Stable heavy isotopes in amide functional groups and uses thereof
AssigneesRisen (Suzhou) Pharma Tech Co., Ltd., Shanghai Junshi Biosciences Co., Ltd.
InventorsJiasheng LU, Jiamin GU, Xiang JI, Dongqing ZHU, Xiaolin HE, Xianqi KONG
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Abstract
There are provided isotope-enriched compounds containing stable heavy isotope-enriched amide functional groups for modulating the pharmacokinetic profile, metabolic profile, and/or delivery efficiency of a drug or prodrug, as well as its therapeutic or prophylactic efficacy and/or adverse effects. Use of the isotope-enriched amide-containing drugs and prodrugs for the treatment or prevention of disease states and conditions is also provided.
Claims62
An isotope-enriched compound of Formula I, or a pharmaceutically acceptable salt, ester, hydrate, chelate, or solvate thereof:
- where:
- n is an integer selected from 1 to 3;
- is an amide functional group isotope-enriched with one or more stable heavy isotope selected from 18O, 17O, 13C, and 15N;
- R is an organic moiety selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and heterocycle, wherein R is substituted or unsubstituted;
- and
- R1 and R2 are independently a hydrogen or an organic moiety selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, heterocycle, alkoxy, acyl and alkylthio, wherein R1 and R2 are independently substituted or unsubstituted;
- provided that the —NR1R2 moiety is not a 3-sulfo-1 -propylamino moiety.
An isotope-enriched compound comprising a heavy isotope-enriched amide functional group, which is:
- or a pharmaceutically acceptable salt, ester, hydrate, chelate, or solvate thereof.
An isotope-enriched compound which is:
- or a pharmaceutically acceptable salt, ester, hydrate, chelate, or solvate thereof.
A method for reducing metabolism of a compound, reducing a compound's therapeutic toxicity, reducing a compound's adverse effects, increasing tolerability of a compound, improving biodistribution of a compound, and/or increasing the therapeutic or prophylactic effect of a compound in a subject, the compound comprising one or more amide functional group, the method comprising:
- (a) enriching one or more amide functional group on the compound with one or more stable heavy isotope selected from 18O, 17O, 13C, and 15N, to form a heavy isotope-enriched compound;
- and
- (b) administering the heavy isotope-enriched compound to the subject, wherein the compound's metabolism is reduced, the compound's therapeutic toxicity is reduced, the compound's adverse effects are reduced, the compound's tolerability is increased, the compound's biodistribution is improved, and/or the therapeutic or prophylactic effect of the compound is increased compared to administration of the non-isotope-enriched compound to the subject.
Dependencies are inferred from the claim text.