Abstract:
:Structure-activity relationships of 2-alkynyladenine derivatives were explored by varying substituents at the 9-, 8- and 2-positions of the purine moiety in order to optimize A2A adenosine receptor antagonist activity in vitro. A propargyl group at the 9-position was found to be important for A2A antagonist activity, and the introduction of a halogen, aryl, or heteroaryl at the 8-position further enhanced activity. A series of 8-substituted 2-alkynyl-N(9)-propargyladenine derivatives exhibited potent antagonist activity, with IC50 values in the low nM range. Compound 4a from this series was found to be orally active at a dose of 3 mg/kg in a mouse catalepsy model and a 6-hydroxydopamine-lesioned rat model of Parkinson's disease.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Endo K,Deguchi K,Matsunaga H,Tomaya K,Yamada Kdoi
10.1016/j.bmc.2014.04.041subject
Has Abstractpub_date
2014-06-15 00:00:00pages
3072-82issue
12eissn
0968-0896issn
1464-3391pii
S0968-0896(14)00306-Xjournal_volume
22pub_type
杂志文章abstract::Four palladium(II) and platinum(II) saccharinate (sac) complexes with 2-(hydroxymethyl)pyridine (2-hmpy) and 2-(2-hydroxyethyl)pyridine (2-hepy), namely trans-[Pd(2-hmpy)2(sac)2]·H2O (1), trans-[Pt(2-hmpy)2(sac)2]·3H2O (2), trans-[Pd(2-hepy)2(sac)2] (3) and trans-[Pt(2-hepy)2(sac)2] (4), have been synthesized and char...
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abstract::The inhibition of two human cytosolic carbonic anhydrase isozymes I and II, with some novel glycine and phenylalanine sulfonamide derivatives were investigated. Newly synthesized compounds G1-4 and P1-4 showed effective inhibition profiles with KI values in the range of 14.66-315μM for hCA I and of 18.31-143.8μM again...
journal_title:Bioorganic & medicinal chemistry
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abstract::Cancer cells reprogram their metabolism due to genetic alteration to compensate for increased energy demand and enhanced anabolism, cell proliferation, and protection from oxidative damage. Here, we assessed the cytotoxicity of three dimeric naphthoquinones against the glycolytic MCF-7 versus the oxidative MDA-453 bre...
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更新日期:2011-12-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.06.041
更新日期:2012-01-15 00:00:00
abstract::Hypoxia is a common characteristic of many types of solid tumors and is associated with tumor propagation, malignant progression, and resistance to anti-cancer therapy. HIF-1 pathway is one of the survival pathways activated in tumor in response to hypoxia. In hypoxic condition, hypoxia-inducible factor-1α (HIF-1α) is...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
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abstract::Quinones are essential components in most cell and organelle bioenergetic processes both for direct electron and/or proton transfer reactions but also as means to regulate various bioenergetic processes by sensing cell redox states. To understand how quinones interact with proteins, it is important to have tools for i...
journal_title:Bioorganic & medicinal chemistry
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abstract::A less than adequate therapeutic plan for the treatment of anthrax in the 2001 bioterrorism attacks has highlighted the importance of developing alternative or complementary therapeutic approaches for biothreat agents. In these regards passive immunization possesses several important advantages over active vaccination...
journal_title:Bioorganic & medicinal chemistry
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abstract::T22 ([Tyr5,12,Lys7]-polyphemusin II) has been shown to have strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2',3'-dideoxythymidine (AZT). T22, an 18-residue peptide amide, takes an antiparallel beta-sheet structure that is maintained by two disulfide bridges. Herein we synthesize...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry
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更新日期:2008-05-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.06.047
更新日期:2014-09-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/j.bmc.2008.01.051
更新日期:2008-04-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/j.bmc.2008.08.079
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/j.bmc.2013.08.053
更新日期:2013-11-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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abstract::Eighty-five arylazoenamines, characterized by different types of aryl and basic moieties, have been synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of ten RNA and DNA viruses. The most commonly affected viruses were, in decreasing order, CVB-2, RSV, BVDV, YFV, and...
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journal_title:Bioorganic & medicinal chemistry
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abstract::Addressing the actin cytoskeleton as future anticancer target can be an innovative chemotherapeutic approach to combat malignancies. Doliculide is a potent stabilizer of actin filaments and can be used as tool and therapeutic lead in cancer research. Though a variety of molecules are known to bind to actin and lead to...
journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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abstract::We have previously found that T22 ([Tyr(5,12), Lys7]-polyphemusin II) has strong anti-human immunodeficiency virus (HIV) activity, and that T22 inhibits T cell-line-tropic HIV-1 infection mediated by CXCR4/fusin. T22 is an 18-residue peptide amide, which takes an antiparallel beta-sheet structure that is maintained by...
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journal_title:Bioorganic & medicinal chemistry
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abstract::The efficacy of anthracycline based anticancer drugs is limited by pleiotropic drug resistance of tumor cells. Aiming at the design of anthracyclinone congeners capable of circumventing drug resistance, we synthesized naphthoindole containing derivatives of tryptophan and tryptamine. In doing so we adapted the traditi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.01.034
更新日期:2007-04-01 00:00:00
abstract::A new (1→6)-linked thiodisaccharide formed by two galactofuranosyl units has been synthesized. Methyl (methyl α,β-D-galactofuranosid)uronate was employed as the starting compound, which was per-O-silylated with TBSCl and reduced with LiAlH4 to afford methyl 2,3,5-tri-O-tert-butyldimethylsilyl-β-D-galactofuranoside (2β...
journal_title:Bioorganic & medicinal chemistry
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更新日期:2013-06-01 00:00:00