Aminopyrrolidineamide inhibitors of site-1 protease.

abstract：:Inhibition of 11beta-HSD1 has demonstrated potential in the treatment of various components of metabolic syndrome. We wish to report herein the discovery of novel azabicyclic sulfonamide based 11beta-HSD1 inhibitors. Highly potent compounds exhibiting inhibitory activities at both human and mouse 11beta-HSD1 were iden...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shah U,Boyle CD,Chackalamannil S,Baker H,Kowalski T,Lee J,Terracina G,Zhang L

更新日期：2010-03-01 00:00:00

abstract：:A novel caspase-3 substrate N-Ac-DEVD-N'-MC-R110, which is a fluorogenic substrate cleavable in a single step, has been prepared. It has a significantly higher enzyme turnover rate and sensitivity for detecting caspase-3 activity both in solution and living cells than existing fluorogenic substrates. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang ZQ,Liao J,Diwu Z

更新日期：2005-05-02 00:00:00

abstract：:A variety of new prodrugs of 2'-methyl cytidine based on acyloxy ethylamino phosphoramidates have been synthesized and tested in vitro and in vivo for their biological activity. Compared with the parent drug a 10- to 20-fold increase in formation of nucleotide triphosphate in rat and human hepatocytes could be achieve...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donghi M,Attenni B,Gardelli C,Marco AD,Fiore F,Giuliano C,Laufer R,Leone JF,Pucci V,Rowley M,Narjes F

更新日期：2009-03-01 00:00:00

abstract：:Vitamin D receptor (VDR) ligands are therapeutic agents for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. VDR ligands also show immense potential as therapeutic agents for autoimmune diseases and cancers of the skin, prostate, colon, and breast as well as leukemia. LG190178 is a novel no...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hakamata W,Sato Y,Okuda H,Honzawa S,Saito N,Kishimoto S,Yamashita A,Sugiura T,Kittaka A,Kurihara M

更新日期：2008-01-01 00:00:00

abstract：:Investigations of a biaryl ether scaffold identified tetrahydronaphthalene Raf inhibitors with good in vivo activity; however these compounds had affinity toward the hERG potassium channel. Herein we describe our work to eliminate this hERG activity via alteration of the substituents on the benzoic amide functionality...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang SC,Adhikari S,Afroze R,Brewer K,Calderwood EF,Chouitar J,England DB,Fisher C,Galvin KM,Gaulin J,Greenspan PD,Harrison SJ,Kim MS,Langston SP,Ma LT,Menon S,Mizutani H,Rezaei M,Smith MD,Zhang DM,Gould AE

更新日期：2016-02-15 00:00:00

abstract：:This report describes the design and synthesis of a series of CCR2 antagonists incorporating novel non-aryl/heteroaryl RHS (right hand side) motifs. Previous SAR in the area has suggested an aryl/heteroaryl substituent as a necessary structural feature for binding to the CCR2 receptor. Herein we describe the SAR with ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Trujillo JI,Huang W,Hughes RO,Rogier DJ,Turner SR,Devraj R,Morton PA,Xue CB,Chao G,Covington MB,Newton RC,Metcalf B

更新日期：2011-03-15 00:00:00

abstract：:The alpha7 subtype of the nicotinic acetylcholine receptor (nAChR) is the target of studies aimed at identifying features that will lead to the development of selective therapeutics. Five arylidine anabaseines, three with pyridine rings and two with the pyrrole rings, were synthesized in 35-65% yield via aldol condens...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang J,Papke RL,Horenstein NA

更新日期：2009-01-15 00:00:00

abstract：:The manuscript reports an identification of a highly potent, orally bioavailable hepatitis C virus entry inhibitor through optimization of a previously reported class of molecules (1) that were not stable in the rat plasma. Compound 39 (ITX 4520) exhibited an excellent PK profile in both rats and dogs with good oral e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mittapalli GK,Zhao F,Jackson A,Gao H,Lee H,Chow S,Kaur MP,Nguyen N,Zamboni R,McKelvy J,Wong-Staal F,Macdonald JE

更新日期：2012-08-01 00:00:00

abstract：:Novel phenethylpyridone derivatives were identified as potent human melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. A search for surrogates for the 4-(2-aminoethoxy)phenyl moiety of 1 resulted in discovery of 2-[4-(aminomethyl)phenyl]ethyl substructure as in 6a. Successive optimization of the right-hand...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ando M,Sekino E,Haga Y,Moriya M,Ito M,Ito J,Iwaasa H,Ishihara A,Kanatani A,Ohtake N

