abstract：:Certain L1210-active bis(guanylhydrazones) have structural and biological properties in common with the DNA minor groove binding, antileukemic, bisquaternary ammonium heterocycles. Monitoring of the DNA binding of the bis(guanylhydrazones), by fluorimetric quantitation of drug displacement of DNA-bound ethidium, shows...

journal_title：Journal of medicinal chemistry

authors： Denny WA,Cain BF

更新日期：1979-10-01 00:00:00

abstract：:(4-Methoyx-2,3,6-trimethylphenyl)nonatetraenoic acids, esters, and amides (analogues of retinoic acid) bearing a fluorine atom(s) or a trifluoromethyl group on the polyene side chain were synthesized. The biological activities of these compounds and of 10-, 12-, and 14-fluororetinoic acid esters were evaluated in vivo...

journal_title：Journal of medicinal chemistry

authors： Pawson BA,Chan KK,DeNoble J,Han RJ,Piermattie V,Specian AC,Srisethnil S,Trown PW,Bohoslawec O,Machlin LJ,Gabriel E

更新日期：1979-09-01 00:00:00

abstract：:An approach to the development of new anticandidal drugs is described that employs peptides as carriers of toxic agents into cells. 5-Flurorcytosine (5-FC) was chosen as a toxic agent with which to prepare 5-FC-peptide conjugates as models to test the carrier proposal. Model compounds were synthesized and then tested ...

journal_title：Journal of medicinal chemistry

authors： Steinfeld AS,Naider F,Becker JM

更新日期：1979-09-01 00:00:00

abstract：:The 5'-phosphate (1) of the antiviral nucleoside 5-cyano-2'-deoxyuridine was synthesized and evaluated for inhibition of thymidylate synthetase purified from methotrexate-resistant Lactobacillus casei. Compound 1 was a potent competitive inhibitor with a K1 of 0.55 microns. Irreversible enzyme inhibition by this compo...

journal_title：Journal of medicinal chemistry

authors： Chang CT,Edwards MW,Torrence PF,Mertes MP

更新日期：1979-09-01 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：:Synthesis of four arabinofuranosyl derivatives of the antitumor agent 3-deazaguanine is described. By the use of 13C and 1H nuclear magnetic resonance spectroscopy, the structures of these nucleosides were established to be alpha and beta pairs of N-7 and N-9 arabinosides of 3-deazaguanine. In contrast to 3-deazaguani...

journal_title：Journal of medicinal chemistry

authors： Poonian MS,McComas WW,Kramer MJ

更新日期：1979-08-01 00:00:00

abstract：:6-Substituted 6-deoxy-L-galactose (L-fucose) derivatives were synthesized as potential antimetabolites of L-fucose. The cytotoxic effects of these compounds were evaluated on P388 leukemia cells in culture. The L-fucose analogues which showed the most potent growth inhibition were the sulfonyl ester, bromo, and iodo d...

journal_title：Journal of medicinal chemistry

authors： May JA Jr,Sartorelli AC

更新日期：1979-08-01 00:00:00

abstract：:Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucle...

journal_title：Journal of medicinal chemistry

authors： García-López MT,Herranz R,Alonso G

更新日期：1979-07-01 00:00:00

abstract：:A series of 3',5'-diesters of a 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine salt bearing functional substituents on the ester side chains (4--16) have been synthesized. The synthesis of these diesters involved the reaction between cytidine and the corresponding acid anhydride or acid chloride in the presence of b...

journal_title：Journal of medicinal chemistry

authors： Kondo K,Nagura T,Arai Y,Inoue I

更新日期：1979-06-01 00:00:00

abstract：:A series of 1-(p-nitrophenyl)-2-aminoethanol derivatives and their morpholine analogues have been synthesized and pharmacologically investigated in order to confirm some pharmacological observations made with the N-isopropyl-substituted compounds. In agreement with the previously obtained results, the weak alpha-adren...

journal_title：Journal of medicinal chemistry

authors： Balsamo A,Crotti P,Lapucci A,Macchia B,Macchia F,Del Tacca M,Mazzanti L,Ceserani R

更新日期：1979-06-01 00:00:00

abstract：:Quantitative structure-activity relationships (QSAR) have been established for the inhibition of dihydrofolate reductase and thymidylate synthetase by 2,4-diaminoquinazoline-glutamic acid analogues. For dihydrofolate reductase from both human acute lymphocytic leukemia cells and murine L1210R cells, QSAR's obtained wi...

journal_title：Journal of medicinal chemistry

authors： Chen BK,Horváth C,Bertino JR

更新日期：1979-05-01 00:00:00

abstract：:1,3-Dipolar cycloaddition of benzyl azide or peracetylated glucopyranosyl azides to propargyl halides or 1,4-dihalobutynes yielded 1-benzyl- or 1-glycosyl(halomethyl)-1,2,3-triazoles. Alkylating chloromethyl- bromomethyl- and iodomethyl-1,2,3-triazoles were also obtained from the corresponding hydroxymethyl derivative...

