Design and synthesis of bridged piperidine and piperazine isosteres.

abstract：:A series of MT-II related cyclic peptides, based on potent but non-selective hMC4R agonist (Penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2)) was prepared in which His(6) residue was systematically substituted. Two of the most interesting peptides identified in this study are Penta-c[Asp-5-ClAtc-DPhe-Arg-Trp-Lys]-N...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheung AW,Danho W,Swistok J,Qi L,Kurylko G,Rowan K,Yeon M,Franco L,Chu XJ,Chen L,Yagaloff K

更新日期：2003-04-07 00:00:00

abstract：:Human telomeric DNA is transcribed into telomeric RNA in cells. Telomeric RNA performs the fundamental biological functions such as regulation and protection of chromosome ends. This digest highlights the human telomere RNA G-quadruplex structures, telomere RNA functions, G-quadruplex-binding small molecules, and futu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu Y

更新日期：2018-08-15 00:00:00

abstract：:Betulinic acid has been modified at C-3, C-20, and C-28 positions and the toxicity of the derivatives has been evaluated against cultured human melanoma (MEL-2) and human epidermoid carcinoma of the mouth (KB) cell lines. This preliminary investigation demonstrates that simple modifications of the parent structure of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim DS,Pezzuto JM,Pisha E

更新日期：1998-07-07 00:00:00

abstract：:A structure-activity relationship study of dorsomorphin, a previously identified inhibitor of SMAD 1/5/8 phosphorylation by bone morphogenetic protein (BMP) type 1 receptors ALK2, 3, and 6, revealed that increased inhibitory activity could be accomplished by replacing the pendent 4-pyridine ring with 4-quinoline. The ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cuny GD,Yu PB,Laha JK,Xing X,Liu JF,Lai CS,Deng DY,Sachidanandan C,Bloch KD,Peterson RT

更新日期：2008-08-01 00:00:00

abstract：:Autotaxin (ATX) is an attractive target for the anticancer therapeutics that inhibits angiogenesis, invasion and migration. ATX is an extracellular lysophospholipase D that hydrolyzes lysophosphatidylcholine to form the bioactive lipid lysophosphatidic acid. The aromatic phosphonate S32826 was the first described nano...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jiang G,Madan D,Prestwich GD

更新日期：2011-09-01 00:00:00

abstract：:The discovery, synthesis, potential binding mode, and in vitro kinase profile of 3-(3-bromo-4-hydroxy-5-(2'-methoxyphenyl)-benzylidene)-5-bromo-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one, 3-[(1-methyl-1H-indol-3-yl)methylene]-1,3-dihydro-2H-pyrrolo[3,2-b]-pyridin-2-one as potent TrkA inhibitors are discussed. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wood ER,Kuyper L,Petrov KG,Hunter RN 3rd,Harris PA,Lackey K

更新日期：2004-02-23 00:00:00

abstract：:Casein kinase 2 catalytic subunit (CK2α) is classified into two subtypes CK2α1 and CK2α2. CK2α1 is a drug discovery target, whereas CK2α2 is an off-target of CK2α1 inhibitors. High amino acid sequence homology between these subtypes hampers efforts to produce ATP competitive inhibitors that are highly selective to CK2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tsuyuguchi M,Nakaniwa T,Hirasawa A,Nakanishi I,Kinoshita T

更新日期：2020-01-15 00:00:00

abstract：:A new method for the synthesis of 2'-O-methyl-2-thiouridine (s2Um) found in thermophilic bacterial tRNA was developed. Structural properties of s2Um and s2Um(p)U were studied by using 1H NMR spectroscopy. A modified nonaribonucleotide (RNA*: 5'-CGUUs2UmUUGC-3') was synthesized to study the base-recognition ability of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shohda K,Okamoto I,Wada T,Seio K,Sekine M

更新日期：2000-08-21 00:00:00

abstract：:A series of acetylenic chalcones were evaluated for antimalarial and antitubercular activity. The antimalarial data for this series suggests that growth inhibition of the W2 strain of Plasmodium falciparum can be imparted by the introduction of a methoxy group ortho to the acetylenic group. Most compounds were more ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hans RH,Guantai EM,Lategan C,Smith PJ,Wan B,Franzblau SG,Gut J,Rosenthal PJ,Chibale K

更新日期：2010-02-01 00:00:00

abstract：:Fragment-based NMR screening of a small literature focused library led to identification of a historical thrombin/FactorXa building block, 17A, that was found to be a ROCK-I inhibitor. In the absence of an X-ray structure, fragment growth afforded 6-substituted isoquinolin-1-amine derivatives which were profiled in th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ray P,Wright J,Adam J,Bennett J,Boucharens S,Black D,Cook A,Brown AR,Epemolu O,Fletcher D,Haunso A,Huggett M,Jones P,Laats S,Lyons A,Mestres J,de Man J,Morphy R,Rankovic Z,Sherborne B,Sherry L,van Straten N,We

