- NITROGEN-CONTAINING COMPOUND, METHOD FOR MANUFACTURING THE SAME, AND OPTICAL FUNCTIONAL MATERIAL INCLUDING THE SAME
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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
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- Design and Discovery of Novel Chiral Antifungal Amides with 2-(2-Oxazolinyl)aniline as a Promising Pharmacophore
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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.
- Zhang, Lu,Li, Wei,Xiao, Taifeng,Song, Zehua,Csuk, René,Li, Shengkun
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p. 8957 - 8965
(2018/09/10)
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- Pd/C-Catalyzed Dehydrogenative [3+2] Cycloaddition for the Synthesis of Functionalized Tropanes
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A Pd/C-catalyzed cascade approach for the synthesis of attractive benzo-fused tropanes was developed. The reaction proceeds through a sequential Pd/C-catalyzed dehydrogenative formation of azomethine ylides from amines and 1,3-dipolar cycloaddition. It allows the generation of structurally complex benzo-fused tropanes in good yields with excellent diastereoselectivities under mild reaction conditions. Preliminary results of asymmetric version of the reaction reveal that the copper catalyst and chiral monophosphoramidite ligand can furnish optically active products with moderate ee.
- Wang, Hai-Jun,Guo, Lei,Zhu, Cheng-Feng,Luo, Yun-Fei,Li, You-Gui,Wu, Xiang
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supporting information
p. 5456 - 5459
(2018/10/20)
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- ISOQUINOLIDINOBENZODIAZEPINES
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This disclosure provides novel isoquinolidinobenzodiazepines. These compounds can also be incorporated into antibody-drug conjugates.
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Paragraph 000476-000478
(2018/04/13)
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- ISOQUINOLIDINOBENZODIAZEPINE (IQB)-1(CHLOROMETHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE (CBI) DIMERS
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Provided herein are isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers, antibody-drug conjugates comprising them and methods of use for killing cells and treating disease.
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Paragraph 0009; 00114; 00122-00124
(2018/04/27)
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- Environment-responsive multivalent isoquinoline-3-carboxylic acid conjugate, and preparation method and application thereof
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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.
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- Anticancer activity of ruthenium(II) arene complexes bearing 1,2,3,4-tetrahydroisoquinoline amino alcohol ligands
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Ruthenium complexes offer potential reduced toxicity compared to current platinum anticancer drugs. 1,2,3,4-tetrahydrisoquinoline amino alcohol ligands were synthesised, characterised and coordinated to an organometallic Ru(II) centre. These complexes were evaluated for activity against the cancer cell lines MCF-7, A549 and MDA-MB-231 as well as for toxicity in the normal cell line MDBK. They were observed to be moderately active against only the MCF-7 cells with the best IC50 value of 34 μM for the cis-dia-stereomeric complex C4. They also displayed excellent selectivity by being relatively inactive against the normal MDBK cell line with SI values ranging from 2.3 to 7.4.
- Chelopo, Madichaba P.,Pawar, Sachin A.,Sokhela, Mxolisi K.,Govender, Thavendran,Kruger, Hendrik G.,Maguire, Glenn E. M.
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p. 407 - 414
(2013/10/01)
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- Design, synthesis and biological evaluation of new thalidomide analogues as TNF-α and IL-6 production inhibitors
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Several thalidomide analogues were synthesized and compared to thalidomide and its more active analogue, lenalidomide, for their ability to inhibit the production of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α and interleukin (IL)-6 by LPS-activated peripheral blood mononuclear cells (PBMCs). Among these compounds, two analogues containing sulfonyl group displayed interesting downregulation of TNF-α and IL-6 production.
