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Chemical & Pharmaceutical Bulletin 2022The atropisomeric properties of N-alkyl and N-aryl 4-substituted 5H-dibenz[b,f]azepines were investigated. The N-alkylation and N-arylation of 4-Cl or 4-Me substituted...
The atropisomeric properties of N-alkyl and N-aryl 4-substituted 5H-dibenz[b,f]azepines were investigated. The N-alkylation and N-arylation of 4-Cl or 4-Me substituted compounds was performed; however, none of the atropisomers produced were separated by chiral HPLC. Notably, we observed that the rotation of the four axes (ax. 1-4) in the 4-substituted 5H-dibenz[b,f]azepine structure is so rapid that N-alkylation or N-arylation is not sufficient to freeze it at room temperature. Additionally, the X-ray crystal structures of N-aryl compounds 13b and 14a indicated that the N atom in the triphenyl amine moiety in their structures shows sp-like property.
Topics: Azepines
PubMed: 35908923
DOI: 10.1248/cpb.c22-00265 -
European Journal of Medicinal Chemistry Dec 2017The search for new lead compounds of simple structure, displaying highest quality anti-tumor potency with new mechanisms of action and least adverse effects is the major... (Review)
Review
The search for new lead compounds of simple structure, displaying highest quality anti-tumor potency with new mechanisms of action and least adverse effects is the major intention of cancer drug discovery now a days. For the time being, indole-fused azepines emerged as a simple class of compounds prolifically designed with strong pharmacological significances in particular of cancer protecting ability. In the recent years from the efforts of our research group, indole-fused heteroazepines, a simple structural class achieved by fusion of indole with oxygen, sulphur and nitrogen containing heteroazepine rings, have known for its superior outcomes in cancer treatment. Surprisingly, the chemistry and biology of these unique families with an amazing role in cancer drug discovery has remained broadly unexplored. This short review is consequently an endeavor to highlight the preliminary ideas over this structural class and to draw the medical attention towards future development of indole-fused azepines and analogues for their promising function in cancer drug discovery.
Topics: Animals; Antineoplastic Agents; Azepines; Chemistry Techniques, Synthetic; Drug Design; Humans; Indoles; Neoplasms; Structure-Activity Relationship
PubMed: 28803677
DOI: 10.1016/j.ejmech.2017.07.042 -
Organic Letters Oct 2022The asymmetric synthesis of bridged tetrahydrobenzo[]azepine and oxepine derivatives through chiral Brønsted acid catalyzed asymmetric aza-Piancatelli...
The asymmetric synthesis of bridged tetrahydrobenzo[]azepine and oxepine derivatives through chiral Brønsted acid catalyzed asymmetric aza-Piancatelli rearrangement/Michael addition sequence has been developed. The reaction proceeds under mild reaction conditions to afford the final bridged cyclic products in good yields with excellent enantio- and diastereoselectivities.
Topics: Azepines; Catalysis; Molecular Structure; Stereoisomerism
PubMed: 36169238
DOI: 10.1021/acs.orglett.2c02833 -
The Journal of Organic Chemistry Apr 2022Herein, we report a multistep synthesis of polycyclic tetrahydroisoquinolines and tetrahydrobenzo[]azepines starting from Wang resin-immobilized allylglycine. After...
Herein, we report a multistep synthesis of polycyclic tetrahydroisoquinolines and tetrahydrobenzo[]azepines starting from Wang resin-immobilized allylglycine. After sulfonylation with 2/4-nitrobenzenesulfonyl chlorides, Mitsunobu alkylation with various phenylalkynols yielded the corresponding (phenylprop-2-yn-1-yl)-sulfonamides. "Interior" ring-closure enyne metathesis (RCEM) using a Grubbs catalyst second generation (Ru2) yielded functionalized tetrahydroisoquinoline/tetrahydrobenzo[]azepine intermediates. "East-side" [4 + 2] cycloaddition with representative dienophiles was followed by the "west-side" construction of different heterocycles using various electrophiles to finally furnish a set of novel molecular frameworks bearing fused [6 + 6] or [6 + 7] rings. The developed methodology enables the facile parallel synthesis of novel, pharmacologically promising compounds derived from privileged scaffolds.
Topics: Allylglycine; Azepines; Cyclization; Polymers; Tetrahydroisoquinolines
PubMed: 35344355
DOI: 10.1021/acs.joc.2c00039 -
Lancet (London, England) Aug 1983
Comparative Study
Topics: Anesthesia, Obstetrical; Animals; Apnea; Azepines; Female; Humans; Infant, Newborn; Meperidine; Meptazinol; Pregnancy
PubMed: 6135879
DOI: No ID Found -
Angewandte Chemie (International Ed. in... Dec 2017Biocatalytic retrosynthetic analysis of dibenz[c,e]azepines has highlighted the use of imine reductase (IRED) and ω-transaminase (ω-TA) biocatalysts to establish the...
