abstract：:The concept of bioisosterism between benzimidazole and catechol was applied to the design and synthesis of benzimidazole analogues of norepinephrine, (R,S)-1-[5(6)-benzimidazolyl]-2-aminoethanol (2), and of isoproterenol, (R,S)-1-[5(6)-benzimidazolyl]-2-isopropylaminoethanol (4). Compound 2 was shown to be a partial b...

journal_title：Journal of medicinal chemistry

authors： Arnett CD,Wright J,Zenker N

更新日期：1978-01-01 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

abstract：:1-(Tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU), which is named Ftorafur or FT-207 and is used clinically as an antitumor agent, was conveniently synthesized by condensation of the trimethylsilyl derivative of 5-fluorouracil with 2-acetoxytetrahydrofuran using NaI as a catalyst. This optically inactive Thf-FU was res...

journal_title：Journal of medicinal chemistry

authors： Yasumoto M,Moriyama A,Unemi N,Hashimoto S,Suzue T

更新日期：1977-12-01 00:00:00

abstract：:The syntheses and antiinflammatory assays of some dibenztroponeacetic and -propionic acids and derivatives are described. The most potent compound, d-2-(5H-dibenzo[a,d]cyclohepten-5-on-2-yl)propionic acid, has a potency of ca, 70 times phenylbutazone in the rat carrageenan paw assay and two to three times indomethacin...

journal_title：Journal of medicinal chemistry

authors： Dunn JP,Green DM,Nelson PH,Rooks WH 2nd,Tomolonis A,Untch KG

更新日期：1977-12-01 00:00:00

abstract：:The interesting bronchodilator activity of certain dl-11-deoxy-3-thiaprostaglandins and their preparation by the conjugate addition of appropriately substituted (E)-1-alkenyllithio cuprate reagents to requisite cyclopentenones are described. ...

journal_title：Journal of medicinal chemistry

authors： Skotnicki JS,Schaub RE,Weiss MJ,Dessy F

更新日期：1977-12-01 00:00:00

abstract：:The objective of this study is the measurement of the rates of hydrolysis of a series of chloroethyl sulfide derivatives, under stimulated physiological conditions. Interferences encountered with the conventional spectrophotometric method prompted the use of a rapid-response, chloride selective electrode. This probe w...

journal_title：Journal of medicinal chemistry

authors： Wright JE,Hayes MJ,Subramanyam V,Soloway AH

更新日期：1977-12-01 00:00:00

abstract：:The synthesis is described of a series of derivatives of 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propranols. The compounds were investigated for their beta-adrenoceptor blocking properties and many showed a surprising degree of cardioselectivity when tested in vivo in anesthetized ...

journal_title：Journal of medicinal chemistry

authors： Smith LH,Tucker H

更新日期：1977-12-01 00:00:00

abstract：:The discovery of the (acryloylaryloxy)acetic acids as a new class of potent diuretics prompted the investigation of related bicyclic compounds. Annelated analogues of the parent series, the (2-alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids, were the subjects of this study. Those compounds, unlike the monocycli...

journal_title：Journal of medicinal chemistry

authors： Woltersdorf OW Jr,deSolms SJ,Schultz EM,Cragoe EJ Jr

更新日期：1977-11-01 00:00:00

abstract：:A series of 3-(4-acylaminopiperazin-1-ylalkyl)indoles was synthesized and tested for antihypertensive activity. Compounds with no substituents in the indole portion of the molecule were generally most effective in lowering blood pressure in the spontaneous hypertensive rat model. Of these several analogues were very p...

journal_title：Journal of medicinal chemistry

authors： Glamkowski EJ,Reitano PA,Woodward DL

更新日期：1977-11-01 00:00:00

abstract：:3-Aminopyrrolidines bearing acyl substituents on either nitrogen and N-acylated 1,4-diazabicyclo[3.2.1]octanes are potent microfilaricides in the Litomosoides carinii gerbil test system but have no effect on adult worms. The high activity of the pyrrolidine derivatives establishes that diethylcarbamazine (DEC) like an...

journal_title：Journal of medicinal chemistry

authors： Sturm P,Cory M,Henry DW

更新日期：1977-10-01 00:00:00

abstract：:A series of 2,6- and 2,4-dihydroxyphenyl alkyl ketones has been investigated as inhibitors of hepatic microsomal aniline hydroxylase and aminopyrine demethylase activities. Structural alterations in both series did little to enhance the inhibitory activity of the parent compounds 2,6-dihydroxyacetophenone (3) and 2,4-...

