Benzoheterocyclic amodiaquine analogues with potent antiplasmodial activity: synthesis and pharmacological evaluation.

abstract：:Three C(60) derivatives [C(60) (NHCH(2)CH(2)COONa)(n)(H)(n)], n=1, 5, 9] (A, B, C) with different additional number of beta-alanine were synthesized by the control of relative amount of C(60) and beta-alanine added. Hydroxyl radical scavenging activity of the adducts was evaluated in a copper-catalyzed Haber-Weiss rea...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun T,Jia Z,Xu Z

更新日期：2004-04-05 00:00:00

abstract：:Menin functions as an oncogenic cofactor of mixed lineage leukaemia (MLL) fusion proteins in leukaemogenesis. The menin-MLL interface is a potential therapeutic target in acute leukaemia cases. In this study, approximately 900 clinical compounds were evaluated and ranked using pharmacophore-based virtual screening, th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li L,Zhou R,Geng H,Yue L,Ye F,Xie Y,Liu J,Kong X,Jiang H,Huang J,Luo C

更新日期：2014-05-01 00:00:00

abstract：:Protein-protein interactions (PPIs) present a formidable challenge to medicinal chemistry. The extended and open nature of many binding sites at protein interfaces has made it difficult to find useful chemical matter by traditional screening methods using standard screening libraries. This Digest focuses on the progre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Magee TV

更新日期：2015-06-15 00:00:00

abstract：:We discovered novel pyrrolidine MCHR1 antagonist 1 possessing moderate potency. Profiling of pyrrolidine 1 demonstrated that it was an inhibitor of the hERG channel. Investigation of the structure-activity relationship of this class of pyrrolidines allowed us to optimize the MCHR1 potency and decrease the hERG inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fox BM,Natero R,Richard K,Connors R,Roveto PM,Beckmann H,Haller K,Golde J,Xiao SH,Kayser F

更新日期：2011-04-15 00:00:00

abstract：:Several recent reports have highlighted the feasibility of the use of penfluridol, a well-known antipsychotic agent, as a chemotherapeutic agent. In vivo experiments have confirmed the cytotoxic activity of penfluridol in triple-negative breast cancer model, lung cancer model, and further studies have been proposed to...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ashraf-Uz-Zaman M,Sajib MS,Cucullo L,Mikelis CM,German NA

更新日期：2018-12-15 00:00:00

abstract：:A series of substituted 3,4-dihydronaphthalen-1(2H)-ones with high binding affinity for the benzodiazepine site of GABAA receptors containing the alpha5-subunit has been identified. These compounds have consistently higher binding affinity for the GABAA alpha5 receptor subtype over the other benzodiazepine-sensitive G...

journal_title：Bioorganic & medicinal chemistry letters

authors： Szekeres HJ,Atack JR,Chambers MS,Cook SM,Macaulay AJ,Pillai GV,MacLeod AM

更新日期：2004-06-07 00:00:00

abstract：:We have investigated phenol replacements in a series of diaryl amino piperidine delta opioid agonists. From this study we have demonstrated that the hydroxy functional group can be replaced with a primary amide group, giving enhanced activity at the delta receptor, increased selectivity versus mu and kappa as well as ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Griffin AM,Brown W,Walpole C,Coupal M,Adam L,Gosselin M,Salois D,Morin PE,Roumi M

更新日期：2009-11-01 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：:Hydroxy urea moieties are introduced as a new class of bradykinin B(1) receptor antagonists. First, the SAR of the lead compound was systematically explored. Subsequent optimization resulted in the identification of several biaryl-based hydroxyurea bradykinin B(1) receptor antagonists with low-nanomolar activity and v...

journal_title：Bioorganic & medicinal chemistry letters

authors： Schnatbaum K,Schaudt M,Stragies R,Pfeifer JR,Gibson C,Locardi E,Scharn D,Richter U,Kalkhof H,Dinkel K,Zischinsky G

更新日期：2010-02-01 00:00:00

abstract：:HCV NS3/4A serine protease is essential for the replication of the HCV virus and has been a clinically validated target. A series of HCV NS3/4A protease inhibitors containing a novel acylsulfamoyl benzoxaborole moiety at the P1' region was synthesized and evaluated. The resulting P1-P3 and P2-P4 macrocyclic inhibitors...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li X,Zhang YK,Liu Y,Zhang S,Ding CZ,Zhou Y,Plattner JJ,Baker SJ,Liu L,Bu W,Kazmierski WM,Wright LL,Smith GK,Jarvest RL,Duan M,Ji JJ,Cooper JP,Tallant MD,Crosby RM,Creech K,Ni ZJ,Zou W,Wright J

