Patent EA-001937-B1 (EA)
Title: Inhibitors of cysteine protease
Inventor: MARQUIS ROBERT W
IPC: C07D207/12
Filed: 1997-08-07
Abstract: l]-3-pyrrolidinone; 4-[[N<α>-(3-isoquinolinecarbonyl)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl)]amino]pentyl]-3-pyrrolidinone; kyl, C3-6-cycloalkyl-C0-6-alkyl, Ar-C0-6-alkyl, Heinyl]amino]-1-[1-(adamantil)carbonyl]-3-pyrrolidinone; 4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-(4-methylpentanoyl)-3-pyrrolidinone; 4-[t-C0-6-alkyl; R''' is H, C1-6-alkyl, C3-6-cycloalkyl-C0-6-alkyl, Ar-C0-6-alkyl, or Het-C0-6-alkyl; each R<3> independently is H, C2-6-alkenyl, C2-6-alycarbonyl)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl)]amino]pentanoyl]-3-piperidinon N(C=NH)NH2, Het or Ar; R<4> is H, C1-6-alkyl, C3-6-cycloalkyl-C0-6-alkyl, Ar-C0-6-alkyl, Het-C0-6-aethyl-2-[[(benzyloxycarbonyl)]amino]pentanoyl]-3-piperidinon; 4-[[N<α>-(4-pyridinylmethoxycarb5>OC(O)NR'CH(R')C(O)-; each R<5> independently is peridinon; 4-[[N<α>-(4-pyridinylmethoxycarbonyl)-L-leucinyl]amino]-1-[2-(benzyloxycarbonyl)]isobutylamino]ethanoyl]-3-piperidinon; 4-[[N-2-(benzC(O)OR<5>, CO2R', CO2NR'2, N(C=NH)NH2, Het or Ar; ethyl-2-[[(benzyloxycarbonyl)]amino]pentanoyl]-3-piperidinon; 4-[[N<α>-(benzyloxycarbonyl)-L-l0-6-alkyl, Ar-C0-6-alkyl, Het-C0-6-alkyl, R<5>C(O)4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]aminR<5>R'NC(S)-, R'HNCH(R')C(O)-, or R<5>OC(O)NR'CH(R')C(O)-; or R<6> and R<7> are connected to form a 1-(8-quinolinesulphonyl)-3-pyrrolidinone; 4-[[N<&aach R' independently is H, C1-6-alkyl, Ar-C0-6-alkno]-1-(2-pyridylsulphonyl)-3-pyrrolidinone; 4-[[N<ycloalkyl-C0-6-alkyl, Ar-C0-6-alkyl, or Het-C0-6-amino]-1-[(2-propoxy)carbonyl]-3-pyrrolidinone; 4-[[N<α>-(4-pyridinylmethoxycarbonyl)-L-leucinyl]amino]-1-[(3-methyl-1-propoxy)carbonyl]-3-pyrrolsists of carbon atoms and of 1-4 heteroatoms, seleinyl]amino]-1-[(4-phenoxy)phenylsulphonyl]-3-pyrrorein heretoatoms of nitrogen and sulfur can be optcinyl]amino]-1-[(4-phenoxy)phenylsulphonyl]-3-piperidinone; 4-[[N<α>-(3,4-dichlorobenzoyl)-L-lroup, wherein any of above-mentioned rings are cononyl)]amino]pentyl]-3-pyrrolidinone; 4-[[N<α ring can be attached to any heteroatom or carbon 4-methyl-2-[[(benzyloxycarbonyl)]amino]pentyl]-3-pyrrolidinone; 4-[(2-dibenzofuransulphonyl)amino]-1oups, selected from C1-4-alkyl, OR', N(R')2, SR', anoyl]-3-pyrrolidinone; 4-[(2-dibenzofuransulphonyl)amino]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl)]methylamino]pentanoyl]-3-pyrrolidinol; 4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-(4-metof. 2. A compound according to Claim 1 wherein R<1ylcarbonyl)-L-leucinyl]amino]-1-(4-methylpentyl]-3-piperidinone; 4-[[N<α>-(3-chlorobenzoyl)-L-leucinyl)amino]-1-[4-methylpentyl)-3-pipridinone; 4-[ [Nα -(2-quinolinecarbonyl)-L-leucinyl]amompound according to Claim 4 wherein R<5> in said alpha;>-(3,4-dichlorobenzoyl)-L-leucinyl]amino]-1-uted or substituted by one or two groups selected inecarbony I)-l-leucinyl]amino]- I -(4-methylpentyl )-3-piperidinone 4-[[N<α>-(3-isoquinolinecedioxy; or   6. A compound according to Claim 2 wherein R' in said group R<1> is H or CH3 and R<3> is isobutyl. 7. A compound according to Claim 1 wheeridinone; 4-[[N<α>-(acetyl)-L-leucinyl]amino]-1-(4-methylpentyl)-3-pipridinone; 4-[[N<α 8 wherein R<7> is K<5>OC(O)-. 