Thiophene systems. 9. Thienopyrimidinedione derivatives as potential antihypertensive agents

Abstract

A series of thieno[3,4-d]-, thieno[3,2-d]-, and thieno[2,3-d]pyrimidine-2,4-diones with (phenylpiperazinyl)alkyl substitution at N-3 have been synthesized and evaluated for antihypertensive effects in spontaneously hypertensive rats (SHR). These 49 compounds were compared to the vasodilator standards prazosin and the isosteric quinazoline-2,4-dione SGB 1534. Substitution at the 2-, 3-, or 4-position of the phenyl ring was examined, with that at the 2-position more potent than 4-substitution while the isomeric 3-substituted compounds were least potent. Neither alkylation nor acylation at the N-1 position improved the antihypertensive effects as compared to hydrogen. The three thienopyrimidine-2,4-diones (3-5) that contain a [(2-methoxyphenyl)piperazinyl]ethyl moiety at N-3 and hydrogen at N-1 were found to be potent oral antihypertensive agents in the SHR with doses (mg/kg, po) for reducing systolic blood pressure (SBP) by 50 mmHg (ED-50SBP) of 0.21, 0.19, and 1.0, respectively. The compounds 1-5 were further evaluated for alpha blocking potency by measuring the iv doses necessary to antagonize the phenylephrine pressor response by 50% (ED50) in the SHR. The ED50 values (micrograms/kg) are 10.4, 3.3, 1.7, 2.1, and 15.4, respectively. These results clearly show that all three thiophene systems have potent activity as antihypertensive agents and that 3 and 4 are more potent than 1 or 2 as alpha 1-antagonists in vivo.

Synthesis and Antibacterial Activity of Thienopyrimidine Amide Derivatives

“…This scaffold shows a broad spectrum of biological activities. The thienopyrimidines were assessed as antitumour [6][7][8][9], medicine [10], enzyme [11][12][13][14], phosphodiesterase inhibitors [15], antioxidative [16,17], antimalarial drug [18,19], antibacterial drug [20], antiviral [21], antifungal [22,23], medication [24], antiplatelet [25] and medicament [26]. In view of these observations, the varied biological property of thienopyrimidine pharmacophore impelled to synthesize the title compounds.…”

Microwave-assisted synthesis of 2-acetyl-5-arylthiophenes and 4-(5-arylthiophen-2-yl)thiazoles via Suzuki coupling in water

“…In addition, thiophene-based molecules have shown numerous biological activities such as antitumor, 4 analgesic, 5 anti-inflammatory, 6 and antibacterial against Gram-positive bacteria. 7 Suzuki-Miyaura reactions are among the most powerful tools for construction of carbon-carbon bond in organic synthesis both in industry and academia.…”

Synthesis, antimicrobial activity and molecular modeling study of some new pyrimidine derivatives

“…The diverse array of biological and pharmacological activities of pyrimidines including antimicrobial [2][3][4][5], antihypertensive [6], antitumor [7][8][9][10][11][12], antiviral [13,14], anti-HIV agents [15][16][17], in addition to their cardiovascular [18,19] and diuretic [20,21] properties. Furthermore, some pyrimidines were used as hypnotic drugs [22], in addition to their activity as calcium-sensing receptor antagonists [23] and as antagonists of the human A2A adenosine receptor [24] as well.…”