- Novel 3,4-dihydroquinolin-2(1H)-one derivatives as dual inhibitor targeting AKR1B1/ROS for treatment of diabetic complications: Design, synthesis and biological evaluation
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AKR1B1 (Aldose reductase) has been used as therapeutic intervention target for treatment of diabetic complications over 50 years, and more recently for inflammation and cancer. However, most developed small molecule inhibitors have the defect of low bioac
- Han, Zhongfei,Qi, Gang,Zhu, Junkai,Zhang, Yundong,Xu, Yin,Yan, Kang,Zhu, Changjin,Hao, Xin
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- Synthesis and Exploration of Abscisic Acid Receptor Agonists Against Dought Stress by Adding Constraint to a Tetrahydroquinoline-Based Lead Structure
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New oxotetrahydroquinolinyl- and oxindolinyl sulfonamides interacting with RCAR/(PYR/PYL) receptor proteins were identified as lead structures against drought stress in crops starting from protein docking studies of a sulfonamide lead structure, followed by in-depth SAR studies. Optimized five to six step synthetic approaches via substituted amino oxo-tetrahydro-quinolines and amino oxo-indolines as essential intermediates gave access to the envisaged oxo-tetrahydroquinolinyl and oxindolinyl sulfonamides. Whilst oxo-tetrahydroquinolinyl sulfonamides with additional carbon substituents or spiro-cycloalkyl groups exhibited only low to moderate target affinities, the corresponding spiro-oxindolinyl and oxo-tetrahydroquinolinyl sulfonamides carrying optimized N-substituents revealed strong interactions with RCAR/(PYR/PYL) receptor proteins in Arabidopsis thaliana. Remarkably, the in vitro activity observed for these new compounds was on the same level as observed for the naturally occurring plant hormone in line with strong efficacy against drought stress in-vivo (canola and wheat as broad-acre crops).
- Baltz, Rachel,Bojack, Guido,Dittgen, Jan,Fischer, Christian,Frackenpohl, Jens,Freigang, J?rg,Getachew, Rahel,Grill, Erwin,Helmke, Hendrik,Hohmann, Sabine,Lange, Gudrun,Lehr, Stefan,Porée, Fabien,Schmidt, Jana,Schmutzler, Dirk,Yang, Zhenyu
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supporting information
p. 3442 - 3457
(2021/06/25)
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- Tetrahydroquinolinyl phosphinamidates and phosphonamidates enhancing tolerance towards drought stress in crops via interaction with ABA receptor proteins
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New phosphorous-containing lead structures against drought stress in crops interacting with RCAR/(PYR/PYL) receptor proteins were identified starting from in-depth SAR studies of related sulfonamide lead structures and protein docking studies. A converging 6-step synthesis via phosphinic chlorides and phosphono chloridates as key intermediates afforded envisaged tetrahydroquinolinyl phosphinamidates and phosphonamidates. Whilst tetrahydroquinolinyl phosphonamidates 13a,b exhibited low to moderate target affinities, the corresponding tetrahydroquinolinyl phosphinamidates 12a,b revealed confirmed strong affinities for RCAR/ (PYR/PYL) receptor proteins in Arabidopsis thaliana on the same level as essential plant hormone abscisic acid (ABA) combined with promising efficacy against drought stress in vivo (broad-acre crops wheat and canola).
- Decker, Luka J. B.,Dittgen, Jan,Frackenpohl, Jens,Freigang, J?rg,Génix, Pierre,Helmke, Hendrik,Lange, Gudrun,Luemmen, Peter,Schmidt, Jana,Schmutzler, Dirk,Vors, Jean-Pierre
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- Preparation method of 6-hydroxy-3,4-dihydro-2(1H)quinolinone
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The invention belongs to the field of preparation of intermediates in chemical engineering, and particularly relates to a preparation method of 6-hydroxy-3,4-dihydro-2(1H)quinolinone. The preparationmethod comprises the following steps of using aniline and 3-chloropropionyl chloride as raw materials; performing cyclization, nitrification, reduction and diazotization hydrolysis, so as to synthesize the target product, namely 6-hydroxy-3,4-dihydro-2(1H)quinolinone. The preparation method has the advantages that the reaction conditions are mild, the cost is reduced, and the yield rate is increased.
