Synthesis and antiarrhythmic activity of cis-2,6-dimethyl-alpha,alpha-diaryl-1-piperidinebutanols.

abstract：:Intravenous administration of N-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin (4) induces an acute toxic reaction, killing animals in a few minutes. This results from its positive charge at physiological pH combined with its propensity to form large aggregates in aqueous solutions. Negatively charged N-capped ve...

journal_title：Journal of medicinal chemistry

authors： Fernandez AM,Van Derpoorten K,Dasnois L,Lebtahi K,Dubois V,Lobl TJ,Gangwar S,Oliyai C,Lewis ER,Shochat D,Trouet A

更新日期：2001-10-25 00:00:00

abstract：:A series of substituted analogues based on the novel 2,3-dihydro-6-hydroxypyrimido[2,1-f]purine-4,8(1H,9H)-dione ring system have been synthesized and shown to exhibit antiinflammatory activity in the adjuvant-induced arthritis rat model (AAR). The activity exhibited by the pyrimidopurinediones in this model of chroni...

journal_title：Journal of medicinal chemistry

authors： Kaminski JJ,Solomon DM,Conn DJ,Wong SC,Chiu PJ,Massa T,Siegel MI,Watnick AS

更新日期：1989-05-01 00:00:00

abstract：:Two products without phosphoryl groups, 1-O-octadecyl-2-O-acetyl-3-O-[gamma-(dimethylamino)propyl]glycerol and its quaternary salt, were synthesized from 1-O-octadecyl-2-O-benzylglycerol. In comparison with PAF-acether, they lost aggregating and bronchoconstrictive activities and did not show any antagonistic effects....

journal_title：Journal of medicinal chemistry

authors： Heymans F,Borrel MC,Broquet C,Lefort J,Godfroid JJ

更新日期：1985-08-01 00:00:00

abstract：:The chelating drugs BAL (2,3-dimercaptopropanol), EDTA (ethylenediaminetetraacetic acid), and penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), which are used for metal poisoning, are toxic and there is a real need for alternatives, especially for severe cases. A novel approach for treatment of heavy-metal poi...

journal_title：Journal of medicinal chemistry

authors： Margel S

更新日期：1981-10-01 00:00:00

abstract：:Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine residues, a process that involves a conserved tryptophan-proline-aspartate (WPD) loop in catalysis. In previously determined structures of PTPs, the WPD-loop has been observed in either an "open" conformation or a "closed" conformation. In...

journal_title：Journal of medicinal chemistry

authors： Sheriff S,Beno BR,Zhai W,Kostich WA,McDonnell PA,Kish K,Goldfarb V,Gao M,Kiefer SE,Yanchunas J,Huang Y,Shi S,Zhu S,Dzierba C,Bronson J,Macor JE,Appiah KK,Westphal RS,O'Connell J,Gerritz SW

更新日期：2011-10-13 00:00:00

abstract：:Quantitative structure-activity relationships (QSAR) have been established for the inhibition of dihydrofolate reductase and thymidylate synthetase by 2,4-diaminoquinazoline-glutamic acid analogues. For dihydrofolate reductase from both human acute lymphocytic leukemia cells and murine L1210R cells, QSAR's obtained wi...

journal_title：Journal of medicinal chemistry

authors： Chen BK,Horváth C,Bertino JR

更新日期：1979-05-01 00:00:00

abstract：:The quinazoline class was exploited to search for a new translocator protein (TSPO) fluorescent probe endowed with improved affinity and residence time (RT). Computational studies on an "in-house" collection of quinazoline derivatives, featuring highly steric demanding groups at the amide nitrogen, suggested that, des...

journal_title：Journal of medicinal chemistry

authors： Milite C,Barresi E,Da Pozzo E,Costa B,Viviano M,Porta A,Messere A,Sbardella G,Da Settimo F,Novellino E,Cosconati S,Castellano S,Taliani S,Martini C

