Effect of acylation with eleostearic acids on the monoamine oxidase inhibitory potency of some hydrazine antidepressants in mice.

abstract：:We previously discovered an orally active human gonadotropin-releasing hormone (GnRH) receptor antagonist, thieno[2,3-d]pyrimidine-2,4-dione derivative 1 (sufugolix). To reduce the cytochrome P450 (CYP) inhibitory activity and improve in vivo GnRH antagonistic activity, further optimization of this scaffold was carrie...

journal_title：Journal of medicinal chemistry

authors： Miwa K,Hitaka T,Imada T,Sasaki S,Yoshimatsu M,Kusaka M,Tanaka A,Nakata D,Furuya S,Endo S,Hamamura K,Kitazaki T

更新日期：2011-07-28 00:00:00

abstract：:Two analogues, 6-(2-aminopropyl)-5-methoxy-2,3-dihydrobenzofuran and 6-(2-aminopropyl)-5-methoxy-2-methyl-2,3-dihydrobenzofuran, of the hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) were synthesized and tested in the two-lever drug discrimination paradigm. In rats trained to discriminate s...

journal_title：Journal of medicinal chemistry

authors： Nichols DE,Hoffman AJ,Oberlender RA,Riggs RM

更新日期：1986-02-01 00:00:00

abstract：:CC chemokine receptors 2 (CCR2) and 5 (CCR5) are involved in many inflammatory diseases; however, most CCR2 and CCR5 clinical candidates have been unsuccessful. (Pre)clinical evidence suggests that dual CCR2/CCR5 inhibition might be more effective in the treatment of such multifactorial diseases. In this regard, the h...

journal_title：Journal of medicinal chemistry

authors： Ortiz Zacarías NV,van Veldhoven JPD,den Hollander LS,Dogan B,Openy J,Hsiao YY,Lenselink EB,Heitman LH,IJzerman AP

更新日期：2019-12-26 00:00:00

abstract：:The dengue virus (DENV) and West Nile Virus (WNV) NS2B-NS3 proteases are attractive targets for the development of dual-acting therapeutics against these arboviral pathogens. We present the synthesis and extensive biological evaluation of inhibitors that contain benzyl ethers of 4-hydroxyphenylglycine as non-natural p...

journal_title：Journal of medicinal chemistry

authors： Behnam MA,Graf D,Bartenschlager R,Zlotos DP,Klein CD

更新日期：2015-12-10 00:00:00

abstract：:The synthesis and in vitro antiplatelet activity significant data of coumarin derivatives 5i-x and quinolin-2(1H)-one derivatives 22a,b, as well as the corresponding structure-activity relationships are described. The recently reported 8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin 5f and its potent 7-(2-morp...

journal_title：Journal of medicinal chemistry

authors： Roma G,Di Braccio M,Grossi G,Piras D,Leoncini G,Bruzzese D,Signorello MG,Fossa P,Mosti L

更新日期：2007-06-14 00:00:00

abstract：:Pyrrolo[1,2-a]benzimidazole(PBI)-based aziridinyl quinones cleave DNA under reducing conditions specifically at G + A bases without any significant cleavage at C + T bases. The postulated mechanisms involve phosphate alkylation by the reductively activated aziridine to afford a hydrolytically labile phosphotriester as...

journal_title：Journal of medicinal chemistry

authors： Skibo EB,Schulz WG

更新日期：1993-10-15 00:00:00

abstract：:Members of a series of basic amide and ester derivatives of 2-substituted pyrido[2,1-b]quinazoline-8-carboxylic acids were prepared and evaluated for their ability to prevent slow-reacting substance of anaphylaxis (SRS-A) induced contractions of guinea pig ilea. The results indicate that the presence of a branched-cha...

journal_title：Journal of medicinal chemistry

authors： Tilley JW,Levitan P,Welton AF,Crowley HJ

更新日期：1983-11-01 00:00:00

abstract：:2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or...

