Photolabile compounds

Patent metadata

Field	Value
Publication number	US-9744236-B2
Application number	US-201113336643-A
Country	US
Kind code	B2
Filing date	Dec 23, 2011
Priority date	Jun 26, 2009
Publication date	Aug 29, 2017
Grant date	Aug 29, 2017

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.

First claim

We 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;
(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 (R 9 ) 3 P, or (R 9 O) 3 P and m is 2; 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 the organic molecule is 4-aminopyridine.

3. The compound of claim 1 , wherein the organic molecule is (RS)-(tetrazol-5-yl) glycine.

4. The compound of claim 1 , wherein the organic molecule is (tetrazol-5-yl) AMPA.

5. The compound of claim 1 , wherein the organic molecule is nicotine or caffeine.

6. The compound of claim 1 , wherein the organic molecule is serotonin, epinephrine, norepinephrine, or dopamine.

7. The compound of claim 1 , wherein the organic molecule is adenosine 5′-diphosphate ADP, adenosine 5′-triphosphate ATP, adenosine 5′-monophosphate AMP, cyclic adenosine 5′-diphosphate ribose, or adenosine 3′, 5′-cyclic monophosphate.

8. The compound of claim 1 , wherein the organic molecule is aminobutyric acid or L-glutamic acid, or methyl-D-aspartic acid.

9. The compound of claim 1 , wherein the organic molecule is methyl beta-D-1-thiogalactopyranoside.

10. The compound of claim 1 , wherein the organic molecule is isopropyl beta-D-1-thiogalactopyranoside.

11. The compound of claim 1 , wherein the organic molecule is mercaptopurine, thioguanine, doxorubicin, cytarabin, temozolomide or gentamicin.

12. The compound of claim 1 , wherein the organic molecule is mercaptopurine.

13. The compound of claim 1 , wherein the organic molecule is thioguanine.

14. The compound of claim 1 , wherein the organic molecule is doxorubicin.

15. The compound of claim 1 , wherein the organic molecule is cytarabin.

16. The compound of claim 1 , wherein the organic molecule is temozolomide.

17. The compound of claim 1 , wherein the organic molecule is gentamicin.

18. The compound of claim 1 , wherein the organic molecule is benzonitrile, 3-butenenitrile or 2-cyanophenol.

19. A method for releasing an organic molecule from a Photolabile Compound, comprising:
exposing a compound of claim 1 to light under conditions sufficient to release the organic molecule.

20. The method of claim 19 , wherein the light comprises a wavelength of about 300 to about 500 nm.

21. The method of claim 19 , wherein the light comprises a wavelength of about 300 to about 360 nm.

22. The method of claim 19 , wherein the light comprises a wavelength of about 450 to about 500 nm.

23. The method of claim 19 , wherein the light comprises visible light or infrared light.

24. The method of claim 19 , wherein the exposing occurs at a temperature from about 0° C. to about 150° C.

25. A method for making an organic molecule bioavailable to a subject, comprising:
(a) administering a compound of claim 1 to the subject; and
(b) exposing the compound to light under conditions sufficient to release the organic molecule from the compound, wherein the organic molecule has:
a 5-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
(ii) a 6-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
(iii) 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;
(iv) an —NH 2 group whose nitrogen atom forms a bond with Ru;
(v) a —COOH group, one of whose oxygen atoms forms a bond with Ru;
(vi) a —PR 2 group whose phosphorus atom forms a bond with Ru, wherein R is independently —H, —C 1 -C 18 alkyl, or aryl;
(vii) an —SR group whose sulfur atom forms a bond with Ru, wherein R is independently —H, —C 1 -C 18 alkyl, or aryl; or
(viii) a —CN group whose nitrogen atom forms a bond with Ru.

26. The method of claim 25 , wherein the organic molecule has:
a 5-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
(ii) a 6-membered monocyclic aromatic ring, one of the ring's members being a nitrogen atom that forms a bond with Ru;
(iii) 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;
(iv) an —NH 2 group whose nitrogen atom forms a bond with Ru;
(v) a —COOH group, one of whose oxygen atoms forms a bond with Ru;
(vi) a —PR 2 group whose phosphorus atom forms a bond with Ru, wherein R is independently —H, —C 1 -C 18 alkyl, or aryl; or
(vii) an —SR group whose sulfur atom forms a bond with Ru, wherein R is independently —H, —C 1 -C 18 alkyl, or aryl.

27. Th

Assignees

• Yuste Rafael
• Etchenique Roberto
• Baraldo Luis
• Univ Columbia
• Univ Buenos Aires

Inventors

• Yuste Rafael
• Etchenique Roberto
• Baraldo Luis

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• A61K31/41

  having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• B01J19/12

  employing electromagnetic waves · CPC title