10. A compound accomino]-1-(4- methylpentyl)-3-piperidinone; 4-[[N<α>-(6-quinolinocarbonyl)-L-leucinyl]amino]-1-(4-methylpentyl)-3- piperidinone; 4-[[2-(RS)-[(3-biphenyl)-4-methxl]amino]pentanoyl]-1-(4-methxlpenty substituted by one or two groups selected from Clucinyl]amino]- 1 [2-[(benzyloxycarbonyl)methylaminH2, NH2, or NO2, or substituted by methylenedioxy;sulphonyl)-L-leucinly]amino]-1-[3-(2-pyridyl)phenylacetyl)]-3- piperidinone; 4-[[N<α>-(2-naphtO, SO2, or CH2-CO and Y is a single bond or O. 13.ylacetyl)]-3- piperidinone; 4-[[N<α>-(benzenesulphonyl)-L-leucinyl]amino]-1-[3-(2-pyridyl)phen 14. A compound according to Claim 1 wherein R<2> is Ar-C0-6-alkyl, Het-C0-6-alkyl, C3-6-cycloalkyl-l)phenylacetyl)]- 3-piperidinone; 4-[3-[(2-pyridyl)-, R<5>C(S)-, R<5>SO2-, R<5>OC(O)-, R<5>R'NC(O)-, R<5>R'NC(S)-, R'HNCH(R')C(O)-, R<5>OC(O)NR'CH(R')[(2-pyridyl)phenylacetyl)]amino]-1-[(2S)-4-methxl-2-[[2 (pyridinylmethoxycarbonyl)]amino]pentanoyl]-3-piperidinone; 4-[[N<α>-(2-phenylacetyl)-L-(benzyloxycarbonyl)-L-leucinyl]amino]-1-[(2S)-4-mebonyl)amino]pentyl]-3-pyrrolidinone; 4-[[N<α>-(tert-butoxycarbonyl)-L-leucinyl]amino]-1-[(2S)-eucinyl]amino]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl)]amino]pentanoyl]-3-pyrrolidinone; 4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-[4-(phenoxybenzamide)]-3pyrrolidinone; (3RS,4RS)-4-[[N<nyl]amino]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl)amino]pentyl]-3-pyrrolidinone; 4-[[N<α>-(pi;>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-[4-(biphenylethanoyl)]-3-pyrrolidinone; (3RS,4RS)-4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-[(amino]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl)amino]pentyl]-3-pyrrolidinone; 4-[[N<α>-(2-pyriycarbonyl)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[[[(benzyloxycarbonyl)amino]pentyl]-3-pyrrolidinone; 4-[[N<α>-(2-nitro-α-toluenesulphonyl)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[(benzyloxutoxyoxycarbonyl)]aminomethyl]pentanoyl]-3-pyrrolipha;>-(8-quinolinesulphonyl)-L-leucinyl]amino]-1-[yl]amino]-1-[(2S)-4-methyl-2-[[tert-butoxyoxycarbonyl)]aminomethyl]pentanoyl]-3-pyrrolidinone; 4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-(aminomethyl)pentanoyl]-3-pyrroli-[[N<α>-(2-quinolinylcarbonyl)-L-leucinyl]aminomethyl]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-3-pyrrolidinone; 4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[(N-ter 4-[[N<α>-(4-pyridinylmethoxycarbonyl)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl)amino]pentyl]-3-piperidinone; 4-[[N<α>-(4minomethyl]pentanoyl]-3-pyrrolidinone; (3RS,4RS)-4R)-4-methyl-2-[[(benzyloxycarbonyl)amino]pentyl]-3]-1-[(2S)-4-methyl-2[[(tert-butoxyoxycarbonyl)]amicinyl]amino]-1-[(2R)-4-methyl-2-[[(benzyloxycarbonyloxycarbonyl)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[(tert-butoxycarbonyl)]amino]pentanoyl]-3-pyrroyl-2-[[(benzyloxycarbonyl)amino]pentyl]-3-piperidinyl)-L-leucinyl]amino]-1-[(2R)-4-methyl-2-[[(benzyl]amino]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl)amino]pentyl]-3-piperidinone; 4-[[N<α>-(4-pyr1-[(2R)-4-methyl-2-[[(benzyloxycarbonyl)]amino]pen-2-[[(benzyloxycarbonyl)amino]pentyl-3-piperidinone; 4-[[N<α>-(tert-butoxycarbonyl)-L-leucinyl]amino]-1-(benzyloxycarbonyl)-3-piperidinone; 4-[[<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-]-1-(benzyloxycarbonyl)-3-piperidinone; 