Design, synthesis and biological evaluation of novel arachidonic acid derivatives as highly potent and selective endocannabinoid transporter inhibitors.

abstract：:Newly synthesized benzamide derivatives were evaluated for their inhibitory activity against histone deacetylase. The structure of these derivatives was unrelated to the known inhibitors, and IC(50) values of the active compounds were in the range of 2-50 microM. Structure-activity relationship on the benzanilide moie...

journal_title：Journal of medicinal chemistry

authors： Suzuki T,Ando T,Tsuchiya K,Fukazawa N,Saito A,Mariko Y,Yamashita T,Nakanishi O

更新日期：1999-07-29 00:00:00

abstract：:Novel lavendamycins including two water soluble derivatives were synthesized via short and efficient methods. Pictet-Spengler condensation of 7-N-acylamino-2-formylquinoline-5,8-diones with tryptophans produced lavendamycin esters or amides 11-17. Lavendamycins 18-21 were obtained, respectively, by further transformat...

journal_title：Journal of medicinal chemistry

authors： Behforouz M,Cai W,Stocksdale MG,Lucas JS,Jung JY,Briere D,Wang A,Katen KS,Behforouz NC

更新日期：2003-12-18 00:00:00

abstract：:A series of new peroxisome proliferator activated receptors (PPARs) chiral ligands have been designed following the accepted three-module structure comprising a polar head, linker, and hydrophobic tail. The majority of the ligands incorporate the oxazolidinone moiety as a novel polar head, and the nature of the hydrop...

journal_title：Journal of medicinal chemistry

authors： Fresno N,Macías-González M,Torres-Zaguirre A,Romero-Cuevas M,Sanz-Camacho P,Elguero J,Pavón FJ,Rodríguez de Fonseca F,Goya P,Pérez-Fernández R

更新日期：2015-08-27 00:00:00

abstract：:Homology modeling of G-protein-coupled seven-transmembrane receptors (GPCRs) remains a challenge despite the increasing number of released GPCR crystal structures. This challenge can be attributed to the low sequence identity and structural diversity of the ligand-binding pocket of GPCRs. We have developed an optimize...

journal_title：Journal of medicinal chemistry

authors： Yoshikawa Y,Oishi S,Kubo T,Tanahara N,Fujii N,Furuya T

更新日期：2013-06-13 00:00:00

abstract：:We here report the synthesis of compounds structurally related to the high-affinity dopamine D(3) receptor ligand N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-methoxy-2-benzofurancarboxamide (1). All compounds were specifically designed as potential PET radioligands for brain D(3) receptors visualization, havin...

journal_title：Journal of medicinal chemistry

authors： Leopoldo M,Lacivita E,De Giorgio P,Colabufo NA,Niso M,Berardi F,Perrone R

更新日期：2006-01-12 00:00:00

abstract：:5'-Deoxy-5-fluorouridine (5'-dFUrd, 1) possesses a significantly higher chemotherapeutic index than other fluoropyrimidines as a result of its being selectivity cleaved in tumors to 5-fluorouracil (FUra) by uridine phosphorylase. Because 1 is a relatively poor substrate for this enzyme, we synthesized a series of 5'-d...

journal_title：Journal of medicinal chemistry

authors： Ajmera S,Danenberg PV

更新日期：1982-08-01 00:00:00

abstract：:Target identification is a high-priority, albeit challenging, aspect of drug discovery. Diazirine-based photoaffinity probes (PAPs) can facilitate the process by covalently capturing transient molecular interactions. This can help identify target proteins and map the ligand's interactome. Diazirine probes have even be...

journal_title：Journal of medicinal chemistry

authors： Hill JR,Robertson AAB

更新日期：2018-08-23 00:00:00

abstract：:Hepatocyte growth factor (HGF) is an important regulator of normal development and homeostasis, and dysregulated signaling through the HGF receptor, Met, contributes to tumorigenesis, tumor progression, and metastasis in numerous human malignancies. The development of selective small-molecule inhibitors of oncogenic t...

