Nonsteroidal progesterone receptor ligands. 2. High-affinity ligands with selectivity for bone cell progesterone receptors.

abstract：:A series of 59 alpha-aryl-alpha-thioether-alkyl, -alkanenitrile, and -alkanecarboxylic acid methyl ester tetrahydroisoquinoline and isoindoline derivatives (15a-48) were synthesized and evaluated as multidrug resistance (MDR) reversal agents. The compounds were tested on S1-B1-20 human colon carcinoma cells selected f...

journal_title：Journal of medicinal chemistry

authors： Berger D,Citarella R,Dutia M,Greenberger L,Hallett W,Paul R,Powell D

更新日期：1999-06-17 00:00:00

abstract：:Polycomb Repressive Complex 2 (PRC2) modulates the chromatin structure and transcriptional repression by trimethylation lysine 27 of histone H3 (H3K27me3), a process that necessitates the protein-protein interaction (PPI) between the catalytic subunit EZH2 and EED. Deregulated PRC2 is intimately involved in tumorigene...

journal_title：Journal of medicinal chemistry

authors： Kong X,Chen L,Jiao L,Jiang X,Lian F,Lu J,Zhu K,Du D,Liu J,Ding H,Zhang N,Shen J,Zheng M,Chen K,Liu X,Jiang H,Luo C

更新日期：2014-11-26 00:00:00

abstract：:Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical prop...

journal_title：Journal of medicinal chemistry

authors： Koeberle SC,Fischer S,Schollmeyer D,Schattel V,Grütter C,Rauh D,Laufer SA

更新日期：2012-06-28 00:00:00

abstract：:Syntheses of several new analogues of lyngbyatoxin A from a single common intermediate are described. These compounds bear a carbon chain at the 7-position of the indolactam V (ILV) nucleus which contains either a hydrophilic or a lipophilic group. The effect of these minor structural alterations on the ability of the...

journal_title：Journal of medicinal chemistry

authors： Kozikowski AP,Shum PW,Basu A,Lazo JS

更新日期：1991-08-01 00:00:00

abstract：:Thalidomide, 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione, has been shown to inhibit angiogenesis, the formation of new blood vessels from existing vasculature. As a result, there is renewed interest in this drug as a potential therapy for solid tumors. Thalidomide forms a number of metabolites and has been ...

journal_title：Journal of medicinal chemistry

authors： Lepper ER,Ng SS,Gütschow M,Weiss M,Hauschildt S,Hecker TK,Luzzio FA,Eger K,Figg WD

更新日期：2004-04-22 00:00:00

abstract：:The 5'-phosphate (1) of the antiviral nucleoside 5-cyano-2'-deoxyuridine was synthesized and evaluated for inhibition of thymidylate synthetase purified from methotrexate-resistant Lactobacillus casei. Compound 1 was a potent competitive inhibitor with a K1 of 0.55 microns. Irreversible enzyme inhibition by this compo...

journal_title：Journal of medicinal chemistry

authors： Chang CT,Edwards MW,Torrence PF,Mertes MP

更新日期：1979-09-01 00:00:00

abstract：:To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some sigma receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH(3), CH(3)O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-py...

journal_title：Journal of medicinal chemistry

authors： Berardi F,Abate C,Ferorelli S,de Robertis AF,Leopoldo M,Colabufo NA,Niso M,Perrone R

更新日期：2008-12-11 00:00:00

abstract：:FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophospho...

journal_title：Journal of medicinal chemistry

authors： Mahboobi S,Uecker A,Sellmer A,Cénac C,Höcher H,Pongratz H,Eichhorn E,Hufsky H,Trümpler A,Sicker M,Heidel F,Fischer T,Stocking C,Elz S,Böhmer FD,Dove S

更新日期：2006-06-01 00:00:00

abstract：:A molecular model of the alpha(IIb)beta(3) integrin has been developed utilizing (i). the crystal structure of alpha(v)beta(3), (ii). homology model of the alpha(IIb) subdomain, and (iii). the docking of alpha(IIb)beta(3)/alpha(v)beta(3) dual and selective inhibitors into the putative binding sites of alpha(IIb)beta(3...

journal_title：Journal of medicinal chemistry

authors： Feuston BP,Culberson JC,Hartman GD

更新日期：2003-12-04 00:00:00

abstract：:The present study evaluates the utility of the dihydropyridine in equilibrium pyridinium salt redox system for the specific delivery and sustained release of a model 2',3'-dideoxynucleoside to the brain of mice as the initial effort in a search for agents that may prove effective in reversing the complicating neurolog...

