Synthesis of 1-(2-aminophenyl)isoquinolines and the biological activity of their cis-dichloro platinum(II) complexes.

abstract：:The iodinated analogue of 1-[2-(4-aminophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine (PAPP), IPAPP (4), and the corresponding azido compound azido-IPAPP (5) were synthesized. The corresponding no-carrier-added 125I (T1/2 = 60 days, 35-60 keV) labeled compounds were also prepared. High specific binding was obse...

journal_title：Journal of medicinal chemistry

authors： Chumpradit S,Kung HF,Billings J,Guo YZ,Wu Y,Shih J

更新日期：1989-03-01 00:00:00

abstract：:Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that co...

journal_title：Journal of medicinal chemistry

authors： Shi J,Van de Water R,Hong K,Lamer RB,Weichert KW,Sandoval CM,Kasibhatla SR,Boehm MF,Chao J,Lundgren K,Timple N,Lough R,Ibanez G,Boykin C,Burrows FJ,Kehry MR,Yun TJ,Harning EK,Ambrose C,Thompson J,Bixler SA,Dunah

更新日期：2012-09-13 00:00:00

abstract：:The free fatty acid receptor GPR40 is predominantly expressed in pancreatic β-cells and enhances insulin secretion in a glucose dependent manner. Therefore, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia for the treatment of type 2 diabetes mellitus (T2DM). Chemically a...

journal_title：Journal of medicinal chemistry

authors： Li H,Huang Q,Chen C,Xu B,Wang HY,Long YQ

更新日期：2017-04-13 00:00:00

abstract：:Using a combination of in silico and experimental approaches, we present evidence that the G-quadruplex (G4) motif (an alternative higher-order DNA conformation) has regulatory potential. Genome-wide analyses of 99980 human, chimpanzee, mouse, and rat promoters showed enrichment of sequence with potential to adopt G4 ...

journal_title：Journal of medicinal chemistry

authors： Verma A,Halder K,Halder R,Yadav VK,Rawal P,Thakur RK,Mohd F,Sharma A,Chowdhury S

更新日期：2008-09-25 00:00:00

abstract：:The increase in the incidence of both hospital- and community-acquired antibiotic-resistant infections is a major concern to the healthcare community. There have been only two new classes of antibiotics approved by the FDA over the past 40 years, and clearly there is a growing need for additional antimicrobial agents....

journal_title：Journal of medicinal chemistry

authors： Vooturi SK,Cheung CM,Rybak MJ,Firestine SM

更新日期：2009-08-27 00:00:00

abstract：:The diphenylsulfonyl sulfonamide scaffold represented by 1 (WAY-316606) are small molecule inhibitors of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic agents for the treatment of osteoporosis or other bone-related di...

journal_title：Journal of medicinal chemistry

authors： Moore WJ,Kern JC,Bhat R,Commons TJ,Fukayama S,Goljer I,Krishnamurthy G,Magolda RL,Nogle L,Pitts K,Stauffer B,Trybulski EJ,Welmaker GS,Wilson M,Bodine PV

更新日期：2009-01-08 00:00:00

abstract：:We have derivatized Momordica saponins (MS) I and II through their coupling at C3 glucuronic acid site with dodecylamine. The derivatives show significantly different immunostimulant activity profiles from their respective natural parent saponins. In particular, adjuvant VSA-1 (5), the derivative of MS I, potentiates ...

journal_title：Journal of medicinal chemistry

authors： Wang P,Ding X,Kim H,Škalamera Đ,Michalek SM,Zhang P

更新日期：2019-11-14 00:00:00

abstract：:Stabilization of protein-protein interactions (PPIs) holds great potential for therapeutic agents, as illustrated by the successful drugs rapamycin and lenalidomide. However, how such interface-binding molecules can be created in a rational, bottom-up manner is a largely unanswered question. We report here how a fragm...

journal_title：Journal of medicinal chemistry

authors： Guillory X,Wolter M,Leysen S,Neves JF,Kuusk A,Genet S,Somsen B,Morrow JK,Rivers E,van Beek L,Patel J,Goodnow R,Schoenherr H,Fuller N,Cao Q,Doveston RG,Brunsveld L,Arkin MR,Castaldi P,Boyd H,Landrieu I,Chen H,O

更新日期：2020-07-09 00:00:00

abstract：:(E)-5-(2-Bromovinyl)isodideoxyuridine (BVisoDDU), synthesized on the basis of molecular modeling, is selectively active against HSV-1 (three different strains) but inactive against HSV-2. Unlike BVDU, BVisoDDU is completely resistant to cleavage by thymidine phosphorylase. BVisoDDU is also the first nucleoside analogu...

journal_title：Journal of medicinal chemistry

authors： Guenther S,Balzarini J,De Clercq E,Nair V

更新日期：2002-12-05 00:00:00

abstract：:Multidrug resistance (MDR) in cancer is a phenomenon in which administration of a single chemotherapeutic agent causes cross-resistance of cancer cells to a variety of therapies even with different mechanisms of action. Development of MDR against standard therapies is a major challenge in the treatment of cancer. Prev...