journal_title：Journal of medicinal chemistry

authors： van Wijngaarden I,Kruse CG,van Hes R,van der Heyden JA,Tulp MT

更新日期：1987-11-01 00:00:00

abstract：:Dimethylallylguanidine, also known as galegine, isolated from Galega officinalis, has been shown to have weight reducing properties in vivo. Substitution of the guanidine group with an N-cyano group and replacement of guanidine with amidine, pyrimidine, pyridine, or the imidazole moieties removed the weight reducing p...

journal_title：Journal of medicinal chemistry

authors： Coxon GD,Furman BL,Harvey AL,McTavish J,Mooney MH,Arastoo M,Kennedy AR,Tettey JM,Waigh RD

更新日期：2009-06-11 00:00:00

abstract：:We designed three novel positron emission tomography ligands, N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-4-[(11)C]methoxy-N-methylbenzamide ([(11)C]6), 4-[(18)F]fluoroethoxy-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]7), and 4-[(18)F]fluoropropoxy-N-[4-[6-(isopro...

journal_title：Journal of medicinal chemistry

authors： Fujinaga M,Yamasaki T,Yui J,Hatori A,Xie L,Kawamura K,Asagawa C,Kumata K,Yoshida Y,Ogawa M,Nengaki N,Fukumura T,Zhang MR

更新日期：2012-03-08 00:00:00

abstract：:A series of 75 guanidine and 2-aminoimidazoline analogue molecules were assayed in vitro against Trypanosoma brucei rhodesiense STIB900 and Plasmodium falciparum K1. The dicationic diphenyl compounds exhibited the best activities with IC 50 values against T. b. rhodesiense and P. falciparum in the nanomolar range. Fiv...

journal_title：Journal of medicinal chemistry

authors： Rodríguez F,Rozas I,Kaiser M,Brun R,Nguyen B,Wilson WD,García RN,Dardonville C

更新日期：2008-02-28 00:00:00

abstract：:Cyclic and acyclic nitroaryl phosphoramide mustard analogues were activated by E. coli nitroreductase, an enzyme explored in GDEPT. The more active acyclic 4-nitrobenzyl phosphoramide mustard (7) showed 167 500x selective cytotoxicity toward nitroreductase-expressing V79 cells with an IC(50) as low as 0.4 nM. This is ...

journal_title：Journal of medicinal chemistry

authors： Hu L,Yu C,Jiang Y,Han J,Li Z,Browne P,Race PR,Knox RJ,Searle PF,Hyde EI

更新日期：2003-11-06 00:00:00

abstract：:Prolonged drug-target occupancy has become increasingly important in lead optimization, and biophysical assays that measure residence time are in high demand. Here we report a practical label-free assay methodology that provides kinetic and affinity measurements suitable for most target classes without long preincubat...

journal_title：Journal of medicinal chemistry

authors： Quinn JG,Pitts KE,Steffek M,Mulvihill MM

更新日期：2018-06-28 00:00:00

abstract：:We performed comprehensive structure-activity relationship (SAR) studies on the peptide portion of antiproliferative factor (APF), a sialylated frizzled-8 related glycopeptide that inhibits normal bladder epithelial and urothelial carcinoma cell proliferation. Glycopeptide derivatives were synthesized by solid-phase m...

journal_title：Journal of medicinal chemistry

authors： Kaczmarek P,Keay SK,Tocci GM,Koch KR,Zhang CO,Barchi JJ Jr,Grkovic D,Guo L,Michejda CJ

更新日期：2008-10-09 00:00:00

abstract：:Vitamin D compounds possessing A rings prohibited from flipping to the alternative chair form (i.e., analogues 2 and 26) were synthesized. The bicyclic fragment 22 consisting of the fused cyclohexane and dihydropyran rings was constructed via the ring-closing metathesis route. Also, a homologous synthon 23 with an att...

journal_title：Journal of medicinal chemistry

authors： Glebocka A,Sokolowska K,Sicinski RR,Plum LA,Deluca HF

更新日期：2009-06-11 00:00:00

abstract：:We report here the design, preparation, and systematic evaluation of a novel cycloalkane[d]isoxazole pharmacophoric fragment-containing androgen receptor (AR) modulators. Cycloalkane[d]isoxazoles form new core structures that interact with the hydrophobic region of the AR ligand-binding domain. To systematize and rati...

