Synthesis and biological evaluation of a novel 3-sulfonyl-8-azabicyclo[3.2.1]octane class of long chain fatty acid elongase 6 (ELOVL6) inhibitors.

abstract：:An endogenous heptadecapeptide, nociceptin/orphanin FQ (N/OFQ), and a G-protein-coupled receptor, N/OFQ peptide (NOP) receptor [or opioid-receptor-like-1 (ORL1) receptor], have been described in terms of its structure, distribution, and pharmacology. Thus, the N/OFQ and NOP receptor are located in the central nervous ...

journal_title：Journal of medicinal chemistry

authors： Hayashi S,Hirao A,Imai A,Nakamura H,Murata Y,Ohashi K,Nakata E

更新日期：2009-02-12 00:00:00

abstract：:Opical antipodes of the axial phenyl analgetic, alpha-promedol hydrochloride (3), were prepared and the absolute stereochemistry wasd determined by relating one of the enantiomers to its gamme diastereomer having the 2S, 4S,5R configuration. The analegetic potency of (+)-(2R,4S,5S)-3 is 20 times that of morphine, whil...

journal_title：Journal of medicinal chemistry

authors： Fries DF,Portoghese PS

更新日期：1976-09-01 00:00:00

abstract：:Seven 1,2-dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydro-6-demethoxyacronycine esters and diesters were synthesized via osmic oxidation of acronycine or 6-demethoxyacronycine followed by acylation. The 6-demethoxyacronycine derivatives were found to be inactive, whereas in contrast, all of the acronycin...

journal_title：Journal of medicinal chemistry

authors： Elomri A,Mitaku S,Michel S,Skaltsounis AL,Tillequin F,Koch M,Pierré A,Guilbaud N,Léonce S,Kraus-Berthier L,Rolland Y,Atassi G

更新日期：1996-11-22 00:00:00

abstract：:A novel series of nonsteroidal heterocycles was discovered which display cell-type selective, high-affinity (nanomolar) binding to the progesterone receptors from TE85 osteosarcoma cells but > 1 microM binding affinity to the progesterone receptors from T47D and ZR75 human breast carcinoma cells. Structure-activity re...

journal_title：Journal of medicinal chemistry

authors： Combs DW,Reese K,Cornelius LA,Gunnet JW,Cryan EV,Granger KS,Jordan JJ,Demarest KT

更新日期：1995-12-08 00:00:00

abstract：:The polyhalogenated benzimidazole nucleosides 2,5, 6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were synthesized in our laboratory and established as potent and selective inhibitors of human cytomegalovirus (HCMV) with a novel mode of action. In an effort to study the behav...

journal_title：Journal of medicinal chemistry

authors： Zhu Z,Lippa B,Drach JC,Townsend LB

更新日期：2000-06-15 00:00:00

abstract：:A series of 4,5-diaryl-2-(substituted thio)-1H-imidazoles has been synthesized and demonstrated to be potent inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). The design, synthesis, and structure-activity relationships for this series are reported herein. One of the compounds from this series, N'-(2,4-difluor...

journal_title：Journal of medicinal chemistry

authors： Higley CA,Wilde RG,Maduskuie TP,Johnson AL,Pennev P,Billheimer JT,Robinson CS,Gillies PJ,Wexler RR

更新日期：1994-10-14 00:00:00

abstract：:A series of 1-methyl-1H-pyrazole-5-carboxamides were synthesized as potent inhibitors of the parasitic nematode of sheep, Haemonchus contortus. These compounds did not show overt cytotoxicity to a range of mammalian cell lines under standard in vitro culture conditions, had high selectivity indices, and were progresse...

journal_title：Journal of medicinal chemistry

authors： Preston S,Garcia-Bustos J,Hall LG,Martin SD,Le TG,Kundu A,Ghoshal A,Nguyen NH,Jiao Y,Ruan B,Xue L,Huang F,Chang BCH,McGee SL,Wells TNC,Palmer MJ,Jabbar A,Gasser RB,Baell JB