journal_title：Journal of medicinal chemistry

authors： Das SG,Srinivasan B,Hermanson DL,Bleeker NP,Doshi JM,Tang R,Beck WT,Xing C

更新日期：2011-08-25 00:00:00

abstract：:Lipoproteins from gram-positive and -negative bacteria, mycoplasma, and shorter synthetic lipopeptide analogues activate cells of the innate immune system via the Toll-like receptor TLR2/TLR1 or TLR2/TLR6 heterodimers. For this reason, these compounds constitute highly active adjuvants for vaccines either admixed or c...

journal_title：Journal of medicinal chemistry

authors： Seyberth T,Voss S,Brock R,Wiesmüller KH,Jung G

更新日期：2006-03-09 00:00:00

abstract：:Recently, we have discovered that the registered pesticide, tolfenpyrad, unexpectedly and potently inhibits the development of the L4 larval stage of the parasitic nematode Haemonchus contortus with an IC50 value of 0.03 μM while displaying good selectivity, with an IC50 of 37.9 μM for cytotoxicity. As a promising mol...

journal_title：Journal of medicinal chemistry

authors： Le TG,Kundu A,Ghoshal A,Nguyen NH,Preston S,Jiao Y,Ruan B,Xue L,Huang F,Keiser J,Hofmann A,Chang BCH,Garcia-Bustos J,Wells TNC,Palmer MJ,Jabbar A,Gasser RB,Baell JB

更新日期：2019-01-24 00:00:00

abstract：:The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants. However, evidence has emerged that MPO-derived oxidants contribute to propagation of inflammatory diseases. Because of the deleterious effects of circulating MPO, there is a great ...

journal_title：Journal of medicinal chemistry

authors： Soubhye J,Chikh Alard I,Aldib I,Prévost M,Gelbcke M,De Carvalho A,Furtmüller PG,Obinger C,Flemmig J,Tadrent S,Meyer F,Rousseau A,Nève J,Mathieu V,Zouaoui Boudjeltia K,Dufrasne F,Van Antwerpen P

更新日期：2017-08-10 00:00:00

abstract：:Nitrosourea derivatives 9--13 which utilize phensuximide (1) as the carrier were synthesized as potential central nervous system antitumor agents. The N-(2-chloroethyl)-N-nitrosourea 13 was active in the mouse ependymoblastoma brain-tumor system, as well as the intraperitoneal L1210 leukemia system. ...

journal_title：Journal of medicinal chemistry

authors： Crider AM,Kolczynski TM,Yates KM

更新日期：1980-03-01 00:00:00

abstract：:5-Alkoxy-3-(N-substituted carbamoly)-1-phenylpyrazoles were prepared and tested for antiinflammatory and hypnotic activity. Four compounds showed antiinflammatory activity and three possessed hypnotic properties. ...

journal_title：Journal of medicinal chemistry

authors： Sugiura S,Ohno S,Ohtani O,Izumi K,Kitamikado T,Asai H,Kato K

更新日期：1977-01-01 00:00:00

abstract：:A series of transition-state analogues having heterocyclythio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio ...

journal_title：Journal of medicinal chemistry

authors： Ashton WT,Cantone CL,Meurer LC,Tolman RL,Greenlee WJ,Patchett AA,Lynch RJ,Schorn TW,Strouse JF,Siegl PK

更新日期：1992-05-29 00:00:00

abstract：:Symmetrical and asymmetrical fluorinated phenyltriazolyl-thiodigalactoside derivatives have been synthesized and evaluated as inhibitors of galectin-1 and galectin-3. Systematic tuning of the phenyltriazolyl-thiodigalactosides' fluoro-interactions with galectin-3 led to the discovery of inhibitors with exceptional aff...

journal_title：Journal of medicinal chemistry

authors： Peterson K,Kumar R,Stenström O,Verma P,Verma PR,Håkansson M,Kahl-Knutsson B,Zetterberg F,Leffler H,Akke M,Logan DT,Nilsson UJ

更新日期：2018-02-08 00:00:00

abstract：:Aminoglycosides (AGs) constitute a major family of potent and broad-spectrum antibiotics disturbing protein synthesis through binding to the A site of 16S rRNA. Decades of widespread clinical use of AGs strongly reduced their clinical efficacy through the selection of resistant bacteria. Recently, conjugation of lipop...

journal_title：Journal of medicinal chemistry

authors： Zimmermann L,Das I,Désiré J,Sautrey G,Barros R S V,El Khoury M,Mingeot-Leclercq MP,Décout JL

更新日期：2016-10-27 00:00:00

abstract：:A quantitative structure-activity relationship (QSAR) study was performed on a set of 49 negative allosteric modulators of AMPA receptor, acting as anticonvulsant agents, using multiple linear regression. The predictive ability of the resulting model was evaluated against a set of 12 compounds; the results showed good...

journal_title：Journal of medicinal chemistry

authors： Macchiarulo A,De Luca L,Costantino G,Barreca ML,Gitto R,Pellicciari R,Chimirri A

