Antitumor agents. 280. Multidrug resistance-selective desmosdumotin B analogues.

abstract：:Calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated clinical efficacy in the treatment of acute migraine. Herein, we describe the design, synthesis, and preclinical characterization of a highly potent, oral CGRP receptor antagonist BMS-927711 (8). Compound 8 has good oral bioavailability in r...

journal_title：Journal of medicinal chemistry

authors： Luo G,Chen L,Conway CM,Denton R,Keavy D,Signor L,Kostich W,Lentz KA,Santone KS,Schartman R,Browning M,Tong G,Houston JG,Dubowchik GM,Macor JE

更新日期：2012-12-13 00:00:00

abstract：:We report analogues of N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Ilys-Pro-D-Ala- NH2, the parent antagonist (PA), which is a potent antagonist of LHRH. To simplify future radioactive labeling we prepared N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Arg-Pro-D-Ala-NH2 (4), [Arg8]PA, which had good activit...

journal_title：Journal of medicinal chemistry

authors： Flouret G,Mahan K,Majewski T

更新日期：1992-02-21 00:00:00

abstract：:We performed comprehensive structure-activity relationship (SAR) studies on the peptide portion of antiproliferative factor (APF), a sialylated frizzled-8 related glycopeptide that inhibits normal bladder epithelial and urothelial carcinoma cell proliferation. Glycopeptide derivatives were synthesized by solid-phase m...

journal_title：Journal of medicinal chemistry

authors： Kaczmarek P,Keay SK,Tocci GM,Koch KR,Zhang CO,Barchi JJ Jr,Grkovic D,Guo L,Michejda CJ

更新日期：2008-10-09 00:00:00

abstract：:The cesium and tetramethylammonium (TMA) salts of polyoxotungstate anions with covalently attached organosilyl groups of formula [(RSi)2O]SiW11O39(4-), where R = CH2CH2COCH3, (CH2)3CN, and CH==CH2 (1-R, cesium salt, unless otherwise noted) have been prepared, purified, and spectroscopically characterized. The water so...

journal_title：Journal of medicinal chemistry

authors： Weeks MS,Hill CL,Schinazi RF

更新日期：1992-04-03 00:00:00

abstract：:Following the observation that the activity of gonadotropin-releasing hormone III (GnRH-III) in the suppression of growth of MDA-MB-231 and MCF-7 breast cancer cells surpasses that of GnRH and other analogs thereof, analogs of GnRH-III were synthesized to investigate the structural basis for the improved antitumor act...

journal_title：Journal of medicinal chemistry

authors： Mezö I,Lovas S,Pályi I,Vincze B,Kálnay A,Turi G,Vadász Z,Seprödi J,Idei M,Tóth G,Gulyás E,Otvös F,Mák M,Horváth JE,Teplán I,Murphy RF

更新日期：1997-10-10 00:00:00

abstract：:DL-(1-Amino-2-propenyl)phosphonic acid was synthesized through the sequential oxidation, sulfoxide elimination, and deprotection of diphenyl [1-[(benzyloxycarbonyl)amino]-3-(phenylthio)propyl] phosphonate. This analogue of vinylglycine is a strong inhibitor of the alanine racemases from Pseudomonas aeruginosa and Stre...

journal_title：Journal of medicinal chemistry

authors： Vo-Quang Y,Carniato D,Vo-Quang L,Lacoste AM,Neuzil E,Le Goffic F

更新日期：1986-04-01 00:00:00

abstract：:A series of 2-guanidino-4-oxoimidazoline (deoxo-IZ) derivatives was prepared and showed potent antimalarial activities in rodent and Rhesus models. Compound 8e, the most potent analogues of this series, is the first non-8-aminoqinoline antimalarial that demonstrated radical curative activity in non-human primate by or...

journal_title：Journal of medicinal chemistry

authors： Liu X,Wang X,Li Q,Kozar MP,Melendez V,O'Neil MT,Lin AJ

更新日期：2011-07-14 00:00:00

abstract：:Seven transmembrane receptors (7TMRs), also known as G-protein-coupled receptors (GPCRs), have proven to be valuable targets for the development of therapeutics. The expansion of our understanding of 7TMR downstream signaling pathways beyond G-proteins has broadened our appreciation of the versatility of these cell su...

journal_title：Journal of medicinal chemistry

authors： Correll CC,McKittrick BA

更新日期：2014-08-28 00:00:00

abstract：:Thyroid hormone analogues, polychlorinated biphenyls (PCBs), and their derivatives were shown to bind specifically to thyroxine-specific binding sites in rat liver nuclear extracts. The structure-binding relationship for thyroxine binding prealbumin was qualitatively similar to that for the nuclear receptor. In genera...

