Design, synthesis and SAR study of bridged tricyclic pyrimidinone carboxamides as HIV-1 integrase inhibitors

被引：8

作者：

Patel, Manoj ^{[1
,5
]}

Naidu, B. Narasimhulu ^{[1
,5
]}

Dicker, Ira ^{[2
,5
]}

Higley, Helen ^{[2
]}

Lin, Zeyu ^{[2
]}

Terry, Brian ^{[2
]}

Protack, Tricia ^{[2
]}

Krystal, Mark ^{[2
,5
]}

Jenkins, Susan ^{[1
,5
]}

Parker, Dawn ^{[1
,5
]}

Panja, Chiradeep ^{[3
]}

Rampulla, Richard ^{[4
]}

Mathur, Arvind ^{[4
]}

Meanwell, Nicholas A. ^{[1
]}

Walker, Michael A. ^{[1
,6
]}

机构：

[1] Dept Discovery Chem & Mol Technol, 5 Res Pkwy, Wallingford, CT 06492 USA

[2] Bristol Myers Squibb Res & Dev, Virol, 5 Res Pkwy, Wallingford, CT 06492 USA

[3] Biocon Bristol Myers Squibb Res Ctr, Plot 2&3,Bommasandra Ind Estate Phase 4, Bengaluru 560099, Karnataka, India

[4] Bristol Myers Squibb Res & Dev, Dept Discovery Chem Synth, POB 4000, Princeton, NJ 08543 USA

[5] ViiV Healthcare, 36 East Ind Pkwy, Branford, CT 06405 USA

[6] Assembly Biosci Inc, 331 Oyster Point Blvd, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2020年 / 28卷 / 13期

关键词：

RALTEGRAVIR RESISTANCE; DOLUTEGRAVIR; ELVITEGRAVIR; MUTATIONS; EVOLUTION;

D O I：

10.1016/j.bmc.2020.115541

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The design, synthesis and structure-activity relationships associated with a series of bridged tricyclic pyrimidinone carboxamides as potent inhibitors of HIV-1 integrase strand transfer are described. Structural modifications to these molecules were made in order to examine the effect on potency towards wild-type and clinically-relevant resistant viruses. The [3.2.2]-bridged tricyclic system was identified as an advantageous chemotype, with representatives exhibiting excellent antiviral activity against both wild-type viruses and the G140S/Q148H resistant virus that arises in response to therapy with raltegravir and elvitegravir. © 2020 Elsevier Ltd

引用

页数：6

共 50 条

[21] Rapid Catalyst Identification for the Synthesis of the Pyrimidinone Core of HIV Integrase Inhibitors
Bellomo, Ana
Celebi-Olcum, Nihan
Bu, Xiaodong
Rivera, Nelo
Ruck, Rebecca T.
Welch, Christopher J.
Houk, Kendall N.
Dreher, Spencer D.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2012, 51 (28) : 6912 - 6915
[22] Design and synthesis of bicyclic pyrimidinones as potent and orally bioavailable HIV-1 integrase inhibitors
Muraglia, Ester
Kinzel, Olaf
Gardelli, Cristina
Crescenzi, Benedetta
Donghi, Monica
Ferrara, Marco
Nizi, Emanuela
Orvieto, Federica
Pescatore, Giovanna
Laufer, Ralph
Gonzalez-Paz, Odalys
Di Marco, Annalise
Fiore, Fabrizio
Monteagudo, Edith
Fonsi, Massimiliano
Felock, Peter J.
Rowley, Michael
Summa, Vincenzo
JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (04) : 861 - 874
[23] HIV-1 integrase strand transfer inhibitors (INSTIs): Design, synthesis and biological activity
Ferro, S.
Barreca, M. L.
De Luca, L.
Rao, A.
Monforte, A. M.
Michiels, M.
Witvrouw, M.
Debyser, Z.
Chimirri, A.
PROCEEDINGS OF THE 5TH JOINT MEETING ON MEDICINAL CHEMISTRY, 2007, : 11 - 15
[24] Design, synthesis, and biological evaluation of chicoric acid analogs as inhibitors of HIV-1 integrase
Charvat, Trevor T.
Lee, Deborah J.
Robinson, W. Edward
Chamberlin, A. Richard
BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (13) : 4552 - 4567
[25] Design, Synthesis and Biological Activity of Aromatic Diketone Derivatives as HIV-1 Integrase Inhibitors
Hu, Liming
Li, Zhipeng
Wang, Zhanyang
Liu, Gengxin
He, Xianzhuo
Wang, Xiaoli
Zeng, Chengchu
MEDICINAL CHEMISTRY, 2015, 11 (02) : 180 - 187
[26] Design and synthesis of novel indole β-diketo acid derivatives as HIV-1 integrase inhibitors
Sechi, M
Derudas, M
Dallocchio, R
Dessì, A
Bacchi, A
Sannia, L
Carta, F
Palomba, M
Ragab, O
Chan, C
Shoemaker, R
Sei, S
Dayam, R
Neamati, N
JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (21) : 5298 - 5310
[27] Design and synthesis of novel and potent allosteric HIV-1 integrase inhibitors with a spirocyclic moiety
Adachi, Kaoru
Manabe, Tomoyuki
Yamasaki, Takayuki
Suma, Akira
Orita, Takuya
Furuzono, Tomoko
Adachi, Tsuyoshi
Ohata, Yoshitsugu
Akiyama, Yoshiyuki
Miyazaki, Susumu
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2024, 110
[28] 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.
ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (10): : 1065 - 1070
[29] Design, synthesis and structure-activity relationship of HIV-1 integrase inhibitors.
Zhao, H
Neamati, N
Mazumder, A
Pommier, Y
Burke, TR
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1996, 212 : 21 - MEDI
[30] Structural aspects of HIV-1 integrase inhibitors: SAR studies and synthetic strategies
Barik, Pallavi
Gupta, Shankar
Singh, Gurpreet
Bharti, Sanjay Kumar
Asati, Vivek
MOLECULAR DIVERSITY, 2024,

← 1 2 3 4 5 →