Synthesis and biological characterization of protease-activated prodrugs of doxazolidine.

abstract：:The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Rep...

journal_title：Journal of medicinal chemistry

authors： Allen MC,Fuhrer W,Tuck B,Wade R,Wood JM

更新日期：1989-07-01 00:00:00

abstract：:Monosubstituted derivatives of adenosine 5'-phosphate (AMP) with substituents of 1-3 atoms or group replacements at any of 11 positions have been synthesized and examined as substrates and inhibitors of the rat muscle adenylate kinase isozyme (AK-M), and the rat AK II and III isozymes predominant in poorly differentia...

journal_title：Journal of medicinal chemistry

authors： Hai TT,Picker D,Abo M,Hampton A

更新日期：1982-07-01 00:00:00

abstract：:A series of four structurally related carbocyclic nucleosides (6a, 6b, 10a, and 10b) were synthesized and evaluated for their ability to inhibit tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) production from human primary macrophages. These compounds had little effect...

journal_title：Journal of medicinal chemistry

authors： Borcherding DR,Peet NP,Munson HR,Zhang H,Hoffman PF,Bowlin TL,Edwards CK 3rd

更新日期：1996-06-21 00:00:00

abstract：:An atom economic and stereoselective synthesis of several spiro-piperidin-4-ones through 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin and alpha-amino acids viz . proline, phenylglycine, and sarcosine to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones is des...

journal_title：Journal of medicinal chemistry

authors： Kumar RR,Perumal S,Senthilkumar P,Yogeeswari P,Sriram D

更新日期：2008-09-25 00:00:00

abstract：:Adrenomedullin (AM) is a peptide hormone implicated in blood pressure regulation and in the pathophysiology of several diseases such as hypertension, cancer, diabetes, and renal disorders, becoming an interesting new target for the development of drugs. In a recent high-throughput screening study, a positive modulator...

journal_title：Journal of medicinal chemistry

authors： García MA,Martín-Santamaría S,Cacho M,de la Llave FM,Julián M,Martínez A,de Pascual-Teresa B,Ramos A

更新日期：2005-06-16 00:00:00

abstract：:A series of quinone substrates were modeled into the active site of human DT-diaphorase and minimized. Correlation of these models with the substrate specificity k(cat)/K(m) provided insights into the structural requirements of quinone substrates. The W105, F106, and H194 residues can influence the position of the qui...

journal_title：Journal of medicinal chemistry

authors： Suleman A,Skibo EB

更新日期：2002-03-14 00:00:00

abstract：:A series of methanoprolinenitrile-containing dipeptide mimetics were synthesized and assayed as inhibitors of the N-terminal sequence-specific serine protease dipeptidyl peptidase IV (DPP-IV). The catalytic action of DPP-IV is the principle means of degradation of glucagon-like peptide-1, a key mediator of glucose-sti...

journal_title：Journal of medicinal chemistry

authors： Magnin DR,Robl JA,Sulsky RB,Augeri DJ,Huang Y,Simpkins LM,Taunk PC,Betebenner DA,Robertson JG,Abboa-Offei BE,Wang A,Cap M,Xin L,Tao L,Sitkoff DF,Malley MF,Gougoutas JZ,Khanna A,Huang Q,Han SP,Parker RA,Hamann LG

更新日期：2004-05-06 00:00:00

abstract：:Dual-acting kappa opioid receptor (KOR) agonist and mu opioid receptor (MOR) partial agonist ligands have been put forward as potential treatment agents for cocaine and other psychostimulant abuse. Members of the orvinol series of ligands are known for their high binding affinity to both KOR and MOR, but efficacy at t...

journal_title：Journal of medicinal chemistry

authors： Greedy BM,Bradbury F,Thomas MP,Grivas K,Cami-Kobeci G,Archambeau A,Bosse K,Clark MJ,Aceto M,Lewis JW,Traynor JR,Husbands SM

更新日期：2013-04-25 00:00:00

abstract：:The selective inhibition of the lipid signaling enzyme PI3Kγ constitutes an opportunity to mediate immunosuppression and inflammation within the tumor microenvironment but is difficult to achieve due to the high sequence homology across the class I PI3K isoforms. Here, we describe the design of a novel series of poten...

