Etonitat thiab nws cov tshuaj opioid agonist benzimidazole tau tshawb pom nyob rau xyoo 1950 los ntawm ib pab pawg neeg tshawb fawb Swiss ua haujlwm ntawm lub tuam txhab kws tshuaj CIBA (tam sim no Novartis).Ib qho ntawm thawj lub tebchaw kawm los ntawm Swiss pab pawg yog 1-(beta-diethylaminoethyl) -2-benzyl benzimidazole, uas tau pom tias muaj 10% ntawm morphine's analgesic kev ua si hauv nas bioassometry.Qhov kev tshawb pom no tau txhawb pab pawg kom pib txoj kev tshawb fawb dav dav ntawm 2-benzyl benzimidazole thiab tsim kom muaj kev sib raug zoo ntawm kev ua haujlwm rau tsev neeg tshiab ntawm cov tshuaj tua kab mob.Ob txoj kev sib xyaw dav dav tau tsim los npaj cov khoom sib xyaw no.

Thawj txoj kev koom nrog kev sib xyaw ntawm o-phenylenediamine nrog phenylacetonitrile los ua 2-benzylbenzimidazole.Lub benzimidazole yog tom qab ntawd alkylated nrog qhov xav tau 1-chloro-2-dialkyl aminoethane los ua cov khoom kawg.Txoj kev tshwj xeeb no yog qhov tseem ceeb tshaj plaws rau kev npaj benzimidazole yam tsis muaj kev hloov pauv ntawm lub nplhaib benzene

Feem ntau cov synthesis [4] tsim los ntawm Swiss pab neeg ua ntej koom nrog alkylation ntawm 2, 4-dinitrochlorobenzene nrog 1-amino-2-diethylaminoethane los ua N-(β-diethylaminoethyl)-2, 4-dinitroaniline [aka: N' - (2, 4-dinitrophenyl) -n, n-diethyl-ethane-1, 2-diamine].Cov 2-nitro hloov pauv ntawm 2, 4-dinitroaniline tebchaw raug xaiv txo qis rau cov thawj amines los ntawm kev siv ammonium sulfide ua txo tus neeg sawv cev.Ammonium sulfide tuaj yeem tsim cov roj hydrogen sulfide hauv qhov chaw los ntawm kev ntxiv cov tshuaj ammonium hydroxide concentrated thiab saturating nrog cov tshuaj.Ib qho nruab nrab tsim los ntawm kev xaiv txo qis ntawm 2-nitro-substituent 2-(β-diethylaminoethyl aminoethyl) -5-nitroaniline, uas tom qab ntawd ua haujlwm nrog iminoethyl ether hydrochloride ntawm 4-ethoxy phenylacetonitrile (aka: p-ethoxy benzyl cyanide).Iminoether, 2-(4-ethoxy phenyl) -acetyliminoate ethyl ester hydrochloride, yog npaj los ua roj los ntawm kev ua kom 4-hloov benzyl cyanide nyob rau hauv ib tug sib tov ntawm anhydrous ethanol thiab chloroform, thiab ces saturating cov tshuaj nrog anhydrous hydrogen chloride.Cov tshuaj tiv thaiv ntawm 2-(beta-dialkyl aminoalkyl amine) -5-nitroaniline thiab hydrochloride ntawm iminoethyl ether tshwm sim hauv kev tsim ntawm etonitrazine.Cov txheej txheem tshwj xeeb yog tsim rau kev npaj ntawm 4-, 5-, 6- thiab 7-nitrobenzimidazole.Kev xaiv ntawm kev hloov pauv hloov iminoethers ntawm phenylacetic acid tuaj yeem muab cov tshuaj sib xyaw nrog ntau yam hloov pauv ntawm benzene 2-site

Ntau cov analogues paub, tsuas yog lwm qhov tseem ceeb tshaj plaws tau los ntawm qhov kev tshawb fawb thawj xyoo 1950s yog clonitacetone, uas tsis muaj zog dua li etonissini (txog 3 zaug morphine).Tsis ntev los no, txij li thaum kawg ntawm xyoo 2018, ntau tus neeg tsim qauv analogues tau pib tshwm sim hauv kev ua lag luam tsis raug cai thoob ntiaj teb, nrog rau cov ntsiab lus tseem ceeb tshaj plaws yog metronidazole, isonidazole thiab ettazine, tab sis lwm tus tseem tshwm sim.