20569-49-7Relevant academic research and scientific papers
(+/-)-(N-alkylamino)benzazepine analogs: novel dopamine D1 receptor antagonists.
Shah,Izenwasser,Geter-Douglass,Witkin,Newman
, p. 4284 - 4293 (2007/10/03)
(+/-)-(N-Alkylamino)benzazepine analogs were prepared as novel dopamine D1 receptor antagonists to further elucidate the role of these receptor subtypes in the pharmacology and toxicology of cocaine. In the first series of compounds, (+/-)-7-chloro-8-hydroxy-3- [6-(N,N-dimethylamino)-hexyl]-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepi ne (15) showed the highest affinity (Ki = 49.3 nM) and subtype-selectivity for dopamine D1 over dopamine D2, 5-HT2a, and 5-HT2c receptors. Compounds 7a [(+/-)-7-Chloro-8-hydroxy-3-[4-(N,N-dimethylamino)butyl]-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzazepine], 11 [(+/-)-7-chloro-8-hydroxy-3-[6-[(N,N-dimethylamino)hexyl]-1- phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-cyanoborane], and 15 were moderately potent dopamine D1 receptor antagonists as evidenced by their ability to block dopamine-stimulated adenylyl cyclase activity in rat caudate (predicted Ki values = 60, 34, and 21 nM, respectively). Compound 7a appears to be unique in that, despite its relatively potent inhibition of dopamine stimulated adenylyl cyclase, it demonstrated relatively weak binding affinity at the dopamine D1 receptors (Ki = 811 nM). Unlike previously reported N-alkylbenzazepines, where a significant loss in dopamine D1 receptor binding affinity was observed when successive increases in the alkyl side chain size at the benzazepine nitrogen were made, several of these novel N-alkylamino analogs demonstrated high-affinity binding with an optimal chain length of six carbons. This initial series of compounds appears to be identifying another binding domain on the dopamine D1 receptor protein that has not previously been characterized and that accepts an amino function. Further, these compounds may serve as templates for the design of peripherally active dopamine D1 receptor antagonists.
(+/-)-3-Allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin, a New High-Affinity D1 Dopamine Receptor Ligand: Synthesis and Structure-Activity Relationship
Neumeyer, John L.,Baindur, Nandkishore,Niznik, Hyman B.,Guan, H. C.,Seeman, Philip
, p. 3366 - 3371 (2007/10/02)
The 7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines form a series of compounds having a high affinity at the D1 dopamine receptor.The 6-chloro derivative has been previously shown to have enhanced affinity, selectivity, and agonist activity.In an attempt to study the effect of substitution of a 6-bromo group in place of the 6-chloro, we hawe synthesized a series of compounds and evaluaed them for their affinity for the D1 receptor.The results show that the 6-bromo derivatives have virtually identical affinities to their 6-chloro counterparts, a findingsimilar to that found in the D1 antagonist 7-halo-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine series.From the present work, 3-allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (6-Br-APB) has been identified as a suitable candidate for further in vivo studies and resolution into its active and inactive enantiomers.
Tricarbonylchromium(0) Promoted Stereoselective Cyclisations of the N-3,4-Dimethoxyphenethyl Derivatives of the 1-Phenyl Ethanolamines Halostachine, Ephedrine and Pseudoephedrine to 1-Phenyl-N-Methyl-7,8-Dimethoxy-1,2,4,5-Tetrahydrobenzazepines
Coote, Steven J.,Davies, Stephen G.,Middlemiss, David,Naylor, Alan
, p. 33 - 56 (2007/10/02)
Acid promoted cyclisation of homochiral (R)-N-(3,4-dimethoxyphenethyl)-halostachine proceeds with almost total racemisation to yield 1-phenyl-N-methyl-1,2,4,5-tetrahydrobenzazepine (e.e, 6percent).Coordination of the cyclisation precursor to the tricarbonylchromium(0) moiety renders the cyclisation completely stereospecific to afford, after decomplexation, homochiral (+)-(R)-1-phenyl-N-methyl-1,2,4,5-tetrahydrobenzazepine. (-)-(1R,2S)-N-(3,4-Dimethoxyphenethyl)ephedrine undergoes acid mediated cyclisation to furnish trans-(-)-(1R,2S)-1-phenyl-2-methyl-N-methyl-7,8-dimethoxy tetrahydrobenzazepine as a single diastereoisomer.In contrast, the epimeric cyclisation precursor (-)-(1R,2R)-N-(3,4-dimethoxyphenethyl)pseudoephedrine cyclises to give a mixture (ratio 91:9) of trans- and cis-1-phenyl-2-methyl-N-methyl-7,8-dimethoxy tetrahydrobenzazepine.However, cyclisation of the tricarbonylchromium(0) complex of (-)-(1R,2R)-N-(3,4-dimethoxyphenethyl)pseudo-ephedrine is completely stereoselective to yield trans-(+)-(1S,2R)-1-phenyl-2-methyl-N-methyl-7,8-dimethoxy tetrahydrobenzazepine after decomplexation.
ENANTIOSPECIFIC SYNTHESIS OF (+)-(R)-1-PHENYL-3-METHYL-1,2,4,5-TETRAHYDROBENZAZEPINE FROM (+)-(S)-N-METHYL-1-PHENYL ETHANOLAMINE (HALOSTACHINE) via ARENE CHROMIUM TRICARBONYL METHODOLOGY
Coote, Steven J.,Davies, Stephen G.,Middlemiss, David,Naylor, Alan
, p. 3581 - 3584 (2007/10/02)
Acid promoted cyclisation of homochiral (R)-N-(3,4-dimethoxyphenethyl) halostachine chromium tricarbonyl is stereospecific, proceeding with retention of configuration, to afford, after decomplexation, homochiral (+)-(R)-1-phenyl-3-methyl-1,2,4,5-tatrahydr
PHARMACEUTICAL COMPOSITIONS AND METHODS INVOLVING BENZAZEPINE DERIVATIVES
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, (2008/06/13)
Pharmaceutical compositions and a method of stimulating peripheral dopamine receptors by administering internally a nontoxic effective quantity of a benzazepine derivative to an animal. Renal vasodilator and diuretic methods are also disclosed.
Pharmaceutical compositions and method of producing anti-Parkinsonism activity
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, (2008/06/13)
Pharmaceutical compositions and method of producing anti-Parkinsonism activity by administering internally a nontoxic effective quantity of a benzazepine derivative to an animal.
