Synthesis and biological evaluation of a C5-biphenyl thiolactomycin library.

abstract：:Using molecular modeling and rationally designed structural modifications, the multi-target structure-activity relationship for a series of ranitidine analogs has been investigated. Incorporation of a variety of isosteric groups indicated that appropriate aromatic moieties provide optimal interactions with the hydroph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gao J,Midde N,Zhu J,Terry AV,McInnes C,Chapman JM

更新日期：2016-11-15 00:00:00

abstract：:Although PK11195 binds to the peripheral benzodiazepine receptor with nanomolar affinity, significant data exist which suggest that it has another cellular target distinct from the PBR. Here we demonstrate that PK11195 inhibits F(1)F(0)-ATPase activity in an OSCP-dependent manner, similar to the pro-apoptotic benzodia...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cleary J,Johnson KM,Opipari AW Jr,Glick GD

更新日期：2007-03-15 00:00:00

abstract：:Novel conformationally-restricted mTOR kinase inhibitors with cyclic sulfone scaffold were designed. Synthesis and structure-activity relationship (SAR) studies are described with emphasis on optimization of the mTOR potency and selectivity against class I PI3Kα kinase. PF-05139962 was identified with excellent mTOR b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu KK,Bailey S,Dinh DM,Lam H,Li C,Wells PA,Yin MJ,Zou A

更新日期：2012-08-01 00:00:00

abstract：:In order to improve the analgesic activity of lead compound 7a, two series of dispirocyclopiperazinium (DSPZ) salts 9a-h, 10a-e and compounds 14, 15 were synthesized and evaluated for their in vivo analgesic activity both by acetic acid induced writhing test and hot plate test. Compounds 9h, 14, and 15 exhibited bette...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li A,Wang X,Yue CQ,Ye J,Li CL,Li RT

更新日期：2007-09-15 00:00:00

abstract：:Selectivity of enzymatic and chemical methods for transesterifications of cytarabine with divinyl dicarboxylates was described. Catalysis by lipase acrylic resin from Candida antarctica (CAL-B) in acetone facilitated the single step synthesis of polymerizable 5'-O-acyl cytarabine derivatives in high yields, while the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang N,Chen ZC,Lu DS,Lin XF

更新日期：2005-09-15 00:00:00

abstract：:The ability of serine phosphate (SerP) or alpha-amino-gamma-phosphonobutyric acid (AbuP) and arginine to form a salt bridge between their side chains appears to be much greater when they are spaced i/i+4 than when they are spaced i/i+3. The side chain-side chain interaction between SerP/Arg and AbuP/Arg, positioned i/...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liehr S,Chenault HK

更新日期：1999-09-20 00:00:00

abstract：:10, 15, 20-Triphenyl-5-(4-hydroxy-3-(trimethylammonium)methyl)phenylporphyrin 4 and its zinc complex 5 have been synthesized and antibacterial activities have been studied for 4 and its derivative. Compound 4 showed stronger inhibition than that of 10, 15, 20-triphenyl-5-(4-hydroxy-3-(dimethylamine)methyl)phenylporphy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang J,Wu X,Cao X,Yang F,Wang J,Zhou X,Zhang XL

更新日期：2003-03-24 00:00:00

abstract：:We report the use of fragment screening and fragment based drug design to develop a PI3γ kinase fragment hit into a lead. Initial fragment hits were discovered by high concentration biochemical screening, followed by a round of virtual screening to identify additional ligand efficient fragments. These were developed i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hughes SJ,Millan DS,Kilty IC,Lewthwaite RA,Mathias JP,O'Reilly MA,Pannifer A,Phelan A,Stühmeier F,Baldock DA,Brown DG

更新日期：2011-11-01 00:00:00

abstract：:In an effort to identify novel, broad-spectrum inhibitors against the metallo-β-lactamases (MβLs), several N-heterocyclic derivatives were tested as inhibitors of MβLs CcrA, ImiS, and L1, which are representative enzymes from the distinct MβL subclasses. Three N-heterocyclic dicarboxylic acid derivatives were competit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Feng L,Yang KW,Zhou LS,Xiao JM,Yang X,Zhai L,Zhang YL,Crowder MW

更新日期：2012-08-15 00:00:00

abstract：:A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 13b displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-pyrrolidine 13b-1 possessed a Ki of 1....