journal_title：Journal of medicinal chemistry

authors： de las Heras FG,Alonso R,Alonso G

更新日期：1979-05-01 00:00:00

abstract：:Mercapto derivatives of palmitic acid are capable of binding 99mTc. Based on the hypothesis that 99mTc-labeled palmitic acid derivatives would behave biologically like palmitic acid and thus could be used as myocardial imaging agents, three mercaptopalmitic acid derivatives have been prepared. The synthesis of 2-merca...

journal_title：Journal of medicinal chemistry

authors： Livni E,Davis MA,Warner VD

更新日期：1979-05-01 00:00:00

abstract：:A series of cis- and trans-dihydroxycotahydrobenzo[f]quinoline congeners of dopamine has been prepared, in which the N substitutent is H, ethyl, or n-propyl. The trans isomers include the dopamine moiety held rigidly in an antiperiplanar diposition which is believed to be necessary for certian central and peripheral d...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Suarez-Gutierrez C,Lee T,Long JP,Costall B,Fortune DH,Naylor RJ

更新日期：1979-04-01 00:00:00

abstract：:A series of 3-(alkoxymethyl)-alpha-(N-substituted aminomethyl)-4-hydroxybenzyl alcohols was synthesized as potential bronchodilators. The ability to prevent effects against histamine-induced bronchoconstriction in guinea pigs was studied to determine their bronchodilating activity. Introduction of a methoxymethyl grou...

journal_title：Journal of medicinal chemistry

authors： Sohda S,Fujimoto M,Tamegai T,Hirose N

更新日期：1979-03-01 00:00:00

abstract：:Benzimidazoles carrying the 2-hydroxy-3-(isopropylamino)propoxy side chain at either the C-4 or C-5 ring positions were synthesized and investigated for beta-adrenergic blocking activity. Both compounds demonstrated beta2 selectivity when evaluated in guinea pig atrial and tracheal preparations. The C-4 isomer was 17 ...

journal_title：Journal of medicinal chemistry

authors： Crooks CR,Wright J,Callery PS,Moreton JE

更新日期：1979-02-01 00:00:00

abstract：:Four steroidal nitrosoureas with structures which may permit specific binding to estrogen receptor were synthesized. Inhibitory activity was observed against the growth of the DMBA-induced transplantable rat mammary tumor 13762. ...

journal_title：Journal of medicinal chemistry

authors： Lam HY,Begleiter A,Goldenberg GJ,Wong CM

更新日期：1979-02-01 00:00:00

abstract：:The constitution of chlorpromazine has been studied in the context of its phototoxicity. Electron transfer from the side chain to the aromatic nucleus of the drug contributes to its instability to light. Even without the side chain, however, chlorophenothiazines appear to be very photolabile, so that it is unlikely th...

journal_title：Journal of medicinal chemistry

authors： Bunce NJ,Kumar Y,Ravanal L

更新日期：1979-02-01 00:00:00

abstract：:The preparation of a series of indole N-acyl and N-carbamic esters of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazolin-4-one (1) is reported. These derivatives were synthesized as potential water-soluble precursors of the antiviral thiazolinone 1, for evaluation by intranasal administration against i...

journal_title：Journal of medicinal chemistry

authors： Harnden MR,Bailey S,Boyd MR,Wilkinson JB,Wright ND

更新日期：1979-02-01 00:00:00

abstract：:Nitrosourea derivatives of ergolines have been synthesized for the purpose of obtaining agents with both prolactin-and tumor-inhibitory activity. Two derivatives of 8-amino-6-methylergoline (3), 8-[3-(2-chloroethyl)-3-nitrosoureido]-1-nitroso-6-methylergoline (5c) and 8-[3-2-chloroethyl)-3-nitrosoureido]-6-methylergol...

journal_title：Journal of medicinal chemistry

authors： Crider AM,Lu CK,Floss HG,Cassady JM,Clemens JA

更新日期：1979-01-01 00:00:00

abstract：:A series of compounds containing the 3-hydroxy-4H-pyran-4-one nucleus has been synthesized and tested as potential skeletal muscle relaxants. Reduction of 2-(azidomethyl)-5-hydroxy-4H-pyran-4-one (4) with HBr in HOAc--phenol yielded 2-(aminomethyl)-5-hydroxy-4H-pyran-4-one (kojic amine, 3) in 81% yield. Reaction of 2-...

