Design and synthesis of 2-substituted benzoxazoles as novel PTP1B inhibitors.

abstract：:(1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rodrigues T,Guedes RC,dos Santos DJ,Carrasco M,Gut J,Rosenthal PJ,Moreira R,Lopes F

更新日期：2009-07-01 00:00:00

abstract：:A flexible, direct, high yielding synthesis of 2-alkylsulfanyl estrogens from estrone has been developed. 2-Methylsulfanyl estradiol (2-MeSE2) 7 displays a similar anti-proliferative activity to the established 2-methoxyestradiol (2-MeOE2) 1, whilst its 3-O-sulfamate derivative (2-MeSE2MATE) 9 exhibits greatly enhance...

journal_title：Bioorganic & medicinal chemistry letters

authors： Leese MP,Newman SP,Purohit A,Reed MJ,Potter BV

更新日期：2004-06-21 00:00:00

abstract：:Triptolide (TP) is a diterpene epoxide component extracted from Tripterygium wilfordii and has been shown to possess an impressive anticancer effect. However, TP has not yet entered any clinic trials due to the severe adverse effects that resulted from the off-target absorption and distribution found in animal studies...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lou D,Lou Z,Lin Y,Shangguan H,Lin Y,Luo Q,Zhang H,Lin G,Chen R,Kou L,Bao S

更新日期：2020-12-17 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：:Optimization of clearance of adenosine inhibitors of bacterial NAD(+)-dependent DNA ligase is discussed. To reduce Cytochrome P-450-mediated metabolic clearance, many strategies were explored; however, most modifications resulted in compounds with reduced antibacterial activity and/or unchanged total clearance. The al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stokes SS,Gowravaram M,Huynh H,Lu M,Mullen GB,Chen B,Albert R,O'Shea TJ,Rooney MT,Hu H,Newman JV,Mills SD

更新日期：2012-01-01 00:00:00

abstract：:Glycogen synthase kinase 3β (GSK-3β) plays a key role in insulin metabolizing pathway and therefore inhibition of the enzyme might provide an important therapeutic approach for treatment of insulin resistance and type 2 diabetes. Recently, discovery of ATP noncompetitive inhibitors is gaining importance not only due t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang P,Li S,Gao Y,Lu W,Huang K,Ye D,Li X,Chu Y

更新日期：2014-12-15 00:00:00

abstract：:Novel imidazole frameworks have been identified as potent partial agonists of the alpha(1A) adrenergic receptor, with good selectivity over the alpha(1B), alpha(1D) and alpha(2A) receptor sub-types. Nitrile 28 possessed attractive CNS drug-like properties with good membrane permeability and no P-pg mediated efflux. 28...

journal_title：Bioorganic & medicinal chemistry letters

authors： Whitlock GA,Brennan PE,Roberts LR,Stobie A

更新日期：2009-06-01 00:00:00

abstract：:The 2,4,6-trimethylpyridinium derivative of histamine is an effective activator of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). However, unlike other CA activators, which bind at the entrance of the active site cavity, an X-ray crystal structure of hCA II in complex with the 1-[2-(1H-imidazol-4-yl)-ethyl]-2,4,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dave K,Ilies MA,Scozzafava A,Temperini C,Vullo D,Supuran CT

更新日期：2011-05-01 00:00:00

abstract：:A series of (R)-3-(N-methylpyrrolidin-2-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives (2) have been prepared using parallel synthesis, and their structure-activity relationship studied. High affinity human 5-HT(1B/1D) (h5-HT(1B/1D)) ligands have been identified. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Egle I,MacLean N,Demchyshyn L,Edwards L,Slassi A,Tehim A

更新日期：2003-10-20 00:00:00

abstract：:We have designed and synthesized twenty-six N-arylindazole-3-carboxamide (3a-p) and N-benzoylindazole (6a-j) derivatives to discover with excellent inhibition activities of α-MSH-stimulated melanogenesis. In the bio evaluation studies of these compounds, we discovered eighteen compounds, out of twenty-six exhibited mo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arepalli SK,Lee C,Jung JK,Kim Y,Lee K,Lee H

更新日期：2019-09-15 00:00:00

abstract：:In the past few years a significant effort has been devoted by Pharmacia toward the discovery of novel antibiotics. We have recently described the identification of an anthranilic acid lead 1 and the optimization resulting in the advanced lead 2. In this report, we describe the preparation of several selected analogs ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thorarensen A,Li J,Wakefield BD,Romero DL,Marotti KR,Sweeney MT,Zurenko GE,Sarver RW