更新日期：2009-09-01 00:00:00

abstract：:The synthesis of three series of quinol fatty alcohols (QFAs) and their biological activities on the promotion of axonal growth are described. Interestingly, the 15-(2,5-dimethoxyphenyl)pentadecan-1-ol, the QFA bearing 15 carbon atoms on the side chain (n=15), shows the most potent promotion of axonal growth in the pr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanbali M,Vela-Ruiz M,Bagnard D,Luu B

更新日期：2006-05-15 00:00:00

abstract：:The application of a novel solid-phase synthesis of 2,3-disubstituted indoles utilizing a carbamate indole linker is described resulting in the identification of the novel, high-affinity, selective h5-HT2A antagonist 19. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Smith AL,Stevenson GI,Lewis S,Patel S,Castro JL

更新日期：2000-12-18 00:00:00

abstract：:With the aim of improving HCV protease inhibitors reported in our previous manuscripts, we synthesized and evaluated a series of 1a-based tetrapeptidyl alpha-ketoamides with additional P4 modification. The promising analog discovered through this SAR, 5a, was further derivatized at P1' or P1 position. As a result of t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yip Y,Victor F,Lamar J,Johnson R,Wang QM,Glass JI,Yumibe N,Wakulchik M,Munroe J,Chen SH

更新日期：2004-10-04 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：:The structure-activity relationship (SAR) of the vinyl pyridine region of himbacine derived thrombin receptor (PAR-1) antagonists is described. A 2-vinylpyridyl ring substituted with an aryl or a heteroaryl group at the 5-position showed the best overall PAR-1 affinity and pharmacokinetic properties. One of the newly ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xia Y,Chackalamannil S,Clasby M,Doller D,Eagen K,Greenlee WJ,Tsai H,Agans-Fantuzzi J,Ahn HS,Boykow GC,Hsieh Y,Lunn CA,Chintala M

更新日期：2007-08-15 00:00:00

abstract：:Two thermostable α-carbonic anhydrases (α-CAs) isolated from thermophilic Sulfurihydrogenibium spp., namely SspCA (from S. yellowstonensis) and SazCA (from S. azorense), were shown in a previous work to possess interesting complementary properties. SspCA was shown to have an exceptional thermal stability, whereas SazC...

journal_title：Bioorganic & medicinal chemistry letters

authors： De Simone G,Monti SM,Alterio V,Buonanno M,De Luca V,Rossi M,Carginale V,Supuran CT,Capasso C,Di Fiore A

更新日期：2015-05-01 00:00:00

abstract：:Sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Starting from a screening hit 8 that had modest affinity for the cannabinoid CB(2) receptor, a parallel synthesis approach and initial SAR are described, leading to compound 27 with 120-fold functional selectivity for the CB(2) rec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Worm K,Zhou QJ,Saeui CT,Green RC,Cassel JA,Stabley GJ,DeHaven RN,Conway-James N,LaBuda CJ,Koblish M,Little PJ,Dolle RE

更新日期：2008-05-01 00:00:00

abstract：:Previously we reported the optimization of antiviral scaffolds containing benzimidazole and related heterocycles possessing activity against a variety of arenaviruses. These series of compounds were discovered through an HTS campaign of a 400,000 small molecule library using lentivirus-based pseudotypes incorporated w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Burgeson JR,Gharaibeh DN,Moore AL,Larson RA,Amberg SM,Bolken TC,Hruby DE,Dai D

更新日期：2013-11-01 00:00:00

abstract：:Apparent kinetic constants k(cat) and K(m) were determined for tyrocidine thioesterase (TycC TE) using randomized peptide N-acetylcysteamine thioesters as substrate analogues. The enzyme has been found to be adequately active for the synthesis of positional-scanning libraries for novel antibiotic screening with reduce...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xie G,Uttamchandani M,Chen GY,Bu X,Lin SS,Wong KM,Yan W,Yao SQ,Guo Z

更新日期：2002-03-25 00:00:00

abstract：:A library of natural and semi-synthetic Amaryllidaceae alkaloids was screened for cytochrome P450 3A4 (CYP3A4) inhibitory activity. Of the crinane, lycorane and galanthamine representatives examined two semi-synthetic silylated lycorane analogues, accessed via a chemoselective silylation strategy from lycorine, and th...