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen C,Jiang W,Tran JA,Tucci FC,Fleck BA,Markison S,Wen J,Madan A,Hoare SR,Foster AC,Marinkovic D,Chen CW,Arellano M,Saunders J

更新日期：2008-01-01 00:00:00

abstract：:GSK2126458 is a highly potent inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with low picomolar to subnanomolar activity. [(11)C]GSK2126458 and [(18)F]GSK2126458, new potential PET agents for imaging of PI3K and mTOR in cancer, were first designed and synthesized in 40-50% and 2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Gao M,Miller KD,Sledge GW,Zheng QH

更新日期：2012-02-15 00:00:00

abstract：:Ascorbic acid 2-glucoside (AA-2G) has been widely used in cream and lotion types of cosmetic products. Thus, the degradation of AA-2G caused by the temperature change and pH variation was very critical for determining the bio-functionality of cosmetics. Response surface methodology (RSM) was introduced to study the in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang WY,Lee PC,Huang LK,Lu LP,Liao WC

更新日期：2013-03-15 00:00:00

abstract：:A high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li D,Gao N,Zhu N,Lin Y,Li Y,Chen M,You X,Lu Y,Wan K,Jiang JD,Jiang W,Si S

更新日期：2015-11-15 00:00:00

abstract：:A novel series of diphenylpyridylethanamine-based inhibitors of cholesteryl ester transfer protein is described. Optimization of the urea moiety, particularly by incorporation of fluorine, is explored to balance in vitro metabolic stability with CETP potency in the whole plasma assay. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miller MM,Liu Y,Jiang J,Johnson JA,Kamau M,Nirschl DS,Wang Y,Harikrishnan L,Taylor DS,Chen AY,Yin X,Seethala R,Peterson TL,Zvyaga T,Zhang J,Huang CS,Wexler RR,Poss MA,Lawrence RM,Adam LP,Salvati ME

更新日期：2012-10-15 00:00:00

abstract：:The histone methylation on lysine residues is one of the most studied post-translational modifications, and its aberrant states have been associated with many human diseases. In 2012, Kruidenier et al. reported GSK-J1 as a selective Jumonji H3K27 demethylase (JMJD3 and UTX) inhibitor. However, there is limited informa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hu J,Wang X,Chen L,Huang M,Tang W,Zuo J,Liu YC,Shi Z,Liu R,Shen J,Xiong B

更新日期：2016-02-01 00:00:00

abstract：:We disclose a new compound class of potent and selective alpha-1A adrenergic receptor antagonists exemplified by the geminally, disubstituted cyclic imide 7. The optimization of lead compounds resulting in the cyclic imide motif is highlighted. The results of in vitro and in vivo studies of selected compounds are pres...

journal_title：Bioorganic & medicinal chemistry letters

authors： DiPardo RM,Patane MA,Newton RC,Price R,Broten TP,Chang RS,Ransom RW,Di Salvo J,Freidinger RM,Bock MG

更新日期：2001-07-23 00:00:00

abstract：:A rational fluorine scan based on co-crystal structures was explored to increase the potency of a series of selective BTK inhibitors. While fluorine substitution on a saturated bicyclic ring system yields no apparent benefit, the same operation on an unsaturated bicyclic ring can increase HWB activity by up to 40-fold...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lou Y,Sweeney ZK,Kuglstatter A,Davis D,Goldstein DM,Han X,Hong J,Kocer B,Kondru RK,Litman R,McIntosh J,Sarma K,Suh J,Taygerly J,Owens TD

更新日期：2015-01-15 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：:Novel 3,4-diarylpyrazolines 1 as potent CB1 receptor antagonists with lipophilicity lower than that of SLV319 are described. The key change is the replacement of the arylsulfonyl group in the original series by a dialkylaminosulfonyl moiety. The absolute configuration (4S) of eutomer 24 was established by X-ray diffra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lange JH,van Stuivenberg HH,Veerman W,Wals HC,Stork B,Coolen HK,McCreary AC,Adolfs TJ,Kruse CG

更新日期：2005-11-01 00:00:00

abstract：:The design and synthesis of a series of novel, reversible, small molecule inhibitors of caspase-3 are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Allen DA,Pham P,Choong IC,Fahr B,Burdett MT,Lew W,DeLano WL,Gordon EM,Lam JW,O'Brien T,Lee D

更新日期：2003-11-03 00:00:00

abstract：:The synthesis and biological activities of a series of new 1beta-methylcarbapenems 1a-h having heteroaromatic thioether moiety at C-5 position of pyrrolidine were described. Among these compounds, 1,2,3-thiadiazole derivative 1h showed the most potent antibacterial activity and advanced pharmacokinetics in comparison ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shin KJ,Koo KD,Yoo KH,Kang YK,Park SW,Kim DJ

