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methyl (1R,3R)-1-(3,4-methylenedioxyphenyl)-2-chloroacetyl-2,3,4,9-tetrahydro-9H-pyrido[3,4-b]indol-3-carboxylate | 171596-58-0

分子结构分类

有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱

中文名称

——

中文别名

——

英文名称

methyl (1R,3R)-1-(3,4-methylenedioxyphenyl)-2-chloroacetyl-2,3,4,9-tetrahydro-9H-pyrido[3,4-b]indol-3-carboxylate

英文别名

(1R,3R)-1,2,3,4-tetrahydro-2-chloroacetyl-1-(3,4-methylenedioxyphenyl)-9H-pyrido[3, 4-b]indole-3-carboxylic acid methyl ester；methyl (1R,3R)-1-(benzo[d][1,3]dioxol-5-yl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate；(1R,3R)-1-Benzo[1,3]dioxol-5-yl-2-(2-chloroethanoyl)2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic Acid Methyl Ester；Chloropretadalafil；methyl (1R,3R)-1-(1,3-benzodioxol-5-yl)-2-(2-chloroacetyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate

methyl (1R,3R)-1-(3,4-methylenedioxyphenyl)-2-chloroacetyl-2,3,4,9-tetrahydro-9H-pyrido[3,4-b]indol-3-carboxylate化学式

CAS

171596-58-0

化学式

C₂₂H₁₉ClN₂O₅

mdl

——

分子量

426.856

InChiKey

JUKHNCNDFOAFLT-IIBYNOLFSA-N

BEILSTEIN

——

EINECS

——

物化性质

熔点：

215-218 °C
沸点：

627.5±55.0 °C(Predicted)
密度：

1.445±0.06 g/cm3(Predicted)

计算性质

辛醇/水分配系数(LogP)：

3.5
重原子数：

30
可旋转键数：

4
环数：

5.0
sp3杂化的碳原子比例：

0.27
拓扑面积：

80.9
氢给体数：

1
氢受体数：

5

上下游信息

上游原料

中文名称	英文名称	CAS号	化学式	分子量
(1S,3R)-甲基-1,2,3,4-四氢-1-(3,4-亚甲二氧基苯基)-9H-吡啶并[3,4-b]吲哚-3-羧酸酯	(1S,3R)-1-(benzo[1,3]dioxol-5-yl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester	171596-42-2	C₂₀H₁₈N₂O₄	350.374
——	(3R)-1-(3,4-methylenedioxyphenyl)-2,3,4,9-tetrahidro-9H-pyrido[3,4-b]indole-3-carboxylic acid methyl ester	1039484-71-3	C₂₀H₁₈N₂O₄	350.374
(1R,3r)-1,2,3,4-四氢-1-(3,4-亚甲基二氧基苯基)-9h-吡啶并[3,4-b]吲哚-3-羧酸甲酯	(1R,3R)-methyl 1,2,3,4-tetrahydro-1-(3,4-methylenedioxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate	171596-41-1	C₂₀H₁₈N₂O₄	350.374
他达那非	(6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-pyrazino[2',1':6,1]pyrido[3,4-b]indole-1,4-dione	171596-29-5	C₂₂H₁₉N₃O₄	389.411

