Inhibition of homologous recombination in human cells by targeting RAD51 recombinase.

abstract：:Multifunctional ligands with agonist bioactivities at μ/δ opioid receptors (MOR/DOR) and antagonist bioactivity at the neurokinin-1 receptor (NK1R) have been designed and synthesized. These peptide-based ligands are anticipated to produce better biological profiles (e.g., higher analgesic effect with significantly les...

journal_title：Journal of medicinal chemistry

authors： Giri AK,Apostol CR,Wang Y,Forte BL,Largent-Milnes TM,Davis P,Rankin D,Molnar G,Olson KM,Porreca F,Vanderah TW,Hruby VJ

更新日期：2015-11-12 00:00:00

abstract：:The present study describes a novel in vitro platform for physicochemical profiling of compounds, based on their impact on the air/water interfacial tension. Interfacial partitioning coefficient, cross-sectional area, and critical micelle concentration were derived from the Gibbs adsorption isotherms recorded for 76 s...

journal_title：Journal of medicinal chemistry

authors： Suomalainen P,Johans C,Söderlund T,Kinnunen PK

更新日期：2004-03-25 00:00:00

abstract：:Spiropyrimidinetriones are a novel class of antibacterial agents that target the bacterial type II topoisomerase via a new mode of action. Compound ETX0914 is thus far the only drug from this class that is being evaluated in clinical trials. To improve the antibacterial activity and pharmacokinetic properties of ETX09...

journal_title：Journal of medicinal chemistry

authors： Shi C,Zhang Y,Wang T,Lu W,Zhang S,Guo B,Chen Q,Luo C,Zhou X,Yang Y

更新日期：2019-03-28 00:00:00

abstract：:The preparation of a series of indole N-acyl and N-carbamic esters of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazolin-4-one (1) is reported. These derivatives were synthesized as potential water-soluble precursors of the antiviral thiazolinone 1, for evaluation by intranasal administration against i...

journal_title：Journal of medicinal chemistry

authors： Harnden MR,Bailey S,Boyd MR,Wilkinson JB,Wright ND

更新日期：1979-02-01 00:00:00

abstract：:A rapid, efficient procedure useful for the radiosynthesis of [Me-3H]-MPDP+ ([methyl-3H]-4-phenyl-2,3-dihydropyridinium species) is described. Hog liver microsomes or the highly purified flavin-containing monooxygenase from hog liver quantitatively biotransforms [Me-3H]-MPTP to its corresponding radiolabeled N-oxide. ...

journal_title：Journal of medicinal chemistry

authors： Cashman JR

更新日期：1988-06-01 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：:Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been developed using comparative molecular field analysis (CoMFA) on a large data set (118 compounds) of diverse cyclic urea derivatives as protease inhibitors against the human immunodeficiency virus type 1 (HIV-1). X-ray crystal str...

journal_title：Journal of medicinal chemistry

authors： Debnath AK

更新日期：1999-01-28 00:00:00

abstract：:A series of new spiroglumide amido acid derivatives was synthesized and evaluated for their ability to inhibit the binding of cholecystokinin (CCK) to guinea pig brain cortex (CCKB receptors) and peripheral rat pancreatic acini (CCKA receptors), as well as to inhibit in vitro the gastrin-induced Ca2+ increase in rabbi...

journal_title：Journal of medicinal chemistry

authors： Makovec F,Peris W,Frigerio S,Giovanetti R,Letari O,Mennuni L,Revel L

更新日期：1996-01-05 00:00:00

abstract：:Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce...

journal_title：Journal of medicinal chemistry

authors： Khanna S,Sobhia ME,Bharatam PV

更新日期：2005-04-21 00:00:00

abstract：:We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. We report here the sequential modification of UNC1062 to address DMPK properties and yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable o...

journal_title：Journal of medicinal chemistry

authors： Zhang W,DeRyckere D,Hunter D,Liu J,Stashko MA,Minson KA,Cummings CT,Lee M,Glaros TG,Newton DL,Sather S,Zhang D,Kireev D,Janzen WP,Earp HS,Graham DK,Frye SV,Wang X

更新日期：2014-08-28 00:00:00

abstract：:Mechanism-based inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the pyrrolidine-5,5-trans-lactam ring system. New routes to the beta-methyl-, desmethyl-, and alpha-methyl-pyrrolidine-5,5-trans-lactam templates have been developed from 2,4-diaminobutyric acid. ESI/MS studies have shown t...

journal_title：Journal of medicinal chemistry

authors： Borthwick AD,Angier SJ,Crame AJ,Exall AM,Haley TM,Hart GJ,Mason AM,Pennell AM,Weingarten GG

