US2013029901A1PendingUtilityA1
Methods and compounds for the targeted delivery of agents to bone for interaction therewith
Est. expiryFeb 23, 2027(~0.6 yrs left)· nominal 20-yr term from priority
A61P 31/04A61P 35/00A61P 31/00C07C 2603/40A61K 31/70C07D 311/36A61P 19/10A61P 19/00A61P 19/08A61P 21/06C07D 285/125C07C 2603/44C07C 237/44
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Claims
Abstract
Bone targeted compounds and methods are provided. Compounds can include a Bone Targeting Portion (R T ), having an affinity for bone; a Bone Active Portion (R A ) for interacting with and affecting bone; and a Linking Portion (R L ) connecting the Bone Targeting Portion and the Bone Active Portion.
Claims
exact text as granted — not AI-modified1 . A compound of the formula:
or pharmaceutically acceptable salts or solvates thereof,
wherein R T is
wherein R T is connected to the compound at R 1 , R 2 , or R 4 ;
wherein
R 1 is hydrogen, lower alkyl, alkyl, aryl lower alkyl, aryl, or a covalent bond when R T is connected to the compound at R 1 ;
R 2 is hydrogen, lower alkyl, alkyl, aryl lower alkyl, aryl, or a covalent bond when R T is connected to the compound at R 2 ;
R 3 is hydrogen, lower alkyl, alkyl, aryl lower alkyl, aryl, or carbonyl-containing;
R 4 is hydrogen, lower alkyl, alkyl, aryl lower alkyl, aryl, carbonyl-containing, or a covalent bond when R T is connected to the compound at R 4 ;
R 5 and R 6 are independently hydrogen, lower alkyl, or alkyl, or R 5 and R 6 , taken together with the carbon atoms to which they are bonded, form a ring containing about 6 to about 14 ring carbon atoms and up to a total of about 18 carbon atoms, which formed ring can be monocyclic, bicyclic, or tricyclic, wherein the ring can optionally have substituents, including heteroatoms;
R 7 is hydroxy, lower alkoxy, or NR 8 , R 9 ;
R 8 and R 9 are independently hydrogen, or lower alkyl;
wherein i is 0-3, k is 0-3, and p is 1-4;
wherein each R q is independently hydrogen or hydroxy;
wherein X is O, NH, S, or covalent bond;
wherein X′ is O, NH, S, or covalent bond;
wherein m is 1-3, n is 1-4, and when m>1, each n is independently 1-4;
wherein each R S is independently hydrogen, hydroxy, lower alkyl, or lower alkyl with heteroatoms;
wherein D and G are independently covalent bond, carbonyl, epoxy, or anhydride;
wherein E is
covalent bond,
(CT 2 ) r , where T is hydrogen, hydroxy, or lower alkyl, and where r is 0-8, or
(C) r , where r is 2-8, and where the carbons are unsaturated or partially saturated with hydrogen;
so long as n is 2-4 when
D, E, and G are all covalent bond, X is NH or O, and R S is H, or
D is carbonyl, E and G are covalent bond, and R S is H; and
wherein R A is hydrogen, hydroxyl, a protecting group, or a Bone Active Portion derived from a bone active agent.
2 . The compound of claim 1 , wherein R 5 and R 6 are hydrogen.
3 . The compound of claim 1 , wherein R 7 is NR 8 R 9 .
4 . The compound of claim 3 , wherein R 8 and R 9 are both hydrogen.
5 . The compound of claim 1 , wherein R 3 is hydrogen.
6 . The compound of claim 1 , wherein R T is
and R T is connected to the compound at R 1 .
7 . The compound of claim 1 , wherein R T is
and R T is connected to the compound at R 1 .
8 . The compound of claim 1 , wherein R T is
and R T is connected to the compound at R 1 .
9 . The compound of claim 1 , according to the formula
where n′ and n″ are independently 1-4, and X″ is O, NH, S, or covalent bond.
10 . The compound of claim 1 , according to the formula
11 . The compound of claim 1 , according to the formula
12 . The compound of claim 1 , according to the formula
13 . The compound of claim 12 , wherein R T is:
and R T is connected to the compound at R 1 or R 4 .
14 . The compound of claim 13 , according to the formula
15 . The compound of claim 14 , wherein the compound is provided as a salt.
16 . The compound of claim 15 , wherein the salt is a chloride salt.
17 . The compound of claim 1 , according to the formula
18 . The compound of claim 17 , wherein R T is:
and R T is connected to the compound at R 1 or R 4 .
19 . The compound of claim 1 , according to the formula
20 . The compound of claim 19 , wherein R A is hydrogen or hydroxyl.
21 . The compound of claim 19 , wherein R A is a protecting group.
