Nonsteroidal antiinflammatory agents. 14. Synthesis and pharmacological profile of 6-chloro-5-(cyclopentylmethyl)indan-1-carboxylic acid.

abstract：:Conformationally restricted 2'-spironucleosides and their prodrugs were synthesized as potential anti-HCV agents. Although the replicon activity of the new agents containing pyrimidine bases was modest, the triphosphate of a 2'-oxetane cytidine analogue demonstrated potent intrinsic biochemical activity against the NS...

journal_title：Journal of medicinal chemistry

authors： Du J,Chun BK,Mosley RT,Bansal S,Bao H,Espiritu C,Lam AM,Murakami E,Niu C,Micolochick Steuer HM,Furman PA,Sofia MJ

更新日期：2014-03-13 00:00:00

abstract：:Cell division cycle 25 (Cdc25) proteins are highly conserved dual specificity phosphatases that regulate cyclin-dependent kinases and represent attractive drug targets for anticancer therapies. To discover more potent and diverse inhibitors of Cdc25 biological activity, virtual screening was performed by docking 2.1 m...

journal_title：Journal of medicinal chemistry

authors： Lavecchia A,Di Giovanni C,Pesapane A,Montuori N,Ragno P,Martucci NM,Masullo M,De Vendittis E,Novellino E

更新日期：2012-05-10 00:00:00

abstract：:We have synthesized a series of N-phenyl-N'-aralkyl and N-phenyl-N'-(1-phenylcycloalkyl)ureas as inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). This intracellular enzyme is thought to be responsible for the esterification of dietary cholesterol; hence inhibition of this enzyme could reduce diet-induced hyp...

journal_title：Journal of medicinal chemistry

authors： Trivedi BK,Holmes A,Stoeber TL,Blankley CJ,Roark WH,Picard JA,Shaw MK,Essenburg AD,Stanfield RL,Krause BR

更新日期：1993-10-29 00:00:00

abstract：:A novel series of 2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues has been prepared to probe the steric and electronic properties of the binding pocket of the MT(2) receptor accommodating the "out-of-plane" substituent of MT(2)-selective antagonists. The acetamide (6b) bearing an usubstituted indoline moiety ...

journal_title：Journal of medicinal chemistry

authors： Zlotos DP,Attia MI,Julius J,Sethi S,Witt-Enderby PA

更新日期：2009-02-12 00:00:00

abstract：:The prevalence of multidrug resistance among clinically significant bacterial pathogens underscores a critical need for the development of new classes of antibiotics with novel mechanisms of action. Here we describe the synthesis and evaluation of a guanidinomethyl biaryl compound {1-((4'-(tert-butyl)-[1,1'-biphenyl]-...

journal_title：Journal of medicinal chemistry

authors： Kaul M,Parhi AK,Zhang Y,LaVoie EJ,Tuske S,Arnold E,Kerrigan JE,Pilch DS

更新日期：2012-11-26 00:00:00

abstract：:The photoswitchable N-terminal diazo and triazene-dipeptide aldehydes 8a-d, 10a,b, and 17a,b present predominantly as the (E)-isomer, which purportedly binds deep in the S3 pocket of calpain. All compounds are potent inhibitors of m-calpain, with 8b being the most active (IC50 of 35 nM). The diazo-containing inhibitor...

journal_title：Journal of medicinal chemistry

authors： Abell AD,Jones MA,Neffe AT,Aitken SG,Cain TP,Payne RJ,McNabb SB,Coxon JM,Stuart BG,Pearson D,Lee HY,Morton JD

更新日期：2007-06-14 00:00:00

abstract：:In a search for improved multiple drug resistance (MDR) modulators, we identified a novel series of substituted pyrroloquinolines that selectively inhibits the function of P-glycoprotein (Pgp) without modulating multidrug resistance-related protein 1 (MRP1). These compounds were evaluated for their toxicity toward dru...

