Synthesis and evaluation of oxodioxolenylmethyl carbamate prodrugs of pseudomycins.

abstract：:Members of the Wee family of kinases negatively regulate the cell cycle via phosphorylation of CDK1 and are considered potential drug targets. Herein, we investigated the structure-function relationship of human Wee1, Wee2, and Myt1 (PKMYT1). Purified recombinant full-length proteins and kinase domain constructs diffe...

journal_title：Journal of medicinal chemistry

authors： Zhu JY,Cuellar RA,Berndt N,Lee HE,Olesen SH,Martin MP,Jensen JT,Georg GI,Schönbrunn E

更新日期：2017-09-28 00:00:00

abstract：:A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compound 1a [(E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- ...

journal_title：Journal of medicinal chemistry

authors： Nishikawa Y,Shindo T,Ishii K,Nakamura H,Kon T,Uno H

更新日期：1989-03-01 00:00:00

abstract：:A series of 2-aryldopamine analogues were synthesized and evaluated for their effects on D1 and D2 dopamine receptors. The 2-phenyldopamine and 6-phenylbenzazepine analogues exhibited weak binding to both D1 and D2 receptors. The 9-(aminomethyl)fluorenes also exhibited weak D2 binding; however, 2,5,6-trihydroxy-9H-flu...

journal_title：Journal of medicinal chemistry

authors： Ladd DL,Weinstock J,Wise M,Gessner GW,Sawyer JL,Flaim KE

更新日期：1986-10-01 00:00:00

abstract：:In this work, we describe the synthesis and in vitro evaluation of a novel series of multitarget-directed ligands (MTDL) displaying both nanomolar dual-binding site (DBS) acetylcholinesterase inhibitory effects and partial 5-HT4R agonist activity, among which donecopride was selected for further in vivo evaluations in...

journal_title：Journal of medicinal chemistry

authors： Rochais C,Lecoutey C,Gaven F,Giannoni P,Hamidouche K,Hedou D,Dubost E,Genest D,Yahiaoui S,Freret T,Bouet V,Dauphin F,Sopkova de Oliveira Santos J,Ballandonne C,Corvaisier S,Malzert-Fréon A,Legay R,Boulouard M,Claeysen

更新日期：2015-04-09 00:00:00

abstract：:Two molecules with known growth hormone secretagogue (GHS) agonist activity were used as templates to computationally screen approximately 80000 compounds. A total of 108 candidate compounds were selected, and five of them were found to be active in the low-micromolar range in both cell-based and direct binding assays...

journal_title：Journal of medicinal chemistry

authors： Shoda M,Harada T,Kogami Y,Tsujita R,Akashi H,Kouji H,Stahura FL,Xue L,Bajorath J

更新日期：2004-08-12 00:00:00

abstract：:The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationsh...

journal_title：Journal of medicinal chemistry

authors： Azevedo CM,Watterson KR,Wargent ET,Hansen SV,Hudson BD,Kępczyńska MA,Dunlop J,Shimpukade B,Christiansen E,Milligan G,Stocker CJ,Ulven T

更新日期：2016-10-13 00:00:00

abstract：:We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray...

journal_title：Journal of medicinal chemistry

authors： Savechenkov PY,Zhang X,Chiara DC,Stewart DS,Ge R,Zhou X,Raines DE,Cohen JB,Forman SA,Miller KW,Bruzik KS

更新日期：2012-07-26 00:00:00

abstract：:The antibacterial 4H-4-oxoquinolizines were introduced recently to overcome bacterial resistance to fluoroquinolones. They exhibit potent antibacterial activity against Gram-positive, Gram-negative, and anaerobic organisms and are highly active against some quinolone-resistant bacteria including quinolone-resistant MR...

journal_title：Journal of medicinal chemistry

authors： Ma Z,Chu DT,Cooper CS,Li Q,Fung AK,Wang S,Shen LL,Flamm RK,Nilius AM,Alder JD,Meulbroek JA,Or YS

更新日期：1999-10-07 00:00:00

abstract：:Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) and the C-terminal partial sequences down to the tripeptide were synthesized by a solid-phase method. These peptides were assayed for vasodilator, spasmogenic, and venoconstrictor properties using three preparations, viz. the hind limb blood flow of the dog...

journal_title：Journal of medicinal chemistry

authors： Bury RW,Mashford ML

更新日期：1976-06-01 00:00:00

abstract：:The variation in amino acid sequence within sets of peptides is described by three principal properties, z1, z2, and z3, per varied amino acid position. These principal properties are derived from a principal components analysis of a matrix of 29 physicochemical variables for the 20 coded (in mRNA) amino acids. The sc...

journal_title：Journal of medicinal chemistry

authors： Hellberg S,Sjöström M,Skagerberg B,Wold S

更新日期：1987-07-01 00:00:00

abstract：:The preparation and antitubercular properties of a series of 2,8-bis(alkylaminomethyl)phenazines are described. These compounds all inhibited the growth of Mycobacterium smegmatis ATCC 607 in vitro. 2,8-Bis(dibutylaminomethyl)phenazine (5c) was also active against a lethal Mycobacterium tuberculosis H37Rv infection in...

