Dimethyl-diphenyl-propanamide derivatives as nonsteroidal dissociated glucocorticoid receptor agonists.

abstract：:A molecular model of the alpha3beta2 nAChR lumen channel was constructed and hydrophobic clefts were observed near the receptor gate. Docking simulations indicated that ligand-nAChR complexes were formed by hydrophobic interactions with the cleft and hydrogen bond interactions. The equilibrium constants and associatio...

journal_title：Journal of medicinal chemistry

authors： Jozwiak K,Ravichandran S,Collins JR,Moaddel R,Wainer IW

更新日期：2007-11-29 00:00:00

abstract：:Spiropyrimidinetriones are a novel class of antibacterial agents that target the bacterial type II topoisomerase via a new mode of action. Compound ETX0914 is thus far the only drug from this class that is being evaluated in clinical trials. To improve the antibacterial activity and pharmacokinetic properties of ETX09...

journal_title：Journal of medicinal chemistry

authors： Shi C,Zhang Y,Wang T,Lu W,Zhang S,Guo B,Chen Q,Luo C,Zhou X,Yang Y

更新日期：2019-03-28 00:00:00

abstract：:A novel and highly efficient flexible docking approach is presented where the conformations (internal degrees of freedom) and orientations (external degrees of freedom) of the ligands are successively considered. This hybrid method takes advantage of the synergistic effects of structure-based and ligand-based drug des...

journal_title：Journal of medicinal chemistry

authors： Moitessier N,Henry C,Maigret B,Chapleur Y

更新日期：2004-08-12 00:00:00

abstract：:Protein tyrosine phosphatases (PTPases) are involved in the control of tyrosine phosphorylation levels in the cell and are believed to be crucial for the regulation of a multitude of cellular functions. A detailed understanding of the role played by PTPases in various signaling pathways has not yet been achieved, and ...

journal_title：Journal of medicinal chemistry

authors： Sarmiento M,Wu L,Keng YF,Song L,Luo Z,Huang Z,Wu GZ,Yuan AK,Zhang ZY

更新日期：2000-01-27 00:00:00

abstract：:Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that co...

journal_title：Journal of medicinal chemistry

authors： Shi J,Van de Water R,Hong K,Lamer RB,Weichert KW,Sandoval CM,Kasibhatla SR,Boehm MF,Chao J,Lundgren K,Timple N,Lough R,Ibanez G,Boykin C,Burrows FJ,Kehry MR,Yun TJ,Harning EK,Ambrose C,Thompson J,Bixler SA,Dunah

更新日期：2012-09-13 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：:CC-chemokine receptor 5 (CCR5) is an attractive target for preventing the entry of human immunodeficiency virus 1 (HIV-1) into human host cells. Maraviroc is the only CCR5 antagonist, and it was marketed in 2007. To overcome the shortcomings of maraviroc, structure-based drug design was performed to minimize CYP450 in...

journal_title：Journal of medicinal chemistry

authors： Peng P,Chen H,Zhu Y,Wang Z,Li J,Luo RH,Wang J,Chen L,Yang LM,Jiang H,Xie X,Wu B,Zheng YT,Liu H

更新日期：2018-11-08 00:00:00

abstract：:The new pyrimidine derivatives of 2,3-O, O-dibenzyl-6-deoxy-L-ascorbic acid (8-10) were synthesized by condensation of uracil and its 5-fluoro- and 5-trifluoromethyl-substituted derivatives with 4-(5,6-epoxypropyl)-2, 3-O,O-dibenzyl-L-ascorbic acid (7), while pyrimidine derivatives of 4,5-didehydro-5,6-dideoxy-L-ascor...

journal_title：Journal of medicinal chemistry

authors： Raić-Malić S,Svedruzić D,Gazivoda T,Marunović A,Hergold-Brundić A,Nagl A,Balzarini J,De Clercq E,Mintas M

更新日期：2000-12-14 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：:Several pairs of cannabinoid isomers were synthesized and tested for psychotropic activity in rhesus monkeys. Two regularities were observed: (a) In the absence of the other substituents, the equatorial stereochemistry of the substituent at C-1 determines activity. (b) Two groups of THC-type cannabinoids which differ ...

journal_title：Journal of medicinal chemistry

authors： Mechoulam R,Lander N,Varkony TH,Kimmel I,Becker O,Ben-Zvi Z,Edery H,Porath G

更新日期：1980-10-01 00:00:00

abstract：:In an effort to develop selective inhibitors of vesicular acetylcholine storage, we have synthesized a series of semirigid vesamicol receptor ligands based on the structure of 2-(4-phenylpiperidino)-cyclohexanol (vesamicol, AH5183, 1). In these compounds, the planes of the phenyl and piperidyl moieties of the parent l...

