Moenomycin analogs, methods of synthesis, and uses thereof

Patent metadata

Field	Value
Publication number	US-9273084-B2
Application number	US-201314390811-A
Country	US
Kind code	B2
Filing date	Apr 5, 2013
Priority date	Apr 6, 2012
Publication date	Mar 1, 2016
Grant date	Mar 1, 2016

Abstract

The present invention provides compounds of Formula (I); or a pharmaceutically acceptable form thereof; wherein R 1 ,R 2 ,R 3 ,R 6 ,R 7 ,R 12 ,R a , and R b are as defined herein, and G is a group of Formula (a), (b), or (c): Formula (II), wherein X 1 ; X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , Y, R C , R d , R z , a, d, e, x, n, and m are as defined herein. The present invention further provides pharmaceutical compositions comprising a compound of Formula (I), kits comprising such compositions, methods of use and treatment, and preparative methods.

First claim

What is claimed is:

1. A compound of Formula (I):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, isomer, enantiomer, diastereomer, or polymorph thereof;
wherein:
G is a group of Formula (a), (b), or (c):

wherein a is 3, 4, or 5;

wherein:
X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , and X 7 are each independently hydrogen or halogen;
d is an integer between 1 and 25, inclusive; and
e is an integer of between 2 and 25, inclusive;
provided that at least one of X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , and X 7 is halogen; and
the sum of d and e is greater than 16;

or

wherein:
Y is —O—, —S—, —NR Y —, or an optionally substituted methylene group, wherein R Y is hydrogen, optionally substituted aliphatic, or an amino protecting group;
each instance of R c is independently —F, —Br, —I, —Cl, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted carbocycyl, optionally substituted heterocycyl, optionally substituted aryl, optionally substituted heteroaryl, —OR e , —SR e , —NHR e , or —N(R e ) 2 , wherein each instance of R e is independently hydrogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted carbocycyl, optionally substituted heterocycyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R e groups are joined to form a 5- to 6-membered optionally substituted heterocycyl or optionally substituted heteroaryl ring;
each instance of R d is independently —F, —Br, —I, —Cl, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted carbocycyl, optionally substituted heterocycyl, optionally substituted aryl, optionally substituted heteroaryl, —OR f , —SR f , —NHR f , or —N(R f ) 2 , wherein each instance of R f is independently hydrogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted carbocycyl, optionally substituted heterocycyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R f groups are joined to form a 5- to 6-membered optionally substituted heterocycyl or optionally substituted heteroaryl ring;
R z is hydrogen, —F, —Br, —I, —Cl, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted carbocycyl, optionally substituted heterocycyl, optionally substituted aryl, optionally substituted heteroaryl, —OR g , —SR g , —NHR g , or —N(R g ) 2 , wherein each instance of R g is independently hydrogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted carbocycyl, optionally substituted heterocycyl, optionally substituted aryl, or optionally substituted heteroaryl or two R g groups are joined to form a 5- to 6-membered optionally substituted heterocycyl or optionally substituted heteroaryl ring;
each instance of n is, independently, 0, 1, 2, 3, or 4;
each instance of m is, independently, 0, 1, 2, 3, or 4; and
x is 1, 2, 3, 4, 5, or 6;
R xx is hydrogen, a hydroxyl protecting group, or a group of Formula:

R 12 is hydrogen, a hydroxyl protecting group, or the group (D):

wherein R 13 , R 14 , R 15 , R 16 , and R 17 are each independently hydrogen or a hydroxyl protecting group;
R 1 , R 2 , R 3 , and R 4 are each independently hydrogen or an amino protecting group;
R 5 is hydrogen, an amino protecting group, or the group (A):

R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are each independently hydrogen or a hydroxyl protecting group; and
R a and R b are each independently hydrogen or a hydroxyl protecting group.

2. The compound of claim 1 of Formula (II):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, isomer, enantiomer, diastereomer, or polymorph thereof.

3. The compound of claim 1 of Formula (III):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, isomer, enantiomer, diastereomer, or polymorph thereof; wherein R 17 is hydrogen or a hydroxyl protecting group.

4. The compound of claim 1 of Formula (IV):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, isomer, enantiomer, diastereomer, or polymorph thereof; wherein R 18 is hydrogen or a hydroxyl protecting group.

5. The compound of claim 1 wherein G is a group of Formula (a).

6. The compound of claim 5 , wherein the group of Formula (a) is selected from the group consisting of:

7. The compound of claim 1 wherein G is a group of Formula (b).

8. The compound of claim 7 wherein at least one of X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , and X 7 is halogen.

9. The compound of claim 7 wherein X 1 and X 2 are each hydrogen, X 3 and X 4 are each fluoro, and X 5 , X 6 , and X 7 are each fluoro.

10. The compound of claim 7 , wherein the group of Formula (b) is selected from the group consisting of:

Assignees

• Harvard College

Inventors

• Kahne Daniel Evan
• Kahne Suzanne Walker
• Tsukamoto Hirokazu

Classifications

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07H13/12 Primary

  by acids having the group -X-C(=X)-X-, or halides thereof, in which each X means nitrogen, oxygen, sulfur, selenium or tellurium, e.g. carbonic acid, carbamic acid · CPC title

• C07F9/65586

  at least one of the hetero rings does not contain nitrogen as ring hetero atom · CPC title

• C07H5/06

  Aminosugars · CPC title