Compounds, reagents, and uses thereof
The present invention provides a compound of formula (I), formula (II), formula (III), (IV) or a salt thereof, compositions and methods of making the compound, methods and reagents for measuring the compound, and kits using the same. The use of a compound of formula (I), formula (II), formula (III), or formula (IV) for assessing or monitoring kidney function in a subject, determining predisposition to developing reduced kidney function, classifying a subject according to level of kidney function, and diagnosing or monitoring chronic kidney disease is also described.
1. A compound represented by the following formula:
or a salt thereof, wherein *indicates 13 C; and the compound is at least 60% pure.
2. A kit comprising a compound of claim 1 , or a salt thereof, and instructions for measuring the level of the compound in a biological sample obtained from a subject.
3. A method for preparing a compound represented by the following formula:
or a salt thereof, comprising the steps of:
a) reacting a compound represented by the following formula:
or a salt thereof, with a Wittig reagent R′ 3 P═CH 2 SMe, wherein R′ is Ph or an electron withdrawing group, to form a compound of formula (Va) or a salt thereof:
b) deprotecting the compound of (Va) or a salt thereof to form a compound of formula (I) or a salt thereof.
4. The method of claim 3 , wherein the method is for preparing a compound of formula (III):
or a salt thereof, and wherein
(i) the method comprises the steps of:
a) reacting a compound of formula (VI) or a salt thereof:
with a Wittig reagent R′ 3 P═CH 2 SMe, wherein R′ is Ph or an electron-withdrawing group, to form a compound of formula (VIa) or a salt thereof:
b) purifying the compound of (VIa) or a salt thereof to yield a compound of formula (VIb) or a salt thereof:
c) deprotecting the compound of formula (VIb) or a salt thereof to form the compound of formula (III) or a salt thereof; or
(ii) the method comprises the steps of:
a) reacting a compound of formula (VI) or a salt thereof:
with a Wittig reagent R′ 3 P═CH 2 SMe, wherein R′ is Ph or an electron-withdrawing group, to form a compound of formula (VIa) or a salt thereof:
b) deprotecting the compound of formula (VIa) or a salt thereof to form a compound of formula (VIc) or a salt thereof:
and
c) purifying the compound of formula (VIc) or a salt thereof to yield the compound of formula (III) or a salt thereof.
5. A method of preparing a compound represented by the following formula:
or a salt thereof, wherein
(i) the method comprises the steps of:
a) reacting a compound of formula (VII):
or a salt thereof, with a Wittig reagent R′ 3 P═CH 2 SMe, to form a compound of formula (VIIa),
or a salt thereof, wherein R′ is Ph or an electron-withdrawing group, and R 1 and R 2 are each independently a silyl group;
b) purifying the compound of formula (VIIa) or a salt thereof, to yield a compound of formula (VIIb) or a salt thereof:
c) deprotecting the compound of formula (VIIb) or a salt thereof to form the compound of formula (III) or a salt thereof; or
(ii) the method comprises the steps of:
a) reacting a compound of formula (VII):
or a salt thereof, with a Wittig reagent R′ 3 P═CH 2 SMe, to form a compound of formula (VIIa) or a salt thereof,
wherein R′ is Ph or an electon-withdrawing group, and R 1 and R 2 are each independently a silyl group;
b) deprotecting the compound of formula (VIIa) or a salt thereof to form a compound of formula (VIIc) or a salt thereof:
c) purifying the compound of formula (VIIc) or a salt thereof to yield the compound of formula (III) or a salt thereof.
6. A method of preparing a compound represented by the following formula:
or a salt thereof, wherein
(i) the method comprises the steps of:
a) reacting a compound of formula (IX):
with methanethiol to form a compound of formula (VIIIa) or a salt thereof:
b) purifying the compound of formula (VIIIa) or a salt thereof to yield a compound of formula (VIIIb) or a salt thereof:
c) deprotecting the compound of formula (VIIIb) or a salt thereof to form the compound of formula (III) or a salt thereof, or
(ii) the method comprises the steps of:
a) reacting a compound of formula (IX):
with methanethiol to form a compound of formula (VIIIa) or a salt thereof:
b) deprotecting the compound of formula (VIIIa) or a salt thereof to form a compound of formula (VIIIb) or a salt thereof:
c) purifying the compound of formula (VIIIb) or a salt thereof to yield the compound of formula (III) or a salt thereof,
wherein:
R 1 and R 2 are each independently a silyl group and R 3 is a t-butyl group or a silyl group.
