Syntheses of sphingosine-1-phosphate analogues and their interaction with EDG/S1P receptors.

abstract：:Aspartic protease analogues synthesized by covering the surface of silica gel with carboxyl groups effectively hydrolyzed hemoglobin and gamma-globulin. It is proposed that the carboxyl group is involved in both complexation of the protein substrate and the catalytic cleavage of the peptide bonds of the complexed prot...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim H,Chung YS,Paik H,Kim MS,Suh J

更新日期：2002-10-07 00:00:00

abstract：:We report the first synthesis of the C-terminally spermine-conjugated stapled peptide-based inhibitors of the p53-Mdm2 interaction. Subsequent biological, biophysical and cellular uptake assays with the spermine-conjugated stapled peptides revealed that spermine conjugation minimally affects biological activity while ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Muppidi A,Li X,Chen J,Lin Q

更新日期：2011-12-15 00:00:00

abstract：:In this communication, human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitory activities of a novel series of diarylsulfones are described. Optimization of this series resulted in several highly potent 11β-HSD1 inhibitors with excellent pharmacokinetic (PK) properties. Compound (S)-25 showed excellent eff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yan X,Wang Z,Sudom A,Cardozo M,DeGraffenreid M,Di Y,Fan P,He X,Jaen JC,Labelle M,Liu J,Ma J,McMinn D,Miao S,Sun D,Tang L,Tu H,Ursu S,Walker N,Ye Q,Powers JP

更新日期：2010-12-01 00:00:00

abstract：:We have synthesized 3 analogs of the dopamine D2 receptor (D2 DR) antagonist spiperone that can be conjugated to streptavidin-coated quantum dots via a pegylated biotin derivative. Using fluorescent imaging we demonstrate that substitution on the spiro position is tolerated, whilst the length and rigidity of a spacer ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tomlinson ID,Kovtun O,Crescentini TM,Rosenthal SJ

更新日期：2019-04-15 00:00:00

abstract：:Highly potent and novel derivatives of doxorubicin were linked to monoclonal antibodies (mAbs) for site-specific drug delivery. Drug linker 5 consisted of a dipeptide linker attached directly to the daunosamine nitrogen of the n-butyldiacetate doxorubicin derivative 2a. Upon hydrolysis of the peptide linker and acetat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jeffrey SC,Nguyen MT,Andreyka JB,Meyer DL,Doronina SO,Senter PD

更新日期：2006-01-15 00:00:00

abstract：:A series of 1,3,4-oxadiazol-2-ones was synthesized and tested for activity as antagonists at GPR55 in cellular beta-arrestin redistribution assays. The synthesis was designed to be modular in nature so that a sufficient number of analogues could be rapidly accessed to explore initial structure-activity relationships. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Meza-Aviña ME,Lingerfelt MA,Console-Bram LM,Gamage TF,Sharir H,Gettys KE,Hurst DP,Kotsikorou E,Shore DM,Caron MG,Rao N,Barak LS,Abood ME,Reggio PH,Croatt MP

更新日期：2016-04-01 00:00:00

abstract：:New RXR-selective modulators possessing a 6-fluoro trienoic acid moiety (6Z olefin) or a fluorinated/heterocyclic-substituted benzene core ring, were synthesized in an expedient and selective way. A subset of these compounds was evaluated for their metabolic properties (exposure in IRC male mice) and show a dramatic i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Michellys PY,Boehm MF,Chen JH,Grese TA,Karanewsky DS,Leibowitz MD,Liu S,Mais DA,Mapes CM,Reifel-Miller A,Ogilvie KM,Rungta D,Thompson AW,Tyhonas JS,Yumibe N,Ardecky RJ

更新日期：2003-11-17 00:00:00

abstract：:In the course of our studies of the structure-activity relationships of himbacine 1, a potent antagonist of the M(2) subtype of muscarinic receptor, the four title compounds, 2, ent-2, 3, and ent-3, were synthesized with a highly stereoselective intermolecular Diels-Alder reaction of tetrahydroisobenzofuran 4 with ach...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takadoi M,Yamaguchi K,Terashima S

更新日期：2002-11-18 00:00:00

abstract：:A novel series of imidazole-based small molecule antagonists of the melanocortin 4 receptor (MC4-R) is reported. Members of this series have been identified, which exhibit sub-micromolar binding affinity for the MC4-R, functional potency <100nM, and good oral exposure in rat. Antagonists of the MC4-R are potentially u...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marsilje TH,Roses JB,Calderwood EF,Stroud SG,Forsyth NE,Blackburn C,Yowe DL,Miao W,Drabic SV,Bohane MD,Daniels JS,Li P,Wu L,Patane MA,Claiborne CF

