Patent EA-000700-B1 (EA)
Title: Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) n-[(aminoiminomethyl)phenylalkyl]-azaheterocycyllamide compounds
Inventor: EWING WILLIAM R
IPC: C07D401/06
Filed: 1996-06-07
Abstract: 1. A compound of formula I      is phenyl or monocyclic heteroaryl; R is hydrogen, optionally substituted alkyl, optionally substituted aralkyl, optionally substituted heteroaralkyl or hydroxyalkyl; R1 is hydrogen, R3S(O)p or R3R4NS(O)p-; R2 is hydrogen, or when X5 and X5' taken together are -NR5, then R2 is hydrogen, optionally substituted lower alkyl, optionally substituted aralkyl or optionally substituted heteroaralkyl; R3 is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted aralkenyl or optionally substituted heteroaralkenyl, or Rand R3 taken together form a 5 to 7 membered ring; and R4 is optionally suhstituted alkyl, optionally substituted cycloalkyl or optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl or optionally substituted heteroaralkyl, or R3 and R4 taken together with the nitrogen to which R3 and R4 are attached form an optionally substituted 4 to 7 membered heterocyclyl; X1 and X1' are independently selected from hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl or hydroxyalkyl, or X1 and X1' taken together form oxo; X2 and X2' are hydrogen, or taken together form oxo; X3 is hydrogen, hydroxy, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl or optionally substituted heteroaralkyl, or X3 and one of X1 and X1' taken together form a 4 to 7 membered ring; X4 is hydrogen, optionally substituted alkyl, optionally substituted aralkyl, orhydroxyalkyl; X5 and X5' are hydrogen or taken together are =NR5; R5 is hydrogen, R6O2C-, R6O-, cyano, R6CO-, optionally substituted lower alkyl, nitro or Y<1'>Y<2'>N-; Y<1'> and Y<2'> are independently hydrogen, alkyl, aralkyl or heteroaralkyl; X6 and X6' are independently hydrogen, R7R8N-, R9O-, R7R8NCO-, R7R8NSO2-, R9CO-, halo, cyano or nitro; R6 is hydrogen, optionally substituted lower alkyl or optionally substituted aralkyl or optionally substituted heteroaralkyl; R7 and R8 are independently hydrogen or optionally substituted lower alkyl, or one of R7 and R8 is hydrogen and the other of R7 and R8 is R10(O)CCH2- or lower acyl; R9 is hydrogen, optionally substituted lower alkyl, lower acyl or R10(O)CCH2-; R10 is hydrogen, optionally substituted lower alkyl, alkoxy or hydroxy; m is 0, 1,2 or 3; n is 1, 2 or 3; or p is 1 or 2, a pharmaceutically acceptable salt thereof, an N-oxide thereof, a hydrate thereof or a solvate thereof. 2. The compound of claim 1 wherein R3 is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl or optionally substituted benzothienyl. 3. The compound of claim 1 wherein n is 1, and m is 1. 4.The compound of claim 1 wherein X2 and X2' taken together are oxo. 5. The compound of claim 1 wherein X1, X1', X3 and X4 are hydrogen. 6. The compound of claim 1 wherein X5 and X5' taken together are =NH. 7. The compound of claim 1 wherein X5 and X5' taken together are =NR5 wherein R is R6O2C-. 8. The compound of claim 1 wherein   is phenyl and the carbon substituted with X5, X5' and HR2N- is attached to the 3-position of the phenyl. 9. The compound of claim 1 wherein   is of the formula:   10. The compound of claim 1 wherein X1 is hydrogen and X1' is carboxyalkyl, alkoxycarbonylalkyl or aryl, or X1 and X1' taken together form oxo. 11. The compound of claim 1 wherein R1 is R3SO2-. 12. The compound of claim 1 wherein R1 is R3R4NSO2-. 13. The compound of claim 1 wherein one of X6 and X6' is amino in a para position relative to the moiety. 