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Paragraph 0009; 0010
(2019/06/08)
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- SUBSTITUTED OXOTETRAHYDROQUINOLINYLPHOSPHINIC ACID AND PHOSPHINIC ACID AMIDES OR SALTS THEREOF AND USE THEREOF TO INCREASE STRESS TOLERANCE IN PLANTS
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The invention relates to substituted oxotetrahydroquinolinylphosphin- and -phosphonamides of the general formula (I) and salts thereof where the radicals of the formula (I) are each as defined in the description for enhancing stress tolerance in plants to abiotic stress, and for enhancing plant growth and/or for increasing plant yield.
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Paragraph 0153-0154
(2018/08/03)
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- USE OF SUBSTITUTE OXO TETRAHYDROQUINOLINE SULFONAMIDES OR SALTS THEREOF FOR RAISING STRESS TOLERANCE OF PLANTS
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The invention relates to the use of substituted oxotetrahydroquinolinylsulfonamides or salts thereof where the radicals in the general formula (I) correspond to the definitions given in the description, for enhancing stress tolerance in plants to abiotic stress, and/or for increasing plant yield.
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Paragraph 0187; 0173; 0174; 0181; 0183; 0189
(2017/02/28)
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- COMPOUNDS FOR REGULATING FAK AND/OR SRC PATHWAYS
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The present application provides novel optionally substituted fused pyridine and pyrimidine bicyclic compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating FAK and/or Src activity by administering a therapeutically effective amount of one or more of the compounds to a subject. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the FAK and/or Src pathway. Advantageously, these compounds perform as dual FAK and/or Src inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.
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Page/Page column 90
(2015/03/28)
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- A COMPOUND AND PHARMACEUTICAL COMPOUND FOR TREATMENT OF INFLAMMATORY DISEASES
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The present invention relates to a pharmaceutical composition for treating inflammatory diseases, comprising: a compound represented by chemical formula I, a pharmaceutically acceptable salt thereof; a hydrate thereof; or a compound as a solvate thereof,
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Paragraph 0190-0192
(2016/10/07)
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- Aminoluciferins extend firefly luciferase bioluminescence into the near-infrared and can be preferred substrates over d-luciferin
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Firefly luciferase adenylates and oxidizes D-luciferin to chemically generate visible light and is widely used for biological assays and imaging. Here we show that both luciferase and luciferin can be reengineered to extend the scope of this light-emitting reaction. D-Luciferin can be replaced by synthetic luciferin analogues that increase near-infrared photon flux >10-fold over that of D-luciferin in live luciferase-expressing cells. Firefly luciferase can be mutated to accept and utilize rigid aminoluciferins with high activity in both live and lysed cells yet exhibit 10 000-fold selectivity over the natural luciferase substrate. These new luciferin analogues thus pave the way to an extended family of bioluminescent reporters.
- Mofford, David M.,Reddy, Gadarla Randheer,Miller, Stephen C.
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supporting information
p. 13277 - 13282
(2015/03/30)
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- Design, synthesis and evaluation of the antidepressant and anticonvulsant activities of triazole-containing quinolinones
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A series of 1-substituted-6-(4H-1,2,4-triazol-4-yl)-3,4-dihydroquinolin- 2(1H)-ones were designed, synthesized, and screened for their antidepressant and anticonvulsant activities. Interestingly, compounds 5i, 5j, 5m, and 5n led to significant reductions in the immobility time in the forced swimming test at a dose of 50 mg/kg, and exhibited higher levels of efficacy than the reference standard fluoxetine. In addition, compound 5i exhibited greater efficacy than fluoxetine in the tail suspension test. The results of an open field test further confirmed that compound 5i provided a good antidepressant effect. In the maximal electroshock seizure screen, compounds 5c and 5d showed moderate levels of anticonvulsant activity and protected 100% of the animals at a dose of 100 mg/kg. None of the synthesized compounds showed any neurotoxicity in the rotarod test at a dose of 100 mg/kg.
- Deng, Xian-Qing,Song, Ming-Xia,Zheng, Yan,Quan, Zhe-Shan
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p. 217 - 224
(2014/01/23)
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- ROR MODULATORS AND THEIR USES
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The invention relates to ROR modulators; compositions comprising an effective amount of a ROR modulator; and methods for treating or preventing diseases associated with ROR. The invention is based in part on the discovery of ROR modulators which interact with RORa and/or RORy and thereby inhibit or induce RORa and/or RORy-activity, and RORa- and/or RORy-regulated target gene and protein expression.
