5-, 6-, 7- and 8-amino-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalenes: centrally acting DA and 5-HT1A agonists

Stjernlöf, Peter; Åndersson, Bengt; Svensson, Arne; Svensson, Kjell; Ekman, Agneta; Carlsson, Arvid; Wikström, Håkan

doi:10.1016/0223-5234(93)90028-d

Cited by 12 publications

(8 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mixture was stirred for 20 min, filtered, and evaporated to yield 3.3 g (94%) of a pure product. The di-HCl salt was prepared in HCl/ethanol and recrystallized from methanol/diethyl ether for analytical purposes: mp 144-146 °C (di-HCl salt); NMR (300 MHz, CDC13) ó 0.90 (t, 6H), 1.45 (q, 4H), 1.95 (m, 1H), 2.45 (m, 4H), 2.5-2.9 (m, 6H), 3.40 (s, 2H), 6.48 (d, J = 9.0 Hz, 1H), 6.68 (d, J = 11.7 Hz, 1H); MS m/e 264 (M+, 17), 164 (100), 235 (55), 163 (22), 138 (20), 147 (16). Anal.…”

Section: Methodsmentioning

confidence: 99%

“…(4-Fluoro-6,7,8,9-tetrahydro-3ff-benz[e]indol-8-yl)dipropylamine (20). A mixture of e-fluoro-A^A^-dipropyl-l,2,3,4tetrahydronaphthalene-2,7-diamine (19) (3.0 g, 11.3 mmol), chloral hydrate (2.04 g, 12.3 mmol), hydroxylammonium hydrochloride (2.48 g, 35.7 mmol), and sodium sulfate (12.6 g) in distilled water (46 mL) was refluxed for 1.5 h and then cooled to ambient temperature.…”

Section: Methodsmentioning

confidence: 99%

“…(Ci8H25FN2) C, , N. Resolution of (4-Fluoro-6,7,8,9-tetrahydro-3H-benz[e]indol-8-yI)dipropylamine (20, S-(-)-20, andR-(+)-20). (+)-Di-p-toluoyl-D-tartaric acid (2.74 g, 7.11 mmol) and (4-fluoro-6,7,8,9-tetrahydro-3//-benz[e]indol-8-yl)dipropylamine (20) (2.05 g, 7.11 mmol) were dissolved separately in ethanol, mixed, and evaporated. The resulting solid was dissolved in a minimum volume of refluxing ethanol (75 mL) and left to crystallize overnight.…”

Section: Methodsmentioning

confidence: 99%

“…After extraction three times with ethyl acetate, the organic layers were dried (magnesium sulfate), filtered, and evaporated to a residue of 45 mg (71%). Purification on a silica gel column using methanol as eluant afforded 20 mg of pure product: NMR (300 MHz, CDCI3) ó 0.90 (t, 6H), 1.50 (q, 4H), 1.70 (m, 1H), 2.55 (t, 4H), 2.1 (m, 1H), 2.85-3.15 (m, 5H), 3.45 (m, 1H), 6.74 (d, J = 11.1 Hz, 1H), 7.95 (s, 1H), 10.20 (s, 1H); MS m/e 316 (M+, 9), 216 (100), 287 (59), 188 (36), 217 (20), 172 (14).…”

Section: Methodsmentioning

confidence: 99%

“…(s, 3H),7.07 (d, J = 8.3 Hz, 1H), 7.14 (d, J = 8.3 Hz, 1H),10.22 (s, 1H); MS m/e 312 (M+, 25), 283 (100), 212 (82), 184 (28), 213 (25), 284(20). Anal.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Structure-Activity Relationships in the 8-Amino-6,7,8,9-tetrahydro-3H-benz[e]indole Ring System. Part 1: Effects of Substituents in the Aromatic System on Serotonin and Dopamine Receptor Subtypes

Stjernlöf¹,

Ennis²,

Lo³

et al. 1995

J. Med. Chem.

View full text Add to dashboard Cite

A series of 1-, 3-, and 4-substituted analogs to the potent 5-HT1A against 8-(dipropylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (5) were prepared and tested in vitro at 5-HT1A, 5-HT1D alpha, 5-HT1D beta, D2, and D3 receptors and in vivo for agonist activity in the 5-HTP and DOPA accumulation assays in reserpine-pretreated rats. Some of the compounds were resolved. The substituents used in the 1-position were chosen from a principal component analysis (PCA) plot constructed from both tabulated variables and variables calculated by semiempirical methods (PM3) and molecular mechanics software (MMX). Among the analogs prepared, some, e.g., compound 21, were equipotent to compound 5 with respect to 5-HT1A effects. All compounds were more or less selective for the 5-HT1A receptor, but many of the compounds displayed higher affinities for 5-HT1D alpha than for 5-HT1D beta receptors.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…(s, 3H),7.07 (d, J = 8.3 Hz, 1H), 7.14 (d, J = 8.3 Hz, 1H),10.22 (s, 1H); MS m/e 312 (M+, 25), 283 (100), 212 (82), 184 (28), 213 (25), 284(20). Anal.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Structure-Activity Relationships in the 8-Amino-6,7,8,9-tetrahydro-3H-benz[e]indole Ring System. Part 1: Effects of Substituents in the Aromatic System on Serotonin and Dopamine Receptor Subtypes

