Evaluation of anticonvulsant activities of bis(3-aryl-3-oxo-propyl) ethylamine hydrochlorides and 4-aryl-3-arylcarbonyl-1-ethyl-4-piperidinol hydrochlorides

Bis-Mannich bases, bis(3-aryl-3-oxopropyl)ethylamine hydrochlorides 1-4, and their corresponding structural and non-classical isomers, 4-aryl-3-arylcarbonyl-1-ethyl-4-piperidinol hydrochlorides 5-8, were synthesized. The aryl part was phenyl in 1 and 5, p-methylphenyl in 2 and 6, p-chlorophenyl in 3 and 7, and 2-thienyl in 4 and 8. The chemical stuructures of the compounds were confirmed by 1H-NMR, 13C-NMR, UV, IR and elemental analyses. Anticonvulsant activities of the compounds were evaluated by the maximum electroshock (MES) and subcutaneous pentylenetetrazole (scMet) tests in the dose range of 30-300 mg/kg. Alterations in biological activity depending on modifications in chemical structure were also followed. Compounds 1-4, 6, and 8 were toxic and caused death of the animals 20 min after the injection. Compounds 2, 3 and 6 were also neurotoxic at the 100 mg/kg dose level.While only compound 7 was active in the scMet test at 300 mg/kg within 4 h, all the compounds showed activity in the MES test at different dose levels and time periods. In conclusion, compounds 5 and 7, which were not toxic and did not show neurotoxicity, seemed to be candidate compounds to develop new anticonvulsant compounds useful in the treatment of the grand mal (compounds 5, 7) and petit mal (compound 7) epilepsies.     

Chromone glycosides from Knoxia corymbosa

Four new chromone glycosides, corymbosins K1-K4 (3-6), together with two known compounds, noreugenin (1) and undulatoside A (2), were isolated from the whole plant of Knoxiacorymbosa (Rubiaceae). The structures of the new compounds were established through extensive NMR or X-ray spectroscopic analysis as 7-O-beta-D-allopyranosyl-5-hydroxy-2-methylchromone (corymbosin K1, 3), 7-O-beta-D-6-acetylglucopyranosyl-5-hydroxy-2-methylchromone (corymbosin K2, 4), 7-O-[6-O-(4-O-trans-caffeoyl-beta-D-allopyranosyl)]-beta-D-glucopyranosyl-5-hydroxy-2-methylchromone (corymbosin K3, 5) and 7-O-[6-O-(4-O-trans-feruloyl-beta-D-allopyranosyl)]-beta-D-glucopyranosyl-5-hydroxy-2- methylchromone (corymbosin K4, 6). Compounds 2-5 were subjected to test their immunomodulatory activity invitro.     

New inhibitors of aromatase: synthesis and biological activity of pyridyl-substituted phenanthrenone derivatives]

The phenanthrenone derivatives 3-6 were synthesized and tested for their aromatase and desmolase inhibitory potency. Compounds 5 and 6 show a stronger inhibition of aromatase than aminoglutethimide not exceeding, however, the activity of the parent compounds 1 and 2. Compounds 4 and 5 do not inhibit desmolase.     

Analogues of poison ivy urushiol. Synthesis and biological activity of disubstituted n-alkylbenzenes

The total synthesis of different isomers and analogues of poison ivy urushiol is described. These include the positional isomers 1-5 and the nitrogen-containing analogues 6 and 8 and their mesylamino derivatives 7 and 9. 3,4-Dimethoxybenzaldehyde, m-dimethoxybenzene, resorcinol, and p-dimethoxybenzene were used as starting materials for compounds 1, 2, 3, and 4, respectively. Compound 5 is prepared by catalytic hydrogenation of bilobol isolated from Ginkgo biloba. Compounds 6 and 7 were prepared from anacardic acid as the starting material while compounds 8 and 9 were prepared from phenol as the starting material. Compounds 1-9 were tested for their ability to cross-react with poison ivy urushiol in sensitized guinea pigs. Compounds 6 and 8 were reactive at the 10-microgram dose level when applied topically, while compound 1 was a skin irritant at that dose. On the other hand, compounds 2-5, 7, and 9 showed no cross-reactivity up to the 30-micrograms dose level. Structural requirements for cross allergenicity are discussed.     

