N-alkyl-4-[(8-azabicyclo[3.2.1]-oct-3-ylidene)phenylmethyl]benzamides, micro and delta opioid agonists: a micro address.

abstract：:NAD(P)H-dependent oxidoreductases play important roles in biology. Recently, we reported that the luminescence lifetime of some Tb(3+) complexes is sensitive to NAD(P)H, and we used this phenomenon to detect activities of these enzymes. However, conventional time-resolved luminescence assays are susceptible to static ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Terai T,Ito H,Hanaoka K,Komatsu T,Ueno T,Nagano T,Urano Y

更新日期：2016-05-01 00:00:00

abstract：:The design and synthesis of macrocyclic inhibitors of human rhinovirus 3C protease is described. A macrocyclic linkage of the P1 and P3 residues, and the subsequent structure-based optimization of the macrocycle conformation and size led to the identification of a potent biochemical inhibitor 10 with sub-micromolar an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Namoto K,Sirockin F,Sellner H,Wiesmann C,Villard F,Moreau RJ,Valeur E,Paulding SC,Schleeger S,Schipp K,Loup J,Andrews L,Swale R,Robinson M,Farady CJ

更新日期：2018-03-01 00:00:00

abstract：:A modified vancomycin binding pocket (D-O-E ring) incorporating an alpha-hydroxy-beta-amino acid at the AA4 position is designed and synthesized. Some of these compounds display potent bioactivities against both sensitive- and resistant-strains (8 microg/ml against VREF). Both the lipidated aminoglucose and the struct...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jia Y,Gonzalez-Zamora E,Ma N,Liu Z,Bois-Choussy M,Malabarba A,Brunati C,Zhu J

更新日期：2005-10-15 00:00:00

abstract：:A series of substituted 2-aminopyridines was prepared and evaluated as inhibitors of human nitric oxide synthases (NOS). 4,6-Disubstitution enhanced both potency and specificity for the inducible NOS with the most potent compound having an IC50 of 28 nM. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hagmann WK,Caldwell CG,Chen P,Durette PL,Esser CK,Lanza TJ,Kopka IE,Guthikonda R,Shah SK,MacCoss M,Chabin RM,Fletcher D,Grant SK,Green BG,Humes JL,Kelly TM,Luell S,Meurer R,Moore V,Pacholok SG,Pavia T,Williams H

更新日期：2000-09-04 00:00:00

abstract：:Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell line...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alaoui S,Dufies M,Driowya M,Demange L,Bougrin K,Robert G,Auberger P,Pagès G,Benhida R

更新日期：2017-05-01 00:00:00

abstract：:A series of bis(indolyl) hydrazide-hydrazones 5a-n were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines. The reaction of indole-3-carboxaldehyde 2 with indole-3-carbohydrazide 4 in presence of catalytic amount of acetic acid afforded 5a-n in good yields. Among the synthesized ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar D,Maruthi Kumar N,Ghosh S,Shah K

更新日期：2012-01-01 00:00:00

abstract：:Azapeptide ligands of the Insulin Receptor Tyrosine Kinase (IRTK) were developed by solid-phase submonomer azapeptide synthesis in sufficient isolated yields (36-55%) and purities >95% for structure-activity relationship studies. The azapeptides adopted folded geometries with some proportion of random coil according t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kurian LA,Silva TA,Sabatino D

更新日期：2014-09-01 00:00:00

abstract：:An α-carbonic anhydrase (CA, EC 4.2.1.1) isolated from the living fossil sponge Astrosclera willeyana, Astrosclerin, was investigated for its inhibition profile with simple inorganic anions, complex anions and other small molecules known to interact with these zinc enzymes. Astrosclerin is a catalytically highly effic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohradanova A,Vullo D,Pastorekova S,Pastorek J,Jackson DJ,Wörheide G,Supuran CT

更新日期：2012-02-01 00:00:00

abstract：:Structure- and ligand-based virtual-screening methods (docking, 2D- and 3D-similarity searching) were analyzed for their effectiveness in virtual screening against FFAR2. To evaluate the performance of these methods, retrospective virtual screening was performed. Statistical quality of the methods was evaluated by BED...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fells JI,Ai X,Weinglass A,Feng W,Lei Y,Finley M,Hoveyda HR,Fraser GL,Machacek M

更新日期：2020-11-01 00:00:00

abstract：:We describe here the generation of a lead compound and its optimization studies that led to the identification of a novel GPR119 agonist. Based on a spirocyclic cyclohexane structure reported in our previous work, we identified compound 8 as a lead compound, being guided by ligand-lipophilicity efficiency (LLE), which...

journal_title：Bioorganic & medicinal chemistry letters

authors： Harada K,Mizukami J,Watanabe T,Mori G,Ubukata M,Suwa K,Fukuda S,Negoro T,Sato M,Inaba T

