US2015032045A1PendingUtilityA1
Photolabile compounds
Est. expiryDec 23, 2031(~5.4 yrs left)· nominal 20-yr term from priority
A61P 35/00A61P 25/08A61K 31/41A61N 5/062A61N 2005/0661A61K 31/465A61P 21/00A61K 31/4045A61K 31/675A61N 2005/0659C07F 15/0053A61N 2005/0657A61K 31/4409A61K 31/198A61K 47/547A61P 25/00B01J 19/12A61K 41/0042A61N 2005/0662B01J 2219/12A61P 17/00A61N 2005/067A61K 47/48076A61N 5/067
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Claims
Abstract
The present invention describes Photolabile Compounds methods for use of the compounds. The Photolabile Compounds have a photoreleasable ligand, which can be biologically active, and which is photoreleased from the compound upon exposure to light. In some embodiments, the Photolabile Compounds comprise a light antenna, such as a labeling molecule or an active derivative thereof. In one embodiment, the light is visible light, which is not detrimental to the viability of biological samples, such as cells and tissues, in which the released organic molecule is bioactive and can have a therapeutic effect. In another embodiment, the photoreleasable ligand can be a labeling molecule, such as a fluorescent molecule.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . A compound of Formula V:
wherein:
each L 1 is independently an organic molecule having:
(a) a 5-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
(h) a 6-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
(c) an 8-10-membered bicyclic ring, one of the bicyclic rings being aromatic and having a nitrogen atom member that forms a bond with Ru;
(d) an —NH 2 group whose nitrogen atom forms a bond with Ru;
(e) a —COOH group, one of whose oxygen atoms forms a bond with Ru;
(f) a —PR 2 group whose phosphorus atom forms a bond with Ru, wherein R is independently —H, —C 1 -C 18 alkyl, or aryl;
(g) an —SR group whose sulfur atom forms a bond with Ru, wherein R is independently —H, —C 1 -C 18 alkyl, or aryl; or
(h) a —CN group whose nitrogen atom forms a bond with Ru;
L 2 is (R 9 ) 3 P, (R 9 O) 3 P, or L 1 and m is 2; or L 2 is —CN and m is 1; or L 2 is a labeling molecule or an active derivative thereof connected to Ru through the phosphorous atom of (R 9 ) 2 P or (R 9 O) 2 P and m is 2; or L 2 is a labeling molecule or an active derivative thereof connected to Ru through the nitrogen atom of: NHR 9 , N(R 9 ) 2 , pyridyl, C(R 9 )═NH, C(R 9 )═NR 9 cyclic aliphatic amine group or nitrile and m is 2;
wherein each R 9 is independently —C 1 -C 18 alkyl, —C 3 -C 8 cycloalkyl, or phenyl;
wherein when L 2 is P(phenyl) 3 or a labeling molecule or an active derivative thereof connected to Ru through the phosphorous atom of P(phenyl) 2 , each phenyl is independently substituted with —C 1 -C 18 alkyl, —(C 1 -C 18 alkyl)-OH, aryl, —(C 1 -C 18 alkyl)-oxy, —(C 1 -C 18 alkyl)-amino, —(C 1 -C 18 alkyl)-thio, —CO 2 Y, —C(═O)Y, —C(═O)NY 2 , —NH 2 , —NO 2 , —OH, or —SH, and
R 1 to R 4 are independently —H, —C 1 -C 18 alkyl; —NH 2 , —(C 1 -C 18 alkyl)-O—(C 1 -C 18 alkyl), —OC(O)(C 1 -C 18 alkyl), —(C 1 -C 18 alkyl)-OH, aryl, —(C 1 -C 18 alkyl)-oxy, —(C 1 -C 18 alkyl)-amino, —(C 1 -C 18 alkyl)-thio, —CO 2 Y, —C(═O)Y, —C(═O)NY 2 , —NO 2 , or —SH, or R 1 and R 2 and/or R 3 and R 4 can combine to form a carbocyclic ring substituted by one or more oxo groups;
wherein when L 2 is not P(phenyl) 3 , R 1 to R 4 are independently —H, —(C 1 -C 18 alkyl)-OH, aryl, —(C 1 -C 18 alkyl)-oxy, —(C 1 -C 18 alkyl)-amino, —(C 1 -C 18 alkyl)-thio, —CO 2 Y, —C(═O)Y, —C(═O)NY 2 , —NO 2 , —OH, or —SH, or R 1 and R 2 and/or R 3 and R 4 can combine to form a carbocyclic ring substituted by one or more oxo groups, wherein at least one of R 1 to R 4 is not H;
X is Cl − , F − , Br − , I − , PF 6 − , CF 3 SO 3 − , (C 1 -C 18 alkyl)-CO 2 − , or (C 1 -C 18 alkyl)-SO 3 − ; and
Y is selected from the group consisting of —H, —C 1 -C 18 alkyl, aryl, —(C 1 -C 18 alkyl)-aryl, —C 3 -C 8 cycloalkyl, heteroaryl, and heterocyclyl.