journal_title：Journal of medicinal chemistry

authors： Bobik A,Holder GM,Ryan AJ

更新日期：1977-09-01 00:00:00

abstract：:Primaquine (I) has been extensively used in combination with other drugs in the radical cure of relapsing malaria as well as for prophylaxis or the interruption of transmission. This, coupled with the activity data reported for 4-methylprimaquine (II), has led to the synthesis of a series of 14 4-substituted analogues...

journal_title：Journal of medicinal chemistry

authors： LaMontagne MP,Markovac A,Menke JR

更新日期：1977-09-01 00:00:00

abstract：:9,10-Didehydro-6-methyl-8beta-arylergolines 2, in which the carboxyl group of lysergic acid and isolysergic acid is replaced by various aryl groups, were prepared in two steps by alkylation of aromatic substrates with the tetracyclic allylic alcohol 3, followed by aromatization with MnO2. The new ergolines 2 have mode...

journal_title：Journal of medicinal chemistry

authors： Bach NJ,Kornfeld EC,Dorman DE

更新日期：1977-08-01 00:00:00

abstract：:The synthesis and CNS activity of a noval class of annelated 1,4-benzodiazepines, the aminomethylene-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepines, are described. An investigation of the structure--activity relationships in the series derived from 8-chloro-2,4-dihydro-2-dimethylaminomethylene-6-phenyl-1H-imidazo[1...

journal_title：Journal of medicinal chemistry

authors： Ager IR,Danswan GW,Harrison DR,Kay DP,Kennewell PD,Taylor JB

更新日期：1977-08-01 00:00:00

abstract：:Fifteen 7-substituted 4-hydroxyquinoline-3-carboxylic acids have been designed to minimize covariance between the physicochemical substituent parameters: pi, MR, and sigmap. The molecules have been synthesized and evaluated for their ability to inhibit the respiration of Ehrlich ascites cells as a whole cell model and...

journal_title：Journal of medicinal chemistry

authors： Shah KJ,Coats EA

更新日期：1977-08-01 00:00:00

abstract：:A previously outlined general procedure for preparing various 3-substituted cephalosporins from the penicillin nucleus has been used, with modifications where required, to prepare a series of analogues of cephalexin with various substituents in the 3-methyl group. The 3-substituents most conducive to broad-spectrum an...

journal_title：Journal of medicinal chemistry

authors： Brain EG,Eglington AJ,James BG,Nayler JH,Osborne NF,Pearson MJ,Smale TC,Southgate R,Tolliday P,Basker MJ,Mizen LW,Sutherland R

更新日期：1977-08-01 00:00:00

abstract：:Twenty-six episilon-rhodomycinone glycosides have been synthesized. These include the episilon-rhodomycinone glycosides of 2-deoxy-L-fucose, 2-deoxy-L-rhamnose, and 2-deoxy-D-ribose as well as their 2-hydroxyl derivatives. NMR spectroscopy showed that all the glycosides prepared had the saccharide residues linked to p...

journal_title：Journal of medicinal chemistry

authors： Khadem HS,Swartz DL,Cermak RC

更新日期：1977-07-01 00:00:00

abstract：:This paper reports the synthesis of 4-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (2) and 2-(3,4-dihydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)propylamine (3). The biological activity of these agents relative to that of trimetoquinol (1) in guinea pig atria and guinea pig trachea is reported. Th...

journal_title：Journal of medicinal chemistry

authors： Kador PF,Venkatraman R,Feller DR,Miller DD

更新日期：1977-07-01 00:00:00

abstract：:A series of 1-R-5-alkoxy-3H-1,4-benzodiazepin-2(1H)-ones was prepared and evaluated for central nervous system depressant activity. Several of these compounds, in particular, 7-chloro-5-ethoxy-1-methyl-3H-1,4-benzodiazepin-2(1H)-one (2), gave a profile and activity level similar to diazepam when measured in mice. ...

journal_title：Journal of medicinal chemistry

authors： Gogerty JH,Griot RG,Habeck D,Iorio LC,Houlihan WJ

更新日期：1977-07-01 00:00:00

abstract：:A variety of 2,3-disubstituted 5,7-dimethyl-1,8-naphthyridines was synthesized and tested in saline-loaded rats for their diuretic properties. The 2-amino-3-carbomethoxy and four 2-amino-3-N-alkylcarbamoyl compounds exhibited significant activity as measured by volume output; however, they were generally less potent t...

