- Dual role of Rh(III) catalyst enables regioselective halogenation of (electron-rich) heterocycles
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The Rh(III)-catalyzed selective bromination and iodination of electron-rich heterocycles is reported. Kinetic investigations show that Rh plays a dual role in the bromination, catalyzing the directed halogenation and preventing the inherent halogenation of these substrates. As a result, this method gives highly selective access to valuable halogenated heterocycles with regiochemistry complementary to those obtained using uncatalyzed approaches, which rely on the inherent reactivity of these classes of substrates. Furans, thiophenes, benzothiophenes, pyrazoles, quinolones, and chromones can be applied.
- Schr?der, Nils,Lied, Fabian,Glorius, Frank
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- Synthesis of N-methylpyridine-chlorofuranformamide analogs as novel OPG up-regulators and inhibitors of RANKL-induced osteoclastogenesis
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The OPG/RANKL/RANK pathway is a promising target for the design of therapeutic agents used in the treatment of osteoporosis. E09241 with an N-methylpyridine-chlorofuranformamide structural skeleton was previously identified to decrease bone loss and thus protect against osteoporosis in ovariectomized rats through increasing osteoprotegerin (OPG) expression. In this study, 36 derivatives of E09241 (3a) were prepared. The synthesis, up-regulation of OPG activities, SAR (structure–activity relationship), and cytotoxicity of these compounds are presented. Compounds with good up-regulating OPG activities could inhibit RANKL (the receptor activator of nuclear factor-kappa B ligand)-induced osteoclastogenesis in RAW264.7 cells. Particularly, compounds 3c and 3i1 significantly reduced NFATc1 and MMP-9 protein expression through inhibition of the NF-κB and MAPK pathways in RANKL induced RAW264.7 cells. In addition, compounds 3c and 3v significantly promoted osteoblast differentiation in MC3T3-E1 cells in osteogenic medium, and compounds 3c, 3v, and 3i1 obviously increased OPG protein expression and secretion in MC3T3-E1 cells. Furthermore, the pharmacokinetic profiles, acute toxicity, and hERG K+ channel effects of compounds 3a, 3c, 3e, 3v, and 3i1 were investigated. Taken together, these results indicate that N-methylpyridine-chlorofuranformamide analog 3i1 could serve as a promising lead for the development of new agents for treating osteoporosis.
- Liu, Chao,Li, Yining,Sheng, Ren,Han, Xiaowan,Bao, Li,Wang, Chenyin,Wang, Weizhi,Jiang, Xinhai,Han, Jiangxue,Lei, Lijuan,Li, Ni,Zhang, Jing,Chen, Minghua,Li, Yan,Wu, Yexiang,Li, Shunwang,Ren, Yu,Xu, Yanni,Si, Shuyi
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- Diversification of the Renewable Furanic Platform via 5-(Chloromethyl)furfural-Based Carbon Nucleophiles
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Biobased 5-(chloromethyl)furoate and 5-methylfuroate esters can be deprotonated to function as furylogous lithium enolates, and the former can also undergo zinc insertion to access Reformatsky-type chemistry. Carbon nucleophilicity represents hitherto lit
- Miao, Haoqian,Shevchenko, Nikolay,Otsuki, Andrew L.,Mascal, Mark
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p. 303 - 305
(2020/10/12)
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- COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH APJ RECEPTOR ACTIVITY
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This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize) the apelin receptor (also referred to herein as the APJ receptor; gene symbol APLNR). This disclosure also features compositions containing the same as well as other methods of using and making the same. The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which a decrease in APJ receptor activity (e.g., repressed or impaired APJ receptor signaling; e.g., repressed or impaired apelin-APJ receptor signaling) or downregulation of endogenous apelin contributes to the pathology and/or symptoms and/or progression of the disease, disorder, or condition. Non-limiting examples of such diseases, disorders, or conditions include: (i) cardiovascular disease; (ii) metabolic disorders; (iii) diseases, disorders, and conditions associated with vascular pathology; and (iv) organ failure; (v) diseases, disorders, and conditions associated with infections (e.g., microbial infections); and (vi) diseases, disorders, or conditions that are sequela or comorbid with any of the foregoing or any disclosed herein. More particular non-limiting examples of such diseases, disorders, or conditions include pulmonary hypertension (e.g., PAH); heart failure; type II diabetes; renal failure; sepsis; and systemic hypertension.
