compounds having the general structure:
##STR00001##
which are useful for the treatment of a variety of diseases and conditions, such as bone disorders.
|
0. 64. A pharmaceutical composition comprising a compound having the structure:
##STR00063##
wherein
(a) R1 is CO2R3, wherein R3 is a substituted alkyl;
(b) R2 is H or lower alkyl;
(c) x is a covalent bond;
(d) z is a bicyclic heteroaromatic ring, provided that z is attached to C15 via a carbon member atom;
(e) any optical isomer, diastereomer, enantiomer of the above structure or bio-hydrolyzable amide, ester, or imide thereof; and
(f) said composition comprising a pharmaceutically acceptable carrier.
0. 23. A pharmaceutical composition comprising a compound having the structure:
##STR00058##
wherein
(a) R1 is selected from the group consisting of CO2H, CO2R3, S(O)2R3, and C(O)NHR3, wherein R3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R2 is H;
(c) x is a covalent bond;
(d) z is selected from the group consisting of benzo(β)thiazolyl, benzo(β)thiophenyl, thianaphthyl, and benzoxazolyl; and
(e) any optical isomer, diastereomer, enantiomer of the above structure or a pharmaceutically-acceptable salt, or bio-hydrolyzable amide, ester, or imide thereof; and
(f) said composition comprising a pharmaceutically acceptable carrier.
17. A method of treating glaucoma, said method comprising administering to human or other animal a safe and effective amount of a compound according to the structure:
##STR00057##
wherein
(a) R1 is selected from the group consisting of CO3H CO2H, C(O)NHOH, CO2R3, CH2OH, S(O)2R3, and C(O)NHR3, C(O)NHS(O)2R4, and tetrazole;
wherein R1 R3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and R4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R2 is H or lower alkyl;
(c) x is a covalent bond;
(d) z is an aromatic ring or a heteroaromatic ring provided that when z is a heteroaromatic ring and x is a covalent bond, z is attached to C15 via a carbon member atom selected from the group consisting of benzo(β)thiazolyl, benzo(β)thiophenyl, thianaphthyl, and benzoxazolyl; and
(e) any optical isomer, diastereomer, enantiomer of the above structure or a pharmaceutically-acceptable salt, or bio-hydrolyzable, amide, ester, or imide thereof.
0. 68. A compound having the structure:
##STR00064##
wherein
(a) R1 is selected from the group consisting of C(O)NHOH, CO2R3, S(O)2R3, C(O)NHR3, and C(O)NHS(O)2R4, wherein R3 is substituted alkyl, heteroalkyl, substituted carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R4 is heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, or monocyclic heteroaromatic ring;
(b) R2 is H or lower alkyl;
(c) x is a covalent bond;
(d) z is a bicyclic heteroaromatic ring where z is attached to C15 via a carbon member atom; and
(e) any optical isomer, diastereomer, enantiomer of the above structure or a pharmaceutically-acceptable salt, or bio-hydrolyzable amide, ester, or imide thereof.
8. A method of treating a human or other animal subject having a bone disorder, said method comprising administering to said subject a compound according to the structure:
##STR00056##
wherein
(a) R1 is selected from the group consisting of CO2H, C(O)NHOH, CO2R3, CH2OH, S(O)2R3, and C(O)NHR3, C(O)NHS(O)3R4, and tetrazole;
wherein R1 R3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R3 R2 is H or lower alkyl;
(c) x is a covalent bond;
(d) z is an aromatic ring or a heteroaromatic ring provided that when z is a heteroaromatic ring and x is a covalent bond, z is attached to C15 via a carbon member atom selected from the group consisting of benzo(β)thiazolyl, benzo(β)thiophenyl, thianaphthyl, and benzoxazolyl; and
(e) any optical isomer, diastereomer, enantiomer of the above structure or a pharmaceutically-acceptable salt, or bio-hydrolyzable, amide, ester, or imide thereof.
0. 69. A method of treating glaucoma, said method comprising administering to human or other animal a safe and effective amount of a compound according to the structure:
##STR00065##
wherein
(a) R1 is selected from the group consisting of C(O)NHOH, CO2R3, S(O)2R3, C(O)NHR3, and C(O)NHS(O)2R4, wherein R3 is substituted alkyl, heteroalkyl, substituted carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R4 is heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, or monocyclic heteroaromatic ring;
(b) R2 is H or lower alkyl;
(c) x is a covalent bond;
(d) z is a bicyclic heteroaromatic ring where z is attached to C15 via a carbon member atom; and
(e) any optical isomer, diastereomer, enantiomer of the above structure or a pharmaceutically-acceptable salt, or bio-hydrolyzable amide, ester, or imide thereof.
0. 24. A compound having the structure:
##STR00059##
wherein
(a) R1 is selected from the group consisting of C(O)NHOH, CO2R3, S(O)2R3, C(O)NHR3, C(O)NHS(O)2R4, and tetrazole, wherein R3 is substituted alkyl, heteroalkyl, substituted carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R2 is H or lower alkyl;
(c) x is a covalent bond;
(d) z is a bicyclic heteroaromatic ring, where z is attached to C15 via a carbon member atom, and wherein z is selected from the group consisting of benzo (β)thiazolyl, benzo (β)thiophenyl, thianaphthyl, and benzoxazolyl; and
(e) any optical isomer, diastereomer, enantiomer of the above structure or a pharmaceutically-acceptable salt, or bio-hydrolyzable amide, ester, or imide thereof.