2 . The compound of claim 1 , wherein each L 1 is independently an organic molecule having a —CN group whose nitrogen atom forms a bond with Ru.
3 . The compound of claim 1 , wherein the organic molecule is methyl beta-D-1-thiogalactopyranoside.
4 . The compound of claim 1 , wherein the organic molecule is isopropyl beta-D-1-thiogalactopyranoside.
5 . The compound of claim 1 , wherein the organic molecule is mercaptopurine, thioguanine, doxorubicin, cytarabin, temozolomide or gentamicin.
6 . The compound of claim 1 , wherein the organic molecule is mercaptopurine.
7 . The compound of claim 1 , wherein the organic molecule is thioguanine.
8 . The compound of claim 1 , wherein the organic molecule is doxorubicin.
9 . The compound of claim 1 , wherein the organic molecule is cytarabin.
10 . The compound of claim 1 , wherein the organic molecule is temozolomide.
11 . The compound of claim 1 , wherein the organic molecule is gentamicin.
12 . The compound of claim 1 or 2 , wherein the organic molecule is benzonitrile, 3-butenenitrile or 2-cyanophenol.
13 . The compound of claim 1 , wherein the organic molecule is an amino acid or a protected amino acid.
14 . The compound of claim 1 or 13 , wherein the organic molecule is methionine.
15 . The compound of claim 1 or 13 , wherein the organic molecule is an N-FMOC-protected amino acid, or an N-BOC-protected amino acid.
16 . The compound of claim 1 , 13 or 15 , wherein the organic molecule is N-FMOC-methionine, N-FMOC-lysine, N-FMOC-arginine, N-BOC-methionine, N-BOC-lysine, or N-BOC-arginine.
17 . The compound of claim 1 , wherein the organic molecule is a nucleotide analog.
18 . The compound of claim 1 or 17 , wherein the organic molecule is emtricitabine, lamivudine, apricitabine, gemcitabine, cladribine, azathioprine, fludarabin, fludarabine, or 5-fluoracyl.
19 . The compound of claim 1 , herein the organic molecule is methotrexate, folic acid, aminopterin or pemetrexed.
20 . A method for releasing an organic molecule from a Photolabile Compound, comprising:
exposing a compound of any of claims 1 - 19 to light under conditions sufficient to release the organic molecule.
21 . The method of claim 20 , wherein the organic molecule has a —CN group whose nitrogen atom forms a bond with Ru.
22 . The method of claim 20 or 21 , wherein the light comprises a wavelength of about 300 to about 500 nm.
23 . The method of any of claims 20 - 22 , wherein the light comprises a wavelength of about 300 to about 360 nm.
24 . The method of any of claims 20 - 22 , wherein the light comprises a wavelength of about 450 to about 500 nm.
