- Efficient cosubstrate enzyme pairs for sequence-specific methyltransferase-directed photolabile caging of DNA
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Supplemented with synthetic surrogates of their natural cosubstrate S-adenosyl-l-methione (AdoMet), methyltransferases represent a powerful toolbox for the functionalization of biomolecules. By employing novel cosubstrate derivatives in combination with p
- Heimes, Michael,Kolmar, Leonie,Brieke, Clara
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Read Online
- MOLECULES HAVING CERTAIN PESTICIDAL UTILITIES, AND INTERMEDIATES, COMPOSITIONS, AND PROCESSES RELATED THERETO
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This disclosure relates to compounds having pesticidal utility against pests in phyla Nematoda, Arthropoda, and/or Mollusca, processes to produce such compounds and intermediates used in such processes, compositions containing such compounds, and processes of using such compounds against such pests. These compounds/molecules may be used, for example, as nematicides, acaricides, insecticides, miticides, and/or molluscicides. This document discloses compounds having the following formula (Formula One and/or Formula One-A).
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Page/Page column 74; 420-421
(2021/02/12)
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- Intramolecular Pd-catalyzed reductive amination of enolizable sp3-C-H bonds
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A palladium-catalyzed reductive cyclization of nitroarenes has been designed to construct sp3-C-NHAr bonds from sp3-C-H bonds by using an enolizable nucleophile to intercept a nitrosoarene intermediate. Exposure of ortho-substituted nitroarenes to 5 mol ?% of Pd(OAc)2 and 10 mol ?% of phenanthroline under 2 atm of CO constructs partially saturated 5-, 6-, or 7-membered N-heterocycles using α-pyridyl carboxylates, malonates, 1,3-dimethylbarbituric acid, 1,3-diones, or difurans as the nucleophile.
- Ford, Russell L.,Alt, Isabel,Jana, Navendu,Driver, Tom G.
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p. 8827 - 8831
(2019/10/28)
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- Antibodies to aripiprazole haptens and use thereof
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Disclosed is an antibody which binds to aripiprazole, which can be used to detect aripiprazole in a sample such as in a competitive immunoassay method. The antibody can be used in a lateral flow assay device for point-of-care detection of aripiprazole, in
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Page/Page column 42
(2017/05/17)
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- Discovery of Novel Indazole Derivatives as Highly Potent and Selective Human β3-Adrenergic Receptor Agonists with the Possibility of Having No Cardiovascular Side Effects
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Novel indazole derivatives were prepared and evaluated for their biological activity and cardiovascular safety profile as human β3-adrenergic receptor (AR) agonists. Although the initial hit compound 5 exhibited significant β3-AR agonistic activity (EC50 = 21 nM), it also exhibited agonistic activity at the α1A-AR (EC50 = 219 nM, selectivity: α1A/β3 = 10-fold). The major metabolite of 5, which was an oxidative product at the indazole 3-methyl moiety, gave a clue to a strategy for improvement of the selectivity for β3-AR agonistic activity versus α1A-AR agonistic activity. Thus, modification of the 3-substituent of the indazole moiety effectively improved the selectivity to develop compound 11 with potent β3-AR agonistic activity (EC50 = 13 nM) and high selectivity (α1A/β3 = >769-fold). Compound 11 was also inactive toward β1 and β2-ARs and showed dose dependent β3-AR mediated relaxation of marmoset urinary bladder smooth muscle, while it did not obviously affect heart rate or blood pressure (iv, 3 mg/kg) in anesthetized rats.
- Wada, Yasuhiro,Shirahashi, Hiromitsu,Iwanami, Taisuke,Ogawa, Masami,Nakano, Seiji,Morimoto, Akifumi,Kasahara, Ken-Ichi,Tanaka, Eiichi,Takada, Yoshio,Ohashi, Shigeki,Mori, Mutsuhiro,Shuto, Satoshi
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supporting information
p. 6048 - 6057
(2015/08/24)
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- Design, synthesis, and pharmacological evaluation of fused β-homophenylalanine derivatives as potent DPP-4 inhibitors
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Dipeptidyl peptidase-4 (DPP-4) inhibitors are accepted as a favorable class of agents for the treatment of type 2 diabetes. Herein, a series of fused β-homophenylalanine derivatives as novel DPP-4 inhibitors were designed, synthesized, and evaluated for their inhibitory activities against DPP-4. Most of them displayed excellent DPP-4 inhibitory activities and good selectivity. Among them, 9aa, 18a, and 18m also showed good efficacy in an oral glucose tolerance test (OGTT) in ICR mice. Moreover, when dosed 8 h prior to glucose challenge, 18m showed significantly greater potency than sitagliptin. It thus provides potential candidates for the further development into potent drugs targeting DPP-4.
