Design and development of water-soluble curcumin conjugates as potential anticancer agents.

abstract：:The importance of inhibitors of glycosidases as therapeutic agents for viral, proliferative, and metabolic diseases is being increasingly recognised. Several years ago we reported that the activities of mannosidase inhibitors may be explained in terms of their similarity to the mannosyl cation intermediate postulated ...

journal_title：Journal of medicinal chemistry

authors： Winkler DA

更新日期：1996-10-11 00:00:00

abstract：:Membrane-bound aminopeptidase P (AP-P) participates in the degradation of bradykinin in several vascular beds. We have developed an inhibitor of AP-P called apstatin (1) (N-[(2S, 3R)-3-amino-2-hydroxy-4-phenyl-butanoyl]-L-prolyl-L-prolyl-L-al aninam ide); IC50,human = 2.9 microM. In the rat, apstatin can potentiate th...

journal_title：Journal of medicinal chemistry

authors： Maggiora LL,Orawski AT,Simmons WH

更新日期：1999-07-01 00:00:00

abstract：:The discovery of selective endothelin (ET) receptor antagonists will facilitate identification of the physiological and pathological roles for ET and its isopeptides. Structure-activity studies of the C-terminal hexapeptide of ET have been carried out to elucidate those amino acids important for receptor binding and a...

journal_title：Journal of medicinal chemistry

authors： Doherty AM,Cody WL,DePue PL,He JX,Waite LA,Leonard DM,Leitz NL,Dudley DT,Rapundalo ST,Hingorani GP

更新日期：1993-09-03 00:00:00

abstract：:The solid-phase reductive alkylation of the Lys side chain in positions 6 (D) and 8 (L) and position 8 alone of the LH-RH antagonist [N-Ac-D-Nal,D-Ph2,3,D-Arg6,Phe7,D-Ala10]LH-RH was investigated in an attempt to reduce the histamine-releasing activity inherent to most potent antagonists while retaining high antiovula...

journal_title：Journal of medicinal chemistry

authors： Hocart SJ,Nekola MV,Coy DH

更新日期：1987-10-01 00:00:00

abstract：:A number of analogues of ibotenic acid [(RS)-3-hydroxy-5- isoxazoleglycine ] were synthesized; they were tested as excitants on neurons in the cat spinal cord, by using microelectrophoretic techniques, and as inhibitors of the binding of kainic acid (KA) in vitro, by using synaptic membranes prepared from rat brains. ...

journal_title：Journal of medicinal chemistry

authors： Krogsgaard-Larsen P,Nielsen EO,Curtis DR

更新日期：1984-05-01 00:00:00

abstract：:The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we disclosed the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind the KAc region and then building into the LPF shelf. Herein, we report the "hybridization" of a v...

journal_title：Journal of medicinal chemistry

authors： Bronner SM,Murray J,Romero FA,Lai KW,Tsui V,Cyr P,Beresini MH,de Leon Boenig G,Chen Z,Choo EF,Clark KR,Crawford TD,Jayaram H,Kaufman S,Li R,Li Y,Liao J,Liang X,Liu W,Ly J,Maher J,Wai J,Wang F,Zheng A,Zhu X

更新日期：2017-12-28 00:00:00

abstract：:Representatives of three types of side-chain analogues of distamycin A (1) were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured cells, effects on the synthesis of HSV DNA in isolated nuclei in vitro, as well as on DNA synthesis by purified HSV DNA polym...

journal_title：Journal of medicinal chemistry

authors： Bialer M,Yagen B,Mechoulam R,Becker Y

更新日期：1979-11-01 00:00:00

abstract：:N5-Acetyl-N5-hydroxy-L-ornithyl-N5-acetyl-N5-hydroxy-L-ornithyl-N5-acety l- N5-hydroxy-L-ornithine, the functionally instrumental component of the albomycins and ferrichromes, has been incorporated as a "carrier" substructure into both carbacephalosporin and oxamazin type beta-lactam antibiotics. The previously synthe...

