Discovery of ML326: The first sub-micromolar, selective M5 PAM.

abstract：:A protocol applicable for the synthesis of an oseltamivir positron emission tomography (PET) tracer was developed. Acetylation of amine 3 with CH(3)COCl, followed by deprotection and aqueous workup, produced oseltamivir 4 from 3 within 10 min. The obtained 4 was sufficiently pure for PET studies. This method can be ex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morita M,Sone T,Yamatsugu K,Sohtome Y,Matsunaga S,Kanai M,Watanabe Y,Shibasaki M

更新日期：2008-01-15 00:00:00

abstract：:We have developed a new methodology for producing new molecules that bind to dsDNA using DNA-templated click chemistry. The click reactions between the minor groove binding peptide and acridine intercalators were accelerated by the addition of dsDNA. Furthermore, the resulting peptide-acridine conjugate showed a sligh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Imoto S,Hirohama T,Nagatsugi F

更新日期：2008-10-15 00:00:00

abstract：:To obtain modulators for reducing mitochondrial damage by the inhibition of Aβ oligomer formation, 2-phenylbenzofuran derivatives were designed and prepared. Their inhibitory activity against Aβ fibril formation was screened using ThT fluorescence assay, and the effect of derivatives on mitochondrial function was eval...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee YS,Kim HY,Youn HM,Seo JH,Kim Y,Shin KJ

更新日期：2013-11-01 00:00:00

abstract：:Optimisation of a series of 4-piperidinyltriazoles led to the identification of compound 28a which showed good whole cell antiviral activity, excellent selectivity over the hERG ion channel and complete oral absorption. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barber CG,Blakemore DC,Chiva JY,Eastwood RL,Middleton DS,Paradowski KA

更新日期：2009-03-01 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：:Novel 3-[4-(dimethylamino)phenyl]alkyl-2-oxindole analogs were synthesized by either of the following two pathways: (1) a sequence of Knoevenagel condensation of oxindole with (4-dimethylamino)cinnamaldehyde-hydrogenation, or (2) alkylation of oxindole dianion with [(4-dimethylamino)phenyl]alkyl halides. Subsequent al...

journal_title：Bioorganic & medicinal chemistry letters

authors： Furuta K,Kawai Y,Mizuno Y,Hattori Y,Koyama H,Hirata Y

更新日期：2017-09-15 00:00:00

abstract：:We report a fluorinated and iodinated radiotracer as a probe for PET/SPECT to detect of β-amyloid (Aβ) plaques in the brain of patients with Alzheimer's disease (AD). We successfully designed and synthesized the fluorinated and iodinated aurone derivative (3) and its radiolabels ([(125)I]3 and [(18)F]3). In binding ex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watanabe H,Ono M,Kimura H,Kagawa S,Nishii R,Fuchigami T,Haratake M,Nakayama M,Saji H

更新日期：2011-11-01 00:00:00

abstract：:A short synthetic route to the first beta-l-ribo configured locked nucleic acid (LNA), that is, 2'-amino-beta-l-LNA thymine phosphoramidite 6, has been developed from bicyclic nucleoside 1. Incorporation of 2'-amino-beta-l-LNA thymine monomers into alpha-DNA strands results in probes forming stable duplexes with compl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar TS,Ostergaard ME,Sharma PK,Nielsen P,Wengel J,Hrdlicka PJ

更新日期：2009-05-01 00:00:00

abstract：:A remarkable control of the potency of cantharimide is described based on the electronic properties of functional group and it exhibits a relatively less toxic effect to the non-malignant hematological disorder bone marrow cells. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kok SH,Chui CH,Lam WS,Chen J,Lau FY,Wong RS,Cheng GY,Lai PB,Leung TW,Yu MW,Tang JC,Chan AS

更新日期：2007-03-01 00:00:00

abstract：:Homocereulide, isolated from marine bacterium Bacillus cereus, is an analog of emetic toxin cereulide. There is no report on its structure determination and involvement in B. cereus-associated food poisoning. Homocereulide is a cyclic dodecadepsipeptide composed of l-O-Val-l-Val-d-O-Leu-d-Ala and l-O-allo-Ile-d-Val-d-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Naka T,Hattori Y,Takenaka H,Ohta Y,Kirihata M,Tanimori S

