首页 > 最新文献

Drug design and delivery最新文献

英文 中文
Structural and microbiological evaluation of a degradable sustained-release device for use in periodontal therapy. 用于牙周治疗的可降解缓释装置的结构和微生物学评价。
Pub Date : 1991-01-01
M Friedman, D Steinberg, M N Sela, A Soskolne

Degradable protein matrices containing chlorhexidine were tested as intra-pocket drug delivery systems in the treatment of periodontal diseases. The properties of the device were mainly dependent upon the degree of cross linking in the matrix, which could be varied according to the preparative conditions. The degree of cross linking was determined by amino acid analysis based on the amount of free lysine in the protein. The release of chlorhexidine and of the plasticizer used in the preparation of the matrix were determined. The release of chlorhexidine from the matrix was prolonged for a period of 300 hours, and the release of plasticizer ceased after four hours. Limited clinical trials suggest that one of the degradable devices--that containing the highest amount of cross-linking--causes a significant reduction in the amount of perio-pathogenic bacteria following its insertion into the periodontal pockets of patients with periodontal disease.

研究了含氯己定的可降解蛋白基质作为治疗牙周病的口袋内给药系统。该装置的性能主要取决于基质中的交联程度,而交联程度可以根据制备条件的不同而变化。根据蛋白质中游离赖氨酸的数量,通过氨基酸分析来确定交联程度。测定了氯己定的释放度和制备基质所用增塑剂的释放度。氯己定从基质中释放延长300小时,增塑剂在4小时后停止释放。有限的临床试验表明,其中一种可降解装置——含有最多的交联——在将其插入牙周病患者的牙周袋后,可显著减少牙周致病菌的数量。
{"title":"Structural and microbiological evaluation of a degradable sustained-release device for use in periodontal therapy.","authors":"M Friedman,&nbsp;D Steinberg,&nbsp;M N Sela,&nbsp;A Soskolne","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Degradable protein matrices containing chlorhexidine were tested as intra-pocket drug delivery systems in the treatment of periodontal diseases. The properties of the device were mainly dependent upon the degree of cross linking in the matrix, which could be varied according to the preparative conditions. The degree of cross linking was determined by amino acid analysis based on the amount of free lysine in the protein. The release of chlorhexidine and of the plasticizer used in the preparation of the matrix were determined. The release of chlorhexidine from the matrix was prolonged for a period of 300 hours, and the release of plasticizer ceased after four hours. Limited clinical trials suggest that one of the degradable devices--that containing the highest amount of cross-linking--causes a significant reduction in the amount of perio-pathogenic bacteria following its insertion into the periodontal pockets of patients with periodontal disease.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 3","pages":"241-50"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13071444","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
A theoretical model for the histamine H2-receptor. 组胺h2受体的理论模型。
Pub Date : 1991-01-01
R D Enriz, E A Jauregui

We describe an electronic and conformational study of histamine H2-receptor ligands of the imidazole series, in which the possibilities of configurational isomerism (the thiourea group) and N3H and N1H tautomerism (imidazole ring) were considered. The results suggest that the conformational flexibility of the molecules and the properties of the imidazole ring are of special importance in the display of H2-receptor activity. A theoretical model of histamine H2-receptor interactions is proposed on the basis of these and other results. A very important characteristic of our model is its ability to explain H2-receptor activation by compounds which differ structurally, and to explain antagonism at the same receptor. The stereospecificity of rigid analogues of cimetidine and tiotidine, and the importance of chain length in flexible histamine H2-antagonists are also accounted for.

