Potent and selective 5-LO inhibitor bearing benzothiophene pharmacophore: discovery of MK-5286.

abstract：:A series of derivatives of the new ring system pyrrolo[2,3-h]quinoline-2-one was synthesized and evaluated as photoreagents toward cultured human tumor cells. Remarkable phototoxycity resulted for some derivatives, especially those bearing the phenyl group at the 7-position. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barraja P,Diana P,Lauria A,Montalbano A,Almerico AM,Dattolo G,Cirrincione G,Viola G,Dall'Acqua F

更新日期：2003-08-18 00:00:00

abstract：:The formation of blood clots in blood vessels causes severe ischemic diseases such as cerebral infarction and myocardial infarction. While searching for microbial products that increase fibrinolytic activity using an in vitro fibrin degradation assay, we found malformin A1, a disulfide form of cyclo(-d-Cys-d-Cys-l-Val...

journal_title：Bioorganic & medicinal chemistry letters

authors： Koizumi Y,Nagai K,Hasumi K,Kuba K,Sugiyama T

更新日期：2016-11-01 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：:d-Labeled N-alkylmaleimides have been prepared for specific modification of the terminal SH groups of cysteine residues in proteins or peptides. These reagents are useful tools for quantitative analysis of peptides by stable isotope differential mass spectrometry. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Niwayama S,Kurono S,Matsumoto H

更新日期：2001-09-03 00:00:00

abstract：:The synthesis and inhibitory activity against MraY of a series of simplified analogues of liposidomycins are described. These compounds were mainly obtained by performing parallel synthesis in the 6'-position of a scaffold that gathers key features found necessary for the binding to MraY. Thus, inhibitory activity was...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dini C,Didier-Laurent S,Drochon N,Feteanu S,Guillot JC,Monti F,Uridat E,Zhang J,Aszodi J

更新日期：2002-04-22 00:00:00

abstract：:Modulation of DNA repair pathways in oncology has been an area of intense interest in the last decade, not least as a consequence of the promising clinical activity of poly(ADP-ribose) polymerase (PARP) inhibitors. In this review article, we highlight inhibitors of the phosphatidylinositol 3-kinase related kinase (PIK...

journal_title：Bioorganic & medicinal chemistry letters

authors： Finlay MR,Griffin RJ

更新日期：2012-09-01 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：:Esculentoside A (EsA) has been reported to possess anti-inflammatory activity and selective inhibitory activity towards cyclooxygenase-2. A series of derivatives of EsA were synthesized by converting the C-28 carboxylic acid group into amides. The haemolytic activity and inhibitory activity towards cyclooxygenase-2 we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wu F,Yi Y,Sun P,Zhang D

更新日期：2007-12-01 00:00:00

abstract：:Two analogues possessing steric hindered substituents on C-15 of arenastatin A (1), a potent cytotoxic spongean depsipeptide, were synthesized and shown to enhance stability in mouse serum. Notably, 15-tert-butylanalogue (6) with higher cytotoxicity exhibited in vivo anti-tumor activity through iv administration diffe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Murakami N,Tamura S,Koyama K,Sugimoto M,Maekawa R,Kobayashi M

更新日期：2004-05-17 00:00:00

abstract：:A catalyst-free synthesis of 6,9-dihydro-[1,3]dioxolo[4,5-g]thieno[3,4-b]quinolin-8(5H)-ones as novel analogues of podophyllotoxins was developed by a three-component reaction of aldehydes, ethyl 2,4-dioxotetrahydrothiophene-3-carboxylate and 3,4-(methylenedioxy)aniline. This methodology not only provides new chemical...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li T,Lu T,Yu C,Yao C

更新日期：2015-04-01 00:00:00

abstract：:Three new (1-3) and one known (4) bioactive terpenoids were isolated from the seeds of Silybum marianum based on the investigation to get new NO inhibitors. Their structures were determined by extensive NMR (1D and 2D NMR) and MS spectroscopic data, and the absolute configurations were identified by experimental and c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qin NB,Li SG,Yang XY,Gong C,Zhang XY,Wang J,Li DH,Guo YQ,Li ZL,Hua HM

更新日期：2017-05-15 00:00:00

abstract：:We have synthesized a series of 4H,6H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide nucleoside and their anti-vesicular stomatitis virus (VSV) activities in Wish cell were also investigated in vitro. It was found that most compounds showed obvious anti-VSV activities and compound 9 with ribofuranoside improved ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu X,Wang J,Yao Q

