Identification of diarylsulfone sulfonamides as secreted frizzled related protein-1 (sFRP-1) inhibitors.

abstract：:c-Met has emerged as an attractive target for targeted cancer therapy because of its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonylpyrazolo...

journal_title：Journal of medicinal chemistry

authors： Ma Y,Sun G,Chen D,Peng X,Chen YL,Su Y,Ji Y,Liang J,Wang X,Chen L,Ding J,Xiong B,Ai J,Geng M,Shen J

更新日期：2015-03-12 00:00:00

abstract：:A series of betulinic acid (BA) derivatives were designed and synthesized by introducing various fused heterocyclic rings at C-2 and C-3 positions. Their inhibitory effects of RANKL-induced osteoclastogenesis were evaluated by using a cell-based tartrate-resistant acid phosphatase (TRAP) activity assay. To our delight...

journal_title：Journal of medicinal chemistry

authors： Xu J,Li Z,Luo J,Yang F,Liu T,Liu M,Qiu WW,Tang J

更新日期：2012-04-12 00:00:00

abstract：:We recently described a number of inhibitors of P450(17 alpha), the key enzyme of androgen biosynthesis. Here, we report the synthesis and activity of novel 17-imidazolyl, pyrazolyl, and isoxazolyl androstene derivatives as potential agents for the treatment of prostatic cancer. A number of 17-(4'-Imidazolyl) derivati...

journal_title：Journal of medicinal chemistry

authors： Ling YZ,Li JS,Liu Y,Kato K,Klus GT,Brodie A

更新日期：1997-09-26 00:00:00

abstract：:A series of novel cephalosporin compounds which have 3-[(aminopyrimidiniumyl)thio]methyl substituents was synthesized. They show high antimicrobial activity against various bacterial species including Pseudomonas aeruginosa. Structure-activity relationships with various thiopyrimidines, thiopyrimidiniums, bicyclic thi...

journal_title：Journal of medicinal chemistry

authors： Kim YZ,Lim JC,Yeo JH,Bang CS,Kim WS,Kim SS,Woo YM,Yang DH,Oh H,Nahm K

更新日期：1994-10-28 00:00:00

abstract：:A series of novel 3-quinolinecarboxylic acid derivatives have been prepared and their antibacterial activity evaluated. These derivatives are characterized by fluorine attached to the 6-position and substituted amino groups appended to the 1- and 7-positions. Structure-activity relationship studies indicate that antib...

journal_title：Journal of medicinal chemistry

authors： Wentland MP,Bailey DM,Cornett JB,Dobson RA,Powles RG,Wagner RB

更新日期：1984-09-01 00:00:00

abstract：:A series of N-(cyclopropylmethyl)-14 beta-substituted-normorphine analogues was synthesized and tested for opioid agonist and antagonist activity in the guinea pig ileum and mouse vas deferens preparations. The 14 beta-bromo compound proved to be a pure antagonist equal in potency to naloxone in the guinea pig ileum a...

journal_title：Journal of medicinal chemistry

authors： Osei-Gyimah P,Archer S,Gillan MG,Kosterlitz HW

更新日期：1981-02-01 00:00:00

abstract：:5-Oxo-ETE is the most powerful eosinophil chemoattractant among lipid mediators. Eosinophil infiltration into the lungs of asthmatics may be responsible for the late phase of inflammatory asthma. We have designed and synthesized a 5-oxo-ETE receptor antagonist, the purpose of which is to prevent eosinophil migration t...

journal_title：Journal of medicinal chemistry

authors： Gore V,Patel P,Chang CT,Sivendran S,Kang N,Ouedraogo YP,Gravel S,Powell WS,Rokach J

更新日期：2013-05-09 00:00:00

abstract：:Intravenous administration of N-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin (4) induces an acute toxic reaction, killing animals in a few minutes. This results from its positive charge at physiological pH combined with its propensity to form large aggregates in aqueous solutions. Negatively charged N-capped ve...