更新日期：2007-06-01 00:00:00

abstract：:The reaction of methoxypoly(ethylene glycol)-4-nitrophenyl carbonate with amphotericin B has been used to prepare a new conjugate of amphotericin B (mPEG-AmB). A preliminary screening of in vitro antifungal activity has suggested that mPEG-AmB possesses a similar effect and a similar spectrum of activity as the conven...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sedlák M,Buchta V,Kubicová L,Simůnek P,Holcapek M,Kasparová P

更新日期：2001-11-05 00:00:00

abstract：:We synthesized prodrug-type phosphotriester (PTE) oligonucleotides containing the six-membered cyclic disulfide moiety by using phosphoramidite chemistry. Prodrug-type oligonucleotides named "Reducing-Environment-Dependent Uncatalyzed Chemical Transforming (REDUCT) PTE oligonucleotides" were converted into natural oli...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hayashi J,Samezawa Y,Ochi Y,Wada SI,Urata H

更新日期：2017-07-15 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：:5-Methylcytosine (5mC) is oxidized by ten-eleven translocation (TET) enzymes. This process followed by thymine DNA glycosylase is proposed to be the mechanism for methylcytosine demethylation. 5-Hydroxymethylcytosine (5hmC) is one of the most important key oxidative metabolites in the demethylation process, and theref...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fukuzawa S,Tachibana K,Tajima S,Suetake I

更新日期：2015-12-15 00:00:00

abstract：:A series of novel benzoxazole derivatives has been designed and shown to exhibit attractive JAK2 inhibitory profiles in biochemical and cellular assays, capable of delivering compounds with favorable PK properties in rats. Synthesis and structure-activity relationship data are also provided. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gerspacher M,Furet P,Pissot-Soldermann C,Gaul C,Holzer P,Vangrevelinghe E,Lang M,Erdmann D,Radimerski T,Regnier CH,Chene P,De Pover A,Hofmann F,Baffert F,Buhl T,Aichholz R,Blasco F,Endres R,Trappe J,Drueckes P

更新日期：2010-03-01 00:00:00

abstract：:The first examples of thioether-substituted benzonitriles as potential soft-drug androgen receptor antagonists are reported. A number of 4-(alkylthio)- and of 4-(arylthio)-benzonitrile analogs were evaluated in human androgen receptor binding and cellular functional assays. Analogs with potent in vitro binding and cel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mitchell L,Wang Z,Hu LY,Kostlan C,Carroll M,Dettling D,Du D,Pocalyko D,Wade K

更新日期：2009-03-01 00:00:00

abstract：:The synthesis and pharmacological activity of novel nociceptin/orphanin FQ (N/OFQ) analogues modified in the Phe(1)-Gly(2) peptide bond are reported. The aim of the present work was to elucidate the importance of this peptide bond for the N/OFQ receptor (NOP) interaction. Our study indicates that the first peptide bon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guerrini R,Rizzi D,Zucchini M,Tomatis R,Regoli D,Calo' G,Salvadori S

更新日期：2003-02-10 00:00:00

abstract：:Through a systematic modification of the novel angiogenesis inhibitor 4-senecioyloxymethyl-6,7-dimethoxycoumarin (1) we found that a 6,7-dimethoxy moiety is important for bioactivity of 1. Replacement of the lactone functionality in coumarin 1 by an amide decreased its activity. By substitution of the senecioyl chain ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nam NH,Kim Y,You YJ,Hong DH,Kim HM,Ahn BZ

更新日期：2002-09-02 00:00:00

abstract：:Invasive fungal infections have become an important healthcare issue due in large part to high mortality rates under standard of care (SOC) therapies creating an urgent need for new and effective anti-fungal agents. We have developed a series of non-peptide, structurally-constrained analogs of host defence proteins th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baugh SDP,Chaly A,Weaver DG,Pelletier JC,Thanna S,Freeman KB,Reitz AB,Scott RW

更新日期：2020-12-13 00:00:00

abstract：:Novel Leu-enkephalin (Leu-Enk) (1) analogs possessing various types of alpha-substituted serine instead of its glycine residue in the position 2 were synthesized via an efficient O,N-migration method. The binding characteristics of the synthetic analogs using Chinese hamster ovary (CHO) cells expressed cloned rat mu-,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Horikawa M,Shigeri Y,Yumoto N,Yoshikawa S,Nakajima T,Ohfune Y

