abstract：:1-beta-D-Arabinofuranosylthymine (aThy; ara-T) is a potent selective anti herpes simplex virus drug. Its anhydro analogue, 2,2'-anhydro-aThy, was shown to be 9-fold less active and at least 3-fold less toxic than aThy. This compound was relatively stable at physiological pH and in strong acid but was rapidly hydrolyze...

journal_title：Journal of medicinal chemistry

authors： Harrison DH,Schinazi RF,Rubin BH

更新日期：1982-12-01 00:00:00

abstract：:Several new phospholipid-ara-C conjugates have been prepared and tested as prodrugs of the parent ara-C. The new derivative include ara-CMP-L-dipalmitin, ara-CDP-L-distearin, ara-CDP-L dimyristin, ara-CDP-L-diolein, and the radioactively labeled derivative ara-CDP-L-di[1-14C]palmitin. In addition, the unusually stable...

journal_title：Journal of medicinal chemistry

authors： Ryu EK,Ross RJ,Matsushita T,MacCoss M,Hong CI,West CR

更新日期：1982-11-01 00:00:00

abstract：:The synthesis of a series of 1-phenoxy-3-[[(substituted-amido)alkyl]amino]-2-propanols is described. Many of the compounds are more potent than propanolol as beta blockers, while having cardioselectivity comparable to that of practolol, when given intravenously to anesthetized cats. The structure-activity relationship...

journal_title：Journal of medicinal chemistry

authors： Lare MS,Smith LH

更新日期：1982-11-01 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：:An improved method for the synthesis of cardiac glycosides was used to prepare 3 beta-glucosides of digitoxigenin derivatives in which the 17 beta side chain was CH=CHX (X = COOH, CONH2, COCH3, CN, or COOR). We compared the inotropic activity of the compounds with that of digitoxigenin glucoside using guinea pig left ...

journal_title：Journal of medicinal chemistry

authors： Smith P,Brown L,Boutagy J,Thomas R

更新日期：1982-10-01 00:00:00

abstract：:3-O-tert-Butylmorphine (5) was prepared from 6-O-acetylmorphine (3) via alkylation with N,N-dimethylformamide di-tert-butyl acetal, followed by hydrolytic removal of the 3-(dimethylamino)-2-propenoate group. The same process was used to prepare the tert-butyl ether of levorphanol (6), (-)-3-tert-butoxy-N-methylmorphin...

journal_title：Journal of medicinal chemistry

authors： Mohacsi E,Leimgruber W,Baruth H

更新日期：1982-10-01 00:00:00

abstract：:2-Acetamido-5-O-acetyl-6-O-acyl-2-deoxy-3-O-[(R)-2-propionyl-L-alanyl-D- isoglutamine]-D-glucofuranoses, designed as prodrug forms of the corresponding immunoadjuvant-active 6-O-acyl derivatives of N-acetylmuramyl dipeptide (MDP), were synthesized from benzyl 2-acetamido-2-deoxy-5, 6-O-isopropylidene-beta-D-glucofuran...

journal_title：Journal of medicinal chemistry

authors： Durette PL,Dorn CP Jr,Friedman A,Schlabach A

更新日期：1982-09-01 00:00:00

abstract：:The syntheses of 2-amino-N-(2-benzoyl)-4-chlorophenyl)acetamides are reported. The pharmacological properties of these compounds were compared with data obtained from the corresponding cyclized products [5-(2,6-dichlorophenyl)-1,4-benzodiazepin-2-ones]. Evidence is presented which suggests that the central nervous sys...

journal_title：Journal of medicinal chemistry

authors： Fryer RI,Leimgruber W,Trybulski EJ

更新日期：1982-09-01 00:00:00

abstract：:A series of N,N-dialkyltryptamines with methylthio or methylenedioxy substituents in the 4, 5, and 6 positions and methyl or isopropyl on the side-chain nitrogen has been synthesized. The behavioral pharmacology of these compounds showed them to possess Bovet-Gatti profiles characteristic of hallucinogens, and the 5-m...

journal_title：Journal of medicinal chemistry

authors： Kline TB,Benington F,Morin RD,Beaton JM

更新日期：1982-08-01 00:00:00

abstract：:5'-Deoxy-5-fluorouridine (5'-dFUrd, 1) possesses a significantly higher chemotherapeutic index than other fluoropyrimidines as a result of its being selectivity cleaved in tumors to 5-fluorouracil (FUra) by uridine phosphorylase. Because 1 is a relatively poor substrate for this enzyme, we synthesized a series of 5'-d...

