Acryloylamino-salicylanilides as EGFR PTK inhibitors

被引：41

作者：

Deng, W

Guo, ZR ^{[1
]}

Guo, YS

Feng, ZQ

Jiang, Y

Chu, FM

机构：

[1] Chinese Acad Med Sci, Inst Mat Med, Dept Synthet Med Chem, Beijing 100050, Peoples R China

[2] Peking Union Med Coll, Beijing 100050, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 02期

关键词：

EGFR; inhibitors; salicylanilides;

D O I：

10.1016/j.bmcl.2005.06.088

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of acryloylamino-salicylanilides were synthesized as inhibitors of EGFR PTK. A strategy of pseudo six-membered ring formed through intramolecular hydrogen bonding in salicylanilides is employed to mimic the planar pyrimidine ring of quinazoline EGFR inhibitors. Acrylamido moiety is incorporated to target the Cys-773 of EGFR specifically. Some of the obtained compounds exhibited good activity as EGFR inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.

引用

收藏

页码：469 / 472

页数：4

相关论文

共 20 条

[1] GROWTH-FACTORS AND CANCER [J].

AARONSON, SA .

SCIENCE, 1991, 254 (5035) :1146-1153

[2] Tyrosine kinase inhibitors .8. An unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a potent inhibitor of the epidermal growth factor receptor [J].

Bridges, AJ ;

Zhou, H ;

Cody, DR ;

Rewcastle, GW ;

McMichael, A ;

Showalter, HDH ;

Fry, DW ;

Kraker, AJ ;

Denny, WA .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (01) :267-276

[3] Specific, irreversible inactivation of the epidermal growth factor receptor and erbB2, by a new class of tyrosine kinase inhibitor [J].

Fry, DW ;

Bridges, AJ ;

Denny, WA ;

Doherty, A ;

Greis, KD ;

Hicks, JL ;

Hook, KE ;

Keller, PR ;

Leopold, WR ;

Loo, JA ;

McNamara, DJ ;

Nelson, JM ;

Sherwood, V ;

Smaill, JB ;

Trumpp-Kallmeyer, S ;

Dobrusin, EM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (20) :12022-12027

[4] Tyrosine kinase inhibitors .11. Soluble analogues of pyrrolo- and pyrazoloquinazolines as epidermal growth factor receptor inhibitors: Synthesis, biological evaluation, and modeling of the mode of binding [J].

Palmer, BD ;

TrumppKallmeyer, S ;

Fry, DW ;

Nelson, JM ;

Showalter, HDH ;

Denny, WA .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (10) :1519-1529

[5] Tyrosine kinase inhibitors.: 14.: Structure-activity relationships for methylamino-substituted derivatives of 4-[(3-bromophenyl)amino]-6-(methylamino)pyrido[3,4-d]pyrimidine (PD 158780), a potent and specific inhibitor of the tyrosine kinase activity of receptors for the EGF family of growth factors [J].

Rewcastle, GW ;

Murray, DK ;

Elliott, WL ;

Fry, DW ;

Howard, CT ;

Nelson, JM ;

Roberts, BJ ;

Vincent, PW ;

Showalter, HDH ;

Winters, RT ;

Denny, WA .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (05) :742-751

[6] Tyrosine kinase inhibitors .9. Synthesis and evaluation of fused tricyclic quinazoline analogues as ATP site inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor [J].

Rewcastle, GW ;

Palmer, BD ;

Bridges, AJ ;

Showalter, HDH ;

Li, S ;

Nelson, J ;

McMichael, A ;

Kraker, AJ ;

Fry, DW ;

Denny, WA .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (04) :918-928

[7] Tyrosine kinase inhibitors .10. Isomeric 4-[(3-bromophenyl)amino]pyrido[d]-pyrimidines are potent ATP-binding site inhibitors of the tyrosine kinase function of the epidermal growth factor receptor [J].

Rewcastle, GW ;

Palmer, BD ;

Thompson, AM ;

Bridges, AJ ;

Cody, DR ;

Zhou, HR ;

Fry, DW ;

McMichael, A ;

Denny, WA .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (09) :1823-1835

[8] TYROSINE KINASE INHIBITORS .5. SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS FOR 4-[(PHENYLMETHYL)AMINO]-QUINAZOLINES AND 4-(PHENYLAMINO)QUINAZOLINES AS POTENT ADENOSINE 5'-TRIPHOSPHATE BINDING-SITE INHIBITORS OF THE TYROSINE KINASE DOMAIN OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR [J].

REWCASTLE, GW ;

DENNY, WA ;

BRIDGES, AJ ;

ZHOU, HR ;

CODY, DR ;

MCMICHAEL, A ;

FRY, DW .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (18) :3482-3487

[9] Tyrosine kinase inhibitors.: 18.: 6-substituted 4-anilinoquinazolines and 4-anilinopyrido [3,4-d]pyrimidines as soluble, irreversible inhibitors of the epidermal growth factor receptor [J].

Smaill, JB ;

Showalter, HDH ;

Zhou, HR ;

Bridges, AJ ;

McNamara, DJ ;

Fry, DW ;

Nelson, JM ;

Sherwood, V ;

Vincent, PW ;

Roberts, BJ ;

Elliott, WL ;

Denny, WA .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (03) :429-440

[10] Tyrosine kinase inhibitors.: 15.: 4-(phenylamino)quinazoline and 4-(phenylamino)pyrido[d] pyrimidine acrylamides as irreversible inhibitors of the ATP binding site of the epidermal growth factor receptor [J].

Smaill, JB ;

Palmer, BD ;

Rewcastle, GW ;

Denny, WA ;

McNamara, DJ ;

Dobrusin, EM ;

Bridges, AJ ;

Zhou, HR ;

Showalter, HDH ;

Winters, RT ;

Leopold, WR ;

Fry, DW ;

Nelson, JM ;

Slintak, V ;

Elliot, WL ;

Roberts, BJ ;

Vincent, PW ;

Patmore, SJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (10) :1803-1815