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Page/Page column 308
(2020/05/15)
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- Copper-catalyzed: Ortho -C(sp2)-H amination of benzamides and picolinamides with alkylamines using oxygen as a green oxidant
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A versatile Cu-catalyzed direct ortho-C(sp2)-H amination of benzamides and picolinamides with alkylamines has been achieved. This method employs cheap and eco-friendly copper as a catalyst and oxygen as an oxidant, and also has the advantages of straightf
- Chen, Gong,Huang, Jie,Li, Qiong,Wang, Shui-Bo
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p. 4802 - 4814
(2020/07/13)
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- Adenosine receptor antagonists
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The invention provides a compound shown as a formula (I) and a pharmaceutical composition thereof. The compounds of formula (I) of the present invention are useful as adenosine receptor inhibitors, especially A2A and/or A2B inhibitors, for example, the product can be used for prevention or treatment of diseases associated with A2A and/or A2B activity or expression.
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Paragraph 0137-0139
(2020/12/15)
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- Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis
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In order to discover novel hypoxia-inducible factor 1 (HIF-1) inhibitors for the cancer metastasis treatment, 68 new aryl carboxamide compounds were synthesized and evaluated for their inhibitory effect by dual luciferase-reporter assay. Based on five rounds of investigation on structure-activity relationships step by step, compound 30m was discovered as the most active inhibitor (IC50 = 0.32 μM) with no obvious cytotoxicity (CC50 > 50 μM). It effectively attenuated hypoxia-induced HIF-1α protein accumulation and reduced transcription of vascular epidermal growth factor in a dose-dependent manner, which was further demonstrated by its inhibitory potency on capillary-like tube formation, angiogenesis of zebrafish as well as cellular migration and invasion. Importantly, compound 30m exhibited antimetastatic potency in breast cancer lung metastasis in the mice model, indicating its promising therapeutic potential for prevention and treatment of tumor metastasis. These results definitely merit attention for further rational design of more efficient HIF-1 inhibitors in the future.
- Liu, Mingming,Liang, Yuru,Zhu, Zhongzhen,Wang, Jin,Cheng, Xingxing,Cheng, Jiayi,Xu, Binpeng,Li, Rong,Liu, Xinhua,Wang, Yang
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p. 9299 - 9314
(2019/10/16)
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- Catalyst-free synthesis of biodiesel precursors from biomass-based furfuryl alcohols in the presence of H2O and air
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Production of biodiesel from biomass resources usually requires elongation of carbon numbers from typical C5 and C6 platform molecules through C-C coupling reactions, which were catalyzed by acid, base or metal catalysts traditionally. Herein, a catalyst-free method was developed to produce bis(furan-2-yl)methane derivatives (BFMs) from furfuryl alcohol derivatives (FAs) in the presence of H2O and air without any other additional catalysts. An 81% yield of bis(5-methylfuran-2-yl)methane (BMFM) can be obtained from 5-methylfurfuryl alcohol (5-MFA) and a 59% total yield of C11 biodiesel was obtained from 5-methylfurfural (5-MF). In addition, a H2O and air mediated free radical decarboxylation mechanism was proposed based on the detailed mechanistic studies. This strategy offers a green, low-cost and environmentally friendly approach to synthesize biodiesel precursors from biomass based platform molecules.
- Qin, Shengxiang,Li, Teng,Zhang, Man,Liu, Hongyu,Yang, Xin,Rong, Nianxin,Jiang, Jun,Wang, Yalin,Zhang, Hua,Yang, Weiran
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supporting information
p. 6326 - 6334
(2019/12/03)
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- Pd(II)-Catalyzed asymmetric oxidative annulation of N-alkoxyheteroaryl amides and 1,3-dienes
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The first Pd(II)-catalyzed asymmetric oxidative annulation of N-alkoxyaryl amides and 1,3-dienes is reported, which features particular applicability for quick assembly of different types of chiral heterocycles with high yields and enantioselectivities. A novel chiral pyridine-oxazoline bearing a methoxyl group at the C-5 position and a gem-dimethyl group on the oxazoline moiety was found to be crucial for conversion.