journal_title：Journal of medicinal chemistry

authors： Palomino E,Kessel D,Horwitz JP

更新日期：1989-03-01 00:00:00

abstract：:Whereas the 2-propyl- and 2-butyl-5,6-(methylenedioxy)indene calcium antagonists reversed the spasmogenic action of several agonists including PGF2alpha and acetylcholine at 5 X 10(-5) to 10(-4) M on the rat ileum, the corresponding 5,6-dimethoxy analogues exhibited spasmogenic activity at higher concentration (10(-4)...

journal_title：Journal of medicinal chemistry

authors： Witiak DT,Kakodkar SV,Brunst GE,Baldwin JR,Rahwan RG

更新日期：1978-12-01 00:00:00

abstract：:Detailed molecular models of the free C1B domain of protein kinase C-gamma (PKC-gamma) and the C1B domain with its activator phorbol-12-myristate-13-acetate (PMA) in water solution and in the presence of dipalmitoylphosphatidylcholine (DPPC) bilayer are presented. Molecular dynamics of the free C1B domain reveals hydr...

journal_title：Journal of medicinal chemistry

authors： Hritz J,Ulicny J,Laaksonen A,Jancura D,Miskovsky P

更新日期：2004-12-16 00:00:00

abstract：:A three-dimensional structure of the complex of human renin and the scissile site P4 Pro to P1' Val of angiotensinogen was deduced in order to design potent human renin inhibitors rationally. On the basis of this structure, an orally potent human renin inhibitor (1a) was designed from the angiotensinogen transition st...

journal_title：Journal of medicinal chemistry

authors： Iizuka K,Kamijo T,Harada H,Akahane K,Kubota T,Umeyama H,Ishida T,Kiso Y

更新日期：1990-10-01 00:00:00

abstract：:By use of the effectively cleaved beta-secretase (BACE) substrate (1), incorporation of a statine in P(1) resulted in a weak inhibitor 13 of the enzyme. Further substitution of P(1)'-Asp by P(1)'-Val in 13 results in a potent inhibitor 22 of BACE. Removal of the P(10)-P(5) residues on the N-terminal part of inhibitor ...

journal_title：Journal of medicinal chemistry

authors： Tung JS,Davis DL,Anderson JP,Walker DE,Mamo S,Jewett N,Hom RK,Sinha S,Thorsett ED,John V

更新日期：2002-01-17 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：:Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensi...

journal_title：Journal of medicinal chemistry

authors： Ellingboe JW,Collini MD,Quagliato D,Chen J,Antane M,Schmid J,Hartupee D,White V,Park CH,Tanikella T,Bagli JF

更新日期：1998-10-22 00:00:00

abstract：:Analogues of [Leu10]NKA4-10 were synthesized in which each of the amide bonds was sequentially replaced with the reduced amide psi (CH2NH) bond to determine the effect of this structural modification on the antagonism of NKA binding to the HUB NK2 receptor. [psi (CH2-NH)9,Leu10]NKA4-10 (6) retained significant affinit...

journal_title：Journal of medicinal chemistry

authors： Harbeson SL,Shatzer SA,Le TB,Buck SH

更新日期：1992-10-16 00:00:00

abstract：:We previously reported that (+/-)-6-(4-(benzylamino)-7-quinazolinyl)-4,5- dihydro-5-methyl-3(2H)-pyridazinone (+/-)-1, KF15232) showed potent cardiotonic activity with a strong myofibrillar Ca(2+)-sensitizing effect. As an extension of our work, we attempted to synthesize optically active 1. (+/-)-4-(4-(Benzylamino)-7...

journal_title：Journal of medicinal chemistry

authors： Nomoto Y,Takai H,Ohno T,Nagashima K,Yao K,Yamada K,Kubo K,Ichimura M,Mihara A,Kase H

更新日期：1996-01-05 00:00:00

abstract：:A promising strategy for selecting synthetic targets is similarity-based searching of very large "virtual libraries", which comprise all structures accessible by linking two or three commercially available building blocks with combinatorial syntheses. To assess the general applicability of this strategy, leading struc...

journal_title：Journal of medicinal chemistry

authors： Andrews KM,Cramer RD

更新日期：2000-05-04 00:00:00

abstract：:Cdc7 serine/threonine kinase is a key regulator of DNA synthesis in eukaryotic organisms. Cdc7 inhibition through siRNA or prototype small molecules causes p53 independent apoptosis in tumor cells while reversibly arresting cell cycle progression in primary fibroblasts. This implies that Cdc7 kinase could be considere...