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	(1R,3R)-methyl-1,2,3,4-tetrahydro-2-(2-(benzyl(methyl)amino)acetyl)-1-(3,4-methylenedioxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate	1224724-00-8	C₃₀H₂₉N₃O₅	511.577
——	((6R,12aR)-6-benzo[1,3]dioxol-5-yl-1,4-dioxo-3,4,6,7,12,12a-hexahydro-1H-pyrazino-[1',2':1,6]pyrido[3,4-b]indol-2-yl)acetic acid methyl ester	385771-08-4	C₂₄H₂₁N₃O₆	447.447
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	629652-62-6	C₂₁H₁₇N₃O₄	375.384
——	(6R,12AR)-6-benzo[1,3]dioxol-5-yl-2-[2-(2-hydroxyethoxy)ethyl]-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	——	C₂₅H₂₅N₃O₆	463.49
——	((6R,12aR)-6-benzo[1,3]dioxol-5-yl-1,4-dioxo-3,4,6,7,12,12a-hexahydro-1H-pyrazino-[1',2':1,6]pyrido[3,4-b]indol-2-yl)acetic acid	385770-82-1	C₂₃H₁₉N₃O₆	433.42
——	((6R,12aR)-6-benzo[1,3]dioxol-5-yl-1,4-dioxo-3,4,6,7,12,12a-hexahydro-1H-pyrazino-[1',2':1,6]pyrido[3,4-b]indol-2-yl)acetic acid octyl ester;	385771-10-8	C₃₁H₃₅N₃O₆	545.635
他达那非	(6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-pyrazino[2',1':6,1]pyrido[3,4-b]indole-1,4-dione	171596-29-5	C₂₂H₁₉N₃O₄	389.411
他达拉非EP杂质	(6R,12aS)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)-pyrazino[2',1':6,1]pyrido[3,4-b]indole-1,4-dione	171596-27-3	C₂₂H₁₉N₃O₄	389.411
——	(6R,12aR)-6-Benzo[1,3]dioxol-5-yl-2-benzyl-2,3,6,7,12,12a-hexahydro-pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	691871-71-3	C₂₈H₂₃N₃O₄	465.508
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-[2-(4-hydroxyphenyl)ethyl]-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido-[3,4-b]indole-1,4-dione	1295647-19-6	C₂₉H₂₅N₃O₅	495.535
——	(6R,12aR)-6-(benzo[d][1,3]dioxol-5-yl)-2-(2-(benzyl(methyl)amino)ethyl)-2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido-[3,4-b]indole-1,4-dione	1018814-79-3	C₃₁H₃₀N₄O₄	522.604
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-[3-(benzylmethylamino)propyl]-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	1018814-81-7	C₃₂H₃₂N₄O₄	536.63
他达拉非杂质	(6R,12aR)-6-(benzo(d)[1,3]dioxol-5-yl)-2-isopropyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	171596-30-8	C₂₄H₂₃N₃O₄	417.464
N-丁基去甲他达拉非	(6R,12aR)-6-(benzo[d][1,3]dioxol-5-yl)-2-butyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	171596-31-9	C₂₅H₂₅N₃O₄	431.491
——	(6R,12aR)-2,3,6,7,12,12a-hexahydro-2-hydroxy-6-(3,4-methylendioxyphenyl)-pyrazino[2',1':6,1]pyrido[3,4-b]indole-1,4-dione	——	C₂₁H₁₇N₃O₅	391.383
氨基他达那非	(6R,12aR)-2-amino-6-(benzo[d][1,3]dioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	385769-84-6	C₂₁H₁₈N₄O₄	390.398
——	4-[6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2’:1,6]pyrido[3,4-b]indole-1,4-dion-2-yl]piperidine	——	C₂₆H₂₆N₄O₄	458.517
——	3-((6R,12aR)-6-benzo[1,3]dioxol-5-yl-1,4-dioxo-3,4,6,7,12,12a-hexahydro-1H-pyrazino-[1',2':1,6]pyrido[3,4-b]indol-2-yl)-N-cyclohexylpropionamide	385770-31-0	C₃₀H₃₂N₄O₅	528.608
——	4-((6R,12aR)-6-benzo[1,3]dioxol-5-yl-1,4-dioxo-3,4,6,7,12,12a-hexahydro-1H-pyrazino-[1',2':1,6]pyrido[3,4-b]indol-2-yl)-N-cyclohexylbutyramide	385770-34-3	C₃₁H₃₄N₄O₅	542.635
——	(6R,12aR)-6-(benzo[d][1,3]dioxol-5-yl)-2-((R)-1-benzylpyrrolidin-3-yl)-2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione	574730-01-1	C₃₂H₃₀N₄O₄	534.615
