Neomycin-phenolic conjugates: polycationic amphiphiles with broad-spectrum antibacterial activity, low hemolytic activity and weak serum protein binding.

abstract：:A simple and convenient method for the one-pot three-component synthesis of 3-pyranyl indoles has been accomplished by tandem Knoevenagel-Michael reaction of 3-cyanoacetyl indole, various aromatic aldehydes and malononitrile catalyzed by InCl(3) in ethanol under reflux conditions. The newly synthesized 3-pyranyl indol...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lakshmi NV,Thirumurugan P,Noorulla KM,Perumal PT

更新日期：2010-09-01 00:00:00

abstract：:A new triterpenoid saponin, julibroside J(28) (1), was isolated from the stem bark of Albizia julibrissin Durazz (Leguminosae) by using chromatographic method. The structure of 1 was established by spectroscopic methods. 1 displayed significant antitumor activity in vitro against PC-3M-1E8, Bel-7402, and HeLa cancer c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liang H,Tong WY,Zhao YY,Cui JR,Tu GZ

更新日期：2005-10-15 00:00:00

abstract：:Structure-activity relationships for a recently discovered thiazolyl phenyl ether series of acetyl-CoA carboxylase (ACC) inhibitors were investigated. Preliminary efforts to optimize the series through modification of the distal aryl ether moiety of the lead scaffold resulted in the identification of compounds exhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clark RF,Zhang T,Xin Z,Liu G,Wang Y,Hansen TM,Wang X,Wang R,Zhang X,Frevert EU,Camp HS,Beutel BA,Sham HL,Gu YG

更新日期：2006-12-01 00:00:00

abstract：:Structure-based design and synthesis of the 3,4'-bispyridinylethylene series led to the discovery of 3-isoquinolinylpyridine 13a as a potent PKB/Akt inhibitor with an IC(50) of 1.3nM against Akt1. Compound 13a shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li Q,Woods KW,Thomas S,Zhu GD,Packard G,Fisher J,Li T,Gong J,Dinges J,Song X,Abrams J,Luo Y,Johnson EF,Shi Y,Liu X,Klinghofer V,Des Jong R,Oltersdorf T,Stoll VS,Jakob CG,Rosenberg SH,Giranda VL

更新日期：2006-04-01 00:00:00

abstract：:A novel alpha7 nAChR agonist, N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (3a, PHA-709829), has been identified for the potential treatment of cognitive deficits in schizophrenia. The compound shows potent and selective alpha7 in vitro activity, excellent brain penetration, good rat oral b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Acker BA,Jacobsen EJ,Rogers BN,Wishka DG,Reitz SC,Piotrowski DW,Myers JK,Wolfe ML,Groppi VE,Thornburgh BA,Tinholt PM,Walters RR,Olson BA,Fitzgerald L,Staton BA,Raub TJ,Krause M,Li KS,Hoffmann WE,Hajos M,Hurst RS,

更新日期：2008-06-15 00:00:00

abstract：:Alpha-keto ester and amides were found to be potent inhibitors of histone deacetylase. Nanomolar inhibitors against the isolated enzyme and sub-micromolar inhibitors of cellular proliferation were obtained. The alpha-keto amide 30 also exhibited significant anti-tumor effects in an in vivo tumor model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wada CK,Frey RR,Ji Z,Curtin ML,Garland RB,Holms JH,Li J,Pease LJ,Guo J,Glaser KB,Marcotte PA,Richardson PL,Murphy SS,Bouska JJ,Tapang P,Magoc TJ,Albert DH,Davidsen SK,Michaelides MR

更新日期：2003-10-06 00:00:00

abstract：:Opioid receptors play an important role in both behavioral and homeostatic functions. We herein report tetrahydroquinoline derivatives as opioid receptor antagonists. SAR studies led to the identification of the potent antagonist 2v, endowed with 1.58nM (K(i)) functional activity against the μ opioid receptor. DMPK da...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang C,Westaway SM,Speake JD,Bishop MJ,Goetz AS,Carballo LH,Hu M,Epperly AH

更新日期：2011-01-15 00:00:00

abstract：:An efficient and simple polymer-assisted approach has been developed to biotinylate multifunctional compounds bearing an amino functionality. Biotin was immobilized on aminomethylated polystyrene via the Kenner safety catch linker, activated and subsequently transferred to the amino function of the target compounds ch...

journal_title：Bioorganic & medicinal chemistry letters

authors： Golisade A,Herforth C,Wieking K,Kunick C,Link A

更新日期：2001-07-09 00:00:00

abstract：:The synthesis of a series of novel 4-substituted 2,3,6,7-tetrahydrobenzo [1,2-b;4,5-b']difuran-1H-imidazolium salts is presented. The biological properties of the compounds were evaluated in vitro against a panel of human tumor cell lines. Results suggest that the 5,6-dimethyl-benzimidazole or 2-methyl-benzimidazole r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang CB,Liu Y,Liu ZF,Duan SZ,Li MY,Chen W,Li Y,Zhang HB,Yang XD