更新日期：2000-11-16 00:00:00

abstract：:P2Y(2) and P2Y(4) receptors are G protein-coupled receptors, activated by UTP and dinucleoside tetraphosphates, which are difficult to distinguish pharmacologically for lack of potent and selective ligands. We structurally varied phosphate and uracil moieties in analogues of pyrimidine nucleoside 5'-triphosphates and ...

journal_title：Journal of medicinal chemistry

authors： Maruoka H,Jayasekara MP,Barrett MO,Franklin DA,de Castro S,Kim N,Costanzi S,Harden TK,Jacobson KA

更新日期：2011-06-23 00:00:00

abstract：:A series of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines were prepared and tested for alpha 1- and alpha 2-adrenoceptor affinity with radioligand binding. Several compounds, 5-fluoro-(5h), 5-chloro-(5j), 5,8-dimethoxy- (5r), and 5,8-dimethoxy- (5r),1-methyl- (5s) 2-(tetrahydroisoquin...

journal_title：Journal of medicinal chemistry

authors： Clark RD,Berger J,Garg P,Weinhardt KK,Spedding M,Kilpatrick AT,Brown CM,MacKinnon AC

更新日期：1990-02-01 00:00:00

abstract：:Genetic mutations in the phosphatase PTPN11 (SHP2) are associated with childhood leukemias. These mutations cause hyperactivation of SHP2 due to the disruption of the autoinhibitory conformation. By targeting the activation-associated protein conformational change, we have identified an SHP2 inhibitor ( E)-1-(1-(5-(3-...

journal_title：Journal of medicinal chemistry

authors： Wu X,Xu G,Li X,Xu W,Li Q,Liu W,Kirby KA,Loh ML,Li J,Sarafianos SG,Qu CK

更新日期：2019-02-14 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：:An analogue of a tripeptide inhibitor of angiotensin converting enzyme, Bz-Phe-Gly-Pro, has been synthesized in which the amide bond connecting phenylalanine and glycine has been replaced by a ketomethylene group. This nonpeptide analogue, 20, shows more potent converting enzyme inhibiting activity, I50 = 0.07 microM,...

journal_title：Journal of medicinal chemistry

authors： Almquist RG,Chao WR,Ellis ME,Johnson HL

更新日期：1980-12-01 00:00:00

abstract：:The limited number of drug classes licensed for treatment of influenza virus (Flu), together with the continuous emergence of viral variants and drug resistant mutants, highlights the urgent need to find antivirals with novel mechanisms of action. In this context, the viral RNA-dependent RNA polymerase (RdRP) subunits...

journal_title：Journal of medicinal chemistry

authors： Massari S,Nannetti G,Goracci L,Sancineto L,Muratore G,Sabatini S,Manfroni G,Mercorelli B,Cecchetti V,Facchini M,Palù G,Cruciani G,Loregian A,Tabarrini O

更新日期：2013-12-27 00:00:00

abstract：:A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactiva...

journal_title：Journal of medicinal chemistry

authors： Yang BV,Weinstein DS,Doweyko LM,Gong H,Vaccaro W,Huynh T,Xiao HY,Doweyko AM,McKay L,Holloway DA,Somerville JE,Habte S,Cunningham M,McMahon M,Townsend R,Shuster D,Dodd JH,Nadler SG,Barrish JC

更新日期：2010-12-09 00:00:00

abstract：:The specificity of nucleic acids' binders is crucial for developing this kind of drug, especially for novel G-quadruplexes' binders. Quindoline derivatives have been developed as G-quadruplex stabilizers with good interactive activities. In order to improve the selectivity and binding affinity of quindoline derivative...

journal_title：Journal of medicinal chemistry

authors： Zeng DY,Kuang GT,Wang SK,Peng W,Lin SL,Zhang Q,Su XX,Hu MH,Wang H,Tan JH,Huang ZS,Gu LQ,Ou TM

更新日期：2017-07-13 00:00:00

abstract：:A series of heterocyclic quinones, 6-substituted and 6,7-disubstituted 4-(alkylamino)-5,8-quinazolinediones, have been synthesized in order to evaluate their in vitro cytotoxicity on L1210 leukemia cells. Among 14 derivatives that have been prepared and studied for the structure-activity relationship, the most potent ...

journal_title：Journal of medicinal chemistry

authors： Giorgi-Renault S,Renault J,Gebel-Servolles P,Baron M,Paoletti C,Cros S,Bissery MC,Lavelle F,Atassi G

