Rationally based efficacy tuning of selective dopamine d4 receptor ligands leading to the complete antagonist 2-[4-(4-chlorophenyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine (FAUC 213).

abstract：:A series of base- and amino acid modified analogues of S-aristeromycinyl-L-homocysteine, a carbocyclic nucleoside, were synthesized and evaluated as inhibitors of S-adenosyl-L-methionine-dependent methyltransferases, including catechol O-methyltransferase, phenylethanolamine N-methyltransferase, and histamine N-methyl...

journal_title：Journal of medicinal chemistry

authors： Houston DM,Matuszewska B,Borchardt RT

更新日期：1985-04-01 00:00:00

abstract：:Recent studies have indicated several therapeutic applications for delta opioid agonists and antagonists. To exploit the therapeutic potential of delta opioids developing a structural basis for the activity of ligands at the delta opioid receptor is essential. The conformationally sampled pharmacophore (CSP) method (B...

journal_title：Journal of medicinal chemistry

authors： Bernard D,Coop A,MacKerell AD Jr

更新日期：2007-04-19 00:00:00

abstract：:A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1),...

journal_title：Journal of medicinal chemistry

authors： Asano N,Nishida M,Kato A,Kizu H,Matsui K,Shimada Y,Itoh T,Baba M,Watson AA,Nash RJ,Lilley PM,Watkin DJ,Fleet GW

更新日期：1998-07-02 00:00:00

abstract：:Polycomb Repressive Complex 2 (PRC2) modulates the chromatin structure and transcriptional repression by trimethylation lysine 27 of histone H3 (H3K27me3), a process that necessitates the protein-protein interaction (PPI) between the catalytic subunit EZH2 and EED. Deregulated PRC2 is intimately involved in tumorigene...

journal_title：Journal of medicinal chemistry

authors： Kong X,Chen L,Jiao L,Jiang X,Lian F,Lu J,Zhu K,Du D,Liu J,Ding H,Zhang N,Shen J,Zheng M,Chen K,Liu X,Jiang H,Luo C

更新日期：2014-11-26 00:00:00

abstract：:The nortropane cocaine analogue, 2beta-carbomethoxy-3beta-[4'-((Z)-2-iodoethenyl)phenyl]nortropane (ZIENT), is a high affinity, selective serotonin transporter (SERT) ligand that has shown promise as a SERT imaging agent for single photon computed tomography (SPECT) when labeled with I-123. Synthesis of the labeling p...

journal_title：Journal of medicinal chemistry

authors： Plisson C,Jarkas N,McConathy J,Voll RJ,Votaw J,Williams L,Howell LL,Kilts CD,Goodman MM

更新日期：2006-02-09 00:00:00

abstract：:Several norindenoisoquinolines substituted with methoxy or methylenedioxy groups have been prepared and their anticancer properties evaluated in cancer cell cultures and in topoisomerase I inhibition assays. 2,3-Dimethoxy-8,9-methylenedioxy-11H-indeno[1,2-c]isoquinoline hydrochloride (14) is a strong topoisomerase I i...

journal_title：Journal of medicinal chemistry

authors： Ioanoviciu A,Antony S,Pommier Y,Staker BL,Stewart L,Cushman M

更新日期：2005-07-28 00:00:00

abstract：:A series of 1-imidazolyl(alkyl)-substituted quinoline, isoquinoline, naphthalene, benzo[b]furan, and benzo[b]thiophene derivatives was synthesized as dual inhibitors of thromboxane A(2) synthase (P450 TxA(2)) and aromatase (P450 arom). Dual inhibition of these enzymes could be a novel strategy for the treatment of mam...

journal_title：Journal of medicinal chemistry

authors： Jacobs C,Frotscher M,Dannhardt G,Hartmann RW

更新日期：2000-05-04 00:00:00

abstract：:Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. We previously reported that analogs of 1 with thiophene groups at C-7 retained the Src activity of the parent compound. The corresponding C-7 furan analogs were pre...