更新日期：2011-01-01 00:00:00

abstract：:The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this gener...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun W,Chu T

更新日期：2015-10-15 00:00:00

abstract：:A new cyclic heptapeptide, cyclonatsudamine A (1), cyclo (-Gly-Tyr-Leu-Leu-Pro-Pro-Ser-), has been isolated from the peels of Citrus natsudaidai and the structure was elucidated by 2D NMR analysis and chemical degradation. Cyclonatsudamine A (1) relaxed norepinephrine-induced contractions of rat aorta, which may be me...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morita H,Enomoto M,Hirasawa Y,Iizuka T,Ogawa K,Kawahara N,Goda Y,Matsumoto T,Takeya K

更新日期：2007-10-01 00:00:00

abstract：:Two new austalide meroterpenoids, named austalides V and W (1 and 2), were isolated from the fungus Aspergillus ustus VKM F-4692. Their structures were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. The main structural feature of both compounds is a tetrahydrofuranyl rin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Antipova TV,Zaitsev KV,Oprunenko YF,Ya Zherebker A,Rystsov GK,Zemskova MY,Zhelifonova VP,Ivanushkina NE,Kozlovsky AG

更新日期：2019-11-15 00:00:00

abstract：:A group of tri and tetrasubstituted urea derivatives have been found to be hH(3)-antagonists. The most potent compounds were found in the class of (piperazine-1-yl)-(piperidine-1-yl)-methanones which in addition showed negligible hERG inhibition. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lau JF,Jeppesen CB,Rimvall K,Hohlweg R

更新日期：2006-10-15 00:00:00

abstract：:A series of 5-(piperidinylethyloxy)quinoline 5-HT(1) receptor ligands have been studied by elaboration of the series of dual 5-HT(1)-SSRIs reported previously. These new compounds display a different in vitro pharmacological profile with potent affinity across the 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors and selectiv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ward SE,Eddershaw P,Flynn ST,Gordon L,Lovell PJ,Moore SH,Scott CM,Smith PW,Thewlis KM,Wyman PA

更新日期：2009-01-15 00:00:00

abstract：:Phenylpiperazine derivatives were synthesized as dual cytokine regulators with TNF-alpha suppressing and IL-10 augmenting activity. Lead optimization led to compound 5k having the potent regulatory activity and demonstrating remarkable protective effects against the lethal challenge of LPS in mice. suggesting that 5k ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hanano T,Adachi K,Aoki Y,Morimoto H,Naka Y,Hisadome M,Fukuda T,Sumichika H

更新日期：2000-05-01 00:00:00

abstract：:Steroidal glucocorticoids (GR agonists) have been widely used for the topical treatment of skin disorders, including atopic dermatitis. They are a very effective therapy, but they are associated with both unwanted local effects in the skin (skin thinning/atrophy) and systemic side effects. These effects can limit the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dack KN,Johnson PS,Henriksson K,Eirefelt S,Carnerup MA,Stahlhut M,Ollerstam AK

更新日期：2020-09-01 00:00:00

abstract：:Described are the syntheses of three sansalvamide A derivatives that contain biotinylated tags at individual positions around the macrocycle. The tagged derivatives indicated in protein pull-down assays that they bind to Hsp90 at the same binding site (N-Middle domain) as the San A-amide peptide. Further, these compou...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kunicki JB,Petersen MN,Alexander LD,Ardi VC,McConnell JR,McAlpine SR

更新日期：2011-08-15 00:00:00

abstract：:Herein we describe the discovery of a novel series of ATP competitive B-Raf inhibitors via structure based drug design (SBDD). These pyridopyrimidin-7-one based inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 17, a potent, selective ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ren L,Ahrendt KA,Grina J,Laird ER,Buckmelter AJ,Hansen JD,Newhouse B,Moreno D,Wenglowsky S,Dinkel V,Gloor SL,Hastings G,Rana S,Rasor K,Risom T,Sturgis HL,Voegtli WC,Mathieu S

更新日期：2012-05-15 00:00:00

abstract：:Metabolic oligosaccharide engineering is a powerful approach for installing unnatural glycans with unique functional groups into the glycocalyx of living cells and animals. Using this approach, we showed that K(+) channel complexes decorated with thiol-containing sialic acids were irreversibly inhibited with scorpion ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hua Z,Lvov A,Morin TJ,Kobertz WR

更新日期：2011-09-01 00:00:00

abstract：:Matrix metalloproteinase-13 (MMP-13) has been implicated as the protease responsible for collagen degradation in cartilage during osteoarthritis (OA). Compounds that inhibit the metalloproteinase at the Zn binding site typically lack specificity among MMP family members. Analogs of the low-micromolar lead MMP-13 inhib...

