Claims
- 1. A compound of the formula:
- A-B-C
- wherein:
- A is a residue of a hydroxyl containing steroidal hormone possessing human bone resorption antagonist activity or bone formation stimulatory activity;
- C is a residue of an amino or hydroxy alkyl-1,1-bisphosphonate, possessing human bone affinity; and
- B is a covalent linkage selected from the group consisting of carbamate, carbonate, thiocarbamate, and thiocarbonate, connecting A through the hydroxyl moiety to C through the respective amino or hydroxyl moiety, which linkage can hydrolyze in the human body in the vicinity of bone to release steroidal hormone A, and pharmaceutically acceptable salts or esters thereof.
- 2. The compound of claim 1 wherein said steroidal hormone is selected from:
- Androisoxazole,
- Androstenediol,
- Bolandiol,
- Bolasterone,
- Clostebol,
- Ethylestrenol,
- Formyldienolone,
- 4-Hydroxy-19-nortestosterone
- Methandriol,
- Methenolone,
- Methyltrienolone,
- Nandrolone,
- Norbolethone,
- Oxymesterone,
- Stenbolone,
- Trenbolone,
- Boldenone,
- Fluoxymesterone,
- Mestanolone,
- Mesterolone,
- Methandrostenolone,
- 17-Methyltestosterone,
- 17.alpha.-Methyltestosterone 3-Cyclopentyl Enol Ether,
- Norethandrolone,
- Normethandrone,
- Oxandrolone,
- Oxymesterone,
- Oxymetholone,
- Prasterone,
- Stanolone,
- Stanozolol,
- Testosterone,
- Tiomesterone,
- Equilenin,
- Equilin,
- 17.beta.-Estradiol,
- Estradiol Benzoate,
- Estriol,
- Ethinyl Estradiol,
- Mestranol,
- Moxestrol,
- Mytatrienediol,
- Quinestradiol,
- Quinestrol,
- Glucocorticoid
- 21-Acetoxypregnenolone,
- Alclometasone,
- Algestone,
- Amcinonide,
- Beclomethasone,
- Betamethasone,
- Budesonide,
- Chloroprednisone,
- Clobetasol,
- Clocortolone,
- Cloprednol,
- Corticosterone,
- Cortisone,
- Cortivazol,
- Deflazacort,
- Desonide,
- Desoximetasone,
- Dexamethasone,
- Diflorasone,
- Diflucortolone,
- Difluprednate,
- Enoxolone,
- Fluazacort,
- Flucloronide,
- Flumethasone,
- Flunisolide,
- Fluocinolone Acetonide,
- Fluocinonide,
- Fluocortin Butyl,
- Fluocortolone,
- Fluorometholone,
- Fluperolone Acetate,
- Fluprednidene Acetate,
- Fluprednisolone,
- Flurandrenolide,
- Formocortal,
- Halcinonide,
- Halometasone,
- Halopredone Acetate,
- Hydrocortamate,
- Hydrocortisone,
- Hydrocortisone Acetate,
- Hydrocortisone Phosphate,
- Hydrocortisone 21-Sodium Succinate,
- Hydrocortisone Tebutate,
- Mazipredone,
- Medrysone,
- Meprednisone,
- Methylprednisolone,
- Mometasone Furoate,
- Paramethasone,
- Prednicarbate,
- Prenisolone,
- Prednisolone 21-Diethylaminoacetate,
- Prednisolone Sodium Phosphate,
- Prednisolone Sodium Succinate,
- Prednisolone Sodium 21-m-Sulfobenzoate,
- Prednisolone 21-Stearoylglycolate,
- Prednisolone Tebutate,
- Prednisolone 21-Trimethylacetate,
- Prednisone,
- Prednival,
- Prednylidene,
- Prednylidene 21-Diethylaminoacetate,
- Tixocortol,
- Triamcinolone,
- Triamcinolone Acetonide,
- Triamcinolone Benetonide,
- Triamcinolone Hexacetonide,
- Allylestrenol,
- Anagestone,
- Desogestrel,
- Dimethisterone,
- Ethisterone,
- Ethynodiol,
- Flurogestone Acetate,
- Gestodene,
- 17-Hydroxy-16-methylene-.DELTA..sup.6 -progesterone,
- 17.alpha.-Hydroxyprogesterone,
- Lynestrenol,
- Medroxyprogesterone,
- Melengestrol,
- Norethindrone,
- Norethynodrel,
- Norgesterone,
- Norgestrel,
- Norgestrienone,
- Norvinisterone,
- Pentagestrone.