更新日期：2004-07-16 00:00:00

abstract：:New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sasaki S,Hashimoto T,Obana N,Yasuda H,Uehara Y,Maeda M

更新日期：1998-05-05 00:00:00

abstract：:The MAP kinase p38 plays a key role in the biosynthesis of the inflammatory cytokines TNF-alpha and IL-1. We have developed a novel series of potent p38 inhibitors that could lead to new methods of treatment for inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Henry JR,Rupert KC,Dodd JH,Turchi IJ,Wadsworth SA,Cavender DE,Schafer PH,Siekierka JJ

更新日期：1998-12-01 00:00:00

abstract：:AX10185, the phenyl amide of xanthurenic acid, was found to be a sub-100nM inhibitor of Lp-PLA(2). However, in the presence of EDTA the inhibitory activity of AX10185 was extinguished while the enzymatic activity of Lp-PLA(2) did not change. Subsequent metal screening experiments determined the inhibition to be Zn(2+)...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lin EC,Hu Y,Amantea CM,Pham LM,Cajica J,Okerberg E,Brown HE,Fraser A,Du L,Kohno Y,Ishiyama J,Kozarich JW,Shreder KR

更新日期：2012-01-15 00:00:00

abstract：:The first total synthesis of 6(E),8(Z),11(Z),13(E) 5-oxo-15-HETE 4 was accomplished. The synthetic material was evaluated with calcium mobilization assay and compared with 5-oxo-ETE the natural ligand for the OXE receptor. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patel P,Anumolu JR,Powell WS,Rokach J

更新日期：2011-03-15 00:00:00

abstract：:A series of pethidine analogs were synthesized and their affinities for the [(3)H]N-methyl-scopolamine (NMS) binding site on muscarinic acetylcholine receptors (mAChRs) were determined using M1, M3 or M5 human mAChRs expressed by Chinese hamster ovary (CHO) cell membranes. Compound 6b showed the highest binding affini...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee NR,Zhang X,Darna M,Dwoskin LP,Zheng G

更新日期：2015-11-15 00:00:00

abstract：:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as Apo2L, has been investigated in the past decade for its promising anticancer activity due to its ability to selectively induce apoptosis in tumoral cells by binding to TRAIL receptors (TRAIL-R). Macromolecules such as agonistic monoclonal a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ion GND,Nitulescu GM,Popescu CI

更新日期：2019-09-15 00:00:00

abstract：:Continuing study of the ethyl acetate (EtOAc) extract of the cultured soft coral Sinularia brassica afforded five new withanolides, sinubrasolides H-L (1-5). The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The cytotoxicities of new compounds 1-5 and a known compound sinubras...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang CY,Ahmed AF,Su JH,Sung PJ,Hwang TL,Chiang PL,Dai CF,Liaw CC,Sheu JH

更新日期：2017-08-01 00:00:00

abstract：:A stereocontrolled synthetic route has been used to prepare two of the geometric isomers of all-trans-GGPP. Neither of these isomers is effective substrates for mammalian GGTase I, but 3 is a potent inhibitor of this enzyme (IC(50)=100 nM). Surprisingly, both compounds are effective substrates for mammalian FTase. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zahn TJ,Whitney J,Weinbaum C,Gibbs RA

更新日期：2001-06-18 00:00:00

abstract：:We identified and tested bisphosphonates as inhibitors of a protozoan molecular target. Computational modeling studies demonstrated that these compounds are mimics of the natural substrate of the enzyme. The most potent bisphosphonates in vitro are pamidronate and risedronate, which inhibit the purine transferase from...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fernández D,Wenck MA,Craig SP 3rd,Delfino JM

更新日期：2004-09-06 00:00:00

abstract：:8-Iodo-11-(4-methylpiperazino)-5H-dibenzo[b,e][1,4]-diazepine: Iozapine, a potential D(4)-receptor ligand was synthesized using oxidative iodo-destannylation reaction. The preliminary biodistribution studies of radioiodinated iozapine have shown that the compound is taken up in the brains of mice and rabbits. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Joshua AV,Sharma SK,Strelkov A,Scott JR,Martin-Iverson MT,Abrams DN,Silverstone PH,McEwan AJ

更新日期：2007-07-15 00:00:00

abstract：:Human telomeric DNA is transcribed into telomeric RNA in cells. Telomeric RNA performs the fundamental biological functions such as regulation and protection of chromosome ends. This digest highlights the human telomere RNA G-quadruplex structures, telomere RNA functions, G-quadruplex-binding small molecules, and futu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu Y