更新日期：1991-01-01 00:00:00

abstract：:Most non-thiol CAAX-peptidomimetic farnesyltransferase inhibitors bear nitrogen-containing heterocycles in place of the terminal cysteine which are supposed to coordinate the enzyme-bound zinc. However, it has been shown that those nitrogen-containing heterocycles can be replaced by carbocyclic aromatic moieties which...

journal_title：Journal of medicinal chemistry

authors： Böhm M,Mitsch A,Wissner P,Sattler I,Schlitzer M

更新日期：2001-09-13 00:00:00

abstract：:We have previously identified phenylguanidine and phenyl-2-aminoimidazoline compounds as high affinity ligands with conflicting functional activity at the α2-adrenoceptor, a G-protein-coupled receptor with relevance in several neuropsychiatric conditions. In this paper we describe the design, synthesis, and pharmacolo...

journal_title：Journal of medicinal chemistry

authors： Kelly B,McMullan M,Muguruza C,Ortega JE,Meana JJ,Callado LF,Rozas I

更新日期：2015-01-22 00:00:00

abstract：:Cysteine proteases play an important role in cell migration and tumor metastasis. Therefore, their inhibitors are of colossal interest, having potential to be developed as effective antimetastatic drugs for tumor chemotherapy. Traditionally, secondary metabolites from streptomyces show a wide range of diversity with r...

journal_title：Journal of medicinal chemistry

authors： Singh JP,Tamang S,Rajamohanan PR,Jima NC,Chakraborty G,Kundu GC,Gaikwad SM,Khan MI

更新日期：2010-07-22 00:00:00

abstract：:Analogues of luliberin containing an alpha-azaamino acid in position 6, 9, or 10 (I--XIV) have been synthesized by the solution method of peptide synthesis. Two nonaza analogues, [D-Phe6]- and [D-Ser(But)6,des-Gly-NH2(10),Pro-ethylamide9]luliberin, were also synthesized for comparison. The ovulation-inducing activity ...

journal_title：Journal of medicinal chemistry

authors： Dutta AS,Furr BJ,Giles MB,Valcaccia B

更新日期：1978-10-01 00:00:00

abstract：:A series of bisalkamine esters, bis-basic ethers, and bis-basic ketones of carbazole, N-ethylcarbazole, dibenzofuran, and dibenzothiophene was synthesized and evaluated for antiviral activity. The series also included two bis-basic alkanes of N-ethylcarbazole and one bis-basic carboxamide of dibenzofuran. Structure-ac...

journal_title：Journal of medicinal chemistry

authors： Albrecht WL,Fleming RW,Horgan SW,Mayer GD

更新日期：1977-03-01 00:00:00

abstract：:Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable ...

journal_title：Journal of medicinal chemistry

authors： Kakuta H,Zheng X,Oda H,Harada S,Sugimoto Y,Sasaki K,Tai A

更新日期：2008-04-24 00:00:00

abstract：:The three dimers 3, 4, and 5 of mitomycin C (MC), a natural antibiotic and cancer chemotherapeutic agent, were synthesized in which two MC molecules were linked with -(CH(2))(4)-, -(CH(2))(12)-, and -(CH(2))(3)N(CH(3))(CH(2))(3)- tethers, respectively. The dimeric mitomycins were designed to react as polyfunctional DN...

journal_title：Journal of medicinal chemistry

authors： Paz MM,Kumar GS,Glover M,Waring MJ,Tomasz M

更新日期：2004-06-03 00:00:00

abstract：:This paper describes the synthesis and pharmacological evaluation of a number evaluation of a number of substituted 1,3,4-thiadiazoles. The first member of the series, 2-(aminomethyl)-5-(2-biphenylyl)-1,3,4-thiadiazole (7) was found to possess potent anticonvulsant properties in rats and mice and compared favorably wi...

journal_title：Journal of medicinal chemistry

authors： Stillings MR,Welbourn AP,Walter DS

更新日期：1986-11-01 00:00:00

abstract：:We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an endothelin antagonist, binds specifically (Ki = 1.9 microM) to the rat pituitary gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a GnRH agonistic activity, mediated directly by the GnRH receptor. We now report ...

journal_title：Journal of medicinal chemistry

authors： Yahalom D,Rahimipour S,Koch Y,Ben-Aroya N,Fridkin M

更新日期：2000-07-27 00:00:00

abstract：:Virulence gene expression in Staphylococcus aureus is tightly regulated by intricate networks of transcriptional regulators and two-component signal transduction systems. There is now an emerging body of evidence to suggest that the blockade of S. aureus virulence gene expression significantly attenuates infection in ...

journal_title：Journal of medicinal chemistry

authors： Gordon CP,Williams P,Chan WC

更新日期：2013-02-28 00:00:00