2-(Aminomethyl)-benzamide-based glycine transporter type-2 inhibitors.

abstract：:Eight peptoids have been synthesized as peptidomimetics of the cytostatic Dolastatin 15, a depsipeptide isolated from the Indian sea hare Dolabella auricularia. The compounds have been tested against several human cancer cell lines and did not show any cytostatic properties. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schmitt J,Bernd M,Kutscher B,Kessler H

更新日期：1998-02-17 00:00:00

abstract：:Beta-2'-C-methyl purines (1, 2) are known inhibitors of hepatitis C virus (HCV). We herein report the synthesis, biological and enzymatic evaluation of their 5'-phosphoramidate ProTides. Described herein are seven l-alanine phosphoramidate derivatives with variations to the amino acid ester. The 1-naphthyl phosphorami...

journal_title：Bioorganic & medicinal chemistry letters

authors： McGuigan C,Perrone P,Madela K,Neyts J

更新日期：2009-08-01 00:00:00

abstract：:A new near-infrared fluorescent compound containing two cyclic RGD motifs, cypate-[c(RGDfK)](2) (1), was synthesized based on a carbocyanine fluorophore bearing two carboxylic acid groups (cypate) for integrin α(v)β(3)-targeting. Compared with its monovalent counterpart cypate-c(RGDfK) (2), 1 exhibited remarkable impr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ye Y,Akers W,Xu B,Bloch S,Odonkor C,Achilefu S

更新日期：2012-09-01 00:00:00

abstract：:The synthesis and in vitro chemical and enzymatic stability of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine (9) as L-Dopa prodrug are described. Prodrug 9 possesses a good lipophilicity (log P = 2.153 +/- 0.017), is stable in aqueous buffer solutions (pH 1.3 and 7.4), and in 80% rat and human plasma it...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cingolani GM,Di Stefano A,Mosciatti B,Napolitani F,Giorgioni G,Ricciutelli M,Claudi F

更新日期：2000-06-19 00:00:00

abstract：:Towards the development of chemotherapy for the infection by human T-cell leukemia virus type I (HTLV-I), we have established evaluation systems for HTLV-I protease (PR) inhibitors using both recombinant and chemically synthesized HTLV-I PRs. Newly synthesized substrate-based inhibitors containing hydroxymethylcarbony...

journal_title：Bioorganic & medicinal chemistry letters

authors： Maegawa H,Kimura T,Arii Y,Matsui Y,Kasai S,Hayashi Y,Kiso Y

更新日期：2004-12-06 00:00:00

abstract：:The esterase, phosphatase, and sulfatase activities of carbonic anhydrase (CA, EC 4.2.1.1) isozymes, CA I, II, and XIII with 4-nitrophenyl esters as substrates was investigated. These enzymes show esterase activity with 4-nitrophenyl acetate as substrate, with second order rate constants in the range of 753-7706M(-1)s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Innocenti A,Scozzafava A,Parkkila S,Puccetti L,De Simone G,Supuran CT

更新日期：2008-04-01 00:00:00

abstract：:A novel class of 1H-(benzimidazol-2-yl)-1H-pyridin-2-one inhibitors of insulin-like growth factor I (IGF-1R) kinase is described. This report discusses the SAR of 4-(2-hydroxy-2-phenylethylamino)-substituted pyridones with improved IGF-1R potency. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wittman MD,Balasubramanian B,Stoffan K,Velaparthi U,Liu P,Krishnanathan S,Carboni J,Li A,Greer A,Attar R,Gottardis M,Chang C,Jacobson B,Sun Y,Hansel S,Zoeckler M,Vyas DM

更新日期：2007-02-15 00:00:00

abstract：:The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this gener...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun W,Chu T

更新日期：2015-10-15 00:00:00

abstract：:A series of novel oxime-containing pyrazole derivatives were synthesized by the reaction of ethyl 3-phenyl-1H-pyrazole-5-carboxylate derivatives and 2-bromo-1-phenylethanone followed by the reaction with hydroxylamine hydrochloride. The structures were determined by IR, (1)H NMR, HRMS, and X-ray analysis. A dose- and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng LW,Li Y,Ge D,Zhao BX,Liu YR,Lv HS,Ding J,Miao JY

更新日期：2010-08-15 00:00:00

abstract：:5-Methylcytosine (5mC) is oxidized by ten-eleven translocation (TET) enzymes. This process followed by thymine DNA glycosylase is proposed to be the mechanism for methylcytosine demethylation. 5-Hydroxymethylcytosine (5hmC) is one of the most important key oxidative metabolites in the demethylation process, and theref...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fukuzawa S,Tachibana K,Tajima S,Suetake I