journal_title：Journal of medicinal chemistry

authors： Ajmera S,Danenberg PV

更新日期：1982-08-01 00:00:00

abstract：:Two-bivalent ligands (P-X-P) containing the beta-naltrexamine pharmacophore (P) and a connecting oligoethylene glycol spanner (X) were synthesized and evaluated for narcotic antagonistic activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD). The bivalent ligand 2 whose spanner contains three ethylene uni...

journal_title：Journal of medicinal chemistry

authors： Erez M,Takemori AE,Portoghese PS

更新日期：1982-07-01 00:00:00

abstract：:Monosubstituted derivatives of adenosine 5'-phosphate (AMP) with substituents of 1-3 atoms or group replacements at any of 11 positions have been synthesized and examined as substrates and inhibitors of the rat muscle adenylate kinase isozyme (AK-M), and the rat AK II and III isozymes predominant in poorly differentia...

journal_title：Journal of medicinal chemistry

authors： Hai TT,Picker D,Abo M,Hampton A

更新日期：1982-07-01 00:00:00

abstract：:Avermectins A2a, B1a, and B2a (1, 2, and 3) were acetylated to give 4"- and 23-acetates 4 and 5 and 4",23-diacetate 6 from 1, the 4"-and 5-acetates 7 and 8 and 4",5-diacetate 9 from 2, and triacetate 10 from 3. Structure proof by 300-MHz 1H NMR and mass spectral fragmentation is discussed for 10. Forcing acetylation c...

journal_title：Journal of medicinal chemistry

authors： Mrozik H,Eskola P,Fisher MH,Egerton JR,Cifelli S,Ostlind DA

更新日期：1982-06-01 00:00:00

abstract：:The 2S,3S and 2R,3S diastereoisomers of the hydroxy amino acid 3-amino-2-hydroxy-5-methylhexanoic acid (AHMHA) were synthesized and substituted for the leucyl residues of Leu-Leu-Val-Phe-OCH3 to yield the following analogues: AHMHA-Leu-Val-Phe-OCH3, AHMHA-Val-Phe-OCH3, and Leu-AHMHA-Val-Phe-OCH3. These analogues were ...

journal_title：Journal of medicinal chemistry

authors： Johnson RL

更新日期：1982-05-01 00:00:00

abstract：:Absolute configuration assignments have been made for the diastereomers of DL-beta-fluoroaspartate by X-ray analysis. The cytotoxicity of these isomers against various mammalian cells was examined. DL-threo-beta-Fluoroaspartate shows selective cytotoxicity. Growth of the most sensitive cells is completely inhibited by...

journal_title：Journal of medicinal chemistry

authors： Stern AM,Foxman BM,Tashjian AH Jr,Abeles RH

更新日期：1982-05-01 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：:A group of nitro and amino derivatives of lucanthone was prepared and tested for antitumor activity. Reaction of 1-chloro-4-methyl-7-nitrothioxanthenone and N,N-diethylethylenediamine gave the 7-amino analogue (11) directly, accompanied by 7-amino-1-chloro-4-methylthioxanthenone. The antitumor activity of 11 was infer...

journal_title：Journal of medicinal chemistry

authors： Archer S,Rej R

更新日期：1982-03-01 00:00:00

abstract：:A set of 2,4-diamino-5-(3-X-phenyl)-s-triazines was used to inhibit the growth of tumor cells (L5178 leukemia) in culture. The molar concentration (C) of triazine causing 50% reduction in the rate of cell growth was used to develop a quantitative structure-activity relationship: log 1/C = 1.32 pi - 1.70 log (beta.10 p...

journal_title：Journal of medicinal chemistry

authors： Khwaja TA,Pentecost S,Selassie CD,Guo Z,Hansch C

更新日期：1982-02-01 00:00:00

abstract：:In 1869, Crum Brown discovered the first structure-activity link by showing that alkaloids, even convulsive ones, were converted by N-methylation to muscle relaxants resembling curarine (itself a quaternary amine). This led to an attempt to link every type of drug action to its own cluster of atoms. This quest was jol...

journal_title：Journal of medicinal chemistry

authors： Albert A

更新日期：1982-01-01 00:00:00

abstract：:A series of 1-[1-(3,4-dimethoxy-1H-2-benzopyran-1-yl)alkyl]-4-arylpiperazines that shows hypotensive activity in the conscious rat has been investigated. Structure-activity relationships are described. A typical example that was investigated in greater detail is 1-[2-(3,4-dihydro-6,7-dimethoxy-1H-2-benzopyran-1-yl)eth...

journal_title：Journal of medicinal chemistry

authors： McCall JM,McCall RB,TenBrink RE,Kamdar BV,Humphrey SJ,Sethy VH,Harris DW,Daenzer C