Synthesis, antimicrobial, and alkylating properties of 3-phosphonic derivatives of chromone

Dimethyl 2,6-dimethyl-4-oxo-4H-chromen-3-yl-phosphonate (1a) and dimethyl 6-methyl-2-phenyl-4-oxo-4H-chromen-3-yl-phosphonate (1b) were synthesized and reacted with primary aliphatic amines to yield title compounds 4-6. Their antibacterial properties against Gram-positive and Gram-negative bacteria strains were tested by the MIC method. Four of seventeen tested compounds (1d, 3, 4a, and 4b) exhibit detectable activity against S. aureus. Some representative examples of newly synthesized compounds were tested for their alkylating properties in vitro in the Preussmann test. Compounds 1a, 1c, 1d, 3, 5d, and 6a possess highly alkylating activity toward standard derivative 4-(4'-nitrobenzyl)pyridine (NBP).     

亮菌子实体化学成分研究

目的:研究云南丽江地区产亮菌子实体中化学成分,寻找具有药用价值的活性化合物。方法:利用色谱技术对亮菌干燥子实体的甲醇提取物进行化学成分的分离。结果:共分离得到6个化合物,经鉴定分别为油酸甲酯(1)、硬脂酸(2)、3β-羟基-麦角甾-5,7,22-三烯(3)、亮菌乙素(4)、5-羟基尿嘧啶(5)和脑苷酯B(6)。结论:化合物1、2、3、5、6均为首次从亮菌子实体中分离鉴定。     

滨蒿的化学成分

目的进一步研究菊科植物滨蒿(Artemisia scoparia)中的化学成分。方法采用硅胶柱色谱法、中低压柱色谱法、ODS柱色谱法、Sephadex LH 20柱色谱法以及高效液色谱法进行分离和纯化,并依据理化性质和波谱解析鉴定其化学结构。结果从植物滨蒿地上部分的体积分数为60%乙醇提取物(420 g)中分得6个化合物,分别鉴定为3羟基二十二酸2(5乙酰基2,3二氢苯并呋喃2基)丙酯(1)、2′(3′甲氧基3甲基丁烯基)对甲氧基乙酰苯(2)、5,8二甲氧基6,7亚甲二氧基香豆素(3)、8甲氧基6,7亚甲二氧基香豆素(4)、6去甲氧基茵陈色原酮(5)、2,4二羟基6甲氧基乙酰苯(6)。结论化合物1~6均为首次从该植物中得到,其中化合物1、2为新化合物。     

Ring-substituted 1,2-dialkylated 1,2-bis(hydroxyphenyl)ethanes. 3. Synthesis, estrogen receptor binding affinity, and evaluation of antiestrogenic and mammary tumor inhibiting activity of 2,2'-disubstituted butestrols and 6,6'-disubstituted metabutestrols

The synthesis of symmetrically 2,2'-disubstituted butestrols [meso-2,3-bis(4-hydroxyphenyl)butanes] and of 6,6'-disubstituted metabutestrols [meso-2,3-bis(3-hydroxyphenyl)butanes] are described [2,2'-substituents: H (1), OH (2), F (3), Cl (4), Br (5), CH3 (6), and C2H5 (7); 6,6'-substituents: H (8), OH (9), Cl (10), and CH3 (11)]. Compounds 1-11 were obtained by reductive coupling of the corresponding 1-phenylethanols with TiCl3/LiAlH4 and separation of the meso diastereomers. The binding affinity of the test compounds to the calf uterine estrogen receptor was measured relative to that of [3H]estradiol by a competitive binding assay. With the exception of 9, all other compounds showed remarkably high relative binding affinity (RBA) values between 1.0 and 29% that of estradiol. Compounds 3 and 6 (RBA values: 15 and 29), as well as 10 and 11 (1.7 and 5.2), exceeded those of the corresponding unsubstituted compounds 1 and 8 (12 and 1.0). The compounds exhibited strong (3, 4, 6, and 7), moderate (1, 2, and 10), weak (11), or no (8) estrogenic activity in the uterine weight test of the immature mouse. Compounds 1, 2, 8, 10, and 11 showed antiestrogenic activity inhibiting the estrone-stimulated uterine growth (25-35% inhibition). Compound 11 led to a significant inhibition of the tumor growth when tested on the 9,10-dimethyl-1,2-benzanthracene induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat.     

