Antimalarial phenanthrene amino alcohols. 3. Halogen-containing 9-phenanthrenemethanols.

abstract：:Two series of halogenated sulfonamides have been prepared. The first consists of mono/dihalogenated sulfanilamides, whereas the second one consists of the mono/dihalogenated aminobenzolamides, incorporating equal or different halogens (F, Cl, Br, and I). These sulfonamides have been synthesized from the corresponding ...

journal_title：Journal of medicinal chemistry

authors： Ilies MA,Vullo D,Pastorek J,Scozzafava A,Ilies M,Caproiu MT,Pastorekova S,Supuran CT

更新日期：2003-05-22 00:00:00

abstract：:On the basis of the fact that apio dideoxynucleosides, in which the furanose oxygen and the C2 of the 2,3-dideoxyribose are transposed, exhibited potent anti-HIV activity and 2',3'-dideoxy-2',3'-didehydronucleosides also showed potent anti-HIV activity, we synthesized apio dideoxydidehydronucleosides in which the oxyg...

journal_title：Journal of medicinal chemistry

authors： Jeong LS,Kim HO,Moon HR,Hong JH,Yoo SJ,Choi WJ,Chun MW,Lee CK

更新日期：2001-03-01 00:00:00

abstract：:A series of 3-indoleacrylonitrile tyrphostins, 2-chloro-3-phenylquinolines, and 3-arylquinoxalines were prepared and tested for inhibition of platelet-derived growth factor receptor tyrosine kinase (PDGF-RTK) activity. The potency of the inhibitors was found to be quinoxalines > quinolines > indoles. Lipophilic groups...

journal_title：Journal of medicinal chemistry

authors： Gazit A,App H,McMahon G,Chen J,Levitzki A,Bohmer FD

更新日期：1996-05-24 00:00:00

abstract：:Necrosis is the main mode of cell death, which leads to multiple clinical conditions affecting hundreds of millions of people worldwide. Its molecular mechanisms are poorly understood, hampering therapeutics development. Here, we identify key proteolytic activities essential for necrosis using various biochemical appr...

journal_title：Journal of medicinal chemistry

authors： Khalfin B,Lichtenstein A,Albeck A,Nathan I

更新日期：2021-01-31 00:00:00

abstract：:Several polynuclear Pt(II) chelates with biogenic polyamines were synthesized and screened for their potential antiproliferative and cytotoxic activity in different human cancer cell lines. To gather information regarding the structure-activity relationships underlying their biological activity, the complexes studied ...

journal_title：Journal of medicinal chemistry

authors： Teixeira LJ,Seabra M,Reis E,da Cruz MT,de Lima MC,Pereira E,Miranda MA,Marques MP

更新日期：2004-05-20 00:00:00

abstract：:Targeted imaging requires contrast agents that remain in the vasculature for extended periods of time. A new contrast agent is described in which gadolinium is encapsulated within an extremely stable carbon sphere, thus allowing for safe extended residence. Water solubility and small particle size is achieved with nov...

journal_title：Journal of medicinal chemistry

authors： MacFarland DK,Walker KL,Lenk RP,Wilson SR,Kumar K,Kepley CL,Garbow JR

更新日期：2008-07-10 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：:The discovery of selective endothelin (ET) receptor antagonists will facilitate identification of the physiological and pathological roles for ET and its isopeptides. Structure-activity studies of the C-terminal hexapeptide of ET have been carried out to elucidate those amino acids important for receptor binding and a...

journal_title：Journal of medicinal chemistry

authors： Doherty AM,Cody WL,DePue PL,He JX,Waite LA,Leonard DM,Leitz NL,Dudley DT,Rapundalo ST,Hingorani GP

更新日期：1993-09-03 00:00:00

abstract：:In search for prodrugs to address the issue of pH-dependent solubility and exposure associated with 1 (BMS-582949), a previously disclosed phase II clinical p38α MAP kinase inhibitor, a structurally novel clinical prodrug, 2 (BMS-751324), featuring a carbamoylmethylene linked promoiety containing hydroxyphenyl acetic ...

journal_title：Journal of medicinal chemistry

authors： Liu C,Lin J,Hynes J,Wu H,Wrobleski ST,Lin S,Dhar TG,Vrudhula VM,Sun JH,Chao S,Zhao R,Wang B,Chen BC,Everlof G,Gesenberg C,Zhang H,Marathe PH,McIntyre KW,Taylor TL,Gillooly K,Shuster DJ,McKinnon M,Dodd JH,Bar

更新日期：2015-10-08 00:00:00

abstract：:Synthesis and biological activity of 17-esters of 6-dehydro-16-methylene-17 alpha-hydroxyprogesterone are presented. A systematic study of the influence of the alteration of halogen at 6 and the acyl group at 17 on the progestational and antiandrogenic activities of the resulting structures is described. A convenien...

