54851-30-8

Upstream product

• 54527-68-3 2-chloroethyl acetoacetate 
• 40100-28-5 isopropyl 3-aminocrotonate 
• 99-61-6 3-nitro-benzaldehyde 
• 62760-10-5 2-chloroethyl 2-(3-nitrobenzyliden)acetoacetate 
• 542-08-5 isopropyl acetoacetate 

Downstream Products

• 75130-56-2 2-acetoxyethyl isopropyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate 
• 82219-48-5 O-Demethyl-Nimodipine Oxidized 
• 82219-47-4 (+/-)-O-Demethyl-Nimodipine 

Relevant academic research and scientific papers

Asymmetric N-(3,3-diphenylpropyl)aminoalkyl esters of 4-aryl-2,6- dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acids with antihypertensive activity

A series of asymmetric 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates characterized by the presence of a 3,3-diphenylpropylamino moiety in one of the ester groups were synthesized. They exhibited remarkable antihypertensive activity in spontaneously hypertensive rats as well as affinity for the 1,4- dihydropyridines binding site labelled by 3H-nitrendipine in the calcium channel. Introduction of this bulky and lipophilic amine confers to the whole series an elevated level of antihypertensive activity and a long duration of action, a structure-dependent modulation of the activity being found only in the subset characterized by the presence of a branched propylene bridge between the ester and the amino groups. The presence of the amino group is essential for oral activity. Out of this series, compound 9u (Rec 15/2375- lercanidipine) was selected for clinical development and obtained marketing authorization as an antihypertensive in several countries.

Nimodipine: Synthesis and metabolic pathway

Key step of the synthesis of the calcium antagonistic cerebral vasodilator (±) isopropyl-2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (Bay e 9736, nimodipine) is the cyclising Michael addition. A pharmacokinetic study with 14C-nimodipine in the rat revealed as major metabolites the dihydropyridines as well as the pyridines. A potential metabolic pathway is discussed involving ether cleavage and oxidation to the pyridine form as primary biotransformation steps. Reference metabolites were synthesized using 1,4-dihydropyridines with appropriate functionalities as precursors.

1,4-Dihydropyridine derivatives

There are provided novel 1,4-dihydropyridine derivatives, particularly 2,6-dimethyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-β-(N-benzyl-N-methylamino)ethyl ester and 5-methyl ester. The 1,4-dihydropyridine derivatives are characterized by cerebral vascular dilator activity.