更新日期：2021-01-14 00:00:00

abstract：:The synthesis and biological evaluation of a series of 2-substituted 5-phenyl-1,4-benzodiazepines, structurally related to tifluadom (5), the only benzodiazepine that acts simultaneously as a kappa-opioid agonist and a cholecystokinin-A (CCK-A) antagonist, are reported. The radioligand binding models used in these stu...

journal_title：Journal of medicinal chemistry

authors： Cappelli A,Anzini M,Vomero S,Menziani MC,De Benedetti PG,Sbacchi M,Clarke GD,Mennuni L

更新日期：1996-02-16 00:00:00

abstract：:The dopamine D(3) receptor is recognized as a potential therapeutic target for the treatment of various neurological and psychiatric disorders. Targetting high affinity and D(3) versus D(2) receptor-preferring ligands, the partial agonist BP 897 was taken as a lead structure. Variations in the spacer and the aryl moie...

journal_title：Journal of medicinal chemistry

authors： Hackling A,Ghosh R,Perachon S,Mann A,Höltje HD,Wermuth CG,Schwartz JC,Sippl W,Sokoloff P,Stark H

更新日期：2003-08-28 00:00:00

abstract：:Fragment-based drug discovery has become a powerful method for the generation of drug leads against therapeutic targets. Beyond the identification of novel and effective starting points for drug design, fragments have emerged as reliable tools for assessing protein druggability and identifying protein hot spots. Here,...

journal_title：Journal of medicinal chemistry

authors： Krimm I,Lancelin JM,Praly JP

更新日期：2012-02-09 00:00:00

abstract：:Treatment of 14 beta-nitrocodeinone with sodium borohydride gave the codeine derivative which was reduced with zinc dust in acetic anhydride-acetic acid solution to give 14 beta-acetamidocodeine 6-acetate. 14 beta-Thiocyanatocodeinone was obtained from the reaction of thebaine with thiocyanogen and was reduced to 14 b...

journal_title：Journal of medicinal chemistry

authors： Osei-Gyimah P,Archer S

更新日期：1980-02-01 00:00:00

abstract：:An application of the neural network to quantitative structure-activity relationship (QSAR) analysis has been studied. The new method was compared with the linear multiregression analysis in various ways. It was found that the neural network can be a potential tool in the routine work of QSAR analysis. The mathematica...

journal_title：Journal of medicinal chemistry

authors： Aoyama T,Suzuki Y,Ichikawa H

更新日期：1990-09-01 00:00:00

abstract：:Seven 3-alkyl-4-aryl-1,5-dihydro-2H-pyrrol-2-ones were prepared as potential inhibitors of cardiac cAMP phosphodiesterase (PDE). The design of these compounds made use of rolipram, a known inhibitor of the brain cAMP PDE isozyme, as a lead structure and was guided by a model which describes the features required for p...

journal_title：Journal of medicinal chemistry

authors： Lampe JW,Chou YL,Hanna RG,Di Meo SV,Erhardt PW,Hagedorn AA 3rd,Ingebretsen WR,Cantor E

更新日期：1993-04-16 00:00:00

abstract：:The linear interaction energy method with continuum electrostatics (LIECE) is evaluated in depth on five kinases. The two multiplicative coefficients for the van der Waals energy and electrostatic free energy are shown to be transferable among different kinases. Moreover, good enrichment factors are obtained for a lib...

journal_title：Journal of medicinal chemistry

authors： Kolb P,Huang D,Dey F,Caflisch A

更新日期：2008-03-13 00:00:00

abstract：:The binding constants of 15 phenothiazine derivatives to bovine serum albumin were obtained by a circular dichroic probe technique; The lipophilicity of the drugs, measured by a reversed-phase thin-layer technique using oleyl alcohol and methanol-water mixtures as the solvents, is expressed as RMw. The binding constan...