25 . The method of any of claims 20 - 24 , wherein L 2 is L 1 .
26 . The method of any of claims 20 - 25 , wherein the light comprises visible light or infrared light.
27 . The method of any of claims 20 - 26 , wherein the exposing occurs at a temperature from about 0° C. to about 150° C.
28 . A method for making an organic molecule bioavailable to a subject, comprising:
(a) administering a compound of any of claims 1 - 19 to the subject; and (b) exposing the compound to light under conditions sufficient to release the organic molecule from the compound.
29 . The method of claim 28 , wherein the organic molecule has a —CN group whose nitrogen atom forms a bond with Ru.
30 . The method of claim 28 or 29 , wherein the light is sunlight, photo-optic light, or laser light.
31 . The method of claim 28 or 29 , wherein the light is visible light or infrared light.
32 . The method of any of claims 28 - 31 , wherein the exposing occurs at the site of a tumor, cancer, or neoplasm.
33 . The method of any of claims 28 - 31 wherein the exposing occurs at the site of a blood dyscrasia.
34 . The method of any of claims 28 - 33 , wherein the administering occurs intravenously, topically, intradermally, intramuscularly, transdermally, subcutaneously, intranasally, parenterally, intrathecally, vaginally, rectally, colorectally, orally, intracranially, retroorbitally, intrasternally, or by injection.
35 . The method of any of claims 28 - 34 , wherein the administering is via a transdermal patch.
36 . A composition comprising a compound of any of claims 1 - 19 and a physiologically acceptable carrier, vehicle, diluent, or excipient.
37 . A vessel containing a compound of any of claims 1 - 19 .
38 . The vessel of claim 37 , further containing a biological sample.
39 . The vessel of claim 38 , wherein the biological sample is an organ, tissue, cell, or hair sample.
40 . The vessel of claim 39 , wherein the tissue is neuronal tissue.
41 . The vessel of claim 39 , wherein the cell is a neuronal cell.
42 . The vessel of claim 39 , wherein the tissue or cell is a tumor, cancer, or neoplastic tissue or cell.
43 . The vessel of claim 38 , wherein the biological sample is a body fluid sample.
44 . The vessel of claim 43 , wherein the body fluid sample is blood, serum, plasma, lymph, saliva, sputum, tears, semen, or urine.
45 . A kit comprising a compound of any of claims 1 - 19 and instructions for use of the compound.
46 . A method of treating disorders and diseases in a subject, comprising
(a) administering a therapeutically effective amount compound of any of claims 1 - 19 to the subject; and (b) exposing the compound to light under conditions sufficient to release the organic molecule from the compound.
47 . The method of claim 46 , wherein the organic molecule has, a CN group whose nitrogen atom forms a bond with Ru.
48 . The method of claim 46 or 47 , wherein the disorders and diseases are neurological, neurophysiological, or neuromuscular diseases and conditions.
49 . The method of any of claims 46 - 48 , wherein the neurological, neurophysiological, or neuromuscular disease and condition is epilepsy.
50 . The method of any of claims 46 - 48 , wherein the neurological, neurophysiological, or neuromuscular disease and condition is multiple sclerosis.
51 . The method of any of claims 46 - 48 , wherein the disorder is diaphoresis.
52 . The method of any of claims 46 - 48 , wherein the disease is cancer.
53 . A method for enhancing the solubility of an organic molecule, comprising
complexing an organic molecule to a photolabile caging group to form a compound of any of claims 1 - 19 ; wherein exposing the compound to light under sufficient conditions releases the organic molecule from the compound.
54 . The method of claim 53 , wherein the organic molecule has a CN group whose nitrogen atom forms a bond with Ru.
