Claims for Patent: 7,626,040

Summary for Patent: 7,626,040

Title:	Substituted imidazole compounds as KSP inhibitors
Abstract:	The present invention relates to new substituted imidazole compounds and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the derivatives together with pharmaceutically acceptable carriers, and uses of the compounds. The compounds of the invention have the following general formula: ##STR00001##
Inventor(s):	Barsanti; Paul A. (Moraga, CA), Xia; Yi (Palo Alto, CA), Wang; Weibo (Moraga, CA), Mendenhall; Kris G. (Concord, CA), Lagniton; Liana M. (Berkeley, CA), Ramurthy; Savithri (Walnut Creek, CA), Phillips; Megan C. (Walnut Creek, CA), Subramanian; Sharadha (San Ramon, CA), Boyce; Rustum (Singapore, SG), Brammeier; Nathan M. (Walnut Creek, CA), Constantine; Ryan (Oakland, CA), Duhl; David (Oakland, CA), Walter; Annette O. (Mill Valley, CA), Abrams; Tinya J. (Richmond, CA), Renhowe; Paul A. (Danville, CA)
Assignee:	Novartis Vaccines and Diagnostics, Inc. (Emeryville, CA)
Application Number:	11/502,303
Patent Claims:	1. A compound of formula II: ##STR00238## wherein: n is 1, 2, or 3; p is 0, 1, 2, 3, or 4; R.sup.3 and R.sup.4 are independently selected from the group consisting of hydrogen, hydroxy, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic, provided that only 1 of R.sup.3 or R.sup.4 is hydroxy; or R.sup.3 and R.sup.4 together with the nitrogen atom pendent thereto join to form a heterocyclic or substituted heterocyclic; R.sup.10 is selected from the group consisting of hydrogen, alkyl optionally substituted with a substituent selected from the group consisting of hydroxy, alkoxy, substituted alkoxy, amino, substituted amino, acylamino, halo, nitrogen-containing heterocycle, substituted nitrogen-containing heterocycle, nitrogen-containing heteroaryl, and substituted nitrogen-containing heteroaryl; R.sup.11 is selected from the group consisting of cyano, alkyl, alkenyl, alkynyl, --CF.sub.3, alkoxy, halo, and hydroxy, provided that when p is 2-4, then each R.sup.11 may be the same or different; R.sup.12 is alkyl; R.sup.13 is hydrogen or alkyl, R.sup.14 is selected from the group consisting of hydrogen, halo, and alkyl; or R.sup.4 and R.sup.10, together with the atoms bound thereto, form a heterocyclic or substituted heterocyclic group; A.sup.2 is selected from the group consisting of aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, cycloalkyl, and substituted cycloalkyl; or a pharmaceutically acceptable salt or ester thereof. 2. The compound of claim 1, wherein R.sup.12 is selected from the group consisting of isopropyl, t-butyl, and propyl. 3. The compound of claim 1, wherein R.sup.13 is hydrogen. 4. The compound of claim 1, wherein R.sup.3 and/or R.sup.4 is selected from the group consisting of alkyl, substituted alkyl, or cycloalkyl, wherein the alkyl, substituted alkyl or cycloalkyl is selected from the group consisting of methyl, methoxyethyl, furan-2-ylmethyl, 2-hydroxyethyl, cyclopropyl and isopropyl. 5. The compound of claim 1, wherein R.sup.3 and/or R.sup.4 is aryl or substituted aryl, wherein the aryl or substituted aryl is selected from the group consisting of 4-cyanophenyl, 3,4-difluorophenyl, 2,3,5-trifluorophenyl, 3,5-dinitrophenyl, and phenyl. 6. The compound of claim 1, wherein R.sup.3 and/or R.sup.4 is heteroaryl or substituted heteroaryl, wherein the heteroaryl or substituted heteroaryl is selected from the group consisting of thiophen-2-yl, 3,5-dimethylisoxazol-4-yl, and 2,6-dichloropyridin-4-yl. 7. The compound of claim 1, wherein R.sup.3 and/or R.sup.4 is a heterocyclic group or substituted heterocyclic group, wherein the heterocyclic or substituted heterocyclic group is tetrahydropyran-4-yl or 4-(ethoxycarbonyl)piperidin-4-yl. 8. The compound of claim 1, wherein either of R.sup.3 or R.sup.4 or both of R.sup.3 and R.sup.4 are hydrogen. 9. The compound of claim 1, wherein one of R.sup.3 or R.sup.4 is hydroxy. 