journal_title：Journal of medicinal chemistry

authors： Drew SL,Thomas-Tran R,Beatty JW,Fournier J,Lawson KV,Miles DH,Mata G,Sharif EU,Yan X,Mailyan AK,Ginn E,Chen J,Wong K,Soni D,Dhanota P,Chen PY,Shaqfeh SG,Meleza C,Pham AT,Chen A,Zhao X,Banuelos J,Jin L,Schind

更新日期：2020-10-08 00:00:00

abstract：:Cytochrome P450 aromatase catalyzes the conversion of androgen substrates into estrogens. Aromatase inhibitors (AIs) have been used as first-line drugs in the treatment of estrogen-dependent breast cancer in postmenopausal women. However, the search for new, more potent, and selective AIs still remains necessary to av...

journal_title：Journal of medicinal chemistry

authors： Caporuscio F,Rastelli G,Imbriano C,Del Rio A

更新日期：2011-06-23 00:00:00

abstract：:Use of automated synthesis led to the discovery of several 6-membered nitrogen heterocycles as replacements for the N-isoxazolyl substituent present in the 1-naphthalenesulfonamides endothelin-A (ETA) antagonist 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesu lfo namides (BMS 182874). In each of these ...

journal_title：Journal of medicinal chemistry

authors： Bradbury RH,Bath C,Butlin RJ,Dennis M,Heys C,Hunt SJ,James R,Mortlock AA,Sumner NF,Tang EK,Telford B,Whiting E,Wilson C

更新日期：1997-03-14 00:00:00

abstract：:New therapies are needed for the treatment of toxoplasmosis, which is a disease caused by the protozoan parasite Toxoplasma gondii. To this end, we previously developed a potent and selective inhibitor (compound 1) of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) that possesses antitoxoplasmosis activ...

journal_title：Journal of medicinal chemistry

authors： Vidadala RS,Rivas KL,Ojo KK,Hulverson MA,Zambriski JA,Bruzual I,Schultz TL,Huang W,Zhang Z,Scheele S,DeRocher AE,Choi R,Barrett LK,Siddaramaiah LK,Hol WG,Fan E,Merritt EA,Parsons M,Freiberg G,Marsh K,Kempf DJ,Ca

更新日期：2016-07-14 00:00:00

abstract：:New 2-piperazinylbenzothiazole and 2-piperazinylbenzoxazole derivatives were prepared and tested as 5-HT3 receptor antagonists. Some of the new compounds antagonized the effect of 5-HT at the longitudinal muscle myenteric plexus (LMMP) preparation of the guinea pig ileum, and two benzothiazole derivatives, compounds 2...

journal_title：Journal of medicinal chemistry

authors： Monge A,Peña MC,Palop JA,Calderó JM,Roca J,García E,Romero G,del Río J,Lasheras B

更新日期：1994-04-29 00:00:00

abstract：:Macrophage elastase [matrix metalloproteinase (MMP)-12] is the most upregulated MMP in abdominal aortic aneurysm (AAA) and, hence, MMP-12-targeted imaging may predict AAA progression and rupture risk. Here, we report the design, synthesis, and evaluation of three novel hydroxamate-based selective MMP-12 inhibitors (CG...

journal_title：Journal of medicinal chemistry

authors： Gona K,Toczek J,Ye Y,Sanzida N,Golbazi A,Boodagh P,Salarian M,Jung JJ,Rajendran S,Kukreja G,Wu TL,Devel L,Sadeghi MM

更新日期：2020-12-10 00:00:00

abstract：:A new structurally distinct class of 14-membered-ring macrolides is characterized by a keto-function instead of the cladinose sugar, well-known for its fragility even in weakly acidic media. This new class called ketolides is endowed with remarkable antibacterial activity against macrolide-resistant strains. A complet...