0. 47. A method of treating glaucoma, said method comprising administering to human or other animal a safe and effective amount of a compound according to the structure:
##STR00061##
wherein
(a) R1 is selected from the group consisting of C(O)NHOH, CO2R3, S(O)2R3, C(O)NHR3, C(O)NHS(O)2R4, and tetrazole,
wherein R3 is substituted alkyl, heteroalkyl, substituted carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and R4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R2 is H or lower alkyl;
(c) x is a covalent bond;
(d) z is a bicyclic heteroaromatic ring, provided that z is attached to C15 via a carbon member atom; and
(e) any optical isomer, diastereomer, enantiomer of the above structure or a pharmaceutically-acceptable salt, or bio-hydrolyzable amide, ester, or imide thereof.
0. 57. A pharmaceutical composition comprising a compound having the structure:
##STR00062##
wherein
(a) R1 is selected from the group consisting of C(O)NHOH, CO2R3, S(O)2R3, C(O)NHR3, C(O)NHS(O)2R4, and tetrazole, wherein R3 is substituted alkyl, heteroalkyl, substituted carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R2 is H or lower alkyl;
(c) x is a covalent bond;
(d) z is a bicyclic heteroaromatic ring, provided that z is attached to C15 via a carbon member atom, wherein z is selected from the group consisting of benzo(β)thiazolyl, benzo(β)thiophenyl, thianaphthyl, and benzoxazolyl;
(e) any optical isomer, diastereomer, enantiomer of the above structure or bio-hydrolyzable amide, ester, or imide thereof; and
(f) said composition comprising a pharmaceutically acceptable carrier.
0. 37. A method of treating a human or other animal subject having a bone disorder, said method comprising administering to said subject a compound according to the structure:
##STR00060##
wherein
(a) R1 is selected from the group consisting of CO2H, C(O)NHOH, CO2R3, CH2OH, S(O)2R3, C(O)NHR3, C(O)NHS(O)2R4 and tetrazole;
wherein R3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R2 is H or lower alkyl;
(c) x is a covalent bond;
(d) z is an aromatic ring or a heteroaromatic ring provided that when z is a heteroaromatic ring and x is a covalent bond, z is attached to C15 via a carbon member atom; and
(e) any optical isomer, diastereomer, enantiomer of the above structure or a pharmaceutically-acceptable salt, or bio-hydrolyzable amide, ester, or imide thereof.
0. 1. A compound having the structure:
##STR00054##
wherein
a) R1 is selected from the group consisting of CO2H, C(O)NHOH, C2R3,CH2OH, S(O)2R3, C(O)NHR3. C(O)NHS(O)2R4, and tetrazole, wherein R3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic alphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R2 is H or lower alkyl;
(c) x is a covalent bond;
(d) z is an aromatic ring or a heteroaromatic ring provided that when z is a heteroaromatic ring and x is a covalent bond, z is attached to C15 via a carbon member atom; and
(e) any optical isomer, diastereomer enantiomer of the above structure or a pharmaceutically-acceptable salt, or bio-hydrolyzable amide, ester, or imide thereof.
2. The compound of claim 1 4 wherein R1 is selected from the group consisting of CO2H, C(O)NHOH, CO2R3, C(O))NHS(O)2R4, or tetrazole R3 is heteroalkyl, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring.
0. 3. The compound of
##STR00055##
wherein
(a) R1 is selected from the group consisting of CO2H, CO2R3, S(O)2R3, and C(O)NHR3, wherein R3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R2 is H;
(c) x is a covalent bond;
(d) z is selected from the group consisting of: benzo[β](β)thiazolyl, benzo[β](β)thiophenyl, thianaphthyl, and benzoxazolyl; and
(e) any optical isomer, diastereomer, enantiomer of the above structure or a pharmaceutically-acceptable salt, or bio-hydrolyzable amide, ester, or imide thereof.
5. The compound of
0. 6. The compound of
0. 19. The compound of claim 4, wherein z is benzo(β)thiophenyl.
0. 20. The compound of claim 4, wherein R3 is methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, or phenyl.
0. 21. The compound of claim 4, wherein R1 is CO2R3 and wherein R3 is a substituted alkyl.
0. 22. The compound of claim 4, wherein z is thianaphthyl, R1 is CO2R3, and R3 is an alkyl substituted with from 1 to 4 OH groups.
0. 25. The compound of claim 24 wherein R3 is heteroalkyl, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring.
0. 26. The compound of claim 24 wherein z is substituted with a substituent, said substituent being selected from the group consisting of lower alkyl, halo, and haloalkyl.
0. 27. The compound of claim 24 wherein R2 is H.
0. 28. The compound of claim 27 wherein R1 is CO2R3.
0. 29. The compound of claim 24, wherein R1 is CO2R3, and wherein R3 is a substituted alkyl.
0. 30. The compound of claim 29, wherein R3 is substituted with an OH.
0. 31. The compound of claim 29, wherein R3 is substituted with a substituent selected from the group consisting of halo, aryloxy, acyloxy, carboxy, monocyclic aromatic ring, monocyclic heteroaromatic ring, monocyclic carbocyclic aliphatic ring, monocyclic heterocyclic aliphatic ring, lower alkyl, and amino.
0. 32. The compound of claim 29, wherein R3 is substituted with from 1 to 4 substituents.
0. 33. The compound of claim 29, wherein R3 is substituted with from 1 to 4 OH groups.
0. 34. The compound of claim 24, wherein z is thianaphthyl, R1 is CO2R3 and R3 is an alkyl substituted with from 1 to 4 OH groups.
0. 35. The compound of claim 34, wherein z is substituted with a substituent, said substituent being selected from the group consisting of lower alkyl, halo, and haloalkyl.
0. 36. The compound of claim 35, wherein z is substituted with a substituent, said substituent being selected from the group consisting of lower alkyl, halo, and haloalkyl.
