Selective heterocyclic amidine inhibitors of human inducible nitric oxide synthase.

abstract：:The synthesis and biological evaluation of new potent opioid receptor-like 1 antagonists are presented. A structure-activity relationship (SAR) study of arylpyrazole lead compound 1 obtained from library screening identified compound 31, (1S,3R)-N-{[1-(3-chloropyridin-2-yl)-5-(5-fluoro-6-methylpyridin-3-yl)-4-methyl-1...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kobayashi K,Uchiyama M,Ito H,Takahashi H,Yoshizumi T,Sakoh H,Nagatomi Y,Asai M,Miyazoe H,Tsujita T,Hirayama M,Ozaki S,Tani T,Ishii Y,Ohta H,Okamoto O

更新日期：2009-07-01 00:00:00

abstract：:Herein we report the synthesis of a series of bicyclo[3.2.1]octanes and their binding characteristics at the dopamine and serotonin transporters. The data confirm that a heteroatom at position 8 of the tropane nucleus is not a prerequisite for binding since the bicyclo[3.2.1]octanes prove potent inhibitors of both tra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Meltzer PC,Blundell P,Chen Z,Yong YF,Madras BK

更新日期：1999-03-22 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：:A remarkable control of the potency of cantharimide is described based on the electronic properties of functional group and it exhibits a relatively less toxic effect to the non-malignant hematological disorder bone marrow cells. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kok SH,Chui CH,Lam WS,Chen J,Lau FY,Wong RS,Cheng GY,Lai PB,Leung TW,Yu MW,Tang JC,Chan AS

更新日期：2007-03-01 00:00:00

abstract：:Mass-directed isolation of the CH(2)Cl(2)/MeOH extract from the leaves of Cryptocarya obovata resulted in the purification of a new trypanocidal alpha-pyrone, 7',8'-dihydroobolactone (1). The chemical structure of 1 was determined by 1D/2D NMR, MS and CD data analysis. 7',8'-Dihydroobolactone was shown to inhibit Tryp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Davis RA,Demirkiran O,Sykes ML,Avery VM,Suraweera L,Fechner GA,Quinn RJ

更新日期：2010-07-15 00:00:00

abstract：:Three series of rhodanine derivatives bearing a quinoline moiety (6a-h, 7a-g, and 8a-e) have been synthesized, characterized, and evaluated as antibacterial agents. The majority of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-re...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guo M,Zheng CJ,Song MX,Wu Y,Sun LP,Li YJ,Liu Y,Piao HR

更新日期：2013-08-01 00:00:00

abstract：:We proposed a novel QSAR (quantitative structure-activity relationship) procedure called LERE (linear expression by representative energy terms)-QSAR involving molecular calculations such as ab initio fragment molecular orbital and generalized Born/surface area ones. We applied LERE-QSAR to two datasets for the free-e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Munei Y,Shimamoto K,Harada M,Yoshida T,Chuman H

更新日期：2011-01-01 00:00:00

abstract：:Inhibition of BCR-ABL tyrosine kinase activity has shown to be essential for the treatment of chronic myelogenous leukemia (CML). However, drug resistance has quickly arisen in recent clinical trials for STI571 (Gleevec), which is the first approved drug of CML by inhibiting ABL tyrosine kinase. It is desirable to dev...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peng H,Huang N,Qi J,Xie P,Xu C,Wang J,Yang C

更新日期：2003-11-03 00:00:00

abstract：:A new series of quinoline ether inhibitors, which potently and selectively inhibit PDGFR tyrosine kinases, is described in this Letter. Compounds 23 and 33 are selective, low nanomolar inhibitors of PDGFRα and β, display good pharmacokinetics in rat and dog and are active in vivo at low doses when given orally twice d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Plé PA,Jung F,Ashton S,Hennequin L,Laine R,Lambert-van der Brempt C,Morgentin R,Pasquet G,Taylor S

更新日期：2012-05-01 00:00:00

abstract：:The synthesis and pharmacological evaluation of substituted oximino-ethers 1 and 2 of naphth[1,2-b]- and naphth[2,1-b]-oxepin-5-ones (4 and 8) were carried out. The hypotensive activity of oximino-ethers 1 and 2 was evaluated on anaesthetized cats. The results indicated that 1c caused a fall of 80 mm/Hg for >100' at a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tandon VK,Kumar M,Awasthi AK,Saxena HO,Goswamy GK

