Tylosin A analogs and derivatives

Patent metadata

Field	Value
Publication number	US-10072040-B2
Application number	US-201514643858-A
Country	US
Kind code	B2
Filing date	Mar 10, 2015
Priority date	Mar 11, 2014
Publication date	Sep 11, 2018
Grant date	Sep 11, 2018

Abstract

The present invention pertains to derivatives of tylosin A. In particular, the present invention pertains to compounds having a structure of Formula (I). The present invention also pertains to compositions comprising derivatives of tylosin A and methods of treating or preventing conditions or disorders using such compounds and compositions.

First claim

What is claimed is:

1. A compound of Formula (I):

or a salt thereof, wherein:
R 1 represents hydrogen or —C(O)R 3 , wherein R 3 represents an optionally substituted C 1 -C 6 -alkyl or C 1 -C 6 -haloalkyl;
R 2 represents —C(O)C(R 4 )(R 5 )(R 6 ), wherein each of R 4 , R 5 , and R 6 are independently selected from the group consisting of C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, aryl, heteroaryl, C 3 -C 8 -cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, and C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl; or
R 2 represents —C(O)N(R 7 )(R 8 ), wherein each of R 7 and R 8 are independently selected from the group consisting of C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, aryl, heteroaryl, C 3 -C 8 -cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, and C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, or R 7 and R 8 together with the nitrogen atom to which they are attached form an optionally substituted saturated or partially saturated heterocyclic ring; or
R 2 represents —CH 2 -A 1 , wherein A 1 represents a 6- to 10-membered aryl substituted with one or more R A or a 5- to 10-membered heteroaryl, wherein the heteroaryl is unsubstituted or substituted with one or more R A , wherein each R A is independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl;
R 9 represents hydrogen or —C(O)R 10 , wherein R 10 represents an optionally substituted C 1 -C 6 -alkyl or C 1 -C 6 -haloalkyl; and
each of a and b independently represents either a single bond or a double bond.

2. The compound of claim 1 or a salt thereof, wherein R 1 is hydrogen.

3. The compound of claim 1 or a salt thereof, wherein R 1 is —C(O)R 3 .

4. The compound of claim 3 or a salt thereof, wherein R 3 is methyl, isopropyl, or n-butyl.

5. The compound of claim 1 or a salt thereof, wherein R 2 is —C(O)C(R 4 )(R 5 )(R 6 ).

6. The compound of claim 5 or a salt thereof, wherein each of R 4 , R 5 , and R 6 are C 1 -C 6 -alkyl.

7. The compound of claim 1 or a salt thereof, wherein R 2 is —C(O)N(R 7 )(R 8 ).

8. The compound of claim 7 or a salt thereof, wherein each of R 7 and R 8 are independently C 1 -C 6 -alkyl, aryl, or C 3 -C 8 -cycloalkyl.

9. The compound of claim 7 or a salt thereof, wherein R 7 and R 8 together with the nitrogen atom to which they are attached form an optionally substituted saturated or partially saturated heterocyclic ring.

10. The compound of claim 9 or a salt thereof, wherein the heterocyclic ring is a pyrrolidine, a piperidine, an azepane, or a morpholine.

11. The compound of claim 1 or a salt thereof, wherein R 2 is —CH 2 -A 1 .

12. The compound of claim 11 or a salt thereof, wherein A 1 is phenyl substituted with one or more R A .

13. The compound of claim 12 or a salt thereof, wherein R A is halogen.

14. The compound of claim 11 or a salt thereof, wherein A 1 is a 5- to 10-membered heteroaryl optionally substituted with one or more R A .

15. The compound of claim 1 or a salt thereof, wherein R 9 is hydrogen.

16. The compound of claim 1 or a salt thereof, wherein R 9 is —C(O)R 10 .

17. The compound of claim 16 or a salt thereof, wherein R 10 is methyl, isopropyl, or n-butyl.

18. A compound of Formula (I):

or a salt thereof, wherein:
R 1 is —C(O)CH 3 and R 2 is

 R 1 is —C(O)CH 3 and R 2 is

 R 1 is —C(O)CH 3 2 is

 R 1 is —C(O)CH(CH 3 ) 2 and R 2 is

 R 1 is —C(O)CH(CH 3 ) 2 and R 2 is

 R 1 is —C(O)CH(CH 3 ) 2 and R 2 is

 R 1 is —C(O)CH(CH 3 ) 2 and R 2 is

 R 1 is —C(O)CH(CH 3 ) 2 and R 2 is

 R 1 is hydrogen and R 2 is

 R 1 is —C(O)(CH 2 ) 3 CH 3 and R 2 is

 R 1 is —C(O)CH 3 and R 2 is —C(O)C(CH 3 ) 3 ; R 1 is —C(O)CH(CH 3 ) 2 and R 2 is —C(O)C(CH 3 ) 3 ; R 1 is hydrogen and R 2 is —C(O)C(CH 3 ) 3 ; R 1 is —C(O)CH 3 and R 2 is —C(O)N(CH 2 CH 3 ) 2 ; R 1 is —C(O)CH 3 and R 2 is —C(O)N(CH 3 )(C 6 H 5 ); R 1 is —C(O)CH 3 and R 2 is

 R 1 is —C(O)CH(CH 3 ) 2 and R 2 is —C(O)N(CH 2 CH 3 ) 2 ; R 1 is hydrogen and R 2 is —C(O)N(CH 2 CH 3 ) 2 ; R 1 is —C(O)CH 3 and R 2 is

 R 1 is —C(O)CH 3 and R 2 is

 R 1 is —C(O)CH 3 and R 2 is —C(O)N(CH(CH 3 ) 2 ) 2 ; R 1 is —C(O)CH 3 and R 2 is —C(O)N((CH 2 ) 3 CH 3 ) 2 ; R 1 is —C(O)CH 3 and R 2 is —C(O)N(CH 2 CH(CH 3 ) 2 ) 2 ; R 1 is —C(O)CH 3 and R 2 is

 R 1 is —C(O)CH 3 and R 2 is

 R 1 is —C(O)CH(CH 3 ) 2 and R 2 is —C(O)N(CH 3 ) 2 ; R 1 is —C(O)CH(CH 3 ) 2 and R 2 is —C(O)N(CH 2 CH 3 )((CH 2 ) 3 CH 3 ); R 1 is hydrogen and R 2 is —C(O)N(CH(CH 3 ) 2 ) 2 ; R 1 is hydrogen and R 2 is —C(O)N((CH 2 ) 3 CH 3 ) 2 ; R 1 is H and R 2 is

 R 1 is —C(O)CH(CH 3 ) 2 and R 2 is

 R 1 is —C(O)CH 3 and R 2 is

 R 1 is —C(O)(CH 2 ) 3 (CH 3 ) and R 2 is

 R 1 is —C(O)(CH 2 ) 3 (CH 3 ) and R 2 is

 R 1 is hydrogen and R 2 is

 or R 1 is hydrogen and R 2 is

R 9 is hydrogen; and
wherein both a and b represent a double bond.

Assignees

• Abbvie Inc

Inventors

• Von Geldern Thomas W
• Kempf Dale J
• Marsh Kennan C

Classifications

• A61K31/7048

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C07H17/08 Primary

  Hetero rings containing eight or more ring members, e.g. erythromycins · CPC title