脱羧麦角酸

脱羧麦角酸
臨床資料
其他名稱	8-Descarboxylysergic acid; Descarboxyllysergic acid; 9,10-Didehydro-6-methylergoline; 6-Methyl-9,10-didehydroergoline; 6-Methyl-9-ergolene
识别信息
	IUPAC命名法 (6aR)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline; ;
CAS号	51867-17-5
PubChem CID	191210;
ChemSpider	166049;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID00966197 ;
化学信息
化学式	C15H16N2
摩尔质量	224.31 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES CN1CCC=C2[C@H]1CC3=CNC4=CC=CC2=C34;
	InChI InChI=1S/C15H16N2/c1-17-7-3-5-11-12-4-2-6-13-15(12)10(9-16-13)8-14(11)17/h2,4-6,9,14,16H,3,7-8H2,1H3/t14-/m1/s1; Key:AHFZNJIKXMBLTJ-CQSZACIVSA-N;

脱羧麦角酸（英語：Descarboxylysergic acid 或 8-descarboxylysergic acid，也称为9,10-脱氢-6-甲基麦角灵，9,10-didehydro-6-methylergoline，或6-甲基-9-麦角烯，6-methyl-9-ergolene）是一种含氮有机化合物，化学式C
15H
16N
2，是麥角酸以及其衍生物麥角酸二乙酰胺（LSD）的结构母体。^[2]^[3]^[4]^[1]^[5]

参考文献

^ ^1.0 ^1.1 Hauth H. Chemical Aspects of Ergot Derivatives with Central Dopaminergic Activity. Dopaminergic Ergot Derivatives and Motor Function. Elsevier. 1979: 23–32. ISBN 978-0-08-024408-2. doi:10.1016/b978-0-08-024408-2.50007-5. Kornfeld et al. (ref. 12) have likewise attempted to identify the part of the ergoline structure responsible for its pharmacological activity. They have shown that one of the properties of racemic 9.10-didehydro-6-methyl-ergoline (Fig. 10) is the inhibition of prolactin secretion. However, the potency of this activity is less than 10 % of that of ergonine. [...] Fig. 10. dl-9,10-Didehydro-6-methyl-ergoline = dl-6-Methyl-9-ergolene = dl-Descarboxylysergic acid [...] These findings once again confirm the observation that although the ergoline skeleton contains dopaminergic and, obviously, also serotoninergic and noradrenergic components, it is the substituents alone that are responsible for the profile and intensity of the biological activity. The proof is to be found in publications reporting on the effects of substitution in ergolines and ergopeptines on biological activity (ref. 6,7,13).
^ Nichols DE. Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences 36. 2018: 1–43. ISBN 978-3-662-55878-2. PMID 28401524. doi:10.1007/7854_2017_475. 3.1 Amide Modifications of Lysergic Acid Derivatives The simplest ergoline with human psychoactive properties is lysergic acid amide (23, ergine), reported by Hofmann and Tscherter to be the active component in Rivea corymbosa seeds used by the Aztecs in various magical potions and ointments (Hofmann 1971). If the C(8) amide substituent is removed completely to provide the 8-descarboxy 24, the compound is reported to produce a mouse behavioral profile “remarkably similar to that shown by LSD” (Bach et al. 1974). Unfortunately, no other assays were carried out, nor were human studies carried out that would elucidate whether the presence of an amide substituent is an absolute requirement for activity. That is an important question because even slight modifications to the diethylamide moiety of LSD result in dramatic losses of in vivo activity. [...] With respect to lysergic acid amides, it should be pointed out that the high in vivo potency of LSD seems to depend on the presence of the N,N-diethylamide moiety. |journal=被忽略 (帮助)
^ Nichols DE. Structure–activity relationships of serotonin 5-HT2A agonists. Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 2012, 1 (5): 559–579. ISSN 2190-460X. doi:10.1002/wmts.42 . Studies of the Amide Portion of Lysergic Acid Derivatives The simplest ergoline with human psychoactive properties, and presumably 5-HT2A agonist activity, is lysergic acid amide (15, ergine), which was reported by Hofmann and Tscherter36 to be the active component in Rivea corymbosa seeds, used by the Aztecs in various magical potions and ointments (Figure 12). Surprisingly, if the C(8) amide substituent is removed completely to give 8-descarboxy lysergic acid 16, the compound is reported to produce a behavioral profile in mice ‘remarkably similar to that shown by LSD’.37 [...] FIGURE 12 | The structures of lysergic acid amide 15 (ergine) and 8-descarboxy lysergic acid 16.
^ Bach NJ, Hall DA, Kornfeld EC. Descarboxylysergic acid (9,10-didehydro-6-methylergoline). J Med Chem. March 1974, 17 (3): 312–314. PMID 4811227. doi:10.1021/jm00249a011.
^ Nichols DE. Structural correlation between apomorphine and LSD: involvement of dopamine as well as serotonin in the actions of hallucinogens. J Theor Biol. June 1976, 59 (1): 167–177. Bibcode:1976JThBi..59..167N. PMID 7711. doi:10.1016/s0022-5193(76)80030-6. Another important point which should be defined is the relative importance of the substituent at the C-8 position of LSD. It has been demonstrated that small changes in substitution on the amide nitrogen produce, in every instance, a molecule with decreased hallucinogenic activity when compared with the diethylamide (Hofmann, 1968). Speculation concerning the role of the amide function of LSD as a result of this finding continues. However, Bach, Hall & Kornfeld (1974) have shown that 8-descarboxylysergic acid, completely lacking an 8 substituent, still retains a profile of activity in mice similar to LSD. Activity of this compound on rabbit aortic strips was demonstrated to be comparable to ergonovine, and on rat stomach strips was about one-third the potency of methysergide as a serotonin antagonist. Thus the importance of C-8 substitution may lie in metabolic, distribution, or conformational factors, rather than to some receptor requirement for binding at this site.

