Degradable polymers of a cyclic silyl ether and uses thereof

Patent metadata

Field	Value
Publication number	US-10988491-B2
Application number	US-201916542824-A
Country	US
Kind code	B2
Filing date	Aug 16, 2019
Priority date	Aug 17, 2018
Publication date	Apr 27, 2021
Grant date	Apr 27, 2021

Abstract

The present disclosure provides cyclic silyl ethers of the formula:

and salts thereof. The cyclic silyl ethers may be useful as monomers for preparing polymers. Also described herein are polymers prepared by polymerizing a cyclic silyl ether and optionally one or more additional monomers. The polymers may be degradable (e.g., biodegradable). One or more O—Si bonds of the polymers may be the degradation sites. Also described herein are compositions and kits including the cyclic silyl ethers or polymers; methods of preparing the polymers; and methods of using the polymers, compositions, and kits.

First claim

What is claimed is:

1. A compound of Formula (B):

or a salt thereof; wherein
Y is O or C(R Q ) 2 ;
each instance of R Q is independently hydrogen, halogen, or substituted or unsubstituted, C 1-6 alkyl;
j is 1, 2, or 3; k is 2 or 3; the first instance of R K is hydrogen, halogen, unsubstituted C 1-3 alkyl, substituted or unsubstituted n-butyl, substituted or unsubstituted sec-butyl, substituted or unsubstituted iso-butyl, substituted or unsubstituted, C 5-10 alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted aryl, substituted or unsubstituted heteroaryl, or —OR N ; the second instance of R K is hydrogen, halogen, substituted or unsubstituted, C 1-10 alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or —OR N ; and each instance of R N is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted, C 1-10 alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or an oxygen protecting group;
or: j is 1; k is 1; the first instance of R K is halogen, unsubstituted ethyl, substituted or unsubstituted n-butyl, substituted or unsubstituted sec-butyl, substituted or unsubstituted iso-butyl, substituted or unsubstituted, C 5-10 alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted aryl, substituted or unsubstituted heteroaryl, or —OR N ; the second instance of R K is hydrogen, halogen, unsubstituted C 1 alkyl, substituted or unsubstituted, C 2-10 alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or —OR N ; and each instance of R N is independently hydrogen, substituted or unsubstituted acyl, unsubstituted methyl, substituted or unsubstituted, C 3-10 alkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.

2. A composition comprising:
a compound of claim 1 , or a salt thereof; and
optionally an excipient.

3. A kit comprising:
a compound of claim 1 , or a salt thereof; and
instructions for using the compound, or a salt thereof.

4. The compound of claim 1 , or a salt thereof, wherein j is 1, 2, or 3; k is 2 or 3.

5. The compound of claim 1 , or a salt thereof, wherein Y is O.

6. The compound of claim 4 , wherein the compound is of the formula:

or a salt thereof.

7. The compound of claim 4 , wherein the compound is of the formula:

or a salt thereof.

8. The compound of claim 4 , wherein the compound is of the formula:

or a salt thereof.

9. The compound of claim 4 , or a salt thereof, wherein the first instance of R K is unsubstituted C 1-3 alkyl.

10. The compound of claim 4 , or a salt thereof, wherein the second instance of R K is substituted or unsubstituted, C 1-10 alkyl.

11. The compound of claim 9 , or a salt thereof, wherein the second instance of R K is substituted or unsubstituted, C 1-10 alkyl.

12. The compound of claim 4 , or a salt thereof, wherein each instance of R K is unsubstituted C 1-3 alkyl.

13. The compound of claim 1 , or a salt thereof, wherein the second instance of R K is substituted or unsubstituted phenyl.

14. The compound of claim 1 , or a salt thereof, wherein the first instance of R K is substituted or unsubstituted carbocyclyl.

15. The compound of claim 1 , or a salt thereof, wherein each instance of R K is substituted or unsubstituted carbocyclyl.

16. The compound of claim 1 , or a salt thereof, wherein the first instance of R K is substituted or unsubstituted heterocyclyl.

17. The compound of claim 1 , or a salt thereof, wherein each instance of R K is substituted or unsubstituted heterocyclyl.

18. The compound of claim 1 , or a salt thereof, wherein at least one instance of R K is —OR N .

19. The compound of claim 1 , or a salt thereof, wherein each instance of R K is —OR N .

20. The compound of claim 4 , or a salt thereof, wherein each instance of R K is —O(unsubstituted C 1-6 alkyl).

21. The compound of claim 4 , wherein the compound is of the formula:

22. The compound of claim 4 , wherein the compound is of the formula:

23. The compound of claim 4 , wherein the compound is of the formula:

24. The compound of claim 1 , or a salt thereof, wherein j is 1; and k is 1.

25. The compound of claim 24 , or a salt thereof, wherein the compound is of the formula:

or a salt thereof.

Assignees

• Massachusetts Inst Technology

Inventors

• Johnson Jeremiah A
• Shieh Peyton
• Zhang Wenxu

Classifications

• C07F7/1804 Primary

  Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C08G2261/418

  Ring opening metathesis polymerisation [ROMP] · CPC title

• C08G2261/135

  Cross-linked structures · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title