- Discovery of 2H-Chromen-2-one Derivatives as G Protein-Coupled Receptor-35 Agonists
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A family of 2H-chromen-2-one derivatives were identified as G protein-coupled receptor-35 (GPR35) agonists using dynamic mass redistribution assays in HT-29 cells. The compounds with 1H-tetrazol-5-yl in 3-substituted position displayed higher potency than the corresponding carboxyl analogs, and the hydroxyl group in the 7-position also played an important role in GPR35 agonistic activity. 6-Bromo-7-hydroxy-8-nitro-3-(1H-tetrazol-5-yl)-2H-chromen-2-one (50) was found to be the most potent GPR35 agonist with an EC50 of 5.8 nM. Calculating the physicochemical properties of compounds with moderate to high potency suggested that compounds 30, 50, and 51 showed good druggability. This study provides a novel series of GPR35 agonists, and compound 50 may be a powerful tool to study GPR35.
- Wei, Lai,Wang, Jixia,Zhang, Xiuli,Wang, Ping,Zhao, Yaopeng,Li, Jiaqi,Hou, Tao,Qu, Lala,Shi, Liying,Liang, Xinmiao,Fang, Ye
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p. 362 - 372
(2017/04/26)
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- 1,4-DISUBSTITUTED PYRIDAZINE DERIVATIVES AND THEIR USE FOR TREATING SMN-DEFICIENCY-RELATED CONDITIONS
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The present invention provides a compound of formula IA or a pharmaceutically acceptable salt thereof; 5 (IA) a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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Page/Page column 83
(2015/02/25)
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- Synthesis of C4-C5 cycloalkyl-fused and C6-modified chromans via ortho-quinone methides
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Starting from 3,5-dimethoxybenzaldehyde, some functionalized 2,3,4-trisubstituted tricyclic 4,5-cycloalkyl-fused and 6-modified chromans could be prepared via ortho-quinone methides (o-QMs)/hetero-Diels-Alder (HDA) reactions of the appropriate precursors.
- Tangdenpaisal, Kassrin,Chuayboonsong, Kanokpish,Sukjarean, Patchaya,Katesampao, Varisa,Noiphrom, Nok,Ruchirawat, Somsak,Ploypradith, Poonsakdi
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p. 1050 - 1064
(2015/03/31)
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- Aldehyde-Assisted Ruthenium(II)-Catalyzed C-H Oxygenations
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Versatile ruthenium(II) complexes allow for site-selective C-H oxygenations with weakly-coordinating aldehydes. The challenging C-H functionalizations proceed with high chemoselectivity by rate-determining C-H metalation. The new method features an ample substrate scope, which sets the stage for the step-economical preparation of various bioactive heterocycles.
- Yang, Fanzhi,Rauch, Karsten,Kettelhoit, Katharina,Ackermann, Lutz
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supporting information
p. 11285 - 11288
(2016/02/18)
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- Synthesis of 8-aryl-substituted coumarins based on ring-closing metathesis and Suzuki-Miyaura coupling: Synthesis of a furyl coumarin natural product from Galipea panamensis
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The synthesis of 7-methoxy-8-(4-methyl-3-furyl)-2H-chromen-2-one, a natural product with antileishmanial activity recently isolated from the plant Galipea panamensis, is described. The key step is a Suzuki-Miyaura coupling of a furan-3-boronic acid and an
- Schmidt, Bernd,Krehl, Stefan,Kelling, Alexandra,Schilde, Uwe
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supporting information; experimental part
p. 2360 - 2367
(2012/05/31)
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- Discovery of XL413, a potent and selective CDC7 inhibitor
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CDC7 is a serine/threonine kinase that has been shown to be required for the initiation and maintenance of DNA replication. Up-regulation of CDC7 is detected in multiple tumor cell lines, with inhibition of CDC7 resulting in cell cycle arrest. In this paper, we disclose the discovery of a potent and selective CDC7 inhibitor, XL413 (14), which was advanced into Phase 1 clinical trials. Starting from advanced lead 3, described in a preceding communication, we optimized the CDC7 potency and selectivity to demonstrate in vitro CDC7 dependent cell cycle arrest and in vivo tumor growth inhibition in a Colo-205 xenograft model.
