Novel pyridone EP4 agonists featuring allylic alcohol ω-chains.

abstract：:Chimeric molecules which effect intracellular degradation of target proteins via E3 ligase-mediated ubiquitination (e.g., PROTACs) are currently of high interest in medicinal chemistry. However, these entities are relatively large compounds that often possess molecular characteristics which may compromise oral bioavai...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dragovich PS,Adhikari P,Blake RA,Blaquiere N,Chen J,Cheng YX,den Besten W,Han J,Hartman SJ,He J,He M,Rei Ingalla E,Kamath AV,Kleinheinz T,Lai T,Leipold DD,Li CS,Liu Q,Lu J,Lu Y,Meng F,Meng L,Ng C,Peng K,Le

更新日期：2020-02-15 00:00:00

abstract：:Two nemadectin congeners 1 and 2 were isolated from the fermentation broth of a mutant strain (Y-3) of Streptomyces microflavus neau3. Their structures were determined on the basis of extensive spectroscopic analysis and comparison with data from the literature. Compound 2 possessed a 5-membered ring lactone that is u...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang LY,Wang JD,Zhang J,Xue CY,Zhang H,Wang XJ,Xiang WS

更新日期：2013-10-15 00:00:00

abstract：:A series of orthoalkylaminophenol derivatives was synthesized and tested in vitro with respect to their neuroprotective effect. Some of these compounds exhibited a potent antioxidant activity close to that of standard alpha-tocopherol. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Larget R,Lockhart B,Pfeiffer B,Neudorffer A,Fleury MB,Largeron M

更新日期：1999-10-18 00:00:00

abstract：:2-(Anilino)imidazolines were identified as novel human 5-HT(1D) receptor ligands, but offered no particular advantage over previously reported 2-(benzyl)imidazolines. Pharmacokinetic and functional data were obtained for selected 2-(benzyl)imidazoline derivatives. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Prisinzano T,Dukat M,Law H,Slassi A,MacLean N,DeLannoy I,Glennon RA

更新日期：2004-09-20 00:00:00

abstract：:For further structure-activity relationship (SAR) research of OSW saponins, a cholestane glycoside, namely 3beta, 16beta, 26-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)-(1-->3)-2-O-acetyl-alpha-L-arabinopyranoside (1) together with two 1-->4-linked disaccharide analogues (2 and 3) we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng D,Zhou L,Guan Y,Chen X,Zhou W,Chen X,Lei P

更新日期：2010-09-15 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 stereocontrolled synthetic route has been used to prepare two of the geometric isomers of all-trans-GGPP. Neither of these isomers is effective substrates for mammalian GGTase I, but 3 is a potent inhibitor of this enzyme (IC(50)=100 nM). Surprisingly, both compounds are effective substrates for mammalian FTase. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zahn TJ,Whitney J,Weinbaum C,Gibbs RA

更新日期：2001-06-18 00:00:00

abstract：:As part of the presented research, thirteen new aminoalkanol derivatives were designed and obtained by chemical synthesis. In vivo studies (mice, i.p.) showed anticonvulsant activity (MES) of nine compounds, and in the case of one compound (R,S-trans-2-((2-(2,3,5-trimethylphenoxy)ethyl)amino)cyclohexan-1-ol, 4) both a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pańczyk K,Rapacz A,Furgała-Wojas A,Sałat K,Koczurkiewicz-Adamczyk P,Łucjanek M,Skiba-Kurek I,Karczewska E,Sowa A,Żelaszczyk D,Siwek A,Popiół J,Pękala E,Marona H,Waszkielewicz A

更新日期：2020-08-15 00:00:00

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：:Novel L- and D-configuration dioxolane 5-azacytosine and 6-azathymine nucleosides have been synthesized and evaluated for biological activity. (-)-(2S,4S)-1-[2-(Hydroxymethyl)-1,3-dioxolan-4-yl]-5-azacytosine (6) showed significant activity against HBV, whereas the D-configuration analogue (14) has been found to exhib...

journal_title：Bioorganic & medicinal chemistry letters

authors： Luo MZ,Liu MC,Mozdziesz DE,Lin TS,Dutschman GE,Gullen EA,Cheng YC,Sartorelli AC