更新日期：2017-09-28 00:00:00

abstract：:A series of 2-aryldopamine analogues were synthesized and evaluated for their effects on D1 and D2 dopamine receptors. The 2-phenyldopamine and 6-phenylbenzazepine analogues exhibited weak binding to both D1 and D2 receptors. The 9-(aminomethyl)fluorenes also exhibited weak D2 binding; however, 2,5,6-trihydroxy-9H-flu...

journal_title：Journal of medicinal chemistry

authors： Ladd DL,Weinstock J,Wise M,Gessner GW,Sawyer JL,Flaim KE

更新日期：1986-10-01 00:00:00

abstract：:Using the crystal structure of an inhibitor complexed with the serine protease thrombin (PDB code ) and the functional group definitions contained within the Catalyst software, a representation of the enzyme's active site was produced (structure-based pharmacophore model). A training set of 16 homologous non-peptide i...

journal_title：Journal of medicinal chemistry

authors： Greenidge PA,Mérette SA,Beck R,Dodson G,Goodwin CA,Scully MF,Spencer J,Weiser J,Deadman JJ

更新日期：2003-04-10 00:00:00

abstract：:The ever-growing risk of bacterial resistance is a critical concern. Among the various antimicrobial resistant bacterial strains, methicillin and vancomycin resistant Staphylococcus aureus are among the most dreadful, causing serious complications. On the basis of the hypothesis that microbes have reduced ability to d...

journal_title：Journal of medicinal chemistry

authors： Singla P,Dalal P,Kaur M,Arya G,Nimesh S,Singh R,Salunke DB

更新日期：2018-11-21 00:00:00

abstract：:For a fourth approach of quinoxaline N,N'-dioxides as anti-trypanosomatid agents against T. cruzi and Leishmania, we found extremely active derivatives. The present study allows us to state the correct requirements for obtaining optimal in vitro anti-T. cruzi activity. Derivatives possessing electron-withdrawing subst...

journal_title：Journal of medicinal chemistry

authors： Benitez D,Cabrera M,Hernández P,Boiani L,Lavaggi ML,Di Maio R,Yaluff G,Serna E,Torres S,Ferreira ME,Vera de Bilbao N,Torres E,Pérez-Silanes S,Solano B,Moreno E,Aldana I,López de Ceráin A,Cerecetto H,González M,Monge

更新日期：2011-05-26 00:00:00

abstract：:The chemical synthesis of 2-[(2,6-dichloro-4-iodophenyl)imino]imidazolidine (PIC) and its radioiodinated analogue [125I]PIC is described. PIC was synthesized from 2,6-dichloroaniline in five synthetic steps. This agent displayed a high affinity for the alpha 2-adrenergic receptor (IC50 = 1.5 nM) in competitive binding...

journal_title：Journal of medicinal chemistry

authors： Van Dort M,Neubig R,Counsell RE

更新日期：1987-07-01 00:00:00

abstract：:In our search for new therapeutic agents against chronic hepatitis C, a ribonucleoside analogue, 2'-C-methylcytidine, was discovered to be a potent and selective inhibitor in cell culture of a number of RNA viruses, including the pestivirus bovine viral diarrhea virus, a surrogate model for hepatitis C virus (HCV), an...

journal_title：Journal of medicinal chemistry

authors： Pierra C,Amador A,Benzaria S,Cretton-Scott E,D'Amours M,Mao J,Mathieu S,Moussa A,Bridges EG,Standring DN,Sommadossi JP,Storer R,Gosselin G

更新日期：2006-11-02 00:00:00

abstract：:Selective inhibitors of human sirtuin 2 (SIRT2), a deacetylase, are candidate therapeutic agents for neurodegenerative diseases such as Parkinson's disease and Huntington's disease as well as potential tools for elucidating the biological functions of SIRT2. On the basis of homology models of SIRT1 and SIRT2, we desig...

journal_title：Journal of medicinal chemistry

authors： Suzuki T,Khan MN,Sawada H,Imai E,Itoh Y,Yamatsuta K,Tokuda N,Takeuchi J,Seko T,Nakagawa H,Miyata N

更新日期：2012-06-28 00:00:00

abstract：:Vitamin D receptor (VDR) antagonists prevent the VDR activation function helix 12 from folding into its active conformation, thus affecting coactivator recruitment and antagonizing the transcriptional regulation induced by 1α,25-dihydroxyvitamin D3. Here, we report the crystal structure of the zebrafish VDR ligand-bin...

