Inhibition of human O6-alkylguanine-DNA alkyltransferase and potentiation of the cytotoxicity of chloroethylnitrosourea by 4(6)-(benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues.

abstract：:G-protein-coupled receptor 52 (GPR52) is an orphan Gs-coupled G-protein-coupled receptor. GPR52 inhibits dopamine D2 receptor signaling and activates dopamine D1/N-methyl-d-aspartate receptors via intracellular cAMP accumulation, and therefore, GPR52 agonists may have potential as a novel class of antipsychotics. A se...

journal_title：Journal of medicinal chemistry

authors： Setoh M,Ishii N,Kono M,Miyanohana Y,Shiraishi E,Harasawa T,Ota H,Odani T,Kanzaki N,Aoyama K,Hamada T,Kori M

更新日期：2014-06-26 00:00:00

abstract：:A series of bis(hydroxymethyl)-substituted heterocycles were synthesized and converted to the corresponding bis(methylcarbamate) derivatives. The heterocyclic systems studied were based on 2-phenyl-3-methylfuran (2-4), 1-phenylpyrazole (5-7), 1-phenyl-5-methylpyrazole (9-11), 1-phenyl-5-methylthiophene (13), 1-phenyl-...

journal_title：Journal of medicinal chemistry

authors： Anderson WK,Jones AN

更新日期：1984-12-01 00:00:00

abstract：:The synthesis and matrix metalloproteinase (MMP) inhibitory activity of a series of gamma-keto carboxylic acids are described. Among nine MMP isozymes tested, compound 1j displays selective inhibition of MMP-2, -9, and -12 with IC(50) values between 0.20 and 1.51 microuM, and in male golden Syrian hamsters, it shows p...

journal_title：Journal of medicinal chemistry

authors： Ma D,Jiang Y,Chen F,Gong LK,Ding K,Xu Y,Wang R,Ge A,Ren J,Li J,Li J,Ye Q

更新日期：2006-01-26 00:00:00

abstract：:We have focused on optimization of the inadequate pharmacokinetic profile of trans-4-substituted cyclohexanecarboxylic acid 5, which is commonly observed in many small molecule very late antigen-4 (VLA-4) antagonists. We modified the lipophilic moiety in 5 and found that reducing the polar surface area of this moiety ...

journal_title：Journal of medicinal chemistry

authors： Muro F,Iimura S,Sugimoto Y,Yoneda Y,Chiba J,Watanabe T,Setoguchi M,Iigou Y,Matsumoto K,Satoh A,Takayama G,Taira T,Yokoyama M,Takashi T,Nakayama A,Machinaga N

更新日期：2009-12-24 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：:Caveolin-1 is a target for academic and pharmaceutical research due to its many cellular roles and associated diseases. We report peptide WL47 (1), a small, high-affinity, selective disrupter of caveolin-1 oligomers. Developed and optimized through screening and analysis of synthetic peptide libraries, ligand 1 has 75...

journal_title：Journal of medicinal chemistry

authors： Gilliam AJ,Smith JN,Flather D,Johnston KM,Gansmiller AM,Fishman DA,Edgar JM,Balk M,Majumdar S,Weiss GA

更新日期：2016-04-28 00:00:00

abstract：:A small series of compounds is described in which a narrow SAR has identified N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine, 3, as a potential antidepressant with reduced side effects. The isomeric N,N-dimethyl-4,5-diphenyl-1H-pyrazole-1-propanamine was completely inactive in the primary antidepressant screens. ...

journal_title：Journal of medicinal chemistry

authors： Bailey DM,Hansen PE,Hlavac AG,Baizman ER,Pearl J,DeFelice AF,Feigenson ME

更新日期：1985-02-01 00:00:00

abstract：:We previously reported that substrates of semicarbazide-sensitive amine oxidase in combination with low concentrations of vanadate exert potent insulin-like effects. Here we performed homology modeling of the catalytic domain of mouse SSAO/VAP-1 and searched through chemical databases to identify novel SSAO substrates...

