Novel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors: Design, synthesis, and biological activities

被引：48

作者：

Di Santo, Roberto ^{[1
]}

Costi, Roberta ^{[1
]}

Roux, Alessandra ^{[1
]}

Miele, Gaetano ^{[1
]}

Crucitti, Giuliana Cuzzucoli ^{[1
]}

Iacovo, Alberto ^{[1
]}

Rosi, Federica ^{[1
]}

Lavecchia, Antonio ^{[2
]}

Marinelli, Luciana ^{[2
]}

Di Giovanni, Carmen ^{[2
]}

Novellino, Ettore ^{[2
]}

Palmisano, Lucia ^{[3
]}

Andreotti, Mauro ^{[3
]}

Amici, Roberta ^{[3
]}

Galluzzo, Clementina Maria ^{[3
]}

Nencioni, Lucia ^{[4
]}

Palamara, Anna Teresa ^{[4
]}

Pommier, Yves ^{[5
]}

Marchand, Christophe ^{[5
]}

机构：

[1] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur Fdn Cenci Bolognetti, I-00185 Rome, Italy

[2] Univ Naples Federico 2, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy

[3] Ist Super Sanita, Dipartimento Farmaco, I-00161 Rome, Italy

[4] Univ Roma La Sapienza, Dipartimento Sci Sanita Pubbl, I-00185 Rome, Italy

[5] NCI, NIH, Ctr Canc Res, Mol Phys Lab, Bethesda, MD 20892 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 15期

关键词：

D O I：

10.1021/jm8001422

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3'-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.

引用

页码：4744 / 4750

页数：7

共 50 条

[31] Design, Practical Synthesis, and Biological Evaluation of Novel 6-(Pyrazolylmethyl)-4-quinoline-3-carboxylic Acid Derivatives as HIV-1 Integrase Inhibitors
Hu, Liming
Yan, Song
Luo, Zaigang
Han, Xiao
Wang, Yujie
Wang, Zhanyang
Zeng, Chengchu
[J]. MOLECULES, 2012, 17 (09) : 10652 - 10666
[32] Design, Synthesis, and Biological Evaluation of 1,2-Dihydroisoquinolines as HIV-1 Integrase Inhibitors
Tandon, Vibha
Urvashi
Yaday, Pooja
Sur, Souvik
Abbat, Sheenu
Tiwari, Vinod
Hewer, Raymond
Papathanasopoulos, Maria A.
Raja, Rameez
Banerjea, Akhil C.
Verma, Akhilesh K.
Kukreti, Shrikant
Bharatam, Prasad V.
[J]. ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (10): : 1065 - 1070
[33] Design, synthesis and biological evaluation of novel tricyclic HIV-1 integrase inhibitors by modification of its pyridine ring
Metobo, Sammy E.
Jin, Haolun
Tsiang, Manuel
Kim, Choung U.
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (15) : 3985 - 3988
[34] N-Substituted Quinolinonyl Diketo Acid Derivatives as HIV Integrase Strand Transfer Inhibitors and Their Activity against RNase H Function of Reverse Transcriptase
Pescatori, Luca
Metifiot, Mathieu
Chung, Suhman
Masoaka, Takashi
Crucitti, Giuliana Cuzzucoli
Messore, Antonella
Pupo, Giovanni
Madia, Valentina Noemi
Saccoliti, Francesco
Scipione, Luigi
Tortorella, Silvano
Di Leva, Francesco Saverio
Cosconati, Sandro
Marinelli, Luciana
Novellino, Ettore
Le Grice, Stuart F. J.
Pommier, Yves
Marchand, Christophe
Costi, Roberta
Di Santo, Roberto
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (11) : 4610 - 4623
[35] Design and synthesis of hybrids of diarylpyrimidines and diketo acids as HIV-1 inhibitors
Xue, Ping
Lu, Huan-Huan
Zhu, Yuan-Yuan
Ju, Xiu-Lian
Pannecouque, Christophe
Zheng, Xiao-Jiao
Liu, Gen-Yan
Zhang, Xiu-Lan
Gu, Shuang-Xi
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (08) : 1640 - 1643
[36] Styrylquinazoline derivatives as HIV-1 integrase inhibitors
Lee, JY
Park, JH
Lee, SJ
Park, H
Lee, YS
[J]. ARCHIV DER PHARMAZIE, 2002, 335 (06) : 277 - 282
[37] De novo design and synthesis of HIV-1 integrase inhibitors
Makhija, MT
Kasliwal, RT
Kulkarni, VM
Neamati, N
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (09) : 2317 - 2333
[38] Synthesis of novel thiazolothiazepine based HIV-1 integrase inhibitors
Aiello, F
Brizzi, A
Garofalo, A
Grande, F
Ragno, G
Dayam, R
Neamati, N
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (16) : 4459 - 4466
[39] QSAR analysis of chicoric acid derivatives as HIV-1 integrase inhibitors
Sahu, Kamlesh K.
Ravichandran, V.
Jain, Prateek K.
Sharma, Simant
Mourya, V. K.
Agrawal, R. K.
[J]. ACTA CHIMICA SLOVENICA, 2008, 55 (01) : 138 - 145
[40] QSAR study of carboxylic acid derivatives as HIV-1 Integrase inhibitors
Cheng, Zhengjun
Zhang, Yuntao
Fu, Weizhong
[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2010, 45 (09) : 3970 - 3980

← 1 2 3 4 5 →