journal_title：Journal of medicinal chemistry

authors： Boschelli DH,Wu B,Ye F,Wang Y,Golas JM,Lucas J,Boschelli F

更新日期：2006-12-28 00:00:00

abstract：:We previously reported methylstat as a selective inhibitor of jumonji C domain-containing histone demethylases (JHDMs). Herein, we describe the synthesis of a fluorescent analogue of methylstat and its application as a tracer in fluorescence polarization assays. Using this format, we have evaluated the binding affinit...

journal_title：Journal of medicinal chemistry

authors： Xu W,Podoll JD,Dong X,Tumber A,Oppermann U,Wang X

更新日期：2013-06-27 00:00:00

abstract：:Z-D-Phe-Pro-boroMpg-OPin (9a)1,2 has been shown previously to be a highly specific inhibitor of thrombin in spite of lacking an arginine-like guanidino group at the P1 site. A range of compounds have been synthesized based upon this lead compound, varying the neutral side chain at the P1 site. Of the 20 examples based...

journal_title：Journal of medicinal chemistry

authors： Deadman JJ,Elgendy S,Goodwin CA,Green D,Baban JA,Patel G,Skordalakes E,Chino N,Claeson G,Kakkar VV

更新日期：1995-04-28 00:00:00

abstract：:A variety of N-(aminoalkanoyl)-S-acylcysteamine and N,N'-bis(aminoalkanoyl)cystamine salt derivatives were synthesized. Toxicity and radioprotective activity (as the dose reduction factor DRF) were determined in vivo on mice and compared to WR 2721 and S-acetylcysteamine hydrochloride. One of the most interesting comp...

journal_title：Journal of medicinal chemistry

authors： Oiry J,Pue JY,Imbach JL,Fatome M,Sentenac-Roumanou H,Lion C

更新日期：1986-11-01 00:00:00

abstract：:MMP-12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been observed in the lungs of asthmatic patients. Compound 27 was identified as a potent and selective MMP-12 inhibitor possessing good physicochemical properties. In pharmacological studies, the c...

journal_title：Journal of medicinal chemistry

authors： Li W,Li J,Wu Y,Rancati F,Vallese S,Raveglia L,Wu J,Hotchandani R,Fuller N,Cunningham K,Morgan P,Fish S,Krykbaev R,Xu X,Tam S,Goldman SJ,Abraham W,Williams C,Sypek J,Mansour TS

更新日期：2009-09-10 00:00:00

abstract：:The final stages of polio eradication are proving more difficult than the early phases, and the development of effective drugs and treatments is considered a priority; thus, the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to the identification of compounds 5 a...

journal_title：Journal of medicinal chemistry

authors： Madia VN,Messore A,Pescatori L,Saccoliti F,Tudino V,De Leo A,Scipione L,Fiore L,Rhoden E,Manetti F,Oberste MS,Di Santo R,Costi R

更新日期：2019-01-24 00:00:00

abstract：:A focused library approach identifying novel leads to develop a potent ORL1 antagonist is described. Beginning from a compound identified by random screening, an exploratory library that exhibited a diverse display of pharmacophores was designed. After evaluating ORL1 antagonistic activity, a highly focused library wa...

journal_title：Journal of medicinal chemistry

authors： Goto Y,Arai-Otsuki S,Tachibana Y,Ichikawa D,Ozaki S,Takahashi H,Iwasawa Y,Okamoto O,Okuda S,Ohta H,Sagara T

更新日期：2006-02-09 00:00:00

abstract：:A high-throughput screen at 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhibitor interacts with the catalytic aspartates via bridging...

journal_title：Journal of medicinal chemistry

authors： Barrow JC,Stauffer SR,Rittle KE,Ngo PL,Yang Z,Selnick HG,Graham SL,Munshi S,McGaughey GB,Holloway MK,Simon AJ,Price EA,Sankaranarayanan S,Colussi D,Tugusheva K,Lai MT,Espeseth AS,Xu M,Huang Q,Wolfe A,Pietrak B,Z

更新日期：2008-10-23 00:00:00

abstract：:Structure-activity studies have been performed in an attempt to improve the potency of a novel series of azole-based endothelin-A (ET(A)) selective antagonists. Modifications of the hydrophobic group on the terminal urea produced substantial effects on receptor affinity; in particular, the choice of cyclohexyl- or ary...

