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a stable heroin analogue that can serve as a vaccine hapten to induce antibodies that block the effects of heroin and its metabolites in rodents and that cross-react immunologically with related drugs of abuse
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نویسنده
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sulima a. ,jalah r. ,antoline j.f.g. ,torres o.b. ,imler g.h. ,deschamps j.r. ,beck z. ,alving c.r. ,jacobson a.e. ,rice k.c. ,matyas g.r.
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منبع
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journal of medicinal chemistry - 2018 - دوره : 61 - شماره : 1 - صفحه:329 -343
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چکیده
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An improved synthesis of a haptenic heroin surrogate 1 (6-amhap) is reported. the intermediate needed for the preparation of 1 was described in the route in the synthesis of 2 (diamhap). a scalable procedure was developed to install the c-3 amido group. using the boc protectng group in 18 allowed preparation of 1 in an overall yield of 53% from 4 and eliminated the necessity of preparing the diamide 13. hapten 1 was conjugated to tetanus toxoid and mixed with liposomes containing monophosphoryl lipid a as an adjuvant. the 1 vaccine induced high anti-1 igg levels that reduced heroin-induced antinociception and locomotive behavioral changes following repeated subcutaneous and intravenous heroin challenges in mice and rats. vaccinated mice had reduced heroin-induced hyperlocomotion following a 50 mg/kg heroin challenge. the 1 vaccine-induced antibodies bound to heroin and other abused opioids, including hydrocodone, oxycodone, hydromorphone, oxymorphone, and codeine.
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آدرس
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medical center drive, national institute on drug abuse, national institute on alcohol abuse and alcoholism, national institutes of health, department of health and human services, intramural research program, drug design and synthesis section, united states, henry m. jackson foundation for the advancement of military medicine, walter reed army institute of research, military hiv research program, united states, medical center drive, national institute on drug abuse, national institute on alcohol abuse and alcoholism, drug design and synthesis section, intramural research program, united states, walter reed army institute of research, u.s. military hiv research program, united states, center for biomolecular science and engineering, naval research laboratory, united states, center for biomolecular science and engineering, naval research laboratory, united states, walter reed army institute of research, u.s. military hiv research program, united states, walter reed army institute of research, u.s. military hiv research program, united states, medical center drive, national institute on drug abuse, national institute on alcohol abuse and alcoholism, national institutes of health, department of health and human services, drug design and synthesis section, molecular targets and medications discovery branch, intramural research program, united states, medical center drive, national institute on drug abuse, national institute on alcohol abuse and alcoholism, national institutes of health, drug design and synthesis section, molecular targets and medications discovery branch, intramural research program, united states, walter reed army institute of research, u.s. military hiv research program, united states
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Authors
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