Novel pirfenidone analogues: Synthesis of pyridin-2-ones for the treatment of pulmonary fibrosis

被引：25

作者：

Ammar, Yousry A.

Ismail, Magda M. F. ^{[1
]}

El-Sehrawi, Hend M.

Noaman, Eman

Bayomi, Ashraf H.

Shawer, Taghreed Z.

机构：

[1] Al Azhar Univ, Fac Pharm Girls, Dept Pharmaceut Chem, Nasr City 11754, Cairo, Egypt

[2] Al Azhar Univ, Dept Chem, Fac Sci, Nasr City 11754, Cairo, Egypt

[3] Atom Energy Author, Dept Radiat Biol, Nat Ctr Radiat Res & Technol, Cairo, Egypt

[4] Al Azhar Univ, Dept Organ Chem, Fac Pharm, Nasr City, Cairo, Egypt

来源：

ARCHIV DER PHARMAZIE | 2006年 / 339卷 / 08期

关键词：

antifibrotic activity; bicyclic pyridone; 2-pyridone; synthesis;

D O I：

10.1002/ardp.200600017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of polysubstituted 1-aryl-2-oxo-1,2-dihydropyridine-3-carbonitriles and pyrazolo[3,4b]pyridine-5-carbonitriles and pyrido[2,3-dlpyrimidine-6-carbonitriles have been synthesized and tested for their antifibrotic activity. Among the tested compounds, compounds IIc and IVb exhibited higher antifibrotic activity than the standard pirfenidone PD with a reduction of the hydroxyproline level to 50 and 140 mu mol/lung, respectively. However, bicyclic pyridone VIIIb displayed a high mortality rate. Detailed syntheses, spectroscopic and biological data are reported.

引用

页码：429 / 436

页数：8

共 26 条

[1] Studies with polyfunctionally substituted heteroaromatics: A novel synthesis of substituted 4,8-diaminoisoquinolines as potential antiparasitic agents [J].

Al-Omran, F ;

Abou El-Khair, A ;

Elnagdi, MH .

JOURNAL OF CHEMICAL RESEARCH-S, 1998, (12) :798-799

[2]

Al-Shiekh MA, 2004, J CHEM RES, P174

[3]

BOWERS GN, 1966, CLIN CHEM, V12, P70

[4] Effects of dietary vitamin E supplementation on pulmonary morphology and collagen deposition in amiodarone- and vehicle-treated hamsters [J].

Card, JW ;

Leeder, RG ;

Racz, WJ ;

Brien, JF ;

Bray, TM ;

Massey, TE .

TOXICOLOGY, 1999, 133 (2-3) :75-84

[5] PATHOBIOLOGY OF PULMONARY FIBROSIS [J].

CROUCH, E .

AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 259 (04) :L159-L184

[6] INTERSTITIAL LUNG-DISEASE [J].

DEPASO, WJ ;

WINTERBAUER, RH .

DM DISEASE-A-MONTH, 1991, 37 (02) :67-133

[7] Synthesis of novel derivatives of 4-methylthio-N-aryl-2-pyridone and deazapurine analogues: The reaction of ketene dithioacetals with substituted acetanilides [J].

Elgemeie, GH ;

Ali, HA ;

Elghandour, AH ;

Abd Elaziz, GW .

PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS, 2000, 164 :189-197

[8]

GAY RJ, 1968, CLIN CHEM, V14, P740

[9]

GHORAB MM, IN PRESS ARZNEIM FOR

[10]

HUNNINGHAKE GW, 1995, AM J RESP CRIT CARE, V151, P915

← 1 2 3 →