journal_title：Journal of medicinal chemistry

authors： Poutiainen PK,Oravilahti T,Peräkylä M,Palvimo JJ,Ihalainen JA,Laatikainen R,Pulkkinen JT

更新日期：2012-07-26 00:00:00

abstract：:The proprotein convertases (PCs) play an important role in protein precursor activation through processing at paired basic residues. However, significant substrate cleavage redundancy has been reported between PCs. The question remains whether specific PC inhibitors can be designed. This study describes the identifica...

journal_title：Journal of medicinal chemistry

authors： Levesque C,Fugère M,Kwiatkowska A,Couture F,Desjardins R,Routhier S,Moussette P,Prahl A,Lammek B,Appel JR,Houghten RA,D'Anjou F,Dory YL,Neugebauer W,Day R

更新日期：2012-12-13 00:00:00

abstract：:2-(3,4-Dichloroanilino)quinolizinium bromide (3) was prepared by reaction of 2-bromoquinolizinium bromide with 3,4-dichloroaniline in ethanol. This compound possesses unique antispasmodic, antisecretory, and antiulcerogenic properties. ...

journal_title：Journal of medicinal chemistry

authors： Alaimo RJ,Goldenberg MM

更新日期：1975-11-01 00:00:00

abstract：:Four new hybrid analogues of 1alpha,25-dihydroxyvitamin D3 (1) have been synthesized in a convergent manner by joining A-ring and C, D-ring fragments. Each hybrid analogue, having a noncalcemic 1-hydroxymethyl group and a potentiating 16-ene 24,24-difluorinated C,D-ring side chain, was designed to be lipophilic and in...

journal_title：Journal of medicinal chemistry

authors： Posner GH,Lee JK,Wang Q,Peleg S,Burke M,Brem H,Dolan P,Kensler TW

更新日期：1998-07-30 00:00:00

abstract：:A novel series of 16-substituted-4-azasteroids has been identified as potential tissue-selective androgen receptor modulators. These ligands display potent hAR binding and agonist activity, low virilizing potential, and good pharmacokinetic profiles in dogs. On the basis of its in vitro profile, 21 was evaluated in th...

journal_title：Journal of medicinal chemistry

authors： Mitchell HJ,Dankulich WP,Hartman GD,Prueksaritanont T,Schmidt A,Vogel RL,Bai C,McElwee-Witmer S,Zhang HZ,Chen F,Leu CT,Kimmel DB,Ray WJ,Nantermet P,Gentile MA,Duggan ME,Meissner RS

更新日期：2009-08-13 00:00:00

abstract：:Protein arginine methylation is a posttranslational modification critical for a variety of biological processes. Misregulation of protein arginine methyltransferases (PRMTs) has been linked to many pathological conditions. Most current PRMT inhibitors display limited specificity and selectivity, indiscriminately targe...

journal_title：Journal of medicinal chemistry

authors： Yan L,Yan C,Qian K,Su H,Kofsky-Wofford SA,Lee WC,Zhao X,Ho MC,Ivanov I,Zheng YG

更新日期：2014-03-27 00:00:00

abstract：:The simulated binding profiles of acetylcholine, ACh, and the inhibitor (+/-)-2,3-dihydro-5,6- dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-on e hydrochloride (E2020), 1, and some of its analogs to acetylcholinesterase, AChE, were determined using full force field energetics and allowing complete co...

journal_title：Journal of medicinal chemistry

authors： Inoue A,Kawai T,Wakita M,Iimura Y,Sugimoto H,Kawakami Y

更新日期：1996-10-25 00:00:00

abstract：:We have recently reported the phosphodiesterase 10A (PDE10A) inhibitor 2-[4-[1-(2-[(18)F]fluoroethyl)-4-pyridin-4-yl-1H-pyrazol-3-yl]-phenoxymethyl]-quinoline ([(18)F]1a) as a promising candidate for in vivo imaging using positron emission tomography (PET). We now describe the synthesis and biological evaluation of a ...

