기관회원 [로그인]
소속기관에서 받은 아이디, 비밀번호를 입력해 주세요.
개인회원 [로그인]

비회원 구매시 입력하신 핸드폰번호를 입력해 주세요.
본인 인증 후 구매내역을 확인하실 수 있습니다.

회원가입
서지반출
Synthesis of New 4,5-3(2H)pyridazinone Derivatives and Their Cardiotonic, Hypotensive, and Platelet Aggregation Inhibition Activities
[STEP1]서지반출 형식 선택
파일형식
@
서지도구
SNS
기타
[STEP2]서지반출 정보 선택
  • 제목
  • URL
돌아가기
확인
취소
  • Synthesis of New 4,5-3(2H)pyridazinone Derivatives and Their Cardiotonic, Hypotensive, and Platelet Aggregation Inhibition Activities
  • Synthesis of New 4,5-3(2H)pyridazinone Derivatives and Their Cardiotonic, Hypotensive, and Platelet Aggregation Inhibition Activities
저자명
Amin. Enas Nashaat,Abdel-Alim. Abdel-Alim M.,Abdel-Moty. Samia G.,El-Shorbagi. Abdel-Naser A.,Abdel-Rahman. Mahran Sh.
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2010년|33권 1호|pp.25-46 (22 pages)
발행정보
대한약학회
파일정보
정기간행물|ENG|
PDF텍스트
주제분야
기타
이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
서지반출

기타언어초록

4,5-dihydro-3(2H)pyridazinones such as CI-914, CI-930 and pimobendan along with tetrahydropyridopyridazine (endralazine) and perhydropyridazinodiazepine (cilazopril) have been used as potent positive inotropes, antihypertensives as well as platelet aggregation inhibitors. Accordingly, the present work involves the synthesis of 24 target compounds; 4,5-dihydro-3(2H)pyridazinones in addition to seven reported intermediates. The chemical structures of the new compounds were assigned by microanalysis, IR, $^1H$-NMR spectral analysis and some representatives by mass spectrometry. The positive inotropic effect of the final compounds and the intermediates 12a-12d as well as the reported intermediate compound 10 was determined in-vitro on isolated rabbit heart in comparison to digoxin. Data obtained revealed that twelve of the test compounds exhibited higher effective response than digoxin, nine compounds elicited comparable effects to digoxin and eight compounds were less active than digoxin. In addition, four compounds approved marked significant hypotensive effect better than that of the previously reported compound 10. Moreover, two compounds induced complete platelet aggregation inhibition. The last two compounds were also subjected to determination of their $LD_{50}$ and they showed no signs of toxicity up to the dose level 300 mg/kg (i.p.), while the reported oral $LD_{50}$ of digoxin is 17.78 mg/kg. Correlation of cardiotonic and hypotensive activities with structures of compounds was tried and pharmacophore models were computed to get useful insight onto the essential structural features required for inhibiting phosphodiesterase-III in the heart muscles and blood vessels.