- HETEROARYL COMPOUNDS AS KINASE INHIBITOR
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Provided herein are heteroaryl compounds of formula (I) having activity on a receptor protein tyrosine kinase, wherein R 1, R 2, R 3, A, Q, Z, X and W are set forth in the description, as well as solvates, hydrates, tautomers or pharmaceutically acceptable salts thereof.
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Page/Page column 78-79
(2019/10/04)
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- 3-methyl pyridino-[1,2-a] pyrimidone derivative containing 1-((4-benzyl-substituted)oxygroup) and application
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The invention discloses a 3-methyl pyridino-[1,2-a] pyrimidone derivative containing 1-((4-benzyl-substituted)oxygroup) and application. The general formula of the derivative is shown in the description, wherein R1 is a methoxyl group or an oxyethyl group or halogen; R2 is hydroxyl or isobutyl or ethyl or propyl or chloroethyl or 2-methoxyl group benzyl or 2-methoxyl group benzy or 2-fluorine benzyl or 2-cyanogroup benzyl chloride or 4-cyanogroup benzyl2-methyl benzyl chloride or 3-methyl benzyl chloride or 4-methyl benzyl chloride. According to the derivative, the rice bacterial leaf blight and citrus canker can be prevented and treated. The general formula is shown in the description.
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Paragraph 0094; 0096
(2019/04/30)
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- First Discovery of Novel Pyrido[1,2- a]pyrimidinone Mesoionic Compounds as Antibacterial Agents
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Plant bacterial diseases cause tremendous decreases in crop yield and quality, and there is a lack of highly effective and low-risk antibacterial agents. A series of novel pyrido[1,2-a]pyrimidinone mesoionic compounds containing vanillin moieties were synthesized, and the application of these mesoionic compounds as plant antibacterial agents was reported here for the first time. The bioassay results revealed that the mesoionic compounds had good antibacterial activity. Of these compounds, compound 11 showed excellent in vitro activity against Xanthomonas oryzae pv. oryzae, with an EC50 value of 1.1 μg/mL, which was substantially better than that of bismerthiazol (92.7 μg/mL) and thiodiazole copper (105.4 μg/mL). Moreover, greenhouse condition trials indicated that the protective and curative activities of compound 11 against rice bacterial leaf blight were 75.12 and 72.04%, respectively, which were better than those of bismerthiazol (62.24 and 50.83%, respectively) and thiodiazole copper (53.35 and 65.04%, respectively). These results provide a basis for the application of mesoionic vanillin moieties as new antibacterial agents.
- Liu, Dengyue,Zhang, Jian,Zhao, Lei,He, Wengjing,Liu, Zhengjun,Gan, Xiuhai,Song, Baoan
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- TRICYCLIC HETEROCYCLIC DERIVATIVES AND USES THEREOF
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Disclosed are tricyclic heterocyclic compounds having kinase inhibitory activity, pharmaceutical compositions and kits comprising the compounds, and use of the compounds in the treatment of or in medicaments for the treatment of various diseases and conditions. In particular, disclosed are tricyclic heterocyclic compounds of the formula (I) having CSF-1R (c-FMS kinase) inhibitory activity and their use in the treatment of various diseases and conditions, such as those mediated by CSF-1R, including proliferative or neoplastic diseases and conditions, including cancers, and bone, inflammatory, and autoimmune diseases and conditions.
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Paragraph 89; 90
(2018/05/24)
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- Facile and selective deprotection of PMB ethers and esters using oxalyl chloride
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Oxalyl chloride, (0.5 equiv) was found to cleave the PMB group from alkyl, aryl PMB ethers, and esters to give corresponding alcohol and acid in good yields. This method offers simple and efficient protocol for the selective deprotection of PMB ether and ester in DCE at ambient temperature.
- Ilangovan, Andivelu,Anandhan, Karnambaram,Kaushik, Mahabir Prasad
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supporting information
p. 1081 - 1084
(2015/02/19)
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- Vanillin-derived antiproliferative compounds influence Plk1 activity
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We synthesized a series of vanillin-derived compounds and analyzed them in HeLa cells for their effects on the proliferation of cancer cells. The molecules are derivatives of the lead compound SBE13, a potent inhibitor of the inactive conformation of huma
- Carrasco-Gomez, Roberto,Keppner-Witter, Sarah,Hieke, Martina,Lange, Lisa,Schneider, Gisbert,Schubert-Zsilavecz, Manfred,Proschak, Ewgenij,Sp?nkuch, Birgit
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supporting information
p. 5063 - 5069
(2014/12/11)
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- A convenient approach for the deprotection and scavenging of the PMB group using POCl3
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A convenient and high yielding approach for the deprotection and scavenging of the p-methoxybenzyl (PMB) group in PMB ethers and PMB esters was developed using POCl3 as the reagent. 4-Methoxybenzyl chloride, a starting material used for the preparation of PMB ethers and esters was regenerated in the deprotection step. This mild and selective procedure tolerates several acid sensitive functional groups. The Royal Society of Chemistry 2013.
