Design, synthesis and biological evaluation of novel procaine derivatives for intravenous anesthesia

被引：4

作者：

Yin, Jiaqi ^{[1
]}

Zhao, Yi ^{[2
]}

He, Qian ^{[3
]}

Hai, Ao ^{[2
]}

Peng, Yanlai ^{[1
]}

Zuo, Zeping ^{[2
]}

Song, Zhenlei ^{[1
]}

Ke, Bowen ^{[2
]}

机构：

[1] Sichuan Univ, West China Sch Pharm, Chengdu 610041, Sichuan, Peoples R China

[2] Sichuan Univ, Lab Anesthesiol & Crit Care Med, Dept Anesthesiol, West China Hosp,State Key Lab Biotherapy & Canc C, Chengdu 610041, Sichuan, Peoples R China

[3] Sichuan Univ, Dept Emergency, West China Hosp, Chengdu 610041, Sichuan, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2022年 / 60卷

基金：

中国国家自然科学基金;

关键词：

Procaine; Structure-activity relationship; Safety evaluation; NMDA receptor; Continuous infusion; LOCAL-ANESTHETICS; MECHANISMS; KETAMINE; SITES;

D O I：

10.1016/j.bmcl.2022.128587

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel procaine derivatives for intravenous anesthesia were prepared and evaluated by physicochemical properties and pharmaco-dynamic experiments in vivo and in vitro. Systematic optimization of procaine led to the identification of 6f, 6g, 6h, 6o, 6p and 6q with higher TI value and moderate log D. Compared with procaine (TI = 1.65), most procaine derivatives demonstrated better security, among which compound 6h (TI = 2.68) was the most notable one and showed fewer adverse events in animals. The result of hNR2B-HEK293 assay indicated that compound 6h suppressed the NMDA receptor 2B subtype channel activity and it showed more than 80% inhibitory effect at the concentration of 500 mu M.

引用

页数：9

共 26 条

[1] THE DISSOCIATIVE ANESTHETICS, KETAMINE AND PHENCYCLIDINE, SELECTIVELY REDUCE EXCITATION OF CENTRAL MAMMALIAN NEURONS BY N-METHYL-ASPARTATE [J].

ANIS, NA ;

BERRY, SC ;

BURTON, NR ;

LODGE, D .

BRITISH JOURNAL OF PHARMACOLOGY, 1983, 79 (02) :565-575

[2] MOLECULAR MECHANISMS OF LOCAL-ANESTHESIA - A REVIEW [J].

BUTTERWORTH, JF ;

STRICHARTZ, GR .

ANESTHESIOLOGY, 1990, 72 (04) :711-734

[3]

COURTNEY KR, 1978, J PHARMACOL EXP THER, V207, P594

[4]

DOUD E A, 1951, Curr Res Anesth Analg, V30, P174

[5] INTRAVENOUS USE OF PROCAINE IN GENERAL ANESTHESIA [J].

EDMONDS, GW ;

COMER, WH ;

KENNEDY, JD ;

TAYLOR, IB .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1949, 141 (11) :761-765

[6] COMPARATIVE-STUDY OF HUMAN INTESTINAL AND HEPATIC ESTERASES AS RELATED TO ENZYMATIC-PROPERTIES AND HYDROLIZING ACTIVITY FOR ESTER-TYPE DRUGS [J].

INOUE, M ;

MORIKAWA, M ;

TSUBOI, M ;

ITO, Y ;

SUGIURA, M .

JAPANESE JOURNAL OF PHARMACOLOGY, 1980, 30 (04) :529-535

[7] EFFECT OF PROCAINE ON LIVER FUNCTION - AN EXPERIMENTAL AND CLINICAL STUDY [J].

JACOBY, JJ ;

COON, JM ;

WOOLF, MP ;

SALERNO, PR ;

LIVINGSTONE, HM .

ANESTHESIOLOGY, 1948, 9 (05) :481-489

[8] Procaine and mepivacaine have less toxicity in vitro than other clinically used local anesthetics [J].

Kasaba, T ;

Onizuka, S ;

Takasaki, M .

ANESTHESIA AND ANALGESIA, 2003, 97 (01) :85-90

[9] A CONTROLLED STUDY OF PAIN RELIEF BY INTRAVENOUS PROCAINE [J].

KEATS, AS ;

DALESSANDRO, GL ;

BEECHER, HK .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1951, 147 (18) :1761-1763

[10]

KRAFT KA, 1947, CAN MED ASSOC J, V57, P350

← 1 2 3 →