Novel non-cross resistant diaminoanthraquinones as potential chemotherapeutic agents.

abstract：:Stereoisomers of fenoterol and six fenoterol derivatives have been synthesized and their binding affinities for the beta2 adrenergic receptor (Kibeta2-AR), the subtype selectivity relative to the beta1-AR (Kibeta1-AR/Kibeta2-AR) and their functional activities were determined. Of the 26 compounds synthesized in the st...

journal_title：Journal of medicinal chemistry

authors： Jozwiak K,Khalid C,Tanga MJ,Berzetei-Gurske I,Jimenez L,Kozocas JA,Woo A,Zhu W,Xiao RP,Abernethy DR,Wainer IW

更新日期：2007-06-14 00:00:00

abstract：:Seven 1,2-dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydro-6-demethoxyacronycine esters and diesters were synthesized via osmic oxidation of acronycine or 6-demethoxyacronycine followed by acylation. The 6-demethoxyacronycine derivatives were found to be inactive, whereas in contrast, all of the acronycin...

journal_title：Journal of medicinal chemistry

authors： Elomri A,Mitaku S,Michel S,Skaltsounis AL,Tillequin F,Koch M,Pierré A,Guilbaud N,Léonce S,Kraus-Berthier L,Rolland Y,Atassi G

更新日期：1996-11-22 00:00:00

abstract：:In an effort to explore structural features affecting receptor recognition in a series of conformationally restricted tetrapeptides related to the cyclic, delta opioid receptor-selective analogue, [formula: see text] electronic, lipophilic, and steric effects at the Phe3 residue were assessed by substitution at differ...

journal_title：Journal of medicinal chemistry

authors： Heyl DL,Mosberg HI

更新日期：1992-05-01 00:00:00

abstract：:Glycogen synthase kinase 3beta (GSK-3beta) inhibition is expected to be a promising therapeutic approach for treating Alzheimer's disease. Previously we reported a series of 1,3,4-oxadiazole derivatives as potent and highly selective GSK-3beta inhibitors, however, the representative compounds 1a,b showed poor pharmaco...

journal_title：Journal of medicinal chemistry

authors： Saitoh M,Kunitomo J,Kimura E,Iwashita H,Uno Y,Onishi T,Uchiyama N,Kawamoto T,Tanaka T,Mol CD,Dougan DR,Textor GP,Snell GP,Takizawa M,Itoh F,Kori M

更新日期：2009-10-22 00:00:00

abstract：:Natural lipid nanocarriers, exosomes, carry cell-signaling materials such as DNA and RNA for intercellular communications. Exosomes derived from cancer cells contribute to the progression and metastasis of cancer cells by transferring oncogenic signaling molecules to neighboring and remote premetastatic sites. Therefo...

journal_title：Journal of medicinal chemistry

authors： Tamura R,Balabanova A,Frakes SA,Bargmann A,Grimm J,Koch TH,Yin H

更新日期：2019-02-28 00:00:00

abstract：:A series of both aliphatic and aromatic amides and aromatic amidines derived from 2-amino-1,10-phenanthroline (3) according to the Topliss scheme were synthesized and subsequently tested for antimycoplasmal potency. Although the compounds themselves showed no activity, in the presence of a nontoxic copper concentratio...

journal_title：Journal of medicinal chemistry

authors： de Zwart MA,Bastiaans HM,van der Goot H,Timmerman H

更新日期：1991-03-01 00:00:00

abstract：:As a continuation of our efforts to develop innovative ligands for D(3), 5-HT(1A), and 5-HT(2A) receptors with low propensity to block hERG channels, we propose a series bishetero(homo)arylpiperazines 5a-m as novel and potent multifunctional ligands characterized by low occupancy at D(2) and 5-HT(2C) receptors. ...