journal_title：Journal of medicinal chemistry

authors： Fernandez AM,Van Derpoorten K,Dasnois L,Lebtahi K,Dubois V,Lobl TJ,Gangwar S,Oliyai C,Lewis ER,Shochat D,Trouet A

更新日期：2001-10-25 00:00:00

abstract：:Inhibition of the bromodomain of the transcriptional regulator CBP/P300 is an especially interesting new therapeutic approach in oncology. We recently disclosed in vivo chemical tool 1 (GNE-272) for the bromodomain of CBP that was moderately potent and selective over BRD4(1). In pursuit of a more potent and selective ...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Murray J,Lai KW,Tsui V,Albrecht BK,An L,Beresini MH,de Leon Boenig G,Bronner SM,Chan EW,Chen KX,Chen Z,Choo EF,Clagg K,Clark K,Crawford TD,Cyr P,de Almeida Nagata D,Gascoigne KE,Grogan JL,Hatzivassiliou

更新日期：2017-11-22 00:00:00

abstract：:The synthesis, characterization, inhibitory activity against topoisomerase I, and biological evaluation of a series of 14 camptothecin derivatives of polypyrrolecarboxamide (lexitropsin) conjugates of two structural classes: (A) camptothecin-NHCO-lexitropsin 44-51 and (B) camptothecin-CONH-lexitropsin 38-43 are descri...

journal_title：Journal of medicinal chemistry

authors： Zhao R,al-Said NH,Sternbach DL,Lown JW

更新日期：1997-01-17 00:00:00

abstract：:S1P5 is one of 5 receptors for sphingosine-1-phosphate and is highly expressed on endothelial cells within the blood-brain barrier, where it maintains barrier integrity in in vitro models (J. Neuroinflamm. 2012, 9, 133). Little more is known about the effects of S1P5 modulation due to the absence of tool molecules wit...

journal_title：Journal of medicinal chemistry

authors： Hobson AD,Harris CM,van der Kam EL,Turner SC,Abibi A,Aguirre AL,Bousquet P,Kebede T,Konopacki DB,Gintant G,Kim Y,Larson K,Maull JW,Moore NS,Shi D,Shrestha A,Tang X,Zhang P,Sarris KK

更新日期：2015-12-10 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：:Generally, antipsychotic agents are dopamine receptor blocking agents that also block conditioned avoidance responding (CAR) in the rat. Recently, however, both (Q-methoxyphenyl)piperazine (OMPP, 1h) and (m-chlorophenyl)piperazine (MCPP, 1o) have been reported to block conditioned avoidance responding in the rat altho...

journal_title：Journal of medicinal chemistry

authors： Martin GE,Elgin RJ Jr,Mathiasen JR,Davis CB,Kesslick JM,Baldy WJ,Shank RP,DiStefano DL,Fedde CL,Scott MK

更新日期：1989-05-01 00:00:00

abstract：:The first synthesis of the tamoxifen metabolite norendoxifen is reported. This included syntheses of (E)-norendoxifen, (Z)-norendoxifen, and (E,Z)-norendoxifen isomers. (Z)-Norendoxifen displayed affinity for aromatase (Ki 442 nM), estrogen receptor-α (EC50 17 nM), and estrogen receptor-β (EC50 27.5 nM), while the cor...

journal_title：Journal of medicinal chemistry

authors： Lv W,Liu J,Lu D,Flockhart DA,Cushman M

更新日期：2013-06-13 00:00:00

abstract：:A series of tricyclic analogues of 9-oxo-9H-xanthene-4-acetic acid have been prepared and evaluated for their ability to cause hemorrhagic necrosis in subcutaneously implanted colon 38 tumors in mice, in an effort to extend the structure-activity relationships for this series. As was found previously with analogues of...