7. The method of claim 4 , wherein the method comprises the steps of:
a) reacting a compound of formula (VI) or a salt thereof:
with a Wittig reagent R′ 3 P═CH 2 SMe, wherein R′ is Ph or an electron-withdrawing group, to form a compound of formula (VIa) or a salt thereof:
b) purifying the compound of (VIa) or a salt thereof to yield a compound of formula (VIb) or a salt thereof:
c) deprotecting the compound of formula (VIb) or a salt thereof to form the compound of formula (III) or a salt thereof.
8. The method of claim 4 , wherein the method comprises the steps of:
a) reacting a compound of formula (VI) or a salt thereof:
with a Wittig reagent R′ 3 P═CH 2 SMe, wherein R′ is Ph or an electron-withdrawing group, to form a compound of formula (VIa) or a salt thereof:
b) deprotecting the compound of formula (VIa) or a salt thereof to form a compound of formula (VIc) or a salt thereof:
c) purifying the compound of formula (VIc) or a salt thereof to yield the compound of formula (III) or a salt thereof.
9. The method of claim 5 , wherein the method comprises the steps of:
a) reacting a compound of formula (VII):
or a salt thereof, with a Wittig reagent R′ 3 P═CH 2 SMe, to form a compound of formula (VIIa),
or a salt thereof, wherein R′ is Ph or an electron-withdrawing group, and R 1 and R 2 are each independently a silyl group;
b) purifying the compound of formula (VIIa) or a salt thereof, to yield a compound of formula (VIIb) or a salt thereof:
c) deprotecting the compound of formula (VIIb) or a salt thereof to form the compound of formula (III) or a salt thereof.
10. The method of claim 5 , wherein the method comprises the steps of:
a) reacting a compound of formula (VII):
or a salt thereof, with a Wittig reagent R′ 3 P═CH 2 SMe, to form a compound of formula (VIIa) or a salt thereof,
wherein R′ is Ph or an electron-withdrawing group, and R 1 and R 2 are each independently a silyl group;
b) deprotecting the compound of formula (VIIa) or a salt thereof to form a compound of formula (VIIc) or a salt thereof:
c) purifying the compound of formula (VIIc) or a salt thereof to yield the compound of formula (III) or a salt thereof.
11. The method of claim 6 , wherein the method comprises the steps of:
a) reacting a compound of formula (IX):
with methanethiol to form a compound of formula (VIIIa) or a salt thereof:
b) purifying the compound of formula (VIIIa) or a salt thereof to yield a compound of formula (VIIIb) or a salt thereof:
c) deprotecting the compound of formula (VIIIb) or a salt thereof to form the compound of formula (III) or a salt thereof.
12. The method of claim 6 , wherein the method comprises the steps of:
a) reacting a compound of formula (IX):
with methanethiol to form a compound of formula (VIIIa) or a salt thereof:
b) deprotecting the compound of formula (VIIIa) or a salt thereof to form a compound of formula (VIIIb) or a salt thereof:
c) purifying the compound of formula (VIIIb) or a salt thereof to yield the compound of formula (III) or a salt thereof.
13. The compound of claim 1 , wherein the compound is represented by the following formula:
14. The compound of claim 1 , wherein the compound is represented by the following formula:
15. The compound of claim 1 , wherein the compound is represented by the following formula:
16. The compound of claim 1 , wherein the compound is represented by the following formula:
17. The compound of claim 1 , wherein the compound is represented by the following formula:
18. The compound of claim 1 , wherein the compound is represented by the following formula:
19. The compound of claim 1 , wherein the compound is represented by the following formula:
20. The compound of claim 1 , wherein the compound is represented by the following formula: