Claims for Patent: 4,517,199

Summary for Patent: 4,517,199

Title:	Method for lowering intraocular pressure using phenylimino-imidazoles
Abstract:	2-(Trisubstituted phenylimino)-imidazole compounds also known as 2-(trisubstituted anilino)-1,3 diazacyclopentene-(2) compounds are used to lower intraocular pressure.
Inventor(s):	York, Jr.; Billie M. (Fort Worth, TX)
Assignee:	Alcon Laboratories, Inc. (Fort Worth, TX)
Application Number:	06/519,791
Patent Claims:	1. A method for lowering intraocular pressure comprising topically applying to the eye an effective amount for lowering such intraocular pressure of a 2-(trisubstituted phenylimino)-imidazoline, or a pharmaceutically acceptable salt thereof, having the formula ##STR64## where R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are defined in accordance with either I, II, or III as follows: I. R.sub.1 =R.sub.2 =methyl, ethyl, trifluoromethyl, chloro or bromo. R.sub.1 .noteq.R.sub.2 and each=methyl, ethyl, trifluoromethyl, fluoro, chloro and bromo, one of R.sub.3 and R.sub.4 is H and the other is selected from ##STR65## R.sub.5 .noteq.R.sub.6 =H or lower alkyl, R.sub.5 =R.sub.6 and each=H, lower alkyl, R.sub.7 =H, lower alkyl 2-hydroxyethyl, 2-hydroxypropyl or 3-hydroxypropyl, the sum of the carbon atoms in R.sub.5 and R.sub.6 or R.sub.5 and R.sub.7 being 4 or less, or ##STR66## R.sub.8 =lower alkyl; II. R.sub.1 =methyl, ethyl, trifluoromethyl, chloro or bromo, R.sub.2 =H, R.sub.3 =is selected from ##STR67## R.sub.4 =methyl, chloro or bromo R.sub.9 =H or lower alkyl, R.sub.10 =H, lower alkyl, 2-hydroxymethyl, 2-hydroxypropyl or 3-hydroxypropyl, the sum of the carbon atoms in R.sub.9 and R.sub.10 being 4 or less; III. In no event shall said 2-(trisubstituted phenylimino)-imidazoline have the formula: ##STR68## 2. A method in accordance with claim 1 wherein the 2-(trisubstituted phenylimino)-imidazoline or salt is topically applied to the eye in a pharmaceutically acceptable vehicle. 3. A method in accordance with claim 2 wherein the concentration of the 2-(trisubstituted phenylimino)-imidazoline or salt is selected such that intraocular pressure is reduced without significantly affecting the central nervous system. 4. A method in accordance with claim 3 wherein the 2-(trisubstituted phenylimino)-imidazoline is 2,6-Dichloro-N.sup.1 -(2-imidazolidinylidene)-1,4-benzenediamine having the structure: ##STR69## or pharmaceutically acceptable salt thereof. 5. A method in accordance with claim 3 wherein the 2-(trisubstituted phenylimino)-imidazoline is 2,6-Dichloro-N.sup.1 -(2imidazolidinylidene)-1,3-benzenediamine having the structure: ##STR70## or pharmaceutically acceptable salt thereof. 6. A method in accordance with claim 3 wherein the 2-(trisubstituted phenylimino)-imidazoline is 2,6-Diethyl-N.sup.1 -(2-imidazolidinylidene)-1,4-benzenediamine having the structure of: ##STR71## or pharmaceutically acceptable salt thereof. 7. A method in accordance with claim 3 wherein the 2-(trisubstituted phenylimino)-imidazoline is N-[3,5-Diethyl-4-(2-imidazolidinyleneamino)-phenyl]-acetamidne having the structure: ##STR72## or pharmaceutically acceptable salt thereof. 8. A method in accordance with claim 3 wherein the 2(trisubstituted phenylimino)-imidazoline is 3,5-Dichloro-4-(2-imidazolidinylideneamino)-phenol and esters thereof having the structure: ##STR73## or pharmaceutically acceptable salt thereof. 9. A method in accordance with claim 3 wherein the 2-(trisubstituted phenylimino)-imidazoline is 3-chloro-5-methyl-4-(2-imidazolidinylideneamino)-benzoic acid ethyl ester having the structure: ##STR74## or pharmaceutically acceptable salt thereof. 10. A method in accordance with claim 3 wherein the 2-(trisubstituted phenylimino)-imidazoline is 3-chloro-5-ethyl-4-(2-imidazolidinylideneamino)-benzoic acid ethyl ester having the structure: ##STR75## or pharmaceutically acceptable salt thereof. 11. A method in accordance with claim 3 wherein the 2-(trisubstituted phenylimino)-imidazoline is N-[3-chloro-5methyl-4-(2-imidazolidinylideneamino)-phenyl]-acetamide having the structure: ##STR76## or pharmaceutically acceptable salt thereof. 12. A method in accordance with claim 3 wherein the 2-(trisubstituted phenylimino)-imidazoline is 2 chloro-6methyl-N.sup.1 -(2-imidazolidinylidene)-1,4 benzenediamine having the structure: ##STR77## or pharmaceutically acceptable salt thereof. 13. A method in accordance with claim 3 wherein the 2-(trisubstituted phenylimino)-imidazoline is 2-chloro-6ethyl-N.sup.1 -(2-imidazolidinylidene)-1,4 benzenediamine having the structure: ##STR78## or pharmaceutically acceptable salt thereof. 14. A method in accordance wtih claim 3 wherein the 2-(trisubstituted phenylimino)-imidazoline is 3-chloro-5methyl-4-(2-imidazolidinylideneamino)-benzenecarboxamide having the structure: ##STR79## or pharmaceutically acceptable salt thereof.