Dehydrative metabolites of 1-(3-chlorophenyl)-1methyl-2-phenyl-2-(2-pyridine)ethanol as potential hypocholesteremic agents.

abstract：:Thymidylate kinase (TMK), an essential enzyme in bacterial DNA biosynthesis, is an attractive therapeutic target for the development of novel antibacterial agents, and we continue to explore TMK inhibitors with improved potency, protein binding, and pharmacokinetic potential. A structure-guided design approach was emp...

journal_title：Journal of medicinal chemistry

authors： Kawatkar SP,Keating TA,Olivier NB,Breen JN,Green OM,Guler SY,Hentemann MF,Loch JT,McKenzie AR,Newman JV,Otterson LG,Martínez-Botella G

更新日期：2014-06-12 00:00:00

abstract：:A novel class of 21-aminosteroids has been developed. Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 microM. Furthermore, selected members enhance early neurological recovery and survival in a mouse head injury model. Significant...

journal_title：Journal of medicinal chemistry

authors： Jacobsen EJ,McCall JM,Ayer DE,Van Doornik FJ,Palmer JR,Belonga KL,Braughler JM,Hall ED,Houser DJ,Krook MA

更新日期：1990-04-01 00:00:00

abstract：:Membrane-bound aminopeptidase P (AP-P) participates in the degradation of bradykinin in several vascular beds. We have developed an inhibitor of AP-P called apstatin (1) (N-[(2S, 3R)-3-amino-2-hydroxy-4-phenyl-butanoyl]-L-prolyl-L-prolyl-L-al aninam ide); IC50,human = 2.9 microM. In the rat, apstatin can potentiate th...

journal_title：Journal of medicinal chemistry

authors： Maggiora LL,Orawski AT,Simmons WH

更新日期：1999-07-01 00:00:00

abstract：:Syntheses of several tripeptide analogues of leupeptin containing C-terminal argininal, lysinal, or ornithinal units are presented. The synthetic analogues were tested as inhibitors of trypsin, plasmin, and kallikrein. (Benzyloxycarbonyl)-L-leucyl-L-leucyl-L-argininal (2a) was significantly less effective as an inhibi...

journal_title：Journal of medicinal chemistry

authors： McConnell RM,Barnes GE,Hoyng CF,Gunn JM

更新日期：1990-01-01 00:00:00

abstract：:RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as an important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promi...

journal_title：Journal of medicinal chemistry

authors： Deng J,Feng E,Ma S,Zhang Y,Liu X,Li H,Huang H,Zhu J,Zhu W,Shen X,Miao L,Liu H,Jiang H,Li J

更新日期：2011-07-14 00:00:00

abstract：:A series of hexadeoxyribonucleotides (6-mers), d(TGGGAG), substituted with a variety of aromatic groups at the 5'-end were synthesized and tested for anti-human immunodeficiency virus type 1 (HIV-1) activity. While unmodified d(TGGGAG) (31) had no anti-HIV-1 activity, compound 23 with a 3,4-di(benzyloxy)benzyl (DBB) g...

journal_title：Journal of medicinal chemistry

authors： Hotoda H,Koizumi M,Koga R,Kaneko M,Momota K,Ohmine T,Furukawa H,Agatsuma T,Nishigaki T,Sone J,Tsutsumi S,Kosaka T,Abe K,Kimura S,Shimada K

更新日期：1998-09-10 00:00:00

abstract：:Human melanocortin receptors (hMCRs) have been challenging targets to develop ligands that are explicitly selective for each of their subtypes. To modulate the conformational preferences of the melanocortin ligands and improve the biofunctional agonist/antagonist activities and selectivities, we have applied a backbon...

journal_title：Journal of medicinal chemistry

authors： Cai M,Marelli UK,Bao J,Beck JG,Opperer F,Rechenmacher F,McLeod KR,Zingsheim MR,Doedens L,Kessler H,Hruby VJ

更新日期：2015-08-27 00:00:00

abstract：:Three types of brassinosteroid analogues with perfluoroalkylated side chains were synthesized by using alkene cross-metathesis of a brassinosteroid derivative bearing a terminal alkene moiety with different (perfluoroalkyl)propenes. The presence of the double bonds in the cross-metathesis products allowed a facile one...

journal_title：Journal of medicinal chemistry

authors： Eignerová B,Slavíková B,Budĕsínský M,Dracínský M,Klepetárová B,St'astná E,Kotora M

更新日期：2009-09-24 00:00:00

abstract：:Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary b...

journal_title：Journal of medicinal chemistry

authors： Morrell A,Placzek M,Parmley S,Grella B,Antony S,Pommier Y,Cushman M

更新日期：2007-09-06 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：:EGFR-targeted inhibitors (gefitinib and erlotinib) provided an effective strategy for the treatment of non-small-cell lung cancer. However, the EGFR T790M secondary mutation has become a leading cause of clinically acquired resistance to these agents. Herein, on the basis of the previously reported irreversible EGFR i...

