abstract：:A four-step synthesis of 2-chlorodopamine (2b) is presented as well as methods for the syntheses of the N-methyl, ethyl, and n-propyl analogues (2c-e). Compounds 2b and 2c were essentially equipotent to dopamine for increasing renal blood flow in anesthetized dogs that had been treated with the alpha-adrenergic antago...

journal_title：Journal of medicinal chemistry

authors： McCarthy JR,McCowan J,Zimmerman MB,Wenger MA,Emmert LW

更新日期：1986-09-01 00:00:00

abstract：:The preparation of a series of 2-(1H-imidazol-1-ylmethyl)-substituted carboxylic acids of benzo[b]furan, benzo-[b]thiophene, indole, and naphthalene is described. All compounds showed a similar level of activity as TxA2 synthetase inhibitors in vitro, having IC50 values between 1 and 7 X 10(-8) M. In the cases examine...

journal_title：Journal of medicinal chemistry

authors： Cross PE,Dickinson RP,Parry MJ,Randall MJ

更新日期：1986-09-01 00:00:00

abstract：:A recently discovered and structurally distinct class of antiepileptic drugs is the (arylalkyl)imidazoles. Two independently discovered representatives of this class, denzimol (alpha-[4-(2-phenylethyl)phenyl]-1H-imidazole-1-ethanol) and nafimidone (2-(1H-imidazol-1-yl)-1-(2-naphthalenyl)ethanone), are undergoing clini...

journal_title：Journal of medicinal chemistry

authors： Robertson DW,Krushinski JH,Beedle EE,Leander JD,Wong DT,Rathbun RC

更新日期：1986-09-01 00:00:00

abstract：:Three monomethylated derivatives of 4'-hydroxyacetanilide (acetaminophen) were prepared in order to compare their cytotoxic potential and analgesic activity with that of acetaminophen. Only 4'-hydroxy-N-methylacetanilide (N-methylacetaminophen) was devoid of cytotoxic effects to hepatic tissue of mice. Results of comp...

journal_title：Journal of medicinal chemistry

authors： Harvison PJ,Forte AJ,Nelson SD

更新日期：1986-09-01 00:00:00

abstract：:The effect of a variety of aryl substituents on the potency and selectivity of 19 analogues of 1,3-dipropyl-8-phenylxanthine as antagonists at A1- and A2-adenosine receptors in brain tissue was determined. The 4-sulfamoylphenyl and 4-carbamoylphenyl analogues are potent and somewhat selective for the A1 receptor. None...

journal_title：Journal of medicinal chemistry

authors： Daly JW,Padgett WL,Shamim MT

更新日期：1986-08-01 00:00:00

abstract：:Spatial correspondence between apomorphine, a prototype dopaminergic (DA) drug, and ergoline and some of its (partial) analogues were derived by matching their molecular electrostatic potential (MEP) patterns surrounding the aromatic moieties with respect to the coincident aliphatic N atoms. The MEP patterns were calc...

journal_title：Journal of medicinal chemistry

authors： Kocjan D,Hodoscek M,Hadzi D

更新日期：1986-08-01 00:00:00

abstract：:A series of 2- and 3-aminobenzanilides derived from ring-alkylated anilines were prepared and evaluated for anticonvulsant activity. These benzanilides were prepared in the course of studies designed to determine the relationship between the benzamide structure and anticonvulsant effects. The compounds were tested in ...

journal_title：Journal of medicinal chemistry

authors： Clark CR,Lin CM,Sansom RT

更新日期：1986-08-01 00:00:00

abstract：:A series of 2,2'-disubstituted 5,5'-dibenzimidazolyl ketones and related compounds have been synthesized of which 2,2'-bis(carbomethoxyamino)-5,5'-dibenzimidazolyl ketone exhibited a broad spectrum of anthelmintic activity in experimental animals. At doses of 10-50 mg/kg given intraperitoneally, 5 killed 100% of the a...

journal_title：Journal of medicinal chemistry

authors： Abuzar S,Sharma S,Fatma N,Gupta S,Murthy PK,Katiyar JC,Chatterjee RK,Sen AB

更新日期：1986-07-01 00:00:00

abstract：:As part of a study on the antitumor activities of tropolone derivatives prepared from hinokitiol, which naturally occurs in the plants of Chamaecyparis species, effects of aromatic substituents of alpha,alpha-bis(7-hydroxy-5-isopropyltropon-2-yl)toluenes on the activity were examined. Several of the compounds showed h...