journal_title：Journal of medicinal chemistry

authors： von Geldern TW,Kester JA,Bal R,Wu-Wong JR,Chiou W,Dixon DB,Opgenorth TJ

更新日期：1996-02-16 00:00:00

abstract：:Bromodomains (BD) are readers of lysine acetylation marks present in numerous proteins associated with chromatin. Here we describe a dual inhibitor of the bromodomain and PHD finger (BRPF) family member BRPF2 and the TATA box binding protein-associated factors TAF1 and TAF1L. These proteins are found in large chromati...

journal_title：Journal of medicinal chemistry

authors： Bouché L,Christ CD,Siegel S,Fernández-Montalván AE,Holton SJ,Fedorov O,Ter Laak A,Sugawara T,Stöckigt D,Tallant C,Bennett J,Monteiro O,Díaz-Sáez L,Siejka P,Meier J,Pütter V,Weiske J,Müller S,Huber KVM,Hartung IV,H

更新日期：2017-05-11 00:00:00

abstract：:Singlet oxygen can severely damage biological tissue, which is exploited in photodynamic therapy (PDT). In PDT, the effective range is limited by the distribution of the photosensitizer (PS) and the illuminated area. However, no distinction is made between healthy and pathological tissue, which can cause undesired dam...

journal_title：Journal of medicinal chemistry

authors： Radunz S,Wedepohl S,Röhr M,Calderón M,Tschiche HR,Resch-Genger U

更新日期：2020-02-27 00:00:00

abstract：:A series of aryl bicyclic analogs of succinimide and glutarimide was prepared and evaluated for CNS depressant activity. The 8a-aryl-3,4,6,7,8,8a-hexahydro-2H-pyrrolo[2,1-beta][1,3]oxazin-6-ones possessed the best overall spectrum of activity relative to the standard agents glutethimide and phenobarbital. ...

journal_title：Journal of medicinal chemistry

authors： Aeberli P,Gogerty JH,Houlihan WJ,Iorio LC

更新日期：1976-03-01 00:00:00

abstract：:The retinoid 6-[3'-(1-adamantyl)-4'-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN) and its active analogues induce cell-cycle arrest and programmed cell death (apoptosis) in cancer cells independently of retinoic acid receptor (RAR) interaction. Its analogue, (E)-4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-(3'-acetami...

journal_title：Journal of medicinal chemistry

authors： Dawson MI,Harris DL,Liu G,Hobbs PD,Lange CW,Jong L,Bruey-Sedano N,James SY,Zhang XK,Peterson VJ,Leid M,Farhana L,Rishi AK,Fontana JA

更新日期：2004-07-01 00:00:00

abstract：:4,6,6a,7,8,12b-Hexahydroindolo[4,3-ab]phenanthridines ("benzergolines") was the first structural class of potent and selective dopamine D1 agonists lacking a catechol group. In order to determine the enantioselectivity of the 7-methyl derivative in the adenylate cyclase assay, its 5,5a-dihydro precursor was resolved a...

journal_title：Journal of medicinal chemistry

authors： Seiler MP,Floersheim P,Markstein R,Widmer A

更新日期：1993-04-16 00:00:00

abstract：:The coupling of two different pharmacophores, each endowed with different biological properties, afforded the hybrid compound lipocrine (7), whose biological profile was markedly improved relative to those of prototypes tacrine and lipoic acid. Lipocrine is the first compound that inhibits the catalytic activity of AC...

journal_title：Journal of medicinal chemistry

authors： Rosini M,Andrisano V,Bartolini M,Bolognesi ML,Hrelia P,Minarini A,Tarozzi A,Melchiorre C

更新日期：2005-01-27 00:00:00

abstract：:Selective CCK-A agonist activity has been reported to induce satiety in a variety of animals, including man, and thereby suggests a therapeutic role for CCK in the management of obesity. To date, three general classes of CCK-A agonists have been reported, the full-length, sulfated hepta- and hexapeptides, a series of ...