- Jiang, Tao,Zhou, Yuren,Chen, Zhuxi,Sun, Peng,Zhu, Jianming,Zhang, Qiang,Wang, Zhen,Shao, Qiang,Jiang, Xiangrui,Li, Bo,Chen, Kaixian,Jiang, Hualiang,Wang, Heyao,Zhu, Weiliang,Shen, Jingshan
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supporting information
p. 602 - 606
(2015/05/27)
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- Antibodies to Aripiprazole Haptens and Use Thereof
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Disclosed is an antibody which binds to aripiprazole, which can be used to detect aripiprazole in a sample such as in a competitive immunoassay method. The antibody can be used in a lateral flow assay device for point-of-care detection of aripiprazole, in
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Page/Page column
(2014/03/24)
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- HAPTENS OF ARIPIPRAZOLE AND THEIR USE IN IMMUNOASSAYS
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The invention relates to compounds of Formula I, wherein R1, R2, and R3 are defined in the specification, useful for the synthesis of novel conjugates and immunogens derived from aripiprazole. The invention also relates to
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Page/Page column 49
(2014/03/25)
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- Rh2(II)-catalyzed selective aminomethylene migration from styryl azides
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Rh2(II)-Carboxylate complexes were discovered to promote the selective migration of aminomethylenes in β,β-disubstituted styryl azides to form 2,3-disubstituted indoles. Mechanistic data are also presented that suggest that the migration occurs stepwise before diffusion of the iminium ion.
- Kong, Chen,Jana, Navendu,Driver, Tom G.
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p. 824 - 827
(2013/03/29)
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- INDAZOLE ANALOGUE
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[Objective] To provide a drug that selectively stimulates the β3-adrenergic receptors, particularly a drug capable of preferentially stimulating the β3-adrenergic receptors over the α1-adrenergic receptors. This drug can be used in the treatment and prevention of diabetes, obesity, hyperlipidemia, depression, cholelithiasis, diseases caused by biliary hyperkinesia, diseases caused by hyperfunction of the gastrointestinal tract, interstitial cystitis, overactive bladder or urinary incontinence, diseases associated with decreased lacrimation, and the like. [Solution] Indazole analogs represented by the general formula (I) or a salt thereof. Drugs that contains these indazole analogs or a salt thereof as the active ingredient.
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Page/Page column 89; 90
(2012/08/14)
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- Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-methoxy-5-[(2′,4′,6′-trimethoxystyrylsulfonyl)methyl] phenylamino}acetate (ON 01910.Na): Synthesis, structure-activity relationship, and biological activity
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Cyclin D proteins are elevated in many cancer cells, and targeted deletion of cyclin D1 gene in the mammary tissues protects mice from breast cancer. Accordingly, there is an increasing awareness of this novel nonenzymatic target for cancer therapeutics. We have developed novel, nonalkylating styrylbenzylsulfones that induce cell death in wide variety of cancer cells without affecting the proliferation and survival of normal cells. The development of derivatized styrylbenzylsulfones followed logically from a tumor cell cytotoxicity screen performed in our laboratory that did not have an a priori target profile. Modifications of some of the precursor molecules led to lead optimization with regard to tumor cell cytotoxicity. In this report we describe the synthesis and structure-activity relationships of novel, nonalkylating (E)-styrylbenzylsulfones and the development of the novel anticancer agent sodium (E)-2-{2-methoxy-5-[(2′,4′,6′- trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na), which is in phase III trials for myelodysplastic syndromes (MDS) associated with aberrant expression of cyclin D proteins.
- Reddy, M. V. Ramana,Venkatapuram, Padmavathi,Mallireddigari, Muralidhar R.,Pallela, Venkat R.,Cosenza, Stephen C.,Robell, Kimberly A.,Akula, Balaiah,Hoffman, Benjamin S.,Reddy, E. Premkumar
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experimental part
p. 6254 - 6276
(2011/11/01)
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- Selenium-catalyzed reductive cyclization and carbocyclization of 2,2′-dinitrostilbenes with carbon monoxide: One-shot synthesis of indolo[1,2-c]quinazolinones
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When 2,2′-dinitrostilbene derivatives were allowed to react with carbon monoxide in the presence of a catalytic amount of selenium, reductive cyclization and carbocyclization proceeded to give indolo[1,2-c]quinazolin-6(5H) -ones, containing both indole an
- Umeda, Rui,Morishita, Shigeru,Nishiyama, Yutaka
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experimental part
p. 571 - 575
(2012/02/15)
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- A general strategy for the synthesis of cyclic N-aryl hydroxamic acids via partial nitro group reduction
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We describe a generalized approach to stereocontrolled synthesis of substituted cyclic hydroxamic acids (3-amino-1-hydroxy-3,4-dihydroquinolinones) by selective reduction of substituted 2-nitrophenylalanine substrates. Compounds in this series have antibacterial properties and have also recently been reported as KAT II inhibitors. The key nitrophenyl alanine intermediates are prepared enantioselectively in excellent yield by phase transfer catalyzed alkylation of the corresponding nitrobenzyl bromides. The scope and limitations of the reductive cyclization transformation have been explored with attention to the effects of substitution pattern and electronics on reaction efficiency and byproduct formation. In addition, a novel activated trifluoroethyl ester cyclization strategy has been developed as an alternate approach to the most sterically demanding systems in this series.