journal_title：Journal of medicinal chemistry

authors： Dolence EK,Minnick AA,Lin CE,Miller MJ,Payne SM

更新日期：1991-03-01 00:00:00

abstract：:The three dimers 3, 4, and 5 of mitomycin C (MC), a natural antibiotic and cancer chemotherapeutic agent, were synthesized in which two MC molecules were linked with -(CH(2))(4)-, -(CH(2))(12)-, and -(CH(2))(3)N(CH(3))(CH(2))(3)- tethers, respectively. The dimeric mitomycins were designed to react as polyfunctional DN...

journal_title：Journal of medicinal chemistry

authors： Paz MM,Kumar GS,Glover M,Waring MJ,Tomasz M

更新日期：2004-06-03 00:00:00

abstract：:(N)-Methanocarba adenosine 5'-methyluronamides containing known A(3) AR (adenosine receptor)-enhancing modifications, i.e., 2-(arylethynyl)adenine and N(6)-methyl or N(6)-(3-substituted-benzyl), were nanomolar full agonists of human (h) A(3)AR and highly selective (K(i) ∼0.6 nM, N(6)-methyl 2-(halophenylethynyl) analo...

journal_title：Journal of medicinal chemistry

authors： Tosh DK,Deflorian F,Phan K,Gao ZG,Wan TC,Gizewski E,Auchampach JA,Jacobson KA

更新日期：2012-05-24 00:00:00

abstract：:sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2...

journal_title：Journal of medicinal chemistry

authors： Nakazato A,Ohta K,Sekiguchi Y,Okuyama S,Chaki S,Kawashima Y,Hatayama K

更新日期：1999-03-25 00:00:00

abstract：:To improve the biological profile of 20(S)-camptothecin, a novel class of 20-O-linked camptothecin glycoconjugates has been designed for preferential cellular uptake into tumor cells by an active transport mechanism. Such conjugates have been optimized for enhanced solubility, stabilization of the camptothecin lactone...

journal_title：Journal of medicinal chemistry

authors： Lerchen HG,Baumgarten J,von dem Bruch K,Lehmann TE,Sperzel M,Kempka G,Fiebig HH

更新日期：2001-11-22 00:00:00

abstract：:Since the discovery of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU) as a potent anti-HBV and anti-EBV agent, we have studied the structure-activity relationships of 2'-deoxy-2'-fluoro-beta-L-arabinofuranosylpyrimidine nucleosides as anti-HBV agents. Therefore it is rational to extend this study to the pur...

journal_title：Journal of medicinal chemistry

authors： Ma T,Lin JS,Newton MG,Cheng YC,Chu CK

更新日期：1997-08-15 00:00:00

abstract：:There is growing interest in using tumor associated antigens presented by class I major histocompatibility complex (MHC-I) proteins as cancer vaccines. As native peptides are poorly stable in biological fluids, researchers have sought to engineer synthetic peptidomimetics with greater biostability. Here, we demonstrat...

journal_title：Journal of medicinal chemistry

authors： Douat-Casassus C,Borbulevych O,Tarbe M,Gervois N,Jotereau F,Baker BM,Quideau S

更新日期：2010-10-14 00:00:00

abstract：:A novel series of C(3)-substituted piperdinylindoles were developed as nociceptin opioid receptor (NOP) partial agonists to explore a pharmacological hypothesis that NOP partial agonists would afford a dual pharmacological action of attenuating Parkinson's disease (PD) motor symptoms and development of levodopa-induce...

journal_title：Journal of medicinal chemistry

authors： Kamakolanu UG,Meyer ME,Yasuda D,Polgar WE,Marti M,Mercatelli D,Pisanò CA,Brugnoli A,Morari M,Zaveri NT

更新日期：2020-03-12 00:00:00

abstract：:Various substituted isoquinoline-1-carboxaldehyde thiosemicarbazones (12 compounds) have been synthesized and evaluated for antineoplastic activity in mice bearing the L1210 leukemia. Condensation of 4-bromo-1-methylisoquinoline (4) with ammonium hydroxide, methylamine, ethylamine, and N-acetylethylenediamine gave the...