journal_title：Journal of medicinal chemistry

authors： Hulshoff A,Perrin JH

更新日期：1977-03-01 00:00:00

abstract：:A series of biphenyl analogues of the new tuberculosis drug PA-824 was prepared, primarily by coupling the known (6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-ol with iodobenzyl halides, followed by Suzuki coupling of these iodides with appropriate arylboronic acids or by assembly of the complete biaryl side...

journal_title：Journal of medicinal chemistry

authors： Palmer BD,Thompson AM,Sutherland HS,Blaser A,Kmentova I,Franzblau SG,Wan B,Wang Y,Ma Z,Denny WA

更新日期：2010-01-14 00:00:00

abstract：:Cell division cycle 25 (Cdc25) proteins are highly conserved dual specificity phosphatases that regulate cyclin-dependent kinases and represent attractive drug targets for anticancer therapies. To discover more potent and diverse inhibitors of Cdc25 biological activity, virtual screening was performed by docking 2.1 m...

journal_title：Journal of medicinal chemistry

authors： Lavecchia A,Di Giovanni C,Pesapane A,Montuori N,Ragno P,Martucci NM,Masullo M,De Vendittis E,Novellino E

更新日期：2012-05-10 00:00:00

abstract：:Prealbumin is a major thyroxine binding protein in blood that has been well studied crystallographically and has also been proposed as a model for the thyroxine nuclear receptor in tissue. The high-affinity T4 binding site in prealbumin gave a linear plot on Scatchard analysis. The interactions of selected polychlorin...

journal_title：Journal of medicinal chemistry

authors： Rickenbacher U,McKinney JD,Oatley SJ,Blake CC

更新日期：1986-05-01 00:00:00

abstract：:Isolated hepatocytes carry out the N-demethylation of dansylamide at near linear rates for up to 8 h. This reaction was measured by following the release of tritium into water on hydroxylation of 3H-labeled methyl groups. The competitive inhibition of dansylamide by dansylated amino acids was studied in this system as...

journal_title：Journal of medicinal chemistry

authors： Hayes JS,Brendel K

更新日期：1976-11-01 00:00:00

abstract：:We synthesized two series (7a-i and 8a-i) of 2,3,5-substituted [1,2,4]-thiadiazole analogues of SCH-202676 (7a, 2,3-diphenyl-5-N-methylimino-2H-[1,2,4]-thiadiazole) with emphasis on the N-imino substituent. Compounds 7a-g,i and 8a-g at a final concentration of 1 microM significantly inhibited [(3)H]CCPA (2-chloro-N(6)...

journal_title：Journal of medicinal chemistry

authors： Göblyös A,de Vries H,Brussee J,Ijzerman AP

更新日期：2005-02-24 00:00:00

abstract：:Whereas the 2-propyl- and 2-butyl-5,6-(methylenedioxy)indene calcium antagonists reversed the spasmogenic action of several agonists including PGF2alpha and acetylcholine at 5 X 10(-5) to 10(-4) M on the rat ileum, the corresponding 5,6-dimethoxy analogues exhibited spasmogenic activity at higher concentration (10(-4)...

journal_title：Journal of medicinal chemistry

authors： Witiak DT,Kakodkar SV,Brunst GE,Baldwin JR,Rahwan RG

更新日期：1978-12-01 00:00:00

abstract：:Wnt proteins regulate various cellular functions and serve distinct roles in normal development throughout life. Wnt signaling is dysregulated in various diseases including cancers. Porcupine (PORCN) is a membrane-bound O-acyltransferase that palmitoleates the Wnts and hence is essential for their secretion and functi...

journal_title：Journal of medicinal chemistry

authors： Duraiswamy AJ,Lee MA,Madan B,Ang SH,Tan ES,Cheong WW,Ke Z,Pendharkar V,Ding LJ,Chew YS,Manoharan V,Sangthongpitag K,Alam J,Poulsen A,Ho SY,Virshup DM,Keller TH

