Identification of highly potent retinoic acid receptor alpha-selective antagonists.

abstract：:The retinoid 6-[3'-(1-adamantyl)-4'-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN) and its active analogues induce cell-cycle arrest and programmed cell death (apoptosis) in cancer cells independently of retinoic acid receptor (RAR) interaction. Its analogue, (E)-4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-(3'-acetami...

journal_title：Journal of medicinal chemistry

authors： Dawson MI,Harris DL,Liu G,Hobbs PD,Lange CW,Jong L,Bruey-Sedano N,James SY,Zhang XK,Peterson VJ,Leid M,Farhana L,Rishi AK,Fontana JA

更新日期：2004-07-01 00:00:00

abstract：:We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of highly potent, specific, orally active, small molecule kinase inhibitors directed aga...

journal_title：Journal of medicinal chemistry

authors： Pandey A,Volkots DL,Seroogy JM,Rose JW,Yu JC,Lambing JL,Hutchaleelaha A,Hollenbach SJ,Abe K,Giese NA,Scarborough RM

更新日期：2002-08-15 00:00:00

abstract：:In this paper we report the systematic search for new, potent, and selective DPP II inhibitors. A study of the structure-activity relationship was conducted starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of the P(1) and P(2) building blocks led to the discovery of some very potent DPP II ...

journal_title：Journal of medicinal chemistry

authors： Senten K,Van der Veken P,De Meester I,Lambeir AM,Scharpé S,Haemers A,Augustyns K

更新日期：2003-11-06 00:00:00

abstract：:Modern rational drug design not only deals with the search for ligands binding to interesting and promising validated targets but also aims to identify the function and ligands of yet uncharacterized proteins having impact on different diseases. Additionally, it contributes to the design of inhibitors with distinct se...

journal_title：Journal of medicinal chemistry

authors： Ehrt C,Brinkjost T,Koch O

更新日期：2016-05-12 00:00:00

abstract：:The inhibitory effect of 108 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(substituted-phenyl)-s-triazines on murine L5178Y tumor cells, resistant and sensitive to methotrexate (MTX), has been studied. From the pI50 values, quantitative structure-activity relationships have been formulated which show that the lipophilic tri...

journal_title：Journal of medicinal chemistry

authors： Selassie CD,Hansch C,Khwaja TA,Dias CB,Pentecost S

更新日期：1984-03-01 00:00:00

abstract：:Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expe...

journal_title：Journal of medicinal chemistry

authors： Haginoya N,Kobayashi S,Komoriya S,Yoshino T,Suzuki M,Shimada T,Watanabe K,Hirokawa Y,Furugori T,Nagahara T

更新日期：2004-10-07 00:00:00

abstract：:A series of novel pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, a...

journal_title：Journal of medicinal chemistry

authors： Shang R,Pu X,Xu X,Xin Z,Zhang C,Guo W,Liu Y,Liang J

更新日期：2014-07-10 00:00:00

abstract：:17β-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding ...

journal_title：Journal of medicinal chemistry

authors： Bertoletti N,Braun F,Lepage M,Möller G,Adamski J,Heine A,Klebe G,Marchais-Oberwinkler S

更新日期：2016-07-28 00:00:00

abstract：:A family of analogues of des-AA(1,2,5)-[DTrp(8)/D2Nal(8)]-SRIF that contain a 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 was identified that has high affinity and selectivity for human somatostatin receptor subtype 1 (sst1). The binding affinities of des-AA(1,2,5)-[DTrp(8),IAmp(9)]-SRIF (c[H-Cys-Lys...

journal_title：Journal of medicinal chemistry

authors： Rivier JE,Hoeger C,Erchegyi J,Gulyas J,DeBoard R,Craig AG,Koerber SC,Wenger S,Waser B,Schaer JC,Reubi JC

更新日期：2001-06-21 00:00:00

abstract：:Several esters of beta-carboline-3-carboxylic acid were synthesized and tested in respect to their affinity for the benzodiazepine receptor in bovine cortex membranes. Out of these derivatives, the methyl, ethyl, and n-propyl ester were clearly the most potent, while the n-butyl, benzyl, and 3-pyridylmethyl ester were...

journal_title：Journal of medicinal chemistry

authors： Lippke KP,Schunack WG,Wenning W,Müller WE

更新日期：1983-04-01 00:00:00

abstract：:Novel tumor-targeting theranostic conjugates 1 and 2, bearing either a fluorine-labeled prosthetic as a potential (18)F-PET radiotracer (1) or a fluorescence probe (2) for internalization studies in vitro, were designed and synthesized. We confirmed efficient internalization of 2 in biotin-receptor positive (BR+) canc...