journal_title：Journal of medicinal chemistry

authors： Lee BD,Li Z,French KJ,Zhuang Y,Xia Z,Smith CD

更新日期：2004-03-11 00:00:00

abstract：:The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Bart...

journal_title：Journal of medicinal chemistry

authors： Procopiou PA,Biggadike K,English AF,Farrell RM,Hagger GN,Hancock AP,Haase MV,Irving WR,Sareen M,Snowden MA,Solanke YE,Tralau-Stewart CJ,Walton SE,Wood JA

更新日期：2001-02-15 00:00:00

abstract：:The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneou...

journal_title：Journal of medicinal chemistry

authors： Singh J,Zeller W,Zhou N,Hategan G,Mishra RK,Polozov A,Yu P,Onua E,Zhang J,Ramírez JL,Sigthorsson G,Thorsteinnsdottir M,Kiselyov AS,Zembower DE,Andrésson T,Gurney ME

更新日期：2010-01-14 00:00:00

abstract：:Our previous reports have highlighted the first-generation leukotriene B4 (LTB4) receptor antagonist SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]3,4- dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid) which has potent oral, topical, and intracolonic activity in various animal models of inflammation. Ex...

journal_title：Journal of medicinal chemistry

authors： Penning TD,Djuric SW,Miyashiro JM,Yu S,Snyder JP,Spangler D,Anglin CP,Fretland DJ,Kachur JF,Keith RH

更新日期：1995-03-17 00:00:00

abstract：:The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) mod...

journal_title：Journal of medicinal chemistry

authors： Abd El-Salam M,Bastos JK,Han JJ,Previdi D,Coelho EB,Donate PM,Romero MF,Lieske J

更新日期：2018-02-22 00:00:00

abstract：:The goal of this study was to design paclitaxel (PTX)-monoclonal antibody (mAb) prodrug conjugates (PTXMAbs) with the ability to deliver therapeutically significant doses of the drug to the tumor while avoiding the previously observed solubility limitations of conjugates with PTX:mAb molar ratios of >3. New PTX conjug...

journal_title：Journal of medicinal chemistry

authors： Quiles S,Raisch KP,Sanford LL,Bonner JA,Safavy A

更新日期：2010-01-28 00:00:00

abstract：:Singlet oxygen can severely damage biological tissue, which is exploited in photodynamic therapy (PDT). In PDT, the effective range is limited by the distribution of the photosensitizer (PS) and the illuminated area. However, no distinction is made between healthy and pathological tissue, which can cause undesired dam...

journal_title：Journal of medicinal chemistry

authors： Radunz S,Wedepohl S,Röhr M,Calderón M,Tschiche HR,Resch-Genger U

更新日期：2020-02-27 00:00:00

abstract：:Tipifarnib (R115777), an inhibitor of human protein farnesyltransferase (PFT), is shown to be a highly potent inhibitor of Trypanosoma cruzi growth (ED(50) = 4 nM). Surprisingly, this is due to the inhibition of cytochrome P450 sterol 14-demethylase (CYP51, EC 1.14.13.70). Homology models of the T. cruzi CYP51 were us...

journal_title：Journal of medicinal chemistry

authors： Hucke O,Gelb MH,Verlinde CL,Buckner FS

更新日期：2005-08-25 00:00:00

abstract：:2-Hydroxy-5-(3,4-dichlorophenyl)-6,7-bis(hydroxymethyl)-2,3-dihydro-1H- pyrrolizine bis(2-propylcarbamate) (11) was prepared in a multistep synthesis. The 2-hydroxy group was used to prepare ester prodrugs 14 and 15, and the antineoplastic activities of 11, 14, and 15a were compared to 1 (the 2-deoxy analogue of 11) i...

journal_title：Journal of medicinal chemistry

authors： Anderson WK,Chang CP,McPherson HL Jr

更新日期：1983-09-01 00:00:00

abstract：:Molecular modeling methods have been used to design a novel series of conformationally constrained cyclic peptide inhibitors of human renin. Three goals were defined: enhanced inhibitory potency, high specificity for renin, and increased metabolic stability. Three cyclic compounds were synthesized with ring sizes 10, ...

