Mannose derivatives for treating bacterial infections

Patent metadata

Field	Value
Publication number	US-11634447-B2
Application number	US-202017120441-A
Country	US
Kind code	B2
Filing date	Dec 14, 2020
Priority date	Dec 18, 2012
Publication date	Apr 25, 2023
Grant date	Apr 25, 2023

Abstract

The present invention relates to compounds useful for the treatment or prevention of bacteria infections. These compounds have formula I:The invention also provides pharmaceutically acceptable compositions containing the compounds and methods of using the compositions in the treatment of bacteria infections. Finally, the invention provides processes for making compounds of the invention.

First claim

What is claimed is:

1. A pharmaceutical composition in the form of an oral dosage form comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient or carrier:

wherein
Z is

Ring H is an optionally substituted 5-6 membered aromatic monocyclic ring optionally having 1-4 heteroatoms selected from nitrogen, or sulfur; an 8-12 membered aromatic bicyclic ring optionally having 1-6 heteroatoms selected from oxygen, nitrogen, or sulfur; or a 10-14 membered aromatic tricyclic ring optionally having 1-6 heteroatoms selected from oxygen, nitrogen, or sulfur;
L 2 is —X 2 Y 2 — wherein X 2 is a C 1 aliphatic or —C(O)— and Y 2 is C 1 -C 10 aliphatic wherein up to two methylene units of the C 1 -C 10 aliphatic are optionally replaced with —C(O)—, NH, or N(C 1 -C 6 aliphatic); L 2 is optionally substituted with 1-3 halo;
L 3 is C 1 -C 12 aliphatic wherein up to three methylene units of the C 1 -C 12 aliphatic are optionally replaced with —C(O)—, NH, or N(C 1 -C 6 aliphatic); L 3 is optionally substituted with 1-3 halo;
each J H is independently halogen, —CN, —NO 2 , X J , Q J , or X J -Q J ; or two J H groups bound to the same carbon atom, together with the carbon atom to which they are bound, optionally form —C═N—OH, —C(O)—, or Ring HH;
Ring HH is a 3-8 membered saturated monocyclic ring having 0-2 heteroatoms selected from oxygen, nitrogen, or sulfur; optionally substituted with 1-4 occurrences of J HH ;
J HH is halo, CN, oxo, X J , Q J , or X J -Q J ;
X J is a C 1 -C 10 aliphatic, wherein up to 4 methylene units of the C 1 -C 10 aliphatic are optionally replaced with —O—, —NH, N(C 1 C 6 aliphatic), —S—, —C(O)—, —C(═NOH)—, —S(O)—, —S(O) 2 —, P, or P(O); X J is optionally substituted with 0-6 occurrences of halo, OH, or C 1-4 alkyl; or optionally substituted with 0-1 occurrences of CN;
Q J is a 3-7 membered monocyclic saturated, fully unsaturated, partially unsaturated, or aromatic ring optionally having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur; or an 8-12 membered saturated, fully unsaturated, partially unsaturated, or aromatic ring optionally having 1-6 heteroatoms selected from oxygen, nitrogen, or sulfur; wherein each Q J is optionally substituted with 1-6 occurrences of halo, oxo, CN, or C 1-6 alkyl, wherein up to 2 methylene units of said C 1-6 alkyl are optionally replaced with —O—, —NH, N(C 1 -C 6 aliphatic), —S—, —C(O)—, —S(O)—, or —S(O) 2 —.

2. The pharmaceutical composition of claim 1 , wherein, in compound of formula I, Ring H, is phenyl, napthyl, or a 5-6 membered heteroaryl having 1-4 heteroatoms selected from oxygen, nitrogen, or sulfur.

3. The pharmaceutical composition of claim 1 , wherein, in compound of formula I, J H is halo, CN, NO 2 , phenyl, or C 1-10 aliphatic wherein up to 3 methylene units are optionally replaced with O, NH, N(C 1-4 alkyl), S, C(O), SO, or SO 2 ; wherein said J H is optionally substituted with 1-3 occurrences of CN, halo or phenyl.

4. The pharmaceutical composition of claim 1 , wherein, in compound of formula I,
L 2 is C 1-6 aliphatic or —(C 1-4 aliphatic)-C(O)NH—;
L 3 is C 1-6 aliphatic or —NHC(O)—(C 1-4 aliphatic)-;
Ring H is phenyl or naphthyl; and
J H is halo, CN, NO 2 , C 1-6 aliphatic, —OC 1-6 aliphatic, or C(O)O(C 1-6 aliphatic); wherein said J H is optionally substituted with 1-3 occurrences of halo.

5. The pharmaceutical composition of claim 1 , wherein, in compound of formula I, L 2 and L 3 are each independently C 1 -C 4 alkenyl or C 1 -C 4 alkynyl.

6. The pharmaceutical composition of claim 1 , wherein the compound of formula I has formula IB:

7. The pharmaceutical composition of claim 6 , wherein, in compound of formula IB, L 2 and L 3 are bonded to the mannose ring via a carbon atom.

8. The pharmaceutical composition of claim 7 , wherein, in compound of formula IB, L 2 and L 3 are each independently C 1 -C 6 alkenyl or C 1 -C 6 alkynyl.

9. The pharmaceutical composition of claim 8 , wherein, in compound of formula IB, at least one of L 2 and L 3 is —C≡C—.

10. The pharmaceutical composition of claim 1 , wherein the compound of formula I has formula ID:

11. The pharmaceutical composition of claim 10 , wherein in the compound of formula ID, Ring H is an optionally substituted 5-6 membered monocyclic aromatic ring optionally having 1-4 heteroatoms selected from nitrogen, or sulfur; or an 8-12 membered bicyclic aromatic ring optionally having 1-6 heteroatoms selected from oxygen, nitrogen, or sulfur; or a 10-14 tricyclic aromatic ring optionally having 1-6 heteroatoms selected from oxygen, nitrogen, or sulfur.

12. The pharmaceutical composition of claim 10 , wherein in the compound of formula ID, Ring H, together with J H and J HH , is selected from the following:

13. The pharmaceutical composition of claim 10 , wherein in the compound of formula ID, J H is halogen, oxo, CN, X J , Q J , or X J -Q J ; with
X J being C 1 -C 10 aliphatic, wherein up to 4 methylene units of the C 1 -C 10 aliphatic are optionally replaced with —O—, —NH, N(C 1 -C 6 aliphatic), —S—, —C(O)—, —S(O)—, —S(O) 2 —;
Q J being phenyl; and
J H being optionally substituted with 0-3 occurrences of halo or 0-1 occurrences of CN.

14. The pharmaceutical composition of claim 1 , wherein the compound of formula I corresponds to a structural formula selected from the group consisting of:

#
Structure

69

70

71

Assignees

• Vertex Pharma

Inventors

• Ramtohul Yeeman K
• Das Sanjoy Kumar
• Cadilhac Caroline
• Reddy Thumkunta Jagadeeswar
• Vaillancourt Louis
• Gallant Michel
• Liu Bingcan
• Dietrich Evelyne
• Vallee Frederic
• Martel Julien
• Poisson Carl

Classifications

• C07H19/056

  Triazole or tetrazole radicals · CPC title

• C07H15/26

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title

• A61K31/7056

  containing five-membered rings with nitrogen as a ring hetero atom · CPC title

• A61K31/7048

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

• A61K31/517

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title