Piperidine-based renin inhibitors: upper chain optimization.

abstract：:A simple and rapid NMR method is described to determine the logP of pharmaceutical agents. This method is highly versatile and efficient, because it does not require the use of deuterated solvents or the addition of any internal/external standards to the sample. We demonstrate that logP can be accurately measured usin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mo H,Balko KM,Colby DA

更新日期：2010-11-15 00:00:00

abstract：:A series of prenylflavonoids with multiple hydroxyl groups were synthesized and evaluated for their vasorelaxant activities against rat aorta rings pre-contracted by phenylephrine (PE), as well as their neuroprotective effects against OGD induced PC12 cell injury. The results indicated that the prenyl group at A-ring ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dong X,Qi L,Jiang C,Chen J,Wei E,Hu Y

更新日期：2009-06-15 00:00:00

abstract：:A series of 2,6-dimethoxylpyridinyl phosphine oxides have been synthesized and examined for their antitumor activity. 2,6-Dimethoxy-3-phenyl-4-diphenylphosphinoylpyridine 2 has been employed as the lead compound for this study. We found out that the presence of phosphine oxide on the 2,6-dimethoxylpyridine ring is imp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lam KH,Gambari R,Yuen MC,Kan CW,Chan P,Xu L,Tang W,Chui CH,Cheng GY,Wong RS,Lau FY,Tong CS,Chan AK,Lai PB,Kok SH,Cheng CH,Chan AS,Tang JC

更新日期：2009-04-15 00:00:00

abstract：:Surface enhanced resonance Raman scattering (SERRS) is an alternative to fluorescence for use in bioanalysis however due to the different optical mechanism it requires specifically designed reporters. Recently we have reported the use of 8-hydroxyquinolinyl azo dyes and their ester derivatives as reporters of lipase a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ingram A,Moore BD,Graham D

更新日期：2009-03-15 00:00:00

abstract：:To investigate the stability of 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentafuranosylcytosine 3'-phosphoric acid, its thymidine ester was prepared via the phosphoramidite method using allyl protection for the phosphate function. This ester is stable under acidic conditions but extremely labile under basic conditions, de...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hayakawa Y,Kawai R,Otsuki K,Kataoka M,Matsuda A

更新日期：1998-09-22 00:00:00

abstract：:Eighteen new hydrazino-1,3-thiazole derivatives were evaluated against 8 strains of multi-resistant Candida spp. Introduction of an indolyl moiety linked to the hydrazone function enhanced the in vitro anti-Candida activity, with an activity spectrum towards Candida albicans strains. Introduction of a (S)-2-aminoethyl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Maillard LT,Bertout S,Quinonéro O,Akalin G,Turan-Zitouni G,Fulcrand P,Demirci F,Martinez J,Masurier N

更新日期：2013-03-15 00:00:00

abstract：:Novel 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives have been prepared and their synthesis described herein. In vitro affinities for delta-, micro-, and kappa-opioid receptors are reported. Evaluation of some representative compounds from this series in the mouse neonatal ultrasonic vocalization test and the mo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Trabanco AA,Aerts N,Alvarez RM,Andrés JI,Boeckx I,Fernández J,Gómez A,Janssens FE,Leenaerts JE,De Lucas AI,Matesanz E,Steckler T,Pullan S

更新日期：2007-07-15 00:00:00

abstract：:Herein we report the optimization efforts to ameliorate the potent CYP3A4 time-dependent inhibition (TDI) and low aqueous solubility exhibited by a previously identified lead compound from our NAMPT inhibitor program (1, GNE-617). Metabolite identification studies pinpointed the imidazopyridine moiety present in 1 as ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zak M,Liederer BM,Sampath D,Yuen PW,Bair KW,Baumeister T,Buckmelter AJ,Clodfelter KH,Cheng E,Crocker L,Fu B,Han B,Li G,Ho YC,Lin J,Liu X,Ly J,O'Brien T,Reynolds DJ,Skelton N,Smith CC,Tay S,Wang W,Wang Z,Xi

更新日期：2015-02-01 00:00:00

abstract：:Thirty-two new derivatives of cerpegin (1,1,5-trimethylfuro[3,4-c]pyridine-3,4-dione) were designed and synthesized in high yield by a new method, combining several C(1) and N(5) substituents. All compounds were tested for their inhibitory effect on the CT-L, T-L and PA proteolytic activities of a purified mammalian 2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hovhannisyan A,Pham TH,Bouvier D,Qin L,Melikyan G,Reboud-Ravaux M,Bouvier-Durand M

更新日期：2013-05-01 00:00:00

abstract：:Novel quinolone-macrocycle conjugates displayed submicromolar antibacterial activity against Escherichia coli and Staphylococcus aureus bacterial strains. An analogous open-chain structure was not active at 100 microM against the same pathogenic strains. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jefferson EA,Swayze EE,Osgood SA,Miyaji A,Risen LM,Blyn LB