journal_title：Journal of medicinal chemistry

authors： Vineberg JG,Wang T,Zuniga ES,Ojima I

更新日期：2015-03-12 00:00:00

abstract：:Thyroid hormone analogues, polychlorinated biphenyls (PCBs), and their derivatives were shown to bind specifically to thyroxine-specific binding sites in rat liver nuclear extracts. The structure-binding relationship for thyroxine binding prealbumin was qualitatively similar to that for the nuclear receptor. In genera...

journal_title：Journal of medicinal chemistry

authors： McKinney J,Fannin R,Jordan S,Chae K,Rickenbacher U,Pedersen L

更新日期：1987-01-01 00:00:00

abstract：:Ras proteins regulate signal transduction processes that control cell growth and proliferation. Their disregulation is a common cause of human tumors. Atomic level structural and dynamical information in a membrane environment is crucial for understanding signaling specificity among Ras isoforms and for the design of ...

journal_title：Journal of medicinal chemistry

authors： Gorfe AA,Hanzal-Bayer M,Abankwa D,Hancock JF,McCammon JA

更新日期：2007-02-22 00:00:00

abstract：:We have designed and evaluated 45 linear analogues of the natural constrained cyclopeptide TMC-95A. These synthetically less demanding molecules are based on the tripeptide sequence Y-N-W of TMC-95A. Structural variations in the amino acid side chains and termini greatly influenced both the efficiency and selectivity ...

journal_title：Journal of medicinal chemistry

authors： Basse N,Piguel S,Papapostolou D,Ferrier-Berthelot A,Richy N,Pagano M,Sarthou P,Sobczak-Thépot J,Reboud-Ravaux M,Vidal J

更新日期：2007-06-14 00:00:00

abstract：:Recently we have described the antitumor activities of 2-benzoxazolylhydrazones derived from 2-formyl and 2-acetylpyridines. In search of a more efficacious analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2-acylpyridine and alpha-(N)-acetyldiazine/quinoline groups have been synthesized. T...

journal_title：Journal of medicinal chemistry

authors： Easmon J,Pürstinger G,Thies KS,Heinisch G,Hofmann J

更新日期：2006-10-19 00:00:00

abstract：:A practical combination of comparative modeling and NMR spectroscopy was used to generate a three-dimensional structure of the response regulator protein, Spo0F. The backbone structure obtained compares to the Spo0F Y13S mutant X-ray structure with an rmsd of 2.0 A. We provide results which suggest that structures obt...

journal_title：Journal of medicinal chemistry

authors： Podlogar BL,Leo GC,McDonnell PA,Loughney DA,Caldwell GW,Barrett JF

更新日期：1997-10-10 00:00:00

abstract：:Interleukin-2 inducible T-cell kinase (Itk) plays a role in T-cell functions, and its inhibition potentially represents an attractive intervention point to treat autoimmune and allergic diseases. Herein we describe the discovery of a series of potent and selective novel inhibitors of Itk. These inhibitors were identif...

journal_title：Journal of medicinal chemistry

authors： Charrier JD,Miller A,Kay DP,Brenchley G,Twin HC,Collier PN,Ramaya S,Keily SB,Durrant SJ,Knegtel RM,Tanner AJ,Brown K,Curnock AP,Jimenez JM

更新日期：2011-04-14 00:00:00

abstract：:A number of 2-oxoquinoline-1-alkanoic acids that contain the N-acylglycine fragment found in several known inhibitors of aldose reductase were synthesized and tested in the rat lens assay. All of the target compounds were prepared by alkylation of the appropriate 2-oxoquinoline intermediates with a halo ester, followe...

journal_title：Journal of medicinal chemistry

authors： DeRuiter J,Brubaker AN,Whitmer WL,Stein JL Jr

更新日期：1986-10-01 00:00:00

abstract：:The relative simplicity and high specificity of peptide therapeutics has fueled recent interest. However, peptide and protein drugs generally require injection and suffer from low metabolic stability. We report here the design, synthesis, and characterization of fluorinated analogues of the gut hormone peptide, GLP-1....

journal_title：Journal of medicinal chemistry

authors： Meng H,Krishnaji ST,Beinborn M,Kumar K

更新日期：2008-11-27 00:00:00

abstract：:Recently, FXIIa was highlighted as an original attractive target for the development of new anticoagulant drugs with low rates of therapy-related hemorrhages. In this work, we describe the development of a new series of 3-carboxamide-coumarins that are the first potent and selective nonpeptidic inhibitors of FXIIa. ...

journal_title：Journal of medicinal chemistry

authors： Robert S,Bertolla C,Masereel B,Dogné JM,Pochet L

更新日期：2008-06-12 00:00:00

abstract：:Representatives of three types of side-chain analogues of distamycin A (1) were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured cells, effects on the synthesis of HSV DNA in isolated nuclei in vitro, as well as on DNA synthesis by purified HSV DNA polym...