我们描述了咪唑系列组胺h2受体配体的电子和构象研究,其中考虑了构型异构(硫脲基团)和N3H和N1H互变异构(咪唑环)的可能性。结果表明,分子的构象柔韧性和咪唑环的性质对h2受体活性的表现具有特别重要的影响。在这些和其他结果的基础上,提出了组胺h2受体相互作用的理论模型。我们的模型的一个非常重要的特点是它能够解释不同结构的化合物对h2受体的激活,并解释同一受体的拮抗作用。西咪替丁和噻替丁刚性类似物的立体特异性,以及柔性组胺h2拮抗剂链长度的重要性也被考虑在内。
{"title":"A theoretical model for the histamine H2-receptor.","authors":"R D Enriz,&nbsp;E A Jauregui","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We describe an electronic and conformational study of histamine H2-receptor ligands of the imidazole series, in which the possibilities of configurational isomerism (the thiourea group) and N3H and N1H tautomerism (imidazole ring) were considered. The results suggest that the conformational flexibility of the molecules and the properties of the imidazole ring are of special importance in the display of H2-receptor activity. A theoretical model of histamine H2-receptor interactions is proposed on the basis of these and other results. A very important characteristic of our model is its ability to explain H2-receptor activation by compounds which differ structurally, and to explain antagonism at the same receptor. The stereospecificity of rigid analogues of cimetidine and tiotidine, and the importance of chain length in flexible histamine H2-antagonists are also accounted for.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 3","pages":"183-202"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13071442","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
QSAR studies on benzodiazepine receptor binding of purines and amino acid derivatives. 嘌呤和氨基酸衍生物与苯二氮卓受体结合的QSAR研究。
Pub Date : 1991-01-01
R N Saha, J Meera, N Agrawal, S P Gupta

Quantitative structure-activity relationship (QSAR) studies are reported on the benzodiazepine receptor binding of a series of substituted 9-benzyl-6-dimethylamino-9H-purines and N-(indol-3-ylglyoxylyl)amino acid derivatives. The nitrogen of the five membered heterocyclic ring and the polar substituent in the aromatic ring, present in both series of compounds, form important centres in the binding interaction. We conclude that the receptor must possess a strong nucleophilic centre and a polar site, and that a hydrophobic pocket exists to accommodate hydrophobic moieties.

报道了一系列取代的9-苄基-6-二甲氨基- 9h -嘌呤和N-(吲哚-3-基乙基氧基)氨基酸衍生物与苯二氮卓受体结合的定量构效关系(QSAR)研究。五元杂环上的氮和芳香环上的极性取代基都存在于这两个系列化合物中,它们是结合相互作用的重要中心。我们得出结论,受体必须具有强亲核中心和极性位点,并且存在疏水口袋以容纳疏水部分。
{"title":"QSAR studies on benzodiazepine receptor binding of purines and amino acid derivatives.","authors":"R N Saha,&nbsp;J Meera,&nbsp;N Agrawal,&nbsp;S P Gupta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Quantitative structure-activity relationship (QSAR) studies are reported on the benzodiazepine receptor binding of a series of substituted 9-benzyl-6-dimethylamino-9H-purines and N-(indol-3-ylglyoxylyl)amino acid derivatives. The nitrogen of the five membered heterocyclic ring and the polar substituent in the aromatic ring, present in both series of compounds, form important centres in the binding interaction. We conclude that the receptor must possess a strong nucleophilic centre and a polar site, and that a hydrophobic pocket exists to accommodate hydrophobic moieties.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 3","pages":"219-26"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12820376","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
Quantum QSAR of the antirhinoviral activity of 9-benzylpurines. 9-苄基嘌呤抗鼻病毒活性的量子QSAR。
Pub Date : 1991-01-01
Y S Prabhakar

The antirhinoviral activity of previously described 9-benzylpurines was quantitatively analysed using Huckel molecular orbital generated electronic parameters and physicochemical properties of substituents. Correlations with the activity against each of several serotypes of the virus were obtained but very few common requirements emerged. Our results emphasise the difficulties in identifying a compound with optimum structural features for broad spectrum antirhinovirus activity.