55 . A compound of Formula VI:
wherein:
each L 1 is independently an organic molecule having:
(a) a 5-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
(b) a 6-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
(c) an 8-10-membered bicyclic ring, one of the bicyclic rings being aromatic and having a nitrogen atom member that forms a bond with Ru;
(d) an —NH 2 group whose nitrogen atom forms a bond with Ru;
(e) a —COOH group, one of whose oxygen atoms forms a bond with Ru;
(f) a —PR 2 group whose phosphorus atom forms a bond with Ru, wherein R is independently —H, —C 1 -C 18 alkyl, or aryl;
(g) an —SR group whose sulfur atom forms a bond with Ru, wherein R is independently —H, —C 1 -C 18 alkyl, or aryl; or
(h) a —CN group whose nitrogen atom forms a bond with Ru;
L 2 is P(phenyl) 3 , wherein each phenyl is independently substituted with —C 1 -C 18 alkyl, —(C 1 -C 18 alkyl)-OH, aryl, —(C 1 -C 18 alkyl)-oxy, —(C 1 -C 18 alkyl)-amino, —(C 1 -C 18 alkyl)-thio, —CO 2 Y, —C(═O)Y, —C(═O)NY 2 , —NO 2 , —OH, or —SH; or L 2 is a labeling molecule or an active derivative thereof connected to Ru through the phosphorous atom of (R 9 ) 2 P or (R 9 O) 2 P and m is 2; or L 2 is a labeling molecule or an active derivative thereof connected to Ru through the nitrogen atom of: NHR 9 , N(R 9 ) 2 , pyridyl, C(R 9 )═NH, C(R 9 )═NR 9 cyclic aliphatic amine group or nitrile and m is 2;
wherein each R 9 is independently —C 1 -C 18 alkyl, —C 3 -C 8 cycloalkyl, or phenyl;
R 1 to R 4 are independently —H, —C 1 -C 18 alkyl; —NH 2 , —(C 1 -C 18 alkyl)-O—(C 1 -C 18 alkyl), —OC(O)(C 1 -C 18 alkyl), —(C 1 -C 18 alkyl)-OH, aryl, —(C 1 -C 18 alkyl)-oxy, —(C 1 -C 18 alkyl)-amino, —(C 1 -C 18 alkyl)-thio, —CO 2 Y, —C(═O)Y, —C(═O)NY 2 , —NO 2 , or —SH, or R 1 and R 2 and/or R 3 and R 4 can combine to form a carbocyclic ring substituted by one or more oxo groups;
X is Cl − , F − , Br − , I − , PF 6 − , CF 3 SO 3 − , (C 1 -C 18 alkyl)-CO 2 − , or (C 1 -C 18 alkyl)-SO 3 − ; and
Y is selected from the group consisting of —H, —C 1 -C 18 alkyl, aryl, —(C 1 -C 18 alkyl)-aryl, —C 3 -C 8 cycloalkyl, heteroaryl, and heterocyclyl.
56 . The compound of claim 55 , wherein each L 1 is independently an organic molecule having a —CN group whose nitrogen atom forms a bond with Ru.
57 . The compound of claim 55 or 56 , wherein L 2 is P(phenyl) 3 and each phenyl is independently substituted at the 3 or 4 position.
58 . The compound of claim 55 or 56 , wherein L 2 is P(phenyl) 3 and at least one phenyl is substituted with —(C 1 -C 18 alkyl)-OH.
59 . The compound of claim 55 or 56 , wherein L 2 is P(phenyl) 3 and each phenyl is substituted with —(C 1 -C 18 alkyl)-OH.
60 . The compound of claim 55 or 56 , wherein L 2 is P(phenyl) 3 and at least one phenyl is substituted with —COOH.
61 . The compound of claim 55 or 56 , wherein L 2 is P(phenyl) 3 and each phenyl is substituted with —COOH.
62 . The compound of claim 55 or 56 , wherein L 2 is P(phenyl) 3 and at least one phenyl is substituted with —OH.
63 . The compound of claim 55 or 56 , wherein L 2 is P(phenyl) 3 and each phenyl is substituted with —OH.
