TYROSINE DERIVATIVES AND COMPOSITIONS COMPRISING THEM

• US 20170172924A1
• Filed: 03/06/2017
• Published: 06/22/2017
• Est. Priority Date: 10/22/2013
• Status: Active Grant

• Current Assignee: Tyme Inc. (Syros Pharmaceuticals, Inc.)
• Original Assignee: Tyme Inc. (Syros Pharmaceuticals, Inc.)
• Inventors: Hoffman, Steven
• Granted Patent: US 11,058,638 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 33/40 Peroxides
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 45/00 Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 9/141 Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers (co) spray-dried products A61K9/16, (co) lyophilised products A61K9/19; the carrier being chemically bound to the active ingredient A61K47/50
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1682 Processes
• CPC Class Codes: A61N 2005/0659 infrared
• CPC Class Codes: A61N 2005/0661 ultraviolet
• CPC Class Codes: A61N 2005/0662 Visible light
• CPC Class Codes: A61N 2005/1098 Enhancing the effect of the particle by an injected agent or implanted device
• CPC Class Codes: A61N 5/022 Apparatus adapted for a specific treatment
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61N 5/10 X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Provided herein are methods comprising providing a tyrosine derivative and a solid particulate material (and, optionally, melanin) and applying force to said tyrosine derivative and said solid particulate material for a time and under conditions effective to impregnate at least one of said tyrosine derivative and said solid particulate material with the other of said tyrosine derivative and said solid particulate material. The invention also provides compositions comprising at least one of a tyrosine derivative impregnated with a solid particulate material and a solid particulate material impregnated with a tyrosine derivative.

Claims

1. A method comprising:

providing a tyrosine derivative and a solid particulate material; and

applying force to said tyrosine derivative and said solid particulate material for a time and under conditions effective to impregnate at least one of said tyrosine derivative and said solid particulate material with the other of said tyrosine derivative and said solid particulate material.

2. The method of claim 1 further comprising adding hydrogen peroxide to said tyrosine derivative and said solid particulate material after applying said force to said tyrosine derivative and said solid particulate material.

3. A composition comprising at least one of a tyrosine derivative impregnated with a solid particulate material and a solid particulate material impregnated with a tyrosine derivative.

4. The composition of claim 3 wherein the tyrosine derivative is capable of existing in isomeric forms.

5. The composition of claim 4 wherein the tyrosine derivative is in its L-form.

6. The composition of claim 4 wherein the tyrosine derivative is in its D-form.

7. The composition of claim 3 wherein the tyrosine derivative is one or more of methyl (2R)-2-amino-3-(2-chloro-4 hydroxyphenyl) propanoate, D-tyrosine ethyl ester hydrochloride, methyl (2R)-2-amino-3-(2,6-dichloro-3,4-dimethoxyphenyl) propanoate H-D-Tyr(TBU)-allyl ester HCl, methyl (2R)-2-amino-3-(3-chloro-4,5-dimethoxyphenyl) propanoate, methyl (2R)-2-amino-3-(2-chloro-3-hydroxy-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(4-[(2-chloro-6-fluorophenyl) methoxy] phenyl) propanoate, methyl (2R)-2-amino-3-(2-chloro-3,4-dimethoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-5-fluoro-4-hydroxyphenyl) propanoate, diethyl 2-(acetylamino)-2-(4-[(2-chloro-6-fluorobenzyl) oxy] benzyl malonate, methyl (2R)-2-amino-3-(3-chloro-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-4-hydroxy-5-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(2,6-dichloro-3-hydroxy-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-4-hydroxyphenyl) propanoate, H-DL-tyr-OME HCl, H-3,5-diiodo-tyr-OME HCl, H-D-3,5-diiodo-tyr-OME HCl, H-D-tyr-OME HCl, D-tyrosine methyl ester hydrochloride, D-tyrosine-ome HCl, methyl D-tyrosinate hydrochloride, H-D-tyr-OMe.HCl, D-tyrosine methyl ester HCl, H-D-Tyr-OMe-HCl, (2R)-2-amino-3-(4-hydroxyphenyl) propionic acid, (2R)-2-amino-3-(4-hydroxyphenyl) methyl ester hydrochloride, methyl (2R)-2-amino-3-(4-hydroxyphenyl) propanoate hydrochloride, methyl (2R)-2-azanyl-3-(4-hydroxyphenyl) propanoate hydrochloride, 3-chloro-L-tyrosine, 3-nitro-L-tyrosine, 3-nitro-L-tyrosine ethyl ester hydrochloride, DL-m-tyrosine, DL-o-tyrosine, Boc-Tyr (3,5-I2)-OSu, Fmoc-tyr(3-NO2)—

OH, α

-methyl-L-tyrosine, α

-methyl-D-tyrosine, and α

-methyl-DL-tyrosine.

8. The composition of claim 7 wherein the tyrosine derivative is α

-methyl-L-tyrosine.

9. The composition of claim 7 wherein the tyrosine derivative is α

-methyl-D-tyrosine.

10. The composition of claim 3 wherein the solid particulate material is soluble in water.

11. The composition of claim 3 wherein the solid particulate material is not soluble in water.

12. The composition of claim 3 wherein the solid particulate material is or comprises a pharmaceutically active ingredient.

13. The composition of claim 12 wherein the pharmaceutically active ingredient has therapeutic activity in the treatment of cancer.

14. The composition of claim 12 wherein the solid particulate material is or comprises at least one of a selective estrogen receptor modulator, an aromatase inhibitor, a signal transduction inhibitor, a drug that modifies the function of proteins that regulate gene expression and other cellular functions, a drug that induces cancer cells to undergo apoptosis, and a drug that interferes with angiogenesis.