journal_title：Journal of medicinal chemistry

authors： Menichincheri M,Albanese C,Alli C,Ballinari D,Bargiotti A,Caldarelli M,Ciavolella A,Cirla A,Colombo M,Colotta F,Croci V,D'Alessio R,D'Anello M,Ermoli A,Fiorentini F,Forte B,Galvani A,Giordano P,Isacchi A,Martina K,

更新日期：2010-10-28 00:00:00

abstract：:Two molecules with known growth hormone secretagogue (GHS) agonist activity were used as templates to computationally screen approximately 80000 compounds. A total of 108 candidate compounds were selected, and five of them were found to be active in the low-micromolar range in both cell-based and direct binding assays...

journal_title：Journal of medicinal chemistry

authors： Shoda M,Harada T,Kogami Y,Tsujita R,Akashi H,Kouji H,Stahura FL,Xue L,Bajorath J

更新日期：2004-08-12 00:00:00

abstract：:A series of new 5-(1-hydroxy-2-haloethyl)-2'-deoxyuridines (3, 6, 8) were synthesized in 60-70% yields by addition of HOX (X = Br, Cl, I) to the vinyl substituent of the respective 5-vinyl-2'-deoxyuridines (2, 5, 7). Treatment of 3a,b with methanolic sulfuric acid afforded the corresponding 5-(1-methoxy-2-haloethyl)-2...

journal_title：Journal of medicinal chemistry

authors： Kumar R,Wiebe LI,Hall TW,Knaus EE,Tovell DR,Tyrrell DL,Allen TM,Fathi-Afshar R

更新日期：1989-05-01 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：:The intracellular delivery of nucleic acid molecules is a complex process involving several distinct steps; among these the endosomal escape appeared to be of particular importance for an efficient protein production (or inhibition) into host cells. In the present study, a new series of ionizable vectors, derived from...

journal_title：Journal of medicinal chemistry

authors： Habrant D,Peuziat P,Colombani T,Dallet L,Gehin J,Goudeau E,Evrard B,Lambert O,Haudebourg T,Pitard B

更新日期：2016-04-14 00:00:00

abstract：:Antimicrobial peptides (AMPs) are amphipathic molecules displaying broad-spectrum bactericidal activity, providing opportunities to develop a new generation of antibiotics. However, their use is limited either by poor metabolic stability or by high hemolytic activity. We herein addressed the potential of thiazole-base...

journal_title：Journal of medicinal chemistry

authors： Bonnel C,Legrand B,Simon M,Clavié M,Masnou A,Jumas-Bilak E,Kang YK,Licznar-Fajardo P,Maillard LT,Masurier N

更新日期：2020-09-10 00:00:00

abstract：:Utilizing NNC 26-9100 (11) as a structural lead, a variety of nonpeptide derivatives of somatostatin were synthesized and evaluated for sst2 and sst4 receptor binding affinity. A novel thiourea scaffold was utilized to attach (1) a heteroaromatic nucleus to mimic the Trp8 residue, (2) a nonheteroaromatic nucleus to mi...

journal_title：Journal of medicinal chemistry

authors： Liu S,Tang C,Ho B,Ankersen M,Stidsen CE,Crider AM

更新日期：1998-11-19 00:00:00

abstract：:7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661, 1) is a potent inhibitor of the enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28). In contrast to other inhibitors of PNMT, it is also highly selective toward PNMT in comparison with its affinity toward the alpha 2-adrenoceptor (PNMT Ki = 0....

journal_title：Journal of medicinal chemistry

authors： Grunewald GL,Dahanukar VH,Caldwell TM,Criscione KR

更新日期：1997-12-05 00:00:00

abstract：:Continuing structure-activity studies on the anticonvulsant activity of analogs of N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione (2a), which displayed anti-electroshock seizure (MES) activity and a protective index (TD50/ED50) of > 4.5 are reported. An in-depth analysis of this moiety was studied employing the Topliss...

journal_title：Journal of medicinal chemistry

authors： Farrar VA,Ciechanowicz-Rutkowska M,Grochowski J,Serda P,Pilati T,Filippini G,Hinko CN,el-Assadi A,Moore JA,Edafiogho IO

更新日期：1993-11-12 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：:Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme that methylates nicotinamide (NAM) using cofactor S-adenosylmethionine (SAM). NNMT overexpression has been linked to diabetes, obesity, and various cancers. In this work, structure-based rational design led to the development of potent and selective alkynyl...

journal_title：Journal of medicinal chemistry

authors： Policarpo RL,Decultot L,May E,Kuzmič P,Carlson S,Huang D,Chu V,Wright BA,Dhakshinamoorthy S,Kannt A,Rani S,Dittakavi S,Panarese JD,Gaudet R,Shair MD

更新日期：2019-11-14 00:00:00