Conformationally restricted polyamine analogs as disease therapies

• US 6,794,545 B1
• Filed: 04/27/2000
• Issued: 09/21/2004
• Est. Priority Date: 04/30/1999
• Status: Expired due to Fees

• Current Assignee: Cellgate, Inc. (Tbg Diagnostics Limited)
• Original Assignee: Slil Biomedical Corp.
• Inventors: Basu, Hirak S., Blokhin, Andrei V., Reddy, Venodhar K., Frydman, Benjamin, Valasinas, Aldonia, Marton, Laurence J.
• Primary Examiner(s): DAVIS, BRIAN J
• Application Number:
  US09/560,711
• Time in Patent Office: 1,608 Days
• Field of Search: 564/509, 564/503, 564/506, 564/452, 564/453, 564/454, 564/246
• US Class Current: 564/509
• 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 47/65 Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07C 211/09 : Diamines
• CPC Class Codes: C07C 211/18 : containing at least two amino groups bound to the carbon skeleton
• CPC Class Codes: C07C 211/22 : containing at least two amino groups bound to the carbon skeleton
• CPC Class Codes: C07C 211/23 : the carbon skeleton containing carbon-to-carbon triple bonds
• CPC Class Codes: C07C 211/36 : containing at least two amino groups bound to the carbon skeleton
• CPC Class Codes: C07C 215/14 : the nitrogen atom of the amino group being further bound to hydrocarbon groups substituted by amino groups
• CPC Class Codes: C07C 257/18 : having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 2601/04 : with a four-membered ring
• CPC Class Codes: C07C 2601/08 : the ring being saturated
• CPC Class Codes: C07C 45/46 : Friedel-Crafts reactions
• CPC Class Codes: C07C 47/575 : containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 67/343 : by increase in the number of carbon atoms
• CPC Class Codes: C07C 69/734 : Ethers
• CPC Class Codes: C07D 207/34 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 219/10 : attached in position 9
• CPC Class Codes: C07D 235/18 : with aryl radicals directly attached in position 2
• CPC Class Codes: C07D 295/185 : from aliphatic carboxylic acids
• CPC Class Codes: C07D 307/79 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 307/92 : Naphthofurans; Hydrogenated naphthofurans
• CPC Class Codes: C07D 311/92 : Naphthopyrans; Hydrogenated naphthopyrans
• CPC Class Codes: C07D 317/70 : condensed with ring systems containing two or more relevant rings
• CPC Class Codes: C07D 487/22 : in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07D 493/04 : Ortho-condensed systems
• 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

Abstract

Novel conformationally restricted polyamine analogs are provided, as well as compositions comprising these novel polyamine analogs. Methods of using the novel polyamine analogs in treatment of diseases such as cancer are also provided. Also provided is a method of delivering these analogs specifically to tumor cells by covalently attaching polyamine analogs to, porphyrin compounds, along with novel polyamine-porphyrin covalent conjugates.

Claims

1. A conformationally restricted polyamine analog of the formula:

2. A conformationally restricted polyamine analog according to claim 1, selected from the group consisting of

and any salt or stereoisomer thereof.

7. A compound of claim 1, further comprising a pharmaceutically acceptable excipient.

15. A method of treating cancer in an individual comprising the step of administering to the individual a therapeutic amount of a compound of claim 1.

16. The method of claim 15, wherein the cancer is breast cancer.

3. A conformationally restricted polyamine analog of the formula:

4. A conformationally restricted polyamine analog according to claim 3, selected from the group consisting of:

and any salt or stereoisomer thereof.

8. A method of treating cancer in an individual comprising the step of administering to the individual a therapeutic amount of a compound of claim 3.

9. The method of claim 8, wherein the individual is a human.

10. The method of claim 8, wherein the cancer affects cells of the bladder, blood, brain, breast, colon, digestive tract, lung, ovaries, pancreas, prostate gland, or skin.

11. A method of treating a disease in an individual, wherein the disease is selected from Alzheimer'"'"'s disease, psoriasis, or an infection or infestation of parasites, or fungi, comprising administering to the individual a therapeutically effective amount of a compound of claim 3.

12. A method of suppressing cell growth in an individual comprising the step of administering to the individual a therapeutic amount of a compound of claim 3.

13. The method of claim 12, wherein the individual is a human.

14. The method of claim 8, wherein the cancer is breast cancer.

17. A method of treating cancer in an individual comprising the step of administering to the individual a therapeutic amount of a compound of claim 4.

18. The method of claim 17, wherein the cancer is breast cancer.

19. A pharmaceutical composition comprising a compound of claim 3 and a pharmaceutically acceptable excipient.

20. A pharmaceutical composition comprising a compound of claim 4 and a pharmaceutically acceptable excipient.

5. A polyamine analog of the formula:

6. A polyamine analog according to claim 5, selected from the group consisting of:

and all salts and stereoisomers thereof.