2944 (2014/03/21)
N-Substituted aminoethyl groups were attached to 1,4,7,10- tetraazacyclododecane-1,4,7-triacetic acid (DO3A) with the aim to design pH-responsive LnIII complexes based on the pH-dependent on/off ligation of the amine nitrogen to the metal ion. The following ligands were synthesized: AE-DO3A (aminoethyl-DO3A), MAE-DO3A (N-methylaminoethyl-DO3A), DMAE-DO3A (N,N-dimethylaminoethyl-DO3A) and MEM-AE-DO3A (N-methoxyethyl-N- methylaminoethyl-DO3A). The physicochemical properties of the LnIII complexes were investigated for the evaluation of their potential applicability as magnetic resonance imaging (MRI) contrast agents. In particular, a 1H and 17ONMR relaxometric study was carried out for these GdIII complexes at two different pH values: at basic pH (pendant amino group coordinated to the metal centre) and at acidic pH (protonated amine, not interacting with the metal ion). EuIII complexes allow one to estimate the number of inner-sphere water molecules through luminescence lifetime measurements and obtain some structural information through variable-temperature (VT) high-resolution 1HNMR studies. Equilibria between differently hydrated species were found for most of the complexes at both acidic and basic pH. The thermodynamic stability of CaII, ZnII, CuII and LnIII complexes and kinetics of formation and dissociation reactions of LnIII complexes of AE-DO3A and DMAE-DO3A were investigated showing stabilities comparable to currently approved GdIII-based CAs. In detail, higher total basicity (Σlog KiH) and higher stability constants of Ln III complexes were found for AE-DO3A with respect to DMAE-DO3A (i.e., log KGd-AE-DO3A=22.40 and log KGd-DMAE-DO3A=20.56). The transmetallation reactions of GdIII complexes are very slow (Gd-AE-DO3A: t1/2=2.7×104h; Gd-DMAE-DO3A: 1.1×105h at pH7.4 and 298K) and occur through proton-assisted dissociation. pH Switches: N-Substituted aminoethyl-1,4,7,10- tetraazacyclododecane-1,4,7-triacetic acid (DO3A)-based complexes were prepared to obtain pH-sensitive T1-MRI contrast agents. A detailed evaluation of the physicochemical properties of LnIII complexes was undertaken by different techniques, highlighting the structural variations triggered by the protonation of the pendant amine and the effect of the substituents on the corresponding nitrogen atom (see figure).