journal_title：Journal of medicinal chemistry

authors： Sham HL,Bolis G,Stein HH,Fesik SW,Marcotte PA,Plattner JJ,Rempel CA,Greer J

更新日期：1988-02-01 00:00:00

abstract：:The conformation of the sodium salt of mycophenolic acid (MPA), a potent inhibitor of inosine monophosphate dehydrogenase (IMPD), derived from 1D DIFNOE and 2D ROESY experiments in water and molecular dynamics (MD) is described. The hexenoic acid side chain conformation consistent with the NMR data was similar to that...

journal_title：Journal of medicinal chemistry

authors： Makara GM,Keserû GM,Kajtár-Peredy M,Anderson WK

更新日期：1996-03-15 00:00:00

abstract：:To study the influence of substitution of CN for C identical to CH in the anti-herpes virus nucleoside 5-(propynyloxy)-2'-deoxyuridine (1), 5-[(cyanomethylene)oxy]-2'-deoxyuridine (2) was prepared. When the potassium salt of 5-hydroxy-2'-deoxyuridine was reacted with iodoacetonitrile in dry DMF, the bisalkylated produ...

journal_title：Journal of medicinal chemistry

authors： Huang GF,Okada M,De Clercq E,Torrence PF

更新日期：1981-04-01 00:00:00

abstract：:Several compounds having portions of the camptothecin ring system were prepared. These compounds were screened against L1210 lymphoid leukemia with negative results. Two of the analogs which contained the pyridine and hydroxylactone D and E rings were also screened for inhibition of DNA and RNA syntheses in HeLa cells...

journal_title：Journal of medicinal chemistry

authors： Horwitz SB,Bristol JA,Comins DL,Davenport RW,Kane MJ,Lyle RE,Maloney JR,Portlock DE

更新日期：1975-05-01 00:00:00

abstract：:A series of 2-substituted methyl 2,3-dihydroimidazo[1, 2-c]quinazolin-5(6H)-ones (4), 3-substituted methyl 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-ones (5), 3-substituted methyl 2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-ones (15a,b), 3-substituted methyl 2,3-dihydroimidazo[2,1-b]quinazolin-5(1H)-ones (16a,b), 3-su...

journal_title：Journal of medicinal chemistry

authors： Chern JW,Tao PL,Wang KC,Gutcait A,Liu SW,Yen MH,Chien SL,Rong JK

更新日期：1998-08-13 00:00:00

abstract：:Four highly charged, water soluble platinum-acridine bisintercalating agents have been synthesized. Depending on the cis/trans isomerism of the metal and the nature of the acridine side chains, bisintercalation induces/stabilizes the classical Watson-Crick B-form or a non-B-form. Circular dichroism spectra and chemica...

journal_title：Journal of medicinal chemistry

authors： Choudhury JR,Guddneppanavar R,Saluta G,Kucera GL,Bierbach U

更新日期：2008-06-12 00:00:00

abstract：:Since the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) as an attractive target for anticancer therapy in 2003, the search for inhibitors has been intensely pursued both in academia and in pharmaceutical companies. Many novel IDO1 inhibitor scaffolds have been described, and a few potent compounds have entered cli...

journal_title：Journal of medicinal chemistry

authors： Röhrig UF,Majjigapu SR,Vogel P,Zoete V,Michielin O

更新日期：2015-12-24 00:00:00

abstract：:Group VIA calcium-independent phospholipase A(2) (GVIA iPLA(2)) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA(2) inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(na...

journal_title：Journal of medicinal chemistry

authors： Kokotos G,Hsu YH,Burke JE,Baskakis C,Kokotos CG,Magrioti V,Dennis EA

更新日期：2010-05-13 00:00:00

abstract：:A series of tricyclic analogues of 9-oxo-9H-xanthene-4-acetic acid have been prepared and evaluated for their ability to cause hemorrhagic necrosis in subcutaneously implanted colon 38 tumors in mice, in an effort to extend the structure-activity relationships for this series. As was found previously with analogues of...