journal_title：Journal of medicinal chemistry

authors： McKinney J,Fannin R,Jordan S,Chae K,Rickenbacher U,Pedersen L

更新日期：1987-01-01 00:00:00

abstract：:A series of 2,2-diarylethylamine derivatives has been examined for potential antidepressant activity in the tetrabenazine (TBZ) test. Diethanolamine 4 (McN-4187) was one of the more potent compounds despite its polar alcohol functionalities [ED50 values of 15 mg/kg (exploratory activity) and 1.5 mg/kg (ptosis)]. Struc...

journal_title：Journal of medicinal chemistry

authors： Maryanoff BE,Nortey SO,Gardocki JF

更新日期：1984-08-01 00:00:00

abstract：:[4-Threonine, 7-glycine]oxytocin and [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin) were synthesized by a combination of solid-phase and classical methods of peptide synthesis. A protected octapeptide was synthesized by the solid-phase method and following ammo...

journal_title：Journal of medicinal chemistry

authors： Lowbridge J,Manning M,Haldar J,Sawyer WH

更新日期：1977-01-01 00:00:00

abstract：:Pan assay interference compounds (PAINS) have become a paradigm for compound classes that might cause artifacts in biological assays. PAINS-defining substructures are typically contained in larger compounds. We have systematically examined X-ray structures of protein-ligand complexes for compounds containing PAINS mot...

journal_title：Journal of medicinal chemistry

authors： Gilberg E,Gütschow M,Bajorath J

更新日期：2018-02-08 00:00:00

abstract：:The enantiomers of two isosteric phosphonate analogs of the ether-linked antitumor agent 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OMe) were synthesized and evaluated for their cytotoxicity against various mouse leukemic cell lines in vitro and in vivo. The key step in the synthesis of the alkyloxy a...

journal_title：Journal of medicinal chemistry

authors： Bittman R,Byun HS,Mercier B,Salari H

更新日期：1994-02-04 00:00:00

abstract：:Multifunctional ligands with agonist bioactivities at μ/δ opioid receptors (MOR/DOR) and antagonist bioactivity at the neurokinin-1 receptor (NK1R) have been designed and synthesized. These peptide-based ligands are anticipated to produce better biological profiles (e.g., higher analgesic effect with significantly les...

journal_title：Journal of medicinal chemistry

authors： Giri AK,Apostol CR,Wang Y,Forte BL,Largent-Milnes TM,Davis P,Rankin D,Molnar G,Olson KM,Porreca F,Vanderah TW,Hruby VJ

更新日期：2015-11-12 00:00:00

abstract：:Glioblastoma multiforme (GBM) is the deadliest form of brain tumor. It is known for its ability to escape the therapeutic options available to date thanks to the presence of a subset of cells endowed with stem-like properties and ability to resist to cytotoxic treatments. As the cytosolic enzyme aldehyde dehydrogenase...

journal_title：Journal of medicinal chemistry

authors： Quattrini L,Gelardi ELM,Coviello V,Sartini S,Ferraris DM,Mori M,Nakano I,Garavaglia S,La Motta C

更新日期：2020-05-14 00:00:00

abstract：:A series of amide, urea, and carbamate analogues of the muscarinic (M1) ganglionic stimulant [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride (McN-A-343; 1) was prepared. The C1-methyl-substituted carbamates 8-11 were resolved into the enantiomers. In order to investigate the ganglionic stimu...

journal_title：Journal of medicinal chemistry

authors： Nilsson BM,Vargas HM,Hacksell U

更新日期：1992-07-24 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：: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

abstract：:Lipoproteins from gram-positive and -negative bacteria, mycoplasma, and shorter synthetic lipopeptide analogues activate cells of the innate immune system via the Toll-like receptor TLR2/TLR1 or TLR2/TLR6 heterodimers. For this reason, these compounds constitute highly active adjuvants for vaccines either admixed or c...

journal_title：Journal of medicinal chemistry

authors： Seyberth T,Voss S,Brock R,Wiesmüller KH,Jung G

更新日期：2006-03-09 00:00:00

abstract：:A family of analogues of des-AA(1,2,5)-[DTrp(8)/D2Nal(8)]-SRIF that contain a 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 was identified that has high affinity and selectivity for human somatostatin receptor subtype 1 (sst1). The binding affinities of des-AA(1,2,5)-[DTrp(8),IAmp(9)]-SRIF (c[H-Cys-Lys...

journal_title：Journal of medicinal chemistry

authors： Rivier JE,Hoeger C,Erchegyi J,Gulyas J,DeBoard R,Craig AG,Koerber SC,Wenger S,Waser B,Schaer JC,Reubi JC

更新日期：2001-06-21 00:00:00

abstract：:The potency of second generation antisense oligonucleotides (ASOs) in animals was increased 3- to 5 -fold (ED(50) approximately 2-5 mg/kg) without producing hepatotoxicity, by reducing ASO length (20-mer to 14-mer) and by employing novel nucleoside modifications that combine structural elements of 2'-O-methoxyethyl re...

