Aminoacetyl Moiety as a Potential Surrogate for Diacylhydrazine Group of SC-51089, a Potent PGE₂ Antagonist, and Its Analogs

Abstract

8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a functional PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activity. During metabolism in cultured rat hepatocytes, SC-51089, which contains a diacylhydrazine moiety, has been shown to release hydrazine. Analogs of SC-51089, in which the diacylhydrazine functionality has been replaced by isosteric and isoelectronic groups, have been synthesized and have been shown to be analgesics and PGE2 antagonists of the EP1 subtype. This report discusses the structure-activity relationships within these series.

Synthesis of 1,3-Oxazepine Derivatives Derived from 2-(1H-Benzo[d][1,2,3]Triazol-1-yl) Acetohydrazide by Using Microwave Irradiation

“…But protons at carbons (11,12) in seven membered ring appeared at 6.1-6.3 ppm, the peak at 8.1 ppm was attributed to the chemical shift of carbon (9) proton due to between two highly electronegativity atoms (oxygen and nitrogen). The 1HNMR spectrum of the compound (C11 Figure 3) displayed a single peak appeared at 11.8 ppm which was assigned to chemical shift of NH and multiplet peak at 7.2 -7.9 ppm which were assigned to chemical shifts of aromatic protons at carbons (2,3,4,5,6,14,15,16,17). The peak at 5.5 ppm was attri- (13) proton its between carbonyl amide and benzotriazol moiety.…”

“…The 1 HNMR spectrum of compund (c 15 Figure 2) displayed a single peak appeared at 11.8 ppm which was assigned to chemical shift of NH and multiplet peak at 7.3 -7.8 ppm which were assigned to chemical shifts of aromatic protons at carbons (4,5,6,7,8,16,17,18,19). The peak at 5.5 ppm was attributed to the chemical shift of carbon (15) proton its between carbonyl amide and benzotriazol moiety.…”

“…It is prepared by the pericyc-liccyclo addition of Schiff base or hydrazone with maleic, phthalic and succinic anhydrides [7] [8] [9] [10] [11] and also by green chemistry method [12] [13]. Oxazepine derivatives were found to exhibit a vast variety of biological activities like antibacterial [14], antifungal [15], hypnotic muscle relaxant [16], antagonistic [17], inflammatory [18] and antiepileptic [19]. Microwave-assisted reactions within shorter time are becoming popular for organic chemists [20] [21] [22] and had recently been reviewed [23] [24].…”

Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells

“…In order to determine whether EP1 receptors are also involved, the EP1 receptor antagonist SC-51089 [32][33][34] was employed. Initially, the effect of increasing concentrations of SC-51089 on the stimulatory effect of 0.028 μM PGE 1 was examined.…”

Oxazepine Derivative as an Antitumor Agent and Snail1 Inhibitor against Human Colorectal Adenocarcinoma

“…It is prepared by the pericycliccycloaddition of schiff bases with maleic, phthalic, nitrophthalic and succinic anhydrides [1]. Oxazepine derivatives was found to exhibit a vast variety of biological activities like antibacterial [2], antifungal [3], hypnotic muscle relaxant [4], antagonistic [5], antiinflammatory [6], telomerase inhibitors [7] and antiepileptic [8]. Dibenzo[b,f] [1,4]oxazepine has been taken up to the design of potent progesterone receptor antagonists, p38 MAP kinase inhibitors, TRPAI ion channel modulators and histone deacetylase inhibitors [9].…”