Structural Basis of Wee Kinases Functionality and Inactivation by Diverse Small Molecule Inhibitors.

abstract：:A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeli...

journal_title：Journal of medicinal chemistry

authors： Pepe A,Pamment M,Kim YS,Lee S,Lee MJ,Beebe K,Filikov A,Neckers L,Trepel JB,Malhotra SV

更新日期：2013-11-14 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：:New 2-piperazinylbenzothiazole and 2-piperazinylbenzoxazole derivatives were prepared and tested as 5-HT3 receptor antagonists. Some of the new compounds antagonized the effect of 5-HT at the longitudinal muscle myenteric plexus (LMMP) preparation of the guinea pig ileum, and two benzothiazole derivatives, compounds 2...

journal_title：Journal of medicinal chemistry

authors： Monge A,Peña MC,Palop JA,Calderó JM,Roca J,García E,Romero G,del Río J,Lasheras B

更新日期：1994-04-29 00:00:00

abstract：:The modulation of the endocannabinoid system is emerging as a viable avenue for the treatment of neurodegeneration, being involved in neuroprotective and anti-inflammatory processes. In particular, indirectly enhancing endocannabinoid signaling to therapeutic levels through FAAH inhibition might be beneficial for neur...

journal_title：Journal of medicinal chemistry

authors： Montanari S,Scalvini L,Bartolini M,Belluti F,Gobbi S,Andrisano V,Ligresti A,Di Marzo V,Rivara S,Mor M,Bisi A,Rampa A

更新日期：2016-07-14 00:00:00

abstract：:A series of both aliphatic and aromatic amides and aromatic amidines derived from 2-amino-1,10-phenanthroline (3) according to the Topliss scheme were synthesized and subsequently tested for antimycoplasmal potency. Although the compounds themselves showed no activity, in the presence of a nontoxic copper concentratio...

journal_title：Journal of medicinal chemistry

authors： de Zwart MA,Bastiaans HM,van der Goot H,Timmerman H

更新日期：1991-03-01 00:00:00

abstract：:5'-(Bromoacetamido)-2',5'-dideoxyuridine (3) and derivatives (8, 10, 12, and 14) substituted at the 5-position with bromo, iodo, fluoro, and ethyl groups have been synthesized as potential inhibitors of enzymes that metabolize pyrimidine nucleosides. Also prepared were 2',5'-dideoxyuridine derivatives (4-6) substitute...

journal_title：Journal of medicinal chemistry

authors： Elliott RD,Pruett PS,Brockman RW,Montgomery JA

更新日期：1987-05-01 00:00:00

abstract：:The synthesis of the benzothiopyranoindazoles, a new class of chromophore modified anthracenediones related to mitoxantrone, is described. In this structural class the quinone moiety, which is believed to be responsible for the cardiotoxicity of the anthracyclines, has been designed out. The synthesis of the benzothio...

journal_title：Journal of medicinal chemistry

authors： Showalter HD,Angelo MM,Berman EM,Kanter GD,Ortwine DF,Ross-Kesten SG,Sercel AD,Turner WR,Werbel LM,Worth DF

更新日期：1988-08-01 00:00:00

abstract：:A number of 7-benzoylbenzofuran-5-ylacetic acids and 7-benzoylbenzothiophene-5-ylacetic acids were synthesized. The compounds were generally only 1/2 to 3 times as potent as phenylbutazone in the rat paw edema antiinflammatory assay. However, they show greater activity as analgetic agents. The most active compound is ...

journal_title：Journal of medicinal chemistry

authors： Dunn JP,Ackerman NA,Tomolonis AJ

更新日期：1986-11-01 00:00:00

abstract：:A number of fluorenyl and diphenylmethane analogues of verapamil, chosen as having the same substituents arranged in different ways around the quaternary carbon, were synthesized in order to evaluate the importance of the stereoisomerism at that point of the molecule. The compounds were tested with the Langendorff tec...

journal_title：Journal of medicinal chemistry

authors： Gualtieri F,Teodori E,Bellucci C,Pesce E,Piacenza G

更新日期：1985-11-01 00:00:00

abstract：:Series of N-alkylated derivatives of 2-amino-4,6-dihydroxyindan 3 and 6-amino-1,3-dihydroxybenzocycloheptene 2 were prepared for pharmacological testing as congeners of 2-amino-5,7-dihydroxytetralin, which elicits dopaminergic effects in a variety of assays. All of the subject compounds demonstrated a lower order of d...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Pease JP,Hamer RL,Ilhan M,Bhatnagar RK,Long JP

更新日期：1984-02-01 00:00:00

abstract：:The enantiomers of the leukotriene D4 antagonist 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid (L-660,711)(MK-571) have been prepared, their absolute stereochemistry has been assigned as S for (+)-1 and R for (-)-1 by X-ray analysis of a synthetic...

journal_title：Journal of medicinal chemistry

authors： Gauthier JY,Jones T,Champion E,Charette L,Dehaven R,Ford-Hutchinson AW,Hoogsteen K,Lord A,Masson P,Piechuta H

