Identification of novel farnesyl protein transferase inhibitors using three-dimensional database searching methods.

abstract：:The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction...

journal_title：Journal of medicinal chemistry

authors： Green J,Cao J,Bandarage UK,Gao H,Court J,Marhefka C,Jacobs M,Taslimi P,Newsome D,Nakayama T,Shah S,Rodems S

更新日期：2015-06-25 00:00:00

abstract：:Plasmodium falciparum lactate dehydrogenase (pfLDH) is a key enzyme for energy generation of malarial parasites and is a potential antimalarial chemotherapeutic target. It is known that the oxamate moiety, a pyruvate analog, alone shows higher inhibition against pfLDH than human LDHs, suggesting that it can be used fo...

journal_title：Journal of medicinal chemistry

authors： Choi SR,Pradhan A,Hammond NL,Chittiboyina AG,Tekwani BL,Avery MA

更新日期：2007-08-09 00:00:00

abstract：:Appropriately protected nucleoside 5'-O-(2-thio-1,3,2-dithiaphospholanes) react with inorganic pyrophosphate in the presence of a strong base catalyst (DBU) to give nucleoside 5'-O-(1,1-dithiotriphosphates) 1a-g. The latter compounds, including an AZT analogue, show modest antivirial activity against HIV-1 and HIV-2 r...

journal_title：Journal of medicinal chemistry

authors： Okruszek A,Olesiak M,Balzarini J

更新日期：1994-10-28 00:00:00

abstract：:The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride...

journal_title：Journal of medicinal chemistry

authors： Bamford MJ,Coe PL,Walker RT

更新日期：1990-09-01 00:00:00

abstract：:The discovery and structure-activity relationship of first-generation small-molecule malonyl-CoA decarboxylase (MCD; CoA = coenzyme A) inhibitors are reported. We demonstrated that MCD inhibitors increased malonyl-CoA concentration in the isolated working rat hearts. Malonyl-CoA is a potent, endogenous, and allosteric...

journal_title：Journal of medicinal chemistry

authors： Cheng JF,Chen M,Wallace D,Tith S,Haramura M,Liu B,Mak CC,Arrhenius T,Reily S,Brown S,Thorn V,Harmon C,Barr R,Dyck JR,Lopaschuk GD,Nadzan AM

更新日期：2006-03-09 00:00:00

abstract：:The Keap1 (Kelch-like ECH-associated protein 1)-Nrf2 (nuclear factor erythroid 2-related factor 2)-ARE (antioxidant response element) pathway is the major defending mechanism against oxidative stresses, and directly disrupting the Keap1-Nrf2 protein-protein interaction (PPI) has been an attractive strategy to target o...

journal_title：Journal of medicinal chemistry

authors： Zhou HS,Hu LB,Zhang H,Shan WX,Wang Y,Li X,Liu T,Zhao J,You QD,Jiang ZY

更新日期：2020-10-08 00:00:00

abstract：:The N-demethylation of 1-(N-methyl-N-trideuteriomethylamino)-3-phenylpropane (1) by rodent liver homogenates was studied. The ratio of 1-trideuteriomethylamino-3-phenylpropane (2)/1-methylamino-3-phenylpropane (3) was determined by gc-ms. The ratio of 2/3 in the product of N-demethylation of 1 by liver homogenate from...

journal_title：Journal of medicinal chemistry

authors： Abdel-Monem MM

更新日期：1975-04-01 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：:The diphenylsulfonyl sulfonamide scaffold represented by 1 (WAY-316606) are small molecule inhibitors of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic agents for the treatment of osteoporosis or other bone-related di...

journal_title：Journal of medicinal chemistry

authors： Moore WJ,Kern JC,Bhat R,Commons TJ,Fukayama S,Goljer I,Krishnamurthy G,Magolda RL,Nogle L,Pitts K,Stauffer B,Trybulski EJ,Welmaker GS,Wilson M,Bodine PV

更新日期：2009-01-08 00:00:00

abstract：:A series of cis- and trans-dihydroxycotahydrobenzo[f]quinoline congeners of dopamine has been prepared, in which the N substitutent is H, ethyl, or n-propyl. The trans isomers include the dopamine moiety held rigidly in an antiperiplanar diposition which is believed to be necessary for certian central and peripheral d...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Suarez-Gutierrez C,Lee T,Long JP,Costall B,Fortune DH,Naylor RJ

