USRE43372EExpiredUtilityPatentIndex 50
C16 unsaturated FP-selective prostaglandins analogs
Est. expiryMar 5, 2019(expired)· nominal 20-yr term from priority
A61P 9/12A61P 27/06A61P 27/02C07C 405/0016A61P 19/10A61P 19/00A61P 1/00A61P 17/00A61P 13/02C07C 405/0041C07C 405/00
50
PatentIndex Score
1
Cited by
666
References
69
Claims
Abstract
Compounds having the general structure: which are useful for the treatment of a variety of diseases and conditions, such as bone disorders.
Claims
exact text as granted — not AI-modified1. A compound having the structure:
wherein
a) R 1 is selected from the group consisting of CO 2 H, C(O)NHOH, C 2 R 3 ,CH 2 OH, S(O) 2 R 3 , C(O)NHR 3 . C(O)NHS(O) 2 R 4 , and tetrazole, wherein R 3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic alphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R 4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R 2 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 C 15 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 R 1 is selected from the group consisting of CO 2 H, C(O)NHOH, CO 2 R 3 , C(O))NHS(O) 2 R 4 , or tetrazole R 3 is heteroalkyl, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring.
3. The compound of claim 2 wherein Z is a bicyclic heteroaromatic ring.
4. The A compound of claim 3 wherein having the structure:
wherein
(a) R 1 is selected from the group consisting of CO 2 H, CO 2 R 3 , S(O) 2 R 3 , and C(O)NHR 3 , wherein R 3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R 2 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 claim 4 wherein Z is substituted with one a substituent, said one substitutent being selected from the group consisting of: lower alkyl, halo, and haloalkyl.
6. The compound of claim 4 wherein R 2 is H.
7. The compound of claim 6 4 wherein R 1 is CO 2 H or CO 2 R 3 .
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:
wherein
(a) R 1 is selected from the group consisting of CO 2 H, C(O)NHOH, CO 2 R 3 , CH 2 OH, S(O) 2 R 3 , and C(O)NHR 3 , C(O)NHS(O) 3 R 4 , and tetrazole;
wherein R 1 R 3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R 4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R 3 R 2 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 C 15 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.
9. The method of claim 8 wherein said bone disorder is osteoporosis.
10. The method of claim 9 wherein in osteoporosis is post-menopausal.
11. The method of claim 9 wherein in osteoporosis is cortico-steroid induced.
12. The method of claim 8 wherein said bone disorder is osteopenia.
13. The method of claim 8 wherein said bone disorder is a bone fracture.
14. The method of claim 8 wherein said compound is administered orally.
15. The method of claim 8 wherein said compound is administered transdermally.
16. The method of claim 8 wherein said compound is administered intranasally.
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:
wherein
(a) R 1 is selected from the group consisting of CO 3 H CO 2 H, C(O)NHOH, CO 2 R 3 , CH 2 OH, S(O) 2 R 3 , and C(O)NHR 3 , C(O)NHS(O) 2 R 4 , and tetrazole;
wherein R 1 R 3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and R 4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R 2 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 C 15 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.
18. The method of claim 17 , wherein said compound is administered topiclally topically.
19. The compound of claim 4, wherein Z is benzo(β)thiophenyl.
20. The compound of claim 4, wherein R 3 is methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, or phenyl.
21. The compound of claim 4, wherein R 1 is CO 2 R 3 and wherein R 3 is a substituted alkyl.
22. The compound of claim 4, wherein Z is thianaphthyl, R 1 is CO 2 R 3 , and R 3 is an alkyl substituted with from 1 to 4 OH groups.
23. A pharmaceutical composition comprising a compound having the structure:
wherein
(a) R 1 is selected from the group consisting of CO 2 H, CO 2 R 3 , S(O) 2 R 3 , and C(O)NHR 3 , wherein R 3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R 2 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.
24. A compound having the structure:
wherein
(a) R 1 is selected from the group consisting of C(O)NHOH, CO 2 R 3 , S(O) 2 R 3 , C(O)NHR 3 , C(O)NHS(O) 2 R 4 , and tetrazole, wherein R 3 is substituted alkyl, heteroalkyl, substituted carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R 4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R 2 is H or lower alkyl;
(c) X is a covalent bond;
(d) Z is a bicyclic heteroaromatic ring, where Z is attached to C 15 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.
25. The compound of claim 24 wherein R 3 is heteroalkyl, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring.
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.
27. The compound of claim 24 wherein R 2 is H.
28. The compound of claim 27 wherein R 1 is CO 2 R 3 .
29. The compound of claim 24, wherein R 1 is CO 2 R 3 , and wherein R 3 is a substituted alkyl.
30. The compound of claim 29, wherein R 3 is substituted with an OH.
31. The compound of claim 29, wherein R 3 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.
32. The compound of claim 29, wherein R 3 is substituted with from 1 to 4 substituents.
33. The compound of claim 29, wherein R 3 is substituted with from 1 to 4 OH groups.
34. The compound of claim 24, wherein Z is thianaphthyl, R 1 is CO 2 R 3 and R 3 is an alkyl substituted with from 1 to 4 OH groups.
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.
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.