14. A compound according to claim 1 which is: Naphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin- 3-(S)-yl}amide trifluoroacetate; Dibenzofuran-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-5-oxopyrrolidin- 3-yl}amide trifluoroacetate; Toluene-4-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 3,4-Dihydro-1H-isoquinoline-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 3'-Methoxy-biphenyl-4-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; Naphthalene-1-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 5-Pyrid-2-ylthiophene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; Biphenyl-4-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 7-Methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 7-Ethoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 5-Chloro-6-methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 5-Chloro-6,7-dimethoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 7-Aminonaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide bistrifluoroacetate; Naphthalene-2-sulfonic acid {1-[4-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 7-Methoxynaphthalene-2-sulfonic acid [1-(3-aminomethylbenzyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate; Naphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}methyl amide trifluoroacetate; Naphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]pyrrolidin-3-(S)-yl}amide bistrifluoroacetate; 7-Methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2,5-dioxopyrrolidin-3-(S)-yl}amide trifluoroacetate; Naphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopiperidin-3-yl}amide trifluoroacetate; 7-Methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxo-azepan-3-(S)-yl}amide trifluoroacetate; 7-Methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}methyl amide trifluoroacetate; 6-Methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 6-Methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}methyl amide trifluoroacetate; 2-[{1-[3-(Aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}-6-methoxynaphthalene-2-sulfonylamino]-N-phenethylacetamide trifluoroacetate; 9,10-Dioxo-8a, 9, 10, 10a-tetrahydroanthracene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 8-Chloro-7-methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 7-Methoxynaphthalene-2-sulfonic acid {1-[4-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 6,7-Dimethoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; Naphtho(2,3-d)-(1,3)dioxole-6-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]- 2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 7-Benzyloxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 7-Hydroxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 6-Hydroxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 5-Chloro-3-methylbenzo[b]thiophene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 5-Chloro-3-methylbenzo[b]thiophene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}methyl amide trifluoroacetate; 7-Methylnaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 7-Ethylnaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide trifluoroacetate; 5-Chloro-6-aminonaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide bistrifluoroacetate; 7-Methylaminonaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide bistrifluoroacetate; 2-Methyl-1,2,3,4-tetrahydroisoquinolinyl-7-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}amide bistrifluoroacetate; 1,2,3,4-Tetrahydroisoquinolinyl-7-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}methyl amide dihydrochloride; 7-Methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}-(4-nitrobenzyl)amide trifluoroacetate; 7-Methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}-(4-aminobenzyl)amide bistrifluoroacetate; 7-Methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}(3-nitrobenzyl)amide trifluoroacetate; 7-Methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}(3-aminobenzyl)amide bistrifluoroacetate; 7-Methoxynaphthalene-2-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3-(S)-yl}-(2-nitrobenzyl)amide trifluoroacetate; 3-[2-Oxo-3(S)-(2-phenylethenesulfonylamino)pyrrolidin-1-ylmethyl]-benzamidine trifluoroacetate; 3-[2-Oxo-3(S)-(2-phenylethanesulfonylamino)pyrrolidin-1-ylmethyl]-benzamidine trifluoroacetate; [Imino-(3-{3-[7-Methoxynaphthalene-2-sulfonyl)methylamino]-2-oxo-3(S)-pyrrolidin-1-ylmethyl]phenyl)methyl]carbamic acid ethyl ester; 3-[2-Oxo-3(S-{2-(pyridin-4-ylamino)-ethanesulfonylamino}-pyrrolidin-1-ylmethyl]-benzamidine bistrifluoroacetate; 2'-Methoxybiphenyl-4-sulfonic acid {1-[3-(aminoiminomethyl)benzyl]-2-oxopyrrolidin-3(S)-yl} amide trifluoroacetate; 5,6,7,8-Tetrahydrophenanthrene-3-sulfonic acid {1-[3-