Oxadiazole compounds and compositions for delivering active agents

1. A pharmaceutical composition comprising:

(A) an active agent; and

(B) at least one compound selected from:

Cpd #

X

R 2

1

2-OH

(CH 2 ) 8

2

2-OH

(CH 2 ) 6

3

2-OH

(CH 2 ) 4

4

2-OH

(CH 2 ) 7

5

2-OH-5-Cl

(CH 2 ) 6

6

2-OH-3,5-di-Cl

(CH 2 ) 6

7

2-OH-4-methyl

(CH 2 ) 6

8

2-OH-4-OMe

(CH 2 ) 6

9

2-OH-4-OMe

(CH 2 ) 4

and salts thereof.

2. The composition of claim 1 , wherein the active agent is selected from the group consisting of a biologically active agent, a chemically active agent, and a combination thereof.

3. The composition of claim 2 , wherein the biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.

4. The composition of claim 2 , wherein the biologically active agent is selected from the group consisting of growth hormones, human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormones, porcine growth hormones, growth hormone-releasing hormones, interferons, α-interferon, β-interferon, γ-interferon, interleukin-1, interleukin-2, insulin, porcine insulin, bovine insulin, human insulin, human recombinant insulin, insulin-like growth factor (IGF), IGF-1, heparin, unfractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, salmon calcitonin, eel calcitonin, human calcitonin; erythropoietin(EPO), artrial naturetic factor, antigens, monoclonal antibodies, somatostatin, protease inhibitors, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, leutinizing-hormone-releasing-hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, cromolyn sodium, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), fragments of PTH, antimicrobials, anti-fungal agents, vitamins; analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and any combination thereof.

5. The composition of claim 2 , wherein the biologically active agent comprises insulin, unfractionated heparin, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, PTH, EPO, hGH or combinations thereof.

6. The composition of claim 2 , wherein the biologically active agent comprises salmon calcitonin.

7. The composition of claim 1 , wherein the compound is

Cpd #

X

R 2

3

2-OH

(CH 2 ) 4

or a salt thereof.

8. A dosage unit form comprising:

(A) the composition of claim 1 ; and

(B) (a) an excipient,

(b) a diluent,

(c) a disintegrant,

(d) a lubricant,

(e) a plasticizer,

(f) a colorant,

(g) a dosing vehicle, or

(h) any combination thereof.

9. The dosage unit form of claim 8 , wherein the biologically active agent comprises at least one protein, polypeptide, peptide, hormone, polysaccharide, mucopolysaccharide, carbohydrate, or lipid.

10. The dosage unit form of claim 8 , wherein the biologically active agent is selected from the group consisting of growth hormones, human growth hormones (hGH), recombinant human growth hormones (rhGH), bovine growth hormones, porcine growth hormones, growth hormone-releasing hormones, interferons, α-interferon, β-interferon, γ-interferon, interleukin-1, interleukin-2, insulin, porcine insulin, bovine insulin, human insulin, human recombinant insulin, insulin-like growth factor (IGF), IGF-1, heparin, unfractionated heparin, heparinoids, dermatans, chondroitins, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, salmon calcitonin, eel calcitonin, human calcitonin; erythropoietin (EPO), atrial naturetic factor, antigens, monoclonal antibodies, somatostatin, protease inhibitors, andrenocorticotropin, gonadotropin releasing hormone, follicle stimulating hormone, glucocerebrosidase, thrombopoietin, filgrastim, prostaglandins, cyclosporin, vasopressin, cromolyn sodium, sodium chromoglycate, disodium chromoglycate, vancomycin, desferrioxamine (DFO), parathyroid hormone (PTH), fragments of PTH, antimicrobials, anti-fungal agents, vitamins; analogs, fragments, mimetics and polyethylene glycol (PEG)-modified derivatives of these compounds; and any combination thereof.

11. The dosage form of claim 9 , wherein the biologically active agent comprises insulin, unfractionated heparin, low molecular weight heparin, very low molecular weight heparin, ultra low molecular weight heparin, calcitonin, PTH, EPO, hGH, or combinations thereof.

12. The dosage unit form of claim 8 , wherein the active agent comprises salmon calcitonin.

13. The dosage unit form of claim 8 , wherein the dosage unit form is in the form of a tablet, a capsule, a powder, or a liquid.