15. The composition of claim 12 wherein the pharmaceutically active ingredient is one or more of tamoxifen, toremifene, fulvestrant, anastrozole, exemestane, letrozole, imatinib mesylate, dasatinib, nilotinib, bosutinib, lapatinib, gefitinib, erlotinib, temsirolimus, everolimus, vandetanib, vemurafenib, crizotinib, vorinostat, romidepsin, bexarotene, alitretinoin, tretinoin, bortezomib, carfilzomib, pralatrexate, sorafenib, sunitinib, pazopanib, regorafenib, cabozantinib, denileukin, diftitox, ziv-aflibercept, cisplatin, cisplatinum, (cis-diamminedichloroplatinum(II)), carboplatin, oxaliplatin, benzyl isothiocyanate, acetylcholine, and dihydrotestosterone (DHT).

16. The composition of claim 3 further comprising hydrogen peroxide.

17. A method comprising administering a composition of claim 3 to a patient in need thereof.

18. The method of claim 17 wherein the patient has been diagnosed with cancer.

19. The method of claim 17 wherein the composition is administered orally, nasally, subcutaneously, intravenously, intramuscularly, transdermally, vaginally, rectally or in any combination thereof.

20. The method of claim 3 further comprising providing melanin with said tyrosine derivative and said solid particulate material;

and applying said force to said melanin, said tyrosine derivative and said solid particulate material for a time and under conditions effective to impregnate at least one of said tyrosine derivative and said solid particulate material with the other of said tyrosine derivative and said solid particulate material.

21. The method of claim 20 further comprising applying an electromagnetic field to said patient.

22. The method of claim 21 wherein the electromagnetic field is from radio waves, microwaves, infrared light, visible light, ultraviolet light, x-rays or gamma rays.

23. A composition comprising a tyrosine derivative, melanin, and a solid particulate material.

24. The composition of claim 23 wherein the tyrosine derivative is one or more of methyl (2R)-2-amino-3-(2-chloro-4 hydroxyphenyl) propanoate, D-tyrosine ethyl ester hydrochloride, methyl (2R)-2-amino-3-(2,6-dichloro-3,4-dimethoxyphenyl) propanoate H-D-Tyr(TBU)-allyl ester HCl, methyl (2R)-2-amino-3-(3-chloro-4,5-dimethoxyphenyl) propanoate, methyl (2R)-2-amino-3-(2-chloro-3-hydroxy-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(4-[(2-chloro-6-fluorophenyl) methoxy] phenyl) propanoate, methyl (2R)-2-amino-3-(2-chloro-3,4-dimethoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-5-fluoro-4-hydroxyphenyl) propanoate, diethyl 2-(acetylamino)-2-(4-[(2-chloro-6-fluorobenzyl) oxy] benzyl malonate, methyl (2R)-2-amino-3-(3-chloro-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-4-hydroxy-5-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(2,6-dichloro-3-hydroxy-4-methoxyphenyl) propanoate, methyl (2R)-2-amino-3-(3-chloro-4-hydroxyphenyl) propanoate, H-DL-tyr-OME HCl, H-3,5-diiodo-tyr-OME HCl, H-D-3,5-diiodo-tyr-OME HCl, H-D-tyr-OME HCl, D-tyrosine methyl ester hydrochloride, D-tyrosine-ome HCl, methyl D-tyrosinate hydrochloride, H-D-tyr-OMe.HCl, D-tyrosine methyl ester HCl, H-D-Tyr-OMe-HCl, (2R)-2-amino-3-(4-hydroxyphenyl) propionic acid, (2R)-2-amino-3-(4-hydroxyphenyl) methyl ester hydrochloride, methyl (2R)-2-amino-3-(4-hydroxyphenyl) propanoate hydrochloride, methyl (2R)-2-azanyl-3-(4-hydroxyphenyl) propanoate hydrochloride, 3-chloro-L-tyrosine, 3-nitro-L-tyrosine, 3-nitro-L-tyrosine ethyl ester hydrochloride, DL-m-tyrosine, DL-o-tyrosine, Boc-Tyr (3,5-I2)-OSu, Fmoc-tyr(3-NO2)—

OH, α

-methyl-L-tyrosine, α

-methyl-D-tyrosine, and α

-methyl-DL-tyrosine.

25. The composition of claim 24 wherein the tyrosine derivative is α

-methyl-L-tyrosine.

26. The composition of claim 24 wherein the tyrosine derivative is α

-methyl-D-tyrosine.

27. The composition of claim 24 wherein the solid particulate material is or comprises a pharmaceutically active ingredient.

28. The composition of claim 27 wherein the pharmaceutically active ingredient is one or more of tamoxifen, toremifene, fulvestrant, anastrozole, exemestane, letrozole, imatinib mesylate, dasatinib, nilotinib, bosutinib, lapatinib, gefitinib, erlotinib, temsirolimus, everolimus, vandetanib, vemurafenib, crizotinib, vorinostat, romidepsin, bexarotene, alitretinoin, tretinoin, bortezomib, carfilzomib, pralatrexate, sorafenib, sunitinib, pazopanib, regorafenib, cabozantinib, denileukin, diftitox, ziv-aflibercept, cisplatin, cisplatinum, (cis-diamminedichloroplatinum(II)), carboplatin, oxaliplatin, benzyl isothiocyanate, acetylcholine, and dihydrotestosterone (DHT).