journal_title：Journal of medicinal chemistry

authors： Peach ML,Tan N,Choyke SJ,Giubellino A,Athauda G,Burke TR Jr,Nicklaus MC,Bottaro DP

更新日期：2009-02-26 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：:We report herein further insight into the biological activities displayed by a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs). Substitution of the N-hydroxyimide two-metal binding pharmacophore at position 4 by carboxamido side chains was previously shown by us to be fruitful for this scaffold, since strong ...

journal_title：Journal of medicinal chemistry

authors： Suchaud V,Bailly F,Lion C,Calmels C,Andréola ML,Christ F,Debyser Z,Cotelle P

更新日期：2014-06-12 00:00:00

abstract：:Idiopathic pulmonary fibrosis (IPF) is a rare and devastating chronic lung disease of unknown etiology. Despite the approved treatment options nintedanib and pirfenidone, the medical need for a safe and well-tolerated antifibrotic treatment of IPF remains high. The human prostaglandin F receptor (hFP-R) is widely expr...

journal_title：Journal of medicinal chemistry

authors： Beck H,Thaler T,Meibom D,Meininghaus M,Jörißen H,Dietz L,Terjung C,Bairlein M,von Bühler CJ,Anlauf S,Fürstner C,Stellfeld T,Schneider D,Gericke KM,Buyck T,Lovis K,Münster U,Anlahr J,Kersten E,Levilain G,Marossek V

更新日期：2020-10-22 00:00:00

abstract：:The ability to develop a chemical into a drug depends on multiple factors. Beyond potency and selectivity, ADME/PK and the toxicological profile of the compound play a significant role in its evaluation as a candidate for development. Those factors are being brought into bear earlier in the discovery process and even ...

journal_title：Journal of medicinal chemistry

authors： Llorens O,Perez JJ,Villar HO

更新日期：2001-08-16 00:00:00

abstract：:Although there is a significant effort in the design of a selective CDK9/CycT1 inhibitor, no compound has been proven to be a specific inhibitor of this kinase so far. The aim of this research was to develop novel and selective phosphorus containing CDK9/CycT1 inhibitors. Molecules bearing phosphonamidate, phosphonate...

journal_title：Journal of medicinal chemistry

authors： Németh G,Greff Z,Sipos A,Varga Z,Székely R,Sebestyén M,Jászay Z,Béni S,Nemes Z,Pirat JL,Volle JN,Virieux D,Gyuris Á,Kelemenics K,Ay E,Minarovits J,Szathmary S,Kéri G,Orfi L

更新日期：2014-05-22 00:00:00

abstract：:The (E)- and (Z)-m-(trifluoromethyl)-alpha, beta-dimethylcinnamamides and some of their N-alkyl derivatives were prepared and pharmacologically tested as anticonvulsant agents in order to verify if a ring substituent, like the m-CF3 group, different from a halogen but possessing the same electronic effect could lead t...

journal_title：Journal of medicinal chemistry

authors： Balsamo A,Crotti P,Lapucci A,Macchia B,Macchia F,Cuttica A,Passerini N

更新日期：1981-05-01 00:00:00

abstract：:A series of novel thiazolo[4,5- d]pyrimidin-7(6 H)-ones (3aa-3eq) were designed, synthesized, and evaluated as the type I positive allosteric modulators of human α7 nAChR expressed in Xenopus ooctyes by a two-electrode voltage clamp. The structure-activity relationship analysis identified the compound 3ea as a potent ...

journal_title：Journal of medicinal chemistry

authors： Li Y,Sun L,Yang T,Jiao W,Tang J,Huang X,Huang Z,Meng Y,Luo L,Wang X,Bian X,Zhang F,Wang K,Sun Q