0. 38. The method of claim 37 wherein said bone disorder is osteoporosis.
0. 39. The method of claim 38 wherein osteoporosis is post-menopausal.
0. 40. The method of claim 38 wherein osteoporosis is cortico-steroid induced.
0. 41. The method of claim 37 wherein said bone disorder is osteopenia.
0. 42. The method of claim 37 wherein said bone disorder is a bone fracture.
0. 43. The method of claim 37 wherein said compound is administered orally.
0. 44. The method of claim 37 wherein said compound is administered transdermally.
0. 45. The method of claim 37 wherein said compound is administered intranasally.
0. 46. The method of claim 37, wherein z is thianaphthyl, R1 is CO2R3, and R3 is an alkyl substituted with from 1 to 4 OH groups.
0. 48. The method of claim 47, wherein said compound is administered topically.
0. 49. The method of claim 47, wherein R3 is heteroalkyl, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring.
0. 50. The method of claim 47, wherein R1 is CO2R3, and wherein R3 is a substituted alkyl.
0. 51. The method of claim 50, wherein said substituted alkyl is substituted with an OH.
0. 52. The method of claim 47, wherein R3 is an alkyl or carbocyclic aliphatic ring substituted with a substituent selected from the group consisting of hydroxyl, halo, aryloxy, acyloxy, carboxy, monocyclic aromatic ring, monocyclic heteroaromatic ring, monocyclic carbocyclic aliphatic ring, monocyclic heterocyclic aliphatic ring, lower alkyl, and amino.
0. 53. The method of claim 52, wherein R3 is substituted with from 1 to 4 substituents.
0. 54. The method of claim 47, wherein R3 is substituted with from 1 to 4 OH groups.
0. 55. The method of claim 47, wherein z is thianaphthyl, R1 is CO2R3, and R3 is an alkyl substituted with from 1 to 4 OH groups.
0. 56. The method of claim 55, wherein z is substituted with a substituent, said substituent being selected from the group consisting of lower alkyl, halo, and haloalkyl.
0. 58. The pharmaceutical composition of claim 57, wherein R3 is heteroalkyl, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring.
0. 59. The pharmaceutical composition of claim 57, wherein z is substituted with a substituent, said substituent being selected from the group consisting of lower alkyl, halo, and haloalkyl.
0. 60. The pharmaceutical composition of claim 57, wherein R2 is H.
0. 61. The pharmaceutical composition of claim 57, wherein R3 is substituted with a substituent selected from the group consisting of hydroxyl, halo, aryloxy, acyloxy, carboxy, monocyclic aromatic ring, monocyclic heteroaromatic ring, monocyclic carbocyclic aliphatic ring, monocyclic heterocyclic aliphatic ring, lower alkyl, and amino.
0. 62. The pharmaceutical composition of claim 57, wherein the pharmaceutically acceptable carrier is suitable for topical application of the composition.
0. 63. The pharmaceutical composition of claim 57, wherein z is thianaphthyl, R1 is CO2R3 and R3 is an alkyl substituted with from 1 to 4 OH groups.
0. 65. The pharmaceutical composition of claim 64, wherein R3 is substituted with an OH.
0. 66. The pharmaceutical composition of claim 64, wherein R3 is substituted with from 1 to 4 substituents.
0. 67. The pharmaceutical composition of claim 64, wherein R3 is substituted with from 1 to 4 OH groups.
|
|||||||||||||||||||||||||||
This is a and osteoporosis, post-menopausal osteoporosis, osteopenia, and bone fracture.
The compounds of the present invention are useful in increasing bone volume and trabecular number through formation of new trabeculae, bone mass while maintaining a normalized bone turnover rate, and formation at the endosteal surface without removing bone from the existing cortex. Thus, these compounds are useful in the treatment and prevention of bone disorders.
The preferred routes of administration for treating bone disorders are transdermal and intranasal. Other preferred routes of administration include rectal, sublingual, and oral.
The dosage range of the compound for systemic administration is from about 0.01 to about 1000 μg/kg body weight, preferably from about 0.1 to about 100 μg/kg per body weight, most preferably form about 1 to about 50 μg/kg body weight per day. The transdermal dosages will be designed to attain similar serum or plasma levels, based upon techniques known to those skilled in the art of pharmacokinetics and transdermal formulations. Plasma levels for systemic administration are expected to be in the range of 0.01 to 100 nanograms/ml, more preferably from 0.05 to 50 ng/ml, and most preferably from 0.1 to 10 ng/ml. While these dosages are based upon a daily administration rate, weekly or monthly accumulated dosages may also be used to calculate the clinical requirements.
Dosages may be varied based on the patient being treated, the condition being treated, the severity of the condition being treated, the route of administration, etc. to achieve the desired effect.
The compounds of the present invention are also useful in decreasing intraocular pressure. Thus, these compounds are useful in the treatment of glaucoma. The preferred route of administration for treating glaucoma is topically.
The following non-limiting examples illustrate the subject invention. The following composition and method examples do not limit the invention, but provide guidance to the skilled artisan to prepare and use the compounds, compositions and methods of the invention. In each case other compounds within the invention may be substituted for the example compound shown below with similar results. The skilled practitioner will appreciate that the examples provide guidance and may be varied based on the condition being treated and the patient.
Pharmaceutical compositions in the form of tablets are prepared by conventional methods, such as mixing and direct compaction, formulated as follows:
Ingredient
Quantity (mg per tablet)
Compound of Example 1
5
Microcrystalline Cellulose
100
Sodium Starch Glycollate
30
Magnesium Stearate
3
When administered orally once daily, the above composition substantially increases bone volume in a patient suffering from osteoporosis.
Pharmaceutical compositions in liquid form are prepared by conventional methods, formulated as follows:
Ingredient
Quantity
Compound of Example 32
1
mg
Phosphate buffered physiological saline
10
ml
Methyl Paraben
0.05
ml
When 1.0 ml of the above composition is administered subcutaneously once daily, the above composition substantially increases bone volume in a patient suffering from osteoporosis.
Topical pharmaceutical compositions for lowering intraocular pressure are prepared by conventional methods and formulated as follows:
Ingredient
Amount (wt %)
Compound of Example 1
0.004
Dextran 70
0.1
Hydroxypropyl methylcellulose
0.3
Sodium Chloride
0.77
Potassium chloride
0.12
Disodium EDTA (Edetate disodium)
0.05
Benzalkonium chloride
0.01
HCL and/or NaOH
pH 7.2-7.5
Purified water
q.s. to 100%
While particular embodiments of the subject invention have been described, it would be obvious to those skilled in the art that various changes and modifications to the compositions disclosed herein can be made without departing from the spirit and scope of the invention. It is intended to cover, in the appended claims, all such modifications that are within the scope of this invention.
DeLong, Mitchell Anthony, Soper, David Lindsey, Wos, John August, De, Biswanath
| Patent | Priority | Assignee | Title |
| 9579270, | Mar 31 2000 | Duke University | Compositions and methods for treating hair loss using non-naturally occurring prostaglandins |
| Patent | Priority | Assignee | Title |
| 13294, | |||
| 146439, | |||
| 3382247, | |||
| 3435053, | |||
| 3524867, | |||
| 3598858, | |||
| 3636120, | |||
| 3644363, | |||
| 3691216, | |||
| 3706789, | |||
| 3723427, | |||
| 3776938, | |||
| 3776939, | |||
| 37913, | |||
| 37914, | |||
| 3798275, | |||
| 3839409, | |||
| 3852337, | |||
| 3882241, | |||
| 3882245, | |||
| 3896156, | |||
| 3928588, | |||
| 3934013, | Feb 21 1975 | Syntex (U.S.A.) Inc. | Pharmaceutical composition |
| 3966792, | Feb 28 1973 | ONO Pharmaceutical Co., Ltd. | Prostaglandin compounds |
| 3974213, | Jul 13 1972 | Pfizer Inc. | 13,14-Dihydro-15-substituted-ω-pentanorprostaglandins |
| 3984424, | Nov 07 1972 | Pfizer Inc. | P-biphenyl esters of 15-substituted-ω-pentanorprostaglandins |
| 3984455, | Jun 06 1966 | The Upjohn Company | Prostaglandin E1 analogs |
| 4004020, | Dec 21 1973 | Schering Aktiengesellschaft | Novel prostanoic acid derivatives and process for the preparation thereof |
| 4011262, | Jul 13 1972 | Pfizer Inc. | 13,14-Dihydro-15-substituted-ω-pentanorprostaglandins of the two series |
| 4018812, | Jun 16 1975 | ONO Pharmaceutical Co., Ltd. | 16-METHYLENE-PROSTAGLANDIN COMPOUNDS |
| 4024179, | Nov 08 1972 | Pfizer Inc. | Substituted ω-pentanorprostaglandins |
| 4051238, | Jun 03 1976 | The Upjohn Company | Treatment of genital tract diseases of domestic animals with prostaglandins |
| 4061671, | Apr 03 1974 | Hoechst Aktiengesellschaft | Analogues of prostaglandins |
| 4073934, | Apr 18 1975 | Schering Aktiengesellschaft | Novel acetylenic prostaglandin analogs |
| 4089885, | Nov 05 1976 | American Home Products Corporation | Prostaglandin derivatives |
| 4105854, | Apr 22 1974 | PITMAN-MOORE, INC | Prostanoic acid derivatives |
| 4123441, | Aug 23 1976 | The Upjohn Company | Enlarged-hetero-ring prostacyclin analogs |
| 4128577, | Dec 29 1975 | The Upjohn Company | 15-Methyl- and 16-phenoxy-PGF2 α, amides |
| 4128720, | Feb 14 1975 | Ono Pharmaceutical Company | Prostaglandin analogues |
| 4139619, | Dec 29 1971 | UPJOHN COMPANY THE KALAMAZOO, MI A CORP OF DE | 6-Amino-4-(substituted amino)-1,2-dihydro-1-hydroxy-2-iminopyrimidine, topical compositions and process for hair growth |
| 4152527, | Nov 07 1972 | Pfizer Inc. | 15-Substituted-ω-pentanorprostaglandins |
| 4154950, | Mar 31 1975 | The Upjohn Company | 15-Epi-15-methyl-16-phenoxy-PGE compounds |
| 4158667, | Feb 04 1976 | The Upjohn Company | 6-Keto PGF analogs |
| 4171331, | Jun 05 1978 | Miles Laboratories, Inc. | 1 And 2-substituted analogues of certain prostaglandins |
| 4206151, | Dec 21 1978 | American Cyanamid Company | 15-Deoxy-16-hydroxy-16-vinyl or cyclopropyl prostan-1-ols of the E, A and F series |
| 4217360, | Feb 27 1975 | Schering Aktiengesellschaft | Novel 1,3-benzodioxaneprostanoic acid derivatives and process for the preparation thereof |
| 4225507, | Jul 05 1979 | The Upjohn Company | 19-Hydroxy-19-methyl-PGI2 compounds |
| 4225508, | Jul 05 1979 | The Upjohn Company | 19-Hydroxy-PGI2 compounds |
| 4268522, | Jun 14 1976 | Pfizer Inc. | 13,14-Dihydro-15-alkenyl- and 13,14-dihydro-15-alkynyl prostaglandins and analogs thereof |