更新日期：2004-06-21 00:00:00

abstract：:The synthesis and antibacterial activity of 3-methylenepyrrolidine formyl hydroxyamino derivatives are reported. The antibacterial activities of these derivatives were evaluated to discover SAR at P(1') and P(3') positions, and most of these derivatives exhibit better in vitro antibacterial activity than existing drug...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi W,Ma H,Duan Y,Aubart K,Fang Y,Zonis R,Yang L,Hu W

更新日期：2011-02-01 00:00:00

abstract：:We have investigated phenol replacements in a series of diaryl amino piperidine delta opioid agonists. From this study we have demonstrated that the hydroxy functional group can be replaced with a primary amide group, giving enhanced activity at the delta receptor, increased selectivity versus mu and kappa as well as ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Griffin AM,Brown W,Walpole C,Coupal M,Adam L,Gosselin M,Salois D,Morin PE,Roumi M

更新日期：2009-11-01 00:00:00

abstract：:Based on the findings that cholest-4-en-3-one, an intestinal metabolite of cholesterol, has an anti-obesity effect on animals, the structure-effect relationship of its 3-oxo derivatives and related compounds were investigated. Cholesten-3-ones, which possesses an enone structure with a carbonyl group at C3, markedly i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suzuki K,Shimizu T,Nakata T

更新日期：1998-08-18 00:00:00

abstract：:Modifications at C6 and C7 positions of 3-cyanoquinolines 6 and 7 led to potent inhibitors of the ErbB family of kinases particularly against EGFRWT and Her4 enzymes in the radioisotope filter binding assay. The lead (4, SAB402) displayed potent dual biochemical activities with EGFRWT/Her4 IC50 ratio of 80 due to its ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mansour TS,Pallepati RR,Basetti V

更新日期：2020-08-15 00:00:00

abstract：:Oligodeoxynucleotides containing 2'-O-beta-D-ribofuranosyladenosine were prepared and used as modified primers in RNA-templated DNA synthesis catalyzed by HIV reverse transcriptase. It was shown that the additional 2'-ribofuranose residue in specific position of primer prevents its elongation. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Andreeva OI,Golubeva AS,Kochetkov SN,Van Aerschot A,Herdewijn P,Efimtseva EV,Ermolinsky BS,Mikhailov SN

更新日期：2002-02-25 00:00:00

abstract：:On the search for anti-cancer compounds from natural Korean medicinal sources, a bioassay-guided fractionation and chemical investigation of the MeOH extract from the rhizomes of Acorus gramineus resulted in the isolation and identification of thirteen phenolic derivatives (1-13) including two new 8-O-4'-neolignans, n...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim KH,Moon E,Kim HK,Oh JY,Kim SY,Choi SU,Lee KR

更新日期：2012-10-01 00:00:00

abstract：:d-Labeled N-alkylmaleimides have been prepared for specific modification of the terminal SH groups of cysteine residues in proteins or peptides. These reagents are useful tools for quantitative analysis of peptides by stable isotope differential mass spectrometry. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Niwayama S,Kurono S,Matsumoto H

更新日期：2001-09-03 00:00:00

abstract：:New boron-containing chlorin derivatives 9 and 13 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized from photoprotoporphyrin IX dimethyl ester (2) and L-4-boronophenylalanine-related compounds. The in vivo biodistribution and clearance of 9 and 13 were in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Asano R,Nagami A,Fukumoto Y,Miura K,Yazama F,Ito H,Sakata I,Tai A

更新日期：2014-03-01 00:00:00

abstract：:Three new iridoid glycosides, 6"-O-trans-caffeoylgenipin gentiobioside (1), genipin 1-O-β-D-apiofuranosyl (1→6)-β-D-glucopyranoside (2), genipin 1-O-α-D-xylopyranosyl (1→6)-β-D-glucopyranoside (3), three new monocyclic monoterpenoids, jasminoside R (4), jasminoside S (5), jasminoside T (6), together with nine known ir...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peng K,Yang L,Zhao S,Chen L,Zhao F,Qiu F