journal_title：Journal of medicinal chemistry

authors： Atkinson JG,Girard Y,Rokach J,Rooney CS,McFarlane CS,Rackham A,Share NN

更新日期：1979-01-01 00:00:00

abstract：:The synthesis of analogues of the antipsychotic drug butaclamol bearing chloro substituents on the benzene rings is described. On the basis of a perceived topographical similarity of a putative chlorophenylethylamine pharmacophore present in these analogues and in VUFB-10032 and doclothepin, agents related to octoclot...

journal_title：Journal of medicinal chemistry

authors： Humber LG,Sideridis N,Asselin AA,Bruderlein FT,Voith K

更新日期：1978-12-01 00:00:00

abstract：:Whereas the 2-propyl- and 2-butyl-5,6-(methylenedioxy)indene calcium antagonists reversed the spasmogenic action of several agonists including PGF2alpha and acetylcholine at 5 X 10(-5) to 10(-4) M on the rat ileum, the corresponding 5,6-dimethoxy analogues exhibited spasmogenic activity at higher concentration (10(-4)...

journal_title：Journal of medicinal chemistry

authors： Witiak DT,Kakodkar SV,Brunst GE,Baldwin JR,Rahwan RG

更新日期：1978-12-01 00:00:00

abstract：:A series of pyridine-2-carboxaldehyde N-oxide and pyridine-2-carboxaldehyde (thio)phosphoric hydrazones and two cupric chelates was synthesized. The hydrazones, chelates, and combinations of hydrazones and cupric chloride were tested against mice bearing P388 lymphocytic leukemia, Sarcoma 180, or Ehrlich carcinoma asc...

journal_title：Journal of medicinal chemistry

authors： Cates LA,Good DJ,Jones GS,Lemke TL

更新日期：1978-11-01 00:00:00

abstract：:Analogues of luliberin containing an alpha-azaamino acid in position 6, 9, or 10 (I--XIV) have been synthesized by the solution method of peptide synthesis. Two nonaza analogues, [D-Phe6]- and [D-Ser(But)6,des-Gly-NH2(10),Pro-ethylamide9]luliberin, were also synthesized for comparison. The ovulation-inducing activity ...

journal_title：Journal of medicinal chemistry

authors： Dutta AS,Furr BJ,Giles MB,Valcaccia B

更新日期：1978-10-01 00:00:00

abstract：:In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the ...

journal_title：Journal of medicinal chemistry

authors： Clark RL,Pessolano AA,Shen TY,Jacobus DP,Jones H,Lotti VJ,Flataker LM

更新日期：1978-09-01 00:00:00

abstract：:A series of substituted benzenedisulfonamide carbonic anhydrase inhibitors is described and their anticonvulsant activities are listed. One compound, 4-(4-methoxypiperidinosulfonyl)-2-chlorobenzenesulfonamide (19, UK-12130), was found to have anticonvulsant activity in animals at a dose level that gave only a minimal ...

journal_title：Journal of medicinal chemistry

authors： Cross PE,Gadsby B

更新日期：1978-09-01 00:00:00

abstract：:A series of N7-substituted 7-aminoactinomycin D analogues with alkyl, aralkyl, and heteroaralkyl substituents was synthesized and their biological properties were studied. All of these analogues proved to be 22- to 28-fold less toxic than actinomycin D when tested against human lymphoblastic leukemia cells (CCRF-CEM) ...

journal_title：Journal of medicinal chemistry

authors： Madhavarao MS,Chaykovsky M,Sengupta SK

更新日期：1978-09-01 00:00:00

abstract：:A variety of esters of methyldopa was synthesized with the objective of obtaining derivatives that would be more efficiently absorbed from the gastrointestinal tract than the free amino acid and would undergo conversion to methyldopa readily in the blood or target tissues. Two of the esters, alpha-pivaloyloxyethyl (4u...

journal_title：Journal of medicinal chemistry

authors： Saari WS,Freedman MB,Hartman RD,King SW,Raab AW,Randall WC,Engelhardt EL,Hirschmann R,Rosegay A,Ludden CT,Scriabine A

更新日期：1978-08-01 00:00:00

abstract：:The synthesis of several 8-carboxy-6-sulfamyldibenz[b,f][1,4]oxazepines and -thiazepines is described. The results of diuretic screening lend support to the thesis that activity is strongly dependent on the conformational mobility of 4-substituents in the 3-amino-5-sulfamylbenzoic acids. ...

journal_title：Journal of medicinal chemistry

authors： Allen RC,Reitano PA,Urbach H

更新日期：1978-08-01 00:00:00

abstract：:A novel, simple, and efficient method for the chemical resolution of epidithiodioxopiperazines is reported, which is based upon covalent formation of diastereomers. This method might be a general one for the resolution of chiral cyclic disulfides. Dithiol 5, prepared from 2 by reduction with NaBH4, was allowed to reac...