journal_title：Journal of medicinal chemistry

authors： Liu MC,Lin TS,Penketh P,Sartorelli AC

更新日期：1995-10-13 00:00:00

abstract：:We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more p...

journal_title：Journal of medicinal chemistry

authors： Koh JJ,Zou H,Lin S,Lin H,Soh RT,Lim FH,Koh WL,Li J,Lakshminarayanan R,Verma C,Tan DT,Cao D,Beuerman RW,Liu S

更新日期：2016-01-14 00:00:00

abstract：:In order to be used as fertility regulators in humans, gonadotropin releasing hormone (GnRH) antagonists must be extremely potent and long acting and exhibit negligible side effects such as stimulating histamine release. To this aim, we have recently synthesized a series of analogues with the standard Ac-DNal1-DCpa2-D...

journal_title：Journal of medicinal chemistry

authors： Rivier J,Porter J,Hoeger C,Theobald P,Craig AG,Dykert J,Corrigan A,Perrin M,Hook WA,Siraganian RP

更新日期：1992-11-13 00:00:00

abstract：:Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD) by genome-wide association studies (GWAS). The most common LRRK2 mutation, G2019S, which is relatively rare in the total population, gives rise to increased kinase activity. As such, LRRK2 kinase inhibitors are potentially use...

journal_title：Journal of medicinal chemistry

authors： Henderson JL,Kormos BL,Hayward MM,Coffman KJ,Jasti J,Kurumbail RG,Wager TT,Verhoest PR,Noell GS,Chen Y,Needle E,Berger Z,Steyn SJ,Houle C,Hirst WD,Galatsis P

更新日期：2015-01-08 00:00:00

abstract：:5,6-cis-Penem derivatives have been synthesized and evaluated as anti-MRSA antibiotics. The cis-penems 5 and 6 showed potent activities against not only MRSA but also a wide variety of bacteria including beta-lactamase-producing microorganisms. These compounds were designed to have high affinity to the penicillin-bind...

journal_title：Journal of medicinal chemistry

authors： Ishiguro M,Tanaka R,Namikawa K,Nasu T,Inoue H,Nakatsuka T,Oyama Y,Imajo S

更新日期：1997-07-04 00:00:00

abstract：:Resistance to chemotherapy and endocrine therapy is a major cause of breast cancer treatment failure. We have synthesized six novel analogues using C8-ceramide as the lead analogue and studied their effect on hormone therapy resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. Pharmacologic inter...

journal_title：Journal of medicinal chemistry

authors： Antoon JW,Liu J,Gestaut MM,Burow ME,Beckman BS,Foroozesh M

更新日期：2009-09-24 00:00:00

abstract：:Four novel steroidal alpha-methylene delta-lactones have been synthesized and shown to be active against human nasopharyngeal carcinoma (KB) cells in culture. The syntheses involved the use of known alpha-methylenation procedures. In addition, the lactone 6 was directly methylenated by reaction with CH2O/KOH or Et2NH/...

journal_title：Journal of medicinal chemistry

authors： Dehal SS,Marples BA,Stretton RJ,Traynor JR

更新日期：1980-01-01 00:00:00

abstract：:We have previously identified phenylguanidine and phenyl-2-aminoimidazoline compounds as high affinity ligands with conflicting functional activity at the α2-adrenoceptor, a G-protein-coupled receptor with relevance in several neuropsychiatric conditions. In this paper we describe the design, synthesis, and pharmacolo...

journal_title：Journal of medicinal chemistry

authors： Kelly B,McMullan M,Muguruza C,Ortega JE,Meana JJ,Callado LF,Rozas I

更新日期：2015-01-22 00:00:00

abstract：:The endocannabinoid hydrolyzing enzyme FAAH uses a nonclassical catalytic triad (namely, Ser-Ser-Lys instead of Ser-Asp-His) to cleave its endogenous substrates. Because inhibiting FAAH has a clear therapeutic potential, we previously developed β-lactam-type inhibitors of hFAAH. Here, we report the synthesis of five n...