更新日期：2004-03-25 00:00:00

abstract：:Generation of a three-dimensional pharmacophore model (hypothesis) that correlates the biological activity of a series of farnesyl protein transferase (FPT) inhibitors, exemplified by the prototype 1-(4-pyridylacetyl)- 4-(8-chloro-5,6-dihydro-11H-benzo [5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine, Sch 44342, 1,...

journal_title：Journal of medicinal chemistry

authors： Kaminski JJ,Rane DF,Snow ME,Weber L,Rothofsky ML,Anderson SD,Lin SL

更新日期：1997-12-05 00:00:00

abstract：:The synthesis and CNS activity of a noval class of annelated 1,4-benzodiazepines, the aminomethylene-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepines, are described. An investigation of the structure--activity relationships in the series derived from 8-chloro-2,4-dihydro-2-dimethylaminomethylene-6-phenyl-1H-imidazo[1...

journal_title：Journal of medicinal chemistry

authors： Ager IR,Danswan GW,Harrison DR,Kay DP,Kennewell PD,Taylor JB

更新日期：1977-08-01 00:00:00

abstract：:A class of drugs in use for treating type II diabetes mellitus (T2D), typified by the pseudotetrasaccharide acarbose, act by inhibiting the alpha-glucosidase activity present in pancreatic secretions and in the brush border of the small intestine. Herein, we report the synthesis of a series of 4-substituted 1,2,3-tria...

journal_title：Journal of medicinal chemistry

authors： Ferreira SB,Sodero AC,Cardoso MF,Lima ES,Kaiser CR,Silva FP,Ferreira VF

更新日期：2010-03-25 00:00:00

abstract：:A novel series of 3,4-dihydroxychalcones was synthesized to evaluate their effects against 5-lipoxygenase and cyclooxygenase. Almost all compounds exhibited potent inhibitory effects on 5-lipoxygenase with antioxidative effects, and some also inhibited cyclooxygenase. The 2',5'-disubstituted 3,4-dihydroxychalcones wit...

journal_title：Journal of medicinal chemistry

authors： Sogawa S,Nihro Y,Ueda H,Izumi A,Miki T,Matsumoto H,Satoh T

更新日期：1993-11-26 00:00:00

abstract：:Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been validated as an attractive therapeutic target for cancer therapy. To stop both STAT3 activation and dimerization, a viable strategy is to design inhibitors blocking its SH2 domain phosphotyrosine binding site that is respons...

journal_title：Journal of medicinal chemistry

authors： Yu W,Xiao H,Lin J,Li C

更新日期：2013-06-13 00:00:00

abstract：:Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alph...

journal_title：Journal of medicinal chemistry

authors： Nagarathnam D,Miao SW,Lagu B,Chiu G,Fang J,Murali Dhar TG,Zhang J,Tyagarajan S,Marzabadi MR,Zhang F,Wong WC,Sun W,Tian D,Wetzel JM,Forray C,Chang RS,Broten TP,Ransom RW,Schorn TW,Chen TB,O'Malley S,Kling P,Sch

更新日期：1999-11-18 00:00:00

abstract：:Modulation of sphingosine 1-phosphate (S1P) signaling represents a solid opportunity for multiple sclerosis (MS) treatment. In this issue, a team at Novartis reports on the identification of the first direct S1P lyase (S1PL) inhibitors as new MS agents. One of the most potent inhibitors reported in their work was demo...

journal_title：Journal of medicinal chemistry

authors： Cosconati S,Novellino E

更新日期：2014-06-26 00:00:00

abstract：:The synthesis and the X-ray structure of 16a-thiocamptothecin (TCPT), the thiopyridone analog of camptothecin (CPT), are accomplished. The crystal contains two structurally identical, yet independent molecules. Both of them are connected to other molecules via two intermolecular hydrogen bonds. S-methylation of TCPT l...

journal_title：Journal of medicinal chemistry

authors： Samorì C,Guerrini A,Varchi G,Zunino F,Beretta GL,Femoni C,Bombardelli E,Fontana G,Battaglia A

更新日期：2008-05-22 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：:We present Fleksy, a new approach to consider both ligand and receptor flexibility in small molecule docking. Pivotal to our method is the use of a receptor ensemble to describe protein flexibility. To construct these ensembles, we use a backbone-dependent rotamer library and implement the concept of interaction sampl...

journal_title：Journal of medicinal chemistry

authors： Nabuurs SB,Wagener M,de Vlieg J

更新日期：2007-12-27 00:00:00

abstract：:Among a series of benzopyridone-based scaffolds investigated as human transient receptor potential vanilloid 1 (TRPV1) ligands, two isomeric benzopyridone scaffolds demonstrated a consistent and distinctive functional profile in which 2-oxo-1,2-dihydroquinolin-5-yl analogues (e.g., 2) displayed high affinity and poten...

journal_title：Journal of medicinal chemistry

authors： Thorat SA,Lee Y,Jung A,Ann J,Ahn S,Baek J,Zuo D,Do N,Jeong JJ,Blumberg PM,Esch TE,Turcios NA,Pearce LV,Ha HJ,Yoo YD,Hong S,Choi S,Lee J

更新日期：2021-01-14 00:00:00