Podophyllotoxin analogs. 1. Synthesis and biological evaluation of certain trans-2-aryl-trans-6-hydroxymethyl-3-cyclohexenecarboxylic acid gamma-lactones as antimitotic agents.

abstract：:Partition properties, that is partition coefficients and enthalpies (delta Hp degree) and entropies (delta Sp degree) of partition, have been measured for 50 benzoic acids in the 1-octanol/water system, and their role in QSAR (quantitative structure-activity relationship) analysis examined. The novel hydrophobic param...

journal_title：Journal of medicinal chemistry

authors： Da YZ,Ito K,Fujiwara H

更新日期：1992-09-04 00:00:00

abstract：:Homologous recombination repair (HRR), a crucial approach in DNA damage repair, is an attractive target in cancer therapy and drug design. The Bloom syndrome protein (BLM) is a 3'-5' DNA helicase that performs an important role in HRR regulation. However, limited studies about BLM inhibitors and their biological effec...

journal_title：Journal of medicinal chemistry

authors： Yin QK,Wang CX,Wang YQ,Guo QL,Zhang ZL,Ou TM,Huang SL,Li D,Wang HG,Tan JH,Chen SB,Huang ZS

更新日期：2019-03-28 00:00:00

abstract：:We have previously shown that the 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA, 2), binds to AMPA receptors in a manner different from that of AMPA (1) itself and that 2, in contrast to 1, also binds to kainic acid re...

journal_title：Journal of medicinal chemistry

authors： Bang-Andersen B,Ahmadian H,Lenz SM,Stensbøl TB,Madsen U,Bøgesø KP,Krogsgaard-Larsen P

更新日期：2000-12-14 00:00:00

abstract：:A series of 8-(substituted phenyl) derivatives of theophylline and other 1,3-dialkylxanthines were evaluated for potency and selectivity as antagonists at A1- and A2-adenosine receptors in brain tissue. Theophylline has a similar potency (Ki = 14 microM) at both A1 and A2 receptors. 8-Phenyltheophylline is 25-35-fold ...

journal_title：Journal of medicinal chemistry

authors： Daly JW,Padgett W,Shamim MT,Butts-Lamb P,Waters J

更新日期：1985-04-01 00:00:00

abstract：:A series of analogues of the dipeptide sweetener L-aspartyl-L-phenylalanine methyl ester having hydroxy and/or methoxy substitution on the aromatic ring was synthesized and tasted. The introduction of a methoxy group in the para position of the aromatic ring of the peptide sweetener is crucial to the reduction or dest...

journal_title：Journal of medicinal chemistry

authors： Kawai M,Chorev M,Marin-Rose J,Goodman M

更新日期：1980-04-01 00:00:00

abstract：:6-Substituted 6-deoxy-L-galactose (L-fucose) derivatives were synthesized as potential antimetabolites of L-fucose. The cytotoxic effects of these compounds were evaluated on P388 leukemia cells in culture. The L-fucose analogues which showed the most potent growth inhibition were the sulfonyl ester, bromo, and iodo d...

journal_title：Journal of medicinal chemistry

authors： May JA Jr,Sartorelli AC

更新日期：1979-08-01 00:00:00

abstract：:The development of pharmacotherapeutic treatments of psychostimulant abuse has remained a challenge, despite significant efforts made toward relevant mechanistic targets, such as the dopamine transporter (DAT). The atypical DAT inhibitors have received attention due to their promising pharmacological profiles in anima...

journal_title：Journal of medicinal chemistry

authors： Cao J,Slack RD,Bakare OM,Burzynski C,Rais R,Slusher BS,Kopajtic T,Bonifazi A,Ellenberger MP,Yano H,He Y,Bi GH,Xi ZX,Loland CJ,Newman AH

更新日期：2016-12-08 00:00:00

abstract：:Mutations of isocitrate dehydrogenase 1 (IDH1) are frequently found in certain cancers such as glioma. Different from the wild-type (WT) IDH1, the mutant enzymes catalyze the reduction of α-ketoglutaric acid to d-2-hydroxyglutaric acid (D2HG), leading to cancer initiation. Several 1-hydroxypyridin-2-one compounds were...

journal_title：Journal of medicinal chemistry

authors： Liu Z,Yao Y,Kogiso M,Zheng B,Deng L,Qiu JJ,Dong S,Lv H,Gallo JM,Li XN,Song Y

更新日期：2014-10-23 00:00:00

abstract：:Lysosomotropic detergents, which kill mammalian cells by disrupting lysosomal membranes, have now been found to be antifungals also. All strains in our assay are susceptible. The mode of action is as yet undetermined, but intracellular vacuoles may be the primary targets. ...

journal_title：Journal of medicinal chemistry

authors： Firestone RA,Pisano JM,Garrity GM,Fromtling RA,Zimmerman SB

更新日期：1987-08-01 00:00:00

abstract：:The adenosine 5'-triphosphate (ATP) competitive cyclin-dependent kinase inhibitor O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as the lead in a structure-based drug discovery program resulting in the discovery of the potent CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM and 5.4 nM vs CDK1/cyclinB and C...