更新日期：2015-01-15 00:00:00

abstract：:Substituted benzimidazoles were profiled as inhibitors of kinesin spindle protein (KSP), an increasingly important target for the development of anticancer drugs. This series demonstrated the monoastral phenotypic response and was found to be active in both enzymatic and cellular-based assays. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lahue BR,Ma Y,Shipps GW Jr,Seghezzi W,Herbst R

更新日期：2009-07-01 00:00:00

abstract：:The design, synthesis, and enzyme kinetics evaluation of a transition-state inhibitor of glyoxalase-I is described. The union of the hydroxamic acid zinc-chelator with a urea isostere for the glu-cys amide bond led to a glutathione analog which retained inhibitory potency toward glyoxalase-I while possessing resistanc...

journal_title：Bioorganic & medicinal chemistry letters

authors： More SS,Vince R

更新日期：2006-12-01 00:00:00

abstract：:Nicotinic acetylcholine receptors (nAChRs) are downregulated in disease conditions such as Alzheimer's and substance abuse. Presently, (123)I-5-IA-85380 is used in human studies and requires over 6h of scanning time, thus increases patient discomfort. We have designed and synthesized 3-iodo-5-[2-(S)-3-pyrrolinylmethox...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pandey SK,Pan S,Kant R,Kuruvilla SA,Pan ML,Mukherjee J

更新日期：2012-12-15 00:00:00

abstract：:Two classes of compounds, thiocarbamates 1 and triazoles 2, have been identified as HIV RT RNase H inhibitors using a novel FRET-based HTS assay. The potent analogs in each series exhibited selectivity and were active in cell-based assays. In addition, saturable, 1:1 stoichiometric binding to target was established an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Di Grandi M,Olson M,Prashad AS,Bebernitz G,Luckay A,Mullen S,Hu Y,Krishnamurthy G,Pitts K,O'Connell J

更新日期：2010-01-01 00:00:00

abstract：:Molecular hybridization is an emerging structural modification tool to design molecules with better pharmacophoric properties. A series of novel 2-(trifluoromethyl)phenothiazine-1,2,3-triazoles 5a-v designed by hybridizing two antitubercular drugs trifluoperazine and I-A09 in a single molecular architecture, were synt...

journal_title：Bioorganic & medicinal chemistry letters

authors： Addla D,Jallapally A,Gurram D,Yogeeswari P,Sriram D,Kantevari S

更新日期：2014-01-01 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：:The ability of serine phosphate (SerP) or alpha-amino-gamma-phosphonobutyric acid (AbuP) and arginine to form a salt bridge between their side chains appears to be much greater when they are spaced i/i+4 than when they are spaced i/i+3. The side chain-side chain interaction between SerP/Arg and AbuP/Arg, positioned i/...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liehr S,Chenault HK

更新日期：1999-09-20 00:00:00

abstract：:A series of novel amino acid ester derivatives of 2,3-substituted isoindolinones was synthesized and evaluated for p53-mediated apoptotic activity. The rationale for augmentation of the target activity of 2,3-substituted isoindolinones was based on the introduction of new fragments in the structure of the inhibitor th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Grigoreva TA,Novikova DS,Petukhov AV,Gureev MA,Garabadzhiu AV,Melino G,Barlev NA,Tribulovich VG

更新日期：2017-12-01 00:00:00

abstract：:A novel series of acylated omega-aminoalkyl 2-amino-2-deoxy-4-phosphono-beta-D-glucopyranosides (aminoalkyl glucosaminide 4-phosphates) was synthesized and screened for immunostimulant activity. Several of these compounds enhance the production of tetanus toxoid-specific antibodies in mice and augment vaccine-induced ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Johnson DA,Sowell CG,Johnson CL,Livesay MT,Keegan DS,Rhodes MJ,Ulrich JT,Ward JR,Cantrell JL,Brookshire VG

更新日期：1999-08-02 00:00:00

abstract：:Incorporation of a 4-hydroxy-N-acetylprolinol nucleotide analogue at the 3'-terminus of DNA or 2-5A-DNA sequences resulted in a significantly enhanced 3'-exonuclease resistance while the affinity for complementary RNA was only slightly decreased. Furthermore, the binding to and activation of human RNase L by thus modi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Verheijen JC,van Roon AM,Meeuwenoord NJ,Stuivenberg HR,Bayly SF,Chen L,van der Marel GA,Torrence PF,van Boom JH