journal_title：Journal of medicinal chemistry

authors： Bertho G,Gharbi-Benarous J,Delaforge M,Lang C,Parent A,Girault JP

更新日期：1998-08-27 00:00:00

abstract：:A codrug of the anti-Alzheimer drug tacrine and the natural product silibinin was synthesized. The codrug's biological and pharmacological properties were compared to an equimolar mixture of the components. The compound showed potent acetyl- and butyrylcholinesterase inhibition. In a cellular hepatotoxicity model, ana...

journal_title：Journal of medicinal chemistry

authors： Chen X,Zenger K,Lupp A,Kling B,Heilmann J,Fleck C,Kraus B,Decker M

更新日期：2012-06-14 00:00:00

abstract：:(E)-Vinylphosphonate ((E)-VP), a metabolically stable phosphate mimic at the 5'-end of the antisense strand, enhances the in vivo potency of siRNA. Here we describe a straightforward synthetic approach to incorporate a nucleotide carrying a vinylphosphonate (VP) moiety at the 5'-end of oligonucleotides under standard ...

journal_title：Journal of medicinal chemistry

authors： Parmar RG,Brown CR,Matsuda S,Willoughby JLS,Theile CS,Charissé K,Foster DJ,Zlatev I,Jadhav V,Maier MA,Egli M,Manoharan M,Rajeev KG

更新日期：2018-02-08 00:00:00

abstract：:Human melanocortin receptors (hMCRs) have been challenging targets to develop ligands that are explicitly selective for each of their subtypes. To modulate the conformational preferences of the melanocortin ligands and improve the biofunctional agonist/antagonist activities and selectivities, we have applied a backbon...

journal_title：Journal of medicinal chemistry

authors： Cai M,Marelli UK,Bao J,Beck JG,Opperer F,Rechenmacher F,McLeod KR,Zingsheim MR,Doedens L,Kessler H,Hruby VJ

更新日期：2015-08-27 00:00:00

abstract：:A series of 3-aryloxindole derivatives were synthesized and evaluated as activators of the cloned maxi-K channel mSlo expressed in Xenopus laevis oocytes using electrophysiological methods. The most promising maxi-K openers to emerge from this study were (+/-)-3-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-3-hydroxy-6-(trif...

journal_title：Journal of medicinal chemistry

authors： Hewawasam P,Erway M,Moon SL,Knipe J,Weiner H,Boissard CG,Post-Munson DJ,Gao Q,Huang S,Gribkoff VK,Meanwell NA

更新日期：2002-03-28 00:00:00

abstract：:Quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) have been applied to elucidate the mechanisms of genotoxicity (SOSIP) of nitrofuran derivatives on Escherichia coli PQ37. The following equation was developed: log SOSIP = -33.1qc2 + 1.00 log P - 1.50Isat - 1.19MR - 0....

journal_title：Journal of medicinal chemistry

authors： Debnath AK,Hansch C,Kim KH,Martin YC

更新日期：1993-04-16 00:00:00

abstract：:The p38 mitogen-activated protein (MAP) kinase has been implicated in the proinflammatory cytokine signal pathway, and its inhibitors are potentially useful for the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease. To develop a new drug for RA, we synthesized ...

journal_title：Journal of medicinal chemistry

authors： Miwatashi S,Arikawa Y,Kotani E,Miyamoto M,Naruo K,Kimura H,Tanaka T,Asahi S,Ohkawa S

更新日期：2005-09-22 00:00:00

abstract：:Inhibitors of checkpoint kinase 1 (CHK1) are of current interest as potential antitumor agents, but the most advanced inhibitor series reported to date are not orally bioavailable. A novel series of potent and orally bioavailable 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitrile CHK1 inhibitors was generated ...

journal_title：Journal of medicinal chemistry

authors： Lainchbury M,Matthews TP,McHardy T,Boxall KJ,Walton MI,Eve PD,Hayes A,Valenti MR,de Haven Brandon AK,Box G,Aherne GW,Reader JC,Raynaud FI,Eccles SA,Garrett MD,Collins I

更新日期：2012-11-26 00:00:00

abstract：:Hydroxyurea, hydroxyguanidine, and some thiosemicarbazones have been shown to have anticancer and antiviral activities. One of their possible sites of action is the enzyme ribonucleotide reductase (RR). Combination of the structural features of these compounds led to the design and synthesis of the Schiff bases of N-h...

