I-Etonitat kanye ne-opioid agonist benzimidazole ehlobene nayo yatholwa ngasekupheleni kwawo-1950 yiqembu labacwaningi baseSwitzerland abasebenza enkampanini eyenza imithi i-CIBA (manje eyiNovartis).Enye yezinhlanganisela zokuqala ezafundwa ithimba laseSwitzerland kwakuyi-1-(beta-diethylaminoethyl) -2-benzyl benzimidazole, etholakale ino-10% womsebenzi we-morphine we-analgesic ku-rodent bioassometry.Lokhu okutholakele kukhuthaze ithimba ukuthi liqale ucwaningo olunzulu oluhlelekile lwe-2-benzyl benzimidazole kanye nokuthola ubudlelwano besakhiwo nomsebenzi walo mndeni omusha wamaphilisi ezinhlungu.Izindlela ezimbili ezijwayelekile zokuhlanganisa zenziwa ukuze kulungiswe lezi zinhlanganisela.

Indlela yokuqala ibandakanya ukujiya kwe-o-phenylenediamine nge-phenylacetonitrile ukuze yakhe i-2-benzylbenzimidazole.I-benzimidazole ibe isihlanganiswa ne-1-chloro-2-dialkyl aminoethane efunekayo ukuze yakhe umkhiqizo wokugcina.Le ndlela iwusizo kakhulu ekulungiseni i-benzimidazole ngaphandle kokuthatha indawo ye-benzene ring

I-synthesis evamile kakhulu [4] eyakhiwe ithimba laseSwitzerland kuqala ihilela i-alkylation ye-2, 4-dinitrochlorobenzene ne-1-amino-2-diethylaminoethane ukuze yakhe i-N-(β-diethylaminoethyl) -2, 4-dinitroaniline [aka: N' - (2, 4-dinitrophenyl) -n, n-diethyl-ethane-1, 2-diamine].Ama-substituents we-2-nitro ku-2, i-4-dinitroaniline compounds bese encishiswa ngokukhetha kuma-amine ayisisekelo ahambisanayo ngokusebenzisa i-ammonium sulfide njenge-ejenti yokunciphisa.I-Ammonium sulfide ingenza i-hydrogen sulfide gas in situ ngokwengeza isixazululo esigxilile se-ammonium hydroxide futhi iyigcwalise ngesixazululo.Okumaphakathi okwakhiwa ngokuncishiswa okukhethiwe kwe-2-nitro-substituent 2-(β-diethylaminoethyl aminoethyl) -5-nitroaniline, ebese isabela nge-iminoethyl ether hydrochloride ye-4-ethoxy phenylacetonitrile (aka: p-ethoxy benzyl cyanide).I-Iminoether, i-2-(4-ethoxy phenyl) -acetyliminoate ethyl ester hydrochloride, ilungiswa njengegesi ngokuncibilikisa i-benzyl cyanide efakwe esikhundleni se-4 enhlanganisela ye-ethanol anhydrous ne-chloroform, bese igcwalisa isisombululo nge-anhydrous hydrogen chloride.Ukusabela phakathi kwe-2-(beta-dialkyl aminoalkyl amine) -5-nitroaniline kanye ne-hydrochloride ye-iminoethyl ether kubangela ukwakheka kwe-etonitrazine.Inqubo ifaneleka ngokukhethekile ukulungiswa kwe-4-, 5-, 6- kanye ne-7-nitrobenzimidazole.Ukukhethwa kwama-iminoethers ashintshiwe esikhundleni se-phenylacetic acid kunganikeza izinhlanganisela nezinto eziningi endaweni ye-benzene 2-site.

Ama-analogue amaningi ayaziwa, okuwukuphela kwenhlanganisela ephawulekayo etholakala ocwaningweni lwangempela ngawo-1950 i-clonitacetone, ebuthaka kakhulu kune-etonissini (cishe izikhathi ezi-3 ze-morphine).Muva nje, kusukela ngasekupheleni kuka-2018, inani lama-analogues abaklami seliqalile ukuvela emakethe engekho emthethweni emhlabeni jikelele, kanye nezinhlanganisela ezivelele kakhulu i-metronidazole, i-isonidazole ne-ettazine, kodwa ezinye ziyaqhubeka nokuvela.