journal_title：Journal of medicinal chemistry

authors： Bialer M,Yagen B,Mechoulam R,Becker Y

更新日期：1979-11-01 00:00:00

abstract：:In an intensive study of South American medicinal plants, herein we report the isolation, structure elucidation and biological activity of fourteen new and five known dihydro-beta-agarofuran sesquiterpenes from the leaves of Zinowiewia costaricensis (1-19). Their structures were determined by means of (1)H and (13)C N...

journal_title：Journal of medicinal chemistry

authors： Muñoz-Martínez F,Mendoza CR,Bazzocchi IL,Castanys S,Jiménez IA,Gamarro F

更新日期：2005-06-30 00:00:00

abstract：:Human coagulation factor XIa (FXIa), a serine protease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation cascade. To investigate the potential of FXIa inhibitors as safe anticoagulants, a series of potent, selectiv...

journal_title：Journal of medicinal chemistry

authors： Lin J,Deng H,Jin L,Pandey P,Quinn J,Cantin S,Rynkiewicz MJ,Gorga JC,Bibbins F,Celatka CA,Nagafuji P,Bannister TD,Meyers HV,Babine RE,Hayward NJ,Weaver D,Benjamin H,Stassen F,Abdel-Meguid SS,Strickler JE

更新日期：2006-12-28 00:00:00

abstract：:Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA(4)H) as a key target for the treatment of cardiovascular disease. We combined fragment-based crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors of LTA(4)H. Lig...

journal_title：Journal of medicinal chemistry

authors： Sandanayaka V,Mamat B,Mishra RK,Winger J,Krohn M,Zhou LM,Keyvan M,Enache L,Sullins D,Onua E,Zhang J,Halldorsdottir G,Sigthorsdottir H,Thorlaksdottir A,Sigthorsson G,Thorsteinnsdottir M,Davies DR,Stewart LJ,Zembower DE

更新日期：2010-01-28 00:00:00

abstract：:Studies of molecular structure-carcinogenicity relations for a set of 157 aromatic amines are reported. A computer-assisted approach using pattern-recognition methods was used to develop a series of discriminants for aromatic amino carcinogenic potential. The 157 compounds were divided into subsets according to tumor ...

journal_title：Journal of medicinal chemistry

authors： Yuta K,Jurs PC

更新日期：1981-03-01 00:00:00

abstract：:A series of 1-H-pyrazole-3-carboxamide derivatives have been designed and synthesized that exhibit excellent FLT3 and CDK inhibition and antiproliferative activities. A structure-activity-relationship study illustrates that the incorporation of a pyrimidine-fused heterocycle at position 4 of the pyrazole is critical f...

journal_title：Journal of medicinal chemistry

authors： Wang Y,Zhi Y,Jin Q,Lu S,Lin G,Yuan H,Yang T,Wang Z,Yao C,Ling J,Guo H,Li T,Jin J,Li B,Zhang L,Chen Y,Lu T

更新日期：2018-02-22 00:00:00

abstract：:Bis (1-aziridinyl)(hexahydro-1H-azepin-1-yl)phosphine sulfide, an active anticancer agent with low hematopoietic toxicity in animals and man, was recommended several years ago for breast cancer adjuvant chemotherapy as an alternate drug to thiotepa. This hope had led to the syntheses of aziridinylallylaminophosphine o...

journal_title：Journal of medicinal chemistry

authors： Tsou KC,Bender D,Santora N,David L,Damle S

更新日期：1976-06-01 00:00:00

abstract：:To search for new antiestrogens more effective in treating breast cancers, we explored alternatives to the acrylic acid side chain used in many antiestrogens. To facilitate our search, we used a simple adamantyl ligand core that by avoiding stereochemical issues enabled rapid synthesis of acrylate ketone, ester, and a...

journal_title：Journal of medicinal chemistry

authors： Min J,Guillen VS,Sharma A,Zhao Y,Ziegler Y,Gong P,Mayne CG,Srinivasan S,Kim SH,Carlson KE,Nettles KW,Katzenellenbogen BS,Katzenellenbogen JA

更新日期：2017-07-27 00:00:00

abstract：:[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low p...

journal_title：Journal of medicinal chemistry

authors： Kohl B,Sturm E,Senn-Bilfinger J,Simon WA,Krüger U,Schaefer H,Rainer G,Figala V,Klemm K

更新日期：1992-03-20 00:00:00

abstract：:Compound 2 [4-amino-N-(2,6-dimethylphenyl)benzamide] is an effective anticonvulsant in several animal models. For example, following oral administration to mice, it antagonized maximal electroshock (MES) induced seizures with an ED50 of 1.7 mg/kg. During drug disposition studies with 2, we found that it was rapidly me...

journal_title：Journal of medicinal chemistry

authors： Robertson DW,Leander JD,Lawson R,Beedle EE,Clark CR,Potts BD,Parli CJ

更新日期：1987-10-01 00:00:00