journal_title：Journal of medicinal chemistry

authors： Hardcastle IR,Arris CE,Bentley J,Boyle FT,Chen Y,Curtin NJ,Endicott JA,Gibson AE,Golding BT,Griffin RJ,Jewsbury P,Menyerol J,Mesguiche V,Newell DR,Noble ME,Pratt DJ,Wang LZ,Whitfield HJ

更新日期：2004-07-15 00:00:00

abstract：:Since their discovery over 5 decades ago, quinolone antibiotics have found enormous success as broad spectrum agents that exert their activity through dual inhibition of bacterial DNA gyrase and topoisomerase IV. Increasing rates of resistance, driven largely by target-based mutations in the GyrA/ParC quinolone resist...

journal_title：Journal of medicinal chemistry

authors： Skepper CK,Armstrong D,Balibar CJ,Bauer D,Bellamacina C,Benton BM,Bussiere D,De Pascale G,De Vicente J,Dean CR,Dhumale B,Fisher LM,Fuller J,Fulsunder M,Holder LM,Hu C,Kantariya B,Lapointe G,Leeds JA,Li X,Lu P,Lv

更新日期：2020-07-23 00:00:00

abstract：:An analogue of a tripeptide inhibitor of angiotensin converting enzyme, Bz-Phe-Gly-Pro, has been synthesized in which the amide bond connecting phenylalanine and glycine has been replaced by a ketomethylene group. This nonpeptide analogue, 20, shows more potent converting enzyme inhibiting activity, I50 = 0.07 microM,...

journal_title：Journal of medicinal chemistry

authors： Almquist RG,Chao WR,Ellis ME,Johnson HL

更新日期：1980-12-01 00:00:00

abstract：:Cancer cells generally generate higher amounts of reactive oxygen species than normal cells. On the basis of this difference, prodrugs have been developed (e.g., hydroxyferrocifen), which remain inactive in normal cells, but become activated in cancer cells. In this work we describe novel aminoferrocene-based prodrugs...

journal_title：Journal of medicinal chemistry

authors： Hagen H,Marzenell P,Jentzsch E,Wenz F,Veldwijk MR,Mokhir A

更新日期：2012-01-26 00:00:00

abstract：:Protein phosphorylation is the most significant post-translational modification for regulating cellular activities, but site-specific modulation of phosphorylation is still challenging. Using three-dimensional NMR spectra, molecular dynamics simulations, and alanine mutations, we identified that the interaction networ...

journal_title：Journal of medicinal chemistry

authors： Wang Z,Song T,Guo Z,Cao K,Chen C,Feng Y,Wang H,Yin F,Zhou S,Dai J,Zhang Z

更新日期：2020-11-25 00:00:00

abstract：:The family of homodimeric nitric oxide synthases (NOS I-III) catalyzes the generation of the cellular messenger nitric oxide (NO) by oxidation of the substrate L-arginine. The rational design of specific NOS inhibitors is of therapeutic interest in regulating pathological NO levels associated with sepsis, inflammatory...

journal_title：Journal of medicinal chemistry

authors： Matter H,Kotsonis P,Klingler O,Strobel H,Fröhlich LG,Frey A,Pfleiderer W,Schmidt HH

更新日期：2002-07-04 00:00:00

abstract：:A number of cycloalkyl substituents (from C-3 to C-8) have been introduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guano...

journal_title：Journal of medicinal chemistry

authors： Vittori S,Lorenzen A,Stannek C,Costanzi S,Volpini R,IJzerman AP,Kunzel JK,Cristalli G

更新日期：2000-01-27 00:00:00

abstract：:Three series of 4-anilino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic esters were synthesized as part of a program to study potential anti-Leishmania drugs. These compounds were obtained by a condensation reaction of 4-chloro-1H-pyrazolo[3,4-b]pyridine with several aniline derivatives. Some of them were also obtained by a...

journal_title：Journal of medicinal chemistry

authors： de Mello H,Echevarria A,Bernardino AM,Canto-Cavalheiro M,Leon LL

更新日期：2004-10-21 00:00:00

abstract：:As part of an effort to identify novel opioid receptor interactive agents, we recently prepared a series of 8-(substituted)amino analogues of cyclazocine. We found the chiral 8-phenylamino (NHC(6)H(5)) cyclazocine derivative to have subnanomolar affinity for kappa opioid receptors and a 2-fold lower affinity for mu, o...

journal_title：Journal of medicinal chemistry

authors： Wentland MP,Duan W,Cohen DJ,Bidlack JM

更新日期：2000-09-21 00:00:00

abstract：:The dedifferentiation agent "reversine" [2-(4-morpholinoanilino)-N(6)-cyclohexyladenine 2] was found to be a moderately potent antagonist for the human A(3) adenosine receptor (AR) with a K(i) value of 0.66 microM. This result prompted an exploration of the structure-activity relationship of related derivatives, synth...

journal_title：Journal of medicinal chemistry

authors： Perreira M,Jiang JK,Klutz AM,Gao ZG,Shainberg A,Lu C,Thomas CJ,Jacobson KA