更新日期：2000-09-18 00:00:00

abstract：:A series of 4-amino-pyrido[2,3-d]pyrimidin-5(8H)-ones were designed and synthesized as a novel class of inhibitors of NAD(+)-dependent DNA ligase that possess potency against Gram-positive bacteria. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang T,Duncan L,Gu W,O'Dowd H,Wei Y,Perola E,Parsons J,Gross CH,Moody CS,Arends SJ,Charifson PS

更新日期：2012-06-01 00:00:00

abstract：:A series of novel pyrimido and other fused quinoline derivatives like 4-methyl pyrimido [5,4-c]quinoline-2,5(1H,6H)-dione (4a), 4-methyl-2-thioxo-1,2-dihydropyrimido [5,4-c]quinoline-5(6H)-one (4b), 2-amino-4-methyl-1,2-dihydropyrimido [5,4-c]quinolin-5(6H)-one (4c), 3-methylisoxazolo [4,5-c]quinolin-4(5H)-one (4d), 3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sankaran M,Kumarasamy C,Chokkalingam U,Mohan PS

更新日期：2010-12-01 00:00:00

abstract：:Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was con...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song JL,Zhang J,Liu CL,Liu C,Zhu KK,Yang FF,Liu XG,Figueiró Longo JP,Alexandre Muehlmann L,Azevedo RB,Zhang YY,Guo YW,Jiang CS,Zhang H

更新日期：2017-10-15 00:00:00

abstract：:Synthesis and biological evaluation of novel and potent cyclohexylamine-based histamine H3 receptor inverse agonists are described. Compounds in this newly identified series exhibited subnanomolar binding affinities for human receptor and no significant interaction with hERG channel. One derivative (10t) demonstrated ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Labeeuw O,Levoin N,Poupardin-Olivier O,Calmels T,Ligneau X,Berrebi-Bertrand I,Robert P,Lecomte JM,Schwartz JC,Capet M

更新日期：2011-09-15 00:00:00

abstract：:A series of benzotriazole phenyldifluoromethylphosphonic acids were found to be potent PTP-1B inhibitors. Molecular modeling on the X-ray crystal structure of the lead structure led to the design of potent PTP-1B inhibitors that show moderate selectivity against TC-PTP, a very closely related protein tyrosine phosphat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lau CK,Bayly CI,Gauthier JY,Li CS,Therien M,Asante-Appiah E,Cromlish W,Boie Y,Forghani F,Desmarais S,Wang Q,Skorey K,Waddleton D,Payette P,Ramachandran C,Kennedy BP,Scapin G

更新日期：2004-02-23 00:00:00

abstract：:The syntheses and biological profiles of sulfoximine-based Vioxx analogs 2 are described. Interesting data have been obtained for 2a, which shows a selective COX-2 inhibition (albeit not as strong as Vioxx itself) exhibiting reduced hERG activity compare to the parent sulfone Vioxx (1). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park SJ,Buschmann H,Bolm C

更新日期：2011-08-15 00:00:00

abstract：:2'-O-[N-(4-Aminobutylcarbamoyl)]uridine (U(abcm)) was synthesized and incorporated into oligonucleotides. The oligonucleotides incorporating U(abcm) formed more stable duplexes with their complementary and mismatched RNAs than those containing 2'-O-carbamoyluridine (U(cm)). The stability of duplex with a U(abcm)-rG ba...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seio K,Tokugawa M,Kanamori T,Tsunoda H,Ohkubo A,Sekine M

更新日期：2012-04-01 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：:We sought to design dual pharmacology bronchodilators targeting both the M(3) muscarinic acetylcholine and beta-2 adrenergic (β(2)) receptors by applying our multivalent approach to drug discovery. Herein, we describe our initial discovery and the SAR of the first such compounds with matched potencies at both receptor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hughes AD,Chin KH,Dunham SL,Jasper JR,King KE,Lee TW,Mammen M,Martin J,Steinfeld T

更新日期：2011-03-01 00:00:00

abstract：:A versatile synthesis of diazirine-based photoreactive fatty acid analogues is reported. The key step is phenoxy alkylation of diazirine with halo alkyl acid esters. The conditions described will be acceptable for the synthesis of various alkyl-length derivatives. The fatty acid derivatives are acceptors for reverse r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hashimoto M,Hatanaka Y,Nabeta K