22 . The compound of claim 19 , wherein R A is a bone active portion derived from a bone active agent selected from the bone active agents set forth in Tables A-D.
23 . The compound of claim 19 , wherein R A is a bone active agent selected from a steroid, a non-steroidal estrogenic agent, a nitric oxide agent, an androgen, a carbonic anhydrase inhibitor, an anti-cancer agent, and an antimicrobial agent.
24 . The compound of claim 19 , wherein the bone active agent is an anti-cancer agent.
25 . The compound of claim 19 , wherein the bone active agent is a tyrosine kinase inhibitor.
26 . The compound of claim 1 , according to the formula
27 . The compound of claim 1 , according to the formula
28 . The compound of claim 1 , according to the formula
wherein E is CH 2 or (CH 2 ) 2 .
29 . The compound of claim 1 , according to the formula
30 . The compound of claim 1 , according to the formula
wherein E is CH 2 or (CH 2 ) 2 .
31 . The compound of claim 1 , according to the formula
32 . The compound of claim 31 , wherein R A is hydrogen or hydroxyl.
33 . The compound of claim 31 , wherein R A is a protecting group.
34 . The compound of claim 31 , wherein R A is a bone active portion derived from a bone active agent selected from the bone active agents set forth in Tables A-D.
35 . The compound of claim 34 , wherein R A is a bone active portion derived from a steroid.
36 . The compound of claim 34 , wherein R A is a bone active portion derived from an estrogenic agent.
37 . The compound of claim 36 , wherein R A is a bone active portion derived from a steroidal estrogenic agent.
38 . The compound of claim 37 , where the steroidal estrogenic agent is estradiol.
39 . The compound of claim 36 , wherein R A is a bone active portion derived from a non-steroidal estrogenic agent.
40 . The compound of claim 39 , wherein the non-steroidal estrogenic agent is genistein.
41 . The compound of claim 31 , wherein R A is a bone active portion derived from a nitric oxide agent.
42 . The compound of claim 41 , wherein the nitric oxide agent is alkoxy-(NO 2 ) 2 .
43 . The compound of claim 31 , wherein R A is a bone active portion derived from an androgen.
44 . The compound of claim 43 , wherein the androgen is DHEA.
45 . The compound of claim 43 , wherein the androgen is Testosterone.
46 . The compound of claim 31 , wherein R A is a bone active portion derived from a carbonic anhydrase inhibitor
47 . The compound of claim 46 , wherein R A is a bone active portion derived from 2-amino-1,3,4-thiadiazole-5-sulfonamide.
48 . The compound of claim 31 , wherein R A is a bone active portion derived from an anti-cancer agent.
49 . The compound of claim 48 , wherein the anti-cancer agent is doxorubicin.
50 . The compound of claim 31 , wherein R A is a tyrosine kinase inhibitor.
51 . The compound of claim 50 , wherein the tyrosine kinase inhibitor is dasatinib.
52 . The compound of claim 31 , wherein R A is a bone active portion derived from an antimicrobial agent
53 . The compound of claim 52 , wherein the antimicrobial agent is vancomycin.
54 . A method for treating a bone condition in a subject in need thereof, comprising: administering to the subject an effective amount of the compound of claim 1 .
55 . The method of claim 54 , wherein the bone condition is a metabolic bone disease.
56 . The method of claim 55 , wherein the metabolic bone disease is osteoporosis, and wherein R A is a bone active portion derived from a bone active agent selected from: an androgen, a steroidal estrogenic agent, a non-steroidal estrogenic agent, a nitric oxide agent, and a carbonic anhydrase inhibitor.
57 . The method of claim 56 , wherein the subject has a primary condition associated with osteoporosis.
58 . The method of claim 56 , wherein administration of the compound has an anabolic effect on the bone of the subject.
59 . The method of claim 54 , wherein the bone condition is a primary or a secondary bone cancer, and wherein R A is a bone active portion derived from an anti-cancer agent.
60 . The method of claim 59 , wherein the bone condition is a secondary bone cancer.
61 . The method of claim 54 , wherein the subject has a primary cancer associated with a secondary bone cancer.
62 . The method of claim 61 , wherein the primary cancer is breast, lung, prostate, kidney, thyroid cancer, or multiple myeloma.
63 . The method of claim 54 , wherein the bone condition is a microbial infection, and wherein R A is a bone active portion derived from an antimicrobial agent.
64 . The method of claim 63 , wherein the bone condition is osteomyelitis, and wherein R A is a bone active portion derived from an antimicrobial agent.
65 . The method of claim 64 , wherein the osteomyelitis is associated with a prosthetic joint infection.
66 . The method of claim 54 , wherein the subject has a primary infection associated with osteomyelitis.Join the waitlist — get patent alerts
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