Syntheses and in vitro evaluation of water-soluble "cationic metalloporphyrin-ellipticine" molecules having a high affinity for DNA.

abstract：:The family of homodimeric nitric oxide synthases (NOS I-III) catalyzes the generation of the cellular messenger nitric oxide (NO) by oxidation of the substrate L-arginine. The rational design of specific NOS inhibitors is of therapeutic interest in regulating pathological NO levels associated with sepsis, inflammatory...

journal_title：Journal of medicinal chemistry

authors： Matter H,Kotsonis P,Klingler O,Strobel H,Fröhlich LG,Frey A,Pfleiderer W,Schmidt HH

更新日期：2002-07-04 00:00:00

abstract：:In the course of studies on tranquilizers, new non-benzodiazepine-like compounds were synthesized. These are 1-(3,4,5-trimethoxyphenoxy)-3-[4-(2-methoxyphenyl)piperazinyl]prop an-2-ol (INN: enciprazine) and derivatives thereof which were screened pharmacologically in order to evaluate their central nervous system acti...

journal_title：Journal of medicinal chemistry

authors： Engel J,Fleischhauer I,Jakovlev V,Kleemann A,Kutscher B,Nickel B,Rauer H,Werner U,Szelenyi I,Johanson CE

更新日期：1990-11-01 00:00:00

abstract：:The modulation of the endocannabinoid system is emerging as a viable avenue for the treatment of neurodegeneration, being involved in neuroprotective and anti-inflammatory processes. In particular, indirectly enhancing endocannabinoid signaling to therapeutic levels through FAAH inhibition might be beneficial for neur...

journal_title：Journal of medicinal chemistry

authors： Montanari S,Scalvini L,Bartolini M,Belluti F,Gobbi S,Andrisano V,Ligresti A,Di Marzo V,Rivara S,Mor M,Bisi A,Rampa A

更新日期：2016-07-14 00:00:00

abstract：:4-(Dimethylamino)- and 4-(methylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives were prepared as analogues of previously reported 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Metalation of benzanilide with n-butyllithium, addition of 4-(dimethylamino)cyclohexanone, and acidification afforded a...

journal_title：Journal of medicinal chemistry

authors： Martin LL,Worm M,Agnew MN,Kruse H,Wilker JC,Geyer HM 3rd

更新日期：1981-05-01 00:00:00

abstract：:The importance of inhibitors of glycosidases as therapeutic agents for viral, proliferative, and metabolic diseases is being increasingly recognised. Several years ago we reported that the activities of mannosidase inhibitors may be explained in terms of their similarity to the mannosyl cation intermediate postulated ...

journal_title：Journal of medicinal chemistry

authors： Winkler DA

更新日期：1996-10-11 00:00:00

abstract：:A set of 2,4-diamino-5-(3-X-phenyl)-s-triazines was used to inhibit the growth of tumor cells (L5178 leukemia) in culture. The molar concentration (C) of triazine causing 50% reduction in the rate of cell growth was used to develop a quantitative structure-activity relationship: log 1/C = 1.32 pi - 1.70 log (beta.10 p...

journal_title：Journal of medicinal chemistry

authors： Khwaja TA,Pentecost S,Selassie CD,Guo Z,Hansch C

更新日期：1982-02-01 00:00:00

abstract：:The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. Because of its high expression on the surface of melanomas, MC1R has been investigated as a target for selective imaging and therapeutic agents against melanoma. Eight ligands were screened against cell lines engin...

journal_title：Journal of medicinal chemistry

authors： Barkey NM,Tafreshi NK,Josan JS,De Silva CR,Sill KN,Hruby VJ,Gillies RJ,Morse DL,Vagner J

更新日期：2011-12-08 00:00:00

abstract：:Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce...

journal_title：Journal of medicinal chemistry

authors： Khanna S,Sobhia ME,Bharatam PV

更新日期：2005-04-21 00:00:00

abstract：:We report two crystal structures of the PARP domain of human tankyrase-2 (TNKS2). Tankyrases are involved in fundamental cellular processes such as telomere homeostasis and Wnt signaling. The complex of TNKS2 with the potent inhibitor XAV939 provides insights into the molecular basis of the strong interaction and sugg...

journal_title：Journal of medicinal chemistry

authors： Karlberg T,Markova N,Johansson I,Hammarström M,Schütz P,Weigelt J,Schüler H

更新日期：2010-07-22 00:00:00

abstract：:As part of a program aimed at the discovery of antinociceptive therapy for inflammatory conditions, a screening hit was found to inhibit microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 17.4 μM. Structural information was used to improve enzyme potency by over 1000-fold. Addition of an appropriate subst...