journal_title：Bioorganic & medicinal chemistry letters

authors： McNulty J,Nair JJ,Singh M,Crankshaw DJ,Holloway AC,Bastida J

更新日期：2009-06-15 00:00:00

abstract：:Two new cyclic octapeptides, mariannamides A (1) and B (2), have been isolated from Mariannaea elegans NBRC102301, a Pinus densiflora-derived filamentous fungus. Their structures were elucidated to be cyclo-(l-Leu1-l-Pro1-l-Pro2-l-Leu2-l-Ile1-l-Pro3-l-Val1-l-Ile2) and cyclo-(l-Leu1-l-Pro1-l-Pro2-l-Leu2-l-Ile1-l-Pro3-l...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishiuchi K,Hirose D,Kondo T,Watanabe K,Terasaka K,Makino T

更新日期：2020-02-15 00:00:00

abstract：:High-throughput screening of the GSK compound collection against the P2Y(1) receptor identified a novel series of tetrahydro-4-quinolinamine antagonists. Optimal substitution around the piperidine group was pivotal for ensuring activity. An exemplar analog from this series was shown to inhibit platelet aggregation. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morales-Ramos AI,Mecom JS,Kiesow TJ,Graybill TL,Brown GD,Aiyar NV,Davenport EA,Kallal LA,Knapp-Reed BA,Li P,Londregan AT,Morrow DM,Senadhi S,Thalji RK,Zhao S,Burns-Kurtis CL,Marino JP Jr

更新日期：2008-12-01 00:00:00

abstract：:Cocaine binds into beta-cyclodextrin, but not detectably into alpha- or gamma-cyclodextrin, in water solution. NMR studies indicate the geometry of the complex, which is confirmed by molecular mechanics calculations and binding studies on cocaine analogues and cyclodextrin dimers. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nesna N,Lou J,Breslow R

更新日期：2000-09-04 00:00:00

abstract：:The stereoselective synthesis and biological activity of NPS 1407 (4a), (S)-(-)-3-amino-1,1-bis(3-fluorophenyl)butane, a potent, stereoselective antagonist of the NMDA receptor, are described. The racemate (4) was found to be active at the NMDA receptor in an in vitro assay, prompting the synthesis of the individual s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moe ST,Smith DL,DelMar EG,Shimizu SM,Van Wagenen BC,Balandrin MF,Chien YE,Raszkiewicz JL,Artman LD,White HS,Mueller AL

更新日期：2000-11-06 00:00:00

abstract：:Identification of an HIV integrase inhibitor with micromolar affinity for the CGRP receptor led to the discovery of a series of structurally novel CGRP receptor antagonists. Optimization of this series produced compound 16, a low-molecular weight CGRP receptor antagonist with good pharmacokinetic properties in both ra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zartman CB,Bell IM,Gallicchio SN,Graham SL,Kane SA,Mallee JJ,Rutledge RZ,Salvatore CA,Vacca JP,Williams TM

更新日期：2011-11-15 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 report the development of a chemical modification method of general applicability to polyphenols, which increases solubility to influence absorption. Glucosyl groups were added to the resveratrol kernel via a succinate linker, yielding 3,4',5-tri-(alpha-D-glucose-3-O-succinyl) resveratrol. The construct was only sl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Biasutto L,Marotta E,Bradaschia A,Fallica M,Mattarei A,Garbisa S,Zoratti M,Paradisi C

更新日期：2009-12-01 00:00:00

abstract：:Phosphoglycolo amidoxime and phosphoglycolo hydrazide, two new derivatives of phosphoglycolic acid, were synthesised and successfully tested as selective competitive inhibitors of class II FBP-aldolases. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fonvielle M,Weber P,Dabkowska K,Therisod M

更新日期：2004-06-07 00:00:00

abstract：:Hypolipidemic effects of the newly synthesized 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-based fibrates were evaluated in Triton WR-1339 and high-fat diet (HFD)-induced hyperlipidemic mice. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton WR-1339 model), in which compo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen ZZ,Xie YD,Shao LH,Wang QT,Xu YH,Bian XL

更新日期：2018-12-15 00:00:00

abstract：:The structural features of an anthrax lethal factor inhibitor, N-oleoyldopamine (OLDA, 1) have been probed. The oleic acid moiety is critical, but, more interestingly, the presence of the double bond and its geometry were found to play an essential role. One compound, 5, was found to be an uncompetitive inhibitor of l...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gaddis BD,Rubert Pérez CM,Chmielewski J

更新日期：2008-04-01 00:00:00

abstract：:A new class of non-ionic amphiphilic molecules suitable for biological purposes, especially extraction of membrane proteins, is reported. Such surfactants were prepared in two steps: addition of alkyl or fluoroalkyl mercaptan on Tris(hydroxymethyl)acrylamidomethane (THAM) derivatives, followed by the oxydation of sulf...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barthélémy P,Maurizis JC,Lacombe JM,Pucci B

更新日期：1998-06-16 00:00:00