更新日期：2019-02-01 00:00:00

abstract：:DNA G-quadruplex is an attractive drug target for anticancer therapy. Most G-quadruplex ligands have little selectivity, due to π-stacking interaction with common G-tetrads surface. Thanks to the varieties of G-quadruplex grooves, the groove-binding ligand is expected to create high selectivity. Therefore, developing ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li J,Jin X,Hu L,Wang J,Su Z

更新日期：2011-12-01 00:00:00

abstract：:We have recently reported that the elaboration of the N-substituent in the δ opioid receptor (DOR) antagonist naltrindole (NTI) enabled the regulation of the DOR activities from full inverse agonists to weak partial agonists. The investigations of amide-type NTI derivatives revealed that N-phenylacetyl and N-dihydroci...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujii H,Uchida Y,Shibasaki M,Nishida M,Yoshioka T,Kobayashi R,Honjo A,Itoh K,Yamada D,Hirayama S,Saitoh A

更新日期：2020-06-15 00:00:00

abstract：:Four novel mononuclear complexes, [Cd(L)2·2H2O] (1), [Ni(L)2·2H2O] (2) [Cu(L)2·H2O] (3), and [Zn(L)2·2H2O] (4) (CCDC numbers: 1444630-1444633 for complexes 1-4) (HL=4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid) were synthesized, and have been characterized by IR spectroscopy, elemental analysis, and X-ray crysta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang DD,Chen YN,Wu YS,Wang R,Chen ZJ,Qin J,Qian SS,Zhu HL

更新日期：2016-07-15 00:00:00

abstract：:The JAK2/STAT pathway has important roles in hematopoiesis. With the discovery of the JAK2 V617F mutation and its presence in many patients with myeloproliferative neoplasms, research in the JAK2 inhibitor arena has dramatically increased. We report a novel series of potent JAK2 inhibitors containing a 2,7-pyrrolotria...

journal_title：Bioorganic & medicinal chemistry letters

authors： Weinberg LR,Albom MS,Angeles TS,Breslin HJ,Gingrich DE,Huang Z,Lisko JG,Mason JL,Milkiewicz KL,Thieu TV,Underiner TL,Wells GJ,Wells-Knecht KJ,Dorsey BD

更新日期：2011-12-15 00:00:00

abstract：:In this Letter, we report the structure-activity relationship (SAR) studies on series of positional isomers of 5(6)-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles derivatives 7(a-j) and 8(a-j) synthesized in good yields and characterized by (1)H NMR, (13)C NMR and mass spectral analyses. The c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ranjith PK,Rajeesh P,Haridas KR,Susanta NK,Row TN,Rishikesan R,Kumari NS

更新日期：2013-09-15 00:00:00

abstract：:A series of novel hybrid molecules 4a-y containing thiazole and benzotriazole templates were designed and synthesized. The structures of the synthesized compounds were elucidated by IR, (1)H NMR, (13)C NMR and mass spectral data. All the synthesized compounds were tested for their antimicrobial activity (zone of inhib...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gaikwad ND,Patil SV,Bobade VD

更新日期：2012-05-15 00:00:00

abstract：:The synthesis and structure-activity relationships (SAR) of Chk1 inhibitors based on a 5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-one core are described. Specifically, an exploration of the 7 and 8 positions on this previously disclosed core afforded compounds with improved enzymatic and cellular potency. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hasvold LA,Wang L,Przytulinska M,Xiao Z,Chen Z,Gu WZ,Merta PJ,Xue J,Kovar P,Zhang H,Park C,Sowin TJ,Rosenberg SH,Lin NH

更新日期：2008-04-01 00:00:00

abstract：:A series of substituted indoles were examined as selective inhibitors of tropomyosin-related kinase receptor A (TrkA), a therapeutic target for the treatment of pain. An SAR optimization campaign based on ALIS screening lead compound 1 is reported. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hurzy DM,Henze DA,Cabalu TD,Narayan K,Heller A,Cooke AJ

更新日期：2017-06-15 00:00:00

abstract：:A series of 4beta-arylamino-4'-O-demethylepipodophyllotoxins and 4beta-arylaminoepipodophyllotoxins have been synthesized with significant stereoselectivity and improved yields by employing the methanesulphonic acid/sodium iodide reagent system. Compounds NPF. W-68 and other DNA topoisomerase II inhibitors are prepare...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kamal A,Laxman N,Ramesh G

更新日期：2000-09-18 00:00:00

abstract：:Synthesis and characterization of an inert perchlorotriphenylmethyl triester radical, PTM-TE, are reported. PTM-TE was prepared by a facile 3-step synthesis using Friedel-Crafts reaction of tetrachlorobenzene with chloroform followed by ethoxycarbonylation and subsequent oxidation. PTM-TE is paramagnetic and exhibits ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dang V,Wang J,Feng S,Buron C,Villamena FA,Wang PG,Kuppusamy P