利用Huckel分子轨道生成的电子参数和取代基的物理化学性质定量分析了先前描述的9-苄基嘌呤的抗鼻病毒活性。获得了对几种血清型病毒活性的相关性,但出现了很少的共同要求。我们的结果强调了鉴定具有最佳结构特征的化合物具有广谱抗鼻病毒活性的困难。
{"title":"Quantum QSAR of the antirhinoviral activity of 9-benzylpurines.","authors":"Y S Prabhakar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The antirhinoviral activity of previously described 9-benzylpurines was quantitatively analysed using Huckel molecular orbital generated electronic parameters and physicochemical properties of substituents. Correlations with the activity against each of several serotypes of the virus were obtained but very few common requirements emerged. Our results emphasise the difficulties in identifying a compound with optimum structural features for broad spectrum antirhinovirus activity.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 3","pages":"227-39"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12820377","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
Synthesis and antinociceptive activity of 4-pyridyl and -dihydropyridyl analogues of meperidine and ketobemidone. 哌替啶和酮贝酮的4-吡啶和-二氢吡啶类似物的合成及其抗伤活性。
Pub Date : 1990-12-01
J K Buolamwini, E E Knaus

The synthesis and antinociceptive activity of 4-pyridylpiperdines (7 and 10) in which the phenyl group pf meperidine (1) or ketobemidone (3) is replaced by 2'-, 3'- or 4'-pyridyl is described. All were active in a rat writhing test, and the results showed that the point of attachment of the pyridyl ring to the 4-position was an important determinant of the activity; the relative potency order was 3'-pyridyl greater than 4'-pyridyl greater than 2'-pyridyl in each of the two series. The most potent compound (half the potency of meperidine) was 4-ethoxycarbonyl-4-(3'-pyridyl)-l-methylpiperidine (7b). This compound, and the corresponding 4'-isomer (7c), were further elaborated to provide 1'-phenyl, 1',6'-dihydropyridine (11), and 1'-phenyl, methyl or n-butyl. 1',2'-dihydropyridine (12) analogues containing an acyl function on the ring nitrogen. The most active compound in this series was 4-[4'-(1'-phenoxycarbonyl-2'-n-butyl-l',2'-dihydropyridyl)]- 4- ethoxycarbonyl-l-methylpiperdine (12k). Though less potent than the parent pyridyl compound (7c), it induced 70% inhibition in the writhing test at a dose of 8 mg/kg sc. [The ED50 for meperidine was 0.6 mg/kg sc.]

本文描述了4-吡啶基哌替啶(1)或酮苯酮(3)的苯基被2'-、3'-或4'-吡啶基取代的4-吡啶基哌替啶(7和10)的合成及其抗炎活性。在大鼠扭体实验中均有活性,结果表明吡啶环与4位的附着点是决定活性的重要因素;相对效价顺序为3′-吡啶基> 4′-吡啶基> 2′-吡啶基。最有效的化合物是4-乙氧羰基-4-(3'-吡啶基)-l-甲基哌啶(7b)。该化合物和相应的4′-异构体(7c)进一步得到1′-苯基、1′,6′-二氢吡啶(11)和1′-苯基、甲基或正丁基。1',2'-二氢吡啶(12)在环氮上含有酰基的类似物。该系列化合物中活性最高的是4-[4'-(1'-苯氧羰基-2'-正丁基- 1',2'-二氢吡啶)]- 4-乙氧羰基- 1 -甲基哌啶(12k)。虽然药效不如母体吡啶化合物(7c),但在8 mg/kg sc的剂量下,它在扭体试验中有70%的抑制作用[哌替啶的ED50为0.6 mg/kg sc]。
{"title":"Synthesis and antinociceptive activity of 4-pyridyl and -dihydropyridyl analogues of meperidine and ketobemidone.","authors":"J K Buolamwini,&nbsp;E E Knaus","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The synthesis and antinociceptive activity of 4-pyridylpiperdines (7 and 10) in which the phenyl group pf meperidine (1) or ketobemidone (3) is replaced by 2'-, 3'- or 4'-pyridyl is described. All were active in a rat writhing test, and the results showed that the point of attachment of the pyridyl ring to the 4-position was an important determinant of the activity; the relative potency order was 3'-pyridyl greater than 4'-pyridyl greater than 2'-pyridyl in each of the two series. The most potent compound (half the potency of meperidine) was 4-ethoxycarbonyl-4-(3'-pyridyl)-l-methylpiperidine (7b). This compound, and the corresponding 4'-isomer (7c), were further elaborated to provide 1'-phenyl, 1',6'-dihydropyridine (11), and 1'-phenyl, methyl or n-butyl. 1',2'-dihydropyridine (12) analogues containing an acyl function on the ring nitrogen. The most active compound in this series was 4-[4'-(1'-phenoxycarbonyl-2'-n-butyl-l',2'-dihydropyridyl)]- 4- ethoxycarbonyl-l-methylpiperdine (12k). Though less potent than the parent pyridyl compound (7c), it induced 70% inhibition in the writhing test at a dose of 8 mg/kg sc. [The ED50 for meperidine was 0.6 mg/kg sc.]</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 1","pages":"19-31"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13141154","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
Cytotoxicity of Mannich bases of alpha-arylidene-beta-ketoesters and related compounds against EMT6 mammary carcinoma cells. α -芳基烯- β -酮酯曼尼希碱及其相关化合物对EMT6乳腺癌细胞的细胞毒性研究
Pub Date : 1990-12-01
J R Dimmock, E Erciyas, G E Bigam, D L Kirkpatrick, M M Duke

