Successful bridging from a peptide to a non peptide antagonist at the human tachykinin NK-2 receptor.

abstract：:The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antag...

journal_title：Bioorganic & medicinal chemistry letters

authors： Walters I,Austin C,Austin R,Bonnert R,Cage P,Christie M,Ebden M,Gardiner S,Grahames C,Hill S,Hunt F,Jewell R,Lewis S,Martin I,David Nicholls,David Robinson

更新日期：2008-01-15 00:00:00

abstract：:Polymyxin B (1) monohydrochloride was converted to the tetra-BOC derivatives 1b and 1c by reaction with di-tert-butyl dicarbonate. The structures of these protected intermediates were established utilizing a degradative sequence that afforded 3 and 5. A method for the deprotection 2,4-dinitrophenylamines to the free a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Weinstein J,Afonso A,Moss E Jr,Miller GH

更新日期：1998-12-01 00:00:00

abstract：:The design and syntheses of new fluoroquinolone antibacterial agents having pyrrolidine ring at C-7 position are described. The pyrrolidine ring is optically active and possesses methyloxime functional group. Two of them have excellent in vitro antibacterial activities and pharmacokinetic profiles. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Choi DR,Shin JH,Yang J,Yoon SH,Jung YH

更新日期：2004-03-08 00:00:00

abstract：:The synthesis and SAR of benzylamine side chain analogs of the NK-1 receptor antagonist CP-99,994 are described. The 5-trifluoromethoxy analog, CP-122,721, shows superior in vivo blockade of NK-1 receptor mediated responses. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rosen TJ,Coffman KJ,McLean S,Crawford RT,Bryce DK,Gohda Y,Tsuchiya M,Nagahisa A,Nakane M,Lowe JA 3rd

更新日期：1998-02-03 00:00:00

abstract：:Human kallikrein 1 (KLK1) is the most extensively studied member of this family and plays a major role in inflammation processes. From Ugi multicomponent reactions, isomannide-based peptidomimetic 10 and 13 where synthesized and showed low micromolar values of IC50 for KLK1 The most active compound (10) presented comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barros TG,Santos JAN,de Souza BEG,Sodero ACR,de Souza AMT,da Silva DP,Rodrigues CR,Pinheiro S,Dias LRS,Abrahim-Vieira B,Puzer L,Muri EMF

更新日期：2017-01-15 00:00:00

abstract：:The structure-activity relationship (SAR) of the vinyl pyridine region of himbacine derived thrombin receptor (PAR-1) antagonists is described. A 2-vinylpyridyl ring substituted with an aryl or a heteroaryl group at the 5-position showed the best overall PAR-1 affinity and pharmacokinetic properties. One of the newly ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xia Y,Chackalamannil S,Clasby M,Doller D,Eagen K,Greenlee WJ,Tsai H,Agans-Fantuzzi J,Ahn HS,Boykow GC,Hsieh Y,Lunn CA,Chintala M

更新日期：2007-08-15 00:00:00

abstract：:The synthesis and evaluation of tetrasubstituted aminopyridines, bearing novel azaindazole hinge binders, as potent AKT inhibitors are described. Compound 14c was identified as a potent AKT inhibitor that demonstrated reduced CYP450 inhibition and an improved developability profile compared to those of previously desc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lin H,Yamashita DS,Xie R,Zeng J,Wang W,Leber J,Safonov IG,Verma S,Li M,Lafrance L,Venslavsky J,Takata D,Luengo JI,Kahana JA,Zhang S,Robell KA,Levy D,Kumar R,Choudhry AE,Schaber M,Lai Z,Brown BS,Donovan BT,Mi

更新日期：2010-01-15 00:00:00

abstract：:Iminium quaternary protoberberine alkaloids (QPA) have been found to be novel P2X(7) antagonists. To assess their structure-activity relationships, these compounds were modified at their R(1) and R(2) groups and assayed for their ability to inhibit the 2'(3')-O-(4-benzoylbenzoyl)-ATP (BzATP)-induced uptake of fluoresc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee GE,Lee HS,Lee SD,Kim JH,Kim WK,Kim YC

更新日期：2009-02-01 00:00:00

abstract：:A series of substituted indoles were examined as selective inhibitors of tropomyosin-related kinase receptor A (TrkA), a therapeutic target for the treatment of pain. An SAR optimization campaign based on ALIS screening lead compound 1 is reported. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hurzy DM,Henze DA,Cabalu TD,Narayan K,Heller A,Cooke AJ

更新日期：2017-06-15 00:00:00

abstract：:This Letter describes, for the first time, the synthesis and SAR, developed through an iterative analog library approach, that led to the discovery of the positive allosteric modulator (PAM) of the metabotropic glutamate receptor mGluR5 CPPHA. Binding to a unique allosteric binding site distinct from other mGluR5 PAMs...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao Z,Wisnoski DD,O'Brien JA,Lemaire W,Williams DL Jr,Jacobson MA,Wittman M,Ha SN,Schaffhauser H,Sur C,Pettibone DJ,Duggan ME,Conn PJ,Hartman GD,Lindsley CW

