7216-22-0

Usage

Uses

Used in Pharmaceutical Research:
2,3,4,5-Tetrahydro-1H-2-benzazepine Hydrochloride is used as a molecular guide in the comparative molecular field analysis (CoMFA) of phenylethanolamine N-methyltransferase (PNMT) and the α2-adrenoceptor. Its application is crucial for the development of selective inhibitors of PNMT versus the α2-adrenoceptor, which can have significant implications in the treatment of various medical conditions related to these targets.
In the field of medicinal chemistry, 2,3,4,5-Tetrahydro-1H-2-benzazepine Hydrochloride serves as a valuable tool for understanding the structural requirements and interactions of PNMT and α2-adrenoceptor inhibitors. By using 2,3,4,5-Tetrahydro-1H-2-benzazepine Hydrochloride in CoMFA studies, researchers can gain insights into the design and optimization of more potent and selective inhibitors, ultimately leading to the development of novel therapeutic agents.

InChI:InChI=1/C10H13N.ClH/c1-2-5-10-8-11-7-3-6-9(10)4-1;/h1-2,4-5,11H,3,6-8H2;1H

Upstream product

• 861779-45-5 2-(3-chloro-propyl)-benzylamine 
• 6729-50-6 2,3,4,5-tetrahydro-1H-2-benzazepin-1-one 
• 529-34-0 3,4-dihydronaphthalene-1(2H)-one 
• 55223-26-2 3-(2-bromophenyl)propanamide 
• 3433-80-5 1-Bromo-2-bromomethyl-benzene 
• 25040-17-9 methyl 3-[2-(methoxycarbonyl)phenyl]propionate 
• 136863-23-5 3-[2-(hydroxymethyl)phenyl]propan-1-ol 
• 610-94-6 2-bromobenzoic acid methyl ester 
• 34288-40-9 2-(E)-[2-methoxycarbonylphenyl]acrylic acid methylester 
• 17724-38-8 1,2,4,5-tetrahydro-3H-benzo[c]azepin-3-one 
• 530-93-8 1,2,3,4-tetrahydronaphthalen-2-one 
• 861531-44-4 2-(3-phenoxy-propyl)-benzonitrile 
• 861800-20-6 2-(3-phenoxy-propyl)-benzylamine 
• 111874-94-3 C-(3,4-Dichloro-phenyl)-N-(3-phenyl-propyl)-methanesulfonamide 

Downstream Products

• 111908-05-5 Picric acid; compound with 2,3,4,5-tetrahydro-1H-benzo[c]azepine 
• 330182-62-2 (3S,10bR)-3-Phenyl-2,3,4,5,6,10b-hexahydro-1-oxa-3a-aza-benzo[e]azulene 
• 330182-61-1 (2R,10bR)-2-Phenyl-2,3,4,5,6,10b-hexahydro-1-oxa-3a-aza-benzo[e]azulene 
• 330182-59-7 2-(2-oxy-1,3,4,5-tetrahydro-benzo[c]azepin-2-yl)-1-phenyl-ethanol 
• 330182-60-0 2-(2-oxy-1,3,4,5-tetrahydro-benzo[c]azepin-2-yl)-2-phenyl-ethanol 
• 61034-51-3 (+/-)1-benzyl-2,3,4,5-tetrahydro-1H-2-benzazepine 

Relevant academic research and scientific papers

Discovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists

The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound 1 was identified as a weak RORγt agonist during in-house library screening. Changes in LHS core of 1 led to the identification of tetrahydroquinoline compound 6 as a partial RORγt agonist (max. act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound 8g (EC50 = 8.9 ± 0.4 nM, max. act. = 104.5%) and benzomorpholine compound 9g (EC50 = 7.5 ± 0.6 nM, max. act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of 8g; 59.4% activation at 300 nM of 9g). The binding modes of 8g and 9g as well as the two RORγt inverse agonists accidentally discovered were also discussed.

Chemoenzymatic Synthesis of Substituted Azepanes by Sequential Biocatalytic Reduction and Organolithium-Mediated Rearrangement

Enantioenriched 2-aryl azepanes and 2-arylbenzazepines were generated biocatalytically by asymmetric reductive amination using imine reductases or by deracemization using monoamine oxidases. The amines were converted to the corresponding N′-aryl ureas, which rearranged on treatment with base with stereospecific transfer of the aryl substituent to the 2-position of the heterocycle via a configurationally stable benzyllithium intermediate. The products are previously inaccessible enantioenriched 2,2-disubstituted azepanes and benzazepines.

