Structural studies on bioactive compounds. 39. Biological consequences of the structural modification of DHFR-inhibitory 2,4-diamino-6-(4-substituted benzylamino-3-nitrophenyl)-6-ethylpyrimidines ('benzoprims').

abstract：:Derivatives of benzofuran- and indole-2-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. These compounds were found to be excellent inhibitors of carbonic anhydrase and to lower intraocular pressure in a rabbit model of ocular hypertension. However, the development of these compo...

journal_title：Journal of medicinal chemistry

authors： Graham SL,Hoffman JM,Gautheron P,Michelson SR,Scholz TH,Schwam H,Shepard KL,Smith AM,Smith RL,Sondey JM

更新日期：1990-02-01 00:00:00

abstract：:Iodonium ion mediated cyclization of unsaturated hydroperoxides 1 afforded the expected yingzhaosu A analogues 2. In some cases, however, the corresponding cyclic ethers 5 were formed competitively with the cyclic peroxides 2, the ratios of these two products being a marked function of the structure of the starting ma...

journal_title：Journal of medicinal chemistry

authors： Kim HS,Begum K,Ogura N,Wataya Y,Tokuyasu T,Masuyama A,Nojima M,McCullough KJ

更新日期：2002-10-10 00:00:00

abstract：:A number of bis(diazeniumdiolates) that we designed to release up to 4 mol of nitric oxide (NO) and that are structural analogues of the NO prodrug and anticancer lead compound O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2- diolate (PABA/NO) were synthesized and studied...

journal_title：Journal of medicinal chemistry

authors： Andrei D,Maciag AE,Chakrapani H,Citro ML,Keefer LK,Saavedra JE

更新日期：2008-12-25 00:00:00

abstract：:The tremendous therapeutic potential of voltage-gated sodium channels (Na(v)s) has been the subject of many studies in the past and is of intense interest today. Na(v)1.7 channels in particular have received much attention recently because of strong genetic validation of their involvement in nociception. Here we summa...

journal_title：Journal of medicinal chemistry

authors： de Lera Ruiz M,Kraus RL

更新日期：2015-09-24 00:00:00

abstract：:The preparation and activity against Plasmodium berghei of derivatives of 1-(4-methoxycinnamoyl)-4-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazine are described. Replacement of the cinnamoyl group was accomplished by acylation or alkylation of 1-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazine. Modifications of the 5-phenyl grou...

journal_title：Journal of medicinal chemistry

authors： Herrin TR,Pauvlik JM,Schuber EV,Geiszler AO

更新日期：1975-12-01 00:00:00

abstract：:The standard of care for HIV-1 infection, highly active antiretroviral therapy (HAART), combines two or more drugs from at least two classes. Even with the success of HAART, new drugs with novel mechanisms are needed to combat viral resistance, improve adherence, and mitigate toxicities. Active site inhibitors of HIV-...

journal_title：Journal of medicinal chemistry

authors： Li G,Meanwell NA,Krystal MR,Langley DR,Naidu BN,Sivaprakasam P,Lewis H,Kish K,Khan JA,Ng A,Trainor GL,Cianci C,Dicker IB,Walker MA,Lin Z,Protack T,Discotto L,Jenkins S,Gerritz SW,Pendri A

更新日期：2020-03-12 00:00:00

abstract：:To better understand the difficulties surrounding the identification of novel antibacterial compounds from corporate screening collections, physical properties of ∼3200 antibacterial project compounds with whole cell activity against Gram-negative or Gram-positive pathogens were profiled and compared to actives found ...

journal_title：Journal of medicinal chemistry

authors： Brown DG,May-Dracka TL,Gagnon MM,Tommasi R

更新日期：2014-12-11 00:00:00

abstract：:Orally bioavailable SERDs may offer greater systemic drug exposure, improved clinical efficacy, and more durable treatment outcome for patients with ER-positive endocrine-resistant breast cancer. We report the design and synthesis of a boronic acid modified fulvestrant (5, ZB716), which binds to ERα competitively (IC5...