更新日期：2007-03-01 00:00:00

abstract：:Macromolecular chelators have potential applications in the medical area, for instance, in treatment of iron overload-related disorders and in the treatment of external infections. In this investigation, several novel iron(III)-selective hydroxypyridinone hexadentate-terminated first and second generation dendrimeric ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhou T,Chen K,Kong LM,Liu MS,Ma YM,Xie YY,Hider RC

更新日期：2018-08-01 00:00:00

abstract：:Oxidation of 4-methylcatechol previously exposed to aqueous calcium chloride was shown by ion chromatography to be associated with release of calcium ions. The catechol was oxidised to the corresponding orthoquinone by the use of tyrosinase from Agaricus bisporus. The oxidative release of calcium from the catechol is ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Riley PA,Stratford MR

更新日期：2015-04-01 00:00:00

abstract：:A series of substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles has been prepared as Src kinase inhibitors. Optimal activity is observed with compounds that have basic amines attached via the para position of the 7-phenyl ring, and a hydrogen atom at the C-6 position. The best compounds are low nanomolar inhibitor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Berger D,Dutia M,Powell D,Wissner A,DeMorin F,Raifeld Y,Weber J,Boschelli F

更新日期：2002-10-21 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：:Nrf2 is the major transcription factor that regulates many of the cytoprotective enzymes involved in the adaptive stress response. Modulation of Nrf2 could be therapeutically useful in a number of disease states. Activation can occur through either an electrophilic or non-electrophilic mechanism. To date, most of the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Richardson BG,Jain AD,Speltz TE,Moore TW

更新日期：2015-06-01 00:00:00

abstract：:Polyoxometalates (POMs) are interesting biomedical agents due to their versatile anticancer and antiviral properties, such as remarkable anti-HIV activity. Although POMs are tunable and easily accessible inorganic drug prototypes in principle, their full potential can only be tapped by enhancing their biocompatibility...

journal_title：Bioorganic & medicinal chemistry letters

authors： Flütsch A,Schroeder T,Grütter MG,Patzke GR

更新日期：2011-02-15 00:00:00

abstract：:It is well known that resveratrol (RSV) displayed cancer-preventing and anticancer properties but its clinical application is limited because of a low bioavailability and a rapid clearance from the circulation. Aim of this work was to synthesize pharmacologically active resveratrol analogs with an enhanced structural ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sala M,Chimento A,Saturnino C,Gomez-Monterrey IM,Musella S,Bertamino A,Milite C,Sinicropi MS,Caruso A,Sirianni R,Tortorella P,Novellino E,Campiglia P,Pezzi V

更新日期：2013-09-01 00:00:00

abstract：:PTPases are considered to be involved in the etiology of diabetes mellitus and neural diseases, such as Alzheimer's disease and Parkinson's disease. Therefore, PTPase inhibitors should be useful tools to study the role of PTPases in these diseases and other biological phenomena, and which can be developed into chemoth...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ahmad G,Mishra PK,Gupta P,Yadav PP,Tiwari P,Tamrakar AK,Srivastava AK,Maurya R

更新日期：2006-04-15 00:00:00

abstract：:The first demonstration of DNA cleavage by resveratrol '3,5,4'-trihydroxy-trans-stilbene' is presented. Resveratrol mediated relaxation of pBR322 at micromolar concentrations in the presence of Cu2+. Evidence is provided that resveratrol is capable of binding to DNA, and that the Cu(2+)-dependent DNA damage is more li...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fukuhara K,Miyata N

更新日期：1998-11-17 00:00:00

abstract：:The optimization of a novel series of non-nucleoside reverse transcriptase inhibitors (NNRTI) led to the identification of pyridone 36. In cell cultures, this new NNRTI shows a superior potency profile against a range of wild type and clinically relevant, resistant mutant HIV viruses. The overall favorable preclinical...

journal_title：Bioorganic & medicinal chemistry letters

authors： Côté B,Burch JD,Asante-Appiah E,Bayly C,Bédard L,Blouin M,Campeau LC,Cauchon E,Chan M,Chefson A,Coulombe N,Cromlish W,Debnath S,Deschênes D,Dupont-Gaudet K,Falgueyret JP,Forget R,Gagné S,Gauvreau D,Girardin M,Guir

更新日期：2014-02-01 00:00:00

abstract：:Several oximes of triterpenes with a 17-beta hydroxyl and abietane derivatives are inhibitors of pyruvate dehydrogenase kinase (PDK) activity. The oxime 12 and dehydroabietyl amine 2 exhibit a blood glucose lowering effect in the diabetic ob/ob mouse after a single oral dose of 100 micromol/kg. However, the mechanism ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aicher TD,Damon RE,Koletar J,Vinluan CC,Brand LJ,Gao J,Shetty SS,Kaplan EL,Mann WR

