Antimitotic activity of moroidin, a bicyclic peptide from the seeds of Celosia argentea.

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：:2-aminoethylbenzofurans constitute a new class of H(3) antagonists that are more rotationally constrained than most previously reported H(3) antagonists. They retain high potency at human and rat receptors, with efficient CNS penetration observed in 35. The SAR of the basic amine moiety was compared in three different...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cowart M,Pratt JK,Stewart AO,Bennani YL,Esbenshade TA,Hancock AA

更新日期：2004-02-09 00:00:00

abstract：:A series of 7-acyloxymethylcamptothecin and 20-O-acyl-7-acyloxymethylcamptothecin derivatives were regioselectively prepared on different solvents. 7-Acyloxymethylcamptothecins possess more efficacy than 20-O-acyl-7-acyloxymethylcamptothecins against six human cancer cell lines in vitro. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pan XD,Han R,Sun PY

更新日期：2003-11-03 00:00:00

abstract：:A potent and novel class of product-like inhibitors of the HCV NS3 protease was discovered by employing a phosphinic acid as a carboxylate isostere. The replicon activity and pharmacokinetic profile of this series of compounds was optimized by exploring the substitution of the phosphinic acid, as well as conformationa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clarke MO,Chen X,Cho A,Delaney WE 4th,Doerffler E,Fardis M,Ji M,Mertzman M,Pakdaman R,Pyun HJ,Rowe T,Yang CY,Sheng XC,Kim CU

更新日期：2011-06-15 00:00:00

abstract：:Systematic SAR studies of the different regioisomers and homologues of the spiro(indane-1,4-piperidine) moiety in the growth hormone secretagogue L-162,752 are presented. Among them, spiro(3H-1-benzopyran-2,3-piperidine) was found to afford secretagogues with low nanomolar in vitro activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang L,Morriello G,Prendergast K,Cheng K,Jacks T,Chan WW,Schleim KD,Smith RG,Patchett AA

更新日期：1998-01-06 00:00:00

abstract：:Prodrug esters of the indolocarbazole CEP-751 (KT-6587) were prepared with the goal of identifying water soluble, stable but cleavable forms for intravenous dosing. A dipeptide proform Lys-beta-Ala (16, CEP-2563/KT-8391) was identified for advancement to clinical trials. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hudkins RL,Iqbal M,Park CH,Goldstein J,Herman JL,Shek E,Murakata C,Mallamo JP

更新日期：1998-07-21 00:00:00

abstract：:Opuntia ficus-indica L. is known for its beneficial effects on human health, but still little is known on cladodes as a potent source of antioxidants. Here, a direct, economic and safe method was set up to obtain water extracts from Opuntia ficus-indica cladodes rich in antioxidant compounds. When human keratinocytes ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Petruk G,Di Lorenzo F,Imbimbo P,Silipo A,Bonina A,Rizza L,Piccoli R,Monti DM,Lanzetta R

更新日期：2017-12-15 00:00:00

abstract：:In an effort to discover oral inverse agonists of RORγt to treat inflammatory diseases, a new 2,6-difluorobenzyl ether series of cyclopentyl sulfones were found to be surprisingly more potent than the corresponding alcohol derivatives. When combined with a more optimized phenyl ((R)-3-phenylpyrrolidin-3-yl)sulfone tem...

journal_title：Bioorganic & medicinal chemistry letters

authors： Duan JJ,Jiang B,Lu Z,Stachura S,Weigelt CA,Sack JS,Khan J,Ruzanov M,Wu DR,Yarde M,Shen DR,Zhao Q,Salter-Cid LM,Carter PH,Murali Dhar TG

更新日期：2020-10-01 00:00:00

abstract：:Human 5-lipoxygenase (5-LOX) is responsible for the formation of leukotriene (LT)A4, a pivotal intermediate in the biosynthesis of the leukotrienes, a family of proinflammatory lipid mediators. 5-LOX has thus gained attention as a potential drug target. However, details of the kinetic mechanism of 5-LOX are still obsc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mittal M,Kumar RB,Balagunaseelan N,Hamberg M,Jegerschöld C,Rådmark O,Haeggström JZ,Rinaldo-Matthis A

更新日期：2016-08-01 00:00:00

abstract：:A series of multisubstituted indole-acrylonitrile hybrids were designed, synthesized and evaluated for their potential cytotoxic activities. The bio-evaluation results indicated that some of the target compounds (such as 3a, 3f, 3k, 3n) exhibited good to moderate cytotoxic effect on HepG2, BCG-823, BEL-7402, and HL-77...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ke S,Yang Z,Zhang Z,Liang Y,Wang K,Liu M,Shi L