journal_title：Journal of medicinal chemistry

authors： Hawes EM,Gorecki DK,Gedir RG

更新日期：1977-06-01 00:00:00

abstract：:1-(Benzoyloxy), 1-(4-nitrobenzoyloxy), and 1-(3,5-dinitrobenzoyloxy) derivatives of 3-fluoro-, 3-chloro-, and 3-bromopropan-2-one were prepared by oxidation of the 1-benzoyloxy-3-halopropan-2-ols in turn prepared from the appropriate benzoyl chloride and 3-halo-1,2-propanediols, 1-Benzoyloxy-3-fluoropropan-2-one was a...

journal_title：Journal of medicinal chemistry

authors： Pero RW,Babiarz-Tracy P,Fondy TP

更新日期：1977-05-01 00:00:00

abstract：:A series of tetramisole derivatives was synthesized and tested for inhibitory activity against alkaline phosphatase which was partially purified from a murine ascitic neoplasm resistant to 6-thiopurines (Sarcoma 180/TG). These agents included derivatives substituted with halogens, CH3, or NO2 groups at either the meta...

journal_title：Journal of medicinal chemistry

authors： Bhargava KK,Lee MH,Huang Y,Cunningham LS,Agrawal KC,Sartorelli AC

更新日期：1977-04-01 00:00:00

abstract：:A series of 7(8 leads to 11 alpha)abeo steroids was synthesized by a modification of the previously described total synthesis of this class of compounds and evaluated for biological activity. In general, there was a marked reduction in the relative binding affinities of these compounds for the rabbit uterus estrogen a...

journal_title：Journal of medicinal chemistry

authors： Wani MC,Rector DH,White DH,Pitt CG,Kimmel GL

更新日期：1977-04-01 00:00:00

abstract：:The binding constants of 15 phenothiazine derivatives to bovine serum albumin were obtained by a circular dichroic probe technique; The lipophilicity of the drugs, measured by a reversed-phase thin-layer technique using oleyl alcohol and methanol-water mixtures as the solvents, is expressed as RMw. The binding constan...

journal_title：Journal of medicinal chemistry

authors： Hulshoff A,Perrin JH

更新日期：1977-03-01 00:00:00

abstract：:Several known alpha-amino acid analogues and a new compound, N-chloroacetylphosphoramidate, a carbamyl phosphate analogue, were screened as antitumor agents. All gave 50% growth inhibition of cultures of human epidemeroid carcinoma of the nasopharynx at dosage levels of 2-8 mug/ml while showing no activity against L12...

journal_title：Journal of medicinal chemistry

authors： Glover GI,Nelson SO,Kaeder GR

更新日期：1977-03-01 00:00:00

abstract：:A series of substituted chromone-2-carboxylic acids was synthesized and tested as antagonists of SRS-A induced contractions of isolated guinea pig ileum. This work led to the discovery of sodium 7-[3-(4-acetyl-3hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate (FPL 55712) which is...

journal_title：Journal of medicinal chemistry

authors： Appleton RA,Bantick JR,Chamberlain TR,Hardern DN,Lee TB,Pratt AD

更新日期：1977-03-01 00:00:00

abstract：:A series of bisalkamine esters, bis-basic ethers, and bis-basic ketones of carbazole, N-ethylcarbazole, dibenzofuran, and dibenzothiophene was synthesized and evaluated for antiviral activity. The series also included two bis-basic alkanes of N-ethylcarbazole and one bis-basic carboxamide of dibenzofuran. Structure-ac...

journal_title：Journal of medicinal chemistry

authors： Albrecht WL,Fleming RW,Horgan SW,Mayer GD

更新日期：1977-03-01 00:00:00

abstract：:The synthesis of a novel series of antitussive agents is described. Two series of amino-substituted tetra- and hexahydrodibenzofurans were prepared and examined for antitussive activity in the guinea pig after cough elicited by electrical stimulation of the vagus nerve. A significant level of activity, comparable with...

journal_title：Journal of medicinal chemistry

authors： Matharu SS,Rowlands DA,Taylor JB,Westwood R

更新日期：1977-02-01 00:00:00

abstract：:The superior activity of N-(2-chloroethyl)-N'-(trans-4-methylcyclohexyl)-N-nitrosourea (MeCCNU) against advanced murine Lewis lung carcinoma in comparisons with the cis form and other nitrosoureas prompted the synthesis of a number of MeCCNU analogues, including several cis-trans pairs. The methyl group was replaced b...

journal_title：Journal of medicinal chemistry

authors： Johnston TP,McCaleb GS,Clayton SD,Frye JL,Krauth CA,Montgomery JA

更新日期：1977-02-01 00:00:00

abstract：:The syntheses of 1,7,12-trimethyl- and 2,7,12-trimethylbenz[a]anthracenes are described. The lack of carcinogenic activity of these compounds is discussed in relationship to the carcinogenic activity of other substituted benz[a]anthracenes. ...

