BIOLOGICALLY-ACTIVE POLYCYCLOALKANES .1. ANTIVIRAL ADAMANTANE DERIVATIVES
BIOLOGICALLY-ACTIVE POLYCYCLOALKANES .1. ANTIVIRAL ADAMANTANE DERIVATIVES
复制标题
DOI：
10.1021/jm00241a015
复制
发表时间：
1975-01-01
影响因子：
7.3
通讯作者：
HATTORI, K
中科院分区：
文献类型：
--
作者：
AIGAMI, K;INAMOTO, Y;HATTORI, K
本文叙述了1-取代3-金刚烷基氯化物和溴化物（2）、1-金刚烷基苯酚和甲酚（3）、1-金刚烷基乙酸（6）和1，3-金刚烷二乙酸（11）的简便合成方法。从这些关键中间体合成了几种新型衍生物：金刚烷基环己醇（4）和由金刚烷基酚（3）得到的金刚烷基环己酮（5），以及酯（7、12和22），酰胺（13和18），硫代酰胺（9和16）、脒（10）、镍腈（15）和胺（14和17），它们来自1-金刚烷羧酸（19）和-乙酸（6）和1，3-金刚烷二乙酸（11）。还制备了一些金刚烷基嘧啶（24）和-嘌呤（25和26）。用鸡胚成纤维细胞单层培养法测定了本工作合成的化合物和以前合成的一系列新的1-金刚烷基烷基酮以及一些已知的金刚烷衍生物的体外抗纽卡斯尔病病毒活性。[1]然而，迄今为止，除某些氨基金刚烷外，许多化合物似乎仅限于那些具有已知生物活性官能团的衍生物，因此，应将其视为相应药物的金刚烷类似物。我们已经制备了各种新的金刚烷衍生物，如卤化物、醇、酮、羧酸、酯、酰胺、腈等，并发现它们中的许多具有抗病毒活性。值得注意的是，在这项工作中合成的一些化合物比金刚烷胺（1-氨基金刚烷）更有活性; 2尽管它们中的大多数没有具有既定生物活性的特定官能团。
Convenient methods for the synthesis of 1-substituted 3-adamantyl chlorides and bromides (2), 1-adamantylphenols and-cresols (3), and 1-adamantylacetic (6) as well as 1, 3-adamantanediacetic (11) acids are described. Several novel derivatives were synthesized from these key intermediates: adamantylcyclohexanols (4) and-cyclohexanones (5) from adamantylphenols (3), and esters (7, 12, and 22), amides (13 and 18), thioamides (9 and 16), amidine (10), ni-trile (15), and amines (14 and 17) from 1-adamantanecarboxylic (19) and-acetic (6) acids and 1, 3-adamantanediacetic acid (11). Some adamantylpyrimidines (24) and-purines (25 and 26) were also prepared. Antiviral activities of the compounds obtained in this work and a series of new 1-adamantyl alkyl ketones synthesized before, together with those of some known adamantane derivatives, were tested in vitro on monolayer culture of chick embryo fibroblasts against Newcastle disease virus.A number of examples have been documented of the use of adamantane compounds as medicines and drugs. 1 How-ever, it seems that many of the compounds tested so far, except for some aminoadamantanes, have been limited to those derivatives which have functional groups of wellknown biological activities, and which, therefore, should be regarded as adamantyl analogs of the corresponding drugs. We have prepared various new derivatives of adamantane such as halides, alcohols, ketones, carboxylic acids, esters, amides, nitriles, etc., and have found many of them active as antiviral agents. It is interesting to note that some of the compounds synthesized in this work are more active than amantadine (1-aminoadamantane); 2 although most of them have no particular functional group with established biological activity.