- Ilangovan, Andivelu,Saravanakumar, Shanmugasundar,Malayappasamy, Subramani,Manickam, Govindaswamy
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p. 14814 - 14828
(2013/09/02)
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- PROPHYLACTIC OR THERAPEUTIC AGENT FOR CANCER
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A compound represented by the formula (I): wherein each symbol is as described in the specification, or a salt thereof has a superior activity as an estrogen-related receptor-α modulator, and is useful as a prophylactic or therapeutic agent for cancer.
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Page/Page column 70
(2012/05/20)
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- Small molecules that protect against β-amyloid-induced cytotoxicity by inhibiting aggregation of β-amyloid
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Aggregated β-amyloid (Aβ) plays crucial roles in Alzheimer's disease (AD) pathogenesis, therefore blockade of Aβ aggregation is considered as a potential therapeutic target. We designed and synthesized small molecules to reduce Aβ-induced cytotoxicity by inhibiting Aβ aggregation. The small molecules were screened via ThT, MTT, and cell-based cytotoxicity assay (Aβ burden assay). Selected compounds 1c, 1d, 1e, and 1f were then investigated by evaluating their effects on cognitive impairment of acute AD mice model. Learning and memory dysfunction by injection of Aβ(1-42) was recovered by administration of these molecules. Especially, 1d showed the best recovery activity in Y-maze task, object recognition task, and passive avoidance task with dose dependent manner. These results suggest that 1d has high potential as a therapeutic agent for AD.
- Lee, Yun Suk,Kim, Hye Yun,Kim, Youngsoo,Seo, Jae Hong,Roh, Eun Joo,Han, Hogyu,Shin, Kye Jung
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experimental part
p. 4921 - 4935
(2012/10/08)
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- Identification, synthesis, and biological evaluation of metabolites of the experimental cancer treatment drugs indotecan (LMP400) and indimitecan (LMP776) and investigation of isomerically hydroxylated indenoisoquinoline analogues as topoisomerase i poisons
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Hydroxylated analogues of the anticancer topoisomerase I (Top1) inhibitors indotecan (LMP400) and indimitecan (LMP776) have been prepared because (1) a variety of potent Top1 poisons are known that contain strategically placed hydroxyl groups, which provides a clear rationale for incorporating them in the present case, and (2) the hydroxylated compounds could conceivably serve as synthetic standards for the identification of metabolites. Indeed, incubating LMP400 and LMP776 with human liver microsomes resulted in two major metabolites of each drug, which had HPLC retention times and mass fragmentation patterns identical to those of the synthetic standards. The hydroxylated indotecan and indimitecan metabolites and analogues were tested as Top1 poisons and for antiproliferative activity in a variety of human cancer cell cultures and in general were found to be very potent. Differences in activity resulting from the placement of the hydroxyl group are explained by molecular modeling analyses.
- Cinelli, Maris A.,Reddy, P. V. Narasimha,Lv, Peng-Cheng,Liang, Jian-Hua,Chen, Lian,Agama, Keli,Pommier, Yves,Van Breemen, Richard B.,Cushman, Mark
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p. 10844 - 10862
(2013/02/25)
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- Novel diarylheptanoids as inhibitors of TNF-α production
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Synthesis and anti-inflammatory activity of novel diarylheptanoids [5-hydroxy-1-phenyl-7-(pyridin-3-yl)-heptan-3-ones and 1-phenyl-7-(pyridin-3-yl) hept-4-en-3-ones] as inhibitors of tumor necrosis factor-α (TNF-α) production is described in the present article. The key reactions involve the formation of a β-hydroxyketone by the reaction of substituted 4-phenyl butan-2-ones with pyridine-3-carboxaldehyde in presence of LDA and the subsequent dehydration of the same to obtain the α,β-unsaturated ketones. Compounds 4i, 5b, 5d, and 5g significantly inhibit lipopolysaccharide (LPS)-induced TNF-α production from human peripheral blood mononuclear cells in a dose-dependent manner. Of note, the in vitro TNF-α inhibition potential of 5b and 5d is comparable to that of curcumin (a naturally occurring diarylheptanoid). Most importantly, oral administration of 4i, 5b, 5d, and 5g (each at 100 mg/kg) but not curcumin (at 100 mg/kg) significantly inhibits LPS-induced TNF-α production in BALB/c mice. Collectively, our findings indicate that these compounds may have potential therapeutic implications for TNF-α-mediated auto-immune/inflammatory disorders.