更新日期：2018-08-15 00:00:00

abstract：:A new series of diarylureas and diarylamides possessing 1H-pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-9 human melanoma cell line panel were tested. All the target compounds, except three amino derivatives 8g, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jung MH,El-Gamal MI,Abdel-Maksoud MS,Sim T,Yoo KH,Oh CH

更新日期：2012-07-01 00:00:00

abstract：:Using a phenotypic screening and SAR optimization approach, a phenyl-bis-oxazole derivative has been identified with anti-proliferative activity, optimized with the use of a panel of cancer cell lines. The lead compound was synthesized by means of a short and effective two-step synthesis using Pd-catalyzed direct aryl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohnmacht SA,Ciancimino C,Vignaroli G,Gunaratnam M,Neidle S

更新日期：2013-10-01 00:00:00

abstract：:By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 μM; MIC = 0.48 μM) than the positive controls AHA (IC50 = 17.2 μM) and Metronidazole (MIC = 31.3 ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang YS,Su MM,Zhang XP,Liu QX,He ZX,Xu C,Zhu HL

更新日期：2018-10-15 00:00:00

abstract：:In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel structurally diverse PEG-based 20(S)-CPT sulfonylamidine derivatives were designed, synthesized via a Cu-multicomponent reaction (MCR), and evaluated for cytotoxicity against four human tumor cell lines (A-549, MDA-MB-231, KB, and KBvin). A...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song ZL,Chen HL,Wang YH,Goto M,Gao WJ,Cheng PL,Morris-Natschke SL,Liu YQ,Zhu GX,Wang MJ,Lee KH

更新日期：2015-07-01 00:00:00

abstract：:A series of alisol A derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and cytotoxicities in vitro. The preliminary investigation demonstrates that simple modifications of the parent structure of alisol A can produce a number of potentially important derivatives against HBV. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang Q,Jiang ZY,Luo J,Cheng P,Ma YB,Zhang XM,Zhang FX,Zhou J,Chen JJ

更新日期：2008-08-15 00:00:00

abstract：:Lactimidomycin (LTM, 1), iso-migrastatin (iso-MGS, 2) and migrastatin (MGS, 3) are macrolide antitumor antibiotics differing in macrolide ring size but all bearing a glutarimide side chain. To further develop these natural products and related analogs as drug candidates we have produced and evaluated the biological ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ju J,Rajski SR,Lim SK,Seo JW,Peters NR,Hoffmann FM,Shen B

更新日期：2008-11-15 00:00:00

abstract：:The viral enzyme integrase is essential for the replication of HIV-1 and, after the discovery of Isentress, represents a validated target for anti-retroviral therapy. Incorporation of the dihydroxycarbonyl pharmacophore into a pyrrolinone scaffold led to the discovery of 5-pyrrolinone-3-carboxamides as a structurally ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pace P,Spieser SA,Summa V

更新日期：2008-07-15 00:00:00

abstract：:The voltage gated sodium channel Nav1.7 plays an essential role in the transmission of pain signals. Strong human genetic validation has motivated extensive efforts to discover potent, selective, and efficacious Nav1.7 inhibitors for the treatment of chronic pain. This digest will introduce the structure and function ...

journal_title：Bioorganic & medicinal chemistry letters

authors： McKerrall SJ,Sutherlin DP

更新日期：2018-10-15 00:00:00

abstract：:A uHTS campaign led to the discovery of a 5-(5-furan-2-ylpyrazol-1-yl)-1H-benzimidazole series that inhibits assembly of HIV-1 capsid. Synthetic manipulations at N1, C2 and C16 positions improved the antiviral potency by a . The X-ray structure of 33 complexed with the capsid N-terminal domain allowed identification o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tremblay M,Bonneau P,Bousquet Y,DeRoy P,Duan J,Duplessis M,Gagnon A,Garneau M,Goudreau N,Guse I,Hucke O,Kawai SH,Lemke CT,Mason SW,Simoneau B,Surprenant S,Titolo S,Yoakim C

更新日期：2012-12-15 00:00:00

abstract：:In an effort to develop antagonists for kappa-mu opioid receptor heterodimers, a series of bivalent ligands 3-6 containing kappa- and mu-antagonist pharmacophores were designed and synthesized. Evaluation of the series in HEK-293 cells revealed 4 (KMN-21) to selectively antagonize the activation of kappa-mu heterodime...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang S,Yekkirala A,Tang Y,Portoghese PS

更新日期：2009-12-15 00:00:00