journal_title：Journal of medicinal chemistry

authors： Yamato M,Hashigaki K,Kokubu N,Tashiro T,Tsuruo T

更新日期：1986-07-01 00:00:00

abstract：:Several N-2 substituted 1-methyl-1-(4-tolylsulfonyl)hydrazines were synthesized and evaluated for antineoplastic activity against the L1210 leukemia and the B16 melanoma. The most active compound to emerge from this study, 2-(methylsulfonyl)-1-methyl-1-(4-tolylsulfonyl)hydrazine, produced maximum percent T/C values wi...

journal_title：Journal of medicinal chemistry

authors： Hrubiec RT,Shyam K,Cosby LA,Furubayashi R,Sartorelli AC

更新日期：1986-07-01 00:00:00

abstract：:One of the pattern recognition techniques, the SIMCA method, has been applied to structure-taste studies on L-aspartyl dipeptides (L-Asp-NH-R). The sweet and bitter taste class models of the peptides were obtained by using five structural descriptors, such as molar refractivity, and four kinds of STERIMOL parameters. ...

journal_title：Journal of medicinal chemistry

authors： Miyashita Y,Takahashi Y,Takayama C,Sumi K,Nakatsuka K,Ohkubo T,Abe H,Sasaki S

更新日期：1986-06-01 00:00:00

abstract：:Evidence indicating that modifications at the 5- and 10-positions of classical folic acid antimetabolites lead to compounds with favorable differential membrane transport in tumor vs. normal proliferative tissue prompted an investigation of 5-alkyl-5-deaza analogues. 2-Amino-4-methyl-3,5-pyridinedicarbonitrile, prepar...

journal_title：Journal of medicinal chemistry

authors： Piper JR,McCaleb GS,Montgomery JA,Kisliuk RL,Gaumont Y,Sirotnak FM

更新日期：1986-06-01 00:00:00

abstract：:Modification of the 2(S)-methylbutyryl moiety of mevinolin led to a series of side chain ester derivatives. A systematic exploration of the structure-activity relationships showed that the introduction of an additional aliphatic group on the carbon alpha to the carbonyl group increased potency. This observation led to...

journal_title：Journal of medicinal chemistry

authors： Hoffman WF,Alberts AW,Anderson PS,Chen JS,Smith RL,Willard AK

更新日期：1986-05-01 00:00:00

abstract：:The inhibition of chicken liver dihydrofolate reductase by a series of substituted benzylpyrimidines has been investigated. From the inhibition constants a quantitative structure-activity relationship has been formulated. This mathematical model is compared with molecular graphics models constructed from the X-ray cry...

journal_title：Journal of medicinal chemistry

authors： Selassie CD,Fang ZX,Li RL,Hansch C,Klein T,Langridge R,Kaufman BT

更新日期：1986-05-01 00:00:00

abstract：:A convenient route is described for attachment of acyl groups CO(CH2)nN(Et)2(CH2)mNH(Et)2 (n = 3, m = 2; n = 4, m = 2-4), CO(CH2)nN(Et)2(CH2)mNEt3 (n = 4, m = 2-4), or CO(CH2)4N(CH2CH2)3N(CH2)nCH3 (n = 1 or 9) to O-3' of thymidine 5'-phosphate (TMP). The compounds are prototypes of 5'-nucleotide derivatives in which t...

journal_title：Journal of medicinal chemistry

authors： Chawla RR,Freed JJ,Kappler F,Hampton A

更新日期：1986-05-01 00:00:00

abstract：:Prealbumin is a major thyroxine binding protein in blood that has been well studied crystallographically and has also been proposed as a model for the thyroxine nuclear receptor in tissue. The high-affinity T4 binding site in prealbumin gave a linear plot on Scatchard analysis. The interactions of selected polychlorin...

journal_title：Journal of medicinal chemistry

authors： Rickenbacher U,McKinney JD,Oatley SJ,Blake CC

更新日期：1986-05-01 00:00:00

abstract：:Classical potential energy calculations are reported for a series of 11 structurally diverse substrates, products, and inhibitors of dihydrofolate reductase. In almost every case, the calculations reveal a range of potential biologically active conformations accessible to the molecule, and geometry optimization with m...

journal_title：Journal of medicinal chemistry

authors： Andrews PR,Sadek M,Spark MJ,Winkler DA

更新日期：1986-05-01 00:00:00

abstract：:A series of 3-methyl-3-(m-hydroxyphenyl)piperidines with N-substituent variations have been synthesized and resolved, and an X-ray crystal structure of one analogue was determined. The compounds have been characterized, pharmacologically, by detailed opiate receptor binding studies and determination of in vivo analges...

journal_title：Journal of medicinal chemistry

authors： Cheng A,Uyeno E,Polgar W,Toll L,Lawson JA,DeGraw JI,Loew G,Camerman A,Camerman N

更新日期：1986-04-01 00:00:00

abstract：:The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity. Imidazoles VIII a...