journal_title：Journal of medicinal chemistry

authors： Rewcastle GW,Atwell GJ,Palmer BD,Boyd PD,Baguley BC,Denny WA

更新日期：1991-02-01 00:00:00

abstract：:The F9/Yde/Fml pilus, tipped with the FmlH adhesin, has been shown to provide uropathogenic Escherichia coli (UPEC) a fitness advantage in urinary tract infections (UTIs). Here, we used X-ray structure guided design to optimize our previously described ortho-biphenyl Gal and GalNAc FmlH antagonists such as compound 1 ...

journal_title：Journal of medicinal chemistry

authors： Maddirala AR,Klein R,Pinkner JS,Kalas V,Hultgren SJ,Janetka JW

更新日期：2019-01-24 00:00:00

abstract：:Eucalyptin A (1), together with two known compounds 2 and 3 exhibiting potent inhibition on HGF/c-Met axis, was discovered from the fruits of Eucalyptus globulus. 1 possessed an unprecedented carbon framework of phloroglucinol-coupled sesquiterpenoid, and its structure was elucidated by spectroscopic method and ECD ca...

journal_title：Journal of medicinal chemistry

authors： Yang SP,Zhang XW,Ai J,Gan LS,Xu JB,Wang Y,Su ZS,Wang L,Ding J,Geng MY,Yue JM

更新日期：2012-09-27 00:00:00

abstract：:A weak, nonselective G protein-coupled receptor 120 (GPR120) agonist 10 was found by screening a series of carboxylic acids derived from the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist 3. Modification based on the homology model of GPR120 led to the first GPR120-selective agonist 12. These res...

journal_title：Journal of medicinal chemistry

authors： Suzuki T,Igari S,Hirasawa A,Hata M,Ishiguro M,Fujieda H,Itoh Y,Hirano T,Nakagawa H,Ogura M,Makishima M,Tsujimoto G,Miyata N

更新日期：2008-12-11 00:00:00

abstract：:A six-stage stereoselective synthesis of indanyl-7-(3'-pyridyl)-(3R,6R,7R)-2,5-diketopiperazines oxytocin antagonists from indene is described. SAR studies involving mono- and disubstitution in the 3'-pyridyl ring and variation of the 3-isobutyl group gave potent compounds (pK(i) > 9.0) with good aqueous solubility. E...

journal_title：Journal of medicinal chemistry

authors： Borthwick AD,Liddle J,Davies DE,Exall AM,Hamlett C,Hickey DM,Mason AM,Smith IE,Nerozzi F,Peace S,Pollard D,Sollis SL,Allen MJ,Woollard PM,Pullen MA,Westfall TD,Stanislaus DJ

更新日期：2012-01-26 00:00:00

abstract：:Following the observation that the activity of gonadotropin-releasing hormone III (GnRH-III) in the suppression of growth of MDA-MB-231 and MCF-7 breast cancer cells surpasses that of GnRH and other analogs thereof, analogs of GnRH-III were synthesized to investigate the structural basis for the improved antitumor act...

journal_title：Journal of medicinal chemistry

authors： Mezö I,Lovas S,Pályi I,Vincze B,Kálnay A,Turi G,Vadász Z,Seprödi J,Idei M,Tóth G,Gulyás E,Otvös F,Mák M,Horváth JE,Teplán I,Murphy RF

更新日期：1997-10-10 00:00:00

abstract：:Little is known of the conformation of peptide hormones as they interact with their receptors for a number of reasons: peptide hormones are notoriously flexible in solution, their receptors are particularly complex, and there is strong evidence that receptor-ligand interaction leading to activation is a dynamic proces...

journal_title：Journal of medicinal chemistry

authors： Koerber SC,Rizo J,Struthers RS,Rivier JE

更新日期：2000-03-09 00:00:00