更新日期：2015-12-15 00:00:00

abstract：:Three new pseudo-symmetrical tamoxifen derivatives, RID-B (15), C (16), and D (17), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of the pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 15 strongly inhibits the viability of HL-6...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shiina I,Sano Y,Nakata K,Kikuchi T,Sasaki A,Ikekita M,Hasome Y

更新日期：2007-05-01 00:00:00

abstract：:P21-activated kinase 1 (PAK1) plays a vital role in the proliferation, survival and migration of cancer cells, which has emerged as a promising drug target for cancer therapy. In this study, a series of 2-indolinone derivatives were designed and synthesized through a structure-based strategy. A potent PAK1 inhibitor (...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yao D,Ruhan A,Jiang J,Huang J,Wang J,Han W

更新日期：2020-09-01 00:00:00

abstract：:A series of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones was prepared and shown by electrophysiological analysis to activate a cloned maxi-K channel mSlo (or hSlo) expressed in Xenopus laevis oocytes. The effects of these structurally novel maxi-K channel openers on bladder contractile function were studied in vitro using iso...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hewawasam P,Erway M,Thalody G,Weiner H,Boissard CG,Gribkoff VK,Meanwell NA,Lodge N,Starrett JE Jr

更新日期：2002-04-08 00:00:00

abstract：:Herein, we report the design and synthesis of the novel 12-membered non-antibiotic macrolide (8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), which was found to be a potent anti-inflammatory and/or immunomodulatory agent, capable of promoting monocyte to macrophage differentiation. This molecule ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sugawara A,Sueki A,Hirose T,Nagai K,Gouda H,Hirono S,Shima H,Akagawa KS,Omura S,Sunazuka T

更新日期：2011-06-01 00:00:00

abstract：:A new pyrrolidinone diterpenoid, excisusin F (1), was isolated from the aerial parts of Isodon excisus (Lamiaceae), together with four known compounds, and their structures were determined mainly by NMR (1D and 2D) and mass spectrometry. Excisusin F (1) and inflexarabdonin E (3) showed potent inhibitory effects of LPS...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hong SS,Lee SA,Kim N,Hwang JS,Han XH,Lee MK,Jung JK,Hong JT,Kim Y,Lee D,Hwang BY

更新日期：2011-02-15 00:00:00

abstract：:A series of 3-substituted benzamide derivatives structurally related to STI-571 (imatinib mesylate), a Bcr-Abl tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML), was prepared and evaluated for antiproliferative activity against the Bcr-Abl-positive leukemia cell line K562. About ten 3-halogenated ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Asaki T,Sugiyama Y,Hamamoto T,Higashioka M,Umehara M,Naito H,Niwa T

更新日期：2006-03-01 00:00:00

abstract：:Hippuristanol is a natural product that has recently been shown to inhibit eukaryotic translation initiation and tumor cell proliferation. To investigate the structure and activity relationship of hippuristanol, we synthesized a series of analogs by expanding the size of its F ring and determined their effects on the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li W,Dang Y,Liu JO,Yu B

更新日期：2010-05-15 00:00:00

abstract：:IRAK4 has been identified as potential therapeutic target for inflammatory and autoimmune diseases. Herein we report the identification and initial SAR studies of a new class of pyrazole containing IRAK4 inhibitors designed to expand chemical diversity and improve off target activity of a previously identified series....

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanisak J,Seganish WM,McElroy WT,Tang H,Zhang R,Tsui HC,Fischmann T,Tulshian D,Tata J,Sondey C,Devito K,Fossetta J,Garlisi CG,Lundell D,Niu X

更新日期：2016-09-01 00:00:00

abstract：:The structure-based design and synthesis of isothiazolidinone (IZD) inhibitors of PTP1B containing imidazoles and imidazolines and their modification to interact with the B site of PTP1B are described here. The X-ray crystal structures of 3I and 4I complexed with PTP1B were solved and revealed the inhibitors are inter...

journal_title：Bioorganic & medicinal chemistry letters

authors： Douty B,Wayland B,Ala PJ,Bower MJ,Pruitt J,Bostrom L,Wei M,Klabe R,Gonneville L,Wynn R,Burn TC,Liu PC,Combs AP,Yue EW

更新日期：2008-01-01 00:00:00

abstract：:Novel acetyl-CoA carboxylase 2 (ACC2) selective inhibitors were identified by the conversion of the alkyne unit of A-908292 to the olefin linker. Modification of the center and left part of the lead compound 1b improved the ACC2 inhibitory activity and CYP450 inhibition profile, and afforded a highly selective ACC2 in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nishiura Y,Matsumura A,Kobayashi N,Shimazaki A,Sakamoto S,Kitade N,Tonomura Y,Ino A,Okuno T