journal_title：Bioorganic & medicinal chemistry letters

authors： Roth J,Minond D,Darout E,Liu Q,Lauer J,Hodder P,Fields GB,Roush WR

更新日期：2011-12-01 00:00:00

abstract：:Knoevenagel condensation was employed to generate a set of molecules potentially capable of inhibiting the RNA polymerase-σ70/σA interaction in bacteria. Synthesis was achieved via reactions between a variety of indole-7-carbaldehydes and rhodanine, N-allylrhodanine, barbituric acid or thiobarbituric acid. A library o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wenholz DS,Zeng M,Ma C,Mielczarek M,Yang X,Bhadbhade M,Black DSC,Lewis PJ,Griffith R,Kumar N

更新日期：2017-09-15 00:00:00

abstract：:In the present study we report the synthesis of halogen-substituted phenanthrene β-diketo acids as new HIV-1 integrase inhibitors. The target phenanthrenes were obtained using both standard thermal- and microwave-assisted synthesis. 4-(6-Chlorophenanthren-2-yl)-2,4-dioxobutanoic acid (18) was the most active compound ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharma H,Sanchez TW,Neamati N,Detorio M,Schinazi RF,Cheng X,Buolamwini JK

更新日期：2013-11-15 00:00:00

abstract：:New cis-fused tetrahydrochromeno[4,3-b]quinolines have been synthesized by intramolecular [4+2] imino-Diels-Alder reactions of 2-azadienes derived in situ from aromatic amines and 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones in the presence of 20mol% Yb(OTf)(3) in acetonitrile under reflux conditio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nagaiah K,Venkatesham A,Srinivasa Rao R,Saddanapu V,Yadav JS,Basha SJ,Sarma AV,Sridhar B,Addlagatta A

更新日期：2010-06-01 00:00:00

abstract：:Four stereoisomeric hybrids of the polyketide natural products callystatin A and leptomycin B have been prepared by parallel synthetic routes involving chiral allenylstannane methodology. Like their natural counterparts, these hybrids exhibit nanomolar levels of cytotoxicity toward HCT-116 human colon cancer cells. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marshall JA,Mikowski AM,Bourbeau MP,Schaaf GM,Valeriote F

更新日期：2006-01-15 00:00:00

abstract：:A series of P1/P1' substituted cyclic urea analogues were prepared in an attempt to increase the intra-cellular antiviral potency of the nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851. The effect of alkyl substitution of the P1/P1' residues on cellular antiviral potency, protein binding, resistance profile and ph...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kaltenbach RF 3rd,Patel M,Waltermire RE,Harris GD,Stone BR,Klabe RM,Garber S,Bacheler LT,Cordova BC,Logue K,Wright MR,Erickson-Viitanen S,Trainor GL

更新日期：2003-02-24 00:00:00

abstract：:Nobiletin, a major component of polymethoxyflavones in citrus fruits, has a broad spectrum of health beneficial properties including anti-inflammatory and anti-carcinogenic activities. The metabolite identification of nobiletin in mouse urine has concluded that it undergoes mono-demethylation (3'- and 4'-demethylnobil...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li S,Sang S,Pan MH,Lai CS,Lo CY,Yang CS,Ho CT

更新日期：2007-09-15 00:00:00

abstract：:A series of novel 5-trans-hydroxyadamantan-2-yl-5,6,7,8-tetrahydropyrazolo[4,3-c]azepin-4(1H)-ones that inhibit 11beta-hydroxysteroid dehydrogenase type 1 are described. We discovered these 7-membered cyclic amide derivatives by introducing a distinctive linker through pharmacophore analysis of known ligands included ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Udagawa S,Sakami S,Takemura T,Sato M,Arai T,Nitta A,Aoki T,Kawai K,Iwamura T,Okazaki S,Takahashi T,Kaino M

更新日期：2013-03-15 00:00:00

abstract：:An efficient synthesis of [D-lysine](8)cyclosporin A has been developed. Several analogs of [D-lysine](8)cyclosporin A have been synthesized and show promising anti-HCV activity, particularly compounds 39 and 43, which each exhibit an anti-HCV EC(50)<200 nM, and are each ≥50-fold less immunosuppressive than cyclospori...

journal_title：Bioorganic & medicinal chemistry letters

authors： Scribner A,Houck D,Huang Z,Mosier S,Peel M,Scorneaux B

更新日期：2010-11-15 00:00:00

abstract：:A 2-pyrrolidinone ring containing a single hydroxymethyl side chain effectively replaces the N-acetylamino group of 4-(N-acetylamino)-3-guanidinobenzoic acid, a low micromolar inhibitor of influenza neuraminidase. This novel structural template affords new opportunities to evolve more potent benzoic acid inhibitors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Brouillette WJ,Atigadda VR,Luo M,Air GM,Babu YS,Bantia S

更新日期：1999-07-19 00:00:00