更新日期：2019-03-01 00:00:00

abstract：:Here we present first dinucleotide affinity resins for purification of proteins that specifically recognize the 5' end of mRNA. Constructed resins possess either a naturally occurring mono- or trimethylated cap or their analogues resistant towards enzymatic degradation, bearing a CH(2) bridge between β and γ position ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jankowska-Anyszka M,Piecyk K

更新日期：2011-10-15 00:00:00

abstract：:DNA binding ligands with potent antimicrobial activity against Gram-positive bacteria were further optimized by variation of the internal aromatic amino acids. This modification led to compounds with improved in vivo efficacy in lethal murine models of peritonitis (methicillin-resistant S. aureus, MRSA) and lung infec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bürli RW,Kaizerman JA,Duan JX,Jones P,Johnson KW,Iwamoto M,Truong K,Hu W,Stanton T,Chen A,Touami S,Gross M,Jiang V,Ge Y,Moser HE

更新日期：2004-05-03 00:00:00

abstract：:The development of novel non-phosphopeptide inhibitors for the Src family SH2 domain is described. Several commercially available hydroxyl aromatic acids have been appended off the N-terminus of pYEEIE and the potent phosphopeptide inhibitors of GST-Lck-SH2 were identified via ELISA. The most potent inhibitor, caffeic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park SH,Won J,Lee KH

更新日期：2002-10-07 00:00:00

abstract：:A series of Incentrom A analogs that inhibit the chromosome segregation process in yeast were synthesized and tested for their effects on chromosome stability and cell proliferation. Pharmacophore and structure-activity relationship of Incentrom A for the anti-yeast activity were established. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee HY,Jung Y,Kim W,Kim JH,Suh MS,Shin SK,Yoon HJ

更新日期：2008-08-15 00:00:00

abstract：:Two new heterocycles, pyrimido[4,5-c]carbazole and pyrimido[5,4-b]indole, were prepared in three steps from 3-aminocarbazole and 3-aminoindole, respectively. The key Friedel-Crafts intramolecular cyclization was realized under microwave irradiation using montmorillonite K-10 clay as a catalyst. The pyrimido[4,5-c]carb...

journal_title：Bioorganic & medicinal chemistry letters

authors： Debray J,Zeghida W,Baldeyrou B,Mahieu C,Lansiaux A,Demeunynck M

更新日期：2010-07-15 00:00:00

abstract：:A versatile and high yielding synthesis of novel androgen receptor (AR) antagonists is presented. Using this methodology, six 1,4-substituted-1,2,3-triazole derived bicalutamide mimics were synthesised in five steps and in isolated overall yields from 41% to 85%. Evaluation of these compounds for their anti-proliferat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Altimari JM,Niranjan B,Risbridger GP,Schweiker SS,Lohning AE,Henderson LC

更新日期：2014-11-01 00:00:00

abstract：:Betulinic acid and analogous naturally occurring triterpenoid acids were transformed into the corresponding propargyl esters and subsequently deployed as substrates for a click chemistry-mediated coupling with azidothymidine (AZT) en route to novel 1,2,3-triazole-tethered triterpenoid-AZT conjugates. Twelve new hybrid...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dang Thi TA,Kim Tuyet NT,Pham The C,Thanh Nguyen H,Ba Thi C,Doan Duy T,D'hooghe M,Van Nguyen T

更新日期：2014-11-15 00:00:00

abstract：:By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 μM; MIC = 0.48 μM) than the positive controls AHA (IC50 = 17.2 μM) and Metronidazole (MIC = 31.3 ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang YS,Su MM,Zhang XP,Liu QX,He ZX,Xu C,Zhu HL

更新日期：2018-10-15 00:00:00

abstract：:A series of cysteine diazomethyl- and chloromethyl ketone derivatives has been synthesized and evaluated against human B-lineage (Nalm-6) and T-lineage (Molt-3) acute lymphoblastic leukemia cell lines. The chloromethyl ketone compounds showed potent cytotoxicity against these cell lines, with IC50 values in the low mi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Perrey DA,Narla RK,Uckun FM

更新日期：2000-03-20 00:00:00

abstract：:Five new phenoxazine-based alkaloids venezuelines A-E (1-5) and two new aminophenols venezuelines F-G (6-7), as well as three known analogues exfoliazone, chandrananimycin D and carboxyexfoliazone were isolated from the fermentation broth of the marine-derived bacterium Streptomyces venezuelae. The structures of new c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ren J,Liu D,Tian L,Wei Y,Proksch P,Zeng J,Lin W

