69038-55-7

Upstream product

• 74401-96-0 2-(p-dimethylaminostyryl)-N-isopropyl-N'-phenyl-1,3-imidazolidine 
• 226068-21-9 N-benzyl-N-phenyl-2-(p-tolylsulfonyloxy)ethylamine 
• 122-98-5 2-Anilinoethanol 
• 226068-22-0 N-benzyl-N-phenyl-N'-isopropylethylenediamine 
• 6306-61-2 N-(2-chloroethyl)-N-isopropylamine hydrochloride 
• 62-53-3 aniline 

Downstream Products

• 74401-96-0 2-(p-dimethylaminostyryl)-N-isopropyl-N'-phenyl-1,3-imidazolidine 
• 226068-23-1 ethyl 1-phenyl-4-isopropylpiperazine-2-carboxylate 
• 226068-24-2 ethyl 1-isopropyl-4-phenylpiperazine-2-carboxylate 

Relevant academic research and scientific papers

Design and synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type ii diabetes. 2. Syntheses and biological activities of 1,4-dialkyl-, 1,4-dibenzyl, and 1-benzyl-4-alkyl-2-(4',5'- dihydro-1'H-imidazol-2'-yl)piperazines and isosteric analogues of imidazoline

Piperazine derivatives have been identified as new antidiabetic compounds. Structure-activity relationship studies in a series of 1-benzyl- 4-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines resulted in the identification of 1-methyl-4-(2',4'-dichlorobenzyl)-2-(4',5'-dihydro-1'H- imidazol-2'-yl)piperazine, PMS 812 (S-21663), as a highly potent antidiabetic agent on a rat model of diabetes, mediated by an important increase of insulin secretion independently of α2 adrenoceptor blockage. These studies were extended to find additional compounds in these series with improved properties. In such a way, substitution of both piperazine N atoms was first optimized by using various alkyl, branched or not, and benzyl groups. Second, some modifications of the imidazoline ring and its replacement by isosteric heterocycles were carried out, proceeding from PMS 812, to evaluate their influence on the antidiabetic activity. The importance of the distance between the imidazoline ring and the piperazine skeleton was studied third. Finally, the influence of the N-benzyl moiety was also analyzed compared to a direct N-phenyl substitution. The pharmacological evaluation was performed in vivo using glucose tolerance tests on a rat model of type II diabetes. The most active compounds were 1,4-diisopropyl-2-(4',5'-dihydro-1'H-imidazol-2'- yl)piperazine (41a), PMS 847 (S-22068), and 1,4-diisobutyl-2-(4',5'-dihydro- 1'H-imidazol-2'-yl)piperazine (41b), PMS 889 (S-22575), which strongly improved glucose tolerance without any side event or hypoglycemic effect. More particularly, PMS 847 proved to be as potent after po (100 μmol/kg) as after ip administration and appears as a good candidate for clinical investigations.

General-Acid-Catalyzed Imidazolidine Ring Opening. Hydrolysis of Symmetrical and Unsymmetrical 1,3-Imidazolidines of p-Dimethylaminocinnamaldehyde

Rate constants have been obtained for ring opening of a series of symmetrical and unsymmetrical 1,3-imidazolidines of p-dimethylaminocinnamaldehyde in H2O at 30 deg C.Ring opening of the N,N'-diphenyl derivative is catalyzed by hydronium ion (kH = 2290 M-1 s-1), and gives rise to a cationic Schiff base with λmax 505 nm.The reaction is considerably slower in D2O than in H2O, kH/kD = 3.0.At pH greater than 6 ring opening is pH independent (k0' = 1.8 10-2 s-1).Ring opening of the N,N'-dimethylimidazolidine to a species with λmax 480 nm is hydronium ion catalyzed (kH = 2 109 M-1 s-1) and pH independent at pH values above 11.5.The unsymmetrical N-isopropyl-N'-phenyl derivative opens to give a species with λmax 480 nm and with rate constants that are similar to those for the N,N'-dimethyl substituted compound (kH = 4 107 M-1 s-1).Consequently, this species must be the N-isopropyl Schiff base resulting from breaking of the C-N phenyl bond.General acid catalysis of ring opening was observed in trimethylamine buffer.Only at pH values less than 6 does C-N isopropyl bond breaking become competitive, giving the N-phenyl Schiff base (λmax 512 nm).The interconversion of Schiff bases (480 -> 512 nm) is general acid catalyzed by buffer acids or a kinetic equivalent.Thus, ring-opening reactions of imidazolidines have been directly monitored, and general acid catalysis has been observed.It can be concluded that, in reactions of the neutral species and hydronium ion, or a general acid, the imidazolidine ring opens preferentially to give the most stable carbonium ion with expulsion of the least basic nitrogen.In the reaction of the unsymmetrical imidazolidine at low pH when there are two protons in the transition state, either C-N bond may break, and the C-N phenyl Schiff base is the favored product.These results are discussed in relation to reactions of N5,N10-methylenetetrahydrofolic acid.