A-86929

A-86929
	IUPAC名 9,10-Dihydroxy-2-propyl-4,5,5a(R),6,7,11b(S)-hexahydrobenzo[f]thieno[2,3-c]quinoline
識別情報
CAS登録番号	166591-11-3
PubChem	9841398
ChemSpider	8017113
ChEMBL	CHEMBL28338
	SMILES Oc1cc3c(cc1O)CCC4C3c2cc(CCC)sc2CN4;
	InChI InChI=1S/C18H21NO2S/c1-2-3-11-7-13-17(22-11)9-19-14-5-4-10-6-15(20)16(21)8-12(10)18(13)14/h6-8,14,18-21H,2-5,9H2,1H3/t14-,18+/m1/s1 Key: REHAKLRYABHSQJ-KDOFPFPSSA-N ; InChI=1/C18H21NO2S/c1-2-3-11-7-13-17(22-11)9-19-14-5-4-10-6-15(20)16(21)8-12(10)18(13)14/h6-8,14,18-21H,2-5,9H2,1H3/t14-,18+/m1/s1 Key: REHAKLRYABHSQJ-KDOFPFPSBO;
特性
化学式	C18H21NO2S
モル質量	315.429 g/mol
	特記なき場合、データは常温 (25 °C)・常圧 (100 kPa) におけるものである。

A-86929は、選択的にドーパミン受容体 D₁ アゴニストとして作用する合成物質である^[1]^[2]。この物質はパーキンソン病^[3]やコカイン中毒^[4]^[5]の治療のために開発され、ヒトでは十分な有効性が示されたが、ジスキネジアを引き起こし、継続はされていない^[6]^[7]。主に二酢酸エステルのプロドラッグであるアドロゴリド (adrogolide) の方が生物学的利用能が優れている^[8]^[9]。

出典

^ Michaelides MR, Hong Y, DiDomenico S, Asin KE, Britton DR, Lin CW, Williams M, Shiosaki K (September 1995). “(5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopent-1- ena[c]-phenanthrene-9,10-diol (A-86929): a potent and selective dopamine D1 agonist that maintains behavioral efficacy following repeated administration and characterization of its diacetyl prodrug (ABT-431)”. Journal of Medicinal Chemistry 38 (18): 3445–7. doi:10.1021/jm00018a002. PMID 7658429.
^ Ehrlich PP, Ralston JW, Michaelides MR (May 1997). “An Efficient Enantioselective Synthesis of the D1 Agonist (5aR,11bS)-4,5,5a,6,7,11b-Hexahydro-2-propyl-3-thia- 5-azacyclopenta[c]phenanthrene-9,10-diol (A-86929)”. The Journal of Organic Chemistry 62 (9): 2782–2785. doi:10.1021/jo970066l. PMID 11671640.
^ Rascol O, Blin O, Thalamas C, Descombes S, Soubrouillard C, Azulay P, Fabre N, Viallet F, Lafnitzegger K, Wright S, Carter JH, Nutt JG (June 1999). “ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's disease”. Annals of Neurology 45 (6): 736–41. doi:10.1002/1531-8249(199906)45:6<736::AID-ANA7>3.0.CO;2-F. PMID 10360765.
^ Haney M, Collins ED, Ward AS, Foltin RW, Fischman MW (March 1999). “Effect of a selective dopamine D1 agonist (ABT-431) on smoked cocaine self-administration in humans”. Psychopharmacology 143 (1): 102–10. doi:10.1007/s002130050925. PMID 10227086.
^ Gorelick DA, Gardner EL, Xi ZX (2004). “Agents in development for the management of cocaine abuse”. Drugs 64 (14): 1547–73. doi:10.2165/00003495-200464140-00004. PMID 15233592.
^ Rascol O, Nutt JG, Blin O, Goetz CG, Trugman JM, Soubrouillard C, Carter JH, Currie LJ, Fabre N, Thalamas C, Giardina WW, Wright S (February 2001). “Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease”. Archives of Neurology 58 (2): 249–54. doi:10.1001/archneur.58.2.249. PMID 11176963.
^ Zhang J, Xiong B, Zhen X, Zhang A (March 2009). “Dopamine D1 receptor ligands: where are we now and where are we going”. Medicinal Research Reviews 29 (2): 272–94. doi:10.1002/med.20130. PMID 18642350.
^ Shiosaki K, Jenner P, Asin KE, Britton DR, Lin CW, Michaelides M, Smith L, Bianchi B, Didomenico S, Hodges L, Hong Y, Mahan L, Mikusa J, Miller T, Nikkel A, Stashko M, Witte D, Williams M (January 1996). “ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson's disease”. The Journal of Pharmacology and Experimental Therapeutics 276 (1): 150–60. PMID 8558425.
^ Giardina WJ, Williams M (2001). “Adrogolide HCl (ABT-431; DAS-431), a prodrug of the dopamine D1 receptor agonist, A-86929: preclinical pharmacology and clinical data”. CNS Drug Reviews 7 (3): 305–16. doi:10.1111/j.1527-3458.2001.tb00201.x. PMID 11607045.