A number of Mannich bases 2 derived from alpha-arylidene-beta-ketoesters, some corresponding deaminated products 3, and a thiol adduct 5 were prepared. High resolution 1H NMR spectroscopy revealed that, in solution, most of the bases 2 existed principally in acyclic forms, but that all members of this series underwent some intramolecular cyclization. The compounds 2, 3 and 5 possessed activity against EMT6 mammary carcinoma cells. The Mannich bases 2a-e had the highest cytotoxicity. Topliss analysis of these compounds revealed an E4 parameter dependency, in which intramolecular cyclization was minimal. The Mannich base 2f--which existed principally in the cyclic forms 6 in deuterium oxide, the deamination products, and a thiol adduct had approximately one-sixth of the activity of 2a-e.

制备了一系列由-芳基烯- -酮酯衍生的曼尼希碱2、相应的脱胺产物3和巯基加合物5。高分辨率1H核磁共振光谱显示,在溶液中,大多数碱基2主要以无环形式存在,但该系列的所有成员都发生了一些分子内环化。化合物2、3和5具有抗EMT6乳腺癌细胞的活性。曼尼希碱基2a-e具有最高的细胞毒性。这些化合物的Topliss分析揭示了E4参数依赖性,其中分子内环化最小。曼尼希碱主要以氧化氘、脱氨产物和硫醇加合物中的环形式存在,其活性约为2a-e的六分之一。
{"title":"Cytotoxicity of Mannich bases of alpha-arylidene-beta-ketoesters and related compounds against EMT6 mammary carcinoma cells.","authors":"J R Dimmock,&nbsp;E Erciyas,&nbsp;G E Bigam,&nbsp;D L Kirkpatrick,&nbsp;M M Duke","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A number of Mannich bases 2 derived from alpha-arylidene-beta-ketoesters, some corresponding deaminated products 3, and a thiol adduct 5 were prepared. High resolution 1H NMR spectroscopy revealed that, in solution, most of the bases 2 existed principally in acyclic forms, but that all members of this series underwent some intramolecular cyclization. The compounds 2, 3 and 5 possessed activity against EMT6 mammary carcinoma cells. The Mannich bases 2a-e had the highest cytotoxicity. Topliss analysis of these compounds revealed an E4 parameter dependency, in which intramolecular cyclization was minimal. The Mannich base 2f--which existed principally in the cyclic forms 6 in deuterium oxide, the deamination products, and a thiol adduct had approximately one-sixth of the activity of 2a-e.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 1","pages":"51-8"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13251831","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
Inhibitory effect of beta-cyclodextrin on ampicillin polymerization in aqueous solution. 环糊精对氨苄西林水溶液聚合的抑制作用。
Pub Date : 1990-12-01
H Aki, K Yamamoto, N Sawai, M Yamamoto