64 . The compound of claim 55 or 56 , wherein L 2 is P(phenyl) 3 and at least one phenyl is substituted with —NH 2 .
65 . The compound of claim 55 or 56 , wherein L 2 is P(phenyl) 3 and each phenyl is substituted with —NH 2 .
66 . The compound of claim 55 or 56 , wherein L 2 is P(phenyl) 3 and at least one phenyl is substituted with —NO 2 .
67 . The compound of claim 55 or 56 , wherein is P(phenyl) 3 and each phenyl is substituted with —NO 2 .
68 . A compound of Formula VII:
wherein:
each L 1 is independently an organic molecule having:
(a) a 5-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
(b) a 6-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
(c) an 8-10-membered bicyclic ring, one of the bicyclic rings being aromatic and having a nitrogen atom member that forms a bond with Ru;
(d) an —NH 2 group whose nitrogen atom forms a bond with Ru;
(e) a —COOH group, one of whose oxygen atoms forms a bond with Ru;
(f) a —PR 2 group whose phosphorus atom firms a bond with Ru, wherein R is independently —H, —C 1 -C 18 alkyl, or aryl;
(g) an —SR group whose sulfur atom forms a bond with Ru, wherein R is independently —H, —C 1 -C 18 alkyl, or aryl; or
(h) a —CN group whose nitrogen atom forms a bond with Ru;
L 2 is (R 9 ) 3 P, (R 9 O) 3 P, or L 1 , wherein each R 5 is independently —C 1 -C 18 alkyl, —C 3 -C 8 cycloalkyl, or phenyl, m is 2, and L 2 is not P(phenyl) 3 ; or L 2 is —CN and m is 1; or L 2 is a labeling molecule or an active derivative thereof connected to Ru through the phosphorous atom of (R 9 ) 2 P or (R 9 O) 2 P and m is 2; or L 2 is a labeling molecule or an active derivative thereof connected to Ru through the nitrogen atom of: NHR 9 , N(R 9 ) 2 , pyridyl, C(R 9 )═NH, C(R 9 )═NR 9 cyclic aliphatic amine group or nitrile and m is 2;
wherein each R 9 is independently —C 1 -C 18 alkyl, —C 3 -C 8 cycloalkyl, or phenyl;
R 1 to R 4 are independently —H, —(C 1 -C 18 alkyl)-OH, aryl, —(C 1 -C 18 alkyl)-oxy, —(C 1 -C 18 alkyl)-amino, —(C 1 -C 18 alkyl)-thio, —CO 2 Y, —C(═O)Y, —C(═O)NY 2 , —NO 2 , —OH, or —SH, or R 1 and R 2 and/or R 3 and R 4 can combine to form a carbocyclic ring substituted by one or more oxo groups, wherein at least one of R 1 to R 4 is not H;
X is Cl − , F − , Br − , I − , PF 6 − , CF 3 SO 3 − , (C 1 -C 18 alkyl)-CO 2 − , or (C 1 -C 18 alkyl)-SO 3 − ; and
Y is selected from the group consisting of —H, —C 1 -C 18 alkyl, aryl, —(C 1 -C 18 alkyl)-aryl, —C 3 -C 8 cycloalkyl, heteroaryl, and heterocyclyl.
69 . The compound of claim 68 , wherein each L 1 is independently an organic molecule having a —CN group whose nitrogen atom forms a bond with Ru.
70 . The compound of claim 68 or 69 , wherein L 2 is P(methyl)(phenyl) 2 .
71 . The compound of claim 68 or 69 , wherein L 2 is P(methyl) 2 (phenyl).
72 . The compound of claim 69 , wherein L 1 is methyl beta-D-1-thiogalactopyranoside, and L 2 is P(phenyl) 3 .
73 . The compound of claim 69 , wherein L 1 is isopropyl beta-D-1-thiogalactopyranoside, and L 2 is P(phenyl) 3 .Join the waitlist — get patent alerts
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