journal_title：Journal of medicinal chemistry

authors： Rewcastle GW,Atwell GJ,Palmer BD,Boyd PD,Baguley BC,Denny WA

更新日期：1991-02-01 00:00:00

abstract：:Production of the Gag-Pol polyprotein in human immunodeficiency virus (HIV) requires a -1 ribosomal frameshift, which is directed by a highly conserved RNA stem-loop. Building on our discovery of a set of disulfide-containing peptides that bind this RNA, we describe medicinal chemistry efforts designed to begin to und...

journal_title：Journal of medicinal chemistry

authors： Palde PB,Ofori LO,Gareiss PC,Lerea J,Miller BL

更新日期：2010-08-26 00:00:00

abstract：:Many nonquaternary ammonium muscarinic agonists have been developed over the last few years, but most of the existing compounds (e.g., arecoline, RS-86, AF-30) behave as weak partial agonists at cholinergic receptors in tissues of limited receptor reserve. The current paper describes the synthesis and biochemical asse...

journal_title：Journal of medicinal chemistry

authors： Saunders J,Showell GA,Snow RJ,Baker R,Harley EA,Freedman SB

更新日期：1988-02-01 00:00:00

abstract：:Cyclic and acyclic nitroaryl phosphoramide mustard analogues were activated by E. coli nitroreductase, an enzyme explored in GDEPT. The more active acyclic 4-nitrobenzyl phosphoramide mustard (7) showed 167 500x selective cytotoxicity toward nitroreductase-expressing V79 cells with an IC(50) as low as 0.4 nM. This is ...

journal_title：Journal of medicinal chemistry

authors： Hu L,Yu C,Jiang Y,Han J,Li Z,Browne P,Race PR,Knox RJ,Searle PF,Hyde EI

更新日期：2003-11-06 00:00:00

abstract：:Following erythrocyte invasion, malaria parasites export a catalogue of remodeling proteins into the infected cell that enable parasite development in the human host. Export is dependent on the activity of the aspartyl protease, plasmepsin V (PMV), which cleaves proteins within the Plasmodium export element (PEXEL; Rx...

journal_title：Journal of medicinal chemistry

authors： Sleebs BE,Gazdik M,O'Neill MT,Rajasekaran P,Lopaticki S,Lackovic K,Lowes K,Smith BJ,Cowman AF,Boddey JA

更新日期：2014-09-25 00:00:00

abstract：:A primary goal of lead optimization is to identify compounds with improved absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. A number of reports have linked computed molecular properties to desirable in vivo ADMET outcomes, but a significant limitation of these analyses is the failure t...

journal_title：Journal of medicinal chemistry

authors： Sutherland JJ,Raymond JW,Stevens JL,Baker TK,Watson DE

更新日期：2012-07-26 00:00:00

abstract：:The kinase PIM-1 plays a pivotal role in cytokine signaling and is implicated in the development of a number of tumors. The three-dimensional structure of PIM-1 is characterized by an unique hinge region which lacks a second hydrogen bond donor and makes it particularly important to determine how inhibitors bind to th...

journal_title：Journal of medicinal chemistry

authors： Bullock AN,Debreczeni JE,Fedorov OY,Nelson A,Marsden BD,Knapp S

更新日期：2005-12-01 00:00:00

abstract：:The concept of molecular hybridization led us to discover a novel series of coumarin-dihydropyridine hybrids that have potent osteoblastic bone formation in vitro and that prevent ovariectomy-induced bone loss in vivo. In this context, among all the compounds screened for alkaline phosphatase activity, four compounds ...

journal_title：Journal of medicinal chemistry

authors： Sashidhara KV,Kumar M,Khedgikar V,Kushwaha P,Modukuri RK,Kumar A,Gautam J,Singh D,Sridhar B,Trivedi R

更新日期：2013-01-10 00:00:00

abstract：:Low permeability across the outer membrane is a major reason why most antibiotics are ineffective against Gram-negative bacteria. Agents that permeabilize the outer membrane are typically toxic at their effective concentrations. Here, we report the development of a broad-spectrum homodimeric tobramycin adjuvant that i...