| 4284646, | Aug 06 1976 | Schering Aktiengesellschaft | Prostanoic acid derivatives and their preparation |
| 4296504, | Jul 07 1980 | Toilet seat lock | |
| 4311707, | Feb 12 1979 | American Cyanamid Company | Process for topically producing cutaneous vasodilation for the treatment of vasospastic or ischemic conditions |
| 4489092, | Aug 24 1970 | Schering Aktiengesellschaft | Prostanoic acid derivatives and their preparation |
| 4499293, | Aug 23 1976 | The Upjohn Company | PGI2 Salts |
| 4543353, | Nov 27 1981 | Farmitalia Carlo Erba S r l | Ester and amide derivatives of 13,14-didehydro prostaglandins |
| 4596812, | Dec 29 1971 | UPJOHN COMPANY THE KALAMAZOO, MI A DE CORP | Methods and solutions for treating male pattern alopecia |
| 4599353, | May 03 1982 | The Trustees of Columbia University in the City of New York | Use of eicosanoids and their derivatives for treatment of ocular hypertension and glaucoma |
| 4621100, | Mar 25 1981 | The Upjohn Company | Treatment of osteoporosis with prostaglandins |
| 4704386, | Aug 29 1985 | G D SEARLE AND CO , 1751 LAKE COOK RD , DEERFIELD, IL 60015 A CORP OF DE | 8-chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[(phenylsulfinyl-, and phenylsulfonyl)alkanoyl]hydrazides |
| 4757089, | Jun 14 1985 | Allergan | Increasing aqueous humor outflow |
| 4812457, | Nov 21 1984 | Research Development Corporation; Masami, Tsuboshima | Prostaglandin derivatives |
| 4883819, | Mar 13 1986 | The Trustees of Columbia University in the City of New York | Use of A, B and C prostaglandins and derivatives thereof to treat ocular hypertension and glaucoma |
| 4889845, | Jun 09 1986 | American Cyanamid Company | Vehicle for topical application of pharmaceuticals |
| 4952581, | Apr 03 1987 | The Trustees of Columbia University in the City of New York | Use of a prostaglandin in combination with an adrenergic blocking agent for reduction of intraocular pressure |
| 4968812, | Jun 23 1989 | Texas State University-San Marcos | Spirolactonelactams |
| 5001153, | Sep 18 1987 | R-TECH UENO, LTD | Ocular hypotensive agents |
| 5041439, | Jun 13 1986 | The Procter & Gamble Company | Penetrating topical pharmaceutical compositions |
| 5063057, | Sep 26 1990 | FD MANAGEMENT, INC | Cosmetic capsules |
| 5166178, | Sep 18 1987 | R-TECH UENO, LTD A CORP OF JAPAN | Ocular hypotensive agents |
| 5194429, | Oct 01 1988 | R-TECH UENO, LTD | Ocular hypotensive agents |
| 5212324, | Apr 04 1990 | Sucampo AG | Treatment of cataract with 15-keto-prostaglandin compounds |
| 5219885, | Feb 16 1987 | ratiopharm GmbH | Prostaglandin E1 derivatives as pharmaceutically active agents, and pharmaceutical compositions containing these compounds, especially for transcutaneous administration |
| 5280018, | Jun 09 1986 | American Cyanamid Company | Vehicle for optical application of pharmaceuticals |
| 5288754, | Feb 04 1992 | Allergan, Inc | Polar C-1 esters of prostaglandins |
| 5296504, | Sep 06 1988 | Pharmacia Aktiebolag | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| 5302617, | Apr 27 1990 | Sucampo AG | Biochemical treatment with 15-dehydroxy-16-oxoprostaglandin compounds |
| 5312832, | May 17 1991 | Allergan, Inc | Ocular hypotensive 2-decarboxyl-2-acylthioalkyl prostaglandin derivatives |
| 5321128, | Sep 06 1988 | Pharmacia Aktiebolag | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| 5332730, | Oct 16 1992 | Allergan, Inc | Azido derivatives of cyclopentane heptanoic or heptenoic acid |
| 5340813, | Nov 09 1992 | Cell Therapeutics, Inc.; CELL THERAPEUTICS, INC | Substituted aminoalkyl xanthine compounds |
| 5352708, | Sep 21 1992 | Allergan, Inc | Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents |
| 5409911, | Sep 11 1992 | Merck Sharp & Dohme Corp | Prostaglandin analog for treating osteoporosis |
| 5422368, | Sep 06 1988 | Pharmacia Aktiebolag | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| 5422369, | Sep 06 1988 | Pharmacia Aktiebolag | Prostaglanddin derivatives for the treatment of glaucoma or ocular hypertension |
| 5422371, | May 27 1992 | Arch Development Corp. | Methods and compositions for inhibiting 5α-reductase activity |
| 5426115, | Nov 22 1989 | Sucampo AG | Use of 15-keto-prostaglandin compound for improvement of encephalic function |
| 5431881, | Dec 10 1993 | Treatment of hair loss and dermatological problems | |
| 5458883, | Jan 12 1994 | Duke University | Method of treating disorders of the eye |
| 5464868, | Feb 16 1987 | ratiopharm GmbH | Prostaglandin E1 derivatives for transdermal administration and methods of treatment therewith |