更新日期：2002-01-07 00:00:00

abstract：:Based on the information from molecular modeling and X-ray crystal structures, the kinase specificity pocket of ITK could be occupied upon extension of the right-hand-side of the 2-benzimidazole core of the inhibitors. 2-Aminobenzimidazoles with a trans-stilbene-like extension were designed and synthesized as novel IT...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lo HY,Bentzien J,Fleck RW,Pullen SS,Khine HH,Woska JR Jr,Kugler SZ,Kashem MA,Takahashi H

更新日期：2008-12-01 00:00:00

abstract：:Ganglioside GM1 mimics including (R)-2-hydroxy-3-cyclohexylpropionic acid or (R)-2-hydroxy-3-phenylpropionic acid as replacements for NeuAc are stronger cholera toxin binders than the parent ligand 2, which includes (R)-2-hydroxy-propionic acid. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arosio D,Baretti S,Cattaldo S,Potenza D,Bernardi A

更新日期：2003-11-03 00:00:00

abstract：:5-Ethynyl-2'-deoxyuridine is a common base-modified nucleoside analogue that has served in various applications including selection experiments for potent aptamers and in biosensing. The synthesis of the corresponding triphosphates involves a mild acidic deprotection step. Herein, we show that this deprotection leads ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Röthlisberger P,Levi-Acobas F,Hollenstein M

更新日期：2017-02-15 00:00:00

abstract：:A new acylphenol, malabaricone E (1) together with the known malabaricones A-C (2-4), maingayones A and B (5 and 6) and maingayic acid B (7) were isolated from the ethyl acetate extract of the fruits of Myristica cinnamomea King. Their structures were determined by 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Co...

journal_title：Bioorganic & medicinal chemistry letters

authors： Abdul Wahab SM,Sivasothy Y,Liew SY,Litaudon M,Mohamad J,Awang K

更新日期：2016-08-01 00:00:00

abstract：:Incorporation of a 4-hydroxy-N-acetylprolinol nucleotide analogue at the 3'-terminus of DNA or 2-5A-DNA sequences resulted in a significantly enhanced 3'-exonuclease resistance while the affinity for complementary RNA was only slightly decreased. Furthermore, the binding to and activation of human RNase L by thus modi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Verheijen JC,van Roon AM,Meeuwenoord NJ,Stuivenberg HR,Bayly SF,Chen L,van der Marel GA,Torrence PF,van Boom JH

更新日期：2000-04-17 00:00:00

abstract：:A number of analogues of the recently described compound nematophin were prepared and studied for antibacterial activity. The 2-phenyl derivative was found to exhibit exceptional activity against methicillin resistant Staphylococcus aureus (MRSA) whereas the isosteric benzimidazole analogue was much less active. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kennedy G,Viziano M,Winders JA,Cavallini P,Gevi M,Micheli F,Rodegher P,Seneci P,Zumerle A

更新日期：2000-08-07 00:00:00

abstract：:A new series of 2-(benzyloxy)benzamides are presented that are potent functional antagonists of TRPM8 and possess improved LipE and LE compared to the original lead. They were discovered through a series of compound libraries and we present a powerful visualization method for the chemical space explored with each libr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Brown A,Ellis D,Favor DA,Kirkup T,Klute W,MacKenny M,McMurray G,Stennett A

更新日期：2013-11-15 00:00:00

abstract：:Mifepristone is a non-selective antagonist of 3-oxosteroid receptors with both abortifacient and anti-endometriotic activities. Non-steroidal mimetics of mifepristone and progesterone are important templates for modulation of the progesterone receptor (PR). For our PR program, we sought an unexplored, synthetically ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jones DG,Liang X,Stewart EL,Noe RA,Kallander LS,Madauss KP,Williams SP,Thompson SK,Gray DW,Hoekstra WJ

更新日期：2005-07-01 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 analogues of the previously described 3-aryl pyridone KOR agonists have been synthesised by parallel synthetic methods, both in solution- and with solid-phase chemistry, making use of the well known and versatile Mitsunobu, Suzuki and Buchwald reactions. Opioid receptor binding data for the compounds produced is r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Semple G,Andersson BM,Chhajlani V,Georgsson J,Johansson MJ,Rosenquist A,Swanson L

更新日期：2003-03-24 00:00:00