更新日期：2014-04-15 00:00:00

abstract：:We describe the discovery of phenoxymethylbenzamide derivatives as a novel class of glycine transporter type-2 (GlyT-2) inhibitors. We found hit compound 1 (human GlyT-2, IC50=4040 nM) in our library and converted its 1-(1-(naphthalen-2-ylmethyl)piperidin-4-yl)pyrrolidin-3-yl group to an 1-(N,N-dimethylaminopropyl)pip...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takahashi E,Arai T,Akahira M,Nakajima M,Nishimura K,Omori Y,Kumagai H,Suzuki T,Hayashi R

更新日期：2014-09-15 00:00:00

abstract：:We report the results of our study into a series of simple phenyl and alkyl sulfamates and alkyl methanesulfonates as potential inhibitors of the enzyme estrone sulfatase (ES). The results of the study show that the substituted phenyl sulfamates are good irreversible inhibitors; the alkyl sulfamate compounds were foun...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ahmed S,James K,Owen CP,Patel CK,Sampson L

更新日期：2002-05-06 00:00:00

abstract：:A series of optically pure phenyl-and non-phenyl-substituted 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(2-hydroxypropyl)piperazines was synthesized and their binding affinity for dopamine transporter (DAT) was investigated. The analogues with a hydroxyl group in the S configuration were more selective for the DAT over...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hsin LW,Prisinzano T,Wilkerson CR,Dersch CM,Horel R,Jacobson AE,Rothman RB,Rice KC

更新日期：2003-02-10 00:00:00

abstract：:The inhibition of ribonuclease Bi by 3'-N-hydroxyurea-3'-deoxythymidine 5'-phosphate is enhanced by 30-fold in the presence of Zn(2+). Thus, an N-hydroxyurea nucleotide can recruit Zn(2+) to inhibit the enzymatic activity of a ribonuclease. This result engenders a general strategy for the inhibition of non-metalloenzy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Higgin JJ,Yakovlev GI,Mitkevich VA,Makarov AA,Raines RT

更新日期：2003-02-10 00:00:00

abstract：:A series of novel 1,3-benzodiazapine based D1 antagonists was designed according to the understanding of pharmacophore models derived from SCH 23390 (1b), a potent and selective D1 antagonist. The new design features an achiral cyclic-amidine that maintains desired basicity. Solid phase synthesis was developed for SAR...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhu Z,Sun ZY,Ye Y,McKittrick B,Greenlee W,Czarniecki M,Fawzi A,Zhang H,Lachowicz JE

更新日期：2009-09-01 00:00:00

abstract：:Two series of aminosubstituted coumarins were synthesised and evaluated in vitro as inhibitors of DNA gyrase and as potential antibacterials. Novel novobiocin-like coumarins, 4-(dialkylamino)methylcoumarins and 4-((2-alkylamino)ethoxy)coumarins, were discovered as gyrase B inhibitors with promising antibacterial activ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Laurin P,Ferroud D,Schio L,Klich M,Dupuis-Hamelin C,Mauvais P,Lassaigne P,Bonnefoy A,Musicki B

更新日期：1999-10-04 00:00:00

abstract：:Total synthesis of human chymase inhibitor methyllinderone has been achieved in only four steps with an overall yield of 21% from dimethyl squarate. We developed an efficient synthetic method for obtaining methyllinderone derivatives and found the active compound. In addition, we propose the inhibition mechanism of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aoyama Y,Konoike T,Kanda A,Naya N,Nakajima M

更新日期：2001-07-09 00:00:00

abstract：:Oxygen dependent degradation of hypoxia-inducible factor (HIF)-1α is triggered with hydroxylation by proline hydroxylase domain 2 (PHD2) under normoxic conditions. Some of previously developed PHD2 inhibitors show a considerable potency against factor inhibiting HIF (FIH), the HIF asparagine hydroxylase. For specific ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kwon HS,Choi YK,Kim JW,Park YK,Yang EG,Ahn DR

更新日期：2011-07-15 00:00:00

abstract：:Tetrapeptides derived from glycine and beta-alanine were hooked at the C-3beta position of the modified cholic acid to realize novel linear tetrapeptide-linked cholic acid derivatives. All the synthesized compounds were tested against a wide variety of microorganisms (gram-negative bacteria, gram-positive bacteria and...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bavikar SN,Salunke DB,Hazra BG,Pore VS,Dodd RH,Thierry J,Shirazi F,Deshpande MV,Kadreppa S,Chattopadhyay S

