- A substituted benzamide isoxazoline derivative or a salt thereof as a pesticidally acceptable salt. Composition and use thereof
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The invention belongs to the field of pesticides, and particularly relates to a substituted benzamide isoxazoline derivative or a salt, composition and application thereof as a pesticide acceptable salt, and the compound has the structure of the formula (
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Paragraph 0109-0112
(2021/10/30)
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- Synthesis and Evaluation of PPARδAgonists That Promote Osteogenesis in a Human Mesenchymal Stem Cell Culture and in a Mouse Model of Human Osteoporosis
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We synthesized a directed library of compounds to explore the structure-activity relationships of peroxisome proliferator-activated receptor δ(PPARδ) activation relative to mesenchymal stem cell (MSC) osteogenesis. Our scaffold used para-substituted cinnamic acids as a polar headgroup, a heteroatom and heterocycle core connecting units, and substituted phenyl groups for the lipophilic tail. Compounds were screened for their ability to increase osteogenesis in MSCs, and the most promising were examined for subunit specificity using a quantitative PPAR transactivation assay. Six compounds were selected for in vivo studies in an ovariectomized mouse model of human postmenopausal osteoporosis. Four compounds improved bone density in vivo, with two (12d and 31a) having activity comparable to that of GW0742, a well-studied PPARδ-selective agonist. 31a (2-methyl-4-[N-methyl-N-[5-methylene-4-methyl-2-[4-(trifluoromethyl)phenyl]thiazole]]aminocinnamic acid) had the highest selectivity for PPARδcompared to other subtypes, its selectivity far exceeding that of GW0742. Our results confirm that PPARδis a new drug target for possible treatment of osteoporosis via in situ manipulation of MSCs.
- Kress, Brian J.,Kim, Dong Hyun,Mayo, Jared R.,Farris, Jeffery T.,Heck, Benjamin,Sarver, Jeffrey G.,Andy, Divya,Trendel, Jill A.,Heck, Bruce E.,Erhardt, Paul W.
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p. 6996 - 7032
(2021/05/29)
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- Fluorine thramine intermediate and method for preparing flumbine by using same
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The invention discloses a fluororesonide intermediate and a method for preparing the same, and a fluororesonide intermediate -5. Routes include the use of m-xylene as starting materials, halogenation. Oxidation reaction The intermediate -5 is further obtained by hydroximation, cyanolation, hydrolysis reaction or cyanation, oximation, and hydrolysis reaction. As some examples of the present invention, synthetic routes were increased 2 steps from 5 steps in the prior art, but surprisingly high overall yields were obtained and the purity of intermediate -5 was significantly increased. , The starting material of the intermediate -5 is prepared from high 4 - bromo -2 - methylbenzoic acid to low-priced m-xylene, so that the cost of the intermediate -5 is greatly reduced. , The reaction condition is mild, the synthesis difficulty is low, and the environment is more environmentally friendly.
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Paragraph 0111-0114; 0122-0125
(2021/12/07)
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- SELECTIVE FLUORESCENT PROBE FOR ALDEHYDE DEHYDROGENASE
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High aldehyde dehydrogenase 1A1 (ALDH1A1) activity has emerged as a reliable marker for the identification of both normal and cancer stem cells. Herein, is presented AlDeSense, a turn-on green fluorescent probe for aldehyde dehydrogenase 1A1 (ALDH1A1) and Ctrl-AlDeSense, a matching non-responsive reagent. AlDeSense exhibits a 20-fold fluorescent enhancement when treated with ALDH1A1. Through the application of surface marker antibody staining, tumorsphere assays, and assessment of tumorigenicity, the disclosed results show that cells exhibiting high AlDeSense signal intensity have properties of cancer stem cells. Herein, is also reported the development of a red congener, red-AlDeSense. Importantly, red-AlDeSense represents one of only a few examples of a turn-on sensor in the red region using the d-PeT quenching mechanism.
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Paragraph 0237
(2020/07/14)
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- As opioid receptor antagonists or inverse agonists of the novel compounds
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Novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, pharmaceutical compositions containing them, to processes for their preparation.
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Paragraph 0602-0604
(2016/10/08)
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- A one-pot allylation-hydrostannation sequence with recycling of the intermediate tin waste
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A one-pot allylation and hydrostannation of alkynals where the tin byproduct formed in the first step of the reaction is recycled and used in the second step of the sequence is presented. Specifically, a BF3· OEt2-promoted allylstannation of the aldehyde moiety in the alkynal is followed by the introduction of polymethylhydrosiloxane (PMHS) and catalytic B(C6F5)3, which convert the tin byproduct of the allylation into Bu3SnH, which then hydrostannates the alkyne in the molecule. 119Sn and 11B NMR data suggest an organotin fluoride species is formed during the allylation step and involved in the tin recycling step.
- Ghosh, Banibrata,Amado-Sierra, Maria Del Rosario I.,Holmes, Daniel,Maleczka, Robert E.
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supporting information
p. 2318 - 2321
(2014/05/20)
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- BORON-CONTAINING SMALL MOLECULES
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This invention provides novel compounds, methods of using the compounds, and pharmaceutical formulations comprising the compounds.