更新日期：2001-09-03 00:00:00

abstract：:Synthesis and biological evaluation of new chrysene derivatives aimed at the development of anticancer agents were carried out. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Becker FF,Banik BK

更新日期：1998-10-20 00:00:00

abstract：:A series of thieno[3,2-b]quinoline derivatives designed based on A-278637 scaffold, were synthesized efficiently via one-pot three-component reaction under solvent-free and catalyst-free conditions. This work provides a new compound library with potential biological activity for biomedical screening. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li T,Feng X,Yao C,Yu C,Jiang B,Tu S

更新日期：2011-01-01 00:00:00

abstract：:In an effort to find potential anxiolytic and/or antipsychotic agents with selective 5-HT(2C) affinity a series of new pyrimidine derivatives was prepared and the binding affinities for 5-HT(2A) and 5-HT(2C) receptors were determined. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bózsing D,Simonek I,Simig G,Jakóczi I,Gacsályi I,Lévay G,Tihanyi K,Schmidt E

更新日期：2002-11-04 00:00:00

abstract：:The structure-activity relationship and the synthesis of novel N-[(3S)-pyrrolidin-3-yl]benzamides as dual serotonin and noradrenaline monoamine reuptake inhibitors (SNRI) is described. Preferred compound 9 aka PF-184,298 is a potent SNRI with good selectivity over dopamine reuptake inhibition (DRI), good in vitro meta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wakenhut F,Allan GA,Fish PV,Fray MJ,Harrison AC,McCoy R,Phillips SC,Ryckmans T,Stobie A,Westbrook D,Westbrook SL,Whitlock GA

更新日期：2009-09-01 00:00:00

abstract：:A series of benzotriazole phenyldifluoromethylphosphonic acids were found to be potent PTP-1B inhibitors. Molecular modeling on the X-ray crystal structure of the lead structure led to the design of potent PTP-1B inhibitors that show moderate selectivity against TC-PTP, a very closely related protein tyrosine phosphat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lau CK,Bayly CI,Gauthier JY,Li CS,Therien M,Asante-Appiah E,Cromlish W,Boie Y,Forghani F,Desmarais S,Wang Q,Skorey K,Waddleton D,Payette P,Ramachandran C,Kennedy BP,Scapin G

更新日期：2004-02-23 00:00:00

abstract：:Factor Xa, a critical serine protease in the blood coagulation cascade, has become a target for inhibition as a strategy for the invention of novel anti-thrombotic agents. Here we describe the development of phenylglycine containing benzamidine carboxamides as novel, potent and selective inhibitors of factor Xa. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jones SD,Liebeschuetz JW,Morgan PJ,Murray CW,Rimmer AD,Roscoe JM,Waszkowycz B,Welsh PM,Wylie WA,Young SC,Martin H,Mahler J,Brady L,Wilkinson K

更新日期：2001-03-12 00:00:00

abstract：:There is tremendous interest in developing activator artificial transcription factors that functionally mimic endogenous transcriptional activators for use as mechanistic probes, as components of synthetic cell circuitry, and in transcription-targeted therapies. Here, we demonstrate that a phage display selection agai...

journal_title：Bioorganic & medicinal chemistry letters

authors： Majmudar CY,Labut AE,Mapp AK

更新日期：2009-07-15 00:00:00

abstract：:Using clonogenic survival assays, we demonstrated that a new platinum-acridine hybrid agent, PT-ACRAMTU, is cytotoxic in SNB19 and U87MG glioblastoma cells at low-micromolar concentrations. PT-ACRAMTU is more cytotoxic than ACRAMTU (the platinum-free acridine), acts in a time and dose dependent manner, and appears to ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hess SM,Anderson JG,Bierbach U

更新日期：2005-01-17 00:00:00

abstract：:Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V(1b) (V(3)) antagonists are described. 2-(4-Oxo-2-aryl-quinazolin-3(4H)-yl)acetamides have been identified with low nanomolar affinity for the V(1b) receptor and good selectivity with respect to related receptors V(1a), V(2) and oxy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Napier SE,Letourneau JJ,Ansari N,Auld DS,Baker J,Best S,Campbell-Wan L,Chan JH,Craighead M,Desai H,Goan KA,Ho KK,Hulskotte EG,MacSweeney CP,Milne R,Morphy JR,Neagu I,Ohlmeyer MH,Peeters AW,Presland J,Riviello C,

更新日期：2011-03-15 00:00:00