PMID- 36910947
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230314
IS  - 2470-1343 (Electronic)
IS  - 2470-1343 (Linking)
VI  - 8
IP  - 9
DP  - 2023 Mar 7
TI  - Synthesis of C3,C6-Diaryl 7-Azaindoles via One-Pot Suzuki-Miyaura Cross-Coupling 
      Reaction and Evaluation of Their HIV-1 Integrase Inhibitory Activity.
PG  - 8415-8426
LID - 10.1021/acsomega.2c07372 [doi]
AB  - There is a continuing demand of new inhibitors of HIV-1 Integrase (HIV-1 IN) due 
      to mutations of HIV-1. This study aims to develop the synthesis of 3,6-diaryl 
      7-azaindoles and introspect the role of aryl groups on the strand transfer (ST) 
      inhibition of HIV-1 IN. An efficient and chemo-selective one-pot method is 
      established for the synthesis of the unexplored diverse C3 --> C6 diaryl 
      7-azaindoles starting from 6-chloro-3-iodo-N-protected 7-azaindoles. Here we 
      report Pd(2)dba(3)/SPhos catalyzed synthesis of eight selective C3 monoaryl 
      7-azaindoles (10a-h) and eight C3,C6-diaryl 7-azaindoles (11a-f, 12a,b) with 
      yields in the ranges of 67-93% and 43-88% respectively. The synthesized 
      derivatives inhibit the strand transfer (ST) activity of HIV-1 IN enzyme at 10 muM 
      dose with 11d and 11f exhibiting %ST inhibitions of 72% and 71%, respectively. 
      SAR studies indicate the para-substitution on the C3 aryl ring and C6 aryl is 
      essential for enhanced %ST inhibition. 11b,c, 11e-f, and 12b showed lower 
      cytotoxicity (IC(50) > 200 muM) against TZM-bl cells. Molecular docking of the 
      diaryl 7-azaindoles and Raltegravir (RAL), to the PFV-integrase revealed 
      favorable binding interactions.
CI  - (c) 2023 The Authors. Published by American Chemical Society.
FAU - Cardoza, Savio
AU  - Cardoza S
AD  - Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 
      110067, India.
FAU - Yadav, Pooja
AU  - Yadav P
AD  - Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 
      110067, India.
FAU - Ajmani, Abhishek
AU  - Ajmani A
AD  - Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 
      110067, India.
FAU - Das, Parthasarathi
AU  - Das P
AUID- ORCID: 0000-0002-9306-4956
AD  - Department of Chemistry and Chemical Biology, Indian Institute of Technology 
      (Indian School of Mines), Dhanbad 826004, India.
FAU - Tandon, Vibha
AU  - Tandon V
AUID- ORCID: 0000-0001-6146-937X
AD  - Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 
      110067, India.
LA  - eng
PT  - Journal Article
DEP - 20230222
PL  - United States
TA  - ACS Omega
JT  - ACS omega
JID - 101691658
PMC - PMC9996623
COIS- The authors declare no competing financial interest.
EDAT- 2023/03/14 06:00
MHDA- 2023/03/14 06:01
PMCR- 2023/02/22
CRDT- 2023/03/13 04:19
PHST- 2022/11/17 00:00 [received]
PHST- 2023/02/03 00:00 [accepted]
PHST- 2023/03/13 04:19 [entrez]
PHST- 2023/03/14 06:00 [pubmed]
PHST- 2023/03/14 06:01 [medline]
PHST- 2023/02/22 00:00 [pmc-release]
AID - 10.1021/acsomega.2c07372 [doi]
PST - epublish
SO  - ACS Omega. 2023 Feb 22;8(9):8415-8426. doi: 10.1021/acsomega.2c07372. eCollection 
      2023 Mar 7.