更新日期：2000-04-17 00:00:00

abstract：:A polyphemusin peptide analogue, T22 ([Tyr(5,12), Lys7]-polyphemusin II), and its shortened potent analogues, T134 (des-[Cys(8,13), Tyr(9,12)]-[D-Lys10, Pro11, L-citrulline16]-T22 without C-terminal amide) and T140 [[L-3-(2-naphthyl)alanine3]-T134], strongly inhibit the T-cell line-tropic (T-tropic) HIV-1 infection th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tamamura H,Omagari A,Oishi S,Kanamoto T,Yamamoto N,Peiper SC,Nakashima H,Otaka A,Fujii N

更新日期：2000-12-04 00:00:00

abstract：:Novel prostaglandin E2 receptor 4 (EP4) agonists featuring a pyridone core and an allylic alcohol ω-chain were discovered. These agonists were shown to be selective over EP1, EP2 and EP3. Analogs harboring a 4-carboxylic acid phenethyl α-chain displayed improved potency over those containing an n-heptanoic acid chain....

journal_title：Bioorganic & medicinal chemistry letters

authors： Dorich S,Cox JH,Burch JD,Chagnon F,Chen B,Léger S,St-Onge M,Fader LD

更新日期：2020-05-15 00:00:00

abstract：:In an effort to identify a potential back-up to apixaban (Eliquis®), we explored a series of diversified P4 moieties. Several analogs with substituted gem-dimethyl moieties replacing the terminal lactam of apixaban were identified which demonstrated potent FXa binding affinity (FXa Ki), good human plasma anticoagulant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Orwat MJ,Qiao JX,He K,Rendina AR,Luettgen JM,Rossi KA,Xin B,Knabb RM,Wexler RR,Lam PY,Pinto DJ

更新日期：2014-08-01 00:00:00

abstract：:A Hit-to-Lead optimisation programme was carried out on the high throughput screening hit, the triazolethiol 1, resulting in the discovery of the potent, orally bioavailable triazolethiol CXCR2 receptor antagonist 45. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Baxter A,Bennion C,Bent J,Boden K,Brough S,Cooper A,Kinchin E,Kindon N,McInally T,Mortimore M,Roberts B,Unitt J

更新日期：2003-08-18 00:00:00

abstract：:Sulfonyl amidines (1) and phosphoryl amidines (2), which were efficiently synthesized via a Cu-catalyzed one pot reaction, showed potent anti-bone resorptive activity in vitro. Structure activity relationship studies led to the identification of numerous osteoclast differentiation inhibitors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee MY,Kim MH,Kim J,Kim SH,Kim BT,Jeong IH,Chang S,Kim SH,Chang SY

更新日期：2010-01-15 00:00:00

abstract：:Two new trichothecene sesquiterpenes, trichobreols D (1) and E (2), were isolated from the culture broth of marine-derived Trichoderma cf. brevicompactum together with trichobreol A (3). The structures of 1 and 2 were assigned on the basis of their spectroscopic data. Compound 1 inhibited the growth of two yeast-like ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yamazaki H,Yagi A,Takahashi O,Yamaguchi Y,Saito A,Namikoshi M,Uchida R

更新日期：2020-09-01 00:00:00

abstract：:We report here a simple entry into naphtho[2,3-d]isoxazole-4,9-dione system containing a EWG in position 3 using the readily available 2,3-dichloro-1,4-naphthoquinone and nitromethyl derivatives in the presence of base. Antifungal activity of synthesised naphthoquinones was evaluated against ATCC and PYCC reference st...

journal_title：Bioorganic & medicinal chemistry letters

authors： Santos MM,Faria N,Iley J,Coles SJ,Hursthouse MB,Martins ML,Moreira R

更新日期：2010-01-01 00:00:00

abstract：:The purpose of this study was to prepare and characterize nanometer-sized prodrug (nanoprodrug) of camptothecin. The camptothecin prodrug was synthesized using tetraethylene glycol spacer linked via carbonate bond to camptothecin and via ester bond to alpha-lipoic acid. The nanoprodrug was prepared through the spontan...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee BS,Nalla AK,Stock IR,Shear TC,Black KL,Yu JS

更新日期：2010-09-01 00:00:00