journal_title：Journal of medicinal chemistry

authors： Schiffler MA,Antonysamy S,Bhattachar SN,Campanale KM,Chandrasekhar S,Condon B,Desai PV,Fisher MJ,Groshong C,Harvey A,Hickey MJ,Hughes NE,Jones SA,Kim EJ,Kuklish SL,Luz JG,Norman BH,Rathmell RE,Rizzo JR,Seng TW,Thi

更新日期：2016-01-14 00:00:00

abstract：:It is now plausible to dock libraries of 10 million molecules against targets over several days or weeks. When the molecules screened are commercially available, they may be rapidly tested to find new leads. Although docking retains important liabilities (it cannot calculate affinities accurately nor even reliably ran...

journal_title：Journal of medicinal chemistry

authors： Irwin JJ,Shoichet BK

更新日期：2016-05-12 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：:Amantadine inhibits the M2 proton channel of influenza A virus, yet its clinical use has been limited by the rapid emergence of amantadine-resistant virus strains. We have synthesized and characterized a series of polycyclic compounds designed as ring-contracted or ring-expanded analogues of amantadine. Inhibition of ...

journal_title：Journal of medicinal chemistry

authors： Duque MD,Ma C,Torres E,Wang J,Naesens L,Juárez-Jiménez J,Camps P,Luque FJ,DeGrado WF,Lamb RA,Pinto LH,Vázquez S

更新日期：2011-04-28 00:00:00

abstract：:Regioisomeric 3-carboxyisoxazolinyl prolines [CIP-A (+/-)-6 and CIP-B (+/-)-7] and 3-hydroxyisoxazolinyl prolines [(+/-)-8 and (+/-)-9] were synthesized and assayed for glutamate receptor activity. The tests were carried out in vitro by means of receptor binding techniques, second messenger assays, and the rat cortica...

journal_title：Journal of medicinal chemistry

authors： Conti P,De Amici M,De Sarro G,Rizzo M,Stensbøl TB,Bräuner-Osborne H,Madsen U,Toma L,De Micheli C

更新日期：1999-10-07 00:00:00

abstract：:A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands were designed and synthesized. Variation of phenyl substitutions at the P2 and P2' moieties significantly affected the binding affinity and antiviral potency of the inhibitors. In general, compounds w...

journal_title：Journal of medicinal chemistry

authors： Ali A,Reddy GS,Nalam MN,Anjum SG,Cao H,Schiffer CA,Rana TM

更新日期：2010-11-11 00:00:00

abstract：:N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both P...

journal_title：Journal of medicinal chemistry

authors： Rackham MD,Brannigan JA,Rangachari K,Meister S,Wilkinson AJ,Holder AA,Leatherbarrow RJ,Tate EW

更新日期：2014-03-27 00:00:00

abstract：:Iodonium ion mediated cyclization of unsaturated hydroperoxides 1 afforded the expected yingzhaosu A analogues 2. In some cases, however, the corresponding cyclic ethers 5 were formed competitively with the cyclic peroxides 2, the ratios of these two products being a marked function of the structure of the starting ma...

journal_title：Journal of medicinal chemistry

authors： Kim HS,Begum K,Ogura N,Wataya Y,Tokuyasu T,Masuyama A,Nojima M,McCullough KJ

更新日期：2002-10-10 00:00:00

abstract：:Four new hybrid analogues of 1alpha,25-dihydroxyvitamin D3 (1) have been synthesized in a convergent manner by joining A-ring and C, D-ring fragments. Each hybrid analogue, having a noncalcemic 1-hydroxymethyl group and a potentiating 16-ene 24,24-difluorinated C,D-ring side chain, was designed to be lipophilic and in...

journal_title：Journal of medicinal chemistry

authors： Posner GH,Lee JK,Wang Q,Peleg S,Burke M,Brem H,Dolan P,Kensler TW

更新日期：1998-07-30 00:00:00

abstract：:In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release ...

journal_title：Journal of medicinal chemistry

authors： Buckle DR,Outred DJ,Smith H,Spicer BA

更新日期：1984-11-01 00:00:00

abstract：:The CXC chemokine receptor 7 (CXCR7)/ACKR3 is a chemokine receptor that recognizes stromal cell-derived factor 1 (SDF-1)/CXCL12 and interferon-inducible T-cell α chemoattractant (I-TAC)/CXCL11. Here, we report the development of novel CXCR7-selective ligands with a cyclic pentapeptide scaffold through an SAR study of ...

journal_title：Journal of medicinal chemistry

authors： Oishi S,Kuroyanagi T,Kubo T,Montpas N,Yoshikawa Y,Misu R,Kobayashi Y,Ohno H,Heveker N,Furuya T,Fujii N