更新日期：1979-04-01 00:00:00

abstract：:A molecular model of the alpha3beta2 nAChR lumen channel was constructed and hydrophobic clefts were observed near the receptor gate. Docking simulations indicated that ligand-nAChR complexes were formed by hydrophobic interactions with the cleft and hydrogen bond interactions. The equilibrium constants and associatio...

journal_title：Journal of medicinal chemistry

authors： Jozwiak K,Ravichandran S,Collins JR,Moaddel R,Wainer IW

更新日期：2007-11-29 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：:A series of 1-(p-nitrophenyl)-2-aminoethanol derivatives and their morpholine analogues have been synthesized and pharmacologically investigated in order to confirm some pharmacological observations made with the N-isopropyl-substituted compounds. In agreement with the previously obtained results, the weak alpha-adren...

journal_title：Journal of medicinal chemistry

authors： Balsamo A,Crotti P,Lapucci A,Macchia B,Macchia F,Del Tacca M,Mazzanti L,Ceserani R

更新日期：1979-06-01 00:00:00

abstract：:A series of 3-(4-phenoxyphenyl)-1H-pyrazoles were synthesized and characterized as potent state-dependent sodium channel blockers. A limited SAR study was carried out to delineate the chemical requirements for potency. The results indicate that the distal phenyl group is critical for activity but will tolerate lipophi...

journal_title：Journal of medicinal chemistry

authors： Yang J,Gharagozloo P,Yao J,Ilyin VI,Carter RB,Nguyen P,Robledo S,Woodward RM,Hogenkamp DJ

更新日期：2004-03-11 00:00:00

abstract：:The ability of a series of substituted kynurenic acids, thienopyridinonecarboxylic acids, and related compounds to inhibit the binding of nerve growth factor (NGF) to the p75 NGF receptor (NGFR) was evaluated in a radioligand binding assay that utilized a biotinylated derivative of the extracellular domain of p75 NGFR...

journal_title：Journal of medicinal chemistry

authors： Jaen JC,Laborde E,Bucsh RA,Caprathe BW,Sorenson RJ,Fergus J,Spiegel K,Marks J,Dickerson MR,Davis RE

更新日期：1995-10-27 00:00:00

abstract：:A series of analogues of 4,5-bis(((N-methylcarbamoyl)oxy)methyl)-1-methyl-2-(methylthio)-im idazole (1, carmethizole) were synthesized. The chemical reactivities of the analogues (as electrophiles) were evaluated and related to the antitumor activity (in vivo and in vitro). Changes in the alkylthio moiety had a signif...

journal_title：Journal of medicinal chemistry

authors： Jarosinski MA,Reddy PS,Anderson WK

更新日期：1993-11-12 00:00:00

abstract：:The first nonpeptidic, noncovalent inhibitors of the cysteine protease cathepsin S (CatS) are described. Electronic database searching using the program DOCK generated a screening set of potential CatS inhibitors from which two lead structures were identified as promising starting points for a drug discovery effort. L...

journal_title：Journal of medicinal chemistry

authors： Thurmond RL,Beavers MP,Cai H,Meduna SP,Gustin DJ,Sun S,Almond HJ,Karlsson L,Edwards JP

更新日期：2004-09-23 00:00:00

abstract：:A comprehensive herbal medicine information system for cancer (CHMIS-C) has been developed. The current version of the database integrates information on more than 200 anticancer herbal recipes that have been used for the treatment of different types of cancer in clinic, 900 individual ingredients, and 8500 small orga...

journal_title：Journal of medicinal chemistry

authors： Fang X,Shao L,Zhang H,Wang S

更新日期：2005-03-10 00:00:00

abstract：:Dual leucine zipper kinase (DLK, MAP3K12) is an essential driver of the neuronal stress response that regulates neurodegeneration in models of acute neuronal injury and chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, and ALS. In this review, we provide an overview of DLK signaling mechanisms and d...

journal_title：Journal of medicinal chemistry

authors： Siu M,Sengupta Ghosh A,Lewcock JW

更新日期：2018-09-27 00:00:00

abstract：:As described in the preceding paper (Arvanitis et al. J. Med. Chem. 1999, 42), anilinopyrimidines I were identified as potent antagonists of corticotropin-releasing hormone-1 receptor (CRH1-R, also referred to as corticotropin-releasing factor, CRF1-R). Our next goal was to understand the receptor-bound conformation o...