更新日期：2010-12-15 00:00:00

abstract：:We describe the discovery of phenoxymethylbenzamide derivatives as a novel class of glycine transporter type-2 (GlyT-2) inhibitors. We found hit compound 1 (human GlyT-2, IC50=4040 nM) in our library and converted its 1-(1-(naphthalen-2-ylmethyl)piperidin-4-yl)pyrrolidin-3-yl group to an 1-(N,N-dimethylaminopropyl)pip...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takahashi E,Arai T,Akahira M,Nakajima M,Nishimura K,Omori Y,Kumagai H,Suzuki T,Hayashi R

更新日期：2014-09-15 00:00:00

abstract：:Herein we report 6-ethoxy-6-oxo-5-(2-phenylhydrazono) hexanoic acid and 3-(2-carboxyethyl)-1H-indole-2-carboxylic acid derivatives as synthetically accessible leads for human kynurenine aminotransferase-I (KAT-I) inhibitors. In total, 12 compounds were synthesized and their biological activities were determined using ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Akladios FN,Nadvi NA,Park J,Hanrahan JR,Kapoor V,Gorrell MD,Church WB

更新日期：2012-02-15 00:00:00

abstract：:A new glucuronylated prodrug of nornitrogen mustard, incorporating the same spacer group as the doxorubicin prodrug HMR 1826, has been prepared. Upon exposure to E. coli beta-glucuronidase, fast hydrolysis occurs but a lower cytotoxicity against LoVo cancer cells is observed compared to the nornitrogen mustard alone. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Papot S,Combaud D,Bosslet K,Gerken M,Czech J,Gesson JP

更新日期：2000-08-21 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 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 aryl hydrocarbon receptor (AHR) is one of the principal xenobiotic receptors in living organisms and is responsible for interacting with several drugs and environmental toxins, most notably tetrachlorodibenzodioxin (TCDD). Binding of diverse agonists to AHR initiates an extensive set of downstream gene expression ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jogalekar AS,Reiling S,Vaz RJ

更新日期：2010-11-15 00:00:00

abstract：:A tetrahydropyran-based inhibitor (2) of mammalian ribonucleotide reductase (mRR) has been designed and synthesized based on the heptapeptide, N-AcFTLDADF (1), corresponding to the C-terminus of the R2 subunit of mRR. Inhibition studies revealed that 2 is indeed a competent inhibitor, albeit less potent than 1. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Smith AB 3rd,Sasho S,Barwis BA,Sprengeler P,Barbosa J,Hirschmann R,Cooperman BS

更新日期：1998-11-17 00:00:00

abstract：:Aromatase is a target of pharmacological interest for the treatment of estrogen-dependent cancers. Azole derivatives such as letrozole or anastrozole have been developed for aromatase inhibition and are used for the treatment of breast tumors. In this paper, four 4-triazolylflavans were synthesized and were found to e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yahiaoui S,Pouget C,Fagnere C,Champavier Y,Habrioux G,Chulia AJ

更新日期：2004-10-18 00:00:00

abstract：:Strontium fructose 1,6-diphosphate (FDP-Sr) is a new strontium-containing compound. The primary aim of this study was to clarify whether the structure component of FDP-Sr, FDP could benefit the protective effect of Sr (II) against oxidative stress induced apoptosis, and meanwhile to further explore the important role ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qi HH,Bao J,Zhang Q,Ma B,Gu GY,Zhang PL,Ou-Yang G,Wu ZM,Ying HJ,Ou-Yang PK

更新日期：2016-10-01 00:00:00

abstract：:In the past 15 years, fragment-based lead discovery (FBLD) has been adopted widely throughout academia and industry. The approach entails discovering very small molecular fragments and growing, merging, or linking them to produce drug leads. Because the affinities of the initial fragments are often low, detection meth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Davis BJ,Erlanson DA