journal_title：Journal of medicinal chemistry

authors： Butini S,Campiani G,Franceschini S,Trotta F,Kumar V,Guarino E,Borrelli G,Fiorini I,Novellino E,Fattorusso C,Persico M,Orteca N,Sandager-Nielsen K,Jacobsen TA,Madsen K,Scheel-Kruger J,Gemma S

更新日期：2010-06-24 00:00:00

abstract：:To evaluate nonaromatic catechol bioisosteres, the conformationally restrained enynes 1 and enediynes 2 were synthesized via palladium-catalyzed coupling as the key reaction step. Subsequent receptor binding studies at the dopamine receptor subtypes D(1), D(2 long), D(2 short), D(3), and D(4) showed highly interesting...

journal_title：Journal of medicinal chemistry

authors： Hübner H,Haubmann C,Utz W,Gmeiner P

更新日期：2000-02-24 00:00:00

abstract：:A broad screening program previously identified phenprocoumon (1) as a small molecule template for inhibition of HIV protease. Subsequent modification of this lead through iterative cycles of structure-based design led to the activity enhancements of pyrone and dihydropyrone ring systems (II and V) and amide-based sub...

journal_title：Journal of medicinal chemistry

authors： Turner SR,Strohbach JW,Tommasi RA,Aristoff PA,Johnson PD,Skulnick HI,Dolak LA,Seest EP,Tomich PK,Bohanon MJ,Horng MM,Lynn JC,Chong KT,Hinshaw RR,Watenpaugh KD,Janakiraman MN,Thaisrivongs S

更新日期：1998-08-27 00:00:00

abstract：:In the present paper we describe the synthesis of some dermorphin and deltorphin analogues beta-O- and alpha-C-glycosylated on the C-terminal amino acid residue and report their opioid receptor affinity and selectivity as well as their analgesic potency after subcutaneous injection in mice. ...

journal_title：Journal of medicinal chemistry

authors： Negri L,Lattanzi R,Tabacco F,Orrù L,Severini C,Scolaro B,Rocchi R

更新日期：1999-02-11 00:00:00

abstract：:The leukotrienes, metabolites of arachidonic acid produced through the action of the enzyme 5-lipoxygenase, are important mediators of immediate hypersensitivity and inflammation. Among the variety of diseases in which the leukotrienes may play a symptomatic or causative role is the dermatological condition psoriasis,...

journal_title：Journal of medicinal chemistry

authors： Hammond ML,Zambias RA,Chang MN,Jensen NP,McDonald J,Thompson K,Boulton DA,Kopka IE,Hand KM,Opas EE

更新日期：1990-03-01 00:00:00

abstract：:Previous quantitative and qualitative structure-activity studies in antibacterial monosubstituted 1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids prompted us to synthesize the 6,7,8-polysubstituted compounds. In this paper, the preparation and antibacterial activity of the 6,7- and 7,8-disubstituted compounds an...

journal_title：Journal of medicinal chemistry

authors： Koga H,Itoh A,Murayama S,Suzue S,Irikura T

更新日期：1980-12-01 00:00:00

abstract：:A series of novel linear aliphatic amine-linked triaryl derivatives as inhibitors of PD-1/PD-L1 were designed, synthesized, and evaluated in vitro and in vivo. In this chemical series, compound 58 showed the most potent inhibitory activity and binding affinity with hPD-L1, with an IC50 value of 12 nM and a KD value of...

journal_title：Journal of medicinal chemistry

authors： Guo J,Luo L,Wang Z,Hu N,Wang W,Xie F,Liang E,Yan X,Xiao J,Li S

更新日期：2020-11-25 00:00:00

abstract：:Replacement of the catecholic hydroxyl groups of the beta-adrenergic receptor agonist 6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline (trimetoquinol) with chloro substituents results in a compound with marked beta-adrenoceptor antagonist properties. This, therefore, parallels the similar transf...

journal_title：Journal of medicinal chemistry

authors： Kaiser C,Oh HJ,Garcia-Slanga BJ,Sulpizio AC,Hieble JP,Wawro JE,Kruse LI

更新日期：1986-11-01 00:00:00

abstract：:6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring ...