更新日期：1982-01-01 00:00:00

abstract：:A series of [(3-aryl-1,2-benzisoxazol-6-yl)oxy]acetic acids was synthesized and tested for diuretic activity in saline-loaded mice and in conscious, water-loaded dogs. The structural requirements for good diuretic activity in both mice and dogs were found to be very specific. In summary, the compounds with the best di...

journal_title：Journal of medicinal chemistry

authors： Shutske GM,Setescak LL,Allen RC,Davis L,Effland RC,Ranbom K,Kitzen JM,Wilker JC,Novick WJ Jr

更新日期：1982-01-01 00:00:00

abstract：:A facile procedure is described for the conversion of morphine, via the diphosphate ester derivative 1 followed by catalytic reduction and treatment with Li/NH3, to 3-deoxy-7,8-dihydromorphine (3). Oxidation with benzophenone tert-butoxide converted 3 to the ketone 4, which on treatment with Zn/NH4Cl formed (-)-4-hydr...

journal_title：Journal of medicinal chemistry

authors： Manmade A,Dalzell HC,Howes JF,Razdan RK

更新日期：1981-12-01 00:00:00

abstract：:Anthelmintic efficacies of a series of 6-substituted methyl imidazo[1,2-alpha]pyridine-2-carbamates were compared to similarly substituted benzimidazole-2-carbamates. With only one exception, methyl 6-benzoylimidazo[1,2-alpha]pyridine-2-carbamate, both classes of compounds exhibited similar activity vs. Nematospiroide...

journal_title：Journal of medicinal chemistry

authors： Bochis RJ,Olen LE,Waksmunski FS,Mrozik H,Eskola P,Kulsa P,Wilks G,Taylor JE,Egerton JR,Ostlind DA,Olson G

更新日期：1981-12-01 00:00:00

abstract：:Thirty compounds related to the selective dopamine-autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine have been synthesized and tested for central dopamine-autoreceptor stimulating activity. The 3-(3-hydroxyphenyl)piperidine moiety seems indispensable for high potency and selectivity. Introduction of an add...

journal_title：Journal of medicinal chemistry

authors： Hacksell U,Arvidsson LE,Svensson U,Nilsson JL,Sanchez D,Wikström H,Lindberg P,Hjorth S,Carlsson A

更新日期：1981-12-01 00:00:00

abstract：:Three new dimeric analogues of ethidium cation in which the monomeric moieties are linked at the 3' positions by alpha,omega-diethers of varying length and composition have been synthesized. The circular dichroism spectra of all three compounds indicate that they double intercalate, and their effects on the thermal he...

journal_title：Journal of medicinal chemistry

authors： Kuhlmann KF,Mosher CW

更新日期：1981-11-01 00:00:00

abstract：:The N-arginyl derivative of methionine-enkephalin (fragment 60-65 of beta-lipotropin) has been shown to be equiactive with the parent pentapeptide, despite the fact that the tyrosine amino group in this compound has been neutralized by the formation of an amide linkage. A series of N-(amino acid) derivatives of (-)-5,...

journal_title：Journal of medicinal chemistry

authors： Bélanger PC,Scheigetz J,Young RN,Charleson SE,Hudgin RL,Engelhardt EL

更新日期：1981-11-01 00:00:00

abstract：:In order to study the preferential involvement of mu or delta receptors in the analgesic effects of enkephalins, several peptides which selectively interact with these two kinds of receptors in peripheral organs were synthesized. The inhibitory potency on the electrically stimulated mouse vas deferens (delta receptors...

journal_title：Journal of medicinal chemistry

authors： Gacel G,Fournié-Zaluski MC,Fellion E,Roques BP

更新日期：1981-10-01 00:00:00

abstract：:A series of 1-substituted mitosene analogues of the mitomycin antitumor antibiotics was prepared by total synthesis and screened for activity against P388 leukemia in mice. In general, analogues with moderately good leaving groups (mostly esters) at the 1 position were active, whereas analogues without such substituen...

journal_title：Journal of medicinal chemistry

authors： Hodges JC,Remers WA,Bradner WT

更新日期：1981-10-01 00:00:00

abstract：:The chelating drugs BAL (2,3-dimercaptopropanol), EDTA (ethylenediaminetetraacetic acid), and penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), which are used for metal poisoning, are toxic and there is a real need for alternatives, especially for severe cases. A novel approach for treatment of heavy-metal poi...