14. A method for preparing a composition comprising mixing:

(A) at least one active agent;

(B) at least one compound selected from:

Cpd #

R 1

R 2

1

2-OH

(CH 2 ) 8

2

2-OH

(CH 2 ) 6

3

2-OH

(CH 2 ) 4

4

2-OH

(CH 2 ) 7

5

2-OH-5-Cl

(CH 2 ) 6

6

2-OH-3,5-di-Cl

(CH 2 ) 6

7

2-OH-4-methyl

(CH 2 ) 6

8

2-OH-4-OMe

(CH 2 ) 6

9

2-OH-4-OMe

(CH 2 ) 4;

and

(C) optionally, a dosing vehicle.

15. A compound having the formula

or a salt thereof, wherein

R 1 is phenyl substituted with —OH;

R 1 is optionally further substituted with one or more of C 1 -C 4 alkyl or fluoroalkyl, C 2 -C 4 alkenyl, C 1 -C 4 fluoroalkoxy, —OH, —SH, phenyl, phenoxy, —CO 2 R 3 , or —N(CH 3 ) 2 ;

R 2 is C 1 -C 24 alkylene;

R 2 is optionally substituted with one or more of C 1 -C 4 alkyl or fluoroalkyl, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy or fluoroalkoxy, halogens, —OH, —SH, phenyl, phenoxy, —CO 2 R 3 , —N(CH 3 ) 2 , —NO 2 , —NH 2 , C 3 -C 10 cycloalkyl, C 3 -C 10 cycloalkenyl, aryl, or (C 1 -C 10 alkyl)aryl; and

R 3 is C 1 -C 4 alkyl or C 2 -C 4 alkenyl.

16. A pharmaceutical composition comprising:

(A) an active agent; and

(B) a compound having the formula

wherein

R 1 is phenyl substituted with —OH;

R 1 is optionally substituted with C 1 -C 4 alkyl or fluoroalkyl, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy or fluoroalkoxy, halogens, —OH, —SH, phenyl, phenoxy, —CO 2 R 3 , —N(CH 3 ) 2 , —NO 2 , or —NH 2 ;

R 2 is C 1 -C 24 alkylene;

R 2 is optionally substituted with C 1 -C 4 alkyl or fluoroalkyl, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy or fluoroalkoxy, halogens, —OH, —SH, phenyl, phenoxy, —CO 2 R 3 , —N(CH 3 ) 2 , —NO 2 , C 3 -C 10 cycloalkyl, C 3 -C 10 cycloalkenyl, aryl, or (C 1 -C 10 alkyl)aryl; and

R 3 is hydrogen, C 1 -C 4 alkyl, or C 2 -C 4 alkenyl.

17. A compound having the formula

or a salt thereof, wherein

R 1 is phenyl substituted with —OH;

R 1 is optionally further substituted with one or more of C 1 -C 4 alkyl or fluoroalkyl, C 2 -C 4 alkenyl, C 1 -C 4 fluoroalkoxy, halogen, —OH, —SH, phenyl, phenoxy, —CO 2 R 3 , or —N(CH 3 ) 2 ;

R 2 is C 4 -C 8 alkylene;

R 2 is optionally substituted with one or more of C 1 -C 4 alkyl or fluoroalkyl, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy or fluoroalkoxy, halogens, —OH, —SH, phenyl, phenoxy, —CO 2 R 3 , —N(CH 3 ) 2 , —NO 2 , —NH 2 , C 3 -C 10 cycloalkyl, C 3 -C 10 cycloalkenyl, aryl, (C 1 -C 10 alkyl)aryl; and

R 3 is C 1 -C 4 alkyl or C 2 -C 4 alkenyl.

18. A compound having the formula

or a salt thereof, wherein

R 1 is phenyl substituted with —OH;

R 1 is optionally further substituted with one or more of C 1 -C 4 alkyl or fluoroalkyl, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy or fluoroalkoxy, —OH, —SH, phenyl, phenoxy, —CO 2 R 3 , or —N(CH 3 ) 2 ;

R 2 is C 4 -C 8 alkylene;

R 2 is optionally substituted with one or more of C 1 -C 4 alkyl or fluoroalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkoxy or fluoroalkoxy, halogens, —OH, —SH, phenyl, phenoxy, —CO 2 R 3 , —N(CH 3 ) 2 , —NO 2 , —NH 2 , C 3 -C 10 cycloalkyl, C 3 -C 10 cycloalkenyl, aryl, (C 1 -C 10 alkyl)aryl; and

R 3 is C 1 -C 4 alkyl or C 2 -C 4 alkenyl.