journal_title：Journal of medicinal chemistry

authors： Nakagawa-Goto K,Chang PC,Lai CY,Hung HY,Chen TH,Wu PC,Zhu H,Sedykh A,Bastow KF,Lee KH

更新日期：2010-09-23 00:00:00

abstract：:In order to determine the influence of a 6alpha-methyl group activity, the 6alpha-methyl derivative of digitoxigenin 3-acetate 14 was prepared and pharmacologically tested in comparison with digitoxigenen 3-acetate. The synthesis of 6alpha-methyldigitoxigenin 3-acetate (14) was performed starting from 21-hydroxy-4-pre...

journal_title：Journal of medicinal chemistry

authors： Valcavi U,Corsi B,Caponi R,Innocenti S,Martelli P

更新日期：1975-12-01 00:00:00

abstract：:Protein target-based discovery of novel antibiotics has been largely unsuccessful despite rich genome information. Particularly in need are new antibiotics for tuberculosis, which kills 1.6 million people annually and shows a rapid increase in multiple-drug-resistant cases. By combining fragment-based drug discovery w...

journal_title：Journal of medicinal chemistry

authors： Scheich C,Puetter V,Schade M

更新日期：2010-12-09 00:00:00

abstract：:The vinyl ethers of choline and of its alpha- and beta-methyl homologues were prepared to determine their cholinergic effects and to determine whether a separation of the dual physiologic activity (nicotinic and muscarinic) reported for the vinyl ether of choline could be achieved by this modification. A literature me...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Gangjee A

更新日期：1976-07-01 00:00:00

abstract：:Tumor suppressor protein, p53, is an intracellular protein that is critical within the biochemical cascade that leads to cell death via apoptosis. Recent studies identified the tetrahydrobenzothiazole analogue, pifithrin-alpha (2), as a p53 inhibitor that was effective in protecting neuronal cells against a variety of...

journal_title：Journal of medicinal chemistry

authors： Zhu X,Yu QS,Cutler RG,Culmsee CW,Holloway HW,Lahiri DK,Mattson MP,Greig NH

更新日期：2002-11-07 00:00:00

abstract：:The construction of bioactive peptides using β-amino acid-containing sequence patterns is a very promising strategy to obtain analogues that exhibit properties of high interest for medicinal chemistry applications. β-Amino acids have been shown to modulate the conformation, dynamics, and proteolytic susceptibility of ...

journal_title：Journal of medicinal chemistry

authors： Cabrele C,Martinek TA,Reiser O,Berlicki Ł

更新日期：2014-12-11 00:00:00

abstract：:(N)-Methanocarba nucleosides containing bicyclo[3.1.0]hexane replacement of the ribose ring previously demonstrated selectivity as A(3) adenosine receptor (AR) agonists (5'-uronamides) or antagonists (5'-truncated). Here, these two series were modified in parallel at the adenine C2 position. N(6)-3-Chlorobenzyl-5'-N-m...

journal_title：Journal of medicinal chemistry

authors： Tosh DK,Chinn M,Ivanov AA,Klutz AM,Gao ZG,Jacobson KA

更新日期：2009-12-10 00:00:00

abstract：:Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of cdk inhibition showed that the 1, 3; and 7 positions of the purine ring must remain free, probably for a direct interaction, in...

journal_title：Journal of medicinal chemistry

authors： Havlícek L,Hanus J,Veselý J,Leclerc S,Meijer L,Shaw G,Strnad M

更新日期：1997-02-14 00:00:00

abstract：:Inhibition of the menin-mixed lineage leukemia (MLL) protein-protein interaction is a promising new therapeutic strategy for the treatment of acute leukemia carrying MLL fusion (MLL leukemia). We describe herein our structure-based design, synthesis, and evaluation of a new class of small-molecule inhibitors of the me...