journal_title：Journal of medicinal chemistry

authors： Shapiro EL,Weber L,Harris H,Miskowicz C,Neri R,Herzog HL

更新日期：1972-07-01 00:00:00

abstract：:An empirical approach to improve the microsomal stability and CYP inhibition profile of lead compounds 1a and 1b led to the identification of 5 (BMS-341) as a dissociated glucocorticoid receptor modulator. Compound 5 showed significant improvements in pharmacokinetic properties and, unlike compounds 1a-b, displayed a ...

journal_title：Journal of medicinal chemistry

authors： Yang MG,Dhar TG,Xiao Z,Xiao HY,Duan JJ,Jiang B,Galella MA,Cunningham M,Wang J,Habte S,Shuster D,McIntyre KW,Carman J,Holloway DA,Somerville JE,Nadler SG,Salter-Cid L,Barrish JC,Weinstein DS

更新日期：2015-05-28 00:00:00

abstract：:A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones were synthesized and evaluated for anticonvulsant activity in DBA/2 mice against sound-induced seizures and in rats against maximal electroshock-induced seizures. Most of the derivatives showed an anticonvulsant effect better than that of valproate, ...

journal_title：Journal of medicinal chemistry

authors： Chimirri A,De Sarro A,De Sarro G,Grasso S,Trimarchi GR,Zappalà M

更新日期：1989-01-01 00:00:00

abstract：:Forty-three pyrimidine derivatives, mainly containing the 4-aminopyrimidine system, have been prepared and evaluated as inhibitors of deoxycytidine kinase. The most effective inhibitors were 2-alkylthio-4-aminopyrimidines and 1-alky-1-cytosines. The best inhibitors in both groups were those with large alkyl substituen...

journal_title：Journal of medicinal chemistry

authors： Ward AD,Baker BR

更新日期：1977-01-01 00:00:00

abstract：:We have reported that [methyl- (11)C] (3 R,5 R)-5-(3-methoxyphenyl)-3-[(R)-1-phenylethylamino]-1-(4-trifluoromethylphenyl)pyrrolidin-2-one ([(11)C] 8, [(11)C]MePPEP) binds with high selectivity to cannabinoid type-1 (CB 1) receptors in monkey brain in vivo. We now describe the synthesis of 8 and four analogues, namely...

journal_title：Journal of medicinal chemistry

authors： Donohue SR,Krushinski JH,Pike VW,Chernet E,Phebus L,Chesterfield AK,Felder CC,Halldin C,Schaus JM

更新日期：2008-09-25 00:00:00

abstract：:A series of 1-(4-fluorophenyl)-1H-indoles substituted at the 3-position with 1-piperazinyl, 1,2,3,6-tetrahydro-4-pyridinyl, and 4-piperidinyl was synthesized. Within all three subseries potent dopamine D-2 and serotonin 5-HT2 receptor affinity was found in ligand binding studies. Quipazine-induced head twitches in rat...

journal_title：Journal of medicinal chemistry

authors： Perregaard J,Arnt J,Bøgesø KP,Hyttel J,Sánchez C

更新日期：1992-03-20 00:00:00

abstract：:Five dipeptidomimetic-based model prodrugs containing ketomethylene amide bond replacements were synthesized from readily available alpha,beta-unsaturated gamma-ketoesters. The model drug (BnOH) was attached to the C-terminus or to one of the side chain positions of the dipeptidomimetic. The stability, the affinity fo...

journal_title：Journal of medicinal chemistry

authors： Våbenø J,Nielsen CU,Ingebrigtsen T,Lejon T,Steffansen B,Luthman K

更新日期：2004-09-09 00:00:00

abstract：:Conformational and molecular mechanics studies of a new series of tricyclic ligands with affinity for either the dopamine D2 receptor or the 5-HT1A receptor, or both, has enabled us to elaborate considerably on previous pharmacophore models for these receptors. The new tricyclic ligands are either angular, 2,3,3a,4,5,...

journal_title：Journal of medicinal chemistry

authors： Chidester CG,Lin CH,Lahti RA,Haadsma-Svensson SR,Smith MW

更新日期：1993-05-14 00:00:00

abstract：:Using the crystal structure of an inhibitor complexed with the serine protease thrombin (PDB code ) and the functional group definitions contained within the Catalyst software, a representation of the enzyme's active site was produced (structure-based pharmacophore model). A training set of 16 homologous non-peptide i...

journal_title：Journal of medicinal chemistry

authors： Greenidge PA,Mérette SA,Beck R,Dodson G,Goodwin CA,Scully MF,Spencer J,Weiser J,Deadman JJ

更新日期：2003-04-10 00:00:00

abstract：:The interaction between leukocyte function-associated antigen-1 (LFA-1) and intracellular adhesion molecule-1 (ICAM-1) has been implicated in inflammatory and immune diseases. Recently, a novel series of p-arylthio cinnamides has been described as potent antagonists of the LFA-1/ICAM-1 interaction. These compounds wer...

journal_title：Journal of medicinal chemistry

authors： Liu G,Huth JR,Olejniczak ET,Mendoza R,DeVries P,Leitza S,Reilly EB,Okasinski GF,Fesik SW,von Geldern TW

