Drug design and delivery最新文献_第6页

A quantitative structure-activity relationship study on the inhibitory effects of local anesthetics on sodium flux, phosphoinositide breakdown, and binding to sodium channels. 局麻药对钠通量、磷酸肌肽分解和钠通道结合抑制作用的定量构效关系研究。

Drug design and delivery Pub Date : 1990-06-01

S P Gupta, J K Gupta, R N Saha

引用次数: 0

Polymeric controlled release systems. 聚合物控制释放系统。

Drug design and delivery Pub Date : 1990-06-01

J H Braybrook, L D Hall

引用次数: 0

Synthesis and anticonvulsant activity of 3-alkoxycarbonylaminomethylcarbonylamino-4-benzoylpyridines . 3-烷氧羰基氨基甲基羰基氨基-4-苯甲酰吡啶的合成及抗惊厥活性。

Drug design and delivery Pub Date : 1990-06-01

C Y Fiakpui, M N Namchuk, E E Knaus

{"title":"Synthesis and anticonvulsant activity of 3-alkoxycarbonylaminomethylcarbonylamino-4-benzoylpyridines .","authors":"C Y Fiakpui, M N Namchuk, E E Knaus","doi":"","DOIUrl":"","url":null,"abstract":"3-Alkoxycarbonylaminomethylcarbonylamino-4-(arylcarbonyl)pyr idines--in which the chlorophenyl ring of dipeptidylaminobenzophenones is replaced by a pyridyl ring--were synthesized and evaluated as anticonvulsants using subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock (MES) induced seizure screening tests. The substituent on the aryl ring of the 4-arylcarbonyl moiety was a determinant of activity in both tests, the potency order of substituents being generally 2-F greater than 2-H greater than 2-Cl. Compounds possessing a 3-benzyloxycarbonylaminomethylcarbonylamino substituent exhibited moderate activity in the scPTZ test, whereas all 3-tert-butoxycarbonylaminomethylcarbonylamino derivatives were inactive. The test results in the scPTZ screen suggest that the 3-benzyloxycarbonylaminomethylcarbonyl(N-methyl)amino compounds may undergo biotransformation, at least in part, to pyrido[3,4-e]-1,4-diazepin-2-ones. 3-Alkoxycarbonylaminomethylcarbonyl(N-methyl)amino-substituted compounds were always more potent than analogous 3-alkoxycarbonylaminomethylcarbonylamino-substituted compounds in the scPTZ test, whereas they were equipotent in the MES screen. Following oral administration, 3-benzyloxycarbonylaminomethylcarbonyl(N-methyl)amino-4-(2-chlorob enzoyl) pyridine exhibited a potency greater than that of valproic acid but less than that of clonazepam in the rat scPTZ screening test. 3-Benzyloxycarbonylaminomethylcarbonylamino-4-(2-fluorobenzoyl)pyr idine was the most potent compound in the rat oral MES screening test, exhibiting an activity greater than that of clonazepam but less than that of phenytoin. The 3-alkoxycarbonylaminomethylcarbonylamino-4-(arylcarbonylpyridin es had moderate affinity for the benzodiazepine receptor site(s); the IC50s in displacing 10 nM [3H]flunitazepam were in the 0.37-15.11 microM range (clonazepam = 0.003 microM).","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"6 2","pages":"111-21"},"PeriodicalIF":0.0,"publicationDate":"1990-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13122226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transdermal drug delivery: efficacy and potential applications of the penetration enhancer Azone. 经皮给药:渗透增强剂氮酮的疗效和潜在应用。

Drug design and delivery Pub Date : 1990-06-01

J W Wiechers, R A de Zeeuw

引用次数: 0

The discovery of the first beta-adrenergic blocking agents. 第一批肾上腺素能阻滞剂的发现。

Drug design and delivery Pub Date : 1990-06-01

A F Crowther

引用次数: 0

Synthesis and activity of 1,4-dihydropyridine analogues of histamine H2-receptor antagonists. 组胺h2受体拮抗剂1,4-二氢吡啶类似物的合成及活性研究。

