THERAPEUTIC AGENTS FOR REDUCING PARATHYROID HORMONE LEVELS

• US 20120178688A1
• Filed: 02/02/2012
• Published: 07/12/2012
• Est. Priority Date: 07/29/2009
• Status: Active Grant

• Current Assignee: Kai Pharmaceuticals, Inc. (Amgen Inc.)
• Original Assignee: Kai Pharmaceuticals, Inc. (Amgen Inc.)
• Inventors: MACLEAN, DEREK, KARIM, FELIX, BARUCH, AMOS, DAS, KANAD, YIN, QUN
• Granted Patent: US 8,377,880 B2
• Time in Patent Office: Days
• US Class Current: 514/11.8
• 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 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: A61P 5/20 for decreasing, blocking or antagonising the activity of PTH
• CPC Class Codes: C07K 5/1013 the side chain containing O or S as heteroatoms, e.g. Cys, Ser
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

Compounds having activity for lowering parathyroid hormone levels are described. In one embodiment, the compounds are comprised of a contiguous sequence of subunits, X₁-X₂-X₃-X₄-X₅-X₆-X₇, wherein the X₁ subunit comprises a thiol-containing moiety and the distribution of charge on the X₂-X₇ subunits provides the desired activity. Methods of using the compounds for treating hyperparathyroidism, bone disease and/or hypercalcemic disorders are also described, and in particular, methods for lowering plasma PTH and serum calcium are provided. The compounds can be used to treat subjects having, for example: primary, secondary or tertiary hyperparathyroidism; hypercalcemia of malignancy; metastatic bone disease; or osteoporosis.

Claims

1. A compound comprising Ac-c(C)arrrar-NH₂ (SEQ ID NO:

3).

3. The compound of claim 1, wherein the compound comprises a pharmaceutically acceptable salt of Ac-c(C)arrrar-NH₂ (SEQ ID NO:

3).

2. (canceled)

4. A compound consisting of Ac-c(C)arrrar-NH₂ (SEQ ID NO:

3), or a pharmaceutically acceptable salt thereof.

5. The compound of claim 4, wherein the salt is an acid addition salt.

6. The compound of claim 4, wherein the salt is a hydrochloride salt.

7. A pharmaceutical composition comprising a compound comprising Ac-c(C)arrrar-NH₂ (SEQ ID NO:

3) and a pharmaceutically acceptable excipient.

8. The composition of claim 7, wherein the composition is a lyophilized composition.

9. The composition of claim 7, wherein the composition is a solution.

10. A pharmaceutical composition comprising a compound consisting of Ac-c(C)arrrar-NH₂ (SEQ ID NO:

3), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

11. The composition of claim 10, wherein the composition is a lyophilized composition.

12. The composition of claim 10, wherein the composition is a solution.

13. The composition of claim 10, wherein the salt is a hydrochloride salt.

14. The composition of claim 13, wherein the composition is a lyophilized composition.

15. The composition of claim 13, wherein the composition is a solution.