journal_title：Journal of medicinal chemistry

authors： Idowu T,Ammeter D,Rossong H,Zhanel GG,Schweizer F

更新日期：2019-10-24 00:00:00

abstract：:Protein kinase C (PKC) is a widely studied molecular target for the treatment of cancer and other diseases. We have approached the issue of modifying PKC function by targeting the C1 domain in the regulatory region of the enzyme. Using the X-ray crystal structure of the PKC delta C1b domain, we have discovered conveni...

journal_title：Journal of medicinal chemistry

authors： Boije af Gennäs G,Talman V,Aitio O,Ekokoski E,Finel M,Tuominen RK,Yli-Kauhaluoma J

更新日期：2009-07-09 00:00:00

abstract：:Inhibition of embryonic ectoderm development (EED) is a new cancer therapeutic strategy. Herein, we report our discovery of EEDi-5285 as an exceptionally potent, efficacious, and orally active EED inhibitor. EEDi-5285 binds to the EED protein with an IC50 value of 0.2 nM and inhibits cell growth with IC50 values of 20...

journal_title：Journal of medicinal chemistry

authors： Rej RK,Wang C,Lu J,Wang M,Petrunak E,Zawacki KP,McEachern D,Fernandez-Salas E,Yang CY,Wang L,Li R,Chinnaswamy K,Wen B,Sun D,Stuckey J,Zhou Y,Chen J,Tang G,Wang S

更新日期：2020-07-09 00:00:00

abstract：:Synthesis and pharmacological evaluation of a series of 1,2-dihydro-1-[(5-methyl-1-imidazol-4-yl)methyl]-2-oxopyridine 5-HT3 antagonists are described. The key pharmacophoric elements were defined as a basic nitrogen, a linking group capable of hydrogen bonding interactions, and an aromatic moiety. 1,2-Dihydro-2-oxopy...

journal_title：Journal of medicinal chemistry

authors： Matsui T,Sugiura T,Nakai H,Iguchi S,Shigeoka S,Takada H,Odagaki Y,Nagao Y,Ushio Y,Ohmoto K

更新日期：1992-09-04 00:00:00

abstract：:Recently, we have discovered that the registered pesticide, tolfenpyrad, unexpectedly and potently inhibits the development of the L4 larval stage of the parasitic nematode Haemonchus contortus with an IC50 value of 0.03 μM while displaying good selectivity, with an IC50 of 37.9 μM for cytotoxicity. As a promising mol...

journal_title：Journal of medicinal chemistry

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

更新日期：2019-01-24 00:00:00

abstract：:Here we report on the design, synthesis, and biological characterization of novel κ opioid (KOP) receptor ligands of diphenethylamines. In opioid receptor binding and functional assays, the N-cyclobutylmethyl substituted derivative 4 (HS665) showed the highest affinity and selectivity for the KOP receptor and KOP agon...

journal_title：Journal of medicinal chemistry

authors： Spetea M,Berzetei-Gurske IP,Guerrieri E,Schmidhammer H

更新日期：2012-11-26 00:00:00

abstract：:New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cycl...

journal_title：Journal of medicinal chemistry

authors： Ashton WT,Cantone CL,Tolman RL,Greenlee WJ,Lynch RJ,Schorn TW,Strouse JF,Siegl PK

更新日期：1992-07-24 00:00:00

abstract：:Twenty-three acrylonitriles, substituted at position 2 with either triazoles or benzimidazoles and at position 3 with various substituted furan, thiophene, or phenyl rings, were prepared by Knoevenagel condensation and tested for in vitro cytotoxic potency on 11 human cancer cell lines. X-ray crystal analysis of two r...

journal_title：Journal of medicinal chemistry

authors： Saczewski F,Reszka P,Gdaniec M,Grünert R,Bednarski PJ

更新日期：2004-06-17 00:00:00