Synthesis and anticonvulsant activity of some new dioxolane derivatives

In this study, ten 2-acetylnaphthalene derivatives with a dioxolane structure were synthesized and screened for their anticonvulsant activities. Dioxolane derivatives were prepared by the reaction with appropriate ethanone, glycol and p-toluensulphonic acid. The structures of the compounds were elucidated by IR, 1H-NMR and elemental analysis. Anticonvulsant activities of the compounds were determined by maximal electroshock seizure (MES) test and subcutaneous metrazol (ScMet.) test. The rotarod toxicity test was used for the assessment of neurological deficits. According to the activity studies compound 6 was found neurotoxic, compounds, 1, 4, 5, 7-9 were found protective against MES and 7-10 were found protective against ScMet. Compounds 2 and 3 were found inactive.     

板栗种仁化学成分的分离与鉴定

目的对板栗种仁的药用保健部位进行化学成分的分离与鉴定,为开发利用板栗种仁提供依据。方法板栗药用保健部位的正丁醇提取部位,经多次硅胶柱色谱和薄层色谱分离、理化常数测定、波谱分析、标准品比较等方法鉴定化合物的结构。结果分离得到6个化合物,分别为软脂酸-1-甘油单酯(hexadecanoic acid 2,3-dihydroxypropyl ester,1)、麦芽糖(maltose,2)、D-葡萄糖(D-glucose,3)、D-果糖(D-fructose,4)、5-羟甲基糠醛(5-hydroxymethylfurfural,5)、山柰酚(kaempferol,6)。结论化合物1、5为属内首次分离得到,化合物2、3、4、6为该种内首次分离得到。     

益母草化学成分的分离与鉴定

目的分离、鉴定益母草(Leonurus heterophyllusSweet.)提取物中的化学成分。方法采用硅胶柱色谱法、SephadexLH-20柱色谱法等分离,并通过1H-NMR、13C-NMR等谱学技术确定其结构。结果分离得到7个化合物,分别鉴定为薰衣草叶苷(lavandulifolioside,1)、芦丁(rutin,2)、苯甲酸(benzoic acid,3)、邻羟基苯甲酸(salicylic acid,4)、丁香酸(syringic acid,5)、腺苷(adenosine,6)、豆甾醇(stigmasterol,7)。结论其中化合物3、4、6为首次从益母草属中分离得到,1、2、5为首次从本种植物中分离得到。     

当归化学成分研究当归化学成分研究

目的研究当归的化学成分。方法应用色谱技术进行纯化和分离，用UV，IR，NMR和MS等光谱方法鉴定化合物。结果从当归中分得5个化合物，分别鉴定为：Homosenkyunolide H(1),Homosenkyunolide I(2),新藁苯内酯(3),6-甲氧基香豆素(4)，次黄苷(5)。结论Homosenkyunolide H(1)和Homosenkyunolide I(2)为新化合物;新藁苯内酯(3),6-甲氧基香豆素(4)和次黄苷(5)是首次从该植物中得到。     

一类新的羟基苯二磺酰苯胺类化合物的合成及其杀虫活性

目的合成并筛选出杀虫活性较好的新型抗肝片吸虫病化合物。方法分别以邻(间、对)氯苯酚为原料，通过磺酰化和亲核取代反应合成了14种羟基苯二磺酰苯胺类化合物;通过元素分析、红外光谱及核磁共振氢谱对合成的14种新型抗肝片吸虫病化合物羟基苯二磺酰苯胺类化合物(1～14)的结构进行了表征,并测定其对线粒体呼吸控制率的影响以及线粒体呼吸过程无机磷的变化,以此对化合物的解偶联活性(杀虫活性)进行了评价。结果所合成的大部分羟基苯二磺酰苯胺类化合物均具有较好的解偶联活性,其中3,5,6,9的杀虫活性最好。结论 化合物3,5,6,9均有望成为较好的新型抗肝片吸虫病药物。     