- Zhang, Tao,Shen, Hong-Cheng,Xu, Jia-Cheng,Fan, Tao,Han, Zhi-Yong,Gong, Liu-Zhu
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supporting information
p. 2048 - 2051
(2019/03/29)
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- NOVEL AZOLE DERIVATIVES AS APELIN RECEPTOR AGONIST
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The present invention relates to a novel azole derivative as an apelin receptor agonist and a method for treating cardiovascular disease, diabetic disease, renal disease, hypertension, and arteriosclerosis, etc., using the same. The present invention provides a compound represented by formula (I) or a pharmacologically acceptable salt thereof wherein X1 represents -N= or -CH=, X2 represents -CH= or -N=, R1 and R2 each represent a C1 to C6 alkoxy group or the like, R3 represents a heteroaryl group (the heteroaryl group is optionally substituted by a methyl group or the like) or the like, and R4 represents a C1 to C6 alkylthio group or a C2 to C6 alkenyl group (the C1 to C6 alkylthio group and the C2 to C6 alkenyl group are each optionally substituted by one carboxy group or the like) or the like.
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Page/Page column 150; 151
(2017/07/05)
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- Synthesis and in vitro anticancer activity of 6,7-methylenedioxy (or 5-hydroxy-6-methoxy)-2-(substituted selenophenyl)quinolin-4-one analogs
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6,7-Methylenedioxy (or 5-hydroxy-6-methoxy)-2-(substituted selenophenyl)quinolin-4-ones and their isosteric compounds were synthesized and evaluated for anticancer activity. Structure-activity relationships (SAR) of these compounds were established. Among all tested compounds, 6,7-methylenedioxy-2-(5-methylselenophen-2-yl)quinolin-4-one (4d) was found to be the most promising anticancer agent. In screening against NCI's 60 human tumor cell line panel, 4d exhibited highly selective and potent inhibitory activity against MDA-MB-435 melanoma. Furthermore, the results of COMPARE analysis suggested that 4d is an antimitotic agent with a different mechanism of action from the conventional antimitotic agents, such as colchicine, vinca alkaloids and paclitaxel. Therefore, 4d was identified as a new lead compound that merits further optimization.
- Chen, Chien-Ting,Hsu, Mei-Hua,Cheng, Yung-Yi,Liu, Chin-Yu,Chou, Li-Chen,Huang, Li-Jiau,Wu, Tian-Shung,Yang, Xiaoming,Lee, Kuo-Hsiung,Kuo, Sheng-Chu
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experimental part
p. 6046 - 6056
(2012/02/05)
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- Electron-rich heteroaroylphosphonates and their reaction with trimethyl phosphite
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Dialkyl heteroaroylphosphonates based on thiophene, pyrrole or furan have been prepared and their reactions with trimethyl phosphite investigated. Deoxygenation of the carbonyl groups in these heteroaroylphosphonates occurs to give carbene intermediates, which then undergo further reaction. In the case of the furan-3-oylphosphonates and those systems containing a thiophene or pyrrole ring, the major reaction pathway involves intermolecular trapping of the carbene intermediates by the trimethyl phosphite, leading to the formation of ylidic phosphonates that can be readily converted into the corresponding 1,1-bisphosphonates. However, in some furan-2-oylphosphonates the carbenes generated undergo ring-opening to initially give acyclic alkynylphosphonates which may react further to give other novel phosphorus compounds. The effects of substituents on the extent to which intermolecular trapping of the initially formed carbene competes with intramolecular rearrangement has been investigated. The latter process appears to be suppressed by a substituent at the 5-position of the furan ring, the resulting ylidic phosphonates being a rare example of an efficient intermolecular trapping of a furan-2-yl carbene. The Royal Society of Chemistry 2008.
- Griffiths, D. Vaughan,Al-Jeboori, Mohamad J.,Cheong, Yuen-Ki,Duncanson, Philip,Harris, Jayne E.,Salt, Michael C.,Taylor, Helen V.
