Comparison of quantitative structure-activity relationships of the inhibition of leukemia cells in culture with the inhibition of dihydrofolate reductase from leukemia cells and other cell types.

abstract：:Mercaptopurine (6-MP), thioguanine (6-TG), and azathioprine (AZA) are purine antimetabolites introduced as anticancer or immunosuppressive drugs decades ago. Methylated AZA, called MAZA, is among the investigational drugs. The present study compares MAZA to the widely recognized drugs AZA, 6-MP, and 6-TG with respect ...

journal_title：Journal of medicinal chemistry

authors： Hoffmann M,Chrzanowska M,Hermann T,Rychlewski J

更新日期：2005-06-30 00:00:00

abstract：:The five dopamine receptor subtypes (D1-5) are activated by the endogenous catecholamine dopamine. Sustained research has sought to identify selective ligands for receptor subtypes. In particular, activation of the D1 receptor has attracted attention due to its promising role in neurological diseases. Initial attempts...

journal_title：Journal of medicinal chemistry

authors： Hall A,Provins L,Valade A

更新日期：2019-01-10 00:00:00

abstract：:Random screening of compounds in an ETA receptor binding assay led to the discovery of a class of benzenesulfonamide ligands. Optimization led to the development of 5-amino-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamides which were functional antagonists. Structural features which were important to activity in...

journal_title：Journal of medicinal chemistry

authors： Stein PD,Floyd DM,Bisaha S,Dickey J,Girotra RN,Gougoutas JZ,Kozlowski M,Lee VG,Liu EC,Malley MF

更新日期：1995-04-14 00:00:00

abstract：:We recently introduced sulfated pentagalloylglucopyranoside (SPGG) as an allosteric inhibitor of factor XIa (FXIa) (Al-Horani et al., J. Med Chem. 2013, 56, 867-878). To better understand the SPGG-FXIa interaction, we utilized eight SPGG variants and a range of biochemical techniques. The results reveal that SPGG's su...

journal_title：Journal of medicinal chemistry

authors： Al-Horani RA,Desai UR

更新日期：2014-06-12 00:00:00

abstract：:Optimization of a 5-oxopyrrolopyridine series based upon structure-activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the ...

journal_title：Journal of medicinal chemistry

authors： Devasthale P,Wang Y,Wang W,Fevig J,Feng J,Wang A,Harrity T,Egan D,Morgan N,Cap M,Fura A,Klei HE,Kish K,Weigelt C,Sun L,Levesque P,Moulin F,Li YX,Zahler R,Kirby MS,Hamann LG

更新日期：2013-09-26 00:00:00

abstract：:Peptide mimetics of the RGDF sequence in which Arg-Gly has been replaced with 5-(4-amidinophenyl)pentanoyl mimetic has led to a 1000-fold increase in inhibitory potency over the natural RGDF ligand. The guanidine residue of the arginine may be involved in a reinforced ionic interaction with a carboxylate of the recept...

journal_title：Journal of medicinal chemistry

authors： Zablocki JA,Miyano M,Garland RB,Pireh D,Schretzman L,Rao SN,Lindmark RJ,Panzer-Knodle SG,Nicholson NS,Taite BB

更新日期：1993-06-25 00:00:00

abstract：:A common dichotomy exists in inhibitor design: should the compounds be designed to block the enzymes of animals in the preclinical studies or to inhibit the human enzyme? We report that a single mutation of Leu-337 in rat neuronal nitric oxide synthase (nNOS) to His makes the enzyme resemble human nNOS more than rat n...

journal_title：Journal of medicinal chemistry

authors： Fang J,Ji H,Lawton GR,Xue F,Roman LJ,Silverman RB

更新日期：2009-07-23 00:00:00

abstract：:We have introduced topographical constraints at the 9 position of a superpotent cyclic alpha-melanotropin analogue, Ac-Nle4-Asp5-His6-DPhe7-Arg8-Trp9-Lys10-NH2, by incorporating a methyl group at the beta-carbon of Trp9. These studies were performed on the Trp side chain pharmacophore to identify the bioactive topogra...

journal_title：Journal of medicinal chemistry

authors： Haskell-Luevano C,Boteju LW,Miwa H,Dickinson C,Gantz I,Yamada T,Hadley ME,Hruby VJ

更新日期：1995-11-10 00:00:00

abstract：:We have previously described the design and development of CI-988, a peptoid analogue of CCK-4 with excellent binding affinity and selectivity for the CCK-B receptor. Due to its anxiolytic profile in animal models of anxiety, this compound was developed as a clinical candidate. However, during its development, it was ...

journal_title：Journal of medicinal chemistry

authors： Trivedi BK,Padia JK,Holmes A,Rose S,Wright DS,Hinton JP,Pritchard MC,Eden JM,Kneen C,Webdale L,Suman-Chauhan N,Boden P,Singh L,Field MJ,Hill D

更新日期：1998-01-01 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：:Matrix metalloproteinases (MMPs) are a family of over 20 zinc-dependent enzymes that hydrolyze connective tissue and are involved in a variety of diseases, which are associated with undesired tissue breakdown. This paper reports the synthesis, characterization, and biological evaluation of a novel class of MMP inhibit...

journal_title：Journal of medicinal chemistry

authors： Breuer E,Salomon CJ,Katz Y,Chen W,Lu S,Röschenthaler GV,Hadar R,Reich R

更新日期：2004-05-20 00:00:00

abstract：:The synthesis of 19 (5-nitro-2,3-dihydro-1H-benzo[e]indol-1-yl)methyl sulfonate prodrugs containing sulfonate leaving groups and 7-substituted electron-withdrawing groups is reported. These were designed to undergo hypoxia-selective metabolism to form potent DNA minor groove-alkylating agents. Analogues 17 and 24, con...

journal_title：Journal of medicinal chemistry

authors： Stevenson RJ,Denny WA,Tercel M,Pruijn FB,Ashoorzadeh A

更新日期：2012-03-22 00:00:00

abstract：:The synthesis and in vitro and in vivo antibreast and antiprostate cancers activities of novel C-4 heteroaryl 13-cis-retinamides that modulate Mnk-eIF4E and AR signaling are discussed. Modifications of the C-4 heteroaryl substituents reveal that the 1H-imidazole is essential for high anticancer activity. The most pote...

journal_title：Journal of medicinal chemistry

authors： Mbatia HW,Ramalingam S,Ramamurthy VP,Martin MS,Kwegyir-Afful AK,Njar VC

更新日期：2015-02-26 00:00:00

abstract：:Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary b...

journal_title：Journal of medicinal chemistry

authors： Morrell A,Placzek M,Parmley S,Grella B,Antony S,Pommier Y,Cushman M

更新日期：2007-09-06 00:00:00

abstract：:From the results of our previous physicochemical studies of polyamine-nucleic acid interactions, we concluded that polyamine analogues in cisoidal conformation are capable of wrapping around the major groove of the double helix, of displacing natural polyamines from their nucleic acid binding sites, and of inhibiting ...

journal_title：Journal of medicinal chemistry

authors： Reddy VK,Sarkar A,Valasinas A,Marton LJ,Basu HS,Frydman B

更新日期：2001-02-01 00:00:00

abstract：:3-(3-Cyclopentyloxy-4-methoxy-benzyl)-8-isopropyl-adenine V11294 (1) has been identified as a lead structure, which selectively inhibits human lung PDE4 (436 nM) and is also active in a number of in vitro and in vivo models of inflammation. Here we describe the synthesis and pharmacology of a series of highly potent 8...

journal_title：Journal of medicinal chemistry

authors： Whitehead JW,Lee GP,Gharagozloo P,Hofer P,Gehrig A,Wintergerst P,Smyth D,McCoull W,Hachicha M,Patel A,Kyle DJ

更新日期：2005-02-24 00:00:00

abstract：:A series of 3-thioindolamidines (and 3-indolamidines) related to mixidine (1) was studied for cardiac-slowing properties, following the discovery of activity for prototype thioindole 2. Structure-activity relationships were explored, leading to many potent antitachycardiac agents (6-9, 12, 13, 15-17, 20, 23, 24, 30, 3...

journal_title：Journal of medicinal chemistry

authors： Zelesko MJ,McComsey DF,Hageman WE,Nortey SO,Baker CA,Maryanoff BE

更新日期：1983-02-01 00:00:00

abstract：:Dideoxy- and trideoxynucleosides of 5-fluorouracil have been synthesized for antitumor evaluation. 2',5'-Dideoxy-5-fluorouridine (3) was prepared from 2'-deoxy-5-fluorouridine (1) by iodination using methyltriphenoxyphosponium iodide, followed by catalytic reduction. 1-(2',5'-Dideoxy-beta-D-threo-pentofuranosyl)5-fluo...

journal_title：Journal of medicinal chemistry

authors： Cook AF,Holman MJ,Kramer MJ

更新日期：1980-08-01 00:00:00

abstract：:The discovery of a new zinc binding chemotype from screening a nonbiased fragment library is reported. Using the orthogonal fragment screening methods of native state mass spectrometry and surface plasmon resonance a 3-unsubstituted 2,4-oxazolidinedione fragment was found to have low micromolar binding affinity to the...

journal_title：Journal of medicinal chemistry

authors： Chrysanthopoulos PK,Mujumdar P,Woods LA,Dolezal O,Ren B,Peat TS,Poulsen SA

更新日期：2017-09-14 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：:(R)-PCEP (3-amino-3-carboxypropyl-2'-carboxyethyl phosphinic acid, 1), a new metabotropic glutamate receptor 4 (mGlu4R) agonist, was discovered in a previously reported virtual screening. The (S)-enantiomer and a series of derivatives were synthesized and tested on recombinant mGlu4 receptors. A large number of deriva...

journal_title：Journal of medicinal chemistry

authors： Selvam C,Oueslati N,Lemasson IA,Brabet I,Rigault D,Courtiol T,Cesarini S,Triballeau N,Bertrand HO,Goudet C,Pin JP,Acher FC

更新日期：2010-04-08 00:00:00

abstract：:The labeling of proteins with ubiquitin/ubiquitin-like (Ubl) proteins is crucial for several physiological processes and in the onset of various diseases. Recently, targeting ubiquitin protein labeling has shifted toward the use of allosteric mechanisms over classical activity-based approaches. Allosteric enzyme regul...

journal_title：Journal of medicinal chemistry

authors： Paiva SL,da Silva SR,de Araujo ED,Gunning PT

更新日期：2018-01-25 00:00:00

abstract：:A new class of substituted 1-phenyl-3-piperazinyl-2-propanones with antimuscarinic activity is reported. As part of a structure-activity relationship study of this class, various structural modifications, particularly ones involving substitution of position 1 and the terminal piperazine nitrogen, were investigated. Th...

journal_title：Journal of medicinal chemistry

authors： Kaiser C,Audia VH,Carter JP,McPherson DW,Waid PP,Lowe VC,Noronha-Blob L

更新日期：1993-03-05 00:00:00

abstract：:We report novel inhibitors of Gli1-mediated transcription as potential anticancer agents. Focused chemical libraries were designed and assessed for inhibition of functional cell-based Gli1-mediated transcription and selective toxicity toward cancer cells. The SAR was revealed, and the selectivity of the lead compounds...

journal_title：Journal of medicinal chemistry

authors： Mahindroo N,Connelly MC,Punchihewa C,Kimura H,Smeltzer MP,Wu S,Fujii N

更新日期：2009-07-23 00:00:00

abstract：:A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC(50) of the most active compound (5da) was 15.7 nM. ABI analo...

journal_title：Journal of medicinal chemistry

authors： Chen J,Wang Z,Li CM,Lu Y,Vaddady PK,Meibohm B,Dalton JT,Miller DD,Li W

更新日期：2010-10-28 00:00:00

abstract：:We designed a series of benzoic acid derivatives containing the biphenyl ether or biphenyl template on the RHS and a phenylethanolaminotetraline (PEAT) skeleton, which was prepared by highly stereoselective synthesis, to generate two structurally different lead compounds ( 10c, 10m) with a good balance of potency, sel...

journal_title：Journal of medicinal chemistry

authors： Imanishi M,Nakajima Y,Tomishima Y,Hamashima H,Washizuka K,Sakurai M,Matsui S,Imamura E,Ueshima K,Yamamoto T,Yamamoto N,Ishikawa H,Nakano K,Unami N,Hamada K,Matsumura Y,Takamura F,Hattori K

更新日期：2008-08-14 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：:New series of pyrrolidine mercaptosulfide, 2-mercaptocyclopentane arylsulfonamide, and 3-mercapto-4-arylsulfonamidopyrrolidine matrix metalloproteinase inhibitors (MMPIs) were designed, synthesized, and evaluated. Exhibiting unique properties over other MMPIs (e.g., hydroxamates), these newly reported compounds are ca...

journal_title：Journal of medicinal chemistry

authors： Jin Y,Roycik MD,Bosco DB,Cao Q,Constantino MH,Schwartz MA,Sang QX

更新日期：2013-06-13 00:00:00

abstract：:Small molecule protein kinase inhibitors are widely employed as biological reagents and as leads in the design of drugs for a variety of diseases. One of the hardest challenges in kinase inhibitor design is achieving target selectivity. By utilizing X-ray structural information for four promiscuous inhibitors, we prop...

journal_title：Journal of medicinal chemistry

authors： Aronov AM,Murcko MA

更新日期：2004-11-04 00:00:00

abstract：:A new series of zinc(II) phthalocyanine derivatives have been synthesized and characterized. These macrocycles exhibited a sharp absorption band in the red visible region in DMF, which indicated that they were dissolved well and almost did not aggregate in this solvent. Compared with the unsubstituted zinc(II) phthalo...

journal_title：Journal of medicinal chemistry

authors： Jia X,Yang FF,Li J,Liu JY,Xue JP

更新日期：2013-07-25 00:00:00