journal_title：Journal of medicinal chemistry

authors： Belorusova AY,Chalhoub S,Rovito D,Rochel N

更新日期：2020-09-10 00:00:00

abstract：:Little is known of the conformation of peptide hormones as they interact with their receptors for a number of reasons: peptide hormones are notoriously flexible in solution, their receptors are particularly complex, and there is strong evidence that receptor-ligand interaction leading to activation is a dynamic proces...

journal_title：Journal of medicinal chemistry

authors： Koerber SC,Rizo J,Struthers RS,Rivier JE

更新日期：2000-03-09 00:00:00

abstract：:A novel series of diaminoanthraquinones was discovered initially as protein kinase C inhibitors with IC50s in the 50-100 microM range. They exhibited potent tumor cell growth inhibitory activity in vitro without cross resistance to adriamycin. Further evaluation of two of the most active compounds NSC 639365 (3) and N...

journal_title：Journal of medicinal chemistry

authors： Jiang JB,Johnson MG,Defauw JM,Beine TM,Ballas LM,Janzen WP,Loomis CR,Seldin J,Cofield D,Adams L

更新日期：1992-11-13 00:00:00

abstract：:A series of 1-aminopropan-2-ols were synthesized and evaluated against two strains of malaria, Plasmodium falciparum FCR3 (chloroquine-resistant) and 3D7 (chloroquine-sensitive). Microwave-assisted ring opening of epoxides (aryl and alkyl glycidyl ethers, glycidol, epichlorohydrin) with various amines without catalyst...

journal_title：Journal of medicinal chemistry

authors： Robin A,Brown F,Bahamontes-Rosa N,Wu B,Beitz E,Kun JF,Flitsch SL

更新日期：2007-08-23 00:00:00

abstract：:Several N-2 substituted 1-methyl-1-(4-tolylsulfonyl)hydrazines were synthesized and evaluated for antineoplastic activity against the L1210 leukemia and the B16 melanoma. The most active compound to emerge from this study, 2-(methylsulfonyl)-1-methyl-1-(4-tolylsulfonyl)hydrazine, produced maximum percent T/C values wi...

journal_title：Journal of medicinal chemistry

authors： Hrubiec RT,Shyam K,Cosby LA,Furubayashi R,Sartorelli AC

更新日期：1986-07-01 00:00:00

abstract：:Bitter thresholds of a total of 93 amino acids, peptides, and their derivatives were analyzed quantitatively by use of hydrophobicity parameters reported for amino acid side chains and those for the whole molecules estimated from partition coefficients obtained experimentally. We also explored the steric parameters th...

journal_title：Journal of medicinal chemistry

authors： Asao M,Iwamura H,Akamatsu M,Fujita T

更新日期：1987-10-01 00:00:00

abstract：:Methodology is presented for assembling fluorescently labeled bivalent molecules from monovalent constituents, without side chain protection or coupling agents. To illustrate the procedure, a series of bivalent peptidomimetics directed toward the Trk receptors were prepared and screened via fluorescent activated cell ...

journal_title：Journal of medicinal chemistry

authors： Pattarawarapan M,Reyes S,Xia Z,Zaccaro MC,Saragovi HU,Burgess K

更新日期：2003-08-14 00:00:00

abstract：:Inhibitors of checkpoint kinase 1 (CHK1) are of current interest as potential antitumor agents, but the most advanced inhibitor series reported to date are not orally bioavailable. A novel series of potent and orally bioavailable 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitrile CHK1 inhibitors was generated ...

journal_title：Journal of medicinal chemistry

authors： Lainchbury M,Matthews TP,McHardy T,Boxall KJ,Walton MI,Eve PD,Hayes A,Valenti MR,de Haven Brandon AK,Box G,Aherne GW,Reader JC,Raynaud FI,Eccles SA,Garrett MD,Collins I