更新日期：1998-08-04 00:00:00

abstract：:Some novel oxazolidinone derivatives with benzotriazole as pendant have been synthesized and tested for antibacterial activity. Linearly attached benzotriazole derivative showed more potency compared to angular one in vitro. Out of E/Z-isomers of angularly attached derivatives E-isomer was found to be more potent than...

journal_title：Bioorganic & medicinal chemistry letters

authors： Das J,Rao CV,Sastry TV,Roshaiah M,Sankar PG,Khadeer A,Kumar MS,Mallik A,Selvakumar N,Iqbal J,Trehan S

更新日期：2005-01-17 00:00:00

abstract：:Backbone-modified DNA analogs were synthesized in good yields by the boranophosphotriester method on a solid support. The oligodeoxyribonucleoside boranophosphates, protected with 2-(azidomethyl)benzoyl groups for nucleobases, were converted into DNA and its backbone-modified analogs via the corresponding H-phosphonat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kawanaka T,Shimizu M,Shintani N,Wada T

更新日期：2008-07-01 00:00:00

abstract：:We previously identified o-carborane bisphenol BE360 (4) as a selective estrogen receptor modulator (SERM), which ameliorated bone loss without inducing estrogenic action in uterus of OVX and ORX mice. Here, we synthesized a fluorinated derivative, B-fluorinated o-carborane bisphenol BE310 (5) by means of S(N)Ar react...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohta K,Ogawa T,Endo Y

更新日期：2012-07-15 00:00:00

abstract：:A new series of diarylureas and diarylamides possessing 1H-pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-9 human melanoma cell line panel were tested. All the target compounds, except three amino derivatives 8g, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jung MH,El-Gamal MI,Abdel-Maksoud MS,Sim T,Yoo KH,Oh CH

更新日期：2012-07-01 00:00:00

abstract：:Aminoglycosides have been shown to target A-form nucleic acids. Our work has previously shown that neomycin (and other aminoglycosides) bind and stabilize DNA/RNA triplexes and other A-form nucleic acids. We report herein the unexpected B-form duplex stabilization shown by aminoglycoside dimers (neomycin-neomycin and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arya DP,Coffee RL Jr,Xue L

更新日期：2004-09-20 00:00:00

abstract：:A novel series of kappa (kappa) opioid receptor agonists were synthesized by incorporating the key structural features of known kappa opioid agonists while replacing the aryl acetamide portion with substituted amino acid conjugates. Compounds 3j (Ki = 6.7 nM), 3k (Ki = 3.6 nM), 3l (Ki = 4.6 nM), 3m (Ki = 0.83 nM) and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar V,Guo D,Daubert JD,Cassel JA,DeHaven RN,Mansson E,DeHaven-Hudkins DL,Maycock AL

更新日期：2005-03-01 00:00:00

abstract：:3-alkyl-2,4,5-triarylfurans with basic side-chain substituents were prepared as ligands for the estrogen receptor. Those analogues having the basic side chain on the C(4) phenol were high-affinity, ERalpha-selective antagonists. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mortensen DS,Rodriguez AL,Sun J,Katzenellenbogen BS,Katzenellenbogen JA

更新日期：2001-09-17 00:00:00

abstract：:A general protocol for the synthesis of paclitaxel C-10 carbamates is described. The method entails MeI-mediated activation of 2'-O-TBS-7-O-TES-10-O-deacetyl-paclitaxel-10-O-carbonylimidazole prior to reaction with amines. This method is effective for the synthesis of paclitaxel C-10 derivatives, including bifunctiona...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ballatore C,Aspland SE,Castillo R,Desharnais J,Eustaquio T,Sun C,Castellino AJ,Smith AB 3rd

更新日期：2005-05-16 00:00:00

abstract：:This letter describes a multi-dimensional SAR campaign based on a potent, efficacious and selective GIRK1/2 activator (~10-fold versus GIRK1/4 and inactive on nonGIRK 1-containing GIRKs, GIRK 2 or GIRK2/3). Further chemical optimization through an iterative parallel synthesis effort identified multiple 'molecular swit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wen W,Wu W,Romaine IM,Kaufmann K,Du Y,Sulikowski GA,Weaver CD,Lindsley CW

更新日期：2013-08-15 00:00:00