更新日期：2013-01-01 00:00:00

abstract：:Pim kinases are promising targets for the development of cancer therapeutics. Among the three Pim isoforms, Pim-2 is particularly important in multiple myeloma, yet is the most difficult to inhibit due to its high affinity for ATP. We identified compound 1 via high throughput screening. Using property-based drug desig...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang X,Magnuson S,Pastor R,Fan E,Hu H,Tsui V,Deng W,Murray J,Steffek M,Wallweber H,Moffat J,Drummond J,Chan G,Harstad E,Ebens AJ

更新日期：2013-06-01 00:00:00

abstract：:A series of aryl amines was found to induce cleavage of DNA. Subsequent refinement led to an efficient family of dimeric derivatives capable of cleavage at low concentration. Initial investigations suggest this is an unprecedented mode of DNA cleavage, which may be ultimately applied to the development of sequence-spe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Warner PM,Qi J,Meng B,Li G,Xie L,El-Shafey A,Jones GB

更新日期：2002-01-07 00:00:00

abstract：:Although PK11195 binds to the peripheral benzodiazepine receptor with nanomolar affinity, significant data exist which suggest that it has another cellular target distinct from the PBR. Here we demonstrate that PK11195 inhibits F(1)F(0)-ATPase activity in an OSCP-dependent manner, similar to the pro-apoptotic benzodia...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cleary J,Johnson KM,Opipari AW Jr,Glick GD

更新日期：2007-03-15 00:00:00

abstract：:Seedlings of natural crops are valuable sources of pharmacologically active phytochemicals. In this study, we aimed to identify new active secondary metabolites in Avena sativa L. (oat) seedlings. Two new compounds, avenafuranol (1) and diosgenoside (2), along with eight known compounds (3-10) were isolated from the A...

journal_title：Bioorganic & medicinal chemistry letters

authors： Woo SY,Lee KS,Shin HL,Kim SH,Lee MJ,Young Kim H,Ham H,Lee DJ,Choi SW,Seo WD

更新日期：2020-07-15 00:00:00

abstract：:GTP cyclohydrolase (GCYH-I) is an enzyme in the folate biosynthesis pathway that has not been previously exploited as an antibiotic target, although several pathogens including N. gonorrhoeae use a form of the enzyme GCYH-IB that is structurally distinct from the human homologue GCYH-IA. A comparison of the crystal st...

journal_title：Bioorganic & medicinal chemistry letters

authors： Samaan GN,Paranagama N,Haque A,Hecht DA,Swairjo MA,Purse BW

更新日期：2020-01-15 00:00:00

abstract：:It is suggested that the ratio of dopamine D(2) to 5-hydroxytryptamine 5-HT(1A) activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sukalovic V,Ignjatovic D,Tovilovic G,Andric D,Shakib K,Kostic-Rajacic S,Soskic V

更新日期：2012-06-15 00:00:00

abstract：:We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sagar SR,Agarwal JK,Pandya DH,Dash RP,Nivsarkar M,Vasu KK

更新日期：2015-10-15 00:00:00

abstract：:An imbalance between bone resorption by osteoclasts and bone formation by osteoblasts can cause bone loss and bone-related disease. In a previous search for natural products that increase osteogenic activity, we found that 5,6-dehydrokawain (1) from Alpinia zerumbet promotes osteoblastogenesis. In this study, we synth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumagai M,Nishikawa K,Mishima T,Yoshida I,Ide M,Koizumi K,Nakamura M,Morimoto Y

更新日期：2017-06-01 00:00:00

abstract：:Starting from a non-selective pyrazolo-pyrimidone lead, the sequential use of parallel medicinal chemistry and directed synthesis led to the discovery of potent, highly selective, and orally bioavailable PDE9 inhibitors. The availability of these tools allowed for a thorough evaluation of the therapeutic potential of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Deninno MP,Andrews M,Bell AS,Chen Y,Eller-Zarbo C,Eshelby N,Etienne JB,Moore DE,Palmer MJ,Visser MS,Yu LJ,Zavadoski WJ,Michael Gibbs E

更新日期：2009-05-01 00:00:00

abstract：:The use of doxorubicin (DOX) in the treatment of solid tumors is limited by cardiotoxicity essentially due to oxidative stress generation. The aim of this study was to identify coumarin derivatives displaying a protective antioxidant activity without affecting DOX antitumoral efficiency. A set of eighteen coumarinic d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Beillerot A,Domínguez JC,Kirsch G,Bagrel D

更新日期：2008-02-01 00:00:00