journal_title：Journal of medicinal chemistry

authors： Feledziak M,Muccioli GG,Lambert DM,Marchand-Brynaert J

更新日期：2011-10-13 00:00:00

abstract：:Angiogenesis is vital for solid tumor growth, and its prevention is a proven strategy for the treatment of disease states such as cancer. The vascular endothelial growth factor (VEGF) pathway provides several opportunities by which small molecules can act as inhibitors of endothelial proliferation and migration. Criti...

journal_title：Journal of medicinal chemistry

authors： La DS,Belzile J,Bready JV,Coxon A,DeMelfi T,Doerr N,Estrada J,Flynn JC,Flynn SR,Graceffa RF,Harriman SP,Larrow JF,Long AM,Martin MW,Morrison MJ,Patel VF,Roveto PM,Wang L,Weiss MM,Whittington DA,Teffera Y,Zhao Z

更新日期：2008-03-27 00:00:00

abstract：:Farnesoid X receptor (FXR) agonists are emerging as important potential therapeutics for the treatment of nonalcoholic steatohepatitis (NASH) patients, as they exert positive effects on multiple aspects of the disease. FXR agonists reduce lipid accumulation in the liver, hepatocellular inflammation, hepatic injury, an...

journal_title：Journal of medicinal chemistry

authors： Chianelli D,Rucker PV,Roland J,Tully DC,Nelson J,Liu X,Bursulaya B,Hernandez ED,Wu J,Prashad M,Schlama T,Liu Y,Chu A,Schmeits J,Huang DJ,Hill R,Bao D,Zoll J,Kim Y,Groessl T,McNamara P,Liu B,Richmond W,Sancho

更新日期：2020-04-23 00:00:00

abstract：:In this Perspective, recent advances and challenges in the development of GPR119 agonists as new oral antidiabetic drugs will be discussed. Such agonists are expected to exhibit a low risk to induce hypoglycemia as well as to have a beneficial impact on body weight. Many pharmaceutical companies have been active in th...

journal_title：Journal of medicinal chemistry

authors： Ritter K,Buning C,Halland N,Pöverlein C,Schwink L

更新日期：2016-04-28 00:00:00

abstract：:For a fourth approach of quinoxaline N,N'-dioxides as anti-trypanosomatid agents against T. cruzi and Leishmania, we found extremely active derivatives. The present study allows us to state the correct requirements for obtaining optimal in vitro anti-T. cruzi activity. Derivatives possessing electron-withdrawing subst...

journal_title：Journal of medicinal chemistry

authors： Benitez D,Cabrera M,Hernández P,Boiani L,Lavaggi ML,Di Maio R,Yaluff G,Serna E,Torres S,Ferreira ME,Vera de Bilbao N,Torres E,Pérez-Silanes S,Solano B,Moreno E,Aldana I,López de Ceráin A,Cerecetto H,González M,Monge

更新日期：2011-05-26 00:00:00

abstract：:9-acridinyl derivatives of 1,6-hexanediamine, 1,8-octanediamine, bis(3-aminopropyl)amine, N,N'-bis(3-amino-propyl)piperazine, and N-ethyl-1,6-hexanediamine in the form of their hydrochlorides were prepared in high yields and converted into potential hetero bis DNA intercalating diacridines. The corresponding potential...

journal_title：Journal of medicinal chemistry

authors： Hansen JB,Langvad E,Frandsen F,Buchardt O

更新日期：1983-10-01 00:00:00

abstract：:A novel series of oxime ligands has been synthesized that displays potent, specific activation of the retinoid X receptors (RXRs). The oximes of 3-substituted (tetramethyltetrahydronaphthyl)carbonylbenzoic acids are readily available by condensation with hydroxyl- or methoxylamine; alkylation of the hydroxyl oxime pro...

journal_title：Journal of medicinal chemistry

authors： Canan Koch SS,Dardashti LJ,Cesario RM,Croston GE,Boehm MF,Heyman RA,Nadzan AM

更新日期：1999-02-25 00:00:00