journal_title：Journal of medicinal chemistry

authors： T'ang A,Lien EJ,Lai MM

更新日期：1985-08-01 00:00:00

abstract：:The preparation and plasma lipid altering characteristics of a series of 4H-3,1-benzoxazin-4-ones are described. Hypocholesterolemic, hypotriglyceridemic, and high-density-lipoprotein elevating properties are found for derivatives bearing a 4-(1,1-dimethylethyl)phenyl group at the 2-position, and this activity is disp...

journal_title：Journal of medicinal chemistry

authors： Fenton G,Newton CG,Wyman BM,Bagge P,Dron DI,Riddell D,Jones GD

更新日期：1989-01-01 00:00:00

abstract：:A novel class of biphenyl analogues containing a benzoic acid moiety based on lead compound 8i have been identified as potent and selective human beta 3 adrenergic receptor (beta 3-AR) agonists with good oral bioavailability and long plasma half-life. After further substituent effects were investigated at the terminal...

journal_title：Journal of medicinal chemistry

authors： Imanishi M,Tomishima Y,Itou S,Hamashima H,Nakajima Y,Washizuka K,Sakurai M,Matsui S,Imamura E,Ueshima K,Yamamoto T,Yamamoto N,Ishikawa H,Nakano K,Unami N,Hamada K,Matsumura Y,Takamura F,Hattori K

更新日期：2008-03-27 00:00:00

abstract：:The ability of molecular docking, using the program Glide and an MM-GBSA postdocking scoring protocol, to correctly rank a number of congeneric kinase inhibitors was assessed. The approach was successful for the cases considered and suggests that this may be useful for the design of inhibitors in the lead optimization...

journal_title：Journal of medicinal chemistry

authors： Lyne PD,Lamb ML,Saeh JC

更新日期：2006-08-10 00:00:00

abstract：:Fragment-based docking was used to select a conformation for virtual screening from a molecular dynamics trajectory of the West Nile virus nonstructural 3 protease. This conformation was chosen from an ensemble of 100 molecular dynamics snapshots because it optimally accommodates benzene, the most common ring in known...

journal_title：Journal of medicinal chemistry

authors： Ekonomiuk D,Su XC,Ozawa K,Bodenreider C,Lim SP,Otting G,Huang D,Caflisch A

更新日期：2009-08-13 00:00:00

abstract：:A cell-free assay was developed for the orphan nuclear receptor LXRalpha that measures the ligand-dependent recruitment of a peptide from the steroid receptor coactivator 1 (SRC1) to the nuclear receptor. Using this ligand-sensing assay (LiSA), the structural requirements for activation of the receptor by oxysterols a...

journal_title：Journal of medicinal chemistry

authors： Spencer TA,Li D,Russel JS,Collins JL,Bledsoe RK,Consler TG,Moore LB,Galardi CM,McKee DD,Moore JT,Watson MA,Parks DJ,Lambert MH,Willson TM

更新日期：2001-03-15 00:00:00

abstract：:Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor with roles in glucose, lipid, and lipoprotein homeostasis, and PPARγ ligands are expected have therapeutic potential in these as well as other areas. We report here the design, synthesis, crystallographic analysis, and c...

journal_title：Journal of medicinal chemistry

authors： Ohashi M,Oyama T,Nakagome I,Satoh M,Nishio Y,Nobusada H,Hirono S,Morikawa K,Hashimoto Y,Miyachi H

更新日期：2011-01-13 00:00:00

abstract：:The discovery of a series of novel halogenated arylsulfonamides (HAS) as new sigma receptor binding tumor imaging agents is described. Several substituted halogenated sulfonamides have been prepared and characterized. Target compounds were examined for their affinity for sigma1 and sigma2 receptor subtypes using guine...

journal_title：Journal of medicinal chemistry

authors： John CS,Lim BB,Vilner BJ,Geyer BC,Bowen WD

更新日期：1998-07-02 00:00:00