更新日期：2019-01-10 00:00:00

abstract：:Conformationally restricted 2'-spironucleosides and their prodrugs were synthesized as potential anti-HCV agents. Although the replicon activity of the new agents containing pyrimidine bases was modest, the triphosphate of a 2'-oxetane cytidine analogue demonstrated potent intrinsic biochemical activity against the NS...

journal_title：Journal of medicinal chemistry

authors： Du J,Chun BK,Mosley RT,Bansal S,Bao H,Espiritu C,Lam AM,Murakami E,Niu C,Micolochick Steuer HM,Furman PA,Sofia MJ

更新日期：2014-03-13 00:00:00

abstract：:Chemical probes are small molecules designed to bind to a specific protein and disrupt the proteins function. Although many inhibitors are reported for human carbonic anhydrase (CA) enzymes, few may be considered useful as chemical probes as they exhibit broad action against the 12 catalytically active CA isozymes. In...

journal_title：Journal of medicinal chemistry

authors： Rankin GM,Vullo D,Supuran CT,Poulsen SA

更新日期：2015-09-24 00:00:00

abstract：:The thioredoxin system plays an important role in cancer cells. Inhibiting thioredoxin reductase (TrxR) has emerged as an effective strategy to selectively target cancer cells. Withangulatin A (WA), a natural product extracted from the whole herb of Physalis angulata L. (Solanaceae), exhibits potent anticancer activit...

journal_title：Journal of medicinal chemistry

authors： Wang C,Li S,Zhao J,Yang H,Yin F,Ding M,Luo J,Wang X,Kong L

更新日期：2020-10-08 00:00:00

abstract：:The preparation of stable complexes between the N7-[2-(2-pyridyl)ethyl] and N7-(2-piperazinylethyl) derivatives of mitomycin C and metal ions such as Cu(II), Zn(II), and Pt(II) was accomplished. Mitomycin C did not form stable complexes, but it rearranged to a mitosene capable of complex formation. Some of these compl...

journal_title：Journal of medicinal chemistry

authors： Iyengar BS,Takahashi T,Remers WA,Bradner WT

更新日期：1986-01-01 00:00:00

abstract：:The N-arginyl derivative of methionine-enkephalin (fragment 60-65 of beta-lipotropin) has been shown to be equiactive with the parent pentapeptide, despite the fact that the tyrosine amino group in this compound has been neutralized by the formation of an amide linkage. A series of N-(amino acid) derivatives of (-)-5,...

journal_title：Journal of medicinal chemistry

authors： Bélanger PC,Scheigetz J,Young RN,Charleson SE,Hudgin RL,Engelhardt EL

更新日期：1981-11-01 00:00:00

abstract：:Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual in...

journal_title：Journal of medicinal chemistry

authors： Helal CJ,Kang Z,Hou X,Pandit J,Chappie TA,Humphrey JM,Marr ES,Fennell KF,Chenard LK,Fox C,Schmidt CJ,Williams RD,Chapin DS,Siuciak J,Lebel L,Menniti F,Cianfrogna J,Fonseca KR,Nelson FR,O'Connor R,MacDougall M,Mc

更新日期：2011-07-14 00:00:00

abstract：:The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions. An alternative mechanistic proposal involving the ionic scission of the peroxide group and consequent generation of a c...

journal_title：Journal of medicinal chemistry

authors： Drew MG,Metcalfe J,Dascombe MJ,Ismail FM

更新日期：2006-10-05 00:00:00

abstract：:This study aims to identify inhibitors that bind at the interface of HIV-1 integrase (IN) and human LEDGF/p75, which represents a novel target for anti-HIV therapy. To date, only a few such inhibitors have been reported. Here structure-based virtual screening was performed to search for the inhibitors from an in-house...

journal_title：Journal of medicinal chemistry

authors： Hu G,Li X,Zhang X,Li Y,Ma L,Yang LM,Liu G,Li W,Huang J,Shen X,Hu L,Zheng YT,Tang Y