journal_title：Journal of medicinal chemistry

authors： Hao Y,Wang X,Zhang T,Sun D,Tong Y,Xu Y,Chen H,Tong L,Zhu L,Zhao Z,Chen Z,Ding J,Xie H,Xu Y,Li H

更新日期：2016-08-11 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：:The synthesis and biological evaluation of a novel paclitaxel photoaffinity probe is described. The synthesis involved the preparation of an azide-containing C13 side chain through a Staudinger cycloaddition followed by a lipase-mediated kinetic resolution to obtain the azetidinone in 99% ee. Coupling of the enantiopu...

journal_title：Journal of medicinal chemistry

authors： Spletstoser JT,Flaherty PT,Himes RH,Georg GI

更新日期：2004-12-16 00:00:00

abstract：:In previous studies, we have grouped regions in space occupied by the vitamin D side chain into four: A, G, EA, and EG. We showed that the receptor (VDR) affinity of 1alpha,25-dihydroxyvitamin D3 derivatives increases, in terms of side-chain region, in the order EG, G, A, and EA. We called this the active space group ...

journal_title：Journal of medicinal chemistry

authors： Yamada S,Yamamoto K,Masuno H,Ohta M

更新日期：1998-04-23 00:00:00

abstract：:The solid-phase reductive alkylation of the Lys side chain in positions 6 (D) and 8 (L) and position 8 alone of the LH-RH antagonist [N-Ac-D-Nal,D-Ph2,3,D-Arg6,Phe7,D-Ala10]LH-RH was investigated in an attempt to reduce the histamine-releasing activity inherent to most potent antagonists while retaining high antiovula...

journal_title：Journal of medicinal chemistry

authors： Hocart SJ,Nekola MV,Coy DH

更新日期：1987-10-01 00:00:00

abstract：:The pyridine C-nucleosides 5-beta-D-ribofuranosylnicotinamide and its N-methylpyridinium derivative (1 and 2), which are isosteric and isoelectronic, respectively, to nicotinamide nucleoside were synthesized. Condensation of 3-bromo-5-lithiopyridine with 2,4:3,5-di-O-benzylidene-D-aldehydoribose (7) afforded an allo/a...

journal_title：Journal of medicinal chemistry

authors： Kabat MM,Pankiewicz KW,Watanabe KA

更新日期：1987-05-01 00:00:00

abstract：:Among 18 human chemokine receptors, CCR1, CCR4, CCR5, and CCR8 were activated by metal ion Zn(II) or Cu(II) in complex with 2,2'-bipyridine or 1,10-phenanthroline with similar potencies (EC(50) from 3.9 to 172 μM). Besides being agonists, they acted as selective allosteric enhancers of CCL3. These actions were depende...

journal_title：Journal of medicinal chemistry

authors： Thiele S,Malmgaard-Clausen M,Engel-Andreasen J,Steen A,Rummel PC,Nielsen MC,Gloriam DE,Frimurer TM,Ulven T,Rosenkilde MM

更新日期：2012-09-27 00:00:00

abstract：:New benzofuranones were synthesized and evaluated toward NCI-H661 non-small cell lung cancer cells. Benzamide derivatives possessed micromolar antiproliferative and histone deacetylase inhibitory activities and modulate histone H4 acetylation. Hydroxamic acids were found to be potent nanomolar antiproliferative agents...

journal_title：Journal of medicinal chemistry

authors： Charrier C,Clarhaut J,Gesson JP,Estiu G,Wiest O,Roche J,Bertrand P

更新日期：2009-05-14 00:00:00

abstract：:Toward improving pharmacokinetics, in vivo efficacy, and selectivity over hERG, structure-activity relationship studies around the central core of antimalarial imidazopyridazines were conducted. This study led to the identification of potent pyrazolopyridines, which showed good in vivo efficacy and pharmacokinetics pr...

journal_title：Journal of medicinal chemistry

authors： Le Manach C,Paquet T,Brunschwig C,Njoroge M,Han Z,Gonzàlez Cabrera D,Bashyam S,Dhinakaran R,Taylor D,Reader J,Botha M,Churchyard A,Lauterbach S,Coetzer TL,Birkholtz LM,Meister S,Winzeler EA,Waterson D,Witty MJ,Wittl

更新日期：2015-11-12 00:00:00

abstract：:Dihydrofuro[3,4-c]pyridinones are the first class of small molecules reported to inhibit the cytolytic effects of the lymphocyte toxin perforin. A lead structure was identified from a high throughput screen, and a series of analogues were designed and prepared to explore structure-activity relationships around the cor...

journal_title：Journal of medicinal chemistry

authors： Lena G,Trapani JA,Sutton VR,Ciccone A,Browne KA,Smyth MJ,Denny WA,Spicer JA

更新日期：2008-12-11 00:00:00

abstract：:The synthesis, stability, and antitumor activity of a series of water-soluble third generation platinum(II) complexes have been described. Among these complexes, [2,2-bis(aminomethyl)-1,3- propanediol-N,N'] [1,1-cyclobutanedicarboxylato(2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylate(2-)-O,O'](tetrahydro-4H-py...