journal_title：Journal of medicinal chemistry

authors： Efange SM,Khare AB,Foulon C,Akella SK,Parsons SM

更新日期：1994-08-05 00:00:00

abstract：:Alkenylidene bisphenols are prepared by condensation of an appropriate phenol with a haloacetaldehyde, followed by base-induced elimination, or by condensation of the corresponding aryl methyl ether, elimination, and deprotection of the phenol with boron tribromide. The resulting compounds may be further elaborated by...

journal_title：Journal of medicinal chemistry

authors： Conradi RA,Vander Wyk JC,Bowlus SB

更新日期：1979-08-01 00:00:00

abstract：:Contilisant, a permeable, antioxidant, and neuroprotectant agent, showing high nM affinity at H3R and excellent inhibition of the monoamine oxidases and cholinesterases, is an affine and selective S1R agonist in the nanomolar range, based on the binding affinity and functional experiment, a result confirmed by molecul...

journal_title：Journal of medicinal chemistry

authors： Bautista-Aguilera ÓM,Budni J,Mina F,Medeiros EB,Deuther-Conrad W,Entrena JM,Moraleda I,Iriepa I,López-Muñoz F,Marco-Contelles J

更新日期：2018-08-09 00:00:00

abstract：:From a series of small fragments that was designed to probe the histamine H(4) receptor (H(4)R), we previously described quinoxaline-containing fragments that were grown into high affinity H(4)R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silic...

journal_title：Journal of medicinal chemistry

authors： Smits RA,de Esch IJ,Zuiderveld OP,Broeker J,Sansuk K,Guaita E,Coruzzi G,Adami M,Haaksma E,Leurs R

更新日期：2008-12-25 00:00:00

abstract：:Establishing quantitative relationships between molecular structure and broad biological effects has been a long-standing goal in drug discovery. Evaluation of the capacity of molecules to modulate protein functions is a prerequisite for understanding the relationship between molecular structure and in vivo biological...

journal_title：Journal of medicinal chemistry

authors： Fliri AF,Loging WT,Thadeio PF,Volkmann RA

更新日期：2005-11-03 00:00:00

abstract：:(+/-)-7-Aminosulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline (7) is one of the most potent and selective inhibitors of phenylethanolamine N-methyltransferase (PNMT) reported to date, but a blood-brain barrier (BBB) model indicates that it cannot penetrate the BBB. To increase the lipophilicity of 7 by addition ...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Vodonick SM,Criscione KR,McLeish MJ,Grunewald GL

更新日期：2004-08-26 00:00:00

abstract：:The coordination complex cyclo-tetrakis[bis(1-phenyl-3-methyl-4-benzoylpyrazolon-5-ato++ +)mu-o xotitanium(IV)] has been synthesized and characterized with IR and NMR spectroscopies and X-ray diffraction. The core of this species consists of an eight-membered Ti-mu-oxo ring with alternate short-long Ti-O bond lengths....

journal_title：Journal of medicinal chemistry

authors： Caruso F,Rossi M,Tanski J,Sartori R,Sariego R,Moya S,Diez S,Navarrete E,Cingolani A,Marchetti F,Pettinari C

更新日期：2000-10-05 00:00:00

abstract：:Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute the peptide pharmacophore i...

journal_title：Journal of medicinal chemistry

authors： Van der Poorten O,Knuhtsen A,Sejer Pedersen D,Ballet S,Tourwé D

更新日期：2016-12-22 00:00:00

abstract：:The antiproliferative activity of the 14 isomeric monoxylosylated dihydroxynaphthalenes has been tested in vitro toward normal HFL-1 and 3T3 A31 cells as well as transformed T24 and 3T3 SV40 cells. The antiproliferative effect toward HFL-1 cells was correlated with the polarity of the compounds. However, in the case o...

journal_title：Journal of medicinal chemistry

authors： Jacobsson M,Ellervik U,Belting M,Mani K

更新日期：2006-03-23 00:00:00

abstract：:Several 3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives were synthesized in moderate to high yields and found to be highly potent against cancer cells SF295 (central nervous system), HCT8 (colon), MDA-MB435 (melanoma), and HL60 (leukemia), with IC(50) below 2 microM. The arylamino para-nitro and the 2,4-dimeth...

journal_title：Journal of medicinal chemistry

authors： da Silva EN Jr,de Deus CF,Cavalcanti BC,Pessoa C,Costa-Lotufo LV,Montenegro RC,de Moraes MO,Pinto Mdo C,de Simone CA,Ferreira VF,Goulart MO,Andrade CK,Pinto AV

更新日期：2010-01-14 00:00:00

abstract：:A series of quinone substrates were modeled into the active site of human DT-diaphorase and minimized. Correlation of these models with the substrate specificity k(cat)/K(m) provided insights into the structural requirements of quinone substrates. The W105, F106, and H194 residues can influence the position of the qui...