journal_title：Journal of medicinal chemistry

authors： Wright WB Jr,Press JB,Chan PS,Marsico JW,Haug MF,Lucas J,Tauber J,Tomcufcik AS

更新日期：1986-04-01 00:00:00

abstract：:DL-(1-Amino-2-propenyl)phosphonic acid was synthesized through the sequential oxidation, sulfoxide elimination, and deprotection of diphenyl [1-[(benzyloxycarbonyl)amino]-3-(phenylthio)propyl] phosphonate. This analogue of vinylglycine is a strong inhibitor of the alanine racemases from Pseudomonas aeruginosa and Stre...

journal_title：Journal of medicinal chemistry

authors： Vo-Quang Y,Carniato D,Vo-Quang L,Lacoste AM,Neuzil E,Le Goffic F

更新日期：1986-04-01 00:00:00

abstract：:Extensions and refinements of the receptor mapping method as originally developed by Crippen are presented. In a set of newly developed algorithms measures are taken to reduce the number of required energy parameters to a statistically acceptable degree. The most important measure is the incorporation of lipophilicity...

journal_title：Journal of medicinal chemistry

authors： Linschoten MR,Bultsma T,IJzerman AP,Timmerman H

更新日期：1986-02-01 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：:A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives...

journal_title：Journal of medicinal chemistry

authors： Manoury PM,Binet JL,Dumas AP,Lefèvre-Borg F,Cavero I

更新日期：1986-01-01 00:00:00

abstract：:The preparation of stable complexes between the N7-[2-(2-pyridyl)ethyl] and N7-(2-piperazinylethyl) derivatives of mitomycin C and metal ions such as Cu(II), Zn(II), and Pt(II) was accomplished. Mitomycin C did not form stable complexes, but it rearranged to a mitosene capable of complex formation. Some of these compl...

journal_title：Journal of medicinal chemistry

authors： Iyengar BS,Takahashi T,Remers WA,Bradner WT

更新日期：1986-01-01 00:00:00

abstract：:The synthesis of a series N-(4-piperidinyl)-1H-benzimidazol-2-amines and the preliminary evaluation of their in vitro and in vivo antihistaminic activity are described. Cyclodesulfurization of (2-aminophenyl)thioureas with mercury(II) oxide resulted in 2-aminobenzimidazole intermediates, which were monoalkylated on th...

journal_title：Journal of medicinal chemistry

authors： Janssens F,Torremans J,Janssen M,Stokbroekx RA,Luyckx M,Janssen PA

更新日期：1985-12-01 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：:A number of fluorenyl and diphenylmethane analogues of verapamil, chosen as having the same substituents arranged in different ways around the quaternary carbon, were synthesized in order to evaluate the importance of the stereoisomerism at that point of the molecule. The compounds were tested with the Langendorff tec...

journal_title：Journal of medicinal chemistry

authors： Gualtieri F,Teodori E,Bellucci C,Pesce E,Piacenza G

更新日期：1985-11-01 00:00:00

abstract：:Syntheses of 2-fluoroformycin [7-amino-5-fluoro-3-(beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine] (2b) and 2-aminoformycin [5,7-diamino-3-(beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine] (2c) are described. Cytotoxicity data are given for 2b and 2c alone as well as with added pentostatin. Kinetic parameters for adeno...

journal_title：Journal of medicinal chemistry

authors： Secrist JA 3rd,Shortnacy AT,Montgomery JA

更新日期：1985-11-01 00:00:00

abstract：:1-(2-Phenoxyethyl)-1H-imidazole was found to be an inhibitor of thromboxane (TxA2) synthetase, but it also inhibited the adrenal cytochrome P-450 enzyme steroid 11 beta-hydroxylase. The preparation of a series of analogues is described, and activity against TxA2 synthetase, PGI2 synthetase, cyclooxygenase, and steroid...

journal_title：Journal of medicinal chemistry

authors： Cross PE,Dickinson RP,Parry MJ,Randall MJ

更新日期：1985-10-01 00:00:00

abstract：:The synthesis of chiral 1,5-benzothiazepines 2a-c, 14a-c, 15c, and 16a prepared from cysteine is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound. Compound 2c was the most potent in vitro having an IC50 of 2.95 nM. The ester of 2c, i.e. 14c, was found to inhibit the A...

journal_title：Journal of medicinal chemistry

authors： Slade J,Stanton JL,Ben-David D,Mazzenga GC

更新日期：1985-10-01 00:00:00

abstract：:The synthesis of substituted [[3(S)-(acylamino)-2-oxo-1-azetidinyl]oxy]acetic acids (1) is described. 3-[(Carbobenzyloxy)amino]-N-hydroxy-2-azetidinones (13a,b), prepared from serine and threonine, were alkylated with 2-(trimethylsilyl)ethyl bromoacetate in the presence of potassium carbonate in THF/H2O. Alkylation wi...

