Aromatic nitro and nitroso compounds and their metabolites useful as anti-viral and anti-tumor agents

• US 5,670,518 A
• Filed: 06/06/1995
• Issued: 09/23/1997
• Est. Priority Date: 05/12/1993
• Status: Expired due to Term

• Current Assignee: Octamer, Inc.
• Original Assignee: Octamer, Inc.
• Inventors: Mendeleyev, Jerome, Kun, Ernest, Kirsten, Eva
• Primary Examiner(s): Ivy, C. Warren
• Assistant Examiner(s): SEAMAN, D MARGARET M
• Application Number:
  US08/473,043
• Time in Patent Office: 840 Days
• Field of Search: 564/166, 514/617, 514/309, 514/456, 546/141, 549/399
• US Class Current: 514/309
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07C 233/65 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
• CPC Class Codes: C07D 311/14 substituted in position 6 and unsubstituted in position 7
• CPC Class Codes: C07J 41/0005 the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
• CPC Class Codes: C07J 41/0044 with an estrane or gonane skeleton, including 18-substituted derivatives and derivatives where position 17-beta is substituted by a carbon atom not directly bonded to another carbon atom and not being part of an amide group
• CPC Class Codes: C07J 41/0072 the A ring of the steroid being aromatic

Abstract

Unsubstituted or substituted halo nitro and nitroso compounds and their metabolites are potent, selective and non-toxic inhibitors and supressants of cancer growth and viral infections in a mammalian host. The compounds are particularly useful for treatment and supression of tumors and viruses associated with breast cancer, AIDS, herpetic episodes and cytomegaloviral infections. The methods of treatment of tumorigenic and viral diseases by halo nitro and nitroso compounds and their metabolites are described.

Claims

1. A method of treating retroviral infections, said method comprising the step of administering to a subject a therapeutically effective amount of a compound selected from the group consisting of:

a compound having the structural formula;

##STR18## wherein R₁, R₂, R₃, R₄, R₅ and R₆ are, independent of one another, selected from the group consisting of hydrogen, hydroxy, amino, nitroso, nitro, halogen, (C₁ -C₆) alkyl, (C₁ -C₆) alkoxy, (C₃ -C₇) cycloalkyl, and phenyl and pharmaceutically acceptable salts thereof, wherein at least three of the six R₁, R₂, R₃, R₄, R₅ and R₆ substituents are always hydrogen and at least one of the six R₁, R₂, R₃, R₄, R₅ and R₆ substituents are always nitro;

a compound having the structural formula;

##STR19## wherein R₁, R₂, R₃, R₄ and R₅ are, independent of one another, selected from the group consisting of hydrogen, hydroxy, amino, nitroso, nitro, halogen, (C₁ -C₆) alkyl, (C₁ -C₆) alkoxy, (C₃ -C₇) cycloalkyl, and phenyl and pharmaceutically acceptable salts thereof, wherein at least two of the five R₁, R₂, R₃, R₄ and R₅ substituents are always hydrogen and at least one of the five R₁, R₂, R₃, R₄ and R₅ substituents are always nitro;

a compound having the structural formula;

##STR20## wherein R₁, R₂, R₃, R₄ and R₅ are, independent of one another, selected from the group consisting of hydrogen, hydroxy, amino, nitroso, nitro, halogen, (C₁ -C₆) alkyl, (C₁ -C₆) alkoxy, (C₃ -C₇) cycloalkyl, and phenyl and pharmaceutically acceptable salts thereof, wherein at least two of the five R₁, R₂, R₃, R₄ and R₅ substituents are always hydrogen and at least one of the five R₁, R₂, R₃, R₄ and R₅ substituents are always nitro; and

a compound having the structural formula;

##STR21##

2. The method of claim 1, wherein the compound has the structural formula:

##STR22## wherein R₁, R₂, R₃, R₄, R₅ and R₆ are, independent of one another, selected from the group consisting of hydrogen, hydroxy, amino, nitroso, nitro, halogen, (C₁ -C₆) alkyl, (C₁ -C₆) alkoxy, (C₃ -C₇) cycloalkyl, and phenyl and pharmaceutically acceptable salts thereof, wherein at least three of the six R₁, R₂, R₃, R₄, R₅ and R₆ substituents are always hydrogen and at least one of the six R₁, R₂, R₃, R₄, R₅ and R₆ substituents are always nitro.

3. The method of claim 2, wherein R₄ is nitro.

4. The method of claim 2, wherein the halogen is iodine.

5. The method of claim 1, wherein the compound has the structural formula:

##STR23##

6. The method of claim 1, wherein the compound has the structural formula:

##STR24## wherein R₁, R₂, R₃, R₄ and R₅ are, independent of one another, selected from the group consisting of hydrogen, hydroxy, amino, nitroso, nitro, halogen, (C₁ -C₆) alkyl, (C₁ -C₆) alkoxy, (C₃ -C₇) cycloalkyl, and phenyl and pharmaceutically acceptable salts thereof, wherein at least two of the five R₁, R₂, R₃, R₄ and R₅ substituents are always hydrogen and at least one of the five R₁, R₂, R₃, R₄ and R₅ substituents are always nitro.

7. The method of claim 6, wherein R₁, R₄ and R₅ are each hydrogen;

R₂ is nitro; and

R₃ is iodine.

8. The method of claim 1, wherein the compound has the structural formula:

##STR25## wherein R₁, R₂, R₃, R₄ and R₅ are, independent of one another, selected from the group consisting of hydrogen, hydroxy, amino, nitroso, nitro, halogen, (C₁ -C₆) alkyl, (C₁ -C₆) alkoxy, (C₃ -C₇) cycloalkyl, and phenyl and pharmaceutically acceptable salts thereof, wherein at least two of the five R₁, R₂, R₃, R₄ and R₅ substituents are always hydrogen and at least one of the five R₁, R₂, R₃, R₄ and R₅ substituents are always nitro.

9. The method of claim 8, wherein R₂ is nitro.

10. The method of claim 8, wherein the halogen is iodine.

11. The method of claim 8, wherein R₂ is nitro;

R₁ is iodine; and

R₃, R₄ and R₅ are each hydrogen.