Ampicillin polymerizes in aqueous solution to produce antigenic polymers; the polymers were separated by anion-exchange chromatography and shown to consist of a dimer, trimer, tetramer and pentamer of ampicillin by the masses found in fast atom bombardment mass spectroscopy. The presence of an intact beta-lactam ring in each of the polymers was revealed by the characteristic positive Cotton effect near 230 nm in their circular dichroism spectra. beta-Cyclodextrin was found to inhibit this polymerization by complex formation involving equimolar quantities of the constituents. Formation of this complex was complete in 10% aqueous solution within 6 hr at 24 degrees C. The positive Cotton effect arising from the beta-lactam ring decreased as the degree of polymerization increased, but was unchanged by the complex formation with beta-cyclodextrin.

氨苄西林在水溶液中聚合产生抗原聚合物;用阴离子交换色谱法对聚合物进行了分离,并通过快速原子轰击质谱的质量发现,聚合物由氨苄西林的二聚体、三聚体、四聚体和五聚体组成。在其圆二色光谱中,在230 nm附近的特征正棉花效应揭示了每个聚合物中存在完整的β -内酰胺环。β -环糊精被发现抑制这种聚合通过复杂的形成涉及等摩尔量的成分。该络合物在10%的水溶液中,在24℃下6小时内完全形成。随着聚合程度的增加,β -内酰胺环产生的正棉效应降低,但与β -环糊精形成的正棉效应不变。
{"title":"Inhibitory effect of beta-cyclodextrin on ampicillin polymerization in aqueous solution.","authors":"H Aki,&nbsp;K Yamamoto,&nbsp;N Sawai,&nbsp;M Yamamoto","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Ampicillin polymerizes in aqueous solution to produce antigenic polymers; the polymers were separated by anion-exchange chromatography and shown to consist of a dimer, trimer, tetramer and pentamer of ampicillin by the masses found in fast atom bombardment mass spectroscopy. The presence of an intact beta-lactam ring in each of the polymers was revealed by the characteristic positive Cotton effect near 230 nm in their circular dichroism spectra. beta-Cyclodextrin was found to inhibit this polymerization by complex formation involving equimolar quantities of the constituents. Formation of this complex was complete in 10% aqueous solution within 6 hr at 24 degrees C. The positive Cotton effect arising from the beta-lactam ring decreased as the degree of polymerization increased, but was unchanged by the complex formation with beta-cyclodextrin.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 1","pages":"59-63"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13251781","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
Drug release from glutaraldehyde-treated fibrin gels. 戊二醛处理纤维蛋白凝胶的药物释放。
Pub Date : 1990-12-01
H O Ho, M T Sheu, T D Sokoloski, C Y Chen

Glutaraldehyde treatment of dexamethasone-containing cylindrical fibrin gels (obtained by the thrombin-induced polymerization of fibrinogen in the presence of the drug) causes cross-linking of the gels and modification of the pore structure. The effect on the release of dexamethasone was assessed by measuring the diffusion coefficient of the drug across treated and untreated gels; diffusion across the treated gels was significantly decreased as compared with untreated gels, but was little affected by the concentration of glutaraldehyde used in the treatment. In biodegradable tests, the treated gels (all concentrations of glutaraldehyde) were resistant to digestion even in the presence of plasmin, but untreated gels were digested, and the digestion rate was accelerated by plasmin. The volume of the gels was progressively reduced as the concentration of glutaraldehyde was increased or the amount of fibrinogen was decreased, but the extent of the reduction did not correlate with the changes in the diffusion coefficient.