更新日期：1990-10-01 00:00:00

abstract：:The alpha- and beta-D-lyxofuranosyl analogues of the naturally occurring nucleosides have been synthesized and their antiviral properties examined. The alpha anomers were prepared by glycosylation of purine and pyrimidine aglycons with tetra-O-acetyl-alpha-D-lyxofuranose, followed by removal of the blocking groups. Th...

journal_title：Journal of medicinal chemistry

authors： Gosselin G,Bergogne MC,De Rudder J,De Clercq E,Imbach JL

更新日期：1987-06-01 00:00:00

abstract：:The photo "Wolff" rearrangement of readily available 2-diazoceph-3-em oxides (1) directly affords carbapen-2-ems, allowing a facile entry into a ring system previously accessible only by total synthesis, lengthly semisynthesis or fermentation. The chirality of the cephalosporin is accurately translated into the corres...

journal_title：Journal of medicinal chemistry

authors： Rosati RL,Kapili LV,Morrissey P,Retsema JA

更新日期：1990-01-01 00:00:00

abstract：:In this work, we report the multicomponent synthesis of a focused histone deacetylase (HDAC) inhibitor library with peptoid-based cap groups and different zinc-binding groups. All synthesized compounds were tested in a cellular HDAC inhibition assay and an MTT assay for cytotoxicity. On the basis of their noteworthy a...

journal_title：Journal of medicinal chemistry

authors： Krieger V,Hamacher A,Gertzen CGW,Senger J,Zwinderman MRH,Marek M,Romier C,Dekker FJ,Kurz T,Jung M,Gohlke H,Kassack MU,Hansen FK

更新日期：2017-07-13 00:00:00

abstract：:Several 4-alkyl-1-arylpiperazines that present a tetralin moiety on the terminal part of the side chain were synthesized in order to increase the selectivity on the 5-HT1A versus D-2, alpha 1, sigma, and other 5-HT receptors. Many changes have been effected on previous structures of type 3(1-aryl-4-[3-(1,2-dihydronaph...

journal_title：Journal of medicinal chemistry

authors： Perrone R,Berardi F,Colabufo NA,Leopoldo M,Tortorella V,Fiorentini F,Olgiati V,Ghiglieri A,Govoni S

更新日期：1995-03-17 00:00:00

abstract：:A number of derivatives of 4-amino-6-hydroxy-2-mercaptopyrimidine ( 5) were synthesized and biologically evaluated as A 3 adenosine receptor (A 3 AR) antagonists. The new compounds were designed as open chain analogues of a triazolopyrimidinone derivative displaying submicromolar affinity for the A 3 AR, which had bee...

journal_title：Journal of medicinal chemistry

authors： Cosimelli B,Greco G,Ehlardo M,Novellino E,Da Settimo F,Taliani S,La Motta C,Bellandi M,Tuccinardi T,Martinelli A,Ciampi O,Trincavelli ML,Martini C

更新日期：2008-03-27 00:00:00

abstract：:K-Ras is one of the most frequently mutated signal transducing human oncogenes. Ras signaling activity requires correct cellular localization of the GTPase. The spatial organization of K-Ras is controlled by the prenyl binding protein PDEδ, which enhances Ras diffusion in the cytosol. Inhibition of the Ras-PDEδ intera...

journal_title：Journal of medicinal chemistry

authors： Zimmermann G,Schultz-Fademrecht C,Küchler P,Murarka S,Ismail S,Triola G,Nussbaumer P,Wittinghofer A,Waldmann H

更新日期：2014-06-26 00:00:00

abstract：:In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the ...

journal_title：Journal of medicinal chemistry

authors： Clark RL,Pessolano AA,Shen TY,Jacobus DP,Jones H,Lotti VJ,Flataker LM

更新日期：1978-09-01 00:00:00

abstract：:Among the nonclassical cannabinoids, CP-55,244 (4), which incorporates an axial 14 beta-hydroxymethyl group, is pharmacologically 30 times more potent than its prototype CP-47,497 (2) and 300 times more potent than delta 9-THC (1). It has a high degree of stereoselectivity (about 120:1) with respect to its diastereois...

journal_title：Journal of medicinal chemistry

authors： Xie XQ,Pavlopoulos S,DiMeglio CM,Makriyannis A

更新日期：1998-01-15 00:00:00

abstract：:Pseudomonas aeruginosa is a causative agent of chronic infections in immunocompromised patients. Disruption of quorum sensing circuits is an attractive strategy for treating diseases associated with P. aeruginosa infection. In this study, we designed and synthesized a series of gingerol analogs targeting LasR, a maste...

journal_title：Journal of medicinal chemistry

authors： Choi H,Ham SY,Cha E,Shin Y,Kim HS,Bang JK,Son SH,Park HD,Byun Y

更新日期：2017-12-14 00:00:00

abstract：:New efficient antifungal agents are urgently needed to treat drug-resistant fungal infections. Here, we designed and synthesized a series of cationic xanthone amphiphilics as antifungal agents from natural α-mangostin to combat fungal resistance. The attachment of cationic residues on the xanthone scaffold of α-mangos...