更新日期：2005-07-28 00:00:00

abstract：:Reformatski condensation of benzyl 2-bromopropionate with 4-carbomethoxybenzaldehyde, followed by dehydration afforded benzyl 2-methyl-p-carbomethoxycinnamate (4a). Hydrogenation over a Pd catalyst gave the hydrocinnamic acid 5a. Conversion to the chloromethyl (6a) and azidomethyl ketone (7a) was followed by hydrogena...

journal_title：Journal of medicinal chemistry

authors： DeGraw JI,Christie PH,Kisliuk RL,Gaumont Y,Sirotnak FM

更新日期：1990-01-01 00:00:00

abstract：:A series of 8-phenylxanthine derivatives has been synthesized with oxyacetic acid on the para phenyl position to increase aqueous solubility and minimize nonspecific binding and iodinatable groups on the 1- or 3-position of the xanthine ring. The structure-activity relationship for binding of these compounds to A1 ade...

journal_title：Journal of medicinal chemistry

authors： Linden J,Patel A,Earl CQ,Craig RH,Daluge SM

更新日期：1988-04-01 00:00:00

abstract：:Endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH(2)) is an endogenous tetrapeptide that combines potency and efficacy with high affinity and selectivity toward the μ opioid receptor, the most responsible for analgesic effects in the central nervous system. The presence of the Pro(2) represents a crucial factor for the ligand s...

journal_title：Journal of medicinal chemistry

authors： Mollica A,Pinnen F,Stefanucci A,Feliciani F,Campestre C,Mannina L,Sobolev AP,Lucente G,Davis P,Lai J,Ma SW,Porreca F,Hruby VJ

更新日期：2012-04-12 00:00:00

abstract：:A metabolism-based approach toward the optimization of a series of N-arylsulfonamide-based γ-secretase inhibitors is reported. The lead cyclohexyl analogue 6 suffered from extensive oxidation on the cycloalkyl motif by cytochrome P450 3A4, translating into poor human liver microsomal stability. Knowledge of the metabo...

journal_title：Journal of medicinal chemistry

authors： Stepan AF,Karki K,McDonald WS,Dorff PH,Dutra JK,Dirico KJ,Won A,Subramanyam C,Efremov IV,O'Donnell CJ,Nolan CE,Becker SL,Pustilnik LR,Sneed B,Sun H,Lu Y,Robshaw AE,Riddell D,O'Sullivan TJ,Sibley E,Capetta S,Atch

更新日期：2011-11-24 00:00:00

abstract：:Thymidine phosphorylase/platelet-derived endothelial cell growth factor (TP/PD-ECGF) is an enzyme involved in thymidine metabolism and homeostasis, and its catalytic activity appears to play an important role in angiogenesis. Here we describe the cloning and expression of a His-tagged human TP/PD-ECGF and its assay wi...

journal_title：Journal of medicinal chemistry

authors： Focher F,Ubiali D,Pregnolato M,Zhi C,Gambino J,Wright GE,Spadari S

更新日期：2000-06-29 00:00:00

abstract：:As part of our studies on the design of agonists of the luteinizing hormone-releasing hormone (LH-RH), we have synthesized the [des-Gly-NH2(10)]-LH-RH N-methylhydrazide (1), the corresponding thiosemicarbazide (2), and the N-formyl- (3) N-acetyl- (4) and N-(trifluoroacetyl)hydrazide (5). Analogue 1 may be regarded as ...

journal_title：Journal of medicinal chemistry

authors： Nakagawa SH,Yang DC,Flouret G

更新日期：1981-02-01 00:00:00

abstract：:In our efforts to explore marine cyanobacteria as a source of novel bioactive compounds, we discovered a statine unit-containing linear decadepsipeptide, grassystatin A (1), which we screened against a diverse set of 59 proteases. We describe the structure determination of 1 and two natural analogues, grassystatins B ...

journal_title：Journal of medicinal chemistry

authors： Kwan JC,Eksioglu EA,Liu C,Paul VJ,Luesch H

更新日期：2009-09-24 00:00:00

abstract：:3-Phenylpiperidines (PPEs) have been thoroughly investigated in view of their interesting dopaminergic activity, and the N-n-propyl substitution has been suggested as the most effective among several PPEs differently substituted on the phenyl ring. In previous studies, we found that the dimethyl substitution on the ph...

journal_title：Journal of medicinal chemistry

authors： Cervetto L,Demontis GC,Giannaccini G,Longoni B,Macchia B,Macchia M,Martinelli A,Orlandini E

更新日期：1998-12-03 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：:Conformationally restricted 2'-spironucleosides and their prodrugs were synthesized as potential anti-HCV agents. Although the replicon activity of the new agents containing pyrimidine bases was modest, the triphosphate of a 2'-oxetane cytidine analogue demonstrated potent intrinsic biochemical activity against the NS...

journal_title：Journal of medicinal chemistry

authors： Du J,Chun BK,Mosley RT,Bansal S,Bao H,Espiritu C,Lam AM,Murakami E,Niu C,Micolochick Steuer HM,Furman PA,Sofia MJ

更新日期：2014-03-13 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