戊二醛处理含地塞米松的圆柱形纤维蛋白凝胶(在药物存在下由凝血酶诱导的纤维蛋白原聚合得到)引起凝胶的交联和孔结构的修饰。通过测定药物在处理和未处理凝胶中的扩散系数来评估药物对地塞米松释放的影响;与未处理的凝胶相比,处理凝胶的扩散明显减少,但受处理中使用的戊二醛浓度的影响很小。在可生物降解试验中,处理过的凝胶(所有浓度的戊二醛)即使在存在纤溶酶的情况下也不耐消化,但未处理的凝胶可以消化,并且纤溶酶加速了消化速度。随着戊二醛浓度的增加或纤维蛋白原含量的减少,凝胶的体积逐渐减小,但减小的程度与扩散系数的变化无关。
{"title":"Drug release from glutaraldehyde-treated fibrin gels.","authors":"H O Ho,&nbsp;M T Sheu,&nbsp;T D Sokoloski,&nbsp;C Y Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Glutaraldehyde treatment of dexamethasone-containing cylindrical fibrin gels (obtained by the thrombin-induced polymerization of fibrinogen in the presence of the drug) causes cross-linking of the gels and modification of the pore structure. The effect on the release of dexamethasone was assessed by measuring the diffusion coefficient of the drug across treated and untreated gels; diffusion across the treated gels was significantly decreased as compared with untreated gels, but was little affected by the concentration of glutaraldehyde used in the treatment. In biodegradable tests, the treated gels (all concentrations of glutaraldehyde) were resistant to digestion even in the presence of plasmin, but untreated gels were digested, and the digestion rate was accelerated by plasmin. The volume of the gels was progressively reduced as the concentration of glutaraldehyde was increased or the amount of fibrinogen was decreased, but the extent of the reduction did not correlate with the changes in the diffusion coefficient.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 1","pages":"65-73"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13283781","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
Synthesis and calcium channel antagonist activity of nifedipine analogues containing 4-pyridyl and 3-arylethyloxycarbonyl substituents. 含4-吡啶基和3-芳基氧羰基取代基硝苯地平类似物的合成及其钙通道拮抗剂活性。
Pub Date : 1990-12-01
M R Akula, W C Matowe, M W Wolowyk, E E Knaus

A series of unsymmetrical 3-arylethyl 5-isopropyl ester analogues of nifedipine, in which the 2'-nitrophenyl group at the 4 position is replaced by 2'- or 3'-pyridyl, were prepared and evaluated as calcium channel antagonists. The point of attachment of the pyridyl substituent was a determinant of activity, 2'-pyridyl analogues always being more potent than corresponding 3'-pyridyl analogues. The introduction of a substituent at the para-position of the phenethyl group in 3-phenethyl ester analogues usually enhanced the activity. The most potent compound was 3-(4'-bromophenethyl) 5-isopropyl 1,4-dihydro-2,6-dimethyl-4-(2'-pyridyl)-3,5-pyridinedicarboxylate. It was 82-fold more potent than nifedipine, and it did not exhibit a negative inotropic effect on guinea pig left atrium. Desirable features in 1,4-dihydropyridine calcium antagonists of the unsymmetrical 3,5-diester type are therefore a 4-(2-pyridyl) substituent in conjunction with a hydrophobic 3-(4-substituted-phenethyl) ester substituent. The arylethyl ester and the 4-(2'-pyridyl) substituents appear to provide important interdependent contributions to the calcium channel antagonist activity.