journal_title：Journal of medicinal chemistry

authors： Andrés JI,De Angelis M,Alcázar J,Iturrino L,Langlois X,Dedeurwaerdere S,Lenaerts I,Vanhoof G,Celen S,Bormans G

更新日期：2011-08-25 00:00:00

abstract：:The human brain is a uniquely complex organ, which has evolved a sophisticated protection system to prevent injury from external insults and toxins. Designing molecules that can overcome this protection system and achieve optimal concentration at the desired therapeutic target in the brain is a specific and major chal...

journal_title：Journal of medicinal chemistry

authors： Rankovic Z

更新日期：2015-03-26 00:00:00

abstract：:A series of S-alkylated derivatives of 5-mercapto-2'-deoxyuridine have been prepared by alkylation of the preformed nucleoside. Two of these compounds, the S-propargyl and S-allyl derivatives, have shown significant antiviral activity against Herpes simplex type 1 in HeLa TK- cells but appear to be less effective in t...

journal_title：Journal of medicinal chemistry

authors： Dinan FJ,Bardos TJ

更新日期：1980-05-01 00:00:00

abstract：:A broad screening program previously identified phenprocoumon (1) as a small molecule template for inhibition of HIV protease. Subsequent modification of this lead through iterative cycles of structure-based design led to the activity enhancements of pyrone and dihydropyrone ring systems (II and V) and amide-based sub...

journal_title：Journal of medicinal chemistry

authors： Turner SR,Strohbach JW,Tommasi RA,Aristoff PA,Johnson PD,Skulnick HI,Dolak LA,Seest EP,Tomich PK,Bohanon MJ,Horng MM,Lynn JC,Chong KT,Hinshaw RR,Watenpaugh KD,Janakiraman MN,Thaisrivongs S

更新日期：1998-08-27 00:00:00

abstract：:MLL1 is a histone 3 lysine 4 (H3K4) methyltransferase and a promising new cancer therapeutic target. The catalytic activity of MLL1 is regulated by the formation of a core complex consisting of MLL1, WDR5, RbBP5, and Ash2L. The interaction between WDR5 and MLL1 plays an essential role in regulation of the H3K4 methylt...

journal_title：Journal of medicinal chemistry

authors： Karatas H,Townsend EC,Bernard D,Dou Y,Wang S

更新日期：2010-07-22 00:00:00

abstract：:Motivated by the pivotal role of CXCR4 as an HIV entry co-receptor, we herein report a de novo hit-to-lead effort on the identification of subnanomolar purine-based CXCR4 antagonists against HIV-1 infection. Compound 24, with an EC50 of 0.5 nM against HIV-1 entry into host cells and an IC50 of 16.4 nM for inhibition o...

journal_title：Journal of medicinal chemistry

authors： Wu CH,Wang CJ,Chang CP,Cheng YC,Song JS,Jan JJ,Chou MC,Ke YY,Ma J,Wong YC,Hsieh TC,Tien YC,Gullen EA,Lo CF,Cheng CY,Liu YW,Sadani AA,Tsai CH,Hsieh HP,Tsou LK,Shia KS

更新日期：2015-02-12 00:00:00

abstract：:To study the influence of substitution of CN for C identical to CH in the anti-herpes virus nucleoside 5-(propynyloxy)-2'-deoxyuridine (1), 5-[(cyanomethylene)oxy]-2'-deoxyuridine (2) was prepared. When the potassium salt of 5-hydroxy-2'-deoxyuridine was reacted with iodoacetonitrile in dry DMF, the bisalkylated produ...

journal_title：Journal of medicinal chemistry

authors： Huang GF,Okada M,De Clercq E,Torrence PF

更新日期：1981-04-01 00:00:00

abstract：:3',5'-Diamino-3',5'-dideoxythymidine (7) was synthesized via a nine-step synthesis from thymidine in good overall yield. 3'-Amino-3'-deoxythymidine (8) and 5'-amino-5'-deoxythymidine (12) were prepared with a minor modification of the procedure reported by Horwitz and co-workers. Although the 5'-amino analogue 12 had ...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Prusoff WH

更新日期：1978-01-01 00:00:00