journal_title：Journal of medicinal chemistry

authors： Marti L,Abella A,De La Cruz X,García-Vicente S,Unzeta M,Carpéné C,Palacín M,Testar X,Orozco M,Zorzano A

更新日期：2004-09-23 00:00:00

abstract：:Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD) by genome-wide association studies (GWAS). The most common LRRK2 mutation, G2019S, which is relatively rare in the total population, gives rise to increased kinase activity. As such, LRRK2 kinase inhibitors are potentially use...

journal_title：Journal of medicinal chemistry

authors： Henderson JL,Kormos BL,Hayward MM,Coffman KJ,Jasti J,Kurumbail RG,Wager TT,Verhoest PR,Noell GS,Chen Y,Needle E,Berger Z,Steyn SJ,Houle C,Hirst WD,Galatsis P

更新日期：2015-01-08 00:00:00

abstract：:Three series of H(4) receptor ligands, derived from indoly-2-yl-(4-methyl-piperazin-1-yl)-methanones, have been synthesized and their structure-activity relationships evaluated for activity at the H(4) receptor in competitive binding and functional assays. In all cases, substitution of small lipophilic groups in the 4...

journal_title：Journal of medicinal chemistry

authors： Venable JD,Cai H,Chai W,Dvorak CA,Grice CA,Jablonowski JA,Shah CR,Kwok AK,Ly KS,Pio B,Wei J,Desai PJ,Jiang W,Nguyen S,Ling P,Wilson SJ,Dunford PJ,Thurmond RL,Lovenberg TW,Karlsson L,Carruthers NI,Edwards JP

更新日期：2005-12-29 00:00:00

abstract：:Truncated N(6)-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels with corresponding 4'-thioadenosines. Hydrophobic N(6) and/or C2 substituents were tolerated in A3AR binding, but only an unsubstituted 6-amino group with a C2-hexynyl group promoted high...

journal_title：Journal of medicinal chemistry

authors： Nayak A,Chandra G,Hwang I,Kim K,Hou X,Kim HO,Sahu PK,Roy KK,Yoo J,Lee Y,Cui M,Choi S,Moss SM,Phan K,Gao ZG,Ha H,Jacobson KA,Jeong LS

更新日期：2014-02-27 00:00:00

abstract：:The synthesis and gastric antisecretory activities of the delta 4,5-cis, delta 4,5-trans, and 4,5-acetylenic analogues of 15-deoxy-16-hydroxy-16-methyl prostaglandin E1 methyl ester are described. The key step in the preparation of these compounds involved the stereospecific conjugate addition of a cuprate reagent to ...

journal_title：Journal of medicinal chemistry

authors： Collins PW,Dajani EZ,Pappo R,Gasiecki AF,Bianchi RG,Woods EM

更新日期：1983-06-01 00:00:00

abstract：:Protein disulfide isomerase (PDI) is responsible for nascent protein folding in the endoplasmic reticulum (ER) and is critical for glioblastoma survival. To improve the potency of lead PDI inhibitor BAP2 (( E)-3-(3-(4-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzonitrile), we designed and synthesized 67 analogues. We determ...

journal_title：Journal of medicinal chemistry

authors： Yang S,Shergalis A,Lu D,Kyani A,Liu Z,Ljungman M,Neamati N

更新日期：2019-04-11 00:00:00

abstract：:The response profiles of 36 para-substituted diphenylethylenes (DPEs) and triphenylacrylonitriles (TPEs) have been compared by multivariate analysis. The responses measured were (a) relative binding affinity (RBA) for the cytosol estrogen receptor (ER), (b) ability to promote the growth of the human MCF7 breast cancer...

journal_title：Journal of medicinal chemistry

authors： Doré JC,Gilbert J,Bignon E,Crastes de Paulet A,Ojasoo T,Pons M,Raynaud JP,Miquel JF

