74163-81-8Relevant articles and documents
NITROGEN-CONTAINING COMPOUND, METHOD FOR MANUFACTURING THE SAME, AND OPTICAL FUNCTIONAL MATERIAL INCLUDING THE SAME
-
Paragraph 0152-0153, (2021/08/21)
PROBLEM TO BE SOLVED: To provide a novel nitrogen-containing compound having luminescence property. SOLUTION: A nitrogen-containing compound represented by the following formula (I) in which RA, RB, R1, R2, R3, R4, and X are either one of the following (1) and (2). SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
Novel isoquinoline-oxazoline chiral ligand and preparation and application thereof (by machine translation)
-
Paragraph 0021-0022; 0024, (2020/06/20)
The invention relates to a novel isoquinoline-oxazoline chiral ligand as well as preparation and application thereof. Substituted radicals R in the general formula1 And R2 The isoquinoline-oxazoline chiral ligand disclosed by the invention can be used as a ligand and a metal to form a complex or a composition for asymmetric catalysis, and particularly the asymmetric Michael addition of the isoquinoline-oxazoline ligand and the metal palladium can effectively catalyze the asymmetric Michael addition of boric acid and nitroolefin, and has excellent stereoselectivity. (by machine translation)
Chemoenzymatic Approach to (S)-1,2,3,4-Tetrahydroisoquinoline Carboxylic Acids Employing D-Amino Acid Oxidase
Ju, Shuyun,Qian, Mingxin,Xu, Gang,Yang, Lirong,Wu, Jianping
supporting information, p. 3191 - 3199 (2019/05/15)
Optically pure 1,2,3,4-tetrahydroisoquinoline carboxylic acids constitute an important class of building blocks for the synthesis of natural products and synthetic pharmaceuticals. However, redox deracemization of racemic 1,2,3,4-tetrahydroisoquinoline carboxylic acids as an attractive method is still challenging for the lack of suitable oxidoreductases. Herein, a D-amino acid oxidase from Fusarium solani M-0718 (FsDAAO) with broad substrate scope and excellent enantioselectivity was exploited through genome mining, and applied for the kinetic resolution of a number of racemic 1- and 3-carboxyl substituted tetrahydroisoquinolines to yield the corresponding (S)-enantiomers with excellent enantiomeric excess (ee) values (up to >99%). By using FsDAAO in combination with ammonia-borane in one pot, deracemization of these racemic carboxyl-substituted tetrahydroisoquinolines was achieved with conversions up to >98% and >99% ee. Preparative-scale deracemization of racemic 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid and 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was also demonstrated with good isolated yields (82% and 73%, respectively) and ee>99%. Our study provides an effective method for the synthesis of enantiomeric pure 1,2,3,4-tetrahydroisoquinoline carboxylic acids. This method is expected to provide access to chiral carboxyl-substituted 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydro-?-carbolines. (Figure presented.).
Neuroligin-2-derived peptide-covered polyamidoamine-based (PAMAM) dendrimers enhance pancreatic β-cells' proliferation and functions
Munder, Anna,Moskovitz, Yoni,Meir, Aviv,Kahremany, Shirin,Levy, Laura,Kolitz-Domb, Michal,Cohen, Guy,Shtriker, Efrat,Viskind, Olga,Lellouche, Jean-Paul,Senderowitz, Hanoch,Chessler, Steven D.,Korshin, Edward E.,Ruthstein, Sharon,Gruzman, Arie
supporting information, p. 280 - 293 (2019/03/02)
Pancreatic β-cell membranes and presynaptic areas of neurons contain analogous protein complexes that control the secretion of bioactive molecules. These complexes include the neuroligins (NLs) and their binding partners, the neurexins (NXs). It has been recently reported that both insulin secretion and the proliferation rates of β-cells increase when cells are co-cultured with full-length NL-2 clusters. The pharmacological use of full-length protein is always problematic due to its unfavorable pharmacokinetic properties. Thus, NL-2-derived short peptide was conjugated to the surface of polyamidoamine-based (PAMAM) dendrimers. This nanoscale composite improved β-cell functions in terms of the rate of proliferation, glucose-stimulated insulin secretion (GSIS), and functional maturation. This functionalized dendrimer also protected β-cells under cellular stress conditions. In addition, various novel peptidomimetic scaffolds of NL-2-derived peptide were designed, synthesized, and conjugated to the surface of PAMAM in order to increase the biostability of the conjugates. However, after being covered by peptidomimetics, PAMAM dendrimers were inactive. Thus, the original peptide-based PAMAM dendrimer is a leading compound for continued research that might provide a unique starting point for designing an innovative class of antidiabetic therapeutics that possess a unique mode of action.
Multifunctional isoquinoline-oxazoline ligands of chemical and biological importance
Li, Wei,Wang, Guotong,Lai, Jixing,Li, Shengkun
supporting information, p. 5902 - 5905 (2019/05/27)
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.
Design and synthesis of nanoscaled IQCA-TAVV as a delivery system capable of antiplatelet activation, targeting arterial thrombus and releasing IQCA
Wu, Jianhui,Zhu, Haimei,Yang, Guodong,He, Jianhong,Wang, Yuji,Zhao, Shurui,Zhang, Xiaoyi,Gui, Lin,Zhao, Ming,Peng, Shiqi
, p. 1139 - 1158 (2018/03/09)
Background: Arterial thrombosis has been associated with a series of pathological conditions, and the discovery of arterial thrombosis inhibitor is of clinical importance. Methods: By analyzing the pharmacophores of anti-platelet agents, thrombus targeting peptide and anti-thrombotic nano-systems 3S-1,2,3,4-tetrahydroisoquino- line-3-carbonyl-Thr-Ala- Arg-Gly-Asp(Val)-Val (IQCA-TAVV) was designed and prepared as a nano-scaled arterial thrombosis inhibitor. Results: In vitro the nanoparticles of IQCA-TAVV were able to adhere onto the surface of activated platelets, attenuate activated platelets to extend pseudopodia and inhibit activated platelets to form aggregators. In vivo IQCA-TAVV targeted arterial thrombus, dose depend- ently inhibited arterial thrombosis with a 1 nmol/kg of minimal effective dose, and the activity was ~1670 folds of that of aspirin. Conclusion: IQCA-TAVV represented the design, preparation and application of nanomedicine capable of adhering on the surface of activated platelets, attenuating platelet activation, targeting arterial thrombus and inhibiting arterial thrombosis.