| 5480900, | Oct 13 1992 | Alcon Research, Ltd | Combinations of prostaglandins and clonidine derivatives for the treatment of glaucoma |
| 5500230, | Jan 23 1987 | The General Hospital Corporation | Method for treatment of glaucoma with nitrogen containing guanylate cyclase activators |
| 5508303, | May 29 1992 | Toray Industries, Inc. | Hair-growing composition |
| 5510383, | Aug 03 1993 | Alcon Research, Ltd | Use of cloprostenol, fluprostenol and their salts and esters to treat glaucoma and ocular hypertension |
| 5516652, | Oct 06 1993 | Merck Frosst Canada Ltd | DNA encoding prostaglandin receptor IP |
| 5567079, | Nov 17 1992 | Method for the hydraulic branching of an open stream and hydraulically working channel branch | |
| 5576315, | May 03 1991 | G.D. Searle & Co. | Substituted dibenzoxazepine compounds and methods for treating osteoporosis and ischemia |
| 5578618, | Sep 06 1988 | Pharmacia Aktiebolag | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| 5578640, | Aug 04 1994 | Loyola University of Chicago | Protective prostaglandins for use in conjunction with chemotherapeutic agents |
| 5578643, | May 20 1992 | HANSON, WAYNE R | Protective prostaglandins for use in conjunction with chemotherapeutic agents |
| 5587391, | Dec 28 1993 | Allergan, Inc | Cyclopentane(ene) heptenoic or heptanoic acids and derivatives thereof useful as therapeutic agents |
| 5605814, | Aug 31 1993 | Merck Frosst Canada Ltd | DNA encoding human prostaglandin receptor EP2 |
| 5605931, | Aug 04 1994 | HANSON, WAYNE R | Protective prostaglandins for use in conjunction with chemotherapeutic agents |
| 5607978, | Sep 21 1992 | Allergan, Inc | Non-acidic cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents |
| 5627208, | Sep 06 1988 | Pharmacia Aktiebolag | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| 5641494, | Mar 20 1992 | Janssen Pharmaceutica N.V. | Agent for regulating the greasiness of the skin |
| 5658897, | Apr 08 1996 | Allergan, Inc | Cyclopentane(ene) heptanoic or cyclopentane(ene) heptenoic acid, 2-hydrocarbyl phosphinyloxyalkyl or phosphonamidoalkyl as therapeutic agents |
| 5663203, | Sep 11 1986 | Schering Aktiengesellschaft | Agents containing prostacyclin derivatives for topical application |
| 5665773, | Aug 03 1993 | Alcon Research, Ltd | Cloprostenol and fluprostenol analogues and their use to treat glaucoma and ocular hypertension |
| 5670506, | Apr 05 1993 | Cell Therapeutics, Inc.; CELL THERAPEUTICS, INC | Halogen, isothiocyanate or azide substituted xanthines |
| 5681850, | Feb 16 1987 | ratiopharm GmbH | Method of treatment of impotence with prostaglandin E1 derivatives |
| 5688819, | Sep 21 1992 | Allergan, Inc | Cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl derivatives as therapeutic agents |
| 5698733, | Sep 30 1994 | Alcon Research, Ltd | Use of 9-deoxy prostaglandin derivatives to treat glaucoma |
| 5703108, | Feb 28 1996 | Pfizer Inc. | Bone deposition by certain prostaglandin agonists |
| 5716609, | Jul 25 1995 | Panacea Biotec Limited | Therapeutic anti-inflammatory and analgesic composition containing nimesulide for use transdermally and a process for the manufacture thereof |
| 5719140, | Apr 30 1993 | G.D. Searle & Co. | 2, 3-, 4-, 5-, 6-, 7-, 8-, 9- and /or 10-substituted dibenzoxazepine compounds, pharmaceutical compositions and methods of use |
| 5741810, | Feb 29 1996 | Allergan, Inc | Cyclopentane heptan(ene)oic acid, 2- heteroarylalkenyl derivatives as therapeutic agents |
| 5759789, | Aug 31 1993 | Merck Frosst Canada Ltd | Prostaglandin receptor EP2 |
| 5770759, | Apr 30 1987 | R-Tech Ueno, Ltd. | Prostaglandins of the F series |
| 5773472, | Nov 03 1993 | Synphora AB | Method and means for prevention of cataract |
| 5792851, | Sep 03 1996 | Albert Einstein College of Medicine | Human prostaglandin transporter |
| 5834498, | Sep 21 1992 | Allergan, Inc | Cyclopentane heptan(ene)oic acid, 2-heteroarylalkenyl derivatives as therapeutic agents |
| 5840847, | Jun 25 1993 | Merck Frosst Canada Ltd | Purified prostaglandin receptor FP |
| 5849791, | Sep 06 1988 | Pharmacia Aktiebolag | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| 5863948, | Jun 14 1985 | Massachusetts Eye and Ear Infirmary | Increasing aqueous humor outflow |
| 5869281, | Jun 25 1993 | Merck Frosst Canada Ltd | DNA encoding prostaglandin receptor FP |
| 5877211, | Nov 21 1997 | Allergan, Inc | EP2 receptor agonists as neuroprotective agents for the eye |
| 5885766, | Feb 17 1995 | Societe l'Oreal S.A. | Method of screening of substances for their effect on the expression of mediators of inflammation in a hair follicle |