journal_title：Journal of medicinal chemistry

authors： Seth PP,Siwkowski A,Allerson CR,Vasquez G,Lee S,Prakash TP,Wancewicz EV,Witchell D,Swayze EE

更新日期：2009-01-08 00:00:00

abstract：:To search for new antiestrogens more effective in treating breast cancers, we explored alternatives to the acrylic acid side chain used in many antiestrogens. To facilitate our search, we used a simple adamantyl ligand core that by avoiding stereochemical issues enabled rapid synthesis of acrylate ketone, ester, and a...

journal_title：Journal of medicinal chemistry

authors： Min J,Guillen VS,Sharma A,Zhao Y,Ziegler Y,Gong P,Mayne CG,Srinivasan S,Kim SH,Carlson KE,Nettles KW,Katzenellenbogen BS,Katzenellenbogen JA

更新日期：2017-07-27 00:00:00

abstract：:N-Acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. We found that administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure, indicating that this pathway might be useful for treating obesity and associated...

journal_title：Journal of medicinal chemistry

authors： Lin H,Long JZ,Roche AM,Svensson KJ,Dou FY,Chang MR,Strutzenberg T,Ruiz C,Cameron MD,Novick SJ,Berdan CA,Louie SM,Nomura DK,Spiegelman BM,Griffin PR,Kamenecka TM

更新日期：2018-04-12 00:00:00

abstract：:The major mechanism by which the serotonin neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) expresses its neurodegenerative action may involve alkylation of biological nucleophiles by the electrophilic quinoid autoxidation products. To determine the relative importance of various sites on these autoxidation products towar...

journal_title：Journal of medicinal chemistry

authors： Sinhababu AK,Ghosh AK,Borchardt RT

更新日期：1985-09-01 00:00:00

abstract：:The medicinal chemistry community has directed considerable efforts toward the discovery of selective inhibitors of interleukin-2 inducible T-cell kinase (ITK), given its role in T-cell signaling downstream of the T-cell receptor (TCR) and the implications of this target for inflammatory disorders such as asthma. We h...

journal_title：Journal of medicinal chemistry

authors： Burch JD,Barrett K,Chen Y,DeVoss J,Eigenbrot C,Goldsmith R,Ismaili MH,Lau K,Lin Z,Ortwine DF,Zarrin AA,McEwan PA,Barker JJ,Ellebrandt C,Kordt D,Stein DB,Wang X,Chen Y,Hu B,Xu X,Yuen PW,Zhang Y,Pei Z

更新日期：2015-05-14 00:00:00

abstract：:Ligands from the naltrexamine series have consistently demonstrated agonist activity at kappa opioid receptors (KOR), with varying activity at the mu opioid receptor (MOR). Various 6 beta-cinnamoylamino derivatives were made with the aim of generating ligands with a KOR agonist/MOR partial agonist profile, as ligands ...

journal_title：Journal of medicinal chemistry

authors： Cami-Kobeci G,Neal AP,Bradbury FA,Purington LC,Aceto MD,Harris LS,Lewis JW,Traynor JR,Husbands SM

更新日期：2009-03-26 00:00:00

abstract：:Reverse hydroxamate-based inhibitors of IspC, a key enzyme of the non-mevalonate pathway of isoprenoid biosynthesis and a validated antimalarial target, were synthesized and biologically evaluated. The binding mode of one derivative in complex with EcIspC and a divalent metal ion was clarified by X-ray analysis. Pilot...

journal_title：Journal of medicinal chemistry

authors： Behrendt CT,Kunfermann A,Illarionova V,Matheeussen A,Pein MK,Gräwert T,Kaiser J,Bacher A,Eisenreich W,Illarionov B,Fischer M,Maes L,Groll M,Kurz T

更新日期：2011-10-13 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：:Inhibition of histone deacetylase (HDAC) results in growth arrest, differentiation, and apoptosis in nearly all tumor cell lines, promoting HDACs as promising targets for antitumor therapy. In our previous study we developed a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDAC inhibit...

journal_title：Journal of medicinal chemistry

authors： Zhang Y,Feng J,Jia Y,Wang X,Zhang L,Liu C,Fang H,Xu W

更新日期：2011-04-28 00:00:00

abstract：:The use of privileged structures in drug discovery has proven to be an effective strategy, allowing the generation of innovative hits/leads and successful optimization processes. Chromone is recognized as a privileged structure and a useful template for the design of novel compounds with potential pharmacological inte...

journal_title：Journal of medicinal chemistry

authors： Reis J,Gaspar A,Milhazes N,Borges F

更新日期：2017-10-12 00:00:00