- Koltun, Elena S.,Tsuhako, Amy Lew,Brown, David S.,Aay, Naing,Arcalas, Arlyn,Chan, Vicky,Du, Hongwang,Engst, Stefan,Ferguson, Kim,Franzini, Maurizio,Galan, Adam,Holst, Charles R.,Huang, Ping,Kane, Brian,Kim, Moon H.,Li, Jia,Markby, David,Mohan, Manisha,Noson, Kevin,Plonowski, Arthur,Richards, Steven J.,Robertson, Scott,Shaw, Kenneth,Stott, Gordon,Stout, Thomas J.,Young, Jenny,Yu, Peiwen,Zaharia, Cristiana A.,Zhang, Wentao,Zhou, Peiwen,Nuss, John M.,Xu, Wei,Kearney, Patrick C.
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scheme or table
p. 3727 - 3731
(2012/07/16)
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- Aromatic bromination of aldehydes and ketones using 1,3-di-n- butylimidazolium
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An environmentally benign and efficient process for the preparation of monobromo derivatives of aryl aldehydes and ketones was developed by simple and practical reactions of aryl aldehydes or ketones with 1,3-di-n-butylimidazolium tribromide ([BBIm]Br3), as a brominating reagent under solvent-free conditions in very high yields. The process has several advantages: high conversions, short reaction time, mild reaction conditions, simple workup with good to quantitative yields and re-usable ionic liquid.
- Borikar,Daniel
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experimental part
p. 531 - 536
(2012/07/01)
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- Pt(IV)-catalyzed generation and [4+2]-cycloaddition reactions of o-quinone methides
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Novel intermolecular and intramolecular generations of ortho-quinone methides and their formal [4+2]-cycloaddition reactions with olefins catalyzed by PtCl4 and AuCl3 under mild conditions have been developed. Good to excellent yields (up to 99%) and diastereoselectivity (up to >99:1) of the chromans were obtained. PtCl4 was found to be effective and compatible with various functional groups present in the substrates. A mechanism accounting for its catalytic cycle is proposed and discussed.
- Radomkit, Suttipol,Sarnpitak, Pakornwit,Tummatorn, Jumreang,Batsomboon, Paratchata,Ruchirawat, Somsak,Ploypradith, Poonsakdi
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supporting information; experimental part
p. 3904 - 3914
(2011/06/22)
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- Generation of ortho-quinone methides by p-TsOH on silica and their hetero-Diels-Alder reactions with styrenes
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(Chemical Equation Presented) 2-Arylchromans were readily prepared from the hetero-Diels-Alder reactions of styrenes with the ortho-quinone methides (o-QMs) which, in turn, were generated by treating the MOM-protected benzylacetate derivatives with p-TsOH immobilized on silica (PTS-Si) in toluene under mild conditions (0°C to rt). The corresponding chromans were obtained in moderate to excellent yields (42-97%) and in moderate to excellent diastereoselectivity (up to >99:1).
- Batsomboon, Paratchata,Phakhodee, Wong,Ruchirawat, Somsak,Ploypradith, Poonsakdi
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supporting information; experimental part
p. 4009 - 4012
(2009/10/14)
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- ortho-Formylation of oxygenated phenols
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Oxygenated phenols are mono-formylated using a mixture of paraformaldehyde, MgCl2, and Et3N in THF. In all cases but one, only one regioisomer of the salicylaldehyde is obtained in good to high yield.
- Akselsen, ?yvind W.,Skatteb?l, Lars,Hansen, Trond Vidar
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experimental part
p. 6339 - 6341
(2010/02/27)
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- Antiangiogenic versus cytotoxic activity in analogues of aeroplysinin-1
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A series of analogues of the potentially angiogenic inhibitor aeroplysinin-1 1 were synthesized and their in vitro antiangiogenic and cytotoxic activities evaluated. In the case of epoxy ketone 6 and azlactone 36 the relationship sprouting inhibition assay/cytotoxicity in BAE cells was enhanced by one order and two orders of magnitude, respectively, with respect to the reference. These results imply more specific antiangiogenic properties for the synthesized derivatives.