Potential antiestrogens. Synthesis and evaluation of mammary tumor inhibiting activity of 1,2-dialkyl-1,2-bis(3'-hydroxyphenyl)ethanes

The syntheses of the meso-1,2-dialkyl-1,2-bis(3'-hydroxyphenyl)ethanes [alkyl substituent: CH3 (19), C2H5 (20), C3H7 (22), C4H9 (23), i-C4H9 (24), and C5H11 (25)] and of d,l-3,4-bis(3'-hydroxyphenyl)hexane (21) are described. In vitro these compounds inhibited the [3H]estradiol receptor interaction competitively, exhibiting Ka values between 0.20 x 10(9) (20) and 0.11 x 10(6) M-1 (24). In vivo the meso compounds reduced the estrone-stimulated mouse uterine growth; the most effective compounds were 20, 22, and 23 (53, 50, and 45% inhibition, respectively). Compounds 20 and 22-24 showed weak estrogenic activity in the mouse uterine weight test and in the vaginal cornification test. Compounds 19 (NSC-297169), 20 (NSC-297170), and 22 (NSC-297171) exhibited a dose-dependent growth inhibition on the MCF-7 human breast tumor cell line (10(-6) to 10(-9) M). These compounds also showed a marked dose-dependent inhibition on the DMBA-induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat corresponding to their association constants.     

Intestinal permeability of the constituents from the roots of Saposhnikovia divaricata in the human Caco-2 cell monolayer model

The bidirectional intestinal permeability of the active constituents from the roots of Saposhnikovia divaricata, including four coumarins, anomalin (1), 5-methoxy-7-(3,3-dimethylallyloxy)coumarin (2), decursin (3), and decursinol angelate (4), as well as four chromones, cimifugin (5), prim-O-glucosylcimifugin (6), 3'- O-angeloylhamaudol (7), and sec-O-glucosylhamaudol (8), was studied by using the Caco-2 cell monolayer. These compounds were assayed by HPLC, and their transport parameters, including apparent permeability coefficients (P(app)), were then calculated. The bidirectional P(app) values of the compounds were compared with those of the markers, propranolol and atenolol. Compounds 1-5 and 7 were assigned to well-absorbed compounds, while 6 and 8 were assigned to moderately absorbed compounds. The transport of 1-7 increased linearly as a function of time up to 180?min and concentration within the test range of 10-200?μM, thus their passive diffusion mechanism was proposed. The results provided some useful information for predicting the intestinal absorption in vivo of these compounds.     

Ring-substituted 1,2-dialkylated 1,2-bis(hydroxyphenyl)ethanes. 1. Synthesis and estrogen receptor binding affinity of 2,2'- and 3,3'-disubstituted hexestrols

The syntheses of symmetrically 3,3'- and 2,2'-disubstituted meso hexestrol derivatives are described [3,3'-substituents: OH (1), F (2), Cl (3), Br (4), I (5), CH2N(CH3)2 (6), CH3 (7), CH2OCH3 (8), CH2OC2H5 (9), CH2OH (10), NO2 (11), NH2 (12), N(CH3)2 (13), COCH3 (14), and C2H5 (15); 2,2'-substituents: OH (16), F (17), Cl (18), Br (19), CH3 (20), and C2H5 (21)]. The synthesis of 1-3 was accomplished by reductive coupling of the propiophenones with TiCl4/Zn and subsequent hydrogenation of the cis-3,4-diphenylhex-3-enes. Compounds 4-15 were obtained by substitution of hexestrol, while compounds 16-21 were synthesized by coupling the 1-phenyl-1-propanols with TiCl3/LiAlH4 and separation of the meso diastereomers. The binding affinity of these compounds to the calf uterine estrogen receptor was measured relative to that of [3H]estradiol by a competitive binding assay. All test compounds showed relative binding affinity (RBA) values between 32 and less than 0.01% that of estradiol. Only meso-3,4-bis(2,4-dihydroxyphenyl)hexane (16) showed an estrogen receptor binding affinity comparable to that of hexestrol (32 and 27%, respectively). Compounds exhibiting RBA values of greater than 5% were evaluated in the mouse uterine weight test. All of them showed uterotrophic activity. Compounds 2, 7, 16, 17, and 20 were strongly active in very small doses (1 microgram per animal per day), while 1 and 12 produced full uterotrophic effects only in high doses and inhibited the estrone-stimulated uterine growth strongly in small doses (59 and 78% inhibition, respectively).     