Stjernlöf¹,

Ennis²,

Lo³

et al. 1995

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

Synthesis of (r)‐ and (s)‐1‐formyl‐6,7,8,9‐tetrahydro‐ N,N‐(dipropyl)‐3H‐benz[e]indol‐8‐amines: Potent and orally active 5‐ht_1a receptor agonists

Lin

Ennis

Hoffman

et al. 1994

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

An efficient synthesis of the potent and orally active 5‐HT1A agonists, (R)‐(+)‐ and (S)‐(‐)‐1‐formyl‐6,7,8,9‐tetrahydro‐N,N‐dipropyl‐3H‐benz[e]indol‐8‐amines 1a and 1b, is described. This synthesis was accomplished in twelve steps from commercially available 1,5,6,7‐tetrahydro‐4H‐indol‐4‐one (5). The key step involved a regio‐controlled Friedel‐Crafts acylation of 1‐(p‐toluenesulfonyl)indol‐4‐acetyl chloride with ethylene to yield a versatile synthon, 3‐(p‐toluenesulfonyl)‐6,7,8,9‐tetrahydro‐3H‐benz[e]indol‐8‐one (10). Subsequent coupling of this ketone with chiral α‐methylbenzylamine under reductive amination conditions yielded a mixture of diastereomers. These diastereomers were efficiently separated by either chromatography or fractional recrystallization of the derived hydrochloride salts. Debenzylation of the pure diastereomers was followed by alkylation and formylation to yield (R)‐(+)‐ and (S)‐(‐)‐enantiomers 1a and 1b with >99% purity.

show abstract

C8-Substituted derivatives of 2-(dipropylamino)tetralin: exploration of the effect of C8-aryl and heteroaryl substituents on the interaction with 5-HT1A-receptor

Liu

Cortizo

et al. 1995

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

5-, 6-, 7- and 8-amino-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalenes: centrally acting DA and 5-HT1A agonists

Cited by 12 publications

References 16 publications

Structure-Activity Relationships in the 8-Amino-6,7,8,9-tetrahydro-3H-benz[e]indole Ring System. Part 1: Effects of Substituents in the Aromatic System on Serotonin and Dopamine Receptor Subtypes

Structure-Activity Relationships in the 8-Amino-6,7,8,9-tetrahydro-3H-benz[e]indole Ring System. Part 1: Effects of Substituents in the Aromatic System on Serotonin and Dopamine Receptor Subtypes

Synthesis of (r)‐ and (s)‐1‐formyl‐6,7,8,9‐tetrahydro‐ N,N‐(dipropyl)‐3H‐benz[e]indol‐8‐amines: Potent and orally active 5‐ht_1a receptor agonists

C8-Substituted derivatives of 2-(dipropylamino)tetralin: exploration of the effect of C8-aryl and heteroaryl substituents on the interaction with 5-HT1A-receptor

Contact Info

Product

Resources

About

5-, 6-, 7- and 8-amino-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalenes: centrally acting DA and 5-HT1A agonists

Cited by 12 publications

References 16 publications

Structure-Activity Relationships in the 8-Amino-6,7,8,9-tetrahydro-3H-benz[e]indole Ring System. Part 1: Effects of Substituents in the Aromatic System on Serotonin and Dopamine Receptor Subtypes

Structure-Activity Relationships in the 8-Amino-6,7,8,9-tetrahydro-3H-benz[e]indole Ring System. Part 1: Effects of Substituents in the Aromatic System on Serotonin and Dopamine Receptor Subtypes

Synthesis of (r)‐ and (s)‐1‐formyl‐6,7,8,9‐tetrahydro‐ N,N‐(dipropyl)‐3H‐benz[e]indol‐8‐amines: Potent and orally active 5‐ht1a receptor agonists

C8-Substituted derivatives of 2-(dipropylamino)tetralin: exploration of the effect of C8-aryl and heteroaryl substituents on the interaction with 5-HT1A-receptor

Contact Info

Product

Resources

About

Synthesis of (r)‐ and (s)‐1‐formyl‐6,7,8,9‐tetrahydro‐ N,N‐(dipropyl)‐3H‐benz[e]indol‐8‐amines: Potent and orally active 5‐ht_1a receptor agonists