更新日期：2007-07-15 00:00:00

abstract：:Although thrombin has been extensively researched with many examples of potent and selective inhibitors, the key characteristics of oral bioavailability and long half-life have been elusive. We report here a novel series non-peptidic phenyl-based, highly potent, highly selective and orally bioavailable thrombin inhibi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tomczuk B,Lu T,Soll RM,Fedde C,Wang A,Murphy L,Crysler C,Dasgupta M,Eisennagel S,Spurlino J,Bone R

更新日期：2003-04-17 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：:In the quest to discover a potent and selective class of direct agonists to the sphingosine-1-phosphate receptor, we explored the carboxylate functional group as a replacement to previously reported lead phosphates. This has led to the discovery of potent and selective direct agonists with moderate to substantial in v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Evindar G,Deng H,Bernier SG,Doyle E,Lorusso J,Morgan BA,Westlin WF

更新日期：2013-01-15 00:00:00

abstract：:1,2,3,4-Tetrahydropyrazino[1,2-a]indoles are described as a novel class of I(2) imidazoline receptor ligands. In particular, 8-methoxy-1,2,3,4-tetrahydropyrazino[1,2-a]indole (8-OMe THPI; 3c) binds with high affinity at I(2) imidazoline receptors (K(i)=6.2 nM) and with exceptional (> or =1000-fold) selectivity relativ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chang-Fong J,Tyacke RJ,Lau A,Westaway J,Hudson AL,Glennon RA

更新日期：2004-02-23 00:00:00

abstract：:Spiro-carboxamides were identified as inhibitors of 11beta-hydroxysteroid-dehydrogenase type 1 by high-throughput screening. Structure-based drug design was used to optimise the initial hit yielding a sub-nanomolar IC(50) inhibitor (0.5nM) on human 11beta-HSD1 with a high binding efficiency index (BEI of 32.7) which w...

journal_title：Bioorganic & medicinal chemistry letters

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

更新日期：2009-07-01 00:00:00

abstract：:The efficient synthesis of 7-substituted pyrido[2',3':4,5]furo[3,2-d]pyrimidin-4-amines and their N-aryl analogues is described. 3,5-Dibromopyridine was converted into 3-amino-6-bromofuro[3,2-b]pyridine-2-carbonitrile intermediate which was formylated with DMFDMA. Functionalization at position 7 of the tricyclic scaff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Deau E,Loidreau Y,Marchand P,Nourrisson MR,Loaëc N,Meijer L,Levacher V,Besson T

更新日期：2013-12-15 00:00:00

abstract：:A series of potent dual JAK1/3 inhibitors have been developed from a moderately selective JAK3 inhibitor. Substitution at the C6 position of the pyrrolopyridazine core with aryl groups provided exceptional biochemical potency against JAK1 and JAK3 while maintaining good selectivity against JAK2 and Tyk2. Translation t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hynes J Jr,Wu H,Kempson J,Duan JJ,Lu Z,Jiang B,Stachura S,Tokarski JS,Sack JS,Khan JA,Lippy JS,Zhang RF,Pitt S,Shen G,Gillooly K,McIntyre K,Carter PH,Barrish JC,Nadler SG,Salter-Cid LM,Fura A,Schieven GL,Pitts

更新日期：2017-07-15 00:00:00

abstract：:Following the promising activity of Q2FA15 on axonal growth, two new series of N/O-substituted QFAs were synthesized, based on a SN2-type reaction. O-alkylated QFA bearing 14 carbon atoms on the side chain (n=14) shows a very potent activity on axonal growth though lowered when compared to Q2FA15. While O-alkylation a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanbali M,Bagnard D,Luu B

更新日期：2006-08-01 00:00:00

abstract：:This study explores the possible use of reactive oxygen-activated DNA modifying agents against acute myeloid leukemia (AML). A key amine on the lead agent was investigated via cytotoxicity assays and was found necessary for potency. The two best compounds were screened via the NCI-60 cell panel. These two compounds ha...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bell-Horwath TR,Vadukoot AK,Thowfeik FS,Li G,Wunderlich M,Mulloy JC,Merino EJ

更新日期：2013-05-15 00:00:00

abstract：:Novel C(3) propenylamide and propenylsulfonamide cephalosporins have been synthesized and tested for their ability to inhibit the penicillin-binding protein 2' (PBP2') from Staphylococcus epidermidis and the growth of a panel of clinically relevant bacterial species, including methicillin-resistant Staphylococcus aure...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pohlmann J,Vasilevich NI,Glushkov AI,Kellenberger L,Shapiro S,Caspers P,Page MG,Danel F

更新日期：2010-08-01 00:00:00