更新日期：2013-05-15 00:00:00

abstract：:Novel substituted benzylidene-1,3-thiazolidine-2,4-diones (TZDs) have been identified as potent and highly selective inhibitors of the PIM kinases. The synthesis and SAR of these compounds are described, along with X-ray crystallographic, anti-proliferative, and selectivity data. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dakin LA,Block MH,Chen H,Code E,Dowling JE,Feng X,Ferguson AD,Green I,Hird AW,Howard T,Keeton EK,Lamb ML,Lyne PD,Pollard H,Read J,Wu AJ,Zhang T,Zheng X

更新日期：2012-07-15 00:00:00

abstract：:In an effort to identify new protein kinase inhibitors with increased potency and selectivity, we have developed the microwave-assisted synthesis of thiazolo[5,4-f]quinazolin-9-ones. The effects of eighteen derivatives on CDK1/cyclin B, CDK5/p25, and GSK-3 were investigated. Several turned out to inhibit GSK-3 in the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Testard A,Logé C,Léger B,Robert JM,Lozach O,Blairvacq M,Meijer L,Thiéry V,Besson T

更新日期：2006-07-01 00:00:00

abstract：:A series of alpha(v)beta(3) antagonists based on a thiophene scaffold were synthesized via two routes and evaluated for in vitro biological activity. We have identified several structurally similar antagonists with different selectivities towards alpha(IIb)beta(3), alpha(v)beta(5) and alpha(5)beta(1) at the cellular l...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bubenik M,Meerovitch K,Bergeron F,Attardo G,Chan L

更新日期：2003-02-10 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：:A series of SYK inhibitors based on the phenylamino pyrimidine thiazole lead 4 were prepared and evaluated for biological activity. Lead optimization provided compounds with nanomolar K(i)'s against SYK and potent inhibition in mast cell degranulation assays. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Farmer LJ,Bemis G,Britt SD,Cochran J,Connors M,Harrington EM,Hoock T,Markland W,Nanthakumar S,Taslimi P,Ter Haar E,Wang J,Zhaveri D,Salituro FG

更新日期：2008-12-01 00:00:00

abstract：:Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which exhibits selective cytotoxicity against a tumorigenic cell line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)-methanone (18m) was designed and synthesized as a biologically stable derivative c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hayakawa I,Shioya R,Agatsuma T,Furukawa H,Naruto S,Sugano Y

更新日期：2004-01-19 00:00:00

abstract：:We report here the synthesis and biological evaluation of a series of 37 compounds as precursors of potent antimalarial bis-thiazolium salts (T3 and T4). These prodrugs were either thioester, thiocarbonate or thiocarbamate type and were synthesized in one step by reaction of an alkaline solution of the parent drug wit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Caldarelli SA,Boisbrun M,Alarcon K,Hamzé A,Ouattara M,Salom-Roig X,Maynadier M,Wein S,Peyrottes S,Pellet A,Calas M,Vial H

更新日期：2010-07-01 00:00:00

abstract：:Methyl bacteriopheophorbide-f was prepared from methyl bacteriopheophorbide-d with retention of the 3(1)-chirality. The transformation of the methyl to the formyl group at the 7-position of the chlorin moiety will provide an alternative route for the synthesis of bacteriochlorophylls-e and f. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tamiaki H,Omoda M,Kubo M

更新日期：1999-06-21 00:00:00

abstract：:A new family of poly-guanidinium species with a benzene core as the organising agent has been developed. Their antibacterial properties have been evaluated against reference Gram positive and Gram negative bacteria, and their cytotoxicity against eukaryotic cells. Most of these compounds exhibited Minimum Inhibitory C...

journal_title：Bioorganic & medicinal chemistry letters

authors： Massimba Dibama H,Mourer M,Duval RE,Regnouf-de-Vains JB

更新日期：2014-10-15 00:00:00

abstract：:AKT inhibitors containing an imidazopyridine aminofurazan scaffold have been optimized. We have previously disclosed identification of the AKT inhibitor GSK690693, which has been evaluated in clinical trials in cancer patients. Herein we describe recent efforts focusing on investigating a distinct region of this scaff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rouse MB,Seefeld MA,Leber JD,McNulty KC,Sun L,Miller WH,Zhang S,Minthorn EA,Concha NO,Choudhry AE,Schaber MD,Heerding DA

更新日期：2009-03-01 00:00:00