- Cordoba, Ruben,Tormo, Nelida Salvador,Medarde, Antonio Fernandez,Plumet, Joaquin
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p. 5300 - 5315
(2008/03/13)
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- Carboxylated, heteroaryl-substituted chalcones as inhibitors of vascular cell adhesion molecule-1 expression for use in chronic inflammatory diseases
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Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Corr
- Meng, Charles Q.,Ni, Liming,Worsencroft, Kimberly J.,Ye, Zhihong,Weingarten, M. David,Simpson, Jacob E.,Skudlarek, Jason W.,Marino, Elaine M.,Suen, Ki-Ling,Kunsch, Charles,Souder, Amy,Howard, Randy B.,Sundell, Cynthia L.,Wasserman, Martin A.,Sikorski, James A.
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p. 1304 - 1315
(2008/02/02)
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- PROCESS OF MAKING CHALCOME DERIVATIVES
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This invention is a novel methods of manufacturing chalcones that includes reacting a carbon-linked heteroaryl or heterocyclic substituted benzaldehyde with an acetophenone in a solvent or mixture of solvents in the presence of LiOMe. Also provided are new chalcones for the treatment of medical conditions.
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- Indolinone compounds as kinase inhibitors
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The invention relates to certain indolinone compounds, their method of synthesis, and a combinatorial library consisting of the indolinone compounds of the invention. The invention also relates to methods of modulating the function of protein kinases using indolinone compounds of the invention and methods of treating diseases by modulating the function of protein kinases and related signal transduction pathways.
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Page/Page column 70
(2010/11/30)
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- Oxime derivatives for the treatment of dyslipidemia and hypercholesteremia
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The present invention relates to compounds of Formula (I) which may be useful in the treatment of diseases, such as, metabolic disorders, dyslipidemia and/or hyperchloesterolemia: 1
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- Heterocyclic derivatives for the treatment of diabetes and other diseases
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The present invention relates to certain substituted heterocycles of Formula (I) which are useful in the treatment of diseases related to lipid and carbohydrate metabolism, such as type 2 diabetes, adipocyte differentiation, uncontrolled proliferation, such as lymphoma, Hodgkin's Disease, leukemia, breast cancer, prostate cancer or cancers in general; and inflammation, such as osteoarthritis, rheumatoid arthritis, Crohn's Disease or Inflammatory Bowel Disease.
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- 1, 3-bis-(substituted-phenyl)-2-propen-1-ones and their use to treat VCAM-1 mediated disorders
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It has been discovered certain 1,3-bis-(substituted-phenyl)-2-propen-1-ones, including compounds of formula (I) inhibit the expression of VCAM-1, and thus can be used to treat a patient with a disorder mediated by VCAM-1. Examples of inflammatory disorder
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- A facile synthesis of spiroisoxazolines: Intramolecular cyclization of 3-aryl-2-nitroacrylates promoted by titanium tetrachloride
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Titanium tetrachloride-induced cyclization of 3-(o- or m-substituted p- methoxyphenyl)-2-nitro acrylates (1) provided stereoselectively (4α,5β)-1- oxa-2-azaspiro[4, 5]deca-2,6,9-trien-8-ones (2). Ortho-substituted p- methoxyphenyl nitroacrylates gave 2 in good yield. 3-(4'-methoxy-1'- naphthyl)-2-nitroacrylate also reacted with titanium tetrachloride to give quantitatively (4α,5β)-4'-oxospiro[isoxazole(4H)5,1'(4'H)-naphthatene]. 3- (10'-methoxy-9'-anthryl)-2-nitroacrylate was converted to 10- oxospiro[anthracene-(10H)9,5'(4'H)-isoxazole].
- Hirotani, Seiko,Kaji, Eisuke
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p. 4255 - 4270
(2007/10/03)
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