3-[3-[[2-(3,4-DIMETHOXYPHENYL)ETHYL]METHYLAMINO]PROPYL]-1,3,4,5-TETRAHYDRO-7,8-DIMETHOXY-2H-3-BENZAZEPIN-2-ONE HYDROCHLORIDE Chemical Properties

Melting point:

188° and mp 168°

storage temp. 

2-8°C

solubility 

H₂O: ~14 mg/mL

form 

solid

color 

white

Water Solubility 

Soluble in water (100mM)

Safety Information

Safety Statements 

22-24/25

WGK Germany 

3

MSDS

• Language:English Provider:SigmaAldrich

3-[3-[[2-(3,4-DIMETHOXYPHENYL)ETHYL]METHYLAMINO]PROPYL]-1,3,4,5-TETRAHYDRO-7,8-DIMETHOXY-2H-3-BENZAZEPIN-2-ONE HYDROCHLORIDE Usage And Synthesis

Originator

ZATEBRADINE HYDROCHLORIDE,Boenhringer Ingelheim

Uses

Zatebradine Hydrochloride exhibits bradycardic properties and blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN). It is also a sinus node inhibitor.

Manufacturing Process

A suspension of 1-[7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl]-3- (N-benzylmethylamino)propane and 10% palladium-on-charcoal in glacial acetic acid was hydrogenated at 50°C and at a hydrogen pressure of 5 bar. After the catalyst had been filtered off, the solvent was evaporated in vacuum, and the residue was taken up in methylene chloride. After the solution had been extracted with an aqueous sodium bicarbonate solution and washed with water, it was dried over magnesium sulfate, evaporated and purified over silica gel with methylene chloride and then with increasing amounts of methanol (up to 10%). The N-[3-(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3- benzazepin-2-one-3-yl)propyl]methylamine hydrochloride. Yield: 87% of theory. Melting point: 110°C (dec.).
1.26 g (20 mmols) of sodium cyanoborohydride were added to a solution of 3.29 g (10 mmols) of N-[3-(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3- benzazepin-2-one-3-yl)propyl]methylamine hydrochloride and 1.8 g (10 mmol) of 2-(3,4-dimethoxyphenyl)acetaldehyde in 40 ml of ethanol, while maintaining a pH of 6-7 by the addition of 2 N hydrochloric acid, and stirring was continued for 48 h at room temperature. After evaporating the solution in vacuum, the residue was taken up in dilute hydrochloric acid and extracted twice with ether. Subsequently, the aqueous phase was made alkaline and extracted three times with methylene chloride, and the organic phase was evaporated and purified on silica gel. The 1-[7,8-dimethoxy-1,3,4,5- tetrahydro-2H-3-benzazepin-2-on-3-yl]-3-[N-methyl-N-(2-{3,4- dimethoxyphenyl}ethyl)amino]propane was obtained.

Therapeutic Function

Bradycardic

Biological Activity

Bradycardic agent that produces use-dependent inhibition of hyperpolarization-activated current (I f ) in sinoatrial node cells (EC 50 = 480 nM) and Purkinje fibres. Displays negative chronotropic activity in isolated guinea pig atria (EC 50 of 13.4 μ M).

Biochem/physiol Actions

Zatebradine is a bradycardiac agent.

storage

+4°C (desiccate)

3-[3-[[2-(3,4-DIMETHOXYPHENYL)ETHYL]METHYLAMINO]PROPYL]-1,3,4,5-TETRAHYDRO-7,8-DIMETHOXY-2H-3-BENZAZEPIN-2-ONE HYDROCHLORIDE(91940-87-3)Related Product Information

• Zatebradine
• PTH-EPSILON-PHENYLTHIOCARBAMYL-DL-LYSINE
• N-(2-Bromo-3-oxospiro[3.5]non-1-en-1-yl)-4-(2,7-naphthyridin-1-ylamino)-L-phenylalanine