更新日期：2003-05-19 00:00:00

abstract：:A novel indole series of PGD2 receptor (DP receptor) antagonists is presented. Optimization of this series led to the identification of potent and selective DP receptor antagonists. In particular, antagonists 35 and 36 were identified with Ki values of 2.6 and 1.8 nM, respectively. These two antagonists are also poten...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sturino CF,Lachance N,Boyd M,Berthelette C,Labelle M,Li L,Roy B,Scheigetz J,Tsou N,Brideau C,Cauchon E,Carriere MC,Denis D,Greig G,Kargman S,Lamontagne S,Mathieu MC,Sawyer N,Slipetz D,O'Neill G,Wang Z,Zamboni R

更新日期：2006-06-01 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：:A number of molecular recognition features have been exploited in structure-based design of selective Cathepsin inhibitors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bethel PA,Gerhardt S,Jones EV,Kenny PW,Karoutchi GI,Morley AD,Oldham K,Rankine N,Augustin M,Krapp S,Simader H,Steinbacher S

更新日期：2009-08-15 00:00:00

abstract：:A combinatorial synthesis process involving sequential cycles of cutting a membrane support into pieces and combining these into groups and subjecting the groups to simultaneous solid-phase chemical reactions is demonstrated by the rapid assembly of four hundred N-terminally biotinylated, soluble, octameric peptide po...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dittrich F,Tegge W,Frank R

更新日期：1998-09-08 00:00:00

abstract：:Several analogues of the potent anthelmintic praziquantel were prepared with variation in the aromatic ring. The biological activity of these analogues was evaluated and compared against known analogues. Amination of the ring was tolerated while other variations were not. These results have important implications for ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ronketti F,Ramana AV,Chao-Ming X,Pica-Mattoccia L,Cioli D,Todd MH

更新日期：2007-08-01 00:00:00

abstract：:Twenty three side chain analogs of the crambescidin alkaloids were prepared from the corresponding pentacyclic zwitterionic core acid. In the crambescidin 800 and 657 series, potency increased with increasing chain length. In addition, substantial variations in tumor selectivity with structure were seen. Crambescidin ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aron ZD,Pietraszkiewicz H,Overman LE,Valeriote F,Cuevas C

更新日期：2004-07-05 00:00:00

abstract：:The synthesis and biological evaluation of novel human A-FABP inhibitors based on the 6-(trifluoromethyl)pyrimidine-4(1H)-one scaffold is described. Two series of compounds, bearing either an amino or carbon substituent in the 2-position of the pyrimidine ring were investigated. Modification of substituents and chain ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ringom R,Axen E,Uppenberg J,Lundbäck T,Rondahl L,Barf T

更新日期：2004-09-06 00:00:00

abstract：:A series of novel amino acid ester derivatives of 2,3-substituted isoindolinones was synthesized and evaluated for p53-mediated apoptotic activity. The rationale for augmentation of the target activity of 2,3-substituted isoindolinones was based on the introduction of new fragments in the structure of the inhibitor th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grigoreva TA,Novikova DS,Petukhov AV,Gureev MA,Garabadzhiu AV,Melino G,Barlev NA,Tribulovich VG

更新日期：2017-12-01 00:00:00

abstract：:Gynostemma pentaphyllum has been widely used as a traditional herb for its antioxidant and immunostimulatory activities. We have previously reported several useful dammarane-type saponins with cytotoxicity against A549 human lung cancer cells from heat-processed G. pentaphyllum. In this study, a new dammarane-type sap...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xing SF,Jang M,Wang YR,Piao XL

更新日期：2016-04-01 00:00:00

abstract：:The triaryl bis-sulfone 1 was modified by converting the aryl A-ring to a piperidine ring. The piperidine ring was further elaborated to a spirocyclopropyl piperidine moiety. The effect on CB2 binding potency, rat calcium channel affinity, and CYP 2C9 inhibition is described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gilbert EJ,Zhou G,Wong MK,Tong L,Shankar BB,Huang C,Kelly J,Lavey BJ,McCombie SW,Chen L,Rizvi R,Dong Y,Shu Y,Kozlowski JA,Shih NY,Hipkin RW,Gonsiorek W,Malikzay A,Lunn CA,Favreau L,Lundell DJ

更新日期：2010-01-15 00:00:00

abstract：:The strategy and SAR studies that led to the discovery of a novel potent and orally available 5-lipoxygenase (5-LO) inhibitor 3-(4-fluorophenyl)-6-({4-[(1S)-1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-1-benzothiophene-2-carboxamide ((S)-2l or MK-5286) were described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li L,Berthelette C,Chateauneuf A,Ouellet M,Sturino CF,Wang Z