- Dhuru, Sameer,Bhedi, Dilip,Gophane, Dnyaneshwar,Hirbhagat, Kiran,Nadar, Vijaya,More, Dattatray,Parikh, Sapna,Dalal, Roda,Fonseca, Lyle C.,Kharas, Firuza,Vadnal, Prashant Y.,Vishwakarma, Ram A.,Sivaramakrishnan
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supporting information; experimental part
p. 3784 - 3787
(2011/07/31)
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- NOVEL 3-PHENYL ACRYLIC ACID COMPOUND ACTIVATORS OF TYPE PPAR RECEPTORS AND PHARMACEUTICAL/COSMETIC COMPOSITIONS COMPRISED THEREOF
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Novel 3-phenyl acrylic acid compounds have the following general formula (I): and are formulated into pharmaceutical compositions for administration in human or veterinary medicine (in dermatology, as well as in the field of cardiovascular diseases, immune diseases and/or diseases associated with lipid metabolism), or into cosmetic compositions.
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Page/Page column 8
(2010/06/19)
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- Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode
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The work described herein demonstrates the utility of structure-based drug design (SBDD) in shifting the binding mode of an HTS hit from a DFG-in to a DFG-out binding mode resulting in a class of novel potent CSF-1R kinase inhibitors suitable for lead development.
- Meyers, Marvin J.,Pelc, Matthew,Kamtekar, Satwik,Day, Jacqueline,Poda, Gennadiy I.,Hall, Molly K.,Michener, Marshall L.,Reitz, Beverly A.,Mathis, Karl J.,Pierce, Betsy S.,Parikh, Mihir D.,Mischke, Deborah A.,Long, Scott A.,Parlow, John J.,Anderson, David R.,Thorarensen, Atli
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scheme or table
p. 1543 - 1547
(2010/06/21)
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- Efficient preparation and processing of the 4-methoxybenzyl (PMB) group for phenolic protection using ultrasound
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(Chemical Equation Presented) Power ultrasound efficiently facilitates the rapid preparation and reaction of 4-methoxybenzyl chloride (PMB-Cl) 1 in providing protected phenolic ether intermediates for organic synthesis. Using two-phase systems in both the ultrasound-promoted preparation and reactions of PMB-Cl, typical runs produce PMB-protected products within 15 min. When compared with nonsonicated control reactions, the results demonstrate clear advantage in terms of efficiency when the protocol is applied to the mild and selective protection of various multisubstituted phenols including sensitive phenolic aldehydes.
- Luzzio, Frederick A.,Chen, Juan
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p. 5621 - 5624
(2008/12/21)
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- Solid-supported acids as mild and versatile reagents for the deprotection of aromatic ethers
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Equation Presented p-Toluene sulfonic acid (p-TsOH) immobilized either on polystyrene (PS) or silica (Si) was found to be effective in cleaving aromatic ethers containing isopropyl, tert-butyl, allyl, and benzyl groups, as well as mono-, di-, and trimethoxylated benzyl groups, in moderate to excellent yields (54-95%). These protecting groups could be selectively deprotected when they were simultaneously present on the same or different aromatic rings in a substrate.
- Ploypradith, Poonsakdi,Cheryklin, Pannarin,Niyomtham, Nattisa,Bertoni, Daniel R.,Ruchirawat, Somsak
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p. 2637 - 2640
(2008/02/08)
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- Crystal structure of liganded cFMS kinase domain
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A crystal structure of the cfms kinase domain, co-crystal structure with a bound small molecule, as well as methods of using the same in the discovery of cfms inhibitors and in the treatment of diseases mediated by inappropriate cfms activity.
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Page/Page column 19; 21
(2008/06/13)
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- Solid-supported acids for debenzylation of aryl benzyl ethers
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Solid-supported acids have been investigated for aromatic debenzylation reactions. Stoichiometric amounts of solid-supported acids in refluxing toluene with or without 4 equiv of methanol effectively provided the desired aromatic debenzylation products of various systems in moderate to excellent yields (up to 98%).
- Petchmanee, Thaninee,Ploypradith, Poonsakdi,Ruchirawat, Somsak
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p. 2892 - 2895
(2007/10/03)
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- Regioselective protection of the 4-hydroxyl of 3,4-dihydroxy-benzaldehyde
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The regioselective protection of the 4-hydroxyl group of 3,4-dihydroxy-benzaldehyde was accomplished with seven different protecting groups (benzyl, p-methoxybenzyl, o-nitrobenzyl, 2,6-dichlorobenzyl, 3,4-dichlorobenzyl, vinyl and propargyl) in yields ranging between 67-75percent.
- Plourde, Guy L.,Spaetzel, Randy R.
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p. 697 - 705
(2007/10/03)
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