- 3. The compound of claim 2 wherein said steroidal hormone is selected from 17-beta estradiol, norethandrolone, androsterone, norethindrone, and nandrolone.
- 4. The compound of claim 1 wherein B is a carbamate linkage.
- 5. The compound of claim 1 wherein C is of the formula: ##STR11## where Y is NH, O, NR.sup.1, wherein R.sup.1 is H or C.sub.1 -C.sub.4 alkyl;
- n is 1-4; and
- R.sup.2 is H, OH.
- 6. The compound of claim 1 of the formula: ##STR12## where X is O, S;
- Y is NH, O, NR.sup.1, wherein R.sup.1 is H or C.sub.1 -C.sub.4 alkyl;
- n is 1-4;
- R.sup.2 is H, OH,
- and pharmaceutically acceptable salts or thereof.
- 7. The compound of claim 6 being of the formula: ##STR13##
- 8. The compound of claim 1 of the formula: ##STR14## where X is O, S;
- Y is NH, O, NR.sup.1, wherein R.sup.1 is H or C.sub.1 -C.sub.4 alkyl;
- n is 1-4;
- R.sup.2 is H, OH;
- and pharmaceutically acceptable salts thereof.
- 9. The compound of claim 8 being of the formula: ##STR15##
- 10. The compound of claim 1 of the formula: ##STR16## where X is O, S;
- Y is NH, O, NR.sup.1, wherein R.sup.1 is H or C.sub.1 -C.sub.4 alkyl;
- n is 1-4;
- R.sup.2 is H, OH;
- and pharmaceutically acceptable salts thereof.
- 11. The compound of claim 10 being of the formula: ##STR17##
- 12. The compound of claim 1 being of the formula: ##STR18## where X is O, S;
- Y is NH, O, NR.sup.1, wherein R.sup.1 is H or C.sub.1 -C.sub.4 alkyl;
- n is 1-4;
- R.sup.2 is H, OH;
- and pharmaceutically acceptable salts thereof.
- 13. The compound of claim 12 being of the formula: ##STR19##
- 14. A pharmaceutical composition which comprises a compound according to claim 1 and a pharmaceutically acceptable carrier.
- 15. A method for treating bone diseases in a human host which comprises administering to said host a therapeutically effective amount of a compound of claim 1.
Parent Case Info
This is a continuation of application Ser. No. 07/644,178, filed on Jan. 22, 1991, now abandoned.
US Referenced Citations (7)
Foreign Referenced Citations (4)
Number |
Date |
Country |
0088462 |
Sep 1983 |
EPX |
201057 |
Nov 1986 |
EPX |
0341961 |
May 1989 |
EPX |
WO9105791 |
May 1991 |
WOX |
Non-Patent Literature Citations (4)
Entry |
J. Am. Chem. Soc. 78: 4450-4452 (1956). |
Synthesis (2): 135-137 (1990). |
Derwent Abstract 90-161 353/21 of Fujisawa's JO 2104-593A. |
Adzamli, et al., Development of Phosphonate Derivatives of Gadolinium Chelates for NMR Imaging of Calcified Soft Tissues, J. Med. Chem., vol. 32, pp. 139-144 (1989). |
Continuations (1)
|
Number |
Date |
Country |
Parent |
644178 |
Jan 1991 |
|