更新日期：2010-12-15 00:00:00

abstract：:Recent studies have highlighted a key role in regulating gene transcription, in both eukaryotes and prokaryotes, by enzymes that control the acetylation and deacetylation of histones. In particular, inhibitors of histone deacetylases (HDAC-Is) have been shown effective in controlling the development of many parasites,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Giannini G,Battistuzzi G,Vignola D

更新日期：2015-02-01 00:00:00

abstract：:The effect of 2,3 modifications on the antibacterial activity of ketolides was evaluated by introducing substituents in position 2 and converting the C-1, C-2, C-3 beta-keto-ester into stable 2,3 enol-ether or 2,3 anhydro derivatives. Introduction of a fluorine in C-2 is beneficial with regard to the overall antibacte...

journal_title：Bioorganic & medicinal chemistry letters

authors： Denis A,Bretin F,Fromentin C,Bonnet A,Piltan G,Bonnefoy A,Agouridas C

更新日期：2000-09-04 00:00:00

abstract：:In order to exploit cyclophilin as a potential target for neurological drug design, we demonstrate in this presentation that several nonimmunosuppressant analogues of cyclosporin A, modified at the various positions in the 'effector' domain, are equipotent nerve growth agents compared to cyclosporin A. Our results sug...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wei L,Steiner JP,Hamilton GS,Wu YQ

更新日期：2004-09-06 00:00:00

abstract：:A series of analogs of GLP-1(7-36) amide containing a Nepsilon-(2-[2-[2-(3-maleimidopropylamido)ethoxy]ethoxy]acetyl)lysine has been synthesized and the resulting derivatives were bioconjugated to Cys34 of human serum albumin (HSA). The GLP-1-HSA bioconjugates were analyzed in vitro to assess the stabilizing effect of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Léger R,Thibaudeau K,Robitaille M,Quraishi O,van Wyk P,Bousquet-Gagnon N,Carette J,Castaigne JP,Bridon DP

更新日期：2004-09-06 00:00:00

abstract：:A series of amino-pyrimidines was developed based upon an initial kinase cross-screening hit from a CDK2 program. Kinase profiling and structure-based drug design guided the optimization from the initial 1,2,3-benzotriazole hit to a potent and selective JNK inhibitor, compound 24f (JNK1 and 2 IC(50)=16 and 66 nM, resp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Palmer WS,Alam M,Arzeno HB,Chang KC,Dunn JP,Goldstein DM,Gong L,Goyal B,Hermann JC,Hogg JH,Hsieh G,Jahangir A,Janson C,Jin S,Ursula Kammlott R,Kuglstatter A,Lukacs C,Michoud C,Niu L,Reuter DC,Shao A,Silva T,Tr

更新日期：2013-03-01 00:00:00

abstract：:We have focused on the C5-modification of 2'-deoxyuridine with substituted heterocycles for bioactivity, such as antiviral or anticancer activity. Herein, we report a novel class of nucleoside analogues with perfluoroalkyltriazole moiety as an anticancer drug candidate. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park SM,Yang H,Park SK,Kim HM,Kim BH

更新日期：2010-10-01 00:00:00

abstract：:Recently, a new class of selective integrin alpha5beta1inhibitors consisting of a heterocyclic based scaffold was published. Herein the SAR and pharmacokinetic profiles of N-phenyl piperidine derivatives are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zischinsky G,Osterkamp F,Vossmeyer D,Zahn G,Scharn D,Zwintscher A,Stragies R

更新日期：2010-01-01 00:00:00

abstract：:Chelerythrine, an isoquinoline alkaloid isolated from the herbaceous perennial Chelidonium majus, was found to potently and selectively inhibit an isoform of recombinant human monoamine oxidase-A (MAO-A) with an IC50 value of 0.55 µM. Chelerythrine was a reversible competitive MAO-A inhibitor (Ki = 0.22 µM) with a pot...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baek SC,Ryu HW,Kang MG,Lee H,Park D,Cho ML,Oh SR,Kim H

更新日期：2018-08-01 00:00:00

abstract：:A series of new voltage-gated sodium channel blockers were prepared based on the screening lead succinic diamide BPBTS. Replacement of the succinimide linker with the more rigid cyclic 1,2-trans-diamide linker was well tolerated. N-Methylation on the biphenylsulfonamide side of the amide moiety significantly reduced t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shao PP,Ok D,Fisher MH,Garcia ML,Kaczorowski GJ,Li C,Lyons KA,Martin WJ,Meinke PT,Priest BT,Smith MM,Wyvratt MJ,Ye F,Parsons WH

更新日期：2005-04-01 00:00:00