journal_title：Journal of medicinal chemistry

authors： Liu J,Zheng S,Akerstrom VL,Yuan C,Ma Y,Zhong Q,Zhang C,Zhang Q,Guo S,Ma P,Skripnikova EV,Bratton MR,Pannuti A,Miele L,Wiese TE,Wang G

更新日期：2016-09-08 00:00:00

abstract：:A novel class of artemisinin analogs, N-alkyl-11-aza-9-desmethylartemisinins 17-29, were synthesized via ozonolysis and acid-catalyzed cyclization of precursor amides 5-16. These amides were prepared through condensation of an activated ester of the known intermediate acid 2 with the corresponding primary amine. The a...

journal_title：Journal of medicinal chemistry

authors： Avery MA,Bonk JD,Chong WK,Mehrotra S,Miller R,Milhous W,Goins DK,Venkatesan S,Wyandt C,Khan I

更新日期：1995-12-22 00:00:00

abstract：:A series of 6,7-dichloro-1,4-dihydro-(1H, 4H)-quinoxaline-2,3-diones (1-17) were prepared in which the 5-position substituent was a heterocyclylmethyl or 1-(heterocyclyl)-1-propyl group. Structure-activity relationships were evaluated where binding affinity for the glycine site of the N-methyl-D-aspartate (NMDA) recep...

journal_title：Journal of medicinal chemistry

authors： Fray MJ,Bull DJ,Carr CL,Gautier EC,Mowbray CE,Stobie A

更新日期：2001-06-07 00:00:00

abstract：:A series of novel, disulfide-constrained human beta-melanocyte stimulating hormone (beta-MSH)-derived peptides were optimized for in vitro melanocortin-4 receptor (MC-4R) binding affinity, agonist efficacy, and selectivity. The most promising of these, analogue 18, was further studied in vivo using chronic rat food in...

journal_title：Journal of medicinal chemistry

authors： Mayer JP,Hsiung HM,Flora DB,Edwards P,Smith DP,Zhang XY,Gadski RA,Heiman ML,Hertel JL,Emmerson PJ,Husain S,O'brien TP,Kahl SD,Smiley DL,Zhang L,Dimarchi RD,Yan LZ

更新日期：2005-05-05 00:00:00

abstract：:Three [5-t-BuPro(7)]oxytocin analogues were synthesized by substituting (2S,5R)-5-tert-butylproline for proline in oxytocin, [Mpa(1)]oxytocin, and [dPen(1)]oxytocin. Relative to oxytocin, [5-t-BuPro(7)]oxytocin and [Mpa(1),5-t-BuPro(7)]oxytocin exhibited strongly reduced binding affinity to the receptor; however, both...

journal_title：Journal of medicinal chemistry

authors： Bélec L,Slaninova J,Lubell WD

更新日期：2000-04-20 00:00:00

abstract：:With the aim of up-regulating antitumor efficacy and down-regulating adverse effects, three types of aromatic imide and diimides were designed to couple with different polyamines. The in vitro assays revealed that two naphthalene diimide-polyamine conjugates could inhibit the growth of multiple cancer cell lines more ...

journal_title：Journal of medicinal chemistry

authors： Wang Y,Zhang X,Zhao J,Xie S,Wang C

更新日期：2012-04-12 00:00:00

abstract：:New 5'-O-carbonate prodrugs of zidovudine (AZT) have been synthesized in order to enhance its uptake by HIV-1 infected cells, to improve its anti-HIV potency, and to optimize the intramolecular cyclic rearrangement process related to the 5'-O-(4-hydroxybutyl) carbonate moiety. Evidence of this prodrug rearrangement wa...

journal_title：Journal of medicinal chemistry

authors： Vlieghe P,Clerc T,Pannecouque C,Witvrouw M,De Clercq E,Salles JP,Kraus JL