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-(R)-pyrrolidin-3-yl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	574730-02-2	C₂₅H₂₄N₄O₄	444.49
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-((R)-1-phenethylpyrrolidin-3-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	1018815-32-1	C₃₃H₃₂N₄O₄	548.641
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-((R)-1-pyridin-2-ylmethylpyrrolidin-3-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	——	C₃₁H₂₉N₅O₄	535.602
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-(4-morpholin-4-ylbenzyl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido-[3,4-b]indole-1,4-dione	1295647-20-9	C₃₂H₃₀N₄O₅	550.614
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-((R)-1-(2-phenoxyethyl)pyrrolidin-3-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	1018815-33-2	C₃₃H₃₂N₄O₅	564.641
——	2-[(R)-3-((6R,12aR)-6-benzo[1,3]dioxol-5-yl-1,4-idioxo-3,4,6,7,12,12a-hexahydro-1H-pyrazino[1',2':1,6]pyrido[3,4-b]indol-2-yl)pyrrolidin-1-yl]ethylcarbamic acid tert-butyl ester	1018814-88-4	C₃₂H₃₇N₅O₆	587.676
他达那非衍生物	(6R-12aR),6,(1,3-benzodiazepine-5-yl)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino[1'2'-1,6]-pyrido[3,4-b]indole-1,4-dione	477978-84-0	C₂₃H₂₁N₃O₄	403.437
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-((R)-1-cyclopentylmethylpyrrolidin-3-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	1356345-61-3	C₃₁H₃₄N₄O₄	526.635
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-((R)-1-cyclohexylmethylpyrrolidin-3-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	1356345-62-4	C₃₂H₃₆N₄O₄	540.662
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-((R)-1-(4-dimethylaminobenzyl)pyrrolidin-3-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	1018814-83-9	C₃₄H₃₅N₅O₄	577.683
——	N-[4-((6R,12aR)-6-benzo[1,3]dioxol-5-yl-1,4-pyrazino[1',2':1,6]pyrido[3,4-b]indol-2-yl-methyl)phenyl]-1,1,1-trifluoromethanesulfonamide	385770-68-3	C₂₉H₂₃F₃N₄O₆S	612.586
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-[1-(1-methyl-1H-imidazol-2-ylmethyl)piperidin-4-yl]-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	1018815-16-1	C₃₁H₃₂N₆O₄	552.633
——	N-[3-[[(2R,8R)-2-(1,3-benzodioxol-5-yl)-4,7-dioxo-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraen-6-yl]methyl]phenyl]-1,1,1-trifluoromethanesulfonamide	385770-93-4	C₂₉H₂₃F₃N₄O₆S	612.586
——	(6R,12aR)-6-benzo[1,3]dioxol-5-yl-2-(4-morpholin-4-ylmethylphenyl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione	1295647-21-0	C₃₂H₃₀N₄O₅	550.614
——	(6R,12AR)-6-benzo[1,3]dioxol-5-yl-2-phenyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]-pyrido[3,4-b]indole-1,4-dione	385769-88-0	C₂₇H₂₁N₃O₄	451.481
——	4-[4-[(6R,12aR)-6-benzo[1,3]dioxol-5-yl-1,4-dioxo-3,4,6,7,12,12a-hexahydro-1H-pyrazino[1',2':1,6]pyrido[3,4-b]indol-2-yl]phenyl]piperazine-1-carboxylic acid tert-butyl ester	1295647-23-2	C₃₆H₃₇N₅O₆	635.72
——	4-[3-[(6R,12aR)-6-benzo[1,3]dioxol-5-yl-1,4-dioxo-3,4,6,7,12,12a-hexahydro-1H-pyrazino[1',2':1,6]pyrido[3,4-b]indol-2-yl]benzyl]piperazine-1-carboxylic acid tert-butyl ester	1295647-22-1	C₃₇H₃₉N₅O₆	649.747
——	tadalafil	——	C₂₂H₁₇N₃O₅	403.394
——	methyl (2R)-3-[2-(1,3-benzodioxole-5-carbonyl)-1H-indol-3-yl]-2-[(2-chloroacetyl)amino]propanoate	1220393-13-4	C₂₂H₁₉ClN₂O₆	442.856