journal_title：Journal of medicinal chemistry

authors： Hodge CN,Aldrich PE,Wasserman ZR,Fernandez CH,Nemeth GA,Arvanitis A,Cheeseman RS,Chorvat RJ,Ciganek E,Christos TE,Gilligan PJ,Krenitsky P,Scholfield E,Strucely P

更新日期：1999-03-11 00:00:00

abstract：:In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D2 receptors, albeit somewha...

journal_title：Journal of medicinal chemistry

authors： Doll MK,Nichols DE,Kilts JD,Prioleau C,Lawler CP,Lewis MM,Mailman RB

更新日期：1999-03-11 00:00:00

abstract：:Basic side chains determine the pharmacology of selective estrogen receptor modulators such as tamoxifen or raloxifene. In this study we tried to turn the hormonal profile of (4R,5S)/(4S,5R)-4,5-bis(4-hydroxyphenyl)-2-imidazolines from agonistic to antagonistic by introduction of a dimethylaminoethane, a piperidin-1-y...

journal_title：Journal of medicinal chemistry

authors： von Rauch M,Busch S,Gust R

更新日期：2005-01-27 00:00:00

abstract：:Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucle...

journal_title：Journal of medicinal chemistry

authors： García-López MT,Herranz R,Alonso G

更新日期：1979-07-01 00:00:00

abstract：:From salicyclic acid, the two enantiomers of N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2-methoxybenzamide (6b) were prepared in a five-step synthesis. With use of Heindel's triazene method for introduction of the radionuclide, the iodine-125-labeled substituted benzamide was obtained with a calculated specific activit...

journal_title：Journal of medicinal chemistry

authors： de Paulis T,Janowsky A,Kessler RM,Clanton JA,Smith HE

更新日期：1988-10-01 00:00:00

abstract：:N(α)-Boc-l-Asp(OBn)-l-Lys(Z)-OtBu (reversin 121, 1), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-l-pro...

journal_title：Journal of medicinal chemistry

authors： Arnaud O,Koubeissi A,Ettouati L,Terreux R,Alamé G,Grenot C,Dumontet C,Di Pietro A,Paris J,Falson P

更新日期：2010-09-23 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：:By use of standard cuprate methodology, a series of 18-cycloalkyl analogues of enisoprost was prepared in an effort to impede omega chain metabolism and prolong duration of gastric antisecretory activity. An initial product of omega chain oxidation, the C-20 hydroxy analogue, was also synthesized for pharmacological c...

journal_title：Journal of medicinal chemistry

authors： Collins PW,Gasiecki AF,Perkins WE,Gullikson GW,Jones PH,Bauer RF

更新日期：1989-05-01 00:00:00

abstract：:A series of highly potent and specific fibrinogen receptor antagonists have been discovered and optimized through structural modification of the novel amidinoindole and benzofuran compounds, I and II. Systematic linker optimization afforded the amidinobenzofuran-containing inhibitor 29, which displayed an IC50 value o...

journal_title：Journal of medicinal chemistry

authors： Su T,Naughton MA,Smyth MS,Rose JW,Arfsten AE,McCowan JR,Jakubowski JA,Wyss VL,Ruterbories KJ,Sall DJ,Scarborough RM

更新日期：1997-12-19 00:00:00

abstract：:The spread of antibiotic-resistant pathogens is a growing concern, and new families of antibacterials are desperately needed. Odilorhabdins are a new class of antibacterial compounds that bind to the bacterial ribosome and kill bacteria through inhibition of the translation. NOSO-95C, one of the first member of this f...

journal_title：Journal of medicinal chemistry

authors： Sarciaux M,Pantel L,Midrier C,Serri M,Gerber C,Marcia de Figueiredo R,Campagne JM,Villain-Guillot P,Gualtieri M,Racine E

更新日期：2018-09-13 00:00:00

abstract：:In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (MMP-2 IC(50) = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structu...

journal_title：Journal of medicinal chemistry

authors： Cherney RJ,Mo R,Meyer DT,Hardman KD,Liu RQ,Covington MB,Qian M,Wasserman ZR,Christ DD,Trzaskos JM,Newton RC,Decicco CP

更新日期：2004-06-03 00:00:00