Nanomaterials

Patent metadata

Field	Value
Publication number	US-12059477-B2
Application number	US-202217579115-A
Country	US
Kind code	B2
Filing date	Jan 19, 2022
Priority date	Jan 20, 2021
Publication date	Aug 13, 2024
Grant date	Aug 13, 2024

Abstract

The present disclosure describes compositions, preparations, nanoparticles (such as lipid nanoparticles), and/or nanomaterials and methods of their use.

First claim

We claim:

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
each of L 1 and L 1′ is independently a covalent bond, —C(O)—, or —OC(O)—;
each of L 2 and L 2′ is independently a covalent bond, an optionally substituted bivalent saturated or unsaturated, straight or branched C1-C12 hydrocarbon chain, or

each Cy A is independently an optionally substituted ring selected from phenylene or 3- to 7-membered saturated or partially unsaturated carbocyclene;
each m is independently 0, 1, or 2;
each of L 3 and L 3′ is independently a covalent bond, —O—, —C(O)O—, —OC(O)—, or —OC(O)O—;
each of R 1 and R 1′ is independently an optionally substituted group selected from saturated or unsaturated, straight or branched C 1 -C 20 hydrocarbon chain wherein 1-3 methylene units are optionally and independently replaced with —O— or —NR—, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring, 1-adamantyl, 2-adamantyl, sterolyl, phenyl, or

each L 4 is independently a bivalent saturated or unsaturated, straight or branched C 1 -C 20 hydrocarbon chain;
each A 1 and A 2 is independently an optionally substituted C 1 -C 20 aliphatic or -L 5 -R 5 ,
or A 1 and A 2 , together with their intervening atoms, may form an optionally substituted ring:

wherein
x is selected from 1 or 2; and
# represents the point of attachment to L 4 ;

each L 5 is independently a bivalent saturated or unsaturated, straight or branched C 1 -C 20 hydrocarbon chain, wherein 1-3 methylene units are optionally and independently replaced with —O— or —NR—;
each R 5 is independently an optionally substituted group selected from a 6- to 10-membered aryl ring or a 3- to 8-membered carbocyclic ring;
Y 1 is a covalent bond, —C(O)—, or —C(O)O—;
Y 2 is a bivalent saturated or unsaturated, straight or branched C 1 -C 6 hydrocarbon chain, wherein 1-2 methylene units are optionally and independently replaced with cyclopropylene, —O—, or —NR—;
Y 3 is an optionally substituted group selected from saturated or unsaturated, straight or branched C 1 -C 14 hydrocarbon chain, wherein 1-3 methylene units are optionally and independently replaced with —O— or —NR—, a 3- to 7-membered saturated or partially unsaturated carbocyclic ring, 1-adamantyl, 2-adamantyl, or phenyl;
X 1 is a covalent bond, —O—, or —NR—;
X 2 is an optionally substituted bivalent saturated or unsaturated, straight or branched C 1 -C 12 hydrocarbon chain, wherein 1-3 methylene units are optionally and independently replaced with —O—, —NR—, or -Cy B -;
each Cy B is independently an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated carbocyclene, phenylene, 3- to 7-membered heterocyclene having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 5- to 6-membered heteroarylene having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
X 3 is hydrogen or an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated carbocyclyl, phenyl, 3- to 7-membered heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 5- to 6-membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and
each R is independently hydrogen or an optionally substituted C 1 -C 6 aliphatic group.

2. The compound of claim 1 , wherein R 1 is

3. The compound of claim 1 , wherein each of A 1 and A 2 is independently selected from:

4. The compound of claim 1 , wherein R 1′ is selected from:

5. The compound of claim 1 , wherein —X 2 —X 3 is selected from:

6. The compound of claim 1 , wherein the compound is of Formula (II):

or a pharmaceutically acceptable salt thereof, wherein n1 is 1, 2, 3, or 4.

7. The compound of claim 1 , wherein the compound is of Formula (IIA):

or a pharmaceutically acceptable salt thereof, wherein n1 is 1, 2, 3, or 4; and n2 is 1, 2, 3, 4, 5, 6, or 7.

8. The compound of claim 1 , wherein the compound is of Formula (IIB):

or a pharmaceutically acceptable salt thereof, wherein n1 is 1, 2, 3, or 4; and n2 is 1, 2, 3, 4, 5, 6, or 7.

9. The compound of claim 1 , wherein the compound is of Formula (IIC):

or a pharmaceutically acceptable salt thereof, wherein n1 is 1, 2, 3, or 4; and n2 is 1, 2, 3, 4, 5, 6, or 7.

10. The compound of claim 1 , wherein the compound is of Formula (III):

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 1 , wherein the compound is of Formula (IIIA):

or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1 , wherein the compound is of Formula (IV):

or a pharmaceutically acceptable salt thereof, wherein n1 is 1, 2, 3, or 4.

13. The compound of claim 1 , wherein the compound is of Formula (V):

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 , wherein the compound is of Formula (VA):

or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1 , wherein the compound is of Formula (VI):

or a pharmaceutically acceptable salt thereof, wherein n1 is 1, 2, 3, or 4.

16. The compound of claim 1 , wherein the compounds is of Formula (VIA):

or a pharmaceutically acceptable salt thereof, wherein n1 is 1, 2, 3, or 4.

17. The compound of claim 1 , wherein the compound is selected fro

Assignees

• Beam Therapeutics Inc

Inventors

• Sago Cory Dane
• Hamilton Gregory Lawrence

Classifications

• A61K47/24

  containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids · CPC title

• A61K31/711

  Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links · CPC title

• A61K31/7105 Primary

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title