- McAllister, Laura A.,Bechle, Bruce M.,Dounay, Amy B.,Evrard, Edelweiss,Gan, Xinmin,Ghosh, Somraj,Kim, Ji-Young,Parikh, Vinod D.,Tuttle, Jamison B.,Verhoest, Patrick R.
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experimental part
p. 3484 - 3497
(2011/06/24)
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- INDAZOLE COMPOUNDS
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Provided are compounds represented by the following formula (A-1) and formula (1), or salts thereof. The compounds of formula (A-1) and formula (1) or salts thereof have 133 adrenergic receptor agonist activity, and thus are useful as therapeutic and prophylactic agent for diabetes mellitus, obesity, hyperlipidemia, depression, diseases caused by gallstones or hypermotility of the biliary tract, diseases caused by hyperactivity of the digestive tract, interstitial cystitis, overactive bladder or urinary incontinence, or as therapeutic and prophylactic agents for diseases concomitant with decreased tears.
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Page/Page column 54
(2010/07/04)
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- QUINOXALINE COMPOUNDS AND USE THEREOF
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The present invention is related to quinoxaline compounds of Formula (I) in particular for the treatment of autoimmune disorders and/or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, transplantation, graft rejection or lung injuries.
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Page/Page column 52
(2008/12/08)
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- Substituted 2-nitrobenzyltrichloroacetate esters for photodirected oligonucleotide detritylation in solid films
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Oligonucleotide microarray fabrication by chemical synthesis using photoacid generators in solid films could have advantages over existing methods, but has not matched the accuracy of conventional synthesis where detritylation is performed with acid solut
- Serafinowski, Pawel J.,Garland, Peter B.
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supporting information; experimental part
p. 3284 - 3291
(2009/02/05)
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- TETRAHYDRO-PYRIDOAZEPIN-8-ONES AND RELATED COMPOUNDS FOR THE TREATMENT OF SCHIZOPHRENIA
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Compounds of formula 1 are disclosed, wherein G, D, A, Q, Y, Z, and R1 through R10 are defined in the specification. Also provided are descriptions of processes for preparing compounds of formula 1, intermediates used in making the same, and pharmaceutical compositions containing such compounds and their use in the treatment of central nervous system disorders and other disorders.
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- Design, synthesis, and biological evaluation of combretastatin nitrogen-containing derivatives as inhibitors of tubulin assembly and vascular disrupting agents
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A series of analogs with nitro or serinamide substituents at the C-2′-, C-5′-, or C-6′-position of the combretastatin A-4 (CA4) B-ring was synthesized and evaluated for cytotoxic effects against heart endothelioma cells, blood flow reduction to tumors in
- Monk, Keith A.,Siles, Rogelio,Hadimani, Mallinath B.,Mugabe, Benon E.,Ackley, J. Freeland,Studerus, Scott W.,Edvardsen, Klaus,Trawick, Mary Lynn,Garner, Charles M.,Rhodes, Monte R.,Pettit, George R.,Pinney, Kevin G.
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p. 3231 - 3244
(2007/10/03)
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- Ophthalmic compositions for treating ocular hypertension
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This invention relates to potent potassium channel blocker compounds of Formula I or a formulation thereof for the treatment of glaucoma and other conditions which leads to elevated intraoccular pressure in the eye of a patient. This invention also relate
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- Model Compounds of Caged Capsaicin: Design, Synthesis, and Photoreactivity
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Molecules were prepared with substituted nitrobenzyl groups covalently bonded to N-(4-hydroxy-3-methoxybenzyl)acetamide (2) by ether or carbonate linkages. These compounds decomposed under irradiation at 363 nm. Those with carbonate linkages decomposed at
- Katritzky, Alan R.,Xu, Yong-Jiang,Vakulenko, Anatoliy V.,Wilcox, Allan L.,Bley, Keith R.