4-[[N<α>-(4-pyridinylacetyl)-L-leucinyl]amino]-1-(benz-L-leucinyl]amino]-1-[(2S)-3-tert-butoxy-[[(benzyloxycarbonyl)]amino]propanoyl]-3-pyrrolidinol; (3RS,4RS)-4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-[(2S)-2-[[(benzyloxycarbonyl)]amino]pro-piperidinone; 1-benzyl-4-[[N<α>-(3-isoquinolinylcarbonyl)-L-leucinyl]amino]-3-pyrrolidinone; arbonyl)]amino]propanoyl]-3-pyrrolidinone; (3RS,4Rucinyl]amino]-3-pyrrolidinone; 1-benzyl-4-[[N<&alpmino]-1-[cyclohexanepropanoyl]-3-pyrrolidinol; 4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-[cyclohexanepropanoyl]-3-pyrrolidinone; (3RS,4RS)-4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]am)-L-leucinyl]amino]-3-pyrrolidinone; 1-benzyl-4-[[N<α>-(piperonylcarbonyl)-L-leucinyl]amino]-3;>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-[(2S)-4enzoyl)-L-leucinyl]amino]-3-pyrrolidinone; 1-benzyl-4-[[N<α>-(6-hydroxy-2-naphthylcarbonyl)-L-leucinyl]amino]-3-pyrrolidinone; 1-benzyl-4-[[N<&a-2-[[(2-pyridinylmethoxycarbonyl)]amino]pentanoyl]-3-pyrrolidinol; 4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[(2-pyridinylmethoxycarbonyl)]amino]pentanoyl]-3-pyrrolidinoamino]-3-pyrrolidinone; 1-benzyl-4-[[N<α>-(4-pyridinylcarbonyl)-L-leucinyl]amino]-3-pyrrolidinmethoxycarbonyl)]amino]pentanoyl]-3-pyrrolidinol; yl]amino]-1-benzyloxycarbonyl-3-pyrrolidinone; 4-[[N<α>-(4-pyridinylmethoxy)carbonyl]-L-leucinyl]amino]-1-[(2R)-4-methyl-2-[[(benzyloxycarbonyl)[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-pyridinylmethoxy)carbonyl]-L-leucinyl]amino]-1-[(2;>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-(2-pyridylcarbonyl)-3-pyrrolidinone; (3RS,4RS)-4-[[N<&alpoxy)carbonyl]-L-leucinyl]amino]-1-[(2S)-4-methyl-2-(amino)pentyl]-3-pyrrolidinone; 4-[[N<α>-(2-methylpropoxy)carbonyl]-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl)]amino]pentyl]-3-carbonyl)]amino]pentanoyl]-3-piperidinone; (3RS,4Rbonyl]-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[(benmino]-1-[4-(biphenyl)ethanoyl]-3-piperidinol; 4-[[[N<α>-(phenylmethylamino)carbonyl]-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl)]4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amin-dichlorophenylamiono)carbonyl]-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[[(benzyloxycarbonyl)]amino]pentyl]-3-pyrrolidinone; 1-benzyl-4-[[N<α>-(3,4-dichlorophenylamino)-L-leucinyl]amino]-3-pyrrolidinone; 4-[[N<α>-(1,2,3,4-tetrahydro-6-quinolL-leucinyl]amino]-1-tertbutoxycarbonyl-3-piperidinone; (3RS,4RS)-4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-[2-[[(benzyloxycarbonyl)]isobucarbonyl)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[(acetyl)amino]pentyl]-3-pyrrolidinone; 4-[[N<αloxycarbonyl)]isobutylamino]ethanoyl]-3-piperidinone; (3RS,4RS)-4-[[N<α>-(benzyloxycarbonyl)-L[[N<α>-(4-fluorobenzoyl)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[(p-toluenesulphonyl)amino]pentyarbonyl)-L-leucinyl]amino]-1-[2-[[(tertbutoxycarbol)-L-leucinyl]amino]-1-[(2S)-4-methyl-2-[(methanesulphonyl)amino]pentyl]-3-pyrrolidinone; 4-[[N<&alp)ethanoyl]-3-piperidinone; (3RS,4RS)-4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-(4-methylpentanoyl)-3-piperidinol; 4-[[N<α>-(benzyloxycarbonyl)-L-leucinyl]amino]-1-(4-methylpentanoyl; 1-(2-phenethyl)-4-[[N<α>-(2-quinolinylcarboxycarbonyl)-L-leucinyl]amino]-1-(benzoyl)-3-piperidinol; 4-[[N<α>-(benzyloxycarbonyl)-L-leuci