journal_title：Journal of medicinal chemistry

authors： Lin S,Sin WLW,Koh JJ,Lim F,Wang L,Cao D,Beuerman RW,Ren L,Liu S

更新日期：2017-12-28 00:00:00

abstract：:A series of tetramisole derivatives was synthesized and tested for inhibitory activity against alkaline phosphatase which was partially purified from a murine ascitic neoplasm resistant to 6-thiopurines (Sarcoma 180/TG). These agents included derivatives substituted with halogens, CH3, or NO2 groups at either the meta...

journal_title：Journal of medicinal chemistry

authors： Bhargava KK,Lee MH,Huang Y,Cunningham LS,Agrawal KC,Sartorelli AC

更新日期：1977-04-01 00:00:00

abstract：:A series of aryl bicyclic analogs of succinimide and glutarimide was prepared and evaluated for CNS depressant activity. The 8a-aryl-3,4,6,7,8,8a-hexahydro-2H-pyrrolo[2,1-beta][1,3]oxazin-6-ones possessed the best overall spectrum of activity relative to the standard agents glutethimide and phenobarbital. ...

journal_title：Journal of medicinal chemistry

authors： Aeberli P,Gogerty JH,Houlihan WJ,Iorio LC

更新日期：1976-03-01 00:00:00

abstract：:The bioavailability of aromatic azaheterocyclic drugs can be affected by the activity of aldehyde oxidase (AO). Susceptibility to AO metabolism is difficult to predict computationally and can be complicated in vivo by differences between species. Here we report the use of bis(((difluoromethyl)sulfinyl)oxy)zinc (DFMS) ...

journal_title：Journal of medicinal chemistry

authors： O'Hara F,Burns AC,Collins MR,Dalvie D,Ornelas MA,Vaz AD,Fujiwara Y,Baran PS

更新日期：2014-02-27 00:00:00

abstract：:Since the discovery of the serotonin 4 receptor (5-HT(4)R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4-piperidinyl)methyl]-1H-indazol...

journal_title：Journal of medicinal chemistry

authors： Furlotti G,Alisi MA,Apicella C,Capezzone de Joannon A,Cazzolla N,Costi R,Cuzzucoli Crucitti G,Garrone B,Iacovo A,Magarò G,Mangano G,Miele G,Ombrato R,Pescatori L,Polenzani L,Rosi F,Vitiello M,Di Santo R

更新日期：2012-11-26 00:00:00

abstract：:Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP val...

journal_title：Journal of medicinal chemistry

authors： Meng CQ,Ni L,Worsencroft KJ,Ye Z,Weingarten MD,Simpson JE,Skudlarek JW,Marino EM,Suen KL,Kunsch C,Souder A,Howard RB,Sundell CL,Wasserman MA,Sikorski JA

更新日期：2007-03-22 00:00:00

abstract：:Benzimidazole-N-oxide modifications of potent lipophilic dihydrofolate reductase (DHFR) inhibitors (e.g., methylbenzoprim 1 and dichlorobenzoprim 2) have been prepared by base-promoted cyclization of the nitrophenylbenzylamino groups to explore the possibility that abrogation of DHFR-inhibitory activity might reveal c...

journal_title：Journal of medicinal chemistry

authors： Richardson ML,Croughton KA,Matthews CS,Stevens MF

更新日期：2004-07-29 00:00:00

abstract：:We present a comprehensive study of the performance of fast scoring functions for library docking using the program FlexX as the docking engine. Four scoring functions, among them two recently developed knowledge-based potentials, are evaluated on seven target proteins whose binding sites represent a wide range of siz...

journal_title：Journal of medicinal chemistry

authors： Stahl M,Rarey M

更新日期：2001-03-29 00:00:00

abstract：:Protein kinase B (PKB)-selective inhibitors were designed, synthesized, and cocrystallized using the AGC kinase family protein kinase A (PKA, often called cAMP-dependent protein kinase); PKA has been used as a surrogate for other members of this family and indeed for protein kinases in general. The high homology betwe...

journal_title：Journal of medicinal chemistry

authors： Breitenlechner CB,Friebe WG,Brunet E,Werner G,Graul K,Thomas U,Künkele KP,Schäfer W,Gassel M,Bossemeyer D,Huber R,Engh RA,Masjost B

更新日期：2005-01-13 00:00:00

abstract：:We report the activities of 62 bisphosphonates as inhibitors of the Leishmania major mevalonate/isoprene biosynthesis pathway enzyme, farnesyl pyrophosphate synthase. The compounds investigated exhibit activities (IC(50) values) ranging from approximately 100 nM to approximately 80 microM (corresponding to K(i) values...

journal_title：Journal of medicinal chemistry

authors： Sanders JM,Gómez AO,Mao J,Meints GA,Van Brussel EM,Burzynska A,Kafarski P,González-Pacanowska D,Oldfield E

更新日期：2003-11-20 00:00:00