PMID- 35429006
OWN - NLM
STAT- MEDLINE
DCOM- 20220706
LR  - 20220706
IS  - 1521-4184 (Electronic)
IS  - 0365-6233 (Linking)
VI  - 355
IP  - 7
DP  - 2022 Jul
TI  - New pyrimidine/thiazole hybrids endowed with analgesic, anti-inflammatory, and 
      lower cardiotoxic activities: Design, synthesis, and COX-2/sEH dual inhibition.
PG  - e2200024
LID - 10.1002/ardp.202200024 [doi]
AB  - Some cyclooxygenase (COX)-2 selective medications were withdrawn from the market 
      just a few years after their production due to cardiovascular side effects. In 
      this study, a new series of pyrimidine/thiazole hybrids 7a-p was synthesized as 
      selective COX-2/soluble epoxide hydrolase (sEH) inhibitors with analgesic and 
      anti-inflammatory effects, and lower cardiotoxicity effects. The target compounds 
      were synthesized and in vitro tested against COX-1, COX-2, and sEH enzymes. 
      Hybrids 7j, 7k, and 7i showed the greatest COX-2-inhibitory activity and were 
      discovered to be the most potent dual COX-2/sEH inhibitors. In vivo tests 
      revealed that these hybrids were the most active analgesic/anti-inflammatory 
      agents, with improved ulcerogenic and cardioprotective properties. Finally, the 
      most active dual inhibitors were docked into COX-2/sEH active regions to explain 
      their binding mechanisms.
CI  - (c) 2022 Deutsche Pharmazeutische Gesellschaft.
FAU - Abdel-Aziz, Salah A
AU  - Abdel-Aziz SA
AD  - Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Al-Azhar 
      University, Assiut, Egypt.
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, 
      Minia, Egypt.
FAU - Taher, Ehab S
AU  - Taher ES
AD  - Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar 
      University, Assiut, Egypt.
FAU - Lan, Ping
AU  - Lan P
AD  - Institute for Advanced and Applied Chemical Synthesis, Jinan University, 
      Guangzhou, China.
FAU - El-Koussi, Nawal A
AU  - El-Koussi NA
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, 
      Minia, Egypt.
AD  - Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Assiut 
      University, Assiut, Egypt.
FAU - Salem, Ola I A
AU  - Salem OIA
AD  - Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut 
      University, Assiut, Egypt.
FAU - Gomaa, Hesham A M
AU  - Gomaa HAM
AD  - Pharmacology Department, College of Pharmacy, Jouf University, Sakaka, Saudi 
      Arabia.
FAU - Youssif, Bahaa G M
AU  - Youssif BGM
AUID- ORCID: 0000-0002-6834-6548
AD  - Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut 
      University, Assiut, Egypt.
LA  - eng
GR  - None/
PT  - Journal Article
DEP - 20220415
PL  - Germany
TA  - Arch Pharm (Weinheim)
JT  - Archiv der Pharmazie
JID - 0330167
RN  - 0 (Analgesics)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Thiazoles)
RN  - EC 1.14.99.1 (Cyclooxygenase 1)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Analgesics/chemistry
MH  - Anti-Inflammatory Agents/pharmacology
MH  - *Cardiotoxicity/drug therapy/etiology
MH  - Cyclooxygenase 1/metabolism
MH  - Cyclooxygenase 2/metabolism
MH  - Cyclooxygenase 2 Inhibitors/pharmacology
MH  - Edema/chemically induced/drug therapy
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Pyrimidines/pharmacology
MH  - Structure-Activity Relationship
MH  - *Thiazoles/chemistry
OTO - NOTNLM
OT  - COX-2
OT  - anti-inflammatory
OT  - pyrimidine
OT  - sEH
OT  - thiazole
OT  - ulcer
EDAT- 2022/04/17 06:00
MHDA- 2022/07/07 06:00
CRDT- 2022/04/16 05:28
PHST- 2022/03/18 00:00 [revised]
PHST- 2022/01/17 00:00 [received]
PHST- 2022/03/22 00:00 [accepted]
PHST- 2022/04/17 06:00 [pubmed]
PHST- 2022/07/07 06:00 [medline]
PHST- 2022/04/16 05:28 [entrez]
AID - 10.1002/ardp.202200024 [doi]
PST - ppublish
SO  - Arch Pharm (Weinheim). 2022 Jul;355(7):e2200024. doi: 10.1002/ardp.202200024. 
      Epub 2022 Apr 15.