更新日期：1992-02-07 00:00:00

abstract：:A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. On the basis of computational docking combined to in vitro sirtuin 1/2 inhibition assays, ...

journal_title：Journal of medicinal chemistry

authors： Schnekenburger M,Goffin E,Lee JY,Jang JY,Mazumder A,Ji S,Rogister B,Bouider N,Lefranc F,Miklos W,Mathieu V,de Tullio P,Kim KW,Dicato M,Berger W,Han BW,Kiss R,Pirotte B,Diederich M

更新日期：2017-06-08 00:00:00

abstract：:Sildenafil (5-[2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one), a potent and selective phosphodiesterase type 5 (PDE5) inhibitor, provided the first oral treatment for male erectile dysfunction. The objective of the work reported in this paper was t...

journal_title：Journal of medicinal chemistry

authors： Allerton CM,Barber CG,Beaumont KC,Brown DG,Cole SM,Ellis D,Lane CA,Maw GN,Mount NM,Rawson DJ,Robinson CM,Street SD,Summerhill NW

更新日期：2006-06-15 00:00:00

abstract：:In the past few years sirtuins have gained growing attention for their involvement in many biological processes such as cellular metabolism, apoptosis, aging and inflammation. In this contribution, we report the synthesis of a library of thioacetylated pseudopeptides that were screened against human sirtuins 1-3 to re...

journal_title：Journal of medicinal chemistry

authors： Mellini P,Kokkola T,Suuronen T,Salo HS,Tolvanen L,Mai A,Lahtela-Kakkonen M,Jarho EM

更新日期：2013-09-12 00:00:00

abstract：:We report here the optimization of an HldE kinase inhibitor to low nanomolar potency, which resulted in the identification of the first reported compounds active on selected E. coli strains. One of the most interesting candidates, compound 86, was shown to inhibit specifically bacterial LPS heptosylation on efflux pum...

journal_title：Journal of medicinal chemistry

authors： Desroy N,Denis A,Oliveira C,Atamanyuk D,Briet S,Faivre F,LeFralliec G,Bonvin Y,Oxoby M,Escaich S,Floquet S,Drocourt E,Vongsouthi V,Durant L,Moreau F,Verhey TB,Lee TW,Junop MS,Gerusz V

更新日期：2013-02-28 00:00:00

abstract：:N-Benzoyl-DL-phenylalanine (1) was found to possess hypoglycemic activity. A series of the analogues of compound 1 were prepared and evaluated for their blood glucose lowering activity. Both the steric effects of the phenylalanine moiety and the effects of variations in the acyl moiety were investigated. This study el...

journal_title：Journal of medicinal chemistry

authors： Shinkai H,Toi K,Kumashiro I,Seto Y,Fukuma M,Dan K,Toyoshima S

更新日期：1988-11-01 00:00:00

abstract：:Building on the previously and successfully applied hypothesis that stereochemical complication in the proximity of the critical cationic head of a cholinergic agonist would result in subtype selective compounds, we synthesized a series of chiral derivatives of furmethide and 5-methylfurmethide, with the aim of obtain...

journal_title：Journal of medicinal chemistry

authors： Scapecchi S,Nesi M,Matucci R,Bellucci C,Buccioni M,Dei S,Guandalini L,Manetti D,Martini E,Marucci G,Romanelli MN,Teodori E,Cirilli R

更新日期：2008-07-10 00:00:00

abstract：:Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]p...

journal_title：Journal of medicinal chemistry

authors： Ryu H,Jin MK,Kim SY,Choi HK,Kang SU,Kang DW,Lee J,Pearce LV,Pavlyukovets VA,Morgan MA,Tran R,Toth A,Lundberg DJ,Blumberg PM

更新日期：2008-01-10 00:00:00

abstract：:Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved select...

journal_title：Journal of medicinal chemistry

authors： Yang X,Shi Q,Yang SC,Chen CY,Yu SL,Bastow KF,Morris-Natschke SL,Wu PC,Lai CY,Wu TS,Pan SL,Teng CM,Lin JC,Yang PC,Lee KH

更新日期：2011-07-28 00:00:00

abstract：:A series of C7-O- and C20-O-amidated 2,3-dehydrosilybin (DHS) derivatives ((+/-)-1a-f and (+/-)-2), as well as a set of alkenylated DHS analogues ((+/-)-4a-f), were designed and de novo synthesized. A diesteric derivative of DHS ((+/-)-3) and two C23 esterified DHS analogues ((+/-)-5a and (+/-)-5b) were also prepared ...

journal_title：Journal of medicinal chemistry

authors： Yang LX,Huang KX,Li HB,Gong JX,Wang F,Feng YB,Tao QF,Wu YH,Li XK,Wu XM,Zeng S,Spencer S,Zhao Y,Qu J

更新日期：2009-12-10 00:00:00

abstract：:There is reported the first four members of heteroarotinoids, the names of which are ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate (1b), ethyl (E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoate (1c), ethyl (E)-p-[2-(4,4-dimethyl-1-oxothiochroman-6-yl)propenyl]benzoate (1d), and (E)-p-[2-(4,4-dimethy...

journal_title：Journal of medicinal chemistry

authors： Waugh KM,Berlin KD,Ford WT,Holt EM,Carrol JP,Schomber PR,Thompson MD,Schiff LJ

更新日期：1985-01-01 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 synthesis and biological activity of tetrahydronaphthalene derivatives coupled to various heterocycles are described. These compounds are potent glucocorticoid receptor agonists with efficacy selectivity in an NFkappaB glucocorticoid receptor (GR) agonist assay (representing transrepression effects) over an MMTV G...

journal_title：Journal of medicinal chemistry

authors： Biggadike K,Boudjelal M,Clackers M,Coe DM,Demaine DA,Hardy GW,Humphreys D,Inglis GG,Johnston MJ,Jones HT,House D,Loiseau R,Needham D,Skone PA,Uings I,Veitch G,Weingarten GG,McLay IM,Macdonald SJ

更新日期：2007-12-27 00:00:00

abstract：:We have previously shown [Cys-Trp-Arg-Nva-Arg-Tyr-NH(2)](2), 1, to be a moderately selective neuropeptide Y (NPY) Y(4) receptor agonist. Toward improving the selectivity and potency for Y(4) receptors, we studied the effects of dimerizing H-Trp-Arg-Nva-Arg-Tyr-NH(2) using various diamino-dicarboxylic acids containing ...

journal_title：Journal of medicinal chemistry

authors： Balasubramaniam A,Mullins DE,Lin S,Zhai W,Tao Z,Dhawan VC,Guzzi M,Knittel JJ,Slack K,Herzog H,Parker EM

更新日期：2006-04-20 00:00:00

abstract：:1-(Benzoyloxy), 1-(4-nitrobenzoyloxy), and 1-(3,5-dinitrobenzoyloxy) derivatives of 3-fluoro-, 3-chloro-, and 3-bromopropan-2-one were prepared by oxidation of the 1-benzoyloxy-3-halopropan-2-ols in turn prepared from the appropriate benzoyl chloride and 3-halo-1,2-propanediols, 1-Benzoyloxy-3-fluoropropan-2-one was a...

journal_title：Journal of medicinal chemistry

authors： Pero RW,Babiarz-Tracy P,Fondy TP

更新日期：1977-05-01 00:00:00

abstract：:Compounds acting via the neurotensin receptor type 2 (NTS2) are known to be active in animal models of acute and chronic pain. To identify novel NTS2 selective analgesics, we searched for NTS2 selective nonpeptide compounds using a FLIPR assay and identified the title compound (NTRC-824, 5) that, to our knowledge, is ...

journal_title：Journal of medicinal chemistry

authors： Thomas JB,Giddings AM,Wiethe RW,Olepu S,Warner KR,Sarret P,Gendron L,Longpre JM,Zhang Y,Runyon SP,Gilmour BP

更新日期：2014-09-11 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