更新日期：2015-07-09 00:00:00

abstract：:Sulbactam (1) is a beta-lactamase inhibitor with limited oral bioavailability. Lipophilic double-ester prodrug sulbactam pivoxil (2) significantly improves the oral absorption of sulbactam, as does the mutual prodrug double ester sultamicillin (3). We have found that double-ester prodrugs of sulbactam terminating in a...

journal_title：Journal of medicinal chemistry

authors： English AR,Girard D,Jasys VJ,Martingano RJ,Kellogg MS

更新日期：1990-01-01 00:00:00

abstract：:The olefinic dipeptide 5(S)-amino-7-methyl-3(E)-octenoic acid (1) was synthesized and used to make the olefinic peptides Leu psi [E-CH = CH]Gly-Val-Phe-OCH3 (2) and His-Leu psi [E-CH = CH]Gly-Val-Phe-OCH3 (3). These olefinic peptides were found to exhibit renin inhibitory activity against both hog kidney renin and hum...

journal_title：Journal of medicinal chemistry

authors： Johnson RL

更新日期：1984-10-01 00:00:00

abstract：:A new approach to rapidly score protein-ligand interactions is tested on several protein-ligand systems. Results using this approach - the OWFEG free energy grid - are quite promising and are generally in better agreement with experiment (in some cases much better) than those obtained employing scoring techniques curr...

journal_title：Journal of medicinal chemistry

authors： Pearlman DA,Charifson PS

更新日期：2001-02-15 00:00:00

abstract：:N,N-Dialkylated leucine enkephalin analogues containing melphalan (Mel) in place of Phe4 were synthesized as potentially irreversible antagonists of the delta opioid receptor. These compounds, along with the corresponding Phe4 peptides, were tested for both agonist and antagonist activity in the GPI and MVD smooth mus...

journal_title：Journal of medicinal chemistry

authors： Lovett JA,Portoghese PS

更新日期：1987-09-01 00:00:00

abstract：:Since the discovery of the serotonin 4 receptor (5-HT(4)R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4-piperidinyl)methyl]-1H-indazol...

journal_title：Journal of medicinal chemistry

authors： Furlotti G,Alisi MA,Apicella C,Capezzone de Joannon A,Cazzolla N,Costi R,Cuzzucoli Crucitti G,Garrone B,Iacovo A,Magarò G,Mangano G,Miele G,Ombrato R,Pescatori L,Polenzani L,Rosi F,Vitiello M,Di Santo R

更新日期：2012-11-26 00:00:00

abstract：:Chemical probes of microRNA (miRNA) function are potential tools for understanding miRNA biology that also provide new approaches for discovering therapeutics for miRNA-associated diseases. MicroRNA-21 (miR-21) is an oncogenic miRNA that is overexpressed in most cancers and has been strongly associated with driving ch...

journal_title：Journal of medicinal chemistry

authors： Naro Y,Ankenbruck N,Thomas M,Tivon Y,Connelly CM,Gardner L,Deiters A

更新日期：2018-07-26 00:00:00

abstract：:The need for a readily available Gd(III) bifunctional chelate for protein conjugation has led to the development of LDTPA (N,N-bis[2-[N',N'-bis(carboxymethyl)amino]- ethyl]-4-amino-L-phenyl-alanine). The benzylamine group is readily converted to the isothiocyanato group (SCN-LDTPA) by treatment of the lithium salt of ...

journal_title：Journal of medicinal chemistry

authors： Deal KA,Motekaitis RJ,Martell AE,Welch MJ

更新日期：1996-08-02 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：:We have rationally designed a sLe(x) mimetic based on molecular modeling, synthesized type II and type II' beta-turn dipeptides (3a,b), and evaluated their biological profiles both in vitro and in vivo. Against E-selectin-sLe(x) binding, the type II beta-turn dipeptide L-Ser-D-Glu 3a (IC50, 13 microM) and the type II'...

journal_title：Journal of medicinal chemistry

authors： Tsukida T,Hiramatsu Y,Tsujishita H,Kiyoi T,Yoshida M,Kurokawa K,Moriyama H,Ohmoto H,Wada Y,Saito T,Kondo H

更新日期：1997-10-24 00:00:00

abstract：:CC chemokine receptors 2 (CCR2) and 5 (CCR5) are involved in many inflammatory diseases; however, most CCR2 and CCR5 clinical candidates have been unsuccessful. (Pre)clinical evidence suggests that dual CCR2/CCR5 inhibition might be more effective in the treatment of such multifactorial diseases. In this regard, the h...

journal_title：Journal of medicinal chemistry

authors： Ortiz Zacarías NV,van Veldhoven JPD,den Hollander LS,Dogan B,Openy J,Hsiao YY,Lenselink EB,Heitman LH,IJzerman AP

更新日期：2019-12-26 00:00:00