journal_title：Journal of medicinal chemistry

authors： Newman MS,Hung WM

更新日期：1977-01-01 00:00:00

abstract：:5-Nitronicotinamide (1) was prepared from 5-bromonicotinoyl chloride by treatment with ammonia and then oxidation with fuming H2SO4 and 30% H202. 2-Cholor-, 2-alkoxy-2-benzyloxy,2-phenoxy-,2-alkylamino-, and 2-benzylamino-5-nitronicatinamides were also prepared via 2-chloro-3-cyano-5-nitropyridine. 2-Methyl-5-nitronic...

journal_title：Journal of medicinal chemistry

authors： Morisawa Y,Kataoka M,Kitano N,Matsuzawa T

更新日期：1977-01-01 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：:[4-Threonine, 7-glycine]oxytocin and [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin) were synthesized by a combination of solid-phase and classical methods of peptide synthesis. A protected octapeptide was synthesized by the solid-phase method and following ammo...

journal_title：Journal of medicinal chemistry

authors： Lowbridge J,Manning M,Haldar J,Sawyer WH

更新日期：1977-01-01 00:00:00

abstract：:A series of 1-amino- and 1-mercapto-7,8,9,10-tetrahydro-6H-dibenzo[b,d]pyrans was synthesized and subsequently evaluated in three rodent test systems for CNS activity. The structure-activity data generated indicate that, in general, a change of the 1-hydroxy group to an amine results in a retention of pharmacological ...

journal_title：Journal of medicinal chemistry

authors： Matsumoto K,Stark P,Meister RG

更新日期：1977-01-01 00:00:00

abstract：:5-Alkoxy-3-(N-substituted carbamoly)-1-phenylpyrazoles were prepared and tested for antiinflammatory and hypnotic activity. Four compounds showed antiinflammatory activity and three possessed hypnotic properties. ...

journal_title：Journal of medicinal chemistry

authors： Sugiura S,Ohno S,Ohtani O,Izumi K,Kitamikado T,Asai H,Kato K

更新日期：1977-01-01 00:00:00

abstract：:Carbonates containing an iodinated aromatic ring on one side of the carbonate linkage and an alkyl group on the other were prepared. The aromatic side consisted of p-iodophenyl, p-iodobenzyl, m-iodobenzyl, 3,5-diiodobenzyl, m-amino-2,4,6-triiodobenzyl, m-acetamido-2,4,6-triiodobenzyl, p-iodophenethyl, p-iodo-sec-phene...

journal_title：Journal of medicinal chemistry

authors： Newton BN

更新日期：1976-12-01 00:00:00

abstract：:Nineteen derivatives of adenosine 5'-phosphate (AMP) bearing acylaminomethyl, acetoxy, or alkylaminomethyl substituents on the phosphate-ribose bridge (5' and O-5' positions) of AMP together with 2',3'-O-ethylidene, 2',3',-O-isopropylidene, and 2',3'-di-O-acetyl derivatives of AMP have been synthesized. Their substrat...

journal_title：Journal of medicinal chemistry

authors： Hampton A,Slotin LA,Kappler F,Sasaki T,Perini F

更新日期：1976-12-01 00:00:00

abstract：:A potent new class of inhibitors of phenylalanyl-tRNA synthetase from Escherichia coli B is described. N-Benzyl-2-phenylethylamine is a competitive inhibitor with respect to L-phenylalanine and appears to possess the structural features required for near-optimal binding. Hydrophobic substituents at the ortho position ...

journal_title：Journal of medicinal chemistry

authors： Anderson RT Jr,Santi DV

更新日期：1976-11-01 00:00:00

abstract：:Isolated hepatocytes carry out the N-demethylation of dansylamide at near linear rates for up to 8 h. This reaction was measured by following the release of tritium into water on hydroxylation of 3H-labeled methyl groups. The competitive inhibition of dansylamide by dansylated amino acids was studied in this system as...

journal_title：Journal of medicinal chemistry

authors： Hayes JS,Brendel K

更新日期：1976-11-01 00:00:00

abstract：:A series of methylated analogues of 6-hydroxydopamine (6-OHDA) has been synthesized and evaluated as irreversible inhibitors of catechol O-methyltransferase (COMT). These analogues have been prepared in an effort to elucidate the mechanism involved in the inactivation of this enzyme by 6-OHDA. The analogues prepared h...

journal_title：Journal of medicinal chemistry

authors： Borchardt RT,Reid JR,Thakker DR

更新日期：1976-10-01 00:00:00