反应信息

作为反应物：

描述：

methyl (1R,3R)-1-(3,4-methylenedioxyphenyl)-2-chloroacetyl-2,3,4,9-tetrahydro-9H-pyrido[3,4-b]indol-3-carboxylate 在 selenium(IV) oxide 作用下，以四氢呋喃为溶剂，反应 1.5h，生成 methyl (2R)-3-[2-(1,3-benzodioxole-5-carbonyl)-1H-indol-3-yl]-2-[(2-chloroacetyl)amino]propanoate

参考文献：

名称：

[EN] COMPOUNDS DERIVED FROM 2-(3-METHYLENEDIOXY)-BENZOYL INDOL
[FR] COMPOSÉS DÉRIVÉS DU 2-(3-MÉTHYLÈNEDIOXY)-BENZOYL-INDOLE

摘要：

本发明描述了2-(3-甲烯基二氧苯基)-苯甲酰吲哚的一系列衍生物，它们的混合物，它们的药学上可接受的盐，它们的对映体，包括它们的制药组合物，以及用于预防和/或治疗性功能障碍的用途。更具体地，本发明描述了(R)-3-((2-(苯并[d][1,3]二氧杂环[5.5.1.0^2,6]十二烷-5-羰基)-1H-吲哚-3-基)甲基)-1-甲基哌嗪-2,5-二酮和(S)-3-((2-(苯并[d][1,3]二氧杂环[5.5.1.0^2,6]十二烷-5-羰基)-1H-吲哚-3-基)甲基)-1-甲基哌嗪-2,5-二酮的衍生物。

公开号：

WO2010037190A1
作为产物：

描述：

胡椒醇在 manganese(IV) oxide 、三乙胺作用下，以二氯甲烷、异丙醇为溶剂，反应 3.0h，生成 methyl (1R,3R)-1-(3,4-methylenedioxyphenyl)-2-chloroacetyl-2,3,4,9-tetrahydro-9H-pyrido[3,4-b]indol-3-carboxylate

参考文献：

名称：

体内用于治疗阿尔茨海默氏病的化学探针的发现：磷酸二酯酶5（PDE5）和I类组蛋白去乙酰化酶选择性抑制剂

摘要：

为了确定组蛋白脱乙酰基酶（HDAC）同工型对双磷酸二酯酶5（PDE5）和pan-HDAC抑制剂对阿尔茨海默氏病（AD）体内模型的有益作用，我们设计，合成和测试了新的化学试剂具有所需PDE5和I类HDAC选择性抑制剂目标化合物特征的探针。与以前的基于异羟肟酸酯的系列产品相比，这些分子在HDAC上的停留时间更长。在这种情况下，较短或较长的预孵育时间可能会对IC 50产生重大影响这些化合物的值，因此在不同的HDAC亚型上具有相应的选择性。另一方面，已经探索了不同的化学系列，并且如预期的那样，一些成对的比较显示了支架对生物学反应的明显影响（例如35a对40a）。铅的鉴定过程导致了化合物29a的出现，该化合物在中枢神经系统（CNS）中显示出足够的ADME-Tox谱图和体内靶标结合（组蛋白乙酰化和cAMP / cGMP反应元件结合（CREB）磷酸化）。该化合物代表一种优化的化学探针；因此，已经在AD的

DOI：

10.1021/acschemneuro.8b00648

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文献信息

[EN] NOVEL DUAL MODE OF ACTION SOLUBLE GUANYLATE CYCLASE ACTIVATORS AND PHOSPHODIESTERASE INHIBITORS AND USES THEREOF [FR] NOUVEAUX ACTIVATEURS DE LA GUANYLATE CYCLASE SOLUBLE À DOUBLE MODE D'ACTION ET INHIBITEURS DE PHOSPHODIESTÉRASE ET LEURS UTILISATIONS

申请人：TOPADUR PHARMA AG

公开号：WO2021245192A1

公开（公告）日：2021-12-09

The present invention relates to compounds of formula (I), or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein said compound of formula (I) comprises at least one covalently bound -ONO2 or -ONO moiety and at most four covalently bound -ONO2 or -ONO moieties, and wherein AR, R1, X, R3 and R4 are as defined in claim 1; and pharmaceutical compositions thereof, and their use in methods of treating or preventing a disease alleviated by inhibition of PDE5 in a human or in a non-human mammal.

本发明涉及式(I)的化合物，或其药学上可接受的盐、溶剂或水合物，其中所述式(I)的化合物至少包括一个共价结合的-ONO2或-ONO基团，最多包括四个共价结合的-ONO2或-ONO基团，其中AR、R1、X、R3和R4如权利要求1所定义；以及其药物组合物，以及它们在治疗或预防通过抑制人类或非人类哺乳动物中的PDE5而缓解的疾病的方法中的使用。
Chemical compounds

申请人：——

公开号：US20030225094A1

公开（公告）日：2003-12-04

Compounds of the general structural formula (I) and use of the compounds and salts and solvates thereof, as therapeutic agents. 1

通用结构式（I）的化合物及其盐和溶剂合物的用途，作为治疗剂。
[EN] NEW AGENTS FOR THE TREATMENT OF THE LOW URINARY TRACT DYSFUNCTIONS [FR] NOUVEAUX AGENTS POUR LE TRAITEMENT DE DYSFONCTIONNEMENTS DU TRACTUS URINAIRE INFÉRIEUR.