更新日期：2015-08-13 00:00:00

abstract：:Thalidomide, 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione, has been shown to inhibit angiogenesis, the formation of new blood vessels from existing vasculature. As a result, there is renewed interest in this drug as a potential therapy for solid tumors. Thalidomide forms a number of metabolites and has been ...

journal_title：Journal of medicinal chemistry

authors： Lepper ER,Ng SS,Gütschow M,Weiss M,Hauschildt S,Hecker TK,Luzzio FA,Eger K,Figg WD

更新日期：2004-04-22 00:00:00

abstract：:Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been developed using comparative molecular field analysis (CoMFA) on a large data set (118 compounds) of diverse cyclic urea derivatives as protease inhibitors against the human immunodeficiency virus type 1 (HIV-1). X-ray crystal str...

journal_title：Journal of medicinal chemistry

authors： Debnath AK

更新日期：1999-01-28 00:00:00

abstract：:7-Substituted 3-aryl-1,6-naphthyridine-2,7-diamines and related 2-ureas are inhibitors of fibroblast growth factor receptor-1 (FGFR-1) and vascular endothelial growth factor receptor-2 (VEGFR-2). 3-(3,5-Dimethoxyphenyl) and 3-phenyl analogues were prepared from 7-acetamido-2-tert-butylureas by alkylation with benzyl o...

journal_title：Journal of medicinal chemistry

authors： Thompson AM,Delaney AM,Hamby JM,Schroeder MC,Spoon TA,Crean SM,Showalter HD,Denny WA

更新日期：2005-07-14 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：:Antivirulence strategies are now attracting interest for the inherent mechanism of action advantages. In our previous work, diapophytoene desaturase (CrtN) was identified to be an attractive and drugable target for fighting pigmented S. aureus infections. In this research, we developed a series of effective benzocyclo...

journal_title：Journal of medicinal chemistry

authors： Wang Y,Di H,Chen F,Xu Y,Xiao Q,Wang X,Wei H,Lu Y,Zhang L,Zhu J,Lan L,Li J

更新日期：2016-05-26 00:00:00

abstract：:The dynorphin (Dyn) A analogue zyklophin ([N-benzyl-Tyr(1)-cyclo(d-Asp(5),Dap(8))]dynorphin A(1-11)NH2) is a kappa opioid receptor (KOR)-selective antagonist in vitro, is active in vivo, and antagonizes KOR in the CNS after systemic administration. Hence, we synthesized zyklophin analogues to explore the structure-act...

journal_title：Journal of medicinal chemistry

authors： Joshi AA,Murray TF,Aldrich JV

更新日期：2015-11-25 00:00:00

abstract：:Starting from the structure of the novel nonpeptidic angiotensin II antagonist DuP 753, a series of more rigid analogues was prepared by replacing the biphenyl part of DuP 753 with a naphthalene ring. Five different regioisomers (compounds 6a-e) were synthesized, and receptor binding in rat smooth muscle cell preparat...

journal_title：Journal of medicinal chemistry

authors： Bühlmayer P,Criscione L,Fuhrer W,Furet P,de Gasparo M,Stutz S,Whitebread S

更新日期：1991-10-01 00:00:00

abstract：:A series of nitroimidazoles incorporating sulfonamide/sulfamide/sulfamate moieties were designed and synthesized as radio/chemosensitizing agent targeting the tumor-associated carbonic anhydrase (CA) isoforms IX and XII. Most of the new compounds were nanomolar inhibitors of these isoforms. Crystallographic studies on...

journal_title：Journal of medicinal chemistry

authors： Rami M,Dubois L,Parvathaneni NK,Alterio V,van Kuijk SJ,Monti SM,Lambin P,De Simone G,Supuran CT,Winum JY

更新日期：2013-11-14 00:00:00