Identification of a highly potent and selective CB2 agonist, RQ-00202730, for the treatment of irritable bowel syndrome.

abstract：:Huisgen [3+2] dipolar cycloaddition of 6″-azido-6″-deoxy-α-galactosyl ceramide 11 with a range of alkynes (or a benzyne precursor) yielded a series of triazole-containing α-galactosyl ceramide (α-GalCer) analogues in high yield. These α-GalCer analogues and the precursor azide 11 were tested for their ability to activ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jervis PJ,Graham LM,Foster EL,Cox LR,Porcelli SA,Besra GS

更新日期：2012-07-01 00:00:00

abstract：:Halogenated furanones, a group of natural products initially isolated from marine red algae, are known to inhibit bacterial biofilm formation, swarming, and quorum sensing. However, their molecular targets and the precise mode of action remain elusive. Herein, we show that a naturally occurring brominated furanone cov...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zang T,Lee BW,Cannon LM,Ritter KA,Dai S,Ren D,Wood TK,Zhou ZS

更新日期：2009-11-01 00:00:00

abstract：:A series of 1-aryl-6,7-dihydroxyl(methoxy)-1,2,3,4-tetrahydroisoquinolines (compounds 1-36) were synthesized via Pictet-Spengler cyclization. All the synthesized compounds were assayed for activities against HIV-1(IIIB) in C8166 cell cultures by MTT method for the first time. The results of the anti-HIV screening reve...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheng P,Huang N,Jiang ZY,Zhang Q,Zheng YT,Chen JJ,Zhang XM,Ma YB

更新日期：2008-04-01 00:00:00

abstract：:The general strategy and rationale underlying the design of COPD therapeutics that possess protease inhibitory activity and are also capable of releasing a species that attenuates inflammation by inhibiting caspase-1, are described. The synthesis and in vitro biochemical evaluation of a dual function molecule that seq...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dou D,He G,Alliston KR,Groutas WC

更新日期：2011-05-15 00:00:00

abstract：:A series of N-2-(4-(4-(2-substitutedthiazol-4-yl) piperazin-1-yl)-2-oxoethyl)acetamides were synthesized in an effort to prepare novel atypical antipsychotic agents. The compounds were synthesized by either microwave irradiation technique or by conventional synthesis and were characterized by spectral data (IR, (1)H N...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sekhar KV,Rao VS,Devambatla RKV,Kumar MM

更新日期：2008-12-01 00:00:00

abstract：:The synthesis and structure-activity relationship studies of 1,4,5,6-tetrahydropyridazines are described. The target compounds 3-5 represent a novel class of potent and selective CB1 receptor antagonists. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lange JH,den Hartog AP,van der Neut MA,van Vliet BJ,Kruse CG

更新日期：2009-10-01 00:00:00

abstract：:Two regioisomeric isoxazoline monoacetates 1 and 2 were synthesized from the corresponding diacetate 3 via PPL or PLE catalyzed hydrolysis. With both the enzymes, the initial regioselectivity (approximately 3-4:1) was offset by an intramolecular acyl transfer. In addition to a non-enzymatic catalysis for the acyl tran...

journal_title：Bioorganic & medicinal chemistry letters

authors： Basak A,Bisai S

更新日期：2005-05-16 00:00:00

abstract：:The structure-activity relationship studies of a novel series of carboxylic acid derivatives of pyridine-carboxamides as DGAT-1 inhibitors is described. The optimization of the initial lead compound 6 based on in vitro and in vivo activity led to the discovery of key compounds 10j and 17h. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ting PC,Lee JF,Zorn N,Kim HM,Aslanian RG,Lin M,Smith M,Walker SS,Cook J,Van Heek M,Lachowicz J

更新日期：2013-02-15 00:00:00

abstract：:The synthesis and evaluation of small molecule antagonists of the G protein-coupled receptor NPBWR1 (GPR7) are reported for the first time. [4-(5-Chloropyridin-2-yl)piperazin-1-yl][(1S,2S,4R)-4-{[(1R)-1-(4-methoxyphenyl)ethyl]amino}-2-(thiophen-3-yl)cyclohexyl]methanone (1) emerged as a hit from a high-throughput scre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Anthony Romero F,Hastings NB,Moningka R,Guo Z,Wang M,Di Salvo J,Lei Y,Trusca D,Deng Q,Tong V,Terebetski JL,Ball RG,Ujjainwalla F

更新日期：2012-01-15 00:00:00

abstract：:We herein report the discovery of four series of fused 5,6-bicyclic heterocycles as γ-secretase modulators. Synthesis and SAR of these series are discussed. These compounds represent a new class of γ-secretase modulators that demonstrate moderate to good in vitro potency in inhibiting Aβ(42) production. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qin J,Dhondi P,Huang X,Mandal M,Zhao Z,Pissarnitski D,Zhou W,Aslanian R,Zhu Z,Greenlee W,Clader J,Zhang L,Cohen-Williams M,Jones N,Hyde L,Palani A