journal_title：Journal of medicinal chemistry

authors： Bitha P,Carvajal SG,Citarella RV,Child RG,Delos Santos EF,Dunne TS,Durr FE,Hlavka JJ,Lang SA Jr,Lindsay HL

更新日期：1989-08-01 00:00:00

abstract：:Various hydrophilic pyrazine-bis(carboxamides) derived from 3,5-diamino-pyrazine-2,5-dicarboxylic acid bearing neutral and anionic groups were prepared and evaluated for use as fluorescent glomerular filtration rate (GFR) tracer agents. Among these, the dianionic d-serine pyrazine derivatives 2d and 2j, and the neutra...

journal_title：Journal of medicinal chemistry

authors： Rajagopalan R,Neumann WL,Poreddy AR,Fitch RM,Freskos JN,Asmelash B,Gaston KR,Galen KP,Shieh JJ,Dorshow RB

更新日期：2011-07-28 00:00:00

abstract：:SAH 51-641 (1) is a potent hypoglycemic agent, which acts by inhibiting hepatic gluconeogenesis. It is a prodrug of 4-(2, 2-dimethyl-1-oxopropyl)benzoic acid (2) and 4-(2, 2-dimethyl-1-hydroxypropyl)benzoic acid (3), which sequester coenzyme A (CoA) in the mitochondria, and inhibits medium-chain acyltransferase. 1-3 a...

journal_title：Journal of medicinal chemistry

authors： Aicher TD,Bebernitz GR,Bell PA,Brand LJ,Dain JG,Deems R,Fillers WS,Foley JE,Knorr DC,Nadelson J,Otero DA,Simpson R,Strohschein RJ,Young DA

更新日期：1999-01-14 00:00:00

abstract：:Compstatin peptides are complement inhibitors that bind and inhibit cleavage of complement C3. Peptide binding is enhanced by hydrophobic interactions; however, poor solubility promotes aggregation in aqueous environments. We have designed new compstatin peptides derived from the W4A9 sequence (Ac-ICVWQDWGAHRCT-NH2, c...

journal_title：Journal of medicinal chemistry

authors： Gorham RD Jr,Forest DL,Khoury GA,Smadbeck J,Beecher CN,Healy ED,Tamamis P,Archontis G,Larive CK,Floudas CA,Radeke MJ,Johnson LV,Morikis D

更新日期：2015-01-22 00:00:00

abstract：:The synthesis and the X-ray structure of 16a-thiocamptothecin (TCPT), the thiopyridone analog of camptothecin (CPT), are accomplished. The crystal contains two structurally identical, yet independent molecules. Both of them are connected to other molecules via two intermolecular hydrogen bonds. S-methylation of TCPT l...

journal_title：Journal of medicinal chemistry

authors： Samorì C,Guerrini A,Varchi G,Zunino F,Beretta GL,Femoni C,Bombardelli E,Fontana G,Battaglia A

更新日期：2008-05-22 00:00:00

abstract：:Inhibitor of secreted frizzled related protein-1 (sFRP-1) would be a novel potential osteogenic agent, since loss of sFRP-1 affects osteoblast proliferation, differentiation, and activity, resulting in improved bone mineral density, quality, and strength. We have identified small molecule diarylsulfone sulfonamide der...

journal_title：Journal of medicinal chemistry

authors： Gopalsamy A,Shi M,Stauffer B,Bahat R,Billiard J,Ponce-de-Leon H,Seestaller-Wehr L,Fukayama S,Mangine A,Moran R,Krishnamurthy G,Bodine P

更新日期：2008-12-25 00:00:00

abstract：:We have previously reported that compounds dimethyl-substituted on the phenyl ring of N-n-propyl-3-phenylpiperidines (PPEs) have a high (nM) affinity and selectivity toward the D(4) dopamine receptor (D(4) DAR) with m,p-dimethyl PPE (1) having the highest affinity and selectivity. In the present paper we have investig...

journal_title：Journal of medicinal chemistry

authors： Macchia M,Cervetto L,Demontis GC,Longoni B,Minutolo F,Orlandini E,Ortore G,Papi C,Sbrana A,Macchia B

更新日期：2003-01-02 00:00:00

abstract：:The development of novel non-nucleoside inhibitors (NNRTIs) with activity against variants of HIV reverse transcriptase (RT) is crucial for overcoming treatment failure. The NNRTIs bind in an allosteric pocket in RT ∼10 Å away from the active site. Earlier analogues of the catechol diether compound series have picomol...

journal_title：Journal of medicinal chemistry

authors： Frey KM,Puleo DE,Spasov KA,Bollini M,Jorgensen WL,Anderson KS

更新日期：2015-03-26 00:00:00

abstract：:A procedure for analyzing and classifying publicly available crystal structures has been developed. It has been used to identify high-resolution protein-ligand complexes that can be assessed by reconstructing the electron density for the ligand using the deposited structure factors. The complexes have been clustered a...

journal_title：Journal of medicinal chemistry

authors： Hartshorn MJ,Verdonk ML,Chessari G,Brewerton SC,Mooij WT,Mortenson PN,Murray CW

更新日期：2007-02-22 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