公开(公告)号：US4880921A

公开(公告)日：1989-11-14

申请号：US75830

申请日：1987-07-20

申请人： Nicholas S. Bodor

发明人： Nicholas S. Bodor

IPC分类号： A61K38/00 ,  C07D209/32 ,  C07D211/90 ,  C07D213/80 ,  C07D213/82 ,  C07D401/12 ,  C07J43/00 ,  C07K14/70

CPC分类号： C07D213/80 ,  A61K47/48161 ,  C07D209/32 ,  C07D211/90 ,  C07D213/82 ,  C07D401/12 ,  C07J43/003 ,  C07K14/70 ,  A61K38/00

摘要： The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are:(a) compounds of the formula[D--DHC] (I) wherein [D] is a centrally acting drug species, and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine .revreaction. pyridinium salt redox carrier, with the proviso that when [DHC] is ##STR1## wherein R is lower alkyl or benzyl and [D] is a drug species containing a single NH.sub.2 or OH functional group, the single OH group when present being a primary or secondary OH group, said drug species being linked directly through said NH.sub.2 or OH functional group to the carbonyl function of [DHC], then [D] must be other than a sympathetic stimulant, steroid sex hormone or long chain alkanol; and(b) non-boxic pharmaceutically acceptable salts of compounds of formula (I) wherein [D] is a centrally acting drug species and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine .revreaction. pyridinium salt redox carrier. The corresponding ionic pyridinium salt type drug/carrier entities [D--QC].sup.+ X.sup.- are also disclosed.

摘要翻译： 适用于中枢作用药物物种向大脑的位点特异性/持续递送的主题化合物是：（a）式[D-DHC]（I）化合物，其中[D]为中枢作用药物 物种和[DHC]是二氢吡啶 - >β-吡啶鎓盐氧化还原载体的减少的，生物可氧化的血脑屏障穿透脂质形式，条件是当[DHC]为[IMAGE]，其中R为低级烷基或苄基 和[D]是含有单个NH 2或OH官能团的药物，当存在的单个OH基团是伯或仲OH基团时，所述药物物质通过所述NH 2或OH官能团直接连接到[ DHC]，则[D]必须不是交感兴奋剂，类固醇性激素或长链烷醇; 和（b）式（I）化合物的非盒状药学上可接受的盐，其中[D]是中心作用的药物物质，[DHC]是还原的，生物可氧化的，血脑屏障穿透的二氢吡啶 - - 吡啶鎓盐氧化还原载体。 还公开了相应的离子型吡啶鎓盐型药物/载体实体[D-QC] + X-。

公开(公告)号：US4829070A

公开(公告)日：1989-05-09

申请号：US666210

申请日：1984-10-29

申请人： Nicholas S. Bodor

发明人： Nicholas S. Bodor

IPC分类号： A61K38/00 ,  C07D209/32 ,  C07D211/90 ,  C07D213/80 ,  C07D213/82 ,  C07D401/12 ,  C07J43/00 ,  C07K14/70

CPC分类号： C07D213/80 ,  A61K47/48161 ,  C07D209/32 ,  C07D211/90 ,  C07D213/82 ,  C07D401/12 ,  C07J43/003 ,  C07K14/70 ,  A61K38/00

摘要： The invention provides compounds of the formulaD--DHC].sub.n (I)and the nontoxic pharmaceutically acceptable salt thereof, wherein D is the residue of a centrally acting drug containing at least one reactive functional group selected from the group consisting of amino, hydroxyl, mercapto, carboxyl, amide and imide, said residue being characterized by the absence of a hydrogen atom from at least one of said reactive functional groups in said drug; n is a positive integer equal to the number of said functional groups from which a hydrogen atom is absent; and [DHC] is the reduced, biooxidizable, blood-brain barrier penetratring lipoidal form of a dihydropyridine.revreaction.pyridinium salt redox carrier, said carrier comprising a bivalent radical of the formula ##STR1## wherein the alkylene group can be straight or branched and can contain 1 to 3 carbon atoms; R.sub.o is a radical identical to the corresponding portion of a natural amino acid; and p is 1 or 2, provided that, when p is 2, then the alkylene groups can be the same or different and the R.sub.o radicals can be the same or different; said bivalent radical being so positioned that the terminal carbonyl function of the bivalent radical is linked to the drug residue while the terminal amino function of the bivalent radical is linked to the remaining portion of the carrier moiety. The subject compounds are adapted for the site-specific/sustained delivery of centrally acting drugs to the brain. The corresponding pyridinium salt type drug/carrier entities D--QC.sup.+ ].sub.n q.sup.y-t are also disclosed.