更新日期：2011-01-15 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：:Isoxazoles are frequently used amide isosteres, as shown in the context of discovery of CRTh2 antagonists from amide 1 to isoxazole 2. However, persistent agonism and poor solubility in isoxazole series presented challenges to its further development. Based on the concept of quality by design (QbD), 5,5-disubstituted ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiao D,Zhu X,Yu Y,Shao N,Wu J,McCormick KD,Dhondi P,Qin J,Mazzola R,Tang H,Rao A,Siliphaivanh P,Qiu H,Yang X,Rivelli M,Garlisi CG,Eckel S,Mukhopadhyay G,Correll C,Rindgen D,Aslanian R,Palani A

更新日期：2014-03-15 00:00:00

abstract：:A series of analogs of GLP-1(7-36) amide containing a Nepsilon-(2-[2-[2-(3-maleimidopropylamido)ethoxy]ethoxy]acetyl)lysine has been synthesized and the resulting derivatives were bioconjugated to Cys34 of human serum albumin (HSA). The GLP-1-HSA bioconjugates were analyzed in vitro to assess the stabilizing effect of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Léger R,Thibaudeau K,Robitaille M,Quraishi O,van Wyk P,Bousquet-Gagnon N,Carette J,Castaigne JP,Bridon DP

更新日期：2004-09-06 00:00:00

abstract：:Benzylamides of pentanedioic acid were identified as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) by high-throughput screening. Optimisation to 2-adamantyl amides yielded inhibitors with single digit nanomolar IC(50)s on the 11beta-HSD1 human isoform. The hydroxy adamantyl amide lead compound...

journal_title：Bioorganic & medicinal chemistry letters

authors： Roche D,Carniato D,Leriche C,Lepifre F,Christmann-Franck S,Graedler U,Charon C,Bozec S,Doare L,Schmidlin F,Lecomte M,Valeur E

更新日期：2009-05-15 00:00:00

abstract：:Indoleamine 2,3-dioxygenase 2 (IDO2) is a potential therapeutic target for the treatment of diseases that involve immune escape such as cancer. In contrast to IDO1, only a very limited number of inhibitors have been described for IDO2 due to inherent difficulties in expressing and purifying a functionally active, solu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Röhrig UF,Majjigapu SR,Caldelari D,Dilek N,Reichenbach P,Ascencao K,Irving M,Coukos G,Vogel P,Zoete V,Michielin O

更新日期：2016-09-01 00:00:00

abstract：:The peptide ligase subtiligase, derived from subtilisin, has been employed in the identification of protein N-termini in complex mixtures. Here, the peptide ester substrates for the ligation reaction were optimized with respect to solubility, resulting in greater incorporation of the N-terminal tags. Additionally, the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yoshihara HA,Mahrus S,Wells JA

更新日期：2008-11-15 00:00:00

abstract：:Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodelin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wu Y,Li J,Wu J,Morgan P,Xu X,Rancati F,Vallese S,Raveglia L,Hotchandani R,Fuller N,Bard J,Cunningham K,Fish S,Krykbaev R,Tam S,Goldman SJ,Williams C,Mansour TS,Saiah E,Sypek J,Li W

更新日期：2012-01-01 00:00:00

abstract：:It is well known that resveratrol (RSV) displayed cancer-preventing and anticancer properties but its clinical application is limited because of a low bioavailability and a rapid clearance from the circulation. Aim of this work was to synthesize pharmacologically active resveratrol analogs with an enhanced structural ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sala M,Chimento A,Saturnino C,Gomez-Monterrey IM,Musella S,Bertamino A,Milite C,Sinicropi MS,Caruso A,Sirianni R,Tortorella P,Novellino E,Campiglia P,Pezzi V

更新日期：2013-09-01 00:00:00

abstract：:Fifteen novel C5 analogues of thiolactomycin (13 biphenyl analogues and two biphenyl mimics) have been synthesised and assessed for their in vitro mtFabH and whole cell Mycobacterium bovis BCG activity, respectively. Analysis of the 15 compounds revealed that six possessed enhanced in vitro activity in a direct mtFabH...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bhowruth V,Brown AK,Senior SJ,Snaith JS,Besra GS

更新日期：2007-10-15 00:00:00

abstract：:A series of compounds possessing both H(1) histamine receptor antagonist and 5-lipoxygenase (5-LO) inhibitory activities was synthesized. The H(1)-binding scaffolds of cetirizine, efletirizine, and loratadine were linked to a lipophilic N-hydroxyurea, the 5-LO inhibiting moiety of zileuton. Both activities were observ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lewis TA,Young MA,Arrington MP,Bayless L,Cai X,Collart P,Eckman JB,Ellis JL,Ene DG,Libertine L,Nicolas JM,Scannell RT,Wels BF,Wenberg K,Wypij DM