Stereoselective synthesis of 1,3-disubstituted dihydroisoquinolines vial-phenylalanine-derived dihydroisoquinoline N-oxides
Flores-Ferrándiz, Jesús,Carter, Nicholas,González-Soria, Maria José,Wasinska, Malgorzata,Gill, Daniel,Maciá, Beatriz,Caprio, Vittorio
supporting information, p. 6961 - 6968 (2018/10/17)
The preparation of chiral pool-derived nitrone 3 and its use in the protecting-group free, stereoselective synthesis of a range of 1,3-disubstituted tetrahydroisoquinolines is described. Grignard reagent additions to nitrone 3 yielded trans-1,3-disubstituted N-hydroxytetrahydroisoquinolines 6 with good levels of selectivity, while 1,3-dipolar cycloadditions to this nitrone provided access to 3-(2-hydroxyalkyl)isoquinolines 12 as single diastereomers.
Design and Discovery of Novel Chiral Antifungal Amides with 2-(2-Oxazolinyl)aniline as a Promising Pharmacophore
Zhang, Lu,Li, Wei,Xiao, Taifeng,Song, Zehua,Csuk, René,Li, Shengkun
, p. 8957 - 8965 (2018/09/10)
Inspired by established succinate dehydrogenase inhibitors (SDHIs), our continuing efforts toward the discovery of chiral antifungal amides turned to the optimization of their polar regions with 2-(2-oxazolinyl)aniline as a known pharmacophore. Scaffold hopping and bioactivity-guided convergent synthesis enabled the identification of promising antifungal categories. Fine tuning of the substituents and chirality furnished seven amides (1s, 1t, 2d, 2h, 2j, 3k, and 2l) as antifungal candidates, with EC50 values lower than 5 mg/L. The first investigation of chiral amides of acyclic acids as SDHIs was conducted, and compound 2d was selected as a promising candidate against Botrytis cinerea, with a preventative efficacy of up to 93.9% at 50 mg/L, which is better than that of boscalid. The different binding models between compounds with different configurations were simulated for compound 2d and its diastereoisomers. The benefits of synthetic accessibility and cost-effectiveness highlight the practical potential for compound 2d as a good alternative to known SDHI fungicides.
IQCA-TASS: a nano-scaled P-selectin inhibitor capable of targeting thrombus and releasing IQCA/TARGD(S)S in vivo
Wu, Jianhui,Zhu, Haimei,Zhao, Ming,Wang, Yuji,Yang, Guodong,Wang, Yaonan,Zhao, Shurui,Gui, Lin,Zhang, Xiaoyi,Peng, Shiqi
, p. 917 - 927 (2017/02/10)
Thrombosis is a serious threat to human health worldwide. Tetrahydroisoquinoline-3-carboxylic acid (IQCA) is an antithrombotic agent, while Thr-Ala-Arg-Gly-Asp(Ser)-Ser (TASS) can target thrombus. Herein, tetrahydro-isoquinoline-3-carbonyl-Thr-Ala-Arg-Gly-Asp(Ser)-Ser (IQCA-TASS) was designed with the aim towards the discovery of a nano-delivery system for targeting thrombus. In vitro, IQCA-TASS acted on P-selectin and down-regulated P-selectin expression. The IC50 values of IQCA-TASS against the platelet aggregation induced by four aggregators were less than 0.45 nM. In vivo, IQCA-TASS targeted thrombus, released IQCA and TASS inside the thrombus, showed dose-dependent anti-thrombotic action, of which the minimal effective dose was 1 nmol kg-1, and showed anti-inflammatory action. Even with the dose up to 1 μmol kg-1, a dose of 1000 times the minimal effective dose, IQCA-TASS still induced no toxic reaction. In rat plasma, IQCA-TASS formed nanoparticles with diameters of less than 41 nm. The interactions of the nanoparticles with both resting and activated platelets were imaged. IQCA-TASS should be a safe nano-medicine capable of targeting thrombus and releasing anti-thrombotic/anti-inflammatory pharmacophores in disease sites.
Environment-responsive multivalent isoquinoline-3-carboxylic acid conjugate, and preparation method and application thereof
-
Paragraph 0023; 0027; 0028, (2017/09/01)
The invention discloses an environment-responsive multivalent isoquinoline-3-carboxylic acid conjugate, and a preparation method and application thereof, belonging to the field of isoquinoline-3-carboxylic acid conjugates. According to the invention, 3,3'-dithiopropane diacid is used as a linking arm for coupling four isoquinoline-3-carboxylic acids with tris(2-aminoethyl)amine so as to form an isoquinoline derivative; multivalent synergism of a plurality of pharmacophores on a drug carrier is exerted on the lesion site of a tumor, so the antitumor activity of the antitumor drug is substantially improved; and through the environmental redox response of a disulfide bond to tumors, intelligent targeted release of the antitumor drug to a tumor part is realized, and toxicity of the antitumor drug to normal tissue is effectively reduced.