更新日期：2001-04-12 00:00:00

abstract：:A structure-activity analysis of peptides containing backbone C alpha-methyl modification at the P4 site of the angiotensinogen sequence led to the discovery of potent renin inhibitors with apparent in vitro metabolic stability. Boc-alpha-MePro-Phe-His-Leu psi[CHOHCH2]Val-Ile-Amp dicitrate (Va) is a potent inhibitor o...

journal_title：Journal of medicinal chemistry

authors： Thaisrivongs S,Pals DT,Lawson JA,Turner SR,Harris DW

更新日期：1987-03-01 00:00:00

abstract：:The discovery of potent and pan-genotypic HCV NS5A inhibitors faces many challenges including the significant diversity among genotypes, substantial potency shift conferred on some key resistance-associated variants, inconsistent SARs between different genotypes and mutants, and the lacking of models of inhibitor/prot...

journal_title：Journal of medicinal chemistry

authors： Yu W,Tong L,Hu B,Zhong B,Hao J,Ji T,Zan S,Coburn CA,Selyutin O,Chen L,Rokosz L,Agrawal S,Liu R,Curry S,McMonagle P,Ingravallo P,Asante-Appiah E,Chen S,Kozlowski JA

更新日期：2016-11-23 00:00:00

abstract：:Four nucleoside analogues ( 1- 4) containing a common heterocyclic base, 4(7)-amino-6(5) H-imidazo[4,5- d]pyridazin-7(4)one, were screened against calf-intestine adenosine deaminase. Compounds 1 and 3 with K(i) values of 10-12 microM are more than four times as potent inhibitors of ADA compared with 2 and 4, with K(i)...

journal_title：Journal of medicinal chemistry

authors： Ujjinamatada RK,Phatak P,Burger AM,Hosmane RS

更新日期：2008-02-14 00:00:00

abstract：:Upon the basis of The Cancer Genome Atlas (TCGA) data set, we identified that several autophagy-related proteins such as AMP-activated protein kinase (AMPK) were remarkably downregulated in breast cancer. Combined with coimmunoprecipitation assay, we demonstrated that BRD4 might interact with AMPK. After analyses of t...

journal_title：Journal of medicinal chemistry

authors： Ouyang L,Zhang L,Liu J,Fu L,Yao D,Zhao Y,Zhang S,Wang G,He G,Liu B

更新日期：2017-12-28 00:00:00

abstract：:Several substance P analogues containing various D-amino acid modifications have been synthesized by the solid-phase procedure, detached from the solid support by ammonolysis, and purified by gel filtration combined with reversed-phase chromatography. Three compounds were fair to very potent competitive antagonists of...

journal_title：Journal of medicinal chemistry

authors： Caranikas S,Mizrahi J,Escher E,Regoli D

更新日期：1982-11-01 00:00:00

abstract：:We previously reported (J. Med. Chem. 1993, 36, 1188-1193) that changes to the ring size of the piperidine and cyclohexyl rings of the high-affinity and selective dopamine (DA)-uptake inhibitor 1-[1-(2-benzo[b]thienyl)cyclohexyl]piperidine (BTCP, 2) caused different, and in some cases opposite, changes in affinity for...

journal_title：Journal of medicinal chemistry

authors： He X,Raymon LP,Mattson MV,Eldefrawi ME,de Costa BR

更新日期：1993-12-10 00:00:00

abstract：:The recent discovery that the formaldehyde conjugates of doxorubicin and daunorubicin, Doxoform and Daunoform, are cytotoxic to resistant human breast cancer cells prompted the search for hydrolytically more stable anthracycline-formaldehyde conjugates. Doxoform and Daunoform consist of two molecules of the parent dru...

journal_title：Journal of medicinal chemistry

authors： Taatjes DJ,Fenick DJ,Koch TH

更新日期：1998-04-09 00:00:00

abstract：:Three N-C8-bridged analogues 4-6 of the opiate etorphine (3) were synthesized and evaluated for opiate agonism and antagonism. In each case ring closure was effected by intramolecular N-alkylation with a suitably developed C8 side chain. Another key synthetic step was the selective monoprotection of diol 11, which all...

journal_title：Journal of medicinal chemistry

authors： Maurer PJ,Rapoport H

更新日期：1987-11-01 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：:4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with...

journal_title：Journal of medicinal chemistry

authors： Rosen T,Seeger TF,McLean S,Nagel AA,Ives JL,Guarino KJ,Bryce D,Furman J,Roth RW,Chalabi PM

更新日期：1990-11-01 00:00:00

abstract：:We describe the design, synthesis, and evaluation of novel disubstituted cyclohexanes as potent CCR2 antagonists. Exploratory SAR studies led to the cis-disubstituted derivative 22, which displayed excellent binding affinity for CCR2 (binding IC50 = 5.1 nM) and potent functional antagonism (calcium flux IC50 = 18 nM a...

journal_title：Journal of medicinal chemistry

authors： Cherney RJ,Mo R,Meyer DT,Nelson DJ,Lo YC,Yang G,Scherle PA,Mandlekar S,Wasserman ZR,Jezak H,Solomon KA,Tebben AJ,Carter PH,Decicco CP

更新日期：2008-02-28 00:00:00