Anticonvulsant and sedative-hypnotic activities of N-substituted isatin semicarbazones

A series of N-methyl/acetyl, 5-(un)-substituted isatin-3-semicarbazones were screened for anticonvulsant and sedative-hypnotic activities. The results revealed that protection was obtained in all the screens i.e., MES, scPTZ, and scSTY. Compounds 2, 4, 6, 10 but not 1 and 3 showed low neurotoxicity when compared to clinically used drugs. Compounds 5, 7, 8 and 9 were completely non-toxic. Compound 6 showed good activity in the rat oral MES screen. Among all the compounds, 3 and 6 emerged as the most active compounds as indicated by the protection they exhibit in MES, scSTY, and scPTZ screens. All the compounds showed significant sedativehypnotic activity.     

薄荷乙酸乙酯提取部位的化学成分

从薄荷乙酸乙酯提取部位分离鉴定了8个化合物,分别为委陵菜酸（tormenticacid,1）,野椿酸（eusc叩hicacid,2）,乌,$-@（ursolicacid,3）,齐墩果酸（oleanolicacid,4）,尿嘧啶（uracil,5）,琥珀酸（succinicacid,6）,（9E）-8,11,12-trihydroxyoctadecenoicacidmethylester（7）,neoechinulinA（8）。化合物1,2,5,6为首次从该植物中分到;7和8为在唇形科中首次分到。     

灯心草酚性成分的分离与结构鉴定

为研究灯心草科灯心草属植物灯心草(Juncus effusus L.)干燥茎髓中的酚性成分，运用正相和反相硅胶柱色谱法对灯心草乙酸乙酯部位进行分离纯化，并用波谱技术鉴定化合物结构。共分离得到6个酚性成分，其结构分别鉴定为7-羧基-2-羟基-1-甲基-5-乙烯基-9,10-二氢菲(1)，2,3-异丙叉-1-O-阿魏酰甘油酯(2)，(2S)-2,3-异丙叉-1-O-对羟基桂皮酰甘油酯(3)，dehydroeffusal(4)，对羟基苯甲醛(5)和毛地黄黄酮-5,3′-二甲酯(6)。其中化合物1和2为新化合物，化合物5和6为首次从该属植物中分得，本文首次报道了化合物6的¹³C NMR数据。     

黄独的化学成分

目的研究中药黄独(Dioscorea bulbifera L.)乙醇提取物的乙酸乙酯萃取部分的化学成分。方法采用硅胶、Sephadex LH-20柱色谱等方法进行分离,利用理化性质和1H-NMR13C-NMR等谱学技术,对分离得到的化合物进行结构鉴定。结果从中分离得到6个化合物,其结构鉴定为(+)儿茶素(catechin,1)、3,5-二甲氧基山柰酚(3,5-dimethoxykaempferol,2)、山核桃素(caryatin,3)、山柰酚(kaempferol,4)、山柰酚-3-O-β-D-吡喃半乳糖苷(kaempferol-3-O-β-D-galactopyranoside,5)、山柰酚-3-O-β-D-吡喃葡萄糖苷(kaempferol-3-O-β-D-glucopyranoside,6)。结论化合物4、6为首次从薯蓣属植物中分离得到的已知化合物。