制备了一系列硝苯地平的不对称3-芳基乙基5-异丙基酯类似物,其中4位的2'-硝基苯基被2'-或3'-吡啶基取代,并对其作为钙通道拮抗剂进行了评价。吡啶基取代基的附着点是活性的决定因素,2'-吡啶基类似物总是比相应的3'-吡啶基类似物更有效。在3-苯乙酯类似物的对位上引入取代基通常能提高活性。最有效的化合物是3-(4′-溴苯乙基)5-异丙基1,4-二氢-2,6-二甲基-4-(2′-吡啶基)-3,5-吡啶二羧酸酯。它的效力是硝苯地平的82倍,并且对豚鼠左心房没有负性肌力作用。因此,不对称的3,5-二酯型1,4-二氢吡啶钙拮抗剂的理想特征是4-(2-吡啶基)取代基与疏水的3-(4-取代-苯乙酯)取代基结合。芳基乙基酯和4-(2'-吡啶基)取代基似乎对钙通道拮抗剂活性提供了重要的相互依赖的贡献。
{"title":"Synthesis and calcium channel antagonist activity of nifedipine analogues containing 4-pyridyl and 3-arylethyloxycarbonyl substituents.","authors":"M R Akula,&nbsp;W C Matowe,&nbsp;M W Wolowyk,&nbsp;E E Knaus","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A series of unsymmetrical 3-arylethyl 5-isopropyl ester analogues of nifedipine, in which the 2'-nitrophenyl group at the 4 position is replaced by 2'- or 3'-pyridyl, were prepared and evaluated as calcium channel antagonists. The point of attachment of the pyridyl substituent was a determinant of activity, 2'-pyridyl analogues always being more potent than corresponding 3'-pyridyl analogues. The introduction of a substituent at the para-position of the phenethyl group in 3-phenethyl ester analogues usually enhanced the activity. The most potent compound was 3-(4'-bromophenethyl) 5-isopropyl 1,4-dihydro-2,6-dimethyl-4-(2'-pyridyl)-3,5-pyridinedicarboxylate. It was 82-fold more potent than nifedipine, and it did not exhibit a negative inotropic effect on guinea pig left atrium. Desirable features in 1,4-dihydropyridine calcium antagonists of the unsymmetrical 3,5-diester type are therefore a 4-(2-pyridyl) substituent in conjunction with a hydrophobic 3-(4-substituted-phenethyl) ester substituent. The arylethyl ester and the 4-(2'-pyridyl) substituents appear to provide important interdependent contributions to the calcium channel antagonist activity.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 1","pages":"11-7"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13251828","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
Charge densities of atoms of conjugated styryl ketones having activity against L1210 leukemia cells. 对L1210白血病细胞有活性的共轭苯乙烯酮原子的电荷密度。
Pub Date : 1990-12-01
J R Dimmock, E Erciyas, K K Sidhu, X Luo, P G Mezey, T M Allen, L Murray

Electron density calculations were undertaken on several atoms in a series of 3-substituted-4-phenyl-3-buten-2-ones in order to gain insight into the molecular features which affect charge densities. The results indicate that substituents at position 3 alter the electron densities of the olefinic group but have little effect on the acetyl function. The compounds were tested against L1210 cells in vitro, and the results suggest that electronic--but not steric--factors are important in affecting cytotoxicity. The most active compound was 3-phenylmethylene-2,4-pentanedione (1c) with an ED50 value of 1.06 x 10(-8) M.

为了深入了解影响电荷密度的分子特征,对一系列3-取代-4-苯基-3-丁烯-2- 1中的几个原子进行了电子密度计算。结果表明,3位取代基改变了烯烃基团的电子密度,但对乙酰基功能影响不大。这些化合物在体外对L1210细胞进行了测试,结果表明电子因子(而不是位阻因子)在影响细胞毒性方面很重要。活性最高的化合物为3-苯基亚甲基-2,4-戊二酮(1c), ED50值为1.06 × 10(-8) M。
{"title":"Charge densities of atoms of conjugated styryl ketones having activity against L1210 leukemia cells.","authors":"J R Dimmock,&nbsp;E Erciyas,&nbsp;K K Sidhu,&nbsp;X Luo,&nbsp;P G Mezey,&nbsp;T M Allen,&nbsp;L Murray","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Electron density calculations were undertaken on several atoms in a series of 3-substituted-4-phenyl-3-buten-2-ones in order to gain insight into the molecular features which affect charge densities. The results indicate that substituents at position 3 alter the electron densities of the olefinic group but have little effect on the acetyl function. The compounds were tested against L1210 cells in vitro, and the results suggest that electronic--but not steric--factors are important in affecting cytotoxicity. The most active compound was 3-phenylmethylene-2,4-pentanedione (1c) with an ED50 value of 1.06 x 10(-8) M.</p>","PeriodicalId":11271,"journal":{"name":"Drug design and delivery","volume":"7 1","pages":"45-9"},"PeriodicalIF":0.0,"publicationDate":"1990-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13251830","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
期刊
Drug design and delivery
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1