更新日期：2008-10-15 00:00:00

abstract：:A series of 5,6-diaryl-2-amino-pyrazines were prepared and found to have antagonist-like properties at the CB1 receptor. Subsequent SAR studies optimized both receptor potency and drug-like properties including solubility and Cytochrome-P450 inhibition potential. Optimized compounds were demonstrated to be inverse ago...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wustrow DJ,Maynard GD,Yuan J,Zhao H,Mao J,Guo Q,Kershaw M,Hammer J,Brodbeck RM,Near KE,Zhou D,Beers DS,Chenard BL,Krause JE,Hutchison AJ

更新日期：2008-06-01 00:00:00

abstract：:Caffeic acid derivatives are increasingly regarded as potential oncoprotective that could inhibit both the initiation and progression of cancer. Here we have synthesized seven 1-arylnaphthalene lignans and related compounds and tested their impact on breast cancer cell growth in tissue culture. The product of the oxid...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bailly F,Toillon RA,Tomavo O,Jouy N,Hondermarck H,Cotelle P

更新日期：2013-01-15 00:00:00

abstract：:Serine/threonine kinase PIM3 is a potential therapeutic target for pancreatic cancer. Here, we describe the evolution of our previous PIM1 inhibitor 1 into PIM3 inhibitor 11 guided by use of the crystal structure of PIM1 as a surrogate to provide a basis for rational modification. Compound 11 potently inhibits PIM3 ki...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nakano H,Hasegawa T,Saito N,Furukawa K,Mukaida N,Kojima H,Okabe T,Nagano T

更新日期：2015-12-15 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：:The elongation condensing enzymes in the bacterial fatty acid biosynthesis pathway represent desirable targets for the design of novel, broad-spectrum antimicrobial agents. A series of substituted benzoxazolinones was identified in this study as a novel class of elongation condensing enzyme (FabB and FabF) inhibitors ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng Z,Parsons JB,Tangallapally R,Zhang W,Rock CO,Lee RE

更新日期：2014-06-01 00:00:00

abstract：:Series of carbamate and thiocarbamate derivatives were designed and synthesized and their inhibitory activities of NO production in lipopolysaccharide-activated macrophages were evaluated. Several thoicarbamate derivatives revealed promising inhibitory activity. The structure-activity relationship study of these compo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin GH,Lee HJ,Gim HJ,Ryu JH,Jeon R

更新日期：2012-05-01 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：:To develop novel PPARalpha ligands, we designed and synthesized several 3-{3-[2-(nonylpyridin-2-ylamino)ethoxy]phenyl}propanoic acid derivatives. Compound 10, the meta isomer of a PPARgamma agonist 1, has been identified as a PPARalpha ligand. The introduction of methyl and ethyl groups at the C-2 position of the prop...

journal_title：Bioorganic & medicinal chemistry letters

authors： Usui S,Fujieda H,Suzuki T,Yoshida N,Nakagawa H,Miyata N

更新日期：2006-06-15 00:00:00

abstract：:Functionalized 1,3-teraryls, synthesized through ring transformation of 6-aryl-3-carbomethoxy-4-methylthio-2H-pyran-2-one from arylketone have been screened for their hepatoprotective activity and of them have demonstrated significant protection in animal model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ram VJ,Goel A,Patnaik GK

更新日期：1998-03-03 00:00:00

abstract：:Two closely related scaffolds were identified through an uHTS campaign as desirable starting points for the development of Rho-Kinase (ROCK) inhibitors. Here, we describe our hit-to-lead evaluation process which culminated in the rapid discovery of potent leads such as 22 which successfully demonstrated an early in vi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wu F,Büttner FH,Chen R,Hickey E,Jakes S,Kaplita P,Kashem MA,Kerr S,Kugler S,Paw Z,Prokopowicz A,Shih CK,Snow R,Young E,Cywin CL

更新日期：2010-06-01 00:00:00

abstract：:New base-labile acyloxymethyl groups were evaluated to protect 2'-OH functions of ribonucleotides for regular RNA synthesis in order to shorten the deprotection procedure upon ammonia. These same acetalester groups were assessed in 2'-modified proRNA as biolabile 2'-protections removable by cell enzymes to generate pa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Martin AR,Lavergne T,Vasseur JJ,Debart F

更新日期：2009-08-01 00:00:00