- Novel Pyrazole Derivatives Effectively Inhibit Osteoclastogenesis, a Potential Target for Treating Osteoporosis
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As human beings live longer, age-related diseases such as osteoporosis will become more prevalent. Intolerant side effects and poor responses to current treatments are observed. Therefore, novel effective therapeutic agents are greatly needed. Here, pyrazole derivatives were designed and synthesized, and their osteoclastogenesis inhibitory effects both in vitro and in vivo were evaluated. The most promising compound 13 with a 2-(dimethylamino)ethyl group inhibited markedly in vitro osteoclastogenesis as well as the bone resorption activity of osteoclasts. Compound 13 affected osteoclasts early proliferation and differentiation more than later fusion and maturation stages. In ovariectomized (OVX) mice, compound 13 can inhibit the loss of trabecular bone volume, trabecular bone number, and trabecular thickness. Moreover, compound 13 can antagonize OVX-induced reduction of serum bone resorption marker and then compensatory increase of the bone formation marker. To sum up, compound 13 has high potential to be developed into a novel therapeutic agent for treating osteoporosis in the future.
- Kuo, Ting-Hao,Lin, Tzu-Hung,Yang, Rong-Sen,Kuo, Sheng-Chu,Fu, Wen-Mei,Hung, Hsin-Yi
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p. 4954 - 4963
(2015/07/02)
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- Pd- and Cu-catalyzed C-H arylation of indazoles
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The palladium- and copper-catalyzed C-H arylation reactions of 1H- and 2H-indazoles with haloarenes are described. A PdCl2/phen/Ag 2CO3/K3PO4 catalytic system is effective for the C-H arylation of 1H- and 2H-indazoles with haloarenes, whereas a less expensive CuI/phen/LiOt-Bu catalytic system is applicable to the C-H coupling of substituted 2H-indazoles and iodoarenes. The utility of newly developed catalyst was demonstrated in the rapid synthesis of YC-1 (an antitumor agent) and YD-3 (platelet anti-aggregating agent). These new reactions represent important direct functionalization tools of indazoles, well-known bioisosteres of pharmaceutically important indole core.
- Hattori, Keika,Yamaguchi, Kazuya,Yamaguchi, Junichiro,Itami, Kenichiro
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experimental part
p. 7605 - 7612
(2012/09/07)
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- Design, synthesis and insight into the structure-activity relationship of 1,3-disubstituted indazoles as novel HIF-1 inhibitors
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Design, synthesis and insight into the structure-activity relationship (SAR) of 1,3-disubstituted indazoles as novel HIF-1 inhibitors are described. In particular, the substituted furan moiety on indazole skeleton as well as its substitution pattern turns
- An, Hongchan,Kim, Nam-Jung,Jung, Jong-Wha,Jang, Hannah,Park, Jong-Wan,Suh, Young-Ger
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p. 6297 - 6300
(2011/11/29)
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- Novel fused pyrazolyl compound
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A fused pyrazolyl compound of the following formula: wherein A, Ar1, Ar2, R1, R2, R3, and R4, are as defined herein. Also disclosed is a pharmaceutical composition containing an effective a
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Page/Page column 3; 5-6
(2010/02/14)
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- Preparation of highly functionalized heterocyclic zinc organometallics via a Li(acac)-catalysis of the I/Zn-exchange reaction
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The reaction of i-Pr2Zn in the presence of catalytic amount of Li(acac) in NMP with various functionalized heterocyclic iodides provides new polyfunctional diheteroarylzincs, which undergo smooth Negishi cross-coupling reactions and CuCN-2LiCl-
- Gong, Liu-Zhu,Knochel, Paul
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p. 267 - 270
(2007/10/03)
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- Blockade of voltage dependent sodium channels
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Compounds of formula (1), and pharmaceutically acceptable salts thereof, are capable of blockading voltage-dependent sodium channels and are useful in particular, in treating glaucoma and multiple sclerosis.
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- 1-Benzyl-3-(5′-hydroxymethyl-2′-furyl)-indazole (YC-1) derivatives as novel inhibitors against sodium nitroprusside-induced apoptosis
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Antiapoptotic agents based on 1-benzyl-3-(5′-hydroxymethyl-2′-furyl)indazole (22, YC-1) derivatives were explored for effective treatment of sepsis and septic shock. We found that compound 22, 1-benzyl-3-(5′-methoxymethyl-2′-furyl)indazole (27), and 1-phe
- Lien, Jin-Cherng,Lee, Fang-Yu,Huang, Li-Jiau,Pan, Shiow-Lin,Guh, Jih-Hwa,Teng, Che-Ming,Kuo, Sheng-Chu
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p. 4947 - 4949
(2007/10/03)
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- Synthesis of 1-benzyl-3-(5′-hydroxymethyl-2′-furyl)indazole analogues as novel antiplatelet agents
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1-Benzyl-3-(5′-hydroxymethyl-2′-furyl)indazole (28, YC-1) was selected as the lead compound for systemic structural modification. After screening for antiplatelet activity, SARs of YC-1 analogues were established. Among these potent active derivatives, co
- Le,Lien,Huang,Huang,Tsai,Teng,Wu,Cheng,Kuo
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p. 3746 - 3749
(2007/10/03)
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- A Convenient Route to the Soluble Guanylate Cyclase Activator YC-1 and its N2 Regioisomer
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A new route to the soluble guanylate cyclase (sGC) activator YC-1 and its N2 regioisomer has been established with a Mitsunobu mediated N-alkylation as the key step. The route is utilised in the synthesis of a potential photoaffinity label.
- Fernandez, Patricia A.,Bellamy, Tom,Kling, Marcel,Madge, David J.,Selwood, David L.
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p. 1813 - 1816
(2007/10/03)
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- An improved synthesis of YC-1
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A concise synthesis of YC-1 has been achieved in ten-fold enhanced yield over the previously reported method. This new, flexible strategy should readily allow the automated parallel synthesis of analogues.
- Gordon, David W.
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p. 1065 - 1066
(2007/10/03)
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