PMID- 35876064
OWN - NLM
STAT- MEDLINE
DCOM- 20220812
LR  - 20220814
IS  - 1520-4804 (Electronic)
IS  - 0022-2623 (Linking)
VI  - 65
IP  - 15
DP  - 2022 Aug 11
TI  - Convenient Diaryl Ureas as Promising Anti-pseudo-allergic Agents.
PG  - 10626-10637
LID - 10.1021/acs.jmedchem.2c00846 [doi]
AB  - Allergic diseases are a group of allergen-induced unfavorable immune responses 
      initiating various symptoms in different organs. Mas-related G protein-coupled 
      receptor X2 (MRGPRX2) on mast cells has been reported to be responsible for 
      immunoglobulin E (IgE)-independent immune diseases and allergic drug reactions 
      and has therefore been a crucial drug target for the development of 
      anti-pseudo-allergic agents. Considering the active structural features of 
      MRGPRX2, we designed and synthesized a series of diaryl ureas (DPUs). DPUs exert 
      promising potency for inhibiting beta-hexosaminidase release in LAD2 cells with 
      half-maximal inhibitory concentrations (IC(50)) values of 2.51-0.62 muM, as well 
      as favorable antilocal and systemic anaphylaxis in mice at a dosage of 10 mg/kg. 
      MRGPRX2 is further revealed to participate in the anti-pseudo-allergic activity 
      of DPUs by binding with electrophilic urea and trifluoromethyl substituents. In 
      brief, these results highlight entities with powerful electrophilic substituents 
      as a prospective therapeutic strategy for the treatment of IgE-independent 
      disorders.
FAU - Wang, Cheng
AU  - Wang C
AD  - School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, 
      Yanta West Road, Xi'an, Shaanxi 710061, China.
FAU - Hu, Tian
AU  - Hu T
AD  - Department of Pharmacy, 3201 Hospital Affiliated to Xi'an Jiaotong University, 
      Hanzhong, Shaanxi 723000, China.
FAU - Lu, Jiayu
AU  - Lu J
AD  - School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, 
      Yanta West Road, Xi'an, Shaanxi 710061, China.
FAU - Lv, Yuexin
AU  - Lv Y
AD  - School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, 
      Yanta West Road, Xi'an, Shaanxi 710061, China.
FAU - Ge, Shuai
AU  - Ge S
AD  - School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, 
      Yanta West Road, Xi'an, Shaanxi 710061, China.
FAU - Hou, Yajing
AU  - Hou Y
AD  - Department of Pharmacy, Shaanxi Province People's Hospital, Xi'an, Shaanxi 
      710068, China.
FAU - He, Huaizhen
AU  - He H
AUID- ORCID: 0000-0002-2836-2308
AD  - School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, 
      Yanta West Road, Xi'an, Shaanxi 710061, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220724
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Anti-Allergic Agents)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Neuropeptide)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 8W8T17847W (Urea)
SB  - IM
MH  - *Anaphylaxis/chemically induced/metabolism
MH  - Animals
MH  - *Anti-Allergic Agents/pharmacology/therapeutic use
MH  - Cell Degranulation
MH  - Immunoglobulin E/adverse effects/metabolism
MH  - Mast Cells
MH  - Mice
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - Receptors, Neuropeptide/metabolism
MH  - Urea/pharmacology/therapeutic use
EDAT- 2022/07/26 06:00
MHDA- 2022/08/13 06:00
CRDT- 2022/07/25 05:24
PHST- 2022/07/26 06:00 [pubmed]
PHST- 2022/08/13 06:00 [medline]
PHST- 2022/07/25 05:24 [entrez]
AID - 10.1021/acs.jmedchem.2c00846 [doi]
PST - ppublish
SO  - J Med Chem. 2022 Aug 11;65(15):10626-10637. doi: 10.1021/acs.jmedchem.2c00846. 
      Epub 2022 Jul 24.