更新日期：2001-08-30 00:00:00

abstract：:Interleukin-2 inducible T-cell kinase (Itk) plays a role in T-cell functions, and its inhibition potentially represents an attractive intervention point to treat autoimmune and allergic diseases. Herein we describe the discovery of a series of potent and selective novel inhibitors of Itk. These inhibitors were identif...

journal_title：Journal of medicinal chemistry

authors： Charrier JD,Miller A,Kay DP,Brenchley G,Twin HC,Collier PN,Ramaya S,Keily SB,Durrant SJ,Knegtel RM,Tanner AJ,Brown K,Curnock AP,Jimenez JM

更新日期：2011-04-14 00:00:00

abstract：:Five series of pyrrolo[3,2-d]pyrimidines were synthesized and evaluated with respect to potency and selectivity toward multidrug resistance-associated protein 1 (MRP1, ABCC1). This transport protein is a major target to overcome multidrug resistance in cancer patients. We investigated differently substituted pyrrolopy...

journal_title：Journal of medicinal chemistry

authors： Schmitt SM,Stefan K,Wiese M

更新日期：2016-04-14 00:00:00

abstract：:The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 co...

journal_title：Journal of medicinal chemistry

authors： Kukolja S,Pfeil JL,Draheim SE,Ott JL

更新日期：1985-12-01 00:00:00

abstract：:We have developed a fast and robust computational method for prediction of antiviral activity in automated de novo design of HIV-1 reverse transcriptase inhibitors. This is a structure-based approach that uses a linear relation between activity and interaction energy with discrete orientation sampling and with localiz...

journal_title：Journal of medicinal chemistry

authors： de Jonge MR,Koymans LM,Vinkers HM,Daeyaert FF,Heeres J,Lewi PJ,Janssen PA

更新日期：2005-03-24 00:00:00

abstract：:New carboxyalkyl compounds derived from Phe-Leu and Phe-Ala were synthesized and checked as inhibitors of "enkephalinase", a metalloendopeptidase cleaving the Gly3-Phe4 bond of enkephalins from mouse striatal membranes. Differential recognition of both brain enkephalinase and angiotensin-converting enzyme (ACE) cataly...

journal_title：Journal of medicinal chemistry

authors： Fournié-Zaluski MC,Chaillet P,Soroca-Lucas E,Marçais-Collado H,Costentin J,Roques BP

更新日期：1983-01-01 00:00:00

abstract：:A structure-activity relationship for symmetrical cyanine inhibitors of human tau aggregation was elaborated using a filter trap assay. Antagonist activity depended on cyanine heterocycle, polymethine bridge length, and the nature of meso- and N-substituents. One potent member of the series, 3,3'-diethyl-9-methylthiac...

journal_title：Journal of medicinal chemistry

authors： Chang E,Congdon EE,Honson NS,Duff KE,Kuret J

更新日期：2009-06-11 00:00:00

abstract：:AM1 semiempirical molecular orbital calculations have been used to probe the complexation sites for naked and hydrated magnesium ions to the different conformations and protonation states of tetracycline. The calculations reveal a wealth of possible magnesium complexation sites within a small energy range, but also in...

journal_title：Journal of medicinal chemistry

authors： Othersen OG,Lanig H,Clark T

更新日期：2003-12-18 00:00:00

abstract：:Analogues of [Leu10]NKA4-10 were synthesized in which each of the amide bonds was sequentially replaced with the reduced amide psi (CH2NH) bond to determine the effect of this structural modification on the antagonism of NKA binding to the HUB NK2 receptor. [psi (CH2-NH)9,Leu10]NKA4-10 (6) retained significant affinit...

journal_title：Journal of medicinal chemistry

authors： Harbeson SL,Shatzer SA,Le TB,Buck SH

更新日期：1992-10-16 00:00:00

abstract：:The active site of lanosterol 14alpha-demethylase (CYP51) was investigated via MCSS functional group mapping and LUDI calculations. Several non-azole lead molecules were obtained by coupling structure-based de novo design with chemical synthesis and biological evaluation. All of the lead molecules exhibited a strong i...