| 5885974, | Dec 06 1994 | DANIELOV, MICHAEL M | Therapeutic methods utilizing naturally derived bio-active complexes and delivery systems therefor |
| 5889052, | Aug 03 1993 | Alcon Research, Ltd | Use of cloprostenol and fluprostenol analogues to treat glaucoma and ocular hypertension |
| 5892099, | Jan 27 1997 | ONO Pharmaceutical Co., Ltd. | 3,7-dithiaprostanoic acid derivative |
| 5958723, | Jan 26 1995 | Merck Frosst Canada Ltd | DNA encoding prostaglandin receptor DP |
| 5972965, | Jul 21 1995 | Fujisawa Pharmaceutical Co., Ltd. | 4,5-diaryl oxazole derivatives |
| 5973002, | Feb 16 1987 | ratiopharm GmbH | Prostaglandin E1 derivatives as pharmacologically active agents, especially for transcutaneous administration |
| 5977173, | Sep 09 1997 | Duke University | Aromatic C16 -C20 -substituted tetrahydro prostaglandins useful as FP agonists |
| 5985597, | May 26 1993 | Merck Frosst Canada Ltd | DNA encoding prostaglandin receptor EP1 |
| 5990346, | Jun 26 1995 | Teijin Limited | Prostaglandins and processes for production thereof |
| 5994397, | Dec 22 1995 | Alcon Research, Ltd | Substituted tetrahydrofuran analogs of prostaglandins as ocular hypotensives |
| 6013823, | Jun 08 1992 | LITTON FEDERAL CORPORATION | Trans-pentavalent 2-15-deoxy-16-hydroxy-16-methyl-PGE1 methyl ester (B-407) |
| 6025375, | Dec 20 1993 | Fujisawa Pharmaceutical Co., Ltd. | 4,5-diaryloxazole derivatives |
| 6025392, | Dec 22 1995 | Alcon Research, Ltd | substituted tetrahydrofuran analogs of prostaglandins as ocular hypotensives |
| 6030959, | Apr 04 1997 | MONSANTO CO | Gastro-specific prodrugs |
| 6030999, | Apr 10 1990 | Pharmacia Aktiebolag | Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension |
| 6031001, | Sep 21 1994 | Synphora AB | Use of prostaglandins |
| 6031079, | May 26 1993 | Merck Frosst Canada Ltd | Purified prostaglandin receptor EP1 |
| 6037364, | Sep 21 1992 | Allergan, Inc | Cyclopentane heptan(ene)oic acid, 2-heteroarylalkenyl derivatives as therapeutic agents |
| 6037368, | May 09 1997 | Mount Sinai School of Medicine of New York University | 8-iso- prostaglandins for glaucoma therapy |
| 6043264, | Jan 06 1995 | Toray Industries, Inc. | Benzene-condensed heterocyclic derivatives and their uses |
| 6048895, | Sep 09 1997 | Duke University | Aromatic C16-C20 substituted tetrahydro prostaglandins useful as FP agonists |
| 6107338, | Sep 09 1997 | Duke University | Aromatic C16 -C20 -substituted tetrahydro prostaglandins useful as FP agonists |
| 6110969, | Feb 04 1997 | Ono Pharmaceutical Co. Ltd. | Cycloalkyl-prostaglandin E2 derivatives |
| 6121253, | Nov 15 1999 | Merck Frosst Canada Ltd | Prostaglandin conjugates for treating or preventing bone disease |
| 6124344, | Dec 28 1993 | Allergan, Inc | Cyclopentane heptan(ene)oic acid, 2-heteroarylalkenyl derivatives as therapeutic agents |
| 6126957, | Jan 12 1994 | Duke University | Method of treating disorders of the eye |
| 6160129, | Dec 28 1993 | Allergan, Inc | Cyclopentane heptan(ene)oic acid, 2-heteroarylalkenyl derivatives as therapeutic agents |
| 6169111, | Jun 07 1995 | Alcon Research, Ltd | Conformationally rigid aryl prostaglandins for use in glaucoma therapy |
| 6232344, | Dec 22 1997 | Alcon Research, Ltd | 13-Oxa prostaglandins for the treatment of glaucoma and ocular hypertension |
| 6262105, | Feb 04 1997 | Method of enhancing hair growth | |
| 6372730, | Aug 04 1999 | Duke University | 2-decarboxy-2-phosphinico Prostaglandin F analogs |
| 6403649, | Sep 21 1992 | Allergan, Inc | Non-acidic cyclopentane heptanoic acid,2-cycloalkyl or arylalkyl derivatives as therapeutic agents |
| 6410780, | Mar 31 1998 | Duke University | C11 oxymyl and hydroxylamino prostaglandins useful as medicaments |
| 6444840, | Mar 31 1998 | Duke University | C11 oxymyl and hydroxylamino prostaglandins useful as FP agonists |
| 6451859, | Mar 05 1999 | Duke University | C16 unsaturated FP-selective prostaglandins analogs |
| 6534082, | Jan 12 1994 | Duke University | Method of treating disorders of the eye |
| 6548535, | Jan 18 2000 | Merck Sharp & Dohme Corp | Method for treating ocular hypertension |
| 6586463, | Mar 05 1999 | Duke University | C16 unsaturated FP-selective prostaglandins analogs |
| 6716876, | Dec 28 1993 | Allergan, Inc. | Cyclopentane(ENE)heptenoic or heptanoic acids and derivatives thereof useful as therapeutic agents |
| 6894175, | Oct 08 1999 | The Procter & Gamble Company | 2-Decarboxy-2-phosphinico prostaglandin derivatives and methods for their preparation and use |
| 7070768, | Sep 25 2003 | Allergan, Inc.; Allergan, Inc | Method for imparting artificial tan to human skin |