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- Synthesis and evaluation of 1,2,4-methyltriazines as mGluR5 antagonists
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In previous studies we showed that 3-(substituted phenylethynyl)-5- methyl[1,2,4]triazine analogues of MPEP were potent antagonists of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro efficacy assay. In the present study we report
- Olson, Jeremy P.,Gichinga, Moses G.,Butala, Elizabeth,Navarro, Hernan A.,Gilmour, Brian P.,Carroll, F. Ivy
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p. 4276 - 4286
(2011/07/29)
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- INSCETICIDAL COMPOUNDS
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A compound of formula (I): wherein A1, A2, A3, A4, A1', A2', A3', A4', A5', A6', G1, R1, R2,R3,R
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Page/Page column 46
(2010/04/03)
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- NOVEL COMPOUNDS AS ANTAGONISTS OR INVERSE AGONISTS FOR OPIOID RECEPTORS
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This invention relates to novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy.
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Page/Page column 92
(2010/09/07)
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- Discovery of GSK1070916, a potent and selective inhibitor of aurora B/C kinase
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The Aurora kinases play critical roles in the regulation of mitosis and are frequently overexpressed or amplified in human tumors. Selective inhibitors may provide a new therapy for the treatment of tumors with Aurora kinase amplification. Herein we describe our lead optimization efforts within a 7-azaindole-based series culminating in the identification of GSK1070916 (17k). Key to the advancement of the series was the introduction of a 2-aryl group containing a basic amine onto the azaindole leading to significantly improved cellular activity. Compound 17k is a potent and selective ATP-competitive inhibitor of Aurora B and C with Ki* values of 0.38 ± 0.29 and 1.5 ± 0.4 nM, respectively, and is >250-fold selective over Aurora A. Biochemical characterization revealed that compound 17k has an extremely slow dissociation half-life from Aurora B (>480 min), distinguishing it from clinical compounds 1 and 2. In vitro treatment of A549 human lung cancer cells with compound 17k results in a potent antiproliferative effect (EC50 = 7 nM). Intraperitoneal administration of 17k in mice bearing human tumor xenografts leads to inhibition of histone H3 phosphorylation at serine 10 in human colon cancer (Colo205) and tumor regression in human leukemia (HL-60). Compound 17k is being progressed to human clinical trials.
- Adams, Nicholas D.,Adams, Jerry L.,Burgess, Joelle L.,Chaudhari, Amita M.,Copeland, Robert A.,Donatelli, Carla A.,Drewry, David H.,Fisher, Kelly E.,Hamajima, Toshihiro,Hardwicke, Mary Ann,Huffman, William F.,Koretke-Brown, Kristin K.,Lai, Zhihong V.,McDonald, Octerloney B.,Nakamura, Hiroko,Newlander, Ken A.,Oleykowski, Catherine A.,Parrish, Cynthia A.,Patrick, Denis R.,Plant, Ramona,Sarpong, Martha A.,Sasaki, Kosuke,Schmidt, Stanley J.,Silva, Domingos J.,Sutton, David,Tang, Jun,Thompson, Christine S.,Tummino, Peter J.,Wang, Jamin C.,Xiang, Hong,Yang, Jingsong,Dhanak, Dashyant
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experimental part
p. 3973 - 4001
(2010/08/07)
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- INSECTICIDAL COMPOUNDS
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A compound of formula (I) wherein A1, A2, A3, A4, R1, R2, R3 and R4 are as defined in claim 1; or a salt or N-oxide thereof. Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (I), to insecticidal,
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Page/Page column 24
(2009/05/28)
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- INSECTICIDAL COMPOUNDS
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A compound of formula (I), wherein A1, A2, A3, A4, G1, L, R1, R2, R3, R4, Y1, Y2 and Y3 are as defined in claim 1; or a sal
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Page/Page column 42
(2009/07/25)
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- Compounds
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Compounds of Formula (I), compositions containing them, their use in therapy, including their use as antibacterials, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.
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Page/Page column 42
(2009/08/14)
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- DIARYL, DIPYRIDINYL AND ARYL-PYRIDINYL DERIVATIVES AND USES THEREOF
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Compounds of Formula (I) that act as antagonists at the mu, kappa and/or delta opioid receptors and therefore useful in the treatment of diseases, conditions and/or disorders that benefit from such antagonism in animals are described herein. Formula (I) where R, R1, R2a, R2b, R3, R4, V, R6, R7, R8, R9, W and X are described herein.
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Page/Page column 26
(2008/12/05)
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- Synthesis and characterization of aryl thioacetyl styrene monomers: towards a new generation of SERS-active polymers
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A new family of thioacetyl styrene derivatives was synthesized in good isolated yields for the preparation of spectroscopically-encoded SERS-active polymers.