journal_title：Journal of medicinal chemistry

authors： Suleman A,Skibo EB

更新日期：2002-03-14 00:00:00

abstract：:As described in the preceding paper (Arvanitis et al. J. Med. Chem. 1999, 42), anilinopyrimidines I were identified as potent antagonists of corticotropin-releasing hormone-1 receptor (CRH1-R, also referred to as corticotropin-releasing factor, CRF1-R). Our next goal was to understand the receptor-bound conformation o...

journal_title：Journal of medicinal chemistry

authors： Hodge CN,Aldrich PE,Wasserman ZR,Fernandez CH,Nemeth GA,Arvanitis A,Cheeseman RS,Chorvat RJ,Ciganek E,Christos TE,Gilligan PJ,Krenitsky P,Scholfield E,Strucely P

更新日期：1999-03-11 00:00:00

abstract：:Resistance to β-lactam antibiotics can be mediated by metallo-β-lactamase enzymes (MBLs). An MBL inhibitor could restore the effectiveness of β-lactams. We report on the evaluation of approved thiol-containing drugs as inhibitors of NDM-1, VIM-1, and IMP-7. Drugs were assessed by a novel assay using a purchasable fluo...

journal_title：Journal of medicinal chemistry

authors： Klingler FM,Wichelhaus TA,Frank D,Cuesta-Bernal J,El-Delik J,Müller HF,Sjuts H,Göttig S,Koenigs A,Pos KM,Pogoryelov D,Proschak E

更新日期：2015-04-23 00:00:00

abstract：:A molecular model of the alpha(IIb)beta(3) integrin has been developed utilizing (i). the crystal structure of alpha(v)beta(3), (ii). homology model of the alpha(IIb) subdomain, and (iii). the docking of alpha(IIb)beta(3)/alpha(v)beta(3) dual and selective inhibitors into the putative binding sites of alpha(IIb)beta(3...

journal_title：Journal of medicinal chemistry

authors： Feuston BP,Culberson JC,Hartman GD

更新日期：2003-12-04 00:00:00

abstract：:N(α)-Boc-l-Asp(OBn)-l-Lys(Z)-OtBu (reversin 121, 1), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-l-pro...

journal_title：Journal of medicinal chemistry

authors： Arnaud O,Koubeissi A,Ettouati L,Terreux R,Alamé G,Grenot C,Dumontet C,Di Pietro A,Paris J,Falson P

更新日期：2010-09-23 00:00:00

abstract：:A convenient route is described for attachment of acyl groups CO(CH2)nN(Et)2(CH2)mNH(Et)2 (n = 3, m = 2; n = 4, m = 2-4), CO(CH2)nN(Et)2(CH2)mNEt3 (n = 4, m = 2-4), or CO(CH2)4N(CH2CH2)3N(CH2)nCH3 (n = 1 or 9) to O-3' of thymidine 5'-phosphate (TMP). The compounds are prototypes of 5'-nucleotide derivatives in which t...

journal_title：Journal of medicinal chemistry

authors： Chawla RR,Freed JJ,Kappler F,Hampton A

更新日期：1986-05-01 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：:Oxadiazoles, like the benzoyl group in a series of imidazo[1,2-a]pyrimidines, have been found to be metabolically stable alternatives to ester groups in benzodiazepine-receptor ligands. This change has lead to a number of compounds which bind to the receptors and which exhibit potent agonist activity in a food-motivat...

journal_title：Journal of medicinal chemistry

authors： Tully WR,Gardner CR,Gillespie RJ,Westwood R

更新日期：1991-07-01 00:00:00

abstract：:Various semicarbazones derived from aryl aldehydes, phenylalkyl aldehydes, and phenylalkyl ketones as well as some related compounds were evaluated for anticonvulsant activity. Most of the compounds displayed anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens ...

journal_title：Journal of medicinal chemistry

authors： Dimmock JR,Sidhu KK,Thayer RS,Mack P,Duffy MJ,Reid RS,Quail JW,Pugazhenthi U,Ong A,Bikker JA

更新日期：1993-08-06 00:00:00

abstract：:A series of novel cephalosporin compounds which have 3-[(aminopyrimidiniumyl)thio]methyl substituents was synthesized. They show high antimicrobial activity against various bacterial species including Pseudomonas aeruginosa. Structure-activity relationships with various thiopyrimidines, thiopyrimidiniums, bicyclic thi...

journal_title：Journal of medicinal chemistry

authors： Kim YZ,Lim JC,Yeo JH,Bang CS,Kim WS,Kim SS,Woo YM,Yang DH,Oh H,Nahm K

更新日期：1994-10-28 00:00:00