Design and synthesis of new azetidine‐steroid derivative with inotropic activity in a heart failure model

Abstract

Several steroid derivatives have prepared as inotropic drugs; however, there are few reports on azetidine‐steroid derivatives with inotropic activity. The aim of this study was to synthesize four azetidine‐steroid derivatives (compounds 3 to 6) to evaluate their biological activity on left ventricular pressure. The first stage was achieved by preparation of azetidine‐derivatives using reactions of etherification and addition. The second stage involves the evaluation of biological activity from azetidine derivatives on left ventricular pressure in a heart failure model using estrone as control. The results showed that only compound 3 increases left ventricular pressure compared with estrone, compounds 2 and 4 to 6. In conclusion, the positive inotropic effect exerted by compound 3 depends on the functional groups involved in their chemical structure.

Activity Exerted by Fluoro-2,4-Dioxaspiro[Bicyclo[3.3.1]Indene Derivative Against Ischemia/Reperfusion Injury

“…* Krebs-Henseleit was prepared using a previous method [16]. It is noteworthy that the heart was stabilized for a period of 15 minutes at a coronary flow of 10 ml/min; following, the hearts were subjected to ischemia/reperfusion process for 40 minutes by turning off the perfusion system [13]. Then, the perfusion system was restarted, and the hearts were reperfused by 40 minutes with Krebs-Henseleit solution.…”

“…In this way at the end of each experiment, the perfusion pump was stopped, and 0.5 ml of fluorescein solution (0.10%) was injected slowly through a sidearm port connected to the aortic cannula. The areas of the normal left ventricle non-risk region, area at risk, and infarct region were determined using methods previously reported [13]. Group III.…”

“…The compound 8-fluoro-1',3'-dihydro-2,4-dioxaspiro[bicyclo[3.3.1]nonane-3,2'indene]--1(9),5,7-triene (Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative, Figure 1) was prepared using a previously method [14]. In this way, all chemical properties, such as the 1 H and 13 C NMR spectra for the Fluoride-ether derivative, have already been reported. Furthermore, all reagents used in this investigation were acquired from Sigma-Aldrich Co., Ltd.…”

“…Several compounds have been prepared for the treatment of heart failure [5][6][7][8][9][10][11][12][13]; however, the biological activity is very confusing; perhaps this phenomenon could depend on the chemical structure of each compound. Analyzing these data, the aim of this investigation was to evaluate the biological activity exerted by a Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative (Figure 1) against using an ischemia/reperfusion model (Figure 1).…”

“…Other data showed the synthesis of some (N)-methanocarba phosphonate analogs of 5′-AMP with positive inotropic activity for heart failure [11]. Recently, two steroid derivatives have prepared as positive inotropic agents using a heart failure model [12,13]. All these data shown the preparation of several compounds with positive inotropic activity for the treatment of heart failure; however, their molecular mechanism is not clear, perhaps this phenomenon is due to different structure chemical of each compound.…”