- Al-Hourani, Baker Jawabrah,Bravo-Vasquez, Juan P.,Hermann High,Fenniri, Hicham
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p. 9144 - 9147
(2008/09/17)
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- Potent benzimidazole sulfonamide protein tyrosine phosphatase 1B inhibitors containing the heterocyclic (S)-isothiazolidinone phosphotyrosine mimetic
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Potent nonpeptidic benzimidazole sulfonamide inhibitors of protein tyrosine phosphatase 1B (PTP1B) were derived from the optimization of a tripeptide containing the novel (S)-isothiazolidinone ((S)-IZD) phosphotyrosine (pTyr) mimetic. An X-ray cocrystal s
- Combs, Andrew P.,Zhu, Wenyu,Crawley, Matthew L.,Glass, Brian,Polam, Padmaja,Sparks, Richard B.,Modi, Dilip,Takvorian, Amy,McLaughlin, Erin,Yue, Eddy W.,Wasserman, Zelda,Bower, Michael,Wei, Min,Rupar, Mark,Ala, Paul J.,Reid, Brian M.,Ellis, Dawn,Gonneville, Lucie,Emm, Thomas,Taylor, Nancy,Yeleswaram, Swamy,Li, Yanlong,Wynn, Richard,Burn, Timothy C.,Hollis, Gregory,Liu, Phillip C. C.,Metcalf, Brian
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p. 3774 - 3789
(2007/10/03)
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- NOVEL BIAROMATIC COMPOUNDS THAT ACTIVATE PPAR TYPE RECEPTORS, AND USE THEREOF IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS
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The invention relates to novel biaromatic compounds that correspond to the general formula (I) and also to the method for preparing them, and to their use in pharmaceutical compositions for use in human or veterinary medicine (in dermatology, and also in the field of cardiovascular diseases, immune diseases and/or lipid metabolism-related diseases), or alternatively in cosmetic compositions.
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Page/Page column 44
(2010/10/20)
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- Process for the solid phase synthesis of aldehyde, ketone, oxime, amine, hydroxamic acid and αβ-unsaturated carboxylic acid and aldehyde compounds
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This invention is directed to a process for the solid phase synthesis of aldehyde, ketone, oxime, amine, hydroxamic acid and α,β-unsaturated carboxylic acid and aldehyde compounds and to polymeric hydroxylamine resin compounds useful therefor.
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- Parallel synthesis of aldehydes and ketone facilitated by a new solid- phase Weinreb amide
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This paper describes a novel supported Weinreb amide resin that facilitates parallel synthesis of aldehydes and ketones on a scale useful for chemical library synthesis. This new resin makes it possible to produce custom aldehydes and ketones from a wide range of carboxylic acids, including N-BOC-amino acids. A variety of commercially unavailable aldehydes are easily synthesized in parallel and obtained in high purity via a simple filtration workup, thus facilitating parallel synthesis of lead optimization libraries that typically require custom synthesis of aldehyde intermediates for development of structure-activity relationships. To demonstrate the utility of this method, we synthesized a small library based on a supported Horner- Emmons reagent. This is the first time it has been shown that aldehydes generated via a supported Weinreb amide could be used directly as reagents in chemical library synthesis employing moisture-sensitive reactions. The analogous solution reaction is not suited for parallel synthesis because of the laborious extractive workup procedure necessary and, at times, the instability of these reactive intermediates.
- Salvino, Joseph M.,Mervic, Miljenko,Mason, Helen J.,Kiesow, Terence,Teager, David,Airey, John,Labaudiniere, Richard
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p. 1823 - 1830
(2007/10/03)
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- Thiophenesulfonamides as endothelin receptor antagonists
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The synthesis and in vitro binding affinities of a series of thiophenesulfonamides as ET(A) selective endothelin receptor antagonists is described. The most potent inhibitor displayed an IC50 of 43 nM and 3 μM to ET(A) and ET(B) receptors, respectively.
- Raju,Wu, Chengde,Kois, Adam,Verner, Erik,Okun, Ilya,Stavros, Fiona,Chan, Ming Fai
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p. 2651 - 2656
(2007/10/03)
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- Highly Selective Inhibitors of Thromboxane Synthetase. 2. Pyridine Derivatives
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The enzyme thromboxane (TX) synthetase is inhibited by pyridine.The β-substituted pyridine derivatives showed higher inhibitory potency than γ-substituted ones having the side chain.Among the β-substituted derivatives containing the ω-carboxyalkyl group, the compounds with 6-8 carbon atoms in the side chain were especially effective.The derivatives holding the phenylene group in the side chain exhibited much higher inhibitory activity than those of the alkylene type.Among them, (E)-3--2-methylacrylic acid hydrochloride (5a) had the highest potency (IC50 = 3*10-9 M).The β-substituted pyridine derivatives and 1-substituted imidazole derivatives which had the same side chain showed almost the same potency.The β-substituted pyridine derivatives do not inhibit arachidonic acid cyclooxygenase or prostaglandin I2 synthetase, two other enzymes of the arachidonic cascade.
- Tanouchi, Tadao,Kawamura, Masanori,Ohyama, Isao,Kajiwara, Ikuo,Iguchi, Yohichi,et al.
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p. 1149 - 1155
(2007/10/02)
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