摘要翻译： 本发明提供式D-DHC] n（I）化合物及其无毒的药学上可接受的盐，其中D是含有至少一个选自氨基，羟基， 巯基，羧基，酰胺和酰亚胺，所述残基的特征在于所述药物中至少一个所述反应性官能团不存在氢原子; n是与不存在氢原子的所述官能团的数目相等的正整数; 和[DHC]是二氢吡啶 - >β-吡啶鎓盐氧化还原载体的减少的，生物可氧化的血脑屏障穿透脂质形式，所述载体包含式“IMAGE”的二价基团，其中亚烷基可以是直链或支链的 并且可以含有1至3个碳原子; Ro是与天然氨基酸的相应部分相同的基团; p为1或2，条件是当p为2时，亚烷基可以相同或不同，且R f基团可以相同或不同; 所述二价基团的定位使得二价基团的末端羰基官能团与药物残基连接，而二价基团的末端氨基官能团与载体部分的剩余部分连接。 主题化合物适用于将中枢作用药物的位点特异性/持续递送给脑。 还公开了相应的吡啶鎓盐型药物/载体实体D-QC +] n qy-t。

公开(公告)号：US4476117A

公开(公告)日：1984-10-09

申请号：US449880

申请日：1982-12-15

申请人： John S. Morley

发明人： John S. Morley

IPC分类号： A61K38/00 ,  A61P25/00 ,  C07K7/06 ,  C07K14/70 ,  C07C103/52 ,  A61K37/02

CPC分类号： C07K14/70 ,  A61K38/00

摘要： Compounds of the formula: ##STR1## wherein R.sup.1 and R.sup.2 stand for alk-2-enyl radicals of not more than 6 carbon atoms, A stands for Gly or Azgly, B stands for Leu or Met, J stands for --(CH.sub.2).sub.n --, wherein n stands for an integer from 1 to 10, or a phenylene radical, and pharmaceutically-acceptable acid-addition salts thereof. Processes for the manufacture of the compounds. Pharmaceutical compositions comprising one of the compounds and a pharmaceutical diluent or carrier. The compounds are selective .delta.-opiate-receptor antagonists.

摘要翻译： 下式的化合物：其中R1和R2代表不超过6个碳原子的链-2-烯基，A代表Gly或Azgly，B代表Leu或Met，J代表 - （CH 2）n - ，其中n表示1至10的整数，或亚苯基，及其药学上可接受的酸加成盐。 用于制造化合物的方法。 包含化合物之一和药物稀释剂或载体的药物组合物。 化合物是选择性的δ-受体拮抗剂。

公开(公告)号：US4105651A

公开(公告)日：1978-08-08

申请号：US666647

申请日：1976-03-15

申请人： John Hughes

发明人： John Hughes

IPC分类号： A61K38/00 ,  C07K14/70 ,  C07C103/52 ,  A61K37/00

CPC分类号： C07K14/70 ,  A61K38/00 ,  Y10S514/809

摘要： The purification of an endogenous composition isolated from mammalian brain tissue and termed enkephalin ("in the head"). Enkephalin is recovered from brain tissue by acetone solution and purified by means of column and thin layer chromatography. The composition which is a mixture of two pentapeptides, namely, (a) H-Tyr-Gly-Gly-Phe-Met-OH and (b) H-Tyr-Gly-Gly-Phe-Leu-OH wherein the ratio of a:b is from 3:1 to 4:1 has been found to be a non-addictive narcotic and an opiate agonist.The synthesis of the pentapeptide composition from the known structure above is accomplished by conventional solution techniques of protection of the amino groups, such as t-butyloxycarbonyl, benzyloxycarbonyl, and t-amyloxycarbonyl, or the solid phase peptide synthesis of R. Bruce Merrifield using a polymeric support and the same or similar amine protecting groups.

公开(公告)号：US4073885A

公开(公告)日：1978-02-14

申请号：US722207

申请日：1976-09-10

申请人： Candace B. Pert ,  Agu Pert ,  John F. Tallman

发明人： Candace B. Pert ,  Agu Pert ,  John F. Tallman

IPC分类号： A61K38/00 ,  C07K14/70 ,  A61K35/14 ,  A61K37/00

CPC分类号： C07K14/70 ,  A61K38/00 ,  Y10S530/83

摘要： A method of recovering a hormone from human blood plasma which has morphine agonist properties which comprises heating said plasma, extracting into butanol to recover anodynin, and purifying said anodynin by centrifuging and ion exchange column separation. Anodynin has a molecular weight of about 600.

摘要翻译： 从具有吗啡激动剂性质的人血浆中回收激素的方法，包括加热所述血浆，提取到丁醇中以回收anodynin，并通过离心和离子交换柱分离来纯化所述异烟肼。 蒽醌的分子量约为600。