更新日期：2017-04-15 00:00:00

abstract：:A series of novel tetracyclic core-containing HCV NS5A inhibitors has been discovered. Incorporation of tetrahydropyran-substituted amino acid moiety improved their potency and yielded HCV NS5A inhibitors with a minimum potency shift from the GT1a strain compared to other genotypes and mutants. Compounds 53 and 54 sho...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu W,Hu B,Zhong B,Hao J,Lei Z,Agrawal S,Rokosz L,Liu R,Chen S,Asante-Appiah E,Kozlowski JA

更新日期：2019-03-01 00:00:00

abstract：:Tubulin is subject to a reversible post-translational modification involving polyglutamylation and deglutamylation of glutamate residues in its C-terminal tail. This process plays key roles in regulating the function of microtubule associated proteins, neuronal development, and metastatic progression. This study descr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu Y,Garnham CP,Roll-Mecak A,Tanner ME

更新日期：2013-08-01 00:00:00

abstract：:Practical, asymmetric total syntheses of the title phospholipids from a readily available myo-inositol derivative as well as short chain and cross-linkable aminoether analogues are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Falck JR,Krishna UM,Capdevila JH

更新日期：2000-08-07 00:00:00

abstract：:Fatty acylated dipeptides homologous to Gi alpha N-termini affect ligand binding to muscarinic acetylcholine receptors. Myristylglycine-serine containing dipeptides decrease antagonist binding at both M1 and M2 muscarinic receptors. Palmitate on the serine analogous to native palmitoylated cysteine affords dipeptide w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Krishnan V,Pham WN,Messer WS Jr,Peseckis SM

更新日期：1999-12-06 00:00:00

abstract：:A phytochemical investigation into the bark of Erythrophleum fordii yielded four new compounds, two new cassaine diterpenoids (erythrofordin T and U, 1 and 2) and two new cassaine diterpenoid amines (erythroformine A and B, 6 and 7), as well as nine known compounds. We report for the first time the isolation of erythr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ha MT,Tran MH,Phuong TT,Kim JA,Woo MH,Choi JS,Lee S,Lee JH,Lee HK,Min BS

更新日期：2017-07-01 00:00:00

abstract：:We describe the identification, SAR, and in vivo pharmacology of a new series of Src-family selective Lck inhibitors. These thienopyridines were designed based on a desire to access the unique residues in the extended hinge region of Lck. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Abbott L,Betschmann P,Burchat A,Calderwood DJ,Davis H,Hrnciar P,Hirst GC,Li B,Morytko M,Mullen K,Yang B

更新日期：2007-03-01 00:00:00

abstract：:A series of 6-alkoxyisoindolin-1-ones with a magic shotgun pharmacological profile are presented as potential antipsychotics. The in vitro pharmacological profile includes D(2) partial agonism (30-55%), 5-HT(1A) partial agonism (60-90%), and 5-HT(2A) antagonism. Selected compounds in this series displayed good in vivo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Favor DA,Powers JJ,White AD,Fitzgerald LW,Groppi V,Serpa KA

更新日期：2010-10-01 00:00:00

abstract：:Three C(60) derivatives [C(60) (NHCH(2)CH(2)COONa)(n)(H)(n)], n=1, 5, 9] (A, B, C) with different additional number of beta-alanine were synthesized by the control of relative amount of C(60) and beta-alanine added. Hydroxyl radical scavenging activity of the adducts was evaluated in a copper-catalyzed Haber-Weiss rea...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun T,Jia Z,Xu Z

更新日期：2004-04-05 00:00:00

abstract：:Triptolide (TP) is a diterpene epoxide component extracted from Tripterygium wilfordii and has been shown to possess an impressive anticancer effect. However, TP has not yet entered any clinic trials due to the severe adverse effects that resulted from the off-target absorption and distribution found in animal studies...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lou D,Lou Z,Lin Y,Shangguan H,Lin Y,Luo Q,Zhang H,Lin G,Chen R,Kou L,Bao S

更新日期：2020-12-17 00:00:00

abstract：:A non-methionine FT inhibitor lead structure (1) was designed through computer modeling of the peptidomimetic FT inhibitor ABT839. Optimization of this lead resulted in compounds 2e and 2g, with FT IC(50) values of 1.3 and 1.8 nM, GGT IC(50) of 1400 nM, and EC(50) (Ras processing) values of 13 and 11 nM, respectively....

