Glycopeptide derivative compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-2020368312-A1
Application number	US-201816615232-A
Country	US
Kind code	A1
Filing date	May 22, 2018
Priority date	May 22, 2017
Publication date	Nov 26, 2020
Grant date	—

Abstract

Provided herein are methods and compositions for the treatment of Gram positive bacterial infections. The infection in some embodiments, is a pulmonary infection. The method for treating the bacterial infection, comprises in one embodiment, administering to a patient in need thereof, a composition comprising an effective amount of a compound a glycopeptide derivative of Formula (I) or (II), or a pharmaceutically acceptable salt of Formula (I) or (II).

First claim

1 . (canceled)

2 . A method for treating a bacterial pulmonary infection in a patient in need thereof, comprising administering to the lungs of a patient via a nebulizer, metered dose inhaler or a dry powder inhaler, a composition comprising an effective amount of a compound of Formula (II), or a pharmaceutically acceptable salt thereof:

wherein:
R 1 is C 1 -C 18 linear alkyl, C 1 -C 18 branched alkyl, R 5 —Y—R 6 —(Z) n , or

R 2 is —OH or —NH—(CH 2 ) q —R 7 ;
R 3 is H or

R 4 is H or CH 2 NH—CH 2 —PO 3 H 2 ;
n is 1 or 2;
q is 1, 2, 3, 4, or 5;
X is O, S, NH or H 2 ;
each Z is independently selected from hydrogen, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic;
R 5 and R 6 are independently selected from the group consisting of alkylene, alkenylene and alkynylene, wherein the alkylene, alkenylene and alkynylene groups are optionally substituted with from 1 to 3 substituents selected from the group consisting of alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aminoacyloxy, oxyaminoacyl, azido, cyano, halogen, hydroxyl, carboxyl, carboxylalkyl, thioaryloxy, thioheteroaryloxy, thioheterocyclooxy, thiol, thioalkoxy, substituted thioalkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, hydroxyamino, alkoxyamino, nitro, —SO-alkyl, —SO-substituted alkyl, —SO-aryl, —SO-heteroaryl, —SO 2 -alkyl, —SO 2 -substituted alkyl, —SO 2 -aryl and —SO 2 -heteroaryl
R 7 is —N(CH 2 ) 2 ; —N(CH 2 ) 3 ; or

Y is independently selected from the group consisting of oxygen, sulfur, —S—S—, —NR 8 —, —S(O)—, —SO 2 —, —OSO 2 —, —NR 8 SO 2 —, —SO 2 NR 8 —, —SO 2 O—, —P(O)(OR 8 )O—, —P(O)(OR 8 )NR—, —OP(O)(OR 8 )O—, —OP(O)(OR 8 )NR 8 —, —NR 8 C(O)NR 8 —, and —NR 8 SO 2 NR 8 —; and
each R 8 is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic.

3 . The method of claim 2 , wherein R 3 is H.

4 . The method of claim 2 , wherein R 3 is

5 . The method of claim 3 , wherein R 4 is H.

6 . The method of claim 3 , wherein R 4 is CH 2 —NH—CH 2 —PO 3 H 2 .

7 . The method of claim 1 , wherein X is O.

8 - 12 . (canceled)

13 . The method of claim 1 , wherein R 1 is R 5 —Y—R 6 —(Z) n and Y is —NH—.

14 . (canceled)

15 . The method of claim 7 , wherein R 1 is (CH 2 ) 2 —Y—R 6 —(Z) n .

16 - 19 . (canceled)

20 . The method of claim 13 , wherein R 1 is R 5 —Y—(CH 2 ) 10 —(Z).

21 . The method of claim 20 , wherein (Z) n is H and R 4 is H.

22 . The method of claim 1 , wherein R 2 is OH, R 4 is H, Y is —NH—, and (Z) n is H.

23 - 24 . (canceled)

25 . The method of claim 1 , wherein R 1 is n-decyl.

26 - 39 . (canceled)

40 . The method of claim 1 , wherein R 1 is (CH 2 ) 2 —NH—(CH 2 ) 9 —CH 3 .

41 - 43 . (canceled)

44 . The method of claim 40 , wherein R 2 is OH.

45 - 80 . (canceled)

81 . The method of claim 1 , wherein the bacterial infection is a Gram positive bacterial pulmonary infection.

82 - 83 . (canceled)

84 . The method of claim 81 , wherein the Gram-positive bacterial pulmonary infection is a Staphylococcus pulmonary infection.

85 - 86 . (canceled)

87 . The method of claim 84 , wherein the Staphylococcus pulmonary infection is a Staphylococcus aureus ( S. aureus ) pulmonary infection.

88 . The method of claim 87 , wherein the S. aureus pulmonary infection is a methicillin-resistant S. aureus (MRSA) pulmonary infection.

89 . The method of claim 87 , wherein the S. aureus pulmonary infection is a methicillin-sensitive S. aureus (MSSA) pulmonary infection.

90 - 117 . (canceled)

118 . The method of claim 1 , wherein the patient is a cystic fibrosis patient.

119 - 122 . (canceled)

Assignees

• Insmed Inc

Inventors

• Heckler Ryan
• Konicek Donna
• Plaunt Adam
• Malinin Vladimir
• Perkins Walter

Classifications

• C07K9/008

  directly attached to a hetero atom of the saccharide radical, e.g. actaplanin, avoparcin, ristomycin, vancomycin · CPC title

• A61P31/04 Primary

  Antibacterial agents · CPC title

• A61K38/14 Primary

  Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin} · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• A61K9/1617

  Organic compounds, e.g. phospholipids, fats · CPC title