Drug design and delivery Pub Date : 1990-06-01

V K Agrawal, S B Tang, M W Wolowyk, E E Knaus

{"title":"Synthesis and activity of 1,4-dihydropyridine analogues of histamine H2-receptor antagonists.","authors":"V K Agrawal, S B Tang, M W Wolowyk, E E Knaus","doi":"","DOIUrl":"","url":null,"abstract":"Compounds of the type Het-CH2-S-CH2-CH2-Y were prepared, in which Het was 2-, 3- or 4-pyridyl, and Y was a derivative of 2-cyano-1,1-iminodiamine or 2-nitro-1,1-ethenediamine in which the terminal nitrogen was incorporated into a 1,4-dihydropyridine ring (general structure 7; X = NCN or CHNO2). Pharmacological testing using the histamine-induced guinea pig atrial chronotropic response indicated that the pyridyl substituent position was a determinant of activity, the activity order within each isomeric series being usually 2-pyridyl greater than 3- and 4-pyridyl. There was no significant difference in activity between otherwise similar compounds derived from 2-cyano-1,1-iminodiamine (7, X = NCN) or 2-nitro-1,1-ethenediamine (7, X = CHNO2). All compounds had a substituent (R) attached to the C-4 position of the dihydropyridine ring, and the nature of the R substituent influenced the H2-antagonist activity, the relative activity order being usually n-Bu greater than Ph greater than Me. In general, the incorporation of the terminal nitrogen into a 1,4-dihydropyridyl ring system favoured biological activity, 1-(2-[(4-Pyridylmethylthio)ethylamino])-1-(1-[3-(4, 4-dimethyloxazolin-2-yl)-4-n-butyl-1,4-dihydropyridyl)-2- cyanoimine (7f) was the most potent H2-receptor antagonist exhibiting an activity approaching that of cimetidine.","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"6 2","pages":"101-9"},"PeriodicalIF":0.0,"publicationDate":"1990-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13140344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tissue distribution of a brain-enhanced chemical delivery system for estradiol. 脑增强雌二醇化学输送系统的组织分布。

Drug design and delivery Pub Date : 1990-05-01

M H Rahimy, J W Simpkins, N Bodor

{"title":"Tissue distribution of a brain-enhanced chemical delivery system for estradiol.","authors":"M H Rahimy, J W Simpkins, N Bodor","doi":"","DOIUrl":"","url":null,"abstract":"Enhanced delivery and sustained release of estradiol (E2) in the brain could have potential clinical applications in the effective treatment of vasomotor \"hot flushes\" and prostatic cancer. We have, therefore, evaluated a brain-enhanced E2-chemical delivery system (E2-CDS), which is based upon the interconvertible dihydropyridine in equilibrium with pyridinium salt redox reaction. In this study, we evaluated the tissue distributions of E2-Q+ and E2--the inactive and active metabolites of the E2-CDS. Both E2-Q+ and E2 were detected in all tissues analyzed. In peripheral tissues, E2-Q+ and E2 were rapidly cleared, but in brain, concentrations of both compounds exhibited a slow decline with a t1/2 = 8 days. 14 Days after the E2-CDS administration, brain levels of E2-Q+ exceeded plasma levels by 170-fold, fat levels by 20-fold, and liver levels by 8-fold. Similarly, brain-E2 levels exceeded plasma levels by 38-fold, fat levels by 11-fold, and liver levels by 7-fold. Furthermore, levels of E2-Q+ In anterior pituitary, kidney, heart, and lung were initially 2- to 6-fold higher than brain levels, but 14 days after the E2-CDS administration, brain levels of E2-Q+ exceeded E2-Q+ levels in these peripheral tissues by 1.5- to 3-fold. The increased brain/peripheral tissues ratios of E2-Q+ and E2 in rats treated with the E2-CDS support brain-enhanced delivery and sustained release of E2 from this delivery system.","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"6 1","pages":"29-40"},"PeriodicalIF":0.0,"publicationDate":"1990-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13234589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inositol phospholipid-dependent cellular signalling: opportunities for drug discovery. 肌醇磷脂依赖的细胞信号:药物发现的机会。

Drug design and delivery Pub Date : 1990-05-01

R C Young, C P Downes

引用次数: 0

In vitro evaluations of transdermal levonorgestrel. 左炔诺孕酮透皮体外评价。

Drug design and delivery Pub Date : 1990-05-01

P Catz, D R Friend

引用次数: 0

Quantitative structure-activity relationships of salicylamide neuroleptic agents. 水杨胺类抗精神病药的定量构效关系。

Drug design and delivery Pub Date : 1990-05-01

S P Gupta, R N Saha, P Singh

引用次数: 0