更新日期：2013-02-15 00:00:00

abstract：:The in vitro antimycobacterial activity of cobalt(II) and copper(II) complexes of some fluorinated isonicotinoylhydrazones was evaluated in a TB-infected macrophage model; all metalcomplexes exhibited excellent activity against Mycobacterium tuberculosis Erdman growing within macrophages, at concentrations much lower ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Maccari R,Ottanà R,Bottari B,Rotondo E,Vigorita MG

更新日期：2004-12-06 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：:Synthesis of the potent antiplasmodial 4-aminoquinoline, phenylequine (PQ), is reported for the first time. PQ and the two analogues show increased efficacy in moving from the chloroquine sensitive D10 to the chloroquine resistant K1 strain in vitro. The in vivo efficacy of PQ, and salts thereof, have been determined ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Blackie MA,Yardley V,Chibale K

更新日期：2010-02-01 00:00:00

abstract：:A series of novel 1-[(1R,2S)-2-fluorocyclopropyl]naphthyridone derivatives 21-24 containing an oxime-functionalized pyrrolidine moiety were designed, synthesized and evaluated for their biological activity. Our results reveal that compounds 21a, 21e and 21j show considerable activity against MTB H37Rv ATCC 27294 (MICs...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang J,Liu H,Liu M,Zhang R,Li L,Wang B,Wang M,Wang C,Lu Y

更新日期：2015-11-15 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：:A series of α-methylated analogues of the potent sRTX thiourea antagonists were investigated as rTRPV1 ligands in order to examine the effect of α-methylation on receptor activity. The SAR analysis indicated that activity was stereospecific with the (R)-configuration of the newly formed chiral center providing high bi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim HS,Jin MK,Kang SU,Lim JO,Tran PT,Hoang VH,Ann J,Ha TH,Pearce LV,Pavlyukovets VA,Blumberg PM,Lee J

更新日期：2014-06-15 00:00:00

abstract：:Novel imidazole frameworks have been identified as potent partial agonists of the alpha(1A) adrenergic receptor, with good selectivity over the alpha(1B), alpha(1D) and alpha(2A) receptor sub-types. Nitrile 28 possessed attractive CNS drug-like properties with good membrane permeability and no P-pg mediated efflux. 28...

journal_title：Bioorganic & medicinal chemistry letters

authors： Whitlock GA,Brennan PE,Roberts LR,Stobie A

更新日期：2009-06-01 00:00:00

abstract：:Structure-activity relationship (SAR) efforts around our initial lead compound 1 led to the identification of potent P2X(7) receptor antagonists with improved pharmacokinetic profiles. These compounds were potent and selective at the P2X(7) receptor in both human and rodent. Compound (entry 31) exhibited oral efficacy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Matasi JJ,Brumfield S,Tulshian D,Czarnecki M,Greenlee W,Garlisi CG,Qiu H,Devito K,Chen SC,Sun Y,Bertorelli R,Geiss W,Le VD,Martin GS,Vellekoop SA,Haber J,Allard ML

更新日期：2011-06-15 00:00:00

abstract：:In this work, we have designed cyclic peptides (cIBL, cIBR, cIBC, CH4 and CH7) derived from the parent IB peptide (ICAM-1(1-21)) that are inhibitors of ICAM-1/LFA-1-mediated T-cell adhesion to Caco-2 cell monolayers. Cyclic peptide cIBR has the best activity of any of the peptides evaluated. The active ICAM-1 peptides...

journal_title：Bioorganic & medicinal chemistry letters

authors： Anderson ME,Yakovleva T,Hu Y,Siahaan TJ

更新日期：2004-03-22 00:00:00

abstract：:HIV-1 protease inhibitors (PI) with an N-arylpyrrole moiety in the P(3) position afforded excellent antiviral potency and substantially improved aqueous solubility over previously reported variants. The rapid in vitro clearance of these compounds in human liver microsomes prompted oral coadministration with indinavir ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kevin NJ,Duffy JL,Kirk BA,Chapman KT,Schleif WA,Olsen DB,Stahlhut M,Rutkowski CA,Kuo LC,Jin L,Lin JH,Emini EA,Tata JR

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