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Paragraph 0082
(2013/11/05)
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- Synthesis and positive inotropic activity of N-(4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(piperazin-1-yl)ac etamide derivatives
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A series of N-(4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(piperazin-1-yl)ac etamide derivatives were synthesized and their positive inotropic activity was evaluated by measuring left atrium stroke volume on isolated rabbit heart preparations. Several compounds showed favorable activity compared with the standard drug, milrinone, among which N-(1-benzyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(4-benzyl piperazin-1-yl)acetamide 6j was found to be the most potent with the 13.2% increased stroke volume (milrinone 4.7%) at concentration of 3 × 10-5 M in our in vitro study. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.
- Zhang, Chun-Bo,Cui, Xun,Hong, Lan,Quan, Zhe-Shan,Piao, Hu-Ri
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scheme or table
p. 4606 - 4609
(2009/04/06)
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- QUINOLONE AND TETRAHYDROQUINOLONE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY
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The present invention features quinolones, tetrahydroquinolines, and related compounds that inhibit nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions.
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Page/Page column 35
(2008/12/08)
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- Synthesis and positive inotropic evaluation of 2-(4-(4-substituted benzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl-n-(4,5-dihydro-1-methyl[1,2,4] triazolo[4,3-a]quinolin-7-yl)-acetamides
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In an attempt to search for more potent positive inotropic agents, a series of 2-(4-(4-substituted benzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5- dihydro-1-methyl[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides was synthesized and their positive inotropic activities were evaluated by measuring left atrium stroke volume on isolated rabbit-heart preparations. Several compounds showed favorable activity compared with the standard drug Milrinone among which 2-(4-(4-(2-chlorobenzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4, 5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide 6e was found to have the most desirable potency with the 6.79 ± 0.18% increased stroke volume (Milrinone: 1.67 ± 0.64%) at a concentration of 1 × 10 -5 M in our in-vitro study. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.
- Li, Jing-Yuan,Cui, Xun,Liu, Xue-Kun,Hong, Lan,Quan, Zhe-Shan,Piao, Hu-Ri
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scheme or table
p. 794 - 799
(2009/04/07)
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- Multicyclic sulfonamide compounds as inhibitors of histone deacetylase for the treatment of disease
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Disclosed herein are sulfonamide compounds of Formula VII as described herein. Methods and compositions are disclosed for treating disease states including, but not limited to cancers, autoimmune diseases, tissue damage, central nervous system disorders, neurodegenerative disorders, fibrosis, bone disorders, polyglutamine-repeat disorders, anemias, thalassemias, inflammatory conditions, cardiovascular conditions, and disorders in which angiogenesis play a role in pathogenesis, using the compounds of the invention. In addition, methods of modulating the activity of histone deacetylase (HDAC) are also disclosed.
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Page/Page column 18; 25
(2010/11/25)
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- ENZYME MODULATORS AND TREATMENTS
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Novel compounds and methods of using those compounds for the treatment of inflammatory conditions, hyperproliferative diseases, cancer, and diseases characterized by hypervascularization are provided. In a preferred embodiment, modulation of the activation state of p38 kinase protein ab1 kinase protein, bcr-ab1 kinase protein, braf kinase protein, VEGFR kinase protein, or PDGFR kinase protein comprises the step of contacting said kinase protein with the novel compounds.
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Page/Page column 416
(2008/06/13)
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- N-aryl-2-oxazolidinone-5-carboxamides and their derivatives
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The present invention provides antibacterial agents having the formulae I, II, and III described herein.
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- N-ARYL-2-OXAZOLIDINONE-5-CARBOXAMIDES AND THEIR DERIVATIVES AND THEIR USE AS ANTIBACTERIALS
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Compounds of formula B-C-A-CO-NH-R1, wherein A is structure i, ii or iii: formulae (I), (II), (III). C is optionally substituted aryl or heteroaryl, and B is a specified cyclic moiety, or C and B together are a heterobicyclic moiety, are useful as antibacterial agents.
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Page/Page column 150
(2010/02/07)
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- Vanilloid receptor ligands and their use in treatments
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Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritis, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.
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- A new efficient synthesis of 6-nitroquipazine
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A convenient and regioselective synthesis of 6-nitroquipazine from hydrocarbostyril in three steps is described. This synthetic route involved a nitration, a chlorination followed by aromatization, and an aromatic substitution reaction.
- Lee, Byoung Se,Lee, Byung Chul,Jun, Jong-Gab,Chi, Dae Yoon
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p. 2637 - 2641
(2007/10/03)
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