journal_title：Journal of medicinal chemistry

authors： Aguilar A,Zheng K,Xu T,Xu S,Huang L,Fernandez-Salas E,Liu L,Bernard D,Harvey KP,Foster C,McEachern D,Stuckey J,Chinnaswamy K,Delproposto J,Kampf JW,Wang S

更新日期：2019-07-11 00:00:00

abstract：:From salicyclic acid, the two enantiomers of N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2-methoxybenzamide (6b) were prepared in a five-step synthesis. With use of Heindel's triazene method for introduction of the radionuclide, the iodine-125-labeled substituted benzamide was obtained with a calculated specific activit...

journal_title：Journal of medicinal chemistry

authors： de Paulis T,Janowsky A,Kessler RM,Clanton JA,Smith HE

更新日期：1988-10-01 00:00:00

abstract：:We synthesized 5-substituted pyrrolo[2,3-d]pyrimidine antifolates (compounds 5-10) with one-to-six bridge carbons and a benozyl ring in the side chain as antitumor agents. Compound 8 with a 4-carbon bridge was the most active analogue and potently inhibited proliferation of folate receptor (FR) α-expressing Chinese ha...

journal_title：Journal of medicinal chemistry

authors： Mitchell-Ryan S,Wang Y,Raghavan S,Ravindra MP,Hales E,Orr S,Cherian C,Hou Z,Matherly LH,Gangjee A

更新日期：2013-12-27 00:00:00

abstract：:High-resolution, three-dimensional structures of vancomycin and aglyco-vancomycin in DMSO were determined by nuclear magnetic resonance, metric matrix distance geometry, and molecular dynamics calculations. Conformational flexibility fast on the NMR time scale was examined by ensemble-based calculations which apply th...

journal_title：Journal of medicinal chemistry

authors： Grdadolnik SG,Pristovsek P,Mierke DF

更新日期：1998-06-04 00:00:00

abstract：:Methyllycaconitine (MLA, 1) is a novel, potent probe for mammalian and insect nicotinic acetylcholine receptors (nAChR) and displays remarkable selectivity toward neuronal [125I]-alpha-bungarotoxin (alpha BgTX) binding sites that correspond to alpha 7-type nAChR in mammalian brain. We have shown that, among a number o...

journal_title：Journal of medicinal chemistry

authors： Hardick DJ,Blagbrough IS,Cooper G,Potter BV,Critchley T,Wonnacott S

更新日期：1996-11-22 00:00:00

abstract：:Twenty N- and/or C-modified Dmt-Tic analogues yielded similar K(i) values with either [(3)H]DPDPE (delta(1) agonist) or [(3)H]N, N(Me)(2)-Dmt-Tic-OH (delta antagonist). N-Methylation enhanced delta antagonism while N-piperidine-1-yl, N-pyrrolidine-1-yl, and N-pyrrole-1-yl were detrimental. Dmt-Tic-X (X = -NHNH(2), -NH...

journal_title：Journal of medicinal chemistry

authors： Salvadori S,Guerrini R,Balboni G,Bianchi C,Bryant SD,Cooper PS,Lazarus LH

更新日期：1999-12-02 00:00:00

abstract：:A series of homo- and heterodimeric ligands containing kappa agonist and mu agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors. The functional activities of these compounds were measured...

journal_title：Journal of medicinal chemistry

authors： Peng X,Knapp BI,Bidlack JM,Neumeyer JL

更新日期：2006-01-12 00:00:00

abstract：:In this study we present the synthesis and some pharmacological properties of nine new analogues of arginine vasopressin modified in the N-terminal part of the molecule with 2-aminoindane-2-carboxylic acid (Aic). The peptides were tested for their in vitro uterotonic and in vivo pressor and antidiuretic activities. On...

journal_title：Journal of medicinal chemistry

authors： Kowalczyk W,Sobolewski D,Prahl A,Derdowska I,Borovicková L,Slaninová J,Lammek B

更新日期：2007-06-14 00:00:00