Prostaglandin-bisphosphonate conjugate compounds, methods of making same, and uses thereof

Patent metadata

Field	Value
Publication number	US-9611284-B2
Application number	US-201213687762-A
Country	US
Kind code	B2
Filing date	Nov 28, 2012
Priority date	May 28, 2010
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

The invention provides in part, conjugate compounds. The invention also provides synthesis methods for making the compounds, and uses of the compounds.

First claim

What is claimed is:

1. A compound according to Formula I, or a pharmaceutically acceptable salt thereof:

wherein:
X is —CH 2 , —S—, —O—, or —NH—;
R 2 and R 3 are each independently —H or halo;
Ar is aryl;
Y is —C(O)OR 1 , tetrazole, or N-trityl-tetrazole;
R 1 is H or optionally substituted lower alkyl;
W is

R 7 and R 8 are each independently H, small alkyl, cycloalkyl group or CF 3 ;
is a double or single bond,
n is 1, 2 or 3;
m is 1, 2, 3, 4, 5, or 6; and
o is 0, 1, 2, 3, 4, 5, or 6.

2. A pharmaceutical composition comprising the compound of claim 1 in combination with a pharmaceutically acceptable carrier.

3. A method of selectively delivering a compound to bone or an associated site, the method comprising administering an effective amount of the compound of claim 1 to a subject in need thereof.

4. The method of claim 3 wherein the associate site comprises a site adjacent to a bone in need of treatment.

5. The method of claim 3 wherein the bone in need of treatment is selected from the group consisting of a green stick fracture, compound fracture, lateral fracture, pathologic fracture resulting from an invasive tumor, compression fracture, and fracture requiring a surgical procedure for realignment of a bone.

6. A method of treating or preventing a condition associated with abnormal or excessive bone loss, or with abnormal or reduced bone resorption, or with abnormal calcium metabolism comprising administering an effective amount of the compound of claim 1 to a subject in need thereof.

7. The method of claim 6 , wherein the condition is selected from the group consisting of osteoporosis, glucocorticoid-induced osteoporosis, Paget's disease, abnormally increased bone turnover, bone graft, periodontal disease, alveolar bone loss, tooth loss, bone fracture, periprostheticosteolysis, osteogenesisimperfecta, and metastatic bone disease.

8. The method of claim 6 wherein the subject is a human.

9. A compound that is represented by the following chemical structure, or a pharmaceutically acceptable salt thereof:

10. A pharmaceutical composition comprising the compound of claim 9 in combination with a pharmaceutically acceptable carrier.

Assignees

• Univ Fraser Simon

Inventors

• Young Robert N
• Arns Stephen
• Moreau Anne
• Morshed Mohammed Monzur
• Gibe Romelo

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07F9/65583

  each of the hetero rings containing nitrogen as ring hetero atom · CPC title

• C07F9/3873

  containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S) · CPC title

• C07F9/59

  Hydrogenated pyridine rings · CPC title

• C07F9/572 Primary

  Five-membered rings · CPC title