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p. 9100 - 9104
(2007/10/03)
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- Discovery of novel phosphonic acid derivatives as new chemical leads for inhibitors of TNF-α production
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2-(Acylamino)benzylphosphonic acid 6 derived from an artificial substrate of sphingomyelinase was found to show inhibitory activity of TNF-α production. Structural optimization was started with the chemical modification of 6. The discovery of another chem
- Matsui, Toshiaki,Takahashi, Shinya,Matsunaga, Naoki,Nakamura, Kazunori,Omawari, Nagashige,Sakai, Masaru,Kamoshima, Wataru,Terai, Kouichiro,Ohno, Hiroyuki,Obata, Takaaki,Nakai, Hisao,Toda, Masaaki
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p. 3807 - 3815
(2007/10/03)
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- Synthesis of substituted 10,11-dihydro-5H-dibenz[b,f]azepines; key synthons in syntheses of pharmaceutically active compounds
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Substituted 10,11-dihydro-5H-dibenz[b,f]azepines are key synthons in the syntheses of a number of pharmaceutically active compounds such as imipramine, chlorimipramine, and desimipramine analogues. A facile synthesis of substituted 10,11-dihydro-5H-dibenz[b,f]azepines is described, starting out from commercially available 2-bromotoluenes or 2-nitrotoluenes. Initial α-bromination with N-bromosuccinimide and subsequent reaction with triethylphosphite afforded the corresponding benzyl phosphonic ester derivatives. After reaction with benzaldehyde derivatives, the expected Horner-Emmons reaction products were obtained. Hydrogenation gave the amino derivatives which were transformed into the corresponding formamides. Under Goldberg conditions [1], the final ring closing step was performed to give the substituted 10,11-dihydro-5H-dibenz[b,f]azepines in 46-75% yield.
- Jorgensen, Tine Krogh,Andersen, Knud Erik,Lau, Jesper,Madsen, Peter,Huusfeldt, Per Olaf
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- Catalytic processes of oxidation by hydrogen peroxide in the presence of Br2 or HBr. Mechanism and synthetic applications
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The mechanism and the synthetic applications for the oxidation of alcohols, ethers, and aldehydes by H2O2 catalyzed by Bf2 or Br- in a liquid two-phase system (aqueous and organic) are reported. Aliphatic and benzylic primary alcohols and ethers show an opposite behavior, which has been rationalized on the ground of the different electronic configurations of the intermediate alkyl (π-type) and acyl (σ-type) radicals and their influence on enthalpic and polar effects. A two-phase system is particularly useful also for an efficient benzylic bromination by Br2 or Br-; the substitution of the benzyl bromide by OH, OR, and OCOR regenerates Br-, which can be recycled. The evaluation of the relative reactivities of the involved substrates and intermediates has allowed to develop a variety of simple, facile, convenient, and selective syntheses of alcohols, aldehydes, ketones, esters, and benzyl bromides, which fulfill the conditions for practical applications.
- Amati, Alessandro,Dosualdo, Gabriele,Zhao, Lihua,Bravo, Anna,Fontana, Francesca,Minisci, Francesco,Bjorsvik, Hans-Rene
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p. 261 - 269
(2013/09/08)
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- Synthesis of the Indolocarbazole Natural Products Staurosporinone and Arcyriaflavin B
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Flexible synthetic routes involving double nitrene insertions are described leading to the indolocarbazole systems present in a growing group of natural products.The methods are exemplified by the total synthesis of two members of this group stauro
- Hughes, Ian,Nolan, William P.,Raphael, Ralph A.
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p. 2475 - 2480
(2007/10/02)
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- Silicon-Mediated Synthesis of Bibenzyl Systems: Synthesis of Ring and Side-Chain Functionalized Hexestrol Derivatives
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Derivatives of hexestrol , a non-steroidal estrogen, bearing photochemically reactive functional groups or γ-emmitting radionuclides, are useful as affinity labeling agents for the estrogen receptor or as imaging agents for receptor positive breast tumors, respectively.We have developed convenient synthetic routes to two side chain functionalized and aromatic ring functionalized hexestrol derivatives, based on a direct benzylic coupling reaction mediated by allylsilanes or silyl ketene acetals. 1-Dehydrohexestrol and variousaromatic ring substituted 1-dehydrohexestrol derivatives can be prepared by coupling 3-(trimethylsilyl)-1-(4-methoxyphenyl)propene with various reactive benzylic derivatives, and pentestrol derivatives are prepared by the coupling of the silyl ketene acetal derivative of p-methoxyphenyl acetic ester with benzylic derivatives.The R*,S* (erythro) and R*,R* (threo) diastereomers formed in each case can be separated readily by chromatography and recrystallization.This silicon-mediated approach to functionalized hexestrol derivatives provides a convenient route to many compounds of interest as biochemical probes and receptor-based diagnostic reagents.
- Mohan, Raju,Katzenellenbogen, John A.
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p. 1238 - 1246
(2007/10/02)
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