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang GT,Wang X,Wang W,Hasvold LA,Sullivan G,Hutchins CW,O'Conner S,Gentiles R,Sowin T,Cohen J,Gu WZ,Zhang H,Rosenberg SH,Sham HL

更新日期：2005-01-03 00:00:00

abstract：:A novel series of imidazo[1,5-a]pyrazines was synthesized and evaluated as corticotropin releasing hormone (CRH) receptor ligands. SAR studies focused primarily on dialkylamino side chain optimization. SAR of the aryl and small alkyl substituents was also explored. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hartz RA,Gilligan PJ,Nanda KK,Tebben AJ,Fitzgerald LW,Miller K

更新日期：2002-02-11 00:00:00

abstract：:A novel class of Growth Hormone Secretagogues (GHS), based on a tetrazole template, has been discovered. In vitro SAR and in vivo potency within this new class of GHS are described. The tetrazole 9q exhibits good oral bioavailability in rats and dogs as well as efficacy following an oral 10 mg/kg dose in dogs. Solutio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hernández AS,Cheng PT,Musial CM,Swartz SG,George RJ,Grover G,Slusarchyk D,Seethala RK,Smith M,Dickinson K,Giupponi L,Longhi DA,Flynn N,Murphy BJ,Gordon DA,Biller SA,Robl JA,Tino JA

更新日期：2007-11-01 00:00:00

abstract：:In the quest to discover a potent and selective class of direct agonists to the sphingosine-1-phosphate receptor, we explored the carboxylate functional group as a replacement to previously reported lead phosphates. This has led to the discovery of potent and selective direct agonists with moderate to substantial in v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Evindar G,Deng H,Bernier SG,Doyle E,Lorusso J,Morgan BA,Westlin WF

更新日期：2013-01-15 00:00:00

abstract：:A series of 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues were synthesized and evaluated for cytotoxic activity against eight human cancer cell lines. Compounds 18, 21, 28, 29, 30 and 31 showed cytotoxic activity with GI(50) values in the range of 2.1-8.1 microM concentration. Among these, compounds 21...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharma VM,Adi Seshu KV,Vamsee Krishna C,Prasanna P,Chandra Sekhar V,Venkateswarlu A,Rajagopal S,Ajaykumar R,Deevi DS,Rao Mamidi NV,Rajagopalan R

更新日期：2003-05-19 00:00:00

abstract：:Ubiquitin-dependent proteolysis of cellular proteins is one of the major pathways to regulate protein function posttranslationally. Here we demonstrate a potentially general method of degrading any targeted proteins by the ubiquitin-dependent proteolysis in living cells, using small-molecule proteolysis inducer (SMPI)...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang D,Baek SH,Ho A,Kim K

更新日期：2004-02-09 00:00:00

abstract：:Eight new isocoumarin glycosides (1-8) were obtained from the solid culture of the wetland soil-derived fungus Metarhizium anisopliae (No. DTH12-10). Their chemical structures were elucidated by analyses of HR ESI-TOF MS, (1)H, (13)C NMR, (1)H-(1)H COSY, HSQC, and HMBC spectra. The absolute configurations were determi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tian JF,Li PJ,Li XX,Sun PH,Gao H,Liu XZ,Huang P,Tang JS,Yao XS

更新日期：2016-03-01 00:00:00

abstract：:We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, whic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang LX,Zhou XB,Xiao ML,Jiang N,Liu F,Zhou WX,Wang XK,Zheng ZB,Li S

更新日期：2014-08-15 00:00:00

abstract：:A novel series of N-arylidene-2-(2,4-dichloro phenyl)-1-propyl-1H-benzo[d] imidazole-5-carbohydrazides having different substitution on the arylidene part were synthesized in good yield. The core nucleus benzimidazole-5-carboxylate (5) was efficiently synthesized by 'one-pot' nitro reductive cyclization reaction betwe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vasantha K,Basavarajaswamy G,Vaishali Rai M,Boja P,Pai VR,Shruthi N,Bhat M

更新日期：2015-04-01 00:00:00

abstract：:A novel class of MurF inhibitors was discovered and structure-activity relationship studies have led to several potent compounds with IC(50)=22 approximately 70 nM. Unfortunately, none of these potent MurF inhibitors exhibited significant antibacterial activity even in the presence of bacterial cell permeabilizers. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gu YG,Florjancic AS,Clark RF,Zhang T,Cooper CS,Anderson DD,Lerner CG,McCall JO,Cai Y,Black-Schaefer CL,Stamper GF,Hajduk PJ,Beutel BA

更新日期：2004-01-05 00:00:00

abstract：:Relying on the high affinities of the benz-indolo-azecine LE 300 (1) and the hydroxylated dibenz-azecine LE 404 (2b) for the D1/D5 receptor subtypes, we synthesized methoxylated, hydroxylated and an indole-N methylated derivatives of 1 (Fig. 1). Hydroxylation of azecine derivatives is beneficial with regard to the aff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Enzensperger C,Kilian S,Ackermann M,Koch A,Kelch K,Lehmann J

更新日期：2007-03-01 00:00:00

abstract：:Selective inhibition of cyclooxygenase-2 (COX-2) inhibitors is an important strategy in design of potent anti-inflammatory compounds with significantly reduced side effects. Therefore, QSAR studies of 2-acetoxyphenyl alkyl sulfides were performed using Bioloom, CAChe 6.1, and Dragon 3.0 for the COX-2 and COX-1 inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jain HK,Mourya VK,Agrawal RK

更新日期：2006-10-15 00:00:00