- Chaulet, Charlotte,Croix, Cécile,Alagille, David,Normand, Sylvain,Delwail, Adriana,Favot, Laure,Lecron, Jean-Claude,Viaud-Massuard, Marie-Claude
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p. 1019 - 1022
(2011/03/21)
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- 2,3-Diamino acid modifying 3S-tetrahydroisoquinoline-3-carboxylic acids: Leading to a class of novel agents with highly unfolded conformation, selective in vitro anti-platelet aggregation and potent in vivo anti-thrombotic activity
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In the preparation of anti-thrombotic agents the 2- and 3-positions of 3S-tetra-hydroisoquinoline-3-carboxylic acid (THIQA) were simultaneously modified with amino acids to form 20 novel N-(3S-N-aminoacyl-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)amino acids (8a-t). On an in vitro platelet aggregation model 8a-t selectively inhibit ADP-induced platelet aggregation and their IC50 values are leas than 3.5 nM. On an extracorporeal circulation of arterioveinos cannula model of rats both orally and intraveously effective doses of 8a-t are less than 30 nmol/kg. Cerius2 based stereoview of explores 8a-t having highly unfolded conformation. 3D QSAR analysis gives the importance of the unfolded conformation to high in vitro anti-platelet aggregation and in vivo anti-thrombotic potency rational understanding.
- Zhang, Xiaoyi,Wang, Wei,Cheng, Shenling,Zhao, Ming,Zheng, Meiqing,Chang, Heng Wei,Wu, Jianhui,Peng, Shiqi
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experimental part
p. 1536 - 1554
(2010/05/02)
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- (3S)-N-(l-Aminoacyl)-1,2,3,4-tetrahydroisoquinolines, a class of novel antithrombotic agents: Synthesis, bioassay, 3D QSAR, and ADME analysis
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To increase antithrombotic activity, 3S-tetrahydroisoquinoline-3-carboxylic acid (1) was modified with natural amino acids to form 19 novel dipeptide analogs, 3S-tetrahydroisoquinoline-3-carboxyamino acids (5a-s), targeting the intestinal peptide transport system. In vitro assay of 5a-s indicated that their potencies for inhibiting adenosine diphosphate (ADP), arachidonic acid (AA), platelet-activating factor (PAF), and thrombin (TH)-induced platelet aggregations were higher than that of 1. Additionally, in vivo assay of 5a-s indicated that their potencies for inhibiting thrombogenesis in rats were also higher than that of 1. Among the candidates, 5h with Ser attachment showed the most impressive features for further development. According to molecular field analysis based Cerius2 QSAR module, two equations (r, 0.961 and 0.988) correlating the structures with both in vitro and in vivo activities of 5a-s were established. ADMET calculations predict higher intestinal absorption for compounds 5a-s. Further investigation with 5h as a lead compound is underway.
- Zheng, Meiqing,Zhang, Xiaoyi,Zhao, Ming,Chang, Heng Wei,Wang, Wei,Wang, Yuji,Peng, Shiqi
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experimental part
p. 9574 - 9587
(2009/04/06)
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- Derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
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-The following derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid have been prepared in their (S)-form and as racemates: hydrochloride of methyl ester, N-carboxy anhydride, and N-acetyl derivative. All the substances were fully characterised
- Jansa, Petr,Machacek, Vladimir,Bertolasi, Valerio
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- Synthesis and pharmacological evaluation of Tic-hydantoin derivatives as selective σ1 ligands. Part 2
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Herein is described a new class of selective σ1 ligands consisting of tetrahydroisoquinoline-hydantoin (Tic-hydantoin) derivatives. Compound 1a has high affinity (IC50 = 16 nM) for σ1 receptor and is selective in a large panel of therapeutic targets. This study presents structural changes on the side chain of the Tic-hydantoin core. Analogs of higher affinity could be identified (IC50 ≈ 2-3 nM).
- Gassiot, Amaury Cazenave,Charton, Julie,Girault-Mizzi, Sophie,Gilleron, Pauline,Debreu-Fontaine, Marie-Ange,Sergheraert, Christian,Melnyk, Patricia
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p. 4828 - 4832
(2007/10/03)
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- Synthesis and pharmacological evaluation of Tic-hydantoin derivatives as selective σ1 ligands. Part 1
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Herein is described a new class of selective σ1 ligands consisting of tetrahydroisoquinoline-hydantoin (Tic-hydantoin) derivatives. Compound 3a has high affinity (IC50 = 16 nM) for the σ1 receptor and is selective in a large panel of therapeutic targets. This first study presents structural changes around the Tic-hydantoin core, leading to a Tic-hydantoin analogue with a higher σ1 affinity (IC50 ≈ 1 nM).