journal_title：Journal of medicinal chemistry

authors： Woulfe SR,Miller MJ

更新日期：1985-10-01 00:00:00

abstract：:The antimicrobial and cytotoxic properties of a series of 9,10-dihydrophenanthrenes structurally related to juncusol (1a), a postulated phytoalexin with confirmed cytotoxic properties, are detailed. Two simple 9,10-dihydrophenanthrenes, 2,7-dihydroxy-3,8-dimethyl-9,10-dihydrophenanthrene (2h, desvinyljuncusol) and 2-h...

journal_title：Journal of medicinal chemistry

authors： Boger DL,Mitscher LA,Mullican MD,Drake SD,Kitos P

更新日期：1985-10-01 00:00:00

abstract：:The major mechanism by which the serotonin neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) expresses its neurodegenerative action may involve alkylation of biological nucleophiles by the electrophilic quinoid autoxidation products. To determine the relative importance of various sites on these autoxidation products towar...

journal_title：Journal of medicinal chemistry

authors： Sinhababu AK,Ghosh AK,Borchardt RT

更新日期：1985-09-01 00:00:00

abstract：:A series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines were synthesized and tested for their ability to inhibit the binding of [3H]diazepam to rat brain receptors in vitro. Compounds bearing a phenyl, 4-methoxyphenyl, or methyl group at position 3 and a dialkylamino group at position 6 showed the highest affinit...

journal_title：Journal of medicinal chemistry

authors： Toja E,Tarzia G,Barone D,Luzzani F,Gallico L

更新日期：1985-09-01 00:00:00

abstract：:A variety of 8-substituted guanosine and 2'-deoxyguanosine derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells in culture. The most active agents in the guanosine series were 8-substituted-N(CH3)2, -NHCH3, -NH2, -OH, and -SO2CH3, which caused 68, 42, 34, 33...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Cheng JC,Ishiguro K,Sartorelli AC

更新日期：1985-09-01 00:00:00

abstract：:Two products without phosphoryl groups, 1-O-octadecyl-2-O-acetyl-3-O-[gamma-(dimethylamino)propyl]glycerol and its quaternary salt, were synthesized from 1-O-octadecyl-2-O-benzylglycerol. In comparison with PAF-acether, they lost aggregating and bronchoconstrictive activities and did not show any antagonistic effects....

journal_title：Journal of medicinal chemistry

authors： Heymans F,Borrel MC,Broquet C,Lefort J,Godfroid JJ

更新日期：1985-08-01 00:00:00

abstract：:Hydroxyurea, hydroxyguanidine, and some thiosemicarbazones have been shown to have anticancer and antiviral activities. One of their possible sites of action is the enzyme ribonucleotide reductase (RR). Combination of the structural features of these compounds led to the design and synthesis of the Schiff bases of N-h...

journal_title：Journal of medicinal chemistry

authors： T'ang A,Lien EJ,Lai MM

更新日期：1985-08-01 00:00:00

abstract：:Since the Z isomer of chlorprothixene (1) is far more active than its E counterpart, it was of interest to develop a stereoselective synthesis for this class of compounds. Insertion of a benzenesulfonamido group at the peri position of a chlorprothixene precursor did affect the stereochemistry of side-chain olefin for...

journal_title：Journal of medicinal chemistry

authors： Ross BS,Wiley RA

更新日期：1985-07-01 00:00:00

abstract：:Acyclic nucleosides 1-[[2-hydroxy-1-(hydroxymethyl)ethoxy] methyl]-5-benzyluracil (DHPBU) (1) and 1-[[2-hydroxy-1-(aminomethyl)ethoxy]methyl]-5-benzyluracil (AHPBU) (2) have been synthesized by direct coupling of bis(trimethylsilyl)-5-benzyluracil with the corresponding chloromethyl ether, followed by removal of the b...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Liu MC

更新日期：1985-07-01 00:00:00

abstract：:Synthesis and opioid radioreceptor assay data on analogues closely related to 6-desoxy-6-spiro-alpha-methylene-gamma-lactone 5a, a compound with irreversible activity in this assay, are reported. Saturated lactones (7a,b), endocyclic alpha, beta-unsaturated gamma-lactones (8a,b and 9a), and 6 alpha,7 alpha-fused alpha...

journal_title：Journal of medicinal chemistry

authors： Koolpe GA,Nelson WL,Gioannini TL,Angel L,Appelmans N,Simon EJ

更新日期：1985-07-01 00:00:00