更新日期：2018-08-01 00:00:00

abstract：:Starting from our previously identified novel c-Met kinase inhibitors bearing 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one scaffold, a global structural exploration was conducted to furnish an optimal binding motif for further development, directed by the enzyme inhibitory mechanism. First round SAR study picked two i...

journal_title：Bioorganic & medicinal chemistry letters

authors： An XD,Liu H,Xu ZL,Jin Y,Peng X,Yao YM,Geng M,Long YQ

更新日期：2015-02-01 00:00:00

abstract：:p38alpha Mitogen Activated Protein Kinase (MAP kinase) is an intracellular soluble serine threonine kinase. p38alpha kinase is activated in response to cellular stresses, growth factors and cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). The central role of p38alpha activation in se...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mavunkel BJ,Chakravarty S,Perumattam JJ,Luedtke GR,Liang X,Lim D,Xu YJ,Laney M,Liu DY,Schreiner GF,Lewicki JA,Dugar S

更新日期：2003-09-15 00:00:00

abstract：:We describe the synthesis and potency of a novel series of N-substituted 2-phenyl- and 2-methyl-2-phenyl-1,4-diaminobutane- based CCR5 antagonists. Compounds 7a and 12f were found to be potent in anti-HIV assays and bioavailable in the low-dose rat PK model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tallant MD,Duan M,Freeman GA,Ferris RG,Edelstein MP,Kazmierski WM,Wheelan PJ

更新日期：2011-03-01 00:00:00

abstract：:Inhibitors of CYP1 enzymes may play vital roles in the prevention of cancer and overcoming chemo-resistance to anticancer drugs. In this letter, we report synthesis of twenty-three pyrrole based heterocyclic chalcones which were screened for inhibition of CYP1 isoforms. Compound 3n potently inhibited CYP1B1 with an IC...

journal_title：Bioorganic & medicinal chemistry letters

authors： Williams IS,Joshi P,Gatchie L,Sharma M,Satti NK,Vishwakarma RA,Chaudhuri B,Bharate SB

更新日期：2017-08-15 00:00:00

abstract：:Various substituted indazole and benzoxazolone amino acids were investigated as d-tyrosine surrogates in highly potent CGRP receptor antagonists. Compound 3, derived from the 7-methylindazole core, afforded a 30-fold increase in CGRP binding potency compared with its unsubstituted indazole analog 1. When dosed at 0.03...

journal_title：Bioorganic & medicinal chemistry letters

authors： Han X,Civiello RL,Conway CM,Cook DA,Davis CD,Degnan AP,Jiang XJ,Macci R,Mathias NR,Moench P,Pin SS,Schartman R,Signor LJ,Thalody G,Tora G,Whiterock V,Xu C,Macor JE,Dubowchik GM

更新日期：2013-03-15 00:00:00

abstract：:The diastereoselective synthesis and structure activity relationship (SAR) of a series of fused cyclopropyl-3-amino-2,4-oxazine (2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine)-containing BACE inhibitors is described. Through these efforts compound 2 was identified as a potent (cell IC50 = 15 nM) BACE inhibitor with accep...

journal_title：Bioorganic & medicinal chemistry letters

authors： Low JD,Bartberger MD,Cheng Y,Whittington D,Xue Q,Wood S,Allen JR,Minatti AE

更新日期：2018-04-01 00:00:00

abstract：:A series of novel fusidic acid (FA) derivatives was synthesized by replacing the carboxylic acid group with various ester and amide groups and evaluated in vitro for their antiplasmodial activity against the chloroquine-sensitive NF54 and multidrug-resistant K1 strains of the malarial parasite Plasmodium falciparum. M...

journal_title：Bioorganic & medicinal chemistry letters

authors： Espinoza-Moraga M,Singh K,Njoroge M,Kaur G,Okombo J,De Kock C,Smith PJ,Wittlin S,Chibale K

更新日期：2017-02-01 00:00:00

abstract：:Activity-based probes are small molecules that covalently bind to the active site of a protease in an activity-dependent manner. We synthesized and characterized two fluorescent activity-based probes that target serine proteases with trypsin-like or elastase-like activity. We assessed the selectivity and potency of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Edgington-Mitchell LE,Barlow N,Aurelio L,Samha A,Szabo M,Graham B,Bunnett N

更新日期：2017-01-15 00:00:00

abstract：:The synthesis and biological activity of novel glycoprotein IIb-IlIa anatagonists containing 3-azaspiro[5.5]undec-9-yl nucleus are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility of the monoazaspirocyclic structure as central template for nonpeptide RGD mim...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pandey A,Seroogy J,Volkots D,Smyth MS,Rose J,Mehrotra MM,Heath J,Ruhter G,Schotten T,Scarborough RM

更新日期：2001-05-21 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