- Charton, Julie,Gassiot, Amaury Cazenave,Girault-Mizzi, Sophie,Debreu-Fontaine, Marie-Ange,Melnyk, Patricia,Sergheraert, Christian
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p. 4833 - 4837
(2007/10/03)
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- Synthesis of a novel tetrahydroisoquinolino[2,1-c][1,4]benzodiazepine ring system with DNA recognition potential
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The first stereospecific synthesis of a novel tetrahydroisoquinolino[2,1-c] [1,4]benzodiazepine ring system with DNA recognition potential starting from (S)-1,2,3,4-tetrahydroisoquinoline carboxylic acid has been reported. We report the first stereospecif
- Kothakonda, Kiran Kumar,Bose, D. Subhas
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p. 4371 - 4373
(2007/10/03)
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- Optimized synthesis of tetrahydroisoquinoline-hydantoins
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Several methods have been developed and compared for the solution synthesis of tetrahydroisoquinoline-hydantoin derivatives. The best yields were obtained when the imidazolidine-2,4-dione ring was synthesized in two steps: (1) reaction of Tic-OH with the appropriate amine and (2) cyclization with 1,1′-carbonyldiimidazole.
- Charton, Julie,Gassiot, Amaury Cazenave,Melnyk, Patricia,Girault-Mizzi, Sophie,Sergheraert, Christian
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p. 7081 - 7085
(2007/10/03)
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- 2-Substituted-1,2,3,4-tetrahydroisoquinolines and chiral 3-carboxyl analogues from N-benzotriazolylmethyl-N-phenethylamines
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N-Benzotriazolylmethyl-N-phenethylamines 5a-5c and 11a-11c cyclize in the presence of aluminum chloride to produce 1,2,3,4-tetrahydroisoquinolines 6a-6c and 12a-12c (70-89%) via electrophilic attack of a transient iminium cation X on the tethered phenyl r
- Katritzky, Alan R,He, Hai-Ying,Jiang, Rong,Long, Qiuhe
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p. 2427 - 2434
(2007/10/03)
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- Convenient synthesis of tetrahydroisoquinoline-hydantoins
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NaOH/MeOH or DIEA/CH2Cl2 were convenient conditions for the synthesis in solution phase of hydantoins derived from Tic-OH and isocyanates.
- Charton, Julie,Delarue, Sandrine,Vendeville, Sandrine,Debreu-Fontaine, Marie-Ange,Girault-Mizzi, Sophie,Sergheraert, Christian
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p. 7559 - 7561
(2007/10/03)
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- Synthesis, molecular modeling, 2-D NMR, and biological evaluation of ILV mimics as potential modulators of protein kinase C
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To study the structural determinants required for protein kinase C (PKC) activation by indolactam V (ILV) for purposes of arriving at simpler versions of this PKC activator, four simplified analogues of ILV (4a-c and 14a) were synthesized. These analogues contain a benzene ring in place of the indole group of ILV and were designed for synthesis because molecular modeling studies revealed these simplified structures to possess readily accessible [ILV]-sofa-like conformations, thus mimicking the literature-reported bioactive conformation of ILV. During the course of designing these analogues, a more rigorous conformational search program (SysSearch) was developed to analyze the highly functionalized nine-membered lactam ring system present in ILV. The results of the molecular modeling studies using the SysSearch program on which the design of these analogues was based were confirmed by 2-D NMR and X-ray studies. The compounds of this series were constructed by use of the Mitsunobu reaction to generate the unique nine-membered lactam ring present in these structures. Two routes to compound 4a are presented, one of which utilizes the amino acid building blocks, L-valine and L-phenylalanine, to fix the stereochemistry of its two asymmetric centers. The biological studies reveal that these new analogues fail to modulate PKC activity, and thus they exclude the possibility that a benzene ring can serve as a surrogate of the indole ring of ILV. The present work therefore indicates that the nine-membered lactam ring moiety of ILV in an [ILV]sofa conformation is not a sufficient structural determinant for PKC activation.
- Kozikowski, Alan P.,Ma, Dawei,Pang, Yuan-Ping,Shum, Patrick,Likic, Vladimir,Mishra, Prasanna K.,Macura, Slobodan,Basu, Alakananda,Lazo, John S.,Ball, Richard G.
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p. 3957 - 3965
(2007/10/02)
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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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