IP Library Granted Patent US 9,200,026
Granted Patent B2
US 9,200,026 · App. 13/722,058 · Granted Dec 1, 2015

Antibacterial agents

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Quick Facts
Patent No.
US 9,200,026
App. No.
13/722,058
Granted
Dec 1, 2015
Kind
B2
Abstract

Described herein are novel macrolides, the preparation of novel macrolides, the use of novel macrolides for preventing, treating, or ameliorating various conditions, and the use of novel macrolides as antibacterial agents.

Claims (34)

1. A compound of Formula 1 or Formula 2

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is H, cyclic or acyclic alkyl, cyclic or acyclic alkyl-hydroxyamine, aryl, aryl-hydroxyamine, cyclic or acyclic acyl, cyclic or acyclic acyl-hydroxyamine, heteroalkyl, heteroalkyl-hydroxyamine, heteroaryl, heteroaryl-hydroxyamine, acylaryl, acylaryl-hydroxyamine, acylheteroaryl, acylheteroaryl-hydroxyamine, alkylaryl, alkylaryl-hydroxyamine, alkylheteroaryl, alkylheteroaryl-hydroxyamine, sulfonylalkyl, sulfonylalkyl-hydroxyamine, acylalkoxylsulfonylalkyl, or acylalkoxylsulfonylalkyl-hydroxyamine;

or R 1 is C(O)—NR 4 R 5 , where R 4 and R 5 are each independently selected from the group consisting of hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, urea, and carbamate;

or R 1 is a D-glucose, D-mannose, D-xylose, D-galactose, L-fucose, D-ribose, D-arabinose, D-ribulose, D-fructose, sucrose, lactose, maltose, cellobiose, glucosamine, galactosamine, acetylglucose, acetylgalactose, N-acetylglucosamine, N-acetyl-galactosamine, galactosyl-N-acetylglucosamine, N-acetylneuraminic acid, mycaminose, L-vancosamine, 3-desmethyl-vancosamine, 3-epi-vancosamine, 4-epi-vancosamine, acosamine, 3-amino-glucose, 4-deoxy-3-amino-glucose, actinosamine, daunosamine, 3-epi-daunosamine, ristosamine, or N-methyl-D-glucamine, or clindamycin, each of which is optionally oxidized, reduced, or substituted;

R 2 and R 3 are OH, or R 2 and R 3 are taken together to form a carbonate or carbamate of the formula:

where Z is O, or —N(R 6 ); where R 6 is hydrogen, hydroxy, optionally substituted alkyl, optionally substituted alkoxy, heteroalkyl, optionally substituted aryl, optionally substituted heteroaryl, dimethylaminoalkyl, acyl, or sulfonyl, or a group of the formula A-B-T-C, where T is a triazole;

X is H; and Y is OR 7 ; where R 7 is a pentose, hexose, alkyl, aryl, heteroaryl, acyl or —C(O)—NR 8 R 9 , where R 8 and R 9 are each independently selected from the group consisting of hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, heteroalkyl, aryl, heteroaryl, alkoxy, dimethylaminoalkyl, acyl, sulfonyl, ureyl and carbamyl;

or X and Y are taken together with the attached carbon to form carbonyl;

V is —C(O)—, —C(═NR 11 )—, —C(NR 12 R 13 )—, or —N(R 14 )CH 2 —, wherein the first dash of each of the foregoing V groups is attached to the C-10 carbon and the last dash of each group is attached to the C-8 carbon; and R 11 is hydroxy or alkoxy, R 12 and R 13 are each independently selected from the group consisting of hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureyl, and carbamoyl; and R 14 is hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureyl or carbamoyl;

W is H, F, Cl, Br, I, or OH;

A is —CH 2 —, —C(O)—, —C(O)O—, —C(O)NH—, —S(O) 2 —, —S(O) 2 NH—, or —C(O)NHS(O) 2 —;

B is —(CH 2 ) n — where n is an integer ranging from 0-10, or B is an unsaturated carbon chain of 2-10 carbons, which may contain any alkenyl or alkynyl group;

C is alkyl, aralkyl, alkylaryl, heteroalkyl, aryl, heteroaryl, aminoaryl, or alkylaminoaryl and

R 10 is hydrogen or acyl.

2. The compound of claim 1 of Formula 1, or a pharmaceutically acceptable salt thereof, wherein R 1 is a D-glucose, D-mannose, D-xylose, D-galactose, L-fucose, D-ribose, D-arabinose, D-ribulose, D-fructose, sucrose, lactose, maltose, cellobiose, glucosamine, galactosamine, acetylglucose, acetylgalactose, N-acetylglucosamine, N-acetyl-galactosamine, galactosyl-N-acetylglucosamine, N-acetylneuraminic acid, mycaminose, L-vancosamine, 3-desmethyl-vancosamine, 3-epi-vancosamine, 4-epi-vancosamine, acosamine, 3-amino-glucose, 4-deoxy-3-amino-glucose, actinosamine, daunosamine, 3-epi-daunosamine, ristosamine, or N-methyl-D-glucamine, or clindamycin, each of which is optionally oxidized, reduced, or substituted.

3. The compound of claim 2 wherein R 1 is mycaminose or 4-deoxy-3-amino-glucose.

4. The compound of claim 2 wherein R 1 is clindamycin.

5. The compound of claim 1 of Formula 1, wherein R 6 is a group of the formula A-B-T-C, where T is a triazole.

6. The compound of claim 1 of Formula 2, or a pharmaceutically acceptable salt thereof.

7. The compound of claim 6 wherein X and Y are taken together with the attached carbon to form carbonyl.

8. The compound of claim 6 wherein V is —C(O)—.

9. The compound of claim 6 wherein W is H or F.

10. The compound of claim 9 wherein W is F.

11. The compound of claim 6 wherein A is —CH 2 —, B is —(CH 2 ) n —, and n is an integer from 2-4.

12. The compound of claim 11 wherein n is 3.

13. The compound of claim 6 wherein C is optionally substituted aryl or optionally substituted heteroaryl.

14. The compound of claim 13 wherein C is 3-aminophenyl.

15. The compound of claim 6 wherein R 10 is hydrogen.

16. A pharmaceutical composition comprising a compound of claim 6 and one or more carriers, diluents, or excipients, or a combination thereof.

17. A unit dosage form comprising a therapeutically effective amount of a compound of claim 6 .

18. A method for treating a disease comprising a bacterial infection in a host animal, the method comprising the step of administering a therapeutically effective amount of a compound of claim 6 to the host animal.

19. The method of claim 18 wherein the bacterial infection is a respiratory tract infection.

20. The method of claim 18 wherein the disease is pneumonia.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 14, 2019
From: CEMPRA PHARMACEUTICALS, INC.
To: TETARD, INC.
Reel/Frame 050056/0731 →
NUNC PRO TUNC ASSIGNMENT Recorded Aug 14, 2015
From: OPTIMER PHARMACEUTICALS LLC
To: MERCK SHARP & DOHME CORP.
Reel/Frame 036328/0122 →
CHANGE OF NAME Recorded Aug 12, 2015
From: OPTIMER PHARMACEUTICALS, INC.
To: OPTIMER PHARMACEUTICALS LLC
Reel/Frame 036333/0793 →