journal_title：Journal of medicinal chemistry

authors： Ottenheijm HC,Herscheid JD,Tijhuis MW,Nivard RJ,De Clercq E,Prick PA

更新日期：1978-08-01 00:00:00

abstract：:A series of 62 diarylamidine derivatives was evaluated for their antiproteolytic activity. In all but two of the compounds one or both of the amidino-substituted aryl moieties was either an indole or an indole-like ring. The latter included indene, benzimidazole, benzofuran, benzol[beta]thiophene, and several other re...

journal_title：Journal of medicinal chemistry

authors： Tidwell RR,Geratz JD,Dann O,Volz G,Zeh D,Loewe H

更新日期：1978-07-01 00:00:00

abstract：:Proton magnetic spectra have been recorded for muscarine and two biologically active cyclopentane analogues. In order to observe homonuclear intramolecular nuclear Overhauser effects, the -N+(CH3)3 signal was irradiated and increases in integrated intensities for other key signals in the molecule were observed. The re...

journal_title：Journal of medicinal chemistry

authors： de Fontaine DL,Ternai B,Zupan JA,Givens RS,Wiley RA

更新日期：1978-07-01 00:00:00

abstract：:The synthesis of two new nucleotide analogues is described. 5'-Sulfamino-5'-deoxyadenosine (1) was prepared by reaction of 5'-amino-5'-deoxyadenosine with (CH3)3N.203, and 5'-sulfamino-5'-deoxythymidine (2) was prepared from 5'-amino-5'-deoxythymidine by a similar reaction. The 5'-sulfamino nucleosides are shown to be...

journal_title：Journal of medicinal chemistry

authors： Mungall WS,Lemmen LJ,Lemmen KL,Dethmers JK,Norling LL

更新日期：1978-07-01 00:00:00

abstract：:A series of 2-(1-piperazinyl)pyrazines was synthesized and evaluated for central serotonin-like activity. The most interesting member of the series, 6-chloro-2(1-piperazinyl)pyrazine (3a), had pharmacological properties characteristic of potent central serotoninmimetic activity and only weak peripheral serotoninmimeti...

journal_title：Journal of medicinal chemistry

authors： Lumma WC Jr,Hartman RD,Saari WS,Engelhardt EL,Hirschmann R,Clineschmidt BV,Torchiana ML,Stone CA

更新日期：1978-06-01 00:00:00

abstract：:A series of substituted 3-aryl- and hydroxy-3-aryloctahydropyrido[2,1-c][1,4]oxazines has been synthesized for purposes of investigating potentially useful CNS pharmacological actions of this novel heterocyclic system. The preferred conformation of the bicyclic system of the parent compounds, 1 and 2, has been shown t...

journal_title：Journal of medicinal chemistry

authors： Rankin GO,Riley TN,Murphy JC

更新日期：1978-05-01 00:00:00

abstract：:The preparation and antitubercular properties of a series of 2,8-bis(alkylaminomethyl)phenazines are described. These compounds all inhibited the growth of Mycobacterium smegmatis ATCC 607 in vitro. 2,8-Bis(dibutylaminomethyl)phenazine (5c) was also active against a lethal Mycobacterium tuberculosis H37Rv infection in...

journal_title：Journal of medicinal chemistry

authors： Murdock KC,Lin Y,Thomas JP,Lang SA Jr

更新日期：1978-04-01 00:00:00

abstract：:Interesting analgesic activity approaching that of meperidine and codeine was observed in standard animal models for 8-chloro-3,4-dihydro-5-methoxy-2-pyrrolidinomethylnaphthalene (compound 7). This compound was orally effective and its analgesic activity was not reversed by the opiate antagonist, naloxone. A limited n...

journal_title：Journal of medicinal chemistry

authors： Welch WM,Plattner JJ,Stratten WP,Harbert CA

更新日期：1978-03-01 00:00:00

abstract：:The E and Z isomers of 2-[2-(3-chlorophenyl)-1-phenyl-1-propenyl]pyridine (2a,b) and 2-[2-(3-chlorophenyl)-1-(4-hydroxyphenyl)-1-propenyl]pyridine (4a,b) were synthesized and separated as possible metabolites of 1-(3-chlorophenyl)-1-methyl-2-phenyl-2-(2-pyridine)ethanol (1a). Following administration of 1a to rats, a ...

journal_title：Journal of medicinal chemistry

authors： Kokosa JM,Sinsheimer JE,Wade DR,Drach JC,Burckhalter JH

更新日期：1978-02-01 00:00:00

abstract：:The synthesis and some biological activities of [4-beta-(2-thienyl)-L-alanine]oxytocin are reported. This analogue has been studied in an ongoing exploration of the biological effects of introducing amino acid residues with bulky hydrophobic side chains into the second corner position of the beta turn present in the c...

journal_title：Journal of medicinal chemistry

authors： Smith CW,Skala G,Walter R

更新日期：1978-01-01 00:00:00