United States Patent 6,420,438
Liebeschuetz , et al. July 16, 2002
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1-amino-7-isoquinoline derivatives as serine protease inhibitors
Abstract
The invention relates to serine protease inhibitor compounds of formula (I) ##STR1## where R.sub.1 is hydrogen, halo, cyano, nitro or hydroxyl, amino, alkoxy, alkyl, aminoalkyl, hydroxyalkyl, thiol, alkylthio, aminosulphonyl, alkoxyalkyl, alkoxycarbonyl, acyloxymethoxycarbonyl or alkylamino optionally substituted by hydroxy, alkylamino, alkoxy, oxo, aryl, cycloalkyl, amino, halo, cyano, nitro, thiol, alkylthio, alkylsulphonyl, alkylsulphenyl, alkylsulphonamido, alkylaminosulphonyl, haloalkoxy and haloalkyl; R.sub.2 is hydrogen, halo, methyl, amino, hydroxy, or oxo; and R is X--X--Y(R.sub.7)--L--Lp(D)n; wherein each X independently is C, N, O or S atom or a CO, CR.sub.1, C(R.sub.1).sub.2 or NR.sub.1 group, at least one X being C, CO, CR.sub.1 or a C(R.sub.1).sub.2 group; Y (the .alpha.-atom) is a nitrogen atom or a CR.sub.1 group or Y and L taken together form a cyclic group; R.sub.7 is a lipophilic group selected from alkyl, alkenyl, mono- or bi-cycloalkyl, aryl, heteroaryl, mono- or bicycloalkylalkyl, mono- or bicycloalkylalkenyl, aralkyl, heteroaryl-alkyl, arylalkenyl, heteroarylalkenyl all optionally substituted by a group R.sub.1 ; L is an organic linker group containing 1 to 5 backbone atoms selected from C, N, O and S, or a branched alkyl or cyclic group; Lp is a lipophilic organic group selected from alkyl, heterocyclic, alkenyl, alkaryl, cycloalkyl, polycycloalkyl, cycloalkenyl, aryl, aralkyl or haloalkyl group or a combination of two or more such groups optionally substituted by one or more of oxa, thia, aza or R.sub.1 groups; D is a hydrogen bond donor group; and n is 0, 1 or 2 and salts thereof.
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Inventors: Liebeschuetz; John Walter (Bollington, GB); Wylie; William Alexander (Stockport, GB); Waszkowycz; Bohdan (Wilmslow, GB); Murray; Christopher William (Macclesfield, GB); Rimmer; Andrew David (Chorley, GB); Welsh; Pauline Mary (Macclesfield, GB); Jones; Stuart Donald (Prestbury, GB); Roscoe; Jonathan Michael Ernest (Holsworthy, GB); Young; Stephen Clinton (Stockport, GB); Morgan; Phillip John (Congleton, GB); Camp; Nicholas Paul (Macclesfield, GB); Crew; Andrew Philip Austin (Congleton, GB)
Assignee: Tularik Limited (London, GB)
Appl. No.: 865418
Filed: May 29, 2001
This application is a continuation of U.S. application Ser. No. 09/485,677 filed on Feb. 25, 2000, which was the National Stage of International Application No. PCT/GB98/02600 filed Aug. 28, 1998. |