[pmid7658429-1] Michaelides MR, Hong Y, DiDomenico S, Asin KE, Britton DR, Lin CW, Williams M, Shiosaki K (September 1995). “(5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopent-1- ena[c]-phenanthrene-9,10-diol (A-86929): a potent and selective dopamine D1 agonist that maintains behavioral efficacy following repeated administration and characterization of its diacetyl prodrug (ABT-431)”. Journal of Medicinal Chemistry 38 (18): 3445–7. doi:10.1021/jm00018a002. PMID 7658429.

[pmid11671640-2] Ehrlich PP, Ralston JW, Michaelides MR (May 1997). “An Efficient Enantioselective Synthesis of the D1 Agonist (5aR,11bS)-4,5,5a,6,7,11b-Hexahydro-2-propyl-3-thia- 5-azacyclopenta[c]phenanthrene-9,10-diol (A-86929)”. The Journal of Organic Chemistry 62 (9): 2782–2785. doi:10.1021/jo970066l. PMID 11671640.

[pmid10360765-3] Rascol O, Blin O, Thalamas C, Descombes S, Soubrouillard C, Azulay P, Fabre N, Viallet F, Lafnitzegger K, Wright S, Carter JH, Nutt JG (June 1999). “ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson's disease”. Annals of Neurology 45 (6): 736–41. doi:10.1002/1531-8249(199906)45:6<736::AID-ANA7>3.0.CO;2-F. PMID 10360765.

[pmid10227086-4] Haney M, Collins ED, Ward AS, Foltin RW, Fischman MW (March 1999). “Effect of a selective dopamine D1 agonist (ABT-431) on smoked cocaine self-administration in humans”. Psychopharmacology 143 (1): 102–10. doi:10.1007/s002130050925. PMID 10227086.

[pmid15233592-5] Gorelick DA, Gardner EL, Xi ZX (2004). “Agents in development for the management of cocaine abuse”. Drugs 64 (14): 1547–73. doi:10.2165/00003495-200464140-00004. PMID 15233592.

[pmid11176963-6] Rascol O, Nutt JG, Blin O, Goetz CG, Trugman JM, Soubrouillard C, Carter JH, Currie LJ, Fabre N, Thalamas C, Giardina WW, Wright S (February 2001). “Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease”. Archives of Neurology 58 (2): 249–54. doi:10.1001/archneur.58.2.249. PMID 11176963.

[pmid18642350-7] Zhang J, Xiong B, Zhen X, Zhang A (March 2009). “Dopamine D1 receptor ligands: where are we now and where are we going”. Medicinal Research Reviews 29 (2): 272–94. doi:10.1002/med.20130. PMID 18642350.

[pmid8558425-8] Shiosaki K, Jenner P, Asin KE, Britton DR, Lin CW, Michaelides M, Smith L, Bianchi B, Didomenico S, Hodges L, Hong Y, Mahan L, Mikusa J, Miller T, Nikkel A, Stashko M, Witte D, Williams M (January 1996). “ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson's disease”. The Journal of Pharmacology and Experimental Therapeutics 276 (1): 150–60. PMID 8558425.

[pmid11607045-9] Giardina WJ, Williams M (2001). “Adrogolide HCl (ABT-431; DAS-431), a prodrug of the dopamine D1 receptor agonist, A-86929: preclinical pharmacology and clinical data”. CNS Drug Reviews 7 (3): 305–16. doi:10.1111/j.1527-3458.2001.tb00201.x. PMID 11607045.

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