Isotopically Enriched N-Substituted Piperazine Acetic Acids And Methods For The Preparation Thereof
In some embodiments, this invention pertains to isotopically enriched N-substituted piperazine acetic acids. In some embodiments, this invention pertains to methods for the preparation of isotopically enriched N-substituted piperazine acetic acids.
1 . An isotopically enriched N-substituted piperazine acetic acid compound of the formula:
, or a salt thereof, wherein;
X is O or S;
Y is a straight chain or branched C1-C6 alkyl group or a straight chain or branched C1-C6 alkyl ether group wherein the carbon atoms of the alkyl group or alkyl ether group each independently are optionally substituted with linked deuterium or fluorine atoms;
each Z is independently hydrogen, deuterium, fluorine, chlorine, bromine, iodine, an amino acid side chain, a straight chain or branched C1-C6 alkyl group that may optionally contain a substituted or unsubstituted aryl group wherein the carbon atoms of the alkyl and aryl groups each independently are optionally substituted with linked deuterium or fluorine atoms, a straight chain or branched C1-C6 alkyl ether group that may optionally contain a substituted or unsubstituted aryl group wherein the carbon atoms of the alkyl and aryl groups each independently are optionally substituted with linked deuterium or fluorine atoms or a straight chain or branched C1-C6 alkoxy group that may optionally contain a substituted or unsubstituted aryl group wherein the carbon atoms of the alkoxy and aryl groups each independently are optionally substituted with linked deuterium or fluorine atoms.
2 . The compound of claim 1 , wherein the N-substituted piperazine acetic acid is isotopically enriched with two or more heavy atom isotopes.
3 . The compound of claim 1 , wherein the N-substituted piperazine acetic acid is isotopically enriched with three or more heavy atom isotopes.
4 . The compound of claim 1 , wherein the N-substituted piperazine acetic acid is isotopically enriched with four or more heavy atom isotopes.
5 . The compound of claim 2 , wherein the heavy atom isotopes are each independently 18 O, 15 N or 13 C, but not deuterium.
6 . The compound of claim 1 , wherein each Z is independently hydrogen, fluorine, chlorine, bromine or iodine.
7 . The compound of claim 1 , wherein each Z is independently hydrogen, methyl or methoxy.
8 . The compound of claim 1 , wherein Y is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.
9 . The compound of claim 1 , wherein X is 16 O or 18 O.
10 . The compound of claim 1 , wherein each nitrogen atom of the piperazine ring is independently 14 N or 15 N.
11 . The compound of claim 1 of the formula:
wherein
each C* is independently 12 C or 13 C;
X is O or S;
Y is a straight chain or branched C1-C6 alkyl group or a straight chain or branched C1-C6 alkyl ether group wherein the carbon atoms of the alkyl group or alkyl ether group each independently are optionally substituted with linked deuterium or fluorine atoms;
each Z is independently hydrogen, deuterium, fluorine, chlorine, bromine, iodine, an amino acid side chain, a straight chain or branched C1-C6 alkyl group that may optionally contain a substituted or unsubstituted aryl group wherein the carbon atoms of the alkyl and aryl groups each independently are optionally substituted with linked deuterium or fluorine atoms, a straight chain or branched C1-C6 alkyl ether group that may optionally contain a substituted or unsubstituted aryl group wherein the carbon atoms of the alkyl and aryl groups each independently are optionally substituted with linked hydrogen, deuterium or fluorine atoms or a straight chain or branched C1-C6 alkoxy group that may optionally contain a substituted or unsubstituted aryl group wherein the carbon atoms of the alkyl and aryl groups each independently are optionally substituted with linked hydrogen, deuterium or fluorine atoms.
12 . The compound of claim 1 of the formula:
or a salt thereof.
13 . The compound of claim 12 , wherein the compound is a zwitterion, mono-TFA salt, a mono-HCl salt, a bis-TFA salt or a bis-HCl salt.
14 . The compound of claim 12 , wherein each incorporated heavy atom isotope is present in at least 80 percent isotopic purity.
15 . The compound of claim 12 , wherein each incorporated heavy atom isotope is present in at least 93 percent isotopic purity.
16 . The compound of claim 12 , wherein each incorporated heavy atom isotope is present in at least 96 percent isotopic purity.
17 . The compound of claim 1 , wherein the N-substituted piperazine acetic acid is a mono-TFA salt, a mono-HCl salt, a bis-HCl salt or a bis-TFA salt.
18 . The compound of claim 1 , wherein each incorporated heavy atom isotope is present in at least 80 percent isotopic purity.
19 . The compound of claim 1 , wherein each incorporated heavy atom isotope is present in at least 93 percent isotopic purity.
20 . The compound of claim 1 , wherein each incorporated heavy atom isotope is present in at least 96 percent isotopic purity.
21 . The compound of claim 12 , wherein the compound is a carboxylate anion.
22 . The compound of claim 1 , wherein the compound is a carboxylate anion.
23 . An isotopically enriched N-substituted piperazine acetic acid compound of the formula:
or a salt thereof, wherein
each X is O or S;
Y is a straight chain or branched C1-C6 alkyl group or a straight chain or branched C1-C6 alkyl ether group wherein the carbon atoms of the alkyl group or alkyl ether group each independently are optionally substituted with linked deuterium or fluorine atoms; and
each Z is independently hydrogen, fluorine, chlorine, bromine, iodine, an amino acid side chain or a straight chain or branched C1-C6 alkyl group that may optionally contain a substituted or unsubstituted aryl group wherein the carbon atom of the alkyl and aryl groups each independently are optionally substituted with linked fluorine atoms;
wherein the N-substituted piperazine acetic acid is isotopically enriched with one or more 13 C atoms and/or 15 N atoms.
24 . The compound of claim 23 , wherein Y is a straight chain or branched C1-C6 alkyl group and each Z is independently hydrogen, fluorine, chlorine, bromine, iodine, an amino acid side chain or straight chain or branched C1-C6 alkyl group.
25 . An isotopically enriched N-substituted piperazine acetic acid compound of the formula:
or a salt thereof, wherein;
X is O or S;
Y is a straight chain or branched C1-C6 alkyl group or a straight chain or branched C1-C6 alkyl ether group; and
each Z is independently hydrogen, fluorine, chlorine, bromine, iodine, an amino acid side chain or a straight chain or branched C1-C6 alkyl group; and
wherein the N-substituted piperazine is isotopically enriched with one or more 13 C atoms, 15 N atoms and/or 18 O atoms.
26 . An isotopically enriched N-substituted piperazine acetic acid compound of the formula:
or a salt thereof, wherein the N-substituted piperazine is isotopically enriched with one or more 13 C atoms, 15 N atoms and/or 18 O atoms.