journal_title：Journal of medicinal chemistry

authors： Ji H,Zhang W,Zhang M,Kudo M,Aoyama Y,Yoshida Y,Sheng C,Song Y,Yang S,Zhou Y,Lü J,Zhu J

更新日期：2003-02-13 00:00:00

abstract：:The structure-based design, synthesis, and biological activity of a novel indazole-containing inhibitor series for S-adenosyl homocysteine/methylthioadenosine (SAH/MTA) nucleosidase are described. Use of 5-aminoindazole as the core scaffold provided a structure-guided series of low nanomolar inhibitors with broad-spec...

journal_title：Journal of medicinal chemistry

authors： Li X,Chu S,Feher VA,Khalili M,Nie Z,Margosiak S,Nikulin V,Levin J,Sprankle KG,Tedder ME,Almassy R,Appelt K,Yager KM

更新日期：2003-12-18 00:00:00

abstract：:5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated ...

journal_title：Journal of medicinal chemistry

authors： De Croos PZ,Sangdee P,Stockwell BL,Kar L,Thompson EB,Johnson ME,Currie BL

更新日期：1990-12-01 00:00:00

abstract：:Cytochrome P450 aromatase catalyzes the conversion of androgen substrates into estrogens. Aromatase inhibitors (AIs) have been used as first-line drugs in the treatment of estrogen-dependent breast cancer in postmenopausal women. However, the search for new, more potent, and selective AIs still remains necessary to av...

journal_title：Journal of medicinal chemistry

authors： Caporuscio F,Rastelli G,Imbriano C,Del Rio A

更新日期：2011-06-23 00:00:00

abstract：:BRD4 has recently emerged as a promising drug target. Therefore, identifying novel inhibitors with distinct properties could enrich their use in anticancer treatment. Guided by the cocrystal structure of hit compound 4 harboring a five-membered-ring linker motif, we quickly identified lead compound 7, which exhibited ...

journal_title：Journal of medicinal chemistry

authors： Hu J,Tian CQ,Damaneh MS,Li Y,Cao D,Lv K,Yu T,Meng T,Chen D,Wang X,Chen L,Li J,Song SS,Huan XJ,Qin L,Shen J,Wang YQ,Miao ZH,Xiong B

更新日期：2019-09-26 00:00:00

abstract：:A variety of nitroheterocyclic carbamate prodrugs of phenylenediamine mustard and 5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-benz[e]indoline (amino-seco-CBI-TMI), covering a wide range of reduction potential, were prepared and evaluated for use in gene-directed enzyme prodrug ther...

journal_title：Journal of medicinal chemistry

authors： Hay MP,Anderson RF,Ferry DM,Wilson WR,Denny WA

更新日期：2003-12-04 00:00:00

abstract：:Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected to become a new antitumor target. Most known FAP inhibitors often resemble the dipeptide cleavage products, with a boroproline at the P1 site; however, these inhibitors also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Po...

journal_title：Journal of medicinal chemistry

authors： Tsai TY,Yeh TK,Chen X,Hsu T,Jao YC,Huang CH,Song JS,Huang YC,Chien CH,Chiu JH,Yen SC,Tang HK,Chao YS,Jiaang WT

更新日期：2010-09-23 00:00:00

abstract：:The clinical use of anticancer lipids is severely limited by their ability to cause lysis of red blood cells prohibiting intravenous injection. Novel delivery systems are therefore required in order to develop anticancer ether lipids (AELs) into clinically useful anticancer drugs. In a recent article (J. Med. Chem. 20...

journal_title：Journal of medicinal chemistry

authors： Andresen TL,Jensen SS,Madsen R,Jørgensen K

更新日期：2005-11-17 00:00:00