更新日期：2012-11-26 00:00:00

abstract：:The endocannabinoid system consists of two cannabinoid receptors (CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes involved in the metabolism of the endocannabinoids, including fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL). In the present study, virtual screening of MGL inhibitor...

journal_title：Journal of medicinal chemistry

authors： Saario SM,Poso A,Juvonen RO,Järvinen T,Salo-Ahen OM

更新日期：2006-07-27 00:00:00

abstract：:Adenosine induces glioma cell proliferation by means of an antiapoptotic effect, which is blocked by cotreatment with selective A(3) AR antagonists. In this study, a novel series of N(2)-substituted pyrazolo[3,4-d]pyrimidines 2a-u was developed as highly potent and selective A(3) AR antagonists. The most performing co...

journal_title：Journal of medicinal chemistry

authors： Taliani S,La Motta C,Mugnaini L,Simorini F,Salerno S,Marini AM,Da Settimo F,Cosconati S,Cosimelli B,Greco G,Limongelli V,Marinelli L,Novellino E,Ciampi O,Daniele S,Trincavelli ML,Martini C

更新日期：2010-05-27 00:00:00

abstract：:Identification of a selective inhibitor for a particular protein kinase without inhibition of other kinases is critical for use as a biological tool or drug. However, this is very difficult because there are hundreds of homologous kinases and their kinase domains including the ATP binding pocket have a common folding ...

journal_title：Journal of medicinal chemistry

authors： Honma T,Yoshizumi T,Hashimoto N,Hayashi K,Kawanishi N,Fukasawa K,Takaki T,Ikeura C,Ikuta M,Suzuki-Takahashi I,Hayama T,Nishimura S,Morishima H

更新日期：2001-12-20 00:00:00

abstract：:Kadsurenone, a specific receptor antagonist of platelet-activating factor (PAF), and its analogues were prepared from derivatives of cinnamyl alcohol and (allyloxy)phenol. Racemic kadsurenone, resolvable by a Chiralpak column at low temperatures, has an IC50 value of 2 X 10(-7) M, which is about 50% of the activity of...

journal_title：Journal of medicinal chemistry

authors： Ponpipom MM,Bugianesi RL,Brooker DR,Yue BZ,Hwang SB,Shen TY

更新日期：1987-01-01 00:00:00

abstract：:New tuftsin/retro-tuftsin conjugates were designed and synthesized using a classical fluorenylmethoxycarbonyl (Fmoc) solid phase procedure. All the peptide conjugates were divided into three series: 1,4-dihydroxyanthraquinone (type A), 1-nitroacridine (type B), and 4-carboxyacridone (type C) derivatives. In type A con...

journal_title：Journal of medicinal chemistry

authors： Kukowska-Kaszuba M,Dzierzbicka K,Serocki M,Skladanowski A

更新日期：2011-04-14 00:00:00

abstract：:A series of cyclic pseudopeptides of the formula cyclo(Leu psi[CH2NH]Xaa-Gln-Trp-Phe-beta Ala), where Xaa represents the residue of an alpha-amino acid, has been synthesized in order to establish the role of the Xaa side chain for tachykinin NK-2 receptor antagonist activity. Syntheses have been carried out in solid p...

journal_title：Journal of medicinal chemistry

authors： Quartara L,Fabbri G,Ricci R,Patacchini R,Pestellini V,Maggi CA,Pavone V,Giachetti A,Arcamone F

更新日期：1994-10-14 00:00:00

abstract：:Several candidate retinoid antagonists were designed on the basis of the ligand superfamily concept and synthesized. Retinoidal activities of these benzimidazole and benzodiazepine derivatives were examined by assay of differentiation-inducing activity on human promyelocytic leukemia cell line HL-60. The parent benzim...

journal_title：Journal of medicinal chemistry

authors： Eyrolles L,Kagechika H,Kawachi E,Fukasawa H,Iijima T,Matsushima Y,Hashimoto Y,Shudo K

更新日期：1994-05-13 00:00:00