外部链接

Descarboxylysergic acid - isomer design

[Hauth1979-1] 1.0 ^1.1 Hauth H. Chemical Aspects of Ergot Derivatives with Central Dopaminergic Activity. Dopaminergic Ergot Derivatives and Motor Function. Elsevier. 1979: 23–32. ISBN 978-0-08-024408-2. doi:10.1016/b978-0-08-024408-2.50007-5. Kornfeld et al. (ref. 12) have likewise attempted to identify the part of the ergoline structure responsible for its pharmacological activity. They have shown that one of the properties of racemic 9.10-didehydro-6-methyl-ergoline (Fig. 10) is the inhibition of prolactin secretion. However, the potency of this activity is less than 10 % of that of ergonine. [...] Fig. 10. dl-9,10-Didehydro-6-methyl-ergoline = dl-6-Methyl-9-ergolene = dl-Descarboxylysergic acid [...] These findings once again confirm the observation that although the ergoline skeleton contains dopaminergic and, obviously, also serotoninergic and noradrenergic components, it is the substituents alone that are responsible for the profile and intensity of the biological activity. The proof is to be found in publications reporting on the effects of substitution in ergolines and ergopeptines on biological activity (ref. 6,7,13).

[Nichols2018-2] Nichols DE. Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences 36. 2018: 1–43. ISBN 978-3-662-55878-2. PMID 28401524. doi:10.1007/7854_2017_475. 3.1 Amide Modifications of Lysergic Acid Derivatives The simplest ergoline with human psychoactive properties is lysergic acid amide (23, ergine), reported by Hofmann and Tscherter to be the active component in Rivea corymbosa seeds used by the Aztecs in various magical potions and ointments (Hofmann 1971). If the C(8) amide substituent is removed completely to provide the 8-descarboxy 24, the compound is reported to produce a mouse behavioral profile “remarkably similar to that shown by LSD” (Bach et al. 1974). Unfortunately, no other assays were carried out, nor were human studies carried out that would elucidate whether the presence of an amide substituent is an absolute requirement for activity. That is an important question because even slight modifications to the diethylamide moiety of LSD result in dramatic losses of in vivo activity. [...] With respect to lysergic acid amides, it should be pointed out that the high in vivo potency of LSD seems to depend on the presence of the N,N-diethylamide moiety. |journal=被忽略 (帮助)

[Nichols2012-3] Nichols DE. Structure–activity relationships of serotonin 5-HT2A agonists. Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 2012, 1 (5): 559–579. ISSN 2190-460X. doi:10.1002/wmts.42 . Studies of the Amide Portion of Lysergic Acid Derivatives The simplest ergoline with human psychoactive properties, and presumably 5-HT2A agonist activity, is lysergic acid amide (15, ergine), which was reported by Hofmann and Tscherter36 to be the active component in Rivea corymbosa seeds, used by the Aztecs in various magical potions and ointments (Figure 12). Surprisingly, if the C(8) amide substituent is removed completely to give 8-descarboxy lysergic acid 16, the compound is reported to produce a behavioral profile in mice ‘remarkably similar to that shown by LSD’.37 [...] FIGURE 12 | The structures of lysergic acid amide 15 (ergine) and 8-descarboxy lysergic acid 16.

[BachHallKornfeld1974-4] Bach NJ, Hall DA, Kornfeld EC. Descarboxylysergic acid (9,10-didehydro-6-methylergoline). J Med Chem. March 1974, 17 (3): 312–314. PMID 4811227. doi:10.1021/jm00249a011.

[Nichols1976-5] Nichols DE. Structural correlation between apomorphine and LSD: involvement of dopamine as well as serotonin in the actions of hallucinogens. J Theor Biol. June 1976, 59 (1): 167–177. Bibcode:1976JThBi..59..167N. PMID 7711. doi:10.1016/s0022-5193(76)80030-6. Another important point which should be defined is the relative importance of the substituent at the C-8 position of LSD. It has been demonstrated that small changes in substitution on the amide nitrogen produce, in every instance, a molecule with decreased hallucinogenic activity when compared with the diethylamide (Hofmann, 1968). Speculation concerning the role of the amide function of LSD as a result of this finding continues. However, Bach, Hall & Kornfeld (1974) have shown that 8-descarboxylysergic acid, completely lacking an 8 substituent, still retains a profile of activity in mice similar to LSD. Activity of this compound on rabbit aortic strips was demonstrated to be comparable to ergonovine, and on rat stomach strips was about one-third the potency of methysergide as a serotonin antagonist. Thus the importance of C-8 substitution may lie in metabolic, distribution, or conformational factors, rather than to some receptor requirement for binding at this site.

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