Novel Highly Potent and Selective Nonsteroidal Aromatase Inhibitors: Synthesis, Biological Evaluation and Structure-Activity Relationships Investigation

被引：49

作者：

Gobbi, Silvia ^{[1
]}

Zimmer, Christina ^{[2
,3
]}

Belluti, Federica ^{[1
]}

Rampa, Angela ^{[1
]}

Hartmann, Rolf W. ^{[2
,3
]}

Recanatini, Maurizio ^{[1
]}

Bisi, Alessandra ^{[1
]}

机构：

[1] Univ Bologna, Dept Pharmaceut Sci, I-40126 Bologna, Italy

[2] Univ Saarland, D-66041 Saarbrucken, Germany

[3] Helmholtz Inst Pharmaceut Res Saarland, D-66041 Saarbrucken, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 14期

关键词：

ANTITUMOR AGENTS; BREAST-CANCER; XANTHONE DERIVATIVES; PROSTATE-CANCER; IN-VITRO; KETOCONAZOLE; INVIVO; ENZYME; ACIDS; SAR;

D O I：

10.1021/jm100319h

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In further pursuing our search for potent and selective aromatase inhibitors, a new series of molecules was designed and synthesized, exploring possible structural modifications of a previously identified xanthone scaffold. Among them, highly potent compounds, with inhibitory activity in the low nanomolar range, were found. In particular, substitution of the heterocyclic oxygen atom in the xanthone core by a sulfur atom and/or increase in structure flexibility seemed to be favorable for the interaction with the enzyme.

引用

页码：5347 / 5351

页数：5

共 30 条

[21] A new class of nonsteroidal aromatase inhibitors:: Design and synthesis of chromone and xanthone derivatives and inhibition of the P450 enzymes aromatase and 17α-hydroxylase/C17,20-lyase [J].

Recanatini, M ;

Bisi, A ;

Cavalli, A ;

Belluti, F ;

Gobbi, S ;

Rampa, A ;

Valenti, P ;

Palzer, M ;

Palusczak, A ;

Hartmann, RW .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (05) :672-680

[22] POTENTIAL ANTITUMOR AGENTS .62. STRUCTURE-ACTIVITY-RELATIONSHIPS FOR TRICYCLIC COMPOUNDS RELATED TO THE COLON-TUMOR ACTIVE-DRUG 9-OXO-9H-XANTHENE-4-ACETIC ACID [J].

REWCASTLE, GW ;

ATWELL, GJ ;

PALMER, BD ;

BOYD, PDW ;

BAGULEY, BC ;

DENNY, WA .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (02) :491-496

[23] POTENTIAL ANTITUMOR AGENTS .58. SYNTHESIS AND STRUCTURE ACTIVITY RELATIONSHIPS OF SUBSTITUTED XANTHENONE-4-ACETIC ACIDS ACTIVE AGAINST THE COLON 38 TUMOR INVIVO [J].

REWCASTLE, GW ;

ATWELL, GJ ;

BAGULEY, BC ;

CALVELEY, SB ;

DENNY, WA .

JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (04) :793-799

[24] History of Aromatase: Saga of an Important Biological Mediator and Therapeutic Target [J].

Santen, R. J. ;

Brodie, H. ;

Simpson, E. R. ;

Siiteri, P. K. ;

Brodie, A. .

ENDOCRINE REVIEWS, 2009, 30 (04) :343-375

[25] In situ estrogen production and its regulation in human breast carcinoma: From endocrinology to intracrinology [J].

Sasano, Hironobu ;

Miki, Yasuhiro ;

Nagasaki, Shuji ;

Suzuki, Takashi .

PATHOLOGY INTERNATIONAL, 2009, 59 (11) :777-789

[26]

STREHLKE P, 1977, Patent No. 4006243

[27]

THOMPSON EA, 1974, J BIOL CHEM, V249, P5364

[28] First-line endocrine treatment of breast cancer: aromatase inhibitor or antioestrogen? [J].

Wong, ZW ;

Ellis, MJ .

BRITISH JOURNAL OF CANCER, 2004, 90 (01) :20-25

[29] Highly Potent First Examples of Dual Aromatase-Steroid Sulfatase Inhibitors based on a Biphenyl Template [J].

Woo, L. W. Lawrence ;

Jackson, Toby ;

Putey, Aurelien ;

Cozier, Gyles ;

Leonard, Phililp ;

Acharya, K. Ravi ;

Chander, Surinder K. ;

Purohit, Atul ;

Reed, Michael J. ;

Potter, Barry V. L. .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (05) :2155-2170

[30] New 7,8-benzoflavanones as potent aromatase inhibitors: Synthesis and biological evaluation [J].

Yahiaoui, Samir ;

Fagnere, Catherine ;

Pouget, Christelle ;

Buxeraud, Jacques ;

Chulia, Albert-Jose .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (03) :1474-1480

← 1 2 3 →