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:
wherein
(a) R 1 is selected from the group consisting of CO 2 H, C(O)NHOH, CO 2 R 3 , CH 2 OH, S(O) 2 R 3 , C(O)NHR 3 , C(O)NHS(O) 2 R 4 and tetrazole;
wherein R 3 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R 4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R 2 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 C 15 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.
38. The method of claim 37 wherein said bone disorder is osteoporosis.
39. The method of claim 38 wherein osteoporosis is post-menopausal.
40. The method of claim 38 wherein osteoporosis is cortico-steroid induced.
41. The method of claim 37 wherein said bone disorder is osteopenia.
42. The method of claim 37 wherein said bone disorder is a bone fracture.
43. The method of claim 37 wherein said compound is administered orally.
44. The method of claim 37 wherein said compound is administered transdermally.
45. The method of claim 37 wherein said compound is administered intranasally.
46. The method of claim 37, wherein Z is thianaphthyl, R 1 is CO 2 R 3 , and R 3 is an alkyl substituted with from 1 to 4 OH groups.
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:
wherein
(a) R 1 is selected from the group consisting of C(O)NHOH, CO 2 R 3 , S(O) 2 R 3 , C(O)NHR 3 , C(O)NHS(O) 2 R 4 , and tetrazole,
wherein R 3 is substituted alkyl, heteroalkyl, substituted carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and R 4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R 2 is H or lower alkyl;
(c) X is a covalent bond;
(d) Z is a bicyclic heteroaromatic ring, provided that Z is attached to C 15 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.
48. The method of claim 47, wherein said compound is administered topically.
49. The method of claim 47, wherein R 3 is heteroalkyl, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring.
50. The method of claim 47, wherein R 1 is CO 2 R 3 , and wherein R 3 is a substituted alkyl.
51. The method of claim 50, wherein said substituted alkyl is substituted with an OH.
52. The method of claim 47, wherein R 3 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.
53. The method of claim 52, wherein R 3 is substituted with from 1 to 4 substituents.
54. The method of claim 47, wherein R 3 is substituted with from 1 to 4 OH groups.
55. The method of claim 47, wherein Z is thianaphthyl, R 1 is CO 2 R 3 , and R 3 is an alkyl substituted with from 1 to 4 OH groups.
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.
57. A pharmaceutical composition comprising a compound having the structure:
wherein
(a) R 1 is selected from the group consisting of C(O)NHOH, CO 2 R 3 , S(O) 2 R 3 , C(O)NHR 3 , C(O)NHS(O) 2 R 4 , and tetrazole, wherein R 3 is substituted alkyl, heteroalkyl, substituted carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R 4 is alkyl, heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring;
(b) R 2 is H or lower alkyl;
(c) X is a covalent bond;
(d) Z is a bicyclic heteroaromatic ring, provided that Z is attached to C 15 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.
58. The pharmaceutical composition of claim 57, wherein R 3 is heteroalkyl, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring.
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.
60. The pharmaceutical composition of claim 57, wherein R 2 is H.
61. The pharmaceutical composition of claim 57, wherein R 3 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.
62. The pharmaceutical composition of claim 57, wherein the pharmaceutically acceptable carrier is suitable for topical application of the composition.
63. The pharmaceutical composition of claim 57, wherein Z is thianaphthyl, R 1 is CO 2 R 3 and R 3 is an alkyl substituted with from 1 to 4 OH groups.
64. A pharmaceutical composition comprising a compound having the structure:
wherein
(a) R 1 is CO 2 R 3 , wherein R 3 is a substituted alkyl;
(b) R 2 is H or lower alkyl;
(c) X is a covalent bond;
(d) Z is a bicyclic heteroaromatic ring, provided that Z is attached to C 15 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.
65. The pharmaceutical composition of claim 64, wherein R 3 is substituted with an OH.
66. The pharmaceutical composition of claim 64, wherein R 3 is substituted with from 1 to 4 substituents.
67. The pharmaceutical composition of claim 64, wherein R 3 is substituted with from 1 to 4 OH groups.
68. A compound having the structure:
wherein
(a) R 1 is selected from the group consisting of C(O)NHOH, CO 2 R 3 , S(O) 2 R 3 , C(O)NHR 3 , and C(O)NHS(O) 2 R 4 , wherein R 3 is substituted alkyl, heteroalkyl, substituted carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R 4 is heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, or monocyclic heteroaromatic ring;
(b) R 2 is H or lower alkyl;
(c) X is a covalent bond;
(d) Z is a bicyclic heteroaromatic ring where Z is attached to C 15 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.
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:
wherein
(a) R 1 is selected from the group consisting of C(O)NHOH, CO 2 R 3 , S(O) 2 R 3 , C(O)NHR 3 , and C(O)NHS(O) 2 R 4 , wherein R 3 is substituted alkyl, heteroalkyl, substituted carbocyclic aliphatic ring, heterocyclic aliphatic ring, monocyclic aromatic ring, or monocyclic heteroaromatic ring; and
R 4 is heteroalkyl, carbocyclic aliphatic ring, heterocyclic aliphatic ring, or monocyclic heteroaromatic ring;
(b) R 2 is H or lower alkyl;
(c) X is a covalent bond;
(d) Z is a bicyclic heteroaromatic ring where Z is attached to C 15 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.Cited by (0)
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