journal_title：Journal of medicinal chemistry

authors： Murdock KC,Lin Y,Thomas JP,Lang SA Jr

更新日期：1978-04-01 00:00:00

abstract：:Previously reported 2-(hydroxymethyl)indoloquinones, prepared as their acetates or carbamates, were less active than 2-methyl analogues in bacterial cultures and they had no activity in mice, despite functionality appropriate for DNA cross-linking. On the basis of the hypothesis that these compounds might have been to...

journal_title：Journal of medicinal chemistry

authors： Iyengar BS,Remers WA,Catino JJ

更新日期：1989-08-01 00:00:00

abstract：:The synthesis and gastric antisecretory activities of the delta 4,5-cis, delta 4,5-trans, and 4,5-acetylenic analogues of 15-deoxy-16-hydroxy-16-methyl prostaglandin E1 methyl ester are described. The key step in the preparation of these compounds involved the stereospecific conjugate addition of a cuprate reagent to ...

journal_title：Journal of medicinal chemistry

authors： Collins PW,Dajani EZ,Pappo R,Gasiecki AF,Bianchi RG,Woods EM

更新日期：1983-06-01 00:00:00

abstract：:3,4-Dihydro-2(1H)-quinolones, evolved from 2-carboxy-1,2,3,4,- tetrahydroquinolines and 3-carboxy-4-hydroxy-2(1H)-quinolones, have been synthesized and evaluated in vitro for antagonist activity at the glycine site on the NMDA receptor and for AMPA [(RS)-alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid] antag...

journal_title：Journal of medicinal chemistry

authors： Carling RW,Leeson PD,Moore KW,Smith JD,Moyes CR,Mawer IM,Thomas S,Chan T,Baker R,Foster AC

更新日期：1993-10-29 00:00:00

abstract：:Rotigaptide (3) is an antiarrhythmic peptide that improves cardiac conduction by modifying gap-junction communication. Small molecule gap-junction modifiers with improved physical properties were identified from a Zealand Pharma peptide library using pharmaceutical profiling, established SAR around 3, and a putative p...

journal_title：Journal of medicinal chemistry

authors： Butera JA,Larsen BD,Hennan JK,Kerns E,Di L,Alimardanov A,Swillo RE,Morgan GA,Liu K,Wang Q,Rossman EI,Unwalla R,McDonald L,Huselton C,Petersen JS

更新日期：2009-02-26 00:00:00

abstract：:Inherently conducting polymers (ICPs) are a specific category of synthetic polymers with distinctive electro-optic properties, which involve conjugated chains with alternating single and double bonds. Polyaniline (PANI), as one of the most well-known ICPs, has outstanding potential applications in biomedicine because ...

journal_title：Journal of medicinal chemistry

authors： Zare EN,Makvandi P,Ashtari B,Rossi F,Motahari A,Perale G

更新日期：2020-01-09 00:00:00

abstract：:Vacuolar type ATPase (V-ATPase) has recently emerged as a promising novel anticancer target based on extensive in vitro and in vivo studies with archazolids, complex polyketide macrolides, which present the most potent V-ATPase inhibitors known to date. Herein, we report a biomimetic, one-step preparation of archazoli...

journal_title：Journal of medicinal chemistry

authors： Scheeff S,Rivière S,Ruiz J,Abdelrahman A,Schulz-Fincke AC,Köse M,Tiburcy F,Wieczorek H,Gütschow M,Müller CE,Menche D

更新日期：2020-02-27 00:00:00

abstract：:New imidazo[1,2-a]pyridines substituted at the 3-position have been synthesized as potential antisecretory and cytoprotective antiulcer agents. The synthetic routes began with cyclization of aminopyridines 5a,b and chloro ketones 6a,b to give imidazo[1,2-a]pyridines 7-9. The side chain at the 3-position was elaborated...

journal_title：Journal of medicinal chemistry

authors： Starrett JE Jr,Montzka TA,Crosswell AR,Cavanagh RL

更新日期：1989-09-01 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：:In order to increase the retention of drug activity, regiospecific coupling has been used to synthesize conjugates of methotrexate (MTX, 1) with normal rabbit IgG (NRG) and a mouse anti-human renal cancer monoclonal IgG (Dal K-20). MTX gamma-methyl ester (4) was produced either by selective esterification of MTX or by...

journal_title：Journal of medicinal chemistry

authors： Kralovec J,Spencer G,Blair AH,Mammen M,Singh M,Ghose T

更新日期：1989-11-01 00:00:00

abstract：:A pharmacophore-based search led to the identification of thiazolopyridine ureas as a novel scaffold with antitubercular activity acting through inhibition of DNA Gyrase B (GyrB) ATPase. Evaluation of the binding mode of thiazolopyridines in a Mycobacterium tuberculosis (Mtb) GyrB homology model prompted exploration o...

journal_title：Journal of medicinal chemistry

authors： Kale MG,Raichurkar A,P SH,Waterson D,McKinney D,Manjunatha MR,Kranthi U,Koushik K,Jena Lk,Shinde V,Rudrapatna S,Barde S,Humnabadkar V,Madhavapeddi P,Basavarajappa H,Ghosh A,Ramya VK,Guptha S,Sharma S,Vachaspati P,