| 7074942, | Aug 04 1999 | The Procter & Gamble Company | 2-decarboxy-2-phosphinico prostaglandin derivatives and methods for their preparation and use |
| 7115659, | Aug 04 1999 | The Procter & Gamble Company | Method of treating a condition by administering a prostaglandin derivative |
| 7288029, | Jan 19 2005 | GKN Driveline North America, Inc. | Propshaft with crash-worthiness |
| 7388029, | Mar 31 2000 | Duke University | Compositions and methods for treating hair loss using non-naturally occurring prostaglandins |
| 7407987, | Mar 31 2000 | Duke University | Compositions and methods for treating hair loss using C16-C20 aromatic tetrahydro prostaglandins |
| 20010047025, | |||
| 20020013294, | |||
| 20020037914, | |||
| 20020044953, | |||
| 20020146439, | |||
| 20020172693, | |||
| 20030083381, | |||
| 20030147823, | |||
| 20030191173, | |||
| 20030199590, | |||
| 20040157912, | |||
| 20040167190, | |||
| 20040171596, | |||
| 20050058614, | |||
| 20060121069, | |||
| 20060135609, | |||
| 20060247214, | |||
| 20070161699, | |||
| 20070254920, | |||
| 20070282006, | |||
| 20080070988, | |||
| 20080103184, | |||
| 20080241078, | |||
| 20090018204, | |||
| 20090203659, | |||
| 20090286769, | |||
| 20100105771, | |||
| 20100105775, | |||
| AU766163, | |||
| BE746615, | |||
| CA1339132, | |||
| CA2364948, | |||
| DE1617477, | |||
| DE1801750, | |||
| DE2255731, | |||
| DE2355731, | |||
| DE2365101, | |||
| DE2409460, | |||
| DE2460990, | |||
| DE2517771, | |||
| DE2605242, | |||
| DE2605584, | |||
| DE2660990, | |||
| DE2737808, | |||
| EP170258, | |||
| EP295092, | |||
| EP308135, | |||
| EP1008588, | |||
| EP1016660, | |||
| EP1159266, | |||
| EP249194, | |||
| EP572014, | |||
| EP639563, | |||
| EP648488, | |||
| EP857718, | |||
| EP911321, | |||
| EP925787, | |||
| EP947500, | |||
| EP970697, | |||
| FR2108027, | |||
| FR2182928, | |||
| FR2239458, | |||
| FR2314712, | |||
| FR2730811, | |||
| GB1236227, | |||
| GB1251750, | |||
| GB1285371, | |||
| GB1285372, | |||
| GB1456512, | |||
| GB1456513, | |||
| GB1456514, | |||
| GB1456838, | |||
| GB1542569, | |||
| GB1545411, | |||
| GB2048254, | |||
| GB2330307, | |||
| JP10251225, | |||
| JP10287532, | |||
| JP2003180399, | |||
| JP2022226, | |||
| JP3034934, | |||
| JP383925, | |||
| JP383926, | |||
| JP4300833, | |||
| JP49069636, | |||
| JP49093342, | |||
| JP49101356, | |||
| JP49102647, | |||
| JP51086449, | |||
| JP52053841, | |||
| JP53028160, | |||
| JP5331025, | |||
| JP58029710, | |||
| JP61218510, | |||
| JP9295921, | |||
| WO2450, | |||
| WO3736, | |||
| WO3980, | |||
| WO4898, | |||
| WO4899, | |||
| WO7627, | |||
| WO9557, | |||
| WO13664, | |||
| WO15608, | |||
| WO16760, | |||
| WO51971, | |||
| WO51979, | |||
| WO51980, | |||
| WO110873, | |||
| WO174307, | |||
| WO174313, | |||
| WO174314, | |||
| WO174315, | |||
| WO2067901, | |||
| WO3051822, | |||
| WO3066008, | |||
| WO3077910, | |||
| WO2006047466, | |||
| WO2007125818, | |||
| WO2007127639, | |||
| WO8600616, | |||
| WO9002553, | |||
| WO9202495, | |||
| WO9408585, | |||
| WO9500552, | |||
| WO9511003, | |||
| WO9511033, | |||
| WO9518102, | |||
| WO9519165, | |||
| WO9519964, | |||
| WO9610407, | |||
| WO9636599, | |||
| WO9703973, | |||
| WO9709049, | |||
| WO9715319, | |||
| WO9723223, | |||
| WO9723225, | |||
| WO9723226, | |||
| WO9729735, | |||
| WO9731895, | |||
| WO9739754, | |||
| WO9800100, | |||
| WO9812175, | |||
| WO9813016, | |||
| WO9819680, | |||
| WO9820880, | |||
| WO9820881, | |||
| WO9821180, | |||
| WO9821181, | |||
| WO9821182, | |||
| WO9827976, | |||
| WO9828264, | |||
| WO9833497, | |||
| WO9839293, | |||
| WO9847515, | |||
| WO9850024, | |||
| WO9853809, | |||
| WO9857930, | |||
| WO9857942, | |||
| WO9858911, | |||
| WO9902165, | |||
| WO9912550, | |||
| WO9912551, | |||
| WO9912552, | |||
| WO9912553, | |||
| WO9912554, | |||
| WO9912555, | |||
| WO9912556, | |||
| WO9912557, | |||
| WO9912558, | |||
| WO9912559, | |||
| WO9912560, | |||
| WO9912561, | |||
| WO9912563, | |||
| WO9912895, | |||
| WO9912896, | |||
| WO9912897, | |||
| WO9912898, | |||
| WO9912899, | |||
| WO9919300, | |||
| WO9921562, | |||
| WO9922731, | |||
| WO9925357, | |||
| WO9925358, | |||
| WO9930675, | |||
| WO9930718, | |||
| WO9932441, | |||
| WO9932640, | |||
| WO9932641, | |||
| WO9933794, | |||
| WO9947497, | |||
| WO9950241, | |||
| WO9950242, | |||
| WO9961029, | |||
| WO9964621, | |||
| WO9965303, | |||
| WO9965527, | |||
| WO54810, | |||
| WO2009011744, | |||
| WO8903384, | |||
| WO9636599, | |||
| WO9723225, | |||
| WO9912550, | |||
| WO9912551, | |||
| WO9912895, | |||
| WO9912896, | |||
| WO9912899, |
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