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supporting information; experimental part
p. 577 - 585
(2008/10/09)
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- Synthesis of furopyrazole analogs of 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) as novel anti-leukemia agents
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As part of our continuing search for potential anticancer drug candidates in YC-1 analogs, several 1-benzyl-3-(substituted aryl)-5-methylfuro[3,2-c]pyrazoles were synthesized and evaluated for their cytotoxicity against HL-60 cell line. Among these compou
- Chou, Li-Chen,Huang, Li-Jiau,Yang, Jai-Sing,Lee, Fang-Yu,Teng, Che-Ming,Kuo, Sheng-Chu
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p. 1732 - 1740
(2008/02/04)
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- USE OF SELECTIVE ANTAGONISTS OF THE ALPHA 1b-ADRENERGIC RECEPTOR FOR IMPROVEMENT OF SEXUAL DYSFUNCTION
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Described is the use in the treatment of either male or female sexual dysfunction of selective antagonists of the alpha1B-adrenergic receptor and the pharmaceutical compositions containing them as compounds capable of helping the sexual act avoiding at th
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Page/Page column 12
(2010/02/14)
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- Benzothiazole derivatives with activity as adenosine receptor ligands
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The present invention relates to substituted benzothiazole derivitives and to their pharmaceutically acceptable salts useful for the treatment of diseases related to the adenosine receptor.
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- Aroylthioureas: New organic ionophores for heavy-metal ion selective electrodes
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Thiourea derivatives (46 aroylthioureas) having different substituents close to the sulfur atom were synthesized and their ionophore potential in ion selective electrodes (ISEs) was examined. Structural considerations were taken into account based on the corresponding heavy-metal ISE parameters. As ionophores, some 1-furoyl-3-substitnted thioureas (series 2) gave the best results in Pb(II), Hg(II) and Cd(II) ISEs. The strong intramolecular hydrogen bond in series 2 allows ligand interaction only through the C=S group. Substituents on the furan and phenyl rings give rise to low solubility in the membrane plasticizer. 3-Alkyl substituted furoylthioureas improve solubility but enhance oxidative processes with chain length. New X-ray diffraction (XRD) structures and theoretical DFT calculations were considered in the analysis of the substituent influence on the selectivity of ISEs. These new ionophores have advantages because of their stability, simple synthesis and easy modification of the sulfur binding ability resulting from substitution.
- Otazo-Sanchez, Elena,Perez-Marin, Leonel,Estevez-Hernandez, Osvaldo,Rojas-Lima, Susana,Alonso-Chamarro, Julian
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p. 2211 - 2218
(2007/10/03)
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- Use of selective antagonists of the α1B-adrenergic receptor for improvement of sexual dysfunction
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Described is the use in the treatment of either male or female sexual dysfunction of selective antagonists of the α1B-adrenergic receptor and the pharmaceutical compositions containing them as compounds capable of helping the sexual act avoidin
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- Tetrazole amide derivatives of heterocyclic alkenyl acid and their use as antiallergic substances
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Tetrazole amide derivatives of heterocyclic alkenyl acids, of general formula STR1 in which Y=NH, O or S when m=1; Y=N when m=2; m=1 or 2; l=0 or 4; R=H, C1-4 alkyl, Cl, Br, CF3, CH2 OCOCH3, or OCH2 -Ph; R1 =H, alkaline metal or alkaline earth metal, the double bond of the alkenyl chain being of trans or cis configuration and the possible benzene ring being unsubstituted or substituted. Such derivatives possess high antiallergic activity.
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- Tetrazole amide derivatives of heterocyclic alkenyl acids and their use as antiallergic substances
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Tetrazole amide derivatives of heterocyclic alkenyl acids, of general formula (I): in which, Y = NH, O or S when m = 1;, Y = N when m = 2;, m = 1 or 2;, l = 0 or 4;, R = H, C1 4 alkyl, Cl, Br, CF3, CH2OCOCH3, or OCH2-Ph;, R1 = H, alkaline metal or alkaline earth metal;, the double bond of the alkenyl chain being of trans or cis configuration and the possible benzene ring being unsubstituted or substituted. Said derivatives possess high antiallergic activity.
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