Method for treating multiple sclerosis

• US 5,633,283 A
• Filed: 01/23/1995
• Issued: 05/27/1997
• Est. Priority Date: 01/23/1995
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Panetta, Jill A., Kingston, Ann E.
• Primary Examiner(s): Dees, Jos e G.
• Assistant Examiner(s): TILL, MARY C
• Application Number:
  US08/376,619
• Time in Patent Office: 855 Days
• Field of Search: 514/903, 514/653, 514/658
• US Class Current: 514/653
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/166 having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4453 only substituted in position 1, e.g. propipocaine, diperodon
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders

Abstract

Provided is a method of treating multiple sclerosis employing certain phenol and benzamide compounds.

Claims

1. A method of treating multiple sclerosis in a mammal in need of such treatment which comprises administering to said mammal a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, of formula (I) ##STR19## wherein:

R¹ and R² are each independently hydrogen, C₃ -C₆ alkyl, C₁ -C₆ alkoxy or

R³ and R⁴ are each independently hydrogen or C₁ -C₄ alkyl;

n is an integer from 0 to 4, both inclusive; and

R⁵ and R⁶ are each independently hydrogen, C₁ -C₈ alkyl, C₃ -C₈ cycloalkyl, C₂ -C₈ alkenyl, C₂ -C₈ alkynyl, --(CH₂)_q OR⁷, --(CH₂)_q N(R⁷ R⁸), --(CH₂)_q SR⁷, --(CH₂)_r naphthyl or ##STR20## where q is an integer from 1 to 6, both inclusive, R⁷ and R⁸ are each independently hydrogen or C₁ -C₄ alkyl, R⁹ is hydrogen, halo, C₁ -C₄ alkyl, trifluoromethyl, hydroxy, amino, C₁ -C₄ alkylamino, di(C₁ -C₄ alkyl)amino, phenylamino or diphenylamino, and r is an integer from 0 to 4, both inclusive.

2. The method of claim 1 which employs a compound of formula I or a pharmaceutically acceptable salt thereof, wherein:

R¹ and R² are hydrogen or C₃ -C₆ alkyl;

R⁵ and R⁶ are hydrogen, C₁ -C₆ alkyl, C₃ -C₈ cycloalkyl, C₂ -C₆ alkenyl, C₂ -C₆ alkynyl or ##STR21##

3. The method of claim 2 which employs a compound of formula I, or a pharmaceutically acceptable salt thereof, wherein R¹ and R² are either both 1,1-dimethylethyl or one of R¹ and R² is hydrogen and the other is 1,1-dimethylethyl, n is an integer from 1 to 4, both inclusive, R³ and R⁴ are hydrogen and R⁵ and R⁶ are each independently hydrogen or C₁ -C₄ alkyl.

4. The method of claim 3 wherein the compound employed is 4-[(dimethylamino)methyl]-2,6-bis(1,1-dimethylethyl)phenol or a pharmaceutically acceptable salt thereof.

5. The method of claim 4 wherein the pharmaceutically acceptable salt thereof is the hydrochloride salt.

6. The method of claim 4 wherein the pharmaceutically acceptable salt thereof is the methanesulfonate salt.

7. The method of claim 3 wherein the compound employed is 4-[2-(methylamino)ethyl]-2,6-bis(1,1-dimethylethyl)phenol or a pharmaceutically acceptable salt thereof.

8. The method of claim 7 wherein the pharmaceutically acceptable salt thereof is the hydrochloride salt.

9. The method of claim 3 wherein the compound employed is 4-[(methylamino)methyl]-2,6-bis(1,1-dimethylethyl)phenol or a pharmaceutically acceptable salt thereof.

10. The method of claim 9 wherein the pharmaceutically acceptable salt thereof is the hydrochloride salt.

11. The method of claim 3 wherein the compound employed is a [(ethylamino)methyl]-2,6-bis(1,1-dimethylethyl)phenol or a pharmaceutically acceptable salt thereof.

12. The method of claim 11 wherein the pharmaceutically acceptable salt thereof is the hydrochloride salt.

13. The method of claim 3 wherein the compound employed is 4-[2-(methylamino)ethyl]-2-(1,1-dimethylethyl)phenol or a pharmaceutically acceptable salt thereof.

14. The method of claim 13 wherein the pharmaceutically acceptable salt thereof is the hydrochloride salt.

15. The method of claim 1 which employs a compound of formula I, or a pharmaceutically acceptable salt thereof, wherein:

R⁵ and R⁶ are each independently hydrogen, C₁ -C₆ alkyl, C₂ -C₆ alkenyl, C₂ -C₆ alkynyl, --(CH₂)_q OH, --(CH₂)_q NH₂, --(CH₂)_q NH(C₁ -C₄ alkyl), --(CH₂)_q N(C₁ -C₄ alkyl)₂, --(CH₂)_q S(C₁ -C₄ alkyl) or ##STR22##