Structure-Activity Study of N -((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H -indole-2-carboxamide (SB269652), a Bitopic Ligand That Acts as a Negative Allosteric Modulator of the Dopamine D2 Receptor

We recently demonstrated that SB269652 (1) engages one protomer of a dopamine D2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit the binding of dopamine at the other protomer. Herein, we investigate structural determinants for allostery, focusing on modifications to three moieties within 1. We find that orthosteric "head" groups with small 7-substituents were important to maintain the limited negative cooperativity of analogues of 1, and replacement of the tetrahydroisoquinoline head group with other D2R "privileged structures" generated orthosteric antagonists. Additionally, replacement of the cyclohexylene linker with polymethylene chains conferred linker length dependency in allosteric pharmacology. We validated the importance of the indolic NH as a hydrogen bond donor moiety for maintaining allostery. Replacement of the indole ring with azaindole conferred a 30-fold increase in affinity while maintaining negative cooperativity. Combined, these results provide novel SAR insight for bitopic ligands that act as negative allosteric modulators of the D2R.

Facile and simple synthesis of N -alkyl and N -aryl 2-benzazepines by nucleophilic heteroannulation

An efficient and practical synthesis of N-alkyl and N-aryl 2-benzazepine has been developed. The key steps involved in the synthesis were palladium-mediated Heck reaction followed by aza heterocyclic ring construction by nucleophilic heteroannulation. This four-step sequence synthetic protocol gave moderate to good yields for a wide range of substrates. Subsequently, functionalization of the synthesized compound was carried out under Heck and Suzuki reaction conditions.

Neuroprotective tri- and tetracyclic BChE inhibitors releasing reversible inhibitors upon carbamate transfer

Tri- and tetracyclic nitrogen-bridgehead compounds were designed and synthesized to yield micromolar cholinesterase (ChE) inhibitors. Structure-activity relationships identified potent compounds with butyrylcholinesterase selectivity. These compounds were selected as starting points for the design and synthesis of carbamate-based (pseudo)irreversible inhibitors. Compounds with superior inhibitory activity and selectivity were obtained and kinetically characterized also with regard to the velocity of enzyme carbamoylation. Structural elements were identified and introduced that additionally showed neuroprotective properties on a hippocampal neuronal cell line (HT-22) after glutamate-induced intracellular reactive oxygen species generation. We have identified potent and selective pseudoirreversible butyrylcholinesterase inhibitors that release reversible inhibitors with neuroprotective properties after carbamate transfer to the active site of cholinesterases.

BICYCLOANILINE DERIVATIVE

The invention relates to a compound of a general formula (I): wherein A1 and A2 each mean a nitrogen atom or an optionally-substituted methine group; Ring B means a 5-membered to 7-membered aliphatic ring, or a spiro or bicyclo ring formed from the aliphatic ring and any other 3-membered to 7-membered aliphatic ring; R1 means a hydrogen atom, or an optionally-substituted C1-C6 alkyl group, or an optionally-substituted aryl, aralkyl or heteroaryl group; R2 means an optionally-substituted aryl, aralkyl or heteroaryl group; and X means a group of =NH or =O, etc. Based on its excellent Wee1 kinase-inhibitory effect, the compound of the invention has cell growth-inhibitory effect and has an additive/synergistic effect with any other anticancer agent, and is therefore useful in the field of medicine.

SUBSTITUTED PROPIOLIC ACID AMIDES AND THEIR USE FOR PRODUCING DRUGS

The present invention relates to substituted propiolic acid amides, to methods for the production thereof, to medicaments containing these compounds and to the use thereof for producing medicaments.

COMPOUND INHIBITING DIPEPTIDYL PEPTIDASE IV

The invention aims to provide a dipeptidyl peptidase IV inhibitor which is satisfactory in respect of activity, stability and safety and has an excellent action as a pharmaceutical agent. The invention is directed to a compound represented by the following general formula or a pharmaceutically acceptable salt thereof: wherein R1 and R2 each represents hydrogen, an optionally substituted C1-6 alkyl group, or -COOR5 whereupon R5 represents hydrogen or an optionally substituted C1-6 alkyl group, or R1 and R2, together with a carbon atom to which they are bound, represent a 3- to 6-membered cycloalkyl group, R3 represents hydrogen or an optionally substituted C6-10 aryl group, R4 represents a hydrogen or a cyano group, D represents -CONR6-, -CO- or -NR6CO-, R6 represents hydrogen or an optionally substituted C1-6 alkyl group, E represents -(CH2)m- whereupon m is an integer of 1 to 3, -CH2OCH2-, or -SCH2-, n is an integer of 0 to 3, and A represents an optionally substituted bicyclic heterocyclic group or bicyclic hydrocarbon group.

Quinoxaline compounds

Certain amidophenyl-sulfonylamino-quinoxaline compounds are CCK2 modulators useful in the treatment of CCK2 mediated diseases.

Piperadinyl-substituted pyridylalkane, alkene and alkine carboxamides

The invention relates to new piperidinyl-substituted pyridyl carboxamides of the general formula (I), wherein the structure element E has meanings (E1) or (E2) and whereby the heterocyclic ring can optionally have a double bond. These substances have especially high cytostatic activities and pronounced immunosuppressive properties which make them suitable for therapeutic treatment in broad tumor spectrum.