申请人：CTG PHARMA S R L

公开号：WO2009037556A1

公开（公告）日：2009-03-26

The present invention relates to novel compounds that are derivatives of 5 -phosphodiesterase inhibitors that comprise in their formula a polysulfurated group and that are useful for treating dysfunctions of low urinary tract such as incontinence, benign prostatic hyperplasia and erectile dysfunction.

本发明涉及一种新型化合物，它们是5-磷酸二酯酶抑制剂的衍生物，在其化学式中包含一个多硫化基团，可用于治疗低尿路功能障碍，如尿失禁、良性前列腺增生和勃起功能障碍。
Asymmetric N-Hydroxyalkylation of Indoles with Ethyl Glyoxalates Catalyzed by a Chiral Phosphoric Acid: Highly Enantioselective Synthesis of Chiral N,O-Aminal Indole Derivatives

作者：Le Wang、Jia Zhou、Tong-Mei Ding、Zhi-Qiang Yan、Si-Hua Hou、Guo-Dong Zhu、Shu-Yu Zhang

DOI：10.1021/acs.orglett.9b00757

日期：2019.4.19

A method of SPINOL-derived chiral phosphoric acid catalyzed asymmetric intermolecular N-hydroxyalkylation of multisubstituted indoles with ethyl glyoxalates is described in this report. This protocol provides an alternative, convenient, and direct strategy for efficient access to structurally unique α-chiral indole N,O-acyclic aminals with a broad substrate scope and good to excellent enantioselectivities

在该报告中描述了SPINOL衍生的手性磷酸催化的多取代的吲哚的不对称分子间N-羟基烷基化的方法。该方案为有效地获得结构上独特的α-手性吲哚N，O-无环缩醛提供了一种替代，便捷和直接的策略，该结构具有广泛的底物范围，并且具有良好的至优异的对映选择性。该方法的合成效用通过克规模的实验以及随后更有效地合成更复杂的手性N，O-氨基吲哚衍生物进行了说明。
Design, Synthesis, and Biological Evaluation of Orally Available First-Generation Dual-Target Selective Inhibitors of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) for the Treatment of Alzheimer’s Disease

作者：Fei Mao、Huan Wang、Wei Ni、Xinyu Zheng、Manjiong Wang、Keting Bao、Dazheng Ling、Xiaokang Li、Yixiang Xu、Haiyan Zhang、Jian Li

DOI：10.1021/acschemneuro.7b00345

日期：2018.2.21

drug discovery strategies of repurposing and redeveloping existing drugs, a series of novel tadalafil derivatives were rationally designed, synthesized, and evaluated to seek dual-target AChE/PDE5 inhibitors as good candidate drugs for Alzheimer’s disease (AD). Among these derivatives, 1p and 1w exhibited excellent selective dual-target AChE/PDE5 inhibitory activities and improved blood-brain barrier

通过重新利用和重新开发现有药物的药物发现策略，合理地设计，合成和评估了一系列新型他达拉非衍生物，以寻找双靶点AChE / PDE5抑制剂作为阿尔茨海默氏病（AD）的良好候选药物。在这些衍生物中，1p和1w表现出优异的选择性双靶AChE / PDE5抑制活性和改善的血脑屏障（BBB）渗透性。重要的是1w·Cit（柠檬酸盐为1w）可以逆转东pol碱诱导的AD小鼠的认知功能障碍，并在增强体内cAMP反应元件结合蛋白（CREB）磷酸化方面表现出优异的作用，这是记忆形成和突触可塑性的关键因素。此外，与hAChE和hPDE5A的1w分子对接模拟证实了我们的设计策略是合理的。总而言之，我们的研究提供了一种潜在的选择性双靶AChE / PDE5抑制剂，作为治疗AD的良好候选药物，它也可以被视为小分子探针，以验证体内新颖的AD治疗方法。