更新日期：2012-11-26 00:00:00

abstract：:The discovery of inhibitors of bromodomain and extra terminal domain (BET) has achieved great progress, and at least seven inhibitors have progressed into clinical trials for the treatment of cancer or inflammatory diseases. Here, we describe the identification, optimization, and evaluation of benzo[cd]indol-2(1H)-one...

journal_title：Journal of medicinal chemistry

authors： Xue X,Zhang Y,Liu Z,Song M,Xing Y,Xiang Q,Wang Z,Tu Z,Zhou Y,Ding K,Xu Y

更新日期：2016-02-25 00:00:00

abstract：:A novel series of nonsteroidal progestins, 5-benzylidene-1, 2-dihydrochromeno[3,4-f]quinolines (2), was discovered, and a preliminary structure-activity relationship study around the 5-benzylidene ring generated several potent human progesterone receptor agonists (compounds 8, 16). These new progestins showed biologic...

journal_title：Journal of medicinal chemistry

authors： Tegley CM,Zhi L,Marschke KB,Gottardis MM,Yang Q,Jones TK

更新日期：1998-10-22 00:00:00

abstract：:The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Bart...

journal_title：Journal of medicinal chemistry

authors： Procopiou PA,Biggadike K,English AF,Farrell RM,Hagger GN,Hancock AP,Haase MV,Irving WR,Sareen M,Snowden MA,Solanke YE,Tralau-Stewart CJ,Walton SE,Wood JA

更新日期：2001-02-15 00:00:00

abstract：:A series of 3-fluoromethyl-1,2,3,4-tetrahydroisoquinolines (3-fluoromethyl-THIQs) was proposed, and their phenylethanolamine N-methyltransferase (PNMT) and alpha(2)-adrenoceptor affinities were predicted through the use of comparative molecular field analysis (CoMFA) models. These compounds were synthesized and evalua...

journal_title：Journal of medicinal chemistry

authors： Grunewald GL,Caldwell TM,Li Q,Slavica M,Criscione KR,Borchardt RT,Wang W

更新日期：1999-09-09 00:00:00

abstract：:Twenty-nine novel 3'-substituted derivatives of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3) have been synthesized by using established methods and by a new route involving manipulation of a 3'-formyl intermediate. In vitro hormone receptor binding (to intact nuclei) and in vivo thyromimetic activity (induction...

journal_title：Journal of medicinal chemistry

authors： Leeson PD,Ellis D,Emmett JC,Shah VP,Showell GA,Underwood AH

更新日期：1988-01-01 00:00:00

abstract：:Rotigaptide (3) is an antiarrhythmic peptide that improves cardiac conduction by modifying gap-junction communication. Small molecule gap-junction modifiers with improved physical properties were identified from a Zealand Pharma peptide library using pharmaceutical profiling, established SAR around 3, and a putative p...

journal_title：Journal of medicinal chemistry

authors： Butera JA,Larsen BD,Hennan JK,Kerns E,Di L,Alimardanov A,Swillo RE,Morgan GA,Liu K,Wang Q,Rossman EI,Unwalla R,McDonald L,Huselton C,Petersen JS

更新日期：2009-02-26 00:00:00

abstract：:An essential step in the HIV life cycle is integration of the viral DNA into the host chromosome. This step is catalyzed by a 32-kDa viral enzyme HIV integrase (IN). HIV-1 IN is an important and validated target, and the drugs that selectively inhibit this enzyme, when used in combination with reverse transcriptase (R...

journal_title：Journal of medicinal chemistry

authors： Kuo CL,Assefa H,Kamath S,Brzozowski Z,Slawinski J,Saczewski F,Buolamwini JK,Neamati N

更新日期：2004-01-15 00:00:00

abstract：:We previously reported that [[N-[3beta-hydroxyllup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane (A43D, 4) was a potent HIV-1 entry inhibitor. However, 4 was inactive against HIV-2 virus, suggesting the structural requirements for targeting these two retroviruses are different. In this study, a series of new betul...

journal_title：Journal of medicinal chemistry

authors： Dang Z,Lai W,Qian K,Ho P,Lee KH,Chen CH,Huang L

更新日期：2009-12-10 00:00:00