阿拉丙酯

阿拉丙酯
臨床資料
給藥途徑	口服
ATC碼	N06AB07 (WHO) ;
法律規範狀態
法律規範	Uncontrolled;
識別資訊
	IUPAC命名法 1-(4-Chlorophenyl)-2-methylpropan-2-yl 2-aminopropanoate; ;
CAS號	60719-82-6 ; 60719-83-7（鹽酸鹽）
PubChem CID	2081;
ChemSpider	1997 ;
UNII	C4R42570ZO;
KEGG	D02787 ;
ChEMBL	ChEMBL36591 ;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID5045122 ;
化學資訊
化學式	C13H18ClNO2
摩爾質量	255.74 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
	SMILES Clc1ccc(cc1)CC(OC(=O)C(N)C)(C)C;
	InChI InChI=1S/C13H18ClNO2/c1-9(15)12(16)17-13(2,3)8-10-4-6-11(14)7-5-10/h4-7,9H,8,15H2,1-3H3 ; Key:FZSPJBYOKQPKCD-UHFFFAOYSA-N ;

阿拉丙酯（英語：Alaproclate；開發代號：GEA-654）是瑞典製藥公司Astra AB（英語：Astra AB）（現為阿斯利康）在1970年代開發的一種抗抑鬱藥物。它作為一種選擇性血清素再攝取抑制劑（SSRI），與齊美利定和吲達品一起，是同類藥物中最早的一種。由於在齧齒動物研究中觀察到肝臟併發症（英語：Hepatotoxicity），開發被終止開發。除了其SSRI特性外，阿拉丙酯還被發現可作為非競爭性NMDA受體拮抗劑，但不具有類似於苯環己哌啶的區分刺激特性。^[1]^[2]

合成

製備方法：^[3]

合成：^[4]專利：^[5]放射性標記：^[6]^[7]

4-氯苯乙酸甲酯（維基數據所列：Q72489367） (1) 與甲基碘化鎂之間的格氏反應可得到1-(4-氯苯基)-2-甲基-2-丙醇（維基數據所列：Q72457211） (2)。(2)與2-溴丙酰溴（維基數據所列：Q72511577） (3)酰化得到[1-(4-氯苯基)-2-甲基丙-2-基]2-溴丙酸酯 (3)，CID:13695101 （頁面存檔備份，存於互聯網檔案館）。用氨取代鹵素得到丙丙酸 (4)。

參見

參考資料

^ Wilkinson A, Courtney M, Westlind-Danielsson A, Hallnemo G, Akerman KE. Alaproclate acts as a potent, reversible and noncompetitive antagonist of the NMDA receptor coupled ion flow . The Journal of Pharmacology and Experimental Therapeutics. December 1994, 271 (3): 1314–9. PMID 7996440.
^ Nicholson KL, Balster RL. Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats. Psychopharmacology. November 2003, 170 (2): 215–24. PMID 12851738. S2CID 30803162. doi:10.1007/s00213-003-1527-6.
^ Ulf H. A. Lindberg, Sven-Ove gren, 美國專利第4,469,707號 (1984 to Astra Lakemedel Aktiebolag).
^ Lindberg, Ulf Henrik; Thorberg, Seth Olof; Bengtsson, Stefan; Renyi, Anna L.; Ross, Svante B.; Ogren, Sven Ove. Inhibitors of neuronal monoamine uptake. 2. Selective inhibition of 5-hydroxytryptamine uptake by .alpha.-amino acid esters of phenethyl alcohols. Journal of Medicinal Chemistry (American Chemical Society (ACS)). 1978, 21 (5): 448–456. ISSN 0022-2623. doi:10.1021/jm00203a008.
^ Ulf M. A. Lindberg, Svante B. Ross, Seth-Olov Thorberg, Sven O. / gren, 美國專利第4,237,311號 & 美國專利第4,331,684號 (1980 & 1982 both to Astra Lakemedel Aktiebolag).
^ Gawell, Lars. Synthesis of [¹⁴C]alaproclate. Journal of Labelled Compounds and Radiopharmaceuticals (Wiley). 1986, 23 (9): 947–949. ISSN 0362-4803. doi:10.1002/jlcr.2580230905.
^ Bengtsson, Stefan; Gawell, Lars; Högberg, Thomas; Sahlberg, Christer. Synthesis and ³H NMR of ³H‐alaproclate of high specific activity. Journal of Labelled Compounds and Radiopharmaceuticals (Wiley). 1985, 22 (5): 427–435. ISSN 0362-4803. doi:10.1002/jlcr.2580220503.

[1] Wilkinson A, Courtney M, Westlind-Danielsson A, Hallnemo G, Akerman KE. Alaproclate acts as a potent, reversible and noncompetitive antagonist of the NMDA receptor coupled ion flow . The Journal of Pharmacology and Experimental Therapeutics. December 1994, 271 (3): 1314–9. PMID 7996440.

[2] Nicholson KL, Balster RL. Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats. Psychopharmacology. November 2003, 170 (2): 215–24. PMID 12851738. S2CID 30803162. doi:10.1007/s00213-003-1527-6.

[3] Ulf H. A. Lindberg, Sven-Ove gren, 美國專利第4,469,707號 (1984 to Astra Lakemedel Aktiebolag).

[4] Lindberg, Ulf Henrik; Thorberg, Seth Olof; Bengtsson, Stefan; Renyi, Anna L.; Ross, Svante B.; Ogren, Sven Ove. Inhibitors of neuronal monoamine uptake. 2. Selective inhibition of 5-hydroxytryptamine uptake by .alpha.-amino acid esters of phenethyl alcohols. Journal of Medicinal Chemistry (American Chemical Society (ACS)). 1978, 21 (5): 448–456. ISSN 0022-2623. doi:10.1021/jm00203a008.

[5] Ulf M. A. Lindberg, Svante B. Ross, Seth-Olov Thorberg, Sven O. / gren, 美國專利第4,237,311號 & 美國專利第4,331,684號 (1980 & 1982 both to Astra Lakemedel Aktiebolag).

[6] Gawell, Lars. Synthesis of [¹⁴C]alaproclate. Journal of Labelled Compounds and Radiopharmaceuticals (Wiley). 1986, 23 (9): 947–949. ISSN 0362-4803. doi:10.1002/jlcr.2580230905.

[7] Bengtsson, Stefan; Gawell, Lars; Högberg, Thomas; Sahlberg, Christer. Synthesis and ³H NMR of ³H‐alaproclate of high specific activity. Journal of Labelled Compounds and Radiopharmaceuticals (Wiley). 1985, 22 (5): 427–435. ISSN 0362-4803. doi:10.1002/jlcr.2580220503.

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