BIOMAT Database Logo BIOMAT Database Logo

(+/-)-4-Aryl-4,5-dihydro-3H-1,3-benzodiazepines. 2. Nuclear-substituted analogues of (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine and (+/-)-4,5-dihydro-2-ethyl-3-methyl-4-phenyl-3H-1,3-benzodiazepine as potential antidepressant agents. 1982

L L Martin, and L L Setescak, and M Worm, and C A Crichlow, and H M Geyer, and J C Wilker

Antidepressant-like activity, as evidenced by marked inhibition of tetrabenazine-induced ptosis, was previously reported for (+/-)-4,5-dihydro-4-phenyl-3H-1,3-benzodiazepine derivatives. Since optimal antitetrabenazine activity was associated with (+/-)-4,5-dihydro-2,3-dimethyl-4-phenyl-3H-1,3-benzodiazepine (9k, HRP 543) and the 2-ethyl-3-methyl analogue (10k), the synthesis and evaluation of nuclear-substituted derivatives of these two compounds was also investigated. The initial synthesis involved Friedel-Crafts acylation of substituted benzenes with 2-nitrophenylacetyl chloride to afford 1-aryl-2-(2-nitrophenyl)ethanones 2, which were converted in five steps to (+/-)-alpha-aryl-N-methyl-2-nitrobenzeneethanamines 7. Greater flexibility with respect to the introduction of nuclear substituents was achieved by conversion of 2-nitrotoluene derivatives to 2 via acylation of intermediate beta-(dimethylamino)-2-nitrostyrenes with various aroyl chlorides and hydrolysis. Reductive amination of 2 with methylamine and sodium cyanoborohydride afforded 7 directly and significantly reduced the number of synthetic steps. Reduction of 7a-j to diamines 8a-j and cyclization with appropriate ortho esters gave nuclear-substituted analogues of 9k and 10k. Marked antitetrabenazine activity was associated with many of these compounds. Significant enhancement of activity with respect to the unsubstituted analogues 9k and 10k was not observed, with the exception of 9c which appeared to be slightly more potent than 9k.

UI MeSH Term Description Entries
D010433 Pentylenetetrazole A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility. Leptazole,Pentamethylenetetrazole,Pentetrazole,Cardiazol,Corasol,Corazol,Corazole,Korazol,Korazole,Metrazol,Metrazole,Pentazol,Pentylenetetrazol
D001763 Blepharoptosis Drooping of the upper lid due to deficient development or paralysis of the levator palpebrae muscle. Ptosis, Eyelid,Blepharoptoses,Eyelid Ptoses,Eyelid Ptosis,Ptoses, Eyelid
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D000661 Amphetamine A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE. Desoxynorephedrin,Levoamphetamine,Phenopromin,l-Amphetamine,Amfetamine,Amphetamine Sulfate,Amphetamine Sulfate (2:1),Centramina,Fenamine,Mydrial,Phenamine,Thyramine,levo-Amphetamine,Sulfate, Amphetamine,l Amphetamine,levo Amphetamine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000928 Antidepressive Agents Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems. Antidepressant,Antidepressant Drug,Antidepressant Medication,Antidepressants,Antidepressive Agent,Thymoanaleptic,Thymoanaleptics,Thymoleptic,Thymoleptics,Antidepressant Drugs,Agent, Antidepressive,Drug, Antidepressant,Medication, Antidepressant
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D001569 Benzodiazepines A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring. Benzodiazepine,Benzodiazepine Compounds
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D013747 Tetrabenazine A drug formerly used as an antipsychotic and treatment of various movement disorders. Tetrabenazine blocks neurotransmitter uptake into adrenergic storage vesicles and has been used as a high affinity label for the vesicle transport system. Nitoman,Xenazine

Related Publications

L L Martin, and L L Setescak, and M Worm, and C A Crichlow, and H M Geyer, and J C Wilker
Synthesis and evaluation of new 1,5-diaryl-3-[4-(methyl-sulfonyl)phenyl]-4,5-dihydro-1H-pyrazole derivatives as potential antidepressant agents.
February 2015, Molecules (Basel, Switzerland),
L L Martin, and L L Setescak, and M Worm, and C A Crichlow, and H M Geyer, and J C Wilker
Synthesis of 3-aryl-2-substituted-4(3H)-quinazolines as potential antimicrobial agents.
April 1990, Farmaco (Societa chimica italiana : 1989),
L L Martin, and L L Setescak, and M Worm, and C A Crichlow, and H M Geyer, and J C Wilker
Synthesis of 3-[2-(2,3-dihydro-5-phenyl-4-substituted-3H-1,2,4- triazole-3-thione-2-yl)-acetylamino]-2-methyl-4(3H)-quinazolinones and their pharmacological activities.
January 1989, Archiv der Pharmazie,
L L Martin, and L L Setescak, and M Worm, and C A Crichlow, and H M Geyer, and J C Wilker
Synthesis of 2,3-dihydro-3-amino-6-phenyl-2-thioxothieno [2,3-d] pyrimidin-4 (1H)-one and of potential antiinflammatory agents 2-aryl-7-phenyl-3H, 9H-pyrimido [2,1-b]thieno-[2',3':4,5]]1,3,4] thiadiazin-9-ones.
January 1994, Die Pharmazie,
L L Martin, and L L Setescak, and M Worm, and C A Crichlow, and H M Geyer, and J C Wilker
2-Methoxy-4-[(5-oxo-2-phenyl-4,5-dihydro-1,3-oxazol-4-ylidene)methyl]phenyl 4-methylbenzenesulfonate.
April 2007, Acta crystallographica. Section C, Crystal structure communications,
L L Martin, and L L Setescak, and M Worm, and C A Crichlow, and H M Geyer, and J C Wilker
Synthesis of novel 3-(4-acetyl-5H/methyl-5-substituted phenyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-2H-chromen-2-ones as potential anticonvulsant agents.
January 2008, Acta poloniae pharmaceutica,
L L Martin, and L L Setescak, and M Worm, and C A Crichlow, and H M Geyer, and J C Wilker
Ethyl 3-methyl-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyridazine-2-carboxyl-ate.
January 2010, Acta crystallographica. Section E, Structure reports online,
L L Martin, and L L Setescak, and M Worm, and C A Crichlow, and H M Geyer, and J C Wilker
4,5-Dihydro-7,8-dimethoxy-1-phenyl-3H-2,3-benzodiazepin-4-one.
October 2001, Acta crystallographica. Section C, Crystal structure communications,
L L Martin, and L L Setescak, and M Worm, and C A Crichlow, and H M Geyer, and J C Wilker
1-Benzyl-3-[(dimethyl-amino)methyl-ene]-4-phenyl-1H-1,5-benzodiazepine-2(3H)-thione.
April 2010, Acta crystallographica. Section E, Structure reports online,
L L Martin, and L L Setescak, and M Worm, and C A Crichlow, and H M Geyer, and J C Wilker
N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-methyl-benzene-sulfonamide.
December 2007, Acta crystallographica. Section E, Structure reports online,
Copied contents to your clipboard!