journal_title：Journal of medicinal chemistry

authors： Pierson ME,Comstock JM,Simmons RD,Julien R,Kaiser F,Rosamond JD

更新日期：2000-06-15 00:00:00

abstract：:Compound 2 [4-amino-N-(2,6-dimethylphenyl)benzamide] is an effective anticonvulsant in several animal models. For example, following oral administration to mice, it antagonized maximal electroshock (MES) induced seizures with an ED50 of 1.7 mg/kg. During drug disposition studies with 2, we found that it was rapidly me...

journal_title：Journal of medicinal chemistry

authors： Robertson DW,Leander JD,Lawson R,Beedle EE,Clark CR,Potts BD,Parli CJ

更新日期：1987-10-01 00:00:00

abstract：:Antitumor activity in mice was observed for the oxime of the previously reported ethyl [6-amino-4-[(1-methyl-2-phenyl-2-oxoethyl)amino]-5-nitropyridin -2-yl] carbamate (8) and several related compounds. These compounds are precursors of the active ethyl pyrido[3,4-b]pyrazin-7-ylcarbamates (e.g., 4), which are potent a...

journal_title：Journal of medicinal chemistry

authors： Temple C Jr,Rener GA,Waud WR,Noker PE

更新日期：1992-10-02 00:00:00

abstract：:We disclose optimization efforts based on the novel non-nucleoside adenosine deaminase (ADA) inhibitor, 4 (K(i) = 680 nM). Structure-based drug design utilizing the crystal structure of the 4/ADA complex led to discovery of 5 (K(i) = 11 nM, BA = 30% in rats). Furthermore, from metabolic considerations, we discovered t...

journal_title：Journal of medicinal chemistry

authors： Terasaka T,Okumura H,Tsuji K,Kato T,Nakanishi I,Kinoshita T,Kato Y,Kuno M,Seki N,Naoe Y,Inoue T,Tanaka K,Nakamura K

更新日期：2004-05-20 00:00:00

abstract：:It is well established that intramolecular hydrogen bonding and N-methylation play important roles in the passive permeability of cyclic peptides, but other structural features have been explored less intensively. Recent studies on the oral bioavailability of the cyclic heptapeptide sanguinamide A have raised the ques...

journal_title：Journal of medicinal chemistry

authors： Bockus AT,Schwochert JA,Pye CR,Townsend CE,Sok V,Bednarek MA,Lokey RS

更新日期：2015-09-24 00:00:00

abstract：:We have introduced topographical constraints at the 9 position of a superpotent cyclic alpha-melanotropin analogue, Ac-Nle4-Asp5-His6-DPhe7-Arg8-Trp9-Lys10-NH2, by incorporating a methyl group at the beta-carbon of Trp9. These studies were performed on the Trp side chain pharmacophore to identify the bioactive topogra...

journal_title：Journal of medicinal chemistry

authors： Haskell-Luevano C,Boteju LW,Miwa H,Dickinson C,Gantz I,Yamada T,Hadley ME,Hruby VJ

更新日期：1995-11-10 00:00:00

abstract：:HIV-1 replication has been inhibited by using a compound able to target the human cellular cofactor DEAD-box ATPase DDX3, essential for HIV-1 RNA nuclear export. This compound, identified by means of a computational protocol based on pharmacophoric modeling and molecular docking calculations, represents the first smal...

journal_title：Journal of medicinal chemistry

authors： Maga G,Falchi F,Garbelli A,Belfiore A,Witvrouw M,Manetti F,Botta M

更新日期：2008-11-13 00:00:00

abstract：:A new approach to generating information on ligand receptor interactions within the binding pocket of G protein-coupled receptors has been developed, called Biophysical Mapping (BPM). Starting from a stabilized receptor (StaR), minimally engineered for thermostability, additional single mutations are then added at pos...

journal_title：Journal of medicinal chemistry

authors： Zhukov A,Andrews SP,Errey JC,Robertson N,Tehan B,Mason JS,Marshall FH,Weir M,Congreve M

更新日期：2011-07-14 00:00:00