journal_title：Journal of medicinal chemistry

authors： Margel S

更新日期：1981-10-01 00:00:00

abstract：:A series of 2,3-diaminopropionanilides was synthesized by acylation of mono- and disubstituted aniline derivatives with 2,3-dibromopropionyl chloride and subsequent amination with the appropriate secondary amines. The target compounds were evaluated in mice for antiarrhythmic efficacy against chloroform-induced tachyc...

journal_title：Journal of medicinal chemistry

authors： Tenthorey PA,Adams HJ,Kronberg GH,Takman BH

更新日期：1981-09-01 00:00:00

abstract：:(+)-12-Fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2a) and (+)-15-epi-12-fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2b) were prepared from the readily available (-)-7-fluorospiro[bicyclo[2.2.1]hept-5-ene-2,2'-[1,3]dioxolane]-7-methanol (3). Fluoroprostaglandins 2a and 2b possess truly signific...

journal_title：Journal of medicinal chemistry

authors： Grieco PA,Takigawa T

更新日期：1981-07-01 00:00:00

abstract：:Reaction of 3'-acetylthymidine with phosphorus oxychloride in trimethyl phosphate yielded the phosphorodichloridate 5, which was subsequently reacted with aziridine, or 2,2-dimethylaziridine to give compounds 6 and 7, respectively. The 2,2-dimethylaziridine derivative 7 was considerably more active than 6 against leuk...

journal_title：Journal of medicinal chemistry

authors： Hsiao LY,Bardos TJ

更新日期：1981-07-01 00:00:00

abstract：:Thirty-five analogues of Phe-Leu-Glu-Glu-Leu, the pentapeptide sequence 5-9 of bovine prothrombin precursor, were synthesized and assayed as potential substrates or inhibitors of rat liver vitamin K dependent carboxylase. Carboxylation of substrate was determined by measuring the incorporation of carbon-24 labeled bic...

journal_title：Journal of medicinal chemistry

authors： Rich DH,Lehrman SR,Kawai M,Goodman HL,Suttie JW

更新日期：1981-06-01 00:00:00

abstract：:The effect of structural change on the biological activity of a series of imidazothiazoles and thiazolobenzimidazoles is described. It was found that compounds with polar substituents at the 2 or 3 position of the ring system are less acutely toxic while maintaining antiinflammatory activity. Other structural changes,...

journal_title：Journal of medicinal chemistry

authors： Powers LJ,Fogt SW,Ariyan ZS,Rippin DJ,Heilman RD,Matthews RJ

更新日期：1981-05-01 00:00:00

abstract：:The (E)- and (Z)-m-(trifluoromethyl)-alpha, beta-dimethylcinnamamides and some of their N-alkyl derivatives were prepared and pharmacologically tested as anticonvulsant agents in order to verify if a ring substituent, like the m-CF3 group, different from a halogen but possessing the same electronic effect could lead t...

journal_title：Journal of medicinal chemistry

authors： Balsamo A,Crotti P,Lapucci A,Macchia B,Macchia F,Cuttica A,Passerini N

更新日期：1981-05-01 00:00:00

abstract：:4-(Dimethylamino)- and 4-(methylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives were prepared as analogues of previously reported 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Metalation of benzanilide with n-butyllithium, addition of 4-(dimethylamino)cyclohexanone, and acidification afforded a...

journal_title：Journal of medicinal chemistry

authors： Martin LL,Worm M,Agnew MN,Kruse H,Wilker JC,Geyer HM 3rd

更新日期：1981-05-01 00:00:00

abstract：:Factors influencing dose potency of 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) analogues in L1210 assays have been investigated by multiple regression analysis. The dependent variable was D40, the dose to provide 40% life extension in L1210 tests. Independent variables examined were chromatographic Rm val...

journal_title：Journal of medicinal chemistry

authors： Baguley BC,Denny WA,Atwell GJ,Cain BF

更新日期：1981-05-01 00:00:00

abstract：:The agonist selectivities of central (medullary) and peripheral (vascular) alpha-adrenoceptors were compared in order to investigate a possible similarity among these two alpha-adrenoceptor populations. Linear regression equations were derived between the alpha-adrenergic potencies, mediated by these two types of alph...

journal_title：Journal of medicinal chemistry

authors： Timmermans PB,de Jonge A,van Meel JC,Slothorst-Grisdijk FP,Lam E,van Zwieten PA

更新日期：1981-05-01 00:00:00

abstract：:A group of compounds, structurally related to metoprolol, in which the aromatic nucleus is formally moved stepwise away from the ethanolamine side chain, has been studied as adrenergic agonists and antagonists. All the compounds were active on the adrenergic receptors and showed similar affinity for the receptor regar...

journal_title：Journal of medicinal chemistry

authors： Lövgren K,Hedberg A,Nilsson JL

更新日期：1981-04-01 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