更新日期：2004-11-15 00:00:00

abstract：:The optimisation of affinity and selectivity in a novel series of dual 5-HT5A/5-HT7 receptor ligands is described. Brain penetrant 2-aminodihydroquinazolines with low nanomolar affinities were identified. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Peters JU,Lübbers T,Alanine A,Kolczewski S,Blasco F,Steward L

更新日期：2008-01-01 00:00:00

abstract：:Conformationally restricted analogues of the central linker unit of bacterial methionyl tRNA synthetase (MRS) inhibitors have been prepared. The (1S,2R)-cyclopentylmethyl moiety was identified as the preferred cyclic linker, with significant diastereo- and enantioselectivity of activity. Combination of this linker wit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jarvest RL,Berge JM,Brown P,Houge-Frydrych CS,O'Hanlon PJ,McNair DJ,Pope AJ,Rittenhouse S

更新日期：2003-04-07 00:00:00

abstract：:A series of 7-diethylaminocoumarin compounds were synthesized and the cytotoxicities were tested against human umbilical vein endothelial cell (HUVEC) and some cancer cells. We found that the introduction of cyano groups at the 4-position will promote the bioactivity. In particular, compounds 9 and 10 strongly inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee S,Sivakumar K,Shin WS,Xie F,Wang Q

更新日期：2006-09-01 00:00:00

abstract：:Biaryl substituted 2,5-diazabicyclo[2.2.1]heptanes have been synthesized and tested for their affinity toward alpha7 neuronal nicotinic receptors (NNRs). SAR studies established that 5-N-methyl substituent, heteroaryl linker and the nature of terminal aryl group are critical for the ligand to achieve potent alpha7 NNR...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li T,Bunnelle WH,Ryther KB,Anderson DJ,Malysz J,Helfrich R,Grønlien JH,Håkerud M,Peters D,Schrimpf MR,Gopalakrishnan M,Ji J

更新日期：2010-06-15 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：:Chronic hepatitis C infection is the leading causes for cirrhosis of the liver and hepatocellular carcinoma, leading to liver failure and liver transplantation. The etiological agent, HCV virus produces a single positive strand of RNA that is processed with the help of serine protease NS3 to produce mature virus. Inhi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Venkatraman S,Wu W,Prongay A,Girijavallabhan V,George Njoroge F

更新日期：2009-01-01 00:00:00

abstract：:Starting from literature examples of nonsteroidal anti-inflammatory drugs (NSAIDs)-type carboxylic acid γ-secretase modulators (GSMs) and using a scaffold design approach, we identified 4-aminomethylphenylacetic acid 4 with a desirable γ-secretase modulation profile. Scaffold optimization led to the discovery of a nov...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xin Z,Peng H,Zhang A,Talreja T,Kumaravel G,Xu L,Rohde E,Jung MY,Shackett MN,Kocisko D,Chollate S,Dunah AW,Snodgrass-Belt PA,Arnold HM,Taveras AG,Rhodes KJ,Scannevin RH

更新日期：2011-12-15 00:00:00

abstract：:The discovery of a series of novel, potent, and selective blockers of the cyclic nucleotide-modulated channel HCN1 is disclosed. Here we report an SAR study around a series of selective blockers of the HCN1 channel. Utilization of a high-throughput VIPR assay led to the identification of a novel series of 2,2-disubsti...

journal_title：Bioorganic & medicinal chemistry letters

authors： McClure KJ,Maher M,Wu N,Chaplan SR,Eckert WA 3rd,Lee DH,Wickenden AD,Hermann M,Allison B,Hawryluk N,Breitenbucher JG,Grice CA

更新日期：2011-09-15 00:00:00

abstract：:Cyclic azobenzene carboxylic acid was synthesized using a shortened route. After reaction with D-threolinol, the resulting cyclic azobenzene-D-threolinol (cAB-Thr) building block was transformed into the corresponding DMTr-protected phosphoramidite, and incorporated into oligodeoxynucleotides at various positions and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Eljabu F,Dhruval J,Yan H

更新日期：2015-12-01 00:00:00

abstract：:The structure-based approaches were implemented to design and rationally select the molecules for synthesis and anti-HCV activity evaluation. The systematic structure-activity relationships of previously discovered molecules (types I, II, III) were analyzed to design new molecules (type IV) by bioisosteric replacement...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thiyagarajan A,Salim MT,Balaraju T,Bal C,Baba M,Sharon A

更新日期：2012-12-15 00:00:00