Degradable polymers of a cyclic silyl ether and uses thereof

Patent metadata

Field	Value
Publication number	US-11897905-B2
Application number	US-202117204462-A
Country	US
Kind code	B2
Filing date	Mar 17, 2021
Priority date	Aug 17, 2018
Publication date	Feb 13, 2024
Grant date	Feb 13, 2024

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 polymer prepared by a method comprising polymerizing:
one or more instances of a first monomer, or a salt thereof; and
a second monomer, wherein the second monomer is a compound of Formula (B):

 or a salt thereof, wherein any two instances of the first monomer are the same as or different from each other, and the second monomer is the same as or different from any instance of the first monomer;
in the presence of a metathesis catalyst;

wherein:
Y is O or C(R Q ) 2 ;
each instance of e is independently hydrogen, halogen, or substituted or unsubstituted, C 1-6 alkyl;
each instance of R K is independently 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 ;
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;
j is 1, 2, or 3; and
k is 0, 1, 2, or 3.

2. The polymer of claim 1 , wherein each instance of the first monomer is independently of Formula (A1) or (A2):

or a salt thereof;
wherein:
each instance of

 is Ring B, wherein each instance of Ring B is independently a substituted or unsubstituted, monocyclic carbocyclic ring, substituted or unsubstituted, monocyclic heterocyclic ring, substituted or unsubstituted, monocyclic aryl ring, or substituted or unsubstituted, monocyclic heteroaryl ring;
each instance of Z is independently C(R P ) 2 or O;
each instance of R P is independently hydrogen, halogen, or substituted or unsubstituted, C 1-6 alkyl;
each instance of is independently a single bond or double bond;
each instance of L 1 , L 2 , L 3a , and L 3b is independently a single bond, substituted or unsubstituted, C 1-200 alkylene, substituted or unsubstituted, C 2-200 alkenylene, substituted or unsubstituted, C 2-200 alkynylene, substituted or unsubstituted, C 2-200 heteroalkylene, substituted or unsubstituted, C 2-200 heteroalkenylene, or substituted or unsubstituted, C 2-200 heteroalkynylene;
each instance of R 1 , R 2 , R 3 , and R 4 is independently hydrogen, halogen, or substituted or unsubstituted, C 1-6 alkyl, or two instances of R 1 attached to the same carbon atom are taken together to form oxo, or two instances of R 2 attached to the same carbon atom are taken together to form oxo, or two instances of R 3 attached to the same carbon atom are taken together to form oxo, or two instances of R 4 attached to the same carbon atom are taken together to form oxo;
each instance of W 1 and W 2 is independently a single bond,

each instance of R L is independently hydrogen, a nitrogen protecting group when attached to a nitrogen atom, or -L(M) m ;
each instance of M is independently hydrogen or an agent;
each instance of m is independently an integer between 1 and 10, inclusive;
each instance of L is independently substituted or unsubstituted, C 1-200 alkylene, substituted or unsubstituted, C 2-200 alkenylene, substituted or unsubstituted, C 2-200 alkynylene, substituted or unsubstituted, C 2-200 heteroalkylene, substituted or unsubstituted, C 2-200 heteroalkenylene, or substituted or unsubstituted, C 2-200 heteroalkynylene;
optionally one or more carbon atoms in each instance of the substituted or unsubstituted, C 1-200 alkylene, substituted or unsubstituted, C 2-200 alkenylene, substituted or unsubstituted, C 2-200 alkynylene, substituted or unsubstituted, C 2-200 heteroalkylene, substituted or unsubstituted, C 2-200 heteroalkenylene, and substituted or unsubstituted, C 2-200 heteroalkynylene are independently replaced with substituted or unsubstituted carbocyclylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
optionally one or more heteroatoms in each instance of the substituted or unsubstituted, C 2-200 heteroalkylene, substituted or unsubstituted, C 2-200 heteroalkenylene, and substituted or unsubstituted, C 2-200 heteroalkynylene are independently replaced with substituted or unsubstituted carbocyclylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;
each instance of e and f is independently an integer between 0 and 10, inclusive;
each instance of X 1 and X 2 is independently hydrogen, substituted or unsubstituted, C 1-1000 alkyl, substituted or unsubstituted, C 2-1000 alkenyl, substituted or unsubstituted, C 2-1000 alkynyl, substituted or unsubstituted, C 1-1000 heteroalkyl, substituted or unsubstituted, C 2-1000 heteroalkenyl, substituted or unsubstituted, C 2-1000 heteroalkynyl, —OR C , —N(R C ) 2 , —C(═O)R C , —C(═O)OR C , —C(═O)N(R C ) 2 , —NR C C(═O)R C , —NR C C(═O)OR C , —NR C C(═O)N(R C ) 2 , —OC(═O)R C , —OC(═O)OR C , or —OC(═O)N(R C ) 2 ;

each instance of R C is independently hydrogen, substituted or unsubstituted, C 1-1000 alkyl, substituted or unsubstituted, C 2-1000 alkenyl, substituted or unsubstituted, C 2-1000 alkynyl, substituted or unsubstituted, C 1-1000 heteroalkyl, substituted or unsubstituted, C 2-1000 heteroalkenyl, substituted or unsubstituted, C 2-1000 heteroalkynyl, a leaving group, an oxygen protecting group when attached to an oxygen atom, a nitrogen protecting group when attached to a nitrogen atom,

each instance of n is independently an integer between 1 and 300, inclusive; and
each instance of R F is independently hydrogen, substituted or unsubstituted, C 1-6 alkyl, or an oxygen protecting group; or

is hydrogen or absent, as valency permits.

3. A method of preparing the polymer of claim 1 , the method comprises polymerizing one or more instances of the first monomer, and the second monomer in the presence of the metathesis catalyst.

4. A method of delivering an agent to a subject in need thereof, the method comprising administering to the subject in need thereof the polymer of claim 2 , wherein:
the polymer comprises at least one instance of an agent, wherein each instance of the agent is independently a therapeutic agent, prophylactic agent, or diagnostic agent.

5. A method of delivering an agent to a cell, the method comprising contacting the cell with the polymer of claim 2 , wherein:
the polymer comprises at least one instance of an agent, wherein each instance of the agent is independently a therapeutic agent, prophylactic agent, or diagnostic agent.

6. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of the p

Assignees

• Massachusetts Inst Technology

Inventors

• Johnson Jeremiah A
• Shieh Peyton
• Zhang Wenxu

Classifications

• C07F7/0834 Primary

  Compounds having one or more O-Si linkage (for compounds with C-O-Si linkages see C07F7/18) · CPC title

• A61K31/787

  containing heterocyclic rings having nitrogen as a ring hetero atom · CPC title

• C08G61/06

  prepared by ring-opening of carbocyclic compounds · CPC title

• C08L79/08

  Polyimides; Polyester-imides; Polyamide-imides; Polyamide acids or similar polyimide precursors · CPC title

• C08L83/04

  Polysiloxanes · CPC title