更新日期：2013-11-14 00:00:00

abstract：:Thrombin is a serine protease responsible for blood coagulation. Since thrombin inhibitors appear to be effective in the treatment and prevention of thrombotic and embolic disorders, considerable attention has been focused on the structure and interactions of this enzyme. In this work, to evaluate the relative free en...

journal_title：Journal of medicinal chemistry

authors： Guimarães CR,Bicca de Alencastro R

更新日期：2002-11-07 00:00:00

abstract：:The effect of a variety of aryl substituents on the potency and selectivity of 19 analogues of 1,3-dipropyl-8-phenylxanthine as antagonists at A1- and A2-adenosine receptors in brain tissue was determined. The 4-sulfamoylphenyl and 4-carbamoylphenyl analogues are potent and somewhat selective for the A1 receptor. None...

journal_title：Journal of medicinal chemistry

authors： Daly JW,Padgett WL,Shamim MT

更新日期：1986-08-01 00:00:00

abstract：:Two isomeric 6-endo- and 6-exo-(3',4'-dihydroxyphenyl) derivatives (1 and 2) of 2-azabicyclo[2.2.2]octane were synthesized as semirigid analogues of dopamine (DA) to help evaluate the preferred conformation of dopamine at the uptake site of the presynaptic nerve terminal and at the DA receptor. Against the uptake of 0...

journal_title：Journal of medicinal chemistry

authors： Law SJ,Morgan JM,Masten LW,Borne RF,Arana GW,Kula NS,Baldessarini RJ

更新日期：1982-03-01 00:00:00

abstract：:Adverse drug reactions (ADRs) are a common cause of attrition in drug discovery and development and drug-induced liver injury (DILI) is a leading cause of preclinical and clinical drug terminations. This perspective outlines many of the known DILI mechanisms and assessment methods used to evaluate and mitigate DILI ri...

journal_title：Journal of medicinal chemistry

authors： Norman BH

更新日期：2020-10-22 00:00:00

abstract：:Recently, it has been reported that 5-HT2 receptor agonists effectively reduce intraocular pressure (IOP) in a nonhuman primate model of glaucoma. Although 1-[(2S)-2-aminopropyl]indazol-6-ol (AL-34662) was shown to have good efficacy in this nonhuman primate model of ocular hypertension as well as a desirable physicoc...

journal_title：Journal of medicinal chemistry

authors： May JA,Sharif NA,McLaughlin MA,Chen HH,Severns BS,Kelly CR,Holt WF,Young R,Glennon RA,Hellberg MR,Dean TR

更新日期：2015-11-25 00:00:00

abstract：:The discovery of 8-(5,8-dichloro-1,2,3,4-tetrahydro-naphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one, 1a, as a high-affinity ligand for the human ORL1 (orphanin FQ/nociceptin) receptor led to the synthesis of a series of optimized ligands. These compounds exhibit high affinity for the human ORL1 receptor, e...

journal_title：Journal of medicinal chemistry

authors： Röver S,Adam G,Cesura AM,Galley G,Jenck F,Monsma FJ Jr,Wichmann J,Dautzenberg FM

更新日期：2000-04-06 00:00:00

abstract：:Adenosine induces glioma cell proliferation by means of an antiapoptotic effect, which is blocked by cotreatment with selective A(3) AR antagonists. In this study, a novel series of N(2)-substituted pyrazolo[3,4-d]pyrimidines 2a-u was developed as highly potent and selective A(3) AR antagonists. The most performing co...

journal_title：Journal of medicinal chemistry

authors： Taliani S,La Motta C,Mugnaini L,Simorini F,Salerno S,Marini AM,Da Settimo F,Cosconati S,Cosimelli B,Greco G,Limongelli V,Marinelli L,Novellino E,Ciampi O,Daniele S,Trincavelli ML,Martini C

更新日期：2010-05-27 00:00:00

abstract：:The antibacterial properties of glycopeptide antibiotics are based on their interaction with the d-Ala-d-Ala containing pentapeptide of bacterial peptidoglycan. The hydrophobic amides of vancomycin (1), teicoplanin (2), teicoplanin aglycon (3), and eremomycin (4) were compared with similar amides of minimally or low a...

journal_title：Journal of medicinal chemistry

authors： Printsevskaya SS,Pavlov AY,Olsufyeva EN,Mirchink EP,Preobrazhenskaya MN

更新日期：2003-03-27 00:00:00

abstract：:Cell division cycle 25 (Cdc25) proteins are highly conserved dual specificity phosphatases that regulate cyclin-dependent kinases and represent attractive drug targets for anticancer therapies. To discover more potent and diverse inhibitors of Cdc25 biological activity, virtual screening was performed by docking 2.1 m...

journal_title：Journal of medicinal chemistry

authors： Lavecchia A,Di Giovanni C,Pesapane A,Montuori N,Ragno P,Martucci NM,Masullo M,De Vendittis E,Novellino E

更新日期：2012-05-10 00:00:00