Biocatalytic retrosynthetic analysis of dibenz[c,e]azepines has highlighted the use of imine reductase (IRED) and ω-transaminase (ω-TA) biocatalysts to establish the key stereocentres of these molecules. Several enantiocomplementary IREDs were identified for the synthesis of (R)- and (S)-5-methyl-6,7-dihydro-5H-dibenz[c,e]azepine with excellent enantioselectivity, by reduction of the parent imines. Crystallographic evidence suggests that IREDs may be able to bind one conformer of the imine substrate such that, upon reduction, the major product conformer is generated directly. ω-TA biocatalysts were also successfully employed for the production of enantiopure 1-(2-bromophenyl)ethan-1-amine, thus enabling an orthogonal route for the installation of chirality into dibenz[c,e]azepine framework.
Topics: Azepines; Biocatalysis; Molecular Structure; Oxidoreductases Acting on CH-NH Group Donors; Stereoisomerism; Transaminases
PubMed: 29024400
DOI: 10.1002/anie.201708453 -
European Journal of Medicinal Chemistry Aug 2021Hymenialdisine an alkaloid of oroidin class has drawn the attention of researchers owing to its unique structural features and interesting biological properties.... (Review)
Review
Hymenialdisine an alkaloid of oroidin class has drawn the attention of researchers owing to its unique structural features and interesting biological properties. Hymenialdisine exhibited promising inhibitory activity against a number of therapeutically important kinases viz., CDKs, GSK-3β etc., and showed anti-cancer, anti-inflammatory, anti-HIV, neuroprotective, anti-fouling, anti-plasmodium properties. Hymenialdisine and other structurally related oroidin alkaloids such as dibromo-hymenialdisine, stevensine, hymenin, axinohydantoin, spongicidines A-D, latonduines and callyspongisines contain pyrrolo[2,3-c] azepin-8-one core in common. Keeping in view of the interesting structural and therapeutic features of HMD, several structural modifications were carried around the fused-azepinone core which resulted in a number of diverse structural motifs like indolo-azepinones, paullones, aza-paullones, darpones and 5,7-dihydro-6H-benzo[b]pyrimido[4,5-d] azepin-6-one. In this review, an attempt is made to collate and review the structures of diverse hymenialdisine and related fused-azepinones of synthetic/natural origin and their biological properties.
Topics: Animals; Anti-HIV Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Azepines; Humans; Molecular Structure; Neuroprotective Agents; Porifera
PubMed: 33901899
DOI: 10.1016/j.ejmech.2021.113445 -
Journal of Medicinal Chemistry Jan 1968
Topics: Animals; Azepines; Benzene Derivatives; Central Nervous System; Methods; Mice; Pentylenetetrazole
PubMed: 5637170
DOI: 10.1021/jm00307a046 -
Drugs Oct 2014Suvorexant (Belsomra(®)), a first-in-class, orally active dual orexin-1 receptor and orexin-2 receptor antagonist, has been developed by Merck for the treatment of... (Review)
Review
Suvorexant (Belsomra(®)), a first-in-class, orally active dual orexin-1 receptor and orexin-2 receptor antagonist, has been developed by Merck for the treatment of insomnia. Variations in the levels of the neuropeptides orexin A and orexin B have been linked to circadian rhythms and wakefulness. Orexin-producing neurons in the lateral hypothalamus regulate wakefulness by signalling through orexin receptors. Blockade of orexin receptors is known to promote sleep. Suvorexant was approved in the US in August 2014 for the treatment of adults with sleep onset and/or sleep maintenance insomnia. The drug is also preregistration in Japan, with approval submissions planned for other countries worldwide for this indication. This article summarizes the milestones in the development of suvorexant leading to this first approval for insomnia.
Topics: Azepines; Drug Approval; Humans; Orexin Receptor Antagonists; Sleep Initiation and Maintenance Disorders; Triazoles
PubMed: 25227290
DOI: 10.1007/s40265-014-0294-5 -
Organic Letters Oct 2022Herein, we report the first asymmetric total synthesis of iheyamine B from 2,2'-bisindoloazepinone using the stereoselective construction of the -vicinal 2-oxopropyl...
Herein, we report the first asymmetric total synthesis of iheyamine B from 2,2'-bisindoloazepinone using the stereoselective construction of the -vicinal 2-oxopropyl moiety in the azepine scaffold. The asymmetric decarboxylative allylic alkylation provided the α-allylated 2,2'-bisindoloazepinone intermediate. The subsequent conversion of the lactam moiety into another allyl group in a -selective manner followed by Wacker oxidation of each allyl unit to the corresponding 2-oxopropyl group completed the total synthesis of iheyamine B.
Topics: Alkylation; Allyl Compounds; Azepines; Catalysis; Lactams; Palladium; Stereoisomerism
PubMed: 36169573
DOI: 10.1021/acs.orglett.2c02788