更新日期：1999-08-02 00:00:00

abstract：:We report an SAR study of MC4R analogs containing spiroindane heterocyclic privileged structures. Compound 26 with N-Me-1,2,4-triazole moiety possesses exceptional potency at MC4R and potent anti-obesity efficacy in a mouse model. However, the efficacy is not completely mediated through MC4R. Additional SAR studies le...

journal_title：Bioorganic & medicinal chemistry letters

authors： He S,Ye Z,Dobbelaar PH,Bakshi RK,Hong Q,Dellureficio JP,Sebhat IK,Guo L,Liu J,Jian T,Lai Y,Franklin CL,Reibarkh M,Holmes MA,Weinberg DH,MacNeil T,Tang R,Tamvakopoulos C,Peng Q,Miller RR,Stearns RA,Chen HY,Chen

更新日期：2010-11-15 00:00:00

abstract：:The synthesis of six α,β,-unsaturated amides and six 2,4-disubstituted oxazolines derivatives and their evaluation against two Mycobacterium tuberculosis strains (sensitive H37Rv and a resistant clinical isolate) is reported. 2,4-Disubstituted oxazolines (S)-3b,d,e were the most active in the sensitive strain with a M...

journal_title：Bioorganic & medicinal chemistry letters

authors： Avalos-Alanís FG,Hernández-Fernández E,Carranza-Rosales P,López-Cortina S,Hernández-Fernández J,Ordóñez M,Guzmán-Delgado NE,Morales-Vargas A,Velázquez-Moreno VM,Santiago-Mauricio MG

更新日期：2017-02-15 00:00:00

abstract：:Bruton's Tyrosine Kinase (BTK) is one of the crucial kinases for the B cell maturation and mast cell activation, and specific inhibitors of BTK are considered to be attractive targets in drug discovery research. In this Letter, we have designed and synthesized a new fluorescent probe for TR-FRET-based high-throughput ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Asami T,Kawahata W,Sawa M

更新日期：2015-01-01 00:00:00

abstract：:A series of novel 1,3,4-oxadiazole/thiadiazole-chalcone conjugates were synthesized and their in vitro and in vivo antiviral activities were evaluated via microscale thermophoresis method and half-leaf method, respectively. The in vitro results indicated that compounds 7g, 7l, 8h, and 8l displayed good antiviral activ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gan X,Hu D,Chen Z,Wang Y,Song B

更新日期：2017-09-15 00:00:00

abstract：:The study by the molecular orbital theory displayed that morphine and lysine make two types of the interactions between them: type (A) by three hydrogen bondings and type (B) by one hydrogen bonding accompanied with a proton transfer. The stabilization energies were 45.3 and 34.9 kcal/mol for type (A) and type (B), re...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nakai S,Yoneda F

更新日期：2001-06-04 00:00:00

abstract：:Derivatives of a CYP1A2 inhibitor rutaecarpine were synthesized to have potent and selective inhibition of human CYP1 members. Structural modelling shows a good fitting of rutaecarpine with the putative active site of human CYP1A2. Among the derivatives, 10- and 11-methoxyrutaecarpine are the most selective CYP1B1 inh...

journal_title：Bioorganic & medicinal chemistry letters

authors： Don MJ,Lewis DF,Wang SY,Tsai MW,Ueng YF

更新日期：2003-08-04 00:00:00

abstract：:Several novel series of nitrile-containing fluoroquinolones with weakly basic amines are reported which have reduced potential for hERG (human ether-a-go-go gene) channel inhibition as measured by the dofetilide assay. The new fluoroquinolones are potent against both Gram-positive and fastidious Gram-negative strains,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Murphy ST,Case HL,Ellsworth E,Hagen S,Huband M,Joannides T,Limberakis C,Marotti KR,Ottolini AM,Rauckhorst M,Starr J,Stier M,Taylor C,Zhu T,Blaser A,Denny WA,Lu GL,Smaill JB,Rivault F

更新日期：2007-04-15 00:00:00

abstract：:Androgen receptor activity drives incurable castrate-resistant prostate cancer. All approved antiandrogens inhibit androgen receptor-driven transcription, and in addition the second-generation antiandrogen MDV3100 inhibits ligand-activated androgen receptor nuclear translocation, via an unknown mechanism. Here, we rep...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim YS,Kumar V,Lee S,Iwai A,Neckers L,Malhotra SV,Trepel JB

更新日期：2012-03-01 00:00:00

abstract：:Several non-amidino S1 derivatives of the 1,2-diaminobenzene-based scaffold (4) were synthesized and evaluated for their ability to bind to the active site and inhibit the human protease factor Xa. A subset of these compounds were also evaluated for their anticoagulant effects in human plasma as measured by prothrombi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Franciskovich JB,Masters JJ,Tinsley JM,Craft TJ,Froelich LL,Gifford-Moore DS,Klimkowski VJ,Smallwood JK,Smith GF,Smith T,Towner RR,Weir LC,Wiley MR

更新日期：2005-11-01 00:00:00