10. The compound of claim 1, wherein R.sup.3 and R.sup.4 are cyclized with the nitrogen atom bound thereto to form a heterocyclic, substituted heterocyclic, heteroaryl or substituted heteroaryl, wherein the heterocyclic, substituted heterocyclic, heteroaryl or substituted heteroaryl is selected from the group consisting of 1,1-dioxothiamorpholin-N-yl, 1-oxothiamorpholin-1-yl, 2-(aminomethylene)pyrrolidin-N-yl, 2-(methoxycarbonyl)pyrrolidin-N-yl, 2,6-dimethylmorpholin-N-yl, 3-hydroxypiperidin-N-yl, 3-hydroxypyrrolidin-N-yl, 4-(butylsulfonyl)piperazin-N-yl, 4-(cyclopropylsulfonyl)piperazin-N-yl, 4-(dimethylamino)piperidin-N-yl, 4-(ethoxycarbonyl)piperazin-N-yl, 4-(ethylsulfonyl)piperazin-N-yl, 4-(isopropylsulfonyl)piperazin-N-yl, 4-(methylcarbonyl)piperazin-N-yl, 4-(methylsulfonyl)piperidin-N-yl, 4-(methysulfonyl)piperazin-N-yl, 4-(morpholin-N-yl)piperidin-N-yl, 4-(piperidin-N-yl)piperidin-N-yl, 4-(propylsulfonyl)piperazin-N-yl, 4-cyclohexylpiperazin-N-yl, 4-hydroxypiperidin-N-yl, 4-isopropylpiperazin-4-yl, 4-methylpiperidin-N-yl, isoxazolidin-2-yl, morpholin-N-yl, piperazin-N-yl, piperidin-N-yl, 2-(hydrazinocarbonyl)pyrrolidin-N-yl and pyrrolidin-N-yl. 11. The compound of claim 1, wherein R.sup.10 is selected from the group consisting of --(CH.sub.2).sub.3NH.sub.2, --(CH.sub.2).sub.2CH(CH.sub.2OH)NH.sub.2, --CH.sub.2CH(F)CH.sub.2NH.sub.2, --CH.sub.2-[2-(CH.sub.2OH)pyrrolidin-3-yl], --CH.sub.2-[4-(OH)pyrrolidin-3-yl], --CH.sub.2--C(F)(spiropyrrolidin-3-yl), --(CH.sub.2).sub.2CH(CH.sub.2F)NH.sub.2, --(CH.sub.2).sub.2C(CH.sub.3).sub.2NH.sub.2, --(CH.sub.2).sub.2CH(CH.sub.3)NH.sub.2, --(CH.sub.2).sub.2CH(CH.sub.2OCH.sub.3)NH.sub.2, --(CH.sub.2).sub.2CH(CH.sub.2F)NHC(O)-[(2-CH.sub.3NHC(O))benzene], and --(CH.sub.2).sub.2CH(CH.sub.2F)-1,3-dioxo-1,3-dihydroisoindole. 12. The compound of claim 1, wherein ##STR00239## is selected from the group consisting of phenyl, 3-chlorophenyl, 3-fluorophenyl, 2,4-difluorophenyl, 2,5-difluorophenyl, and 2,3,5-trifluorophenyl. 13. The compound of claim 1, wherein R.sup.14 is hydrogen. 14. The compound of claim 1, wherein A.sup.2 is aryl or substituted aryl. 15. The compound of claim 1, wherein R.sup.2 is t-butyl, R.sup.13 and R.sup.3 are hydrogen, n is 1, A.sup.2 is phenyl, p is 1 or 2 and R.sup.1 is halo. 16. The compound of claim 1, wherein R.sup.12 is t-butyl, R.sup.13 and R.sup.3 are hydrogen, n is 1, A.sup.2 is phenyl, R.sup.10 is substituted alkyl, wherein substituted alkyl is selected from the group consisting of --(CH.sub.2).sub.3NH.sub.2, --CH.sub.2CH(F)CH.sub.2NH.sub.2, --(CH.sub.2).sub.2CH(CH.sub.2F)NH.sub.2, --(CH.sub.2).sub.2CH(CH.sub.2OCH.sub.3)NH.sub.2, --(CH.sub.2).sub.2CH(CH.sub.3)NH.sub.2, --(CH.sub.2).sub.2C(CH.sub.3).sub.2NH.sub.2 and --(CH.sub.2).sub.2CH(CH.sub.2OH)NH.sub.2. 17. The compound of claim 1, wherein R.sup.12 is t-butyl, R.sup.13 is hydrogen, R.sup.3 is hydrogen, n is 1, A.sup.2 is phenyl, R.sup.11 is fluoro, R.sup.4 is hydrogen, and R.sup.4 is alkyl. 18. The compound of claim 1, wherein R.sup.12 is isopropyl and R.sup.11 is chloro. 19. A compound selected from the group consisting of: N-(3-aminopropyl)-N-{(1R)-1-[1-benzyl-4-(3-chlorophenyl)-1H-imidazol-2-yl- ]-2-methylpropyl}morpholine-4-carboxamide; N-(3-aminopropyl)-N-{(1R)-1-[1-benzyl-4-(3-chlorophenyl)-1H-imidazol-2-yl- ]-2-methylpropyl}piperidine-1-carboxamide; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]piperidine-1-carboxamide; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N',N'-dimethylurea; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-(2-methoxyethyl)urea; methyl (2S)-1-({(3-aminopropyl)[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-- dimethylpropyl]amino}carbonyl)pyrrolidine-2-carboxylate; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-hydroxyurea; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]pyrrolidine-1-carboxamide; (2R)-2-(aminomethyl)-N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-im- idazol-2-yl)-2,2-dimethylpropyl]pyrrolidine-1-carboxamide; (3S)--N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,- 2-dimethylpropyl]-3-hydroxypyrrolidine-1-carboxamide; (3R)--N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,- 2-dimethylpropyl]-3-hydroxypyrrolidine-1-carboxamide; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-methylurea; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]piperazine-1-carboxamide; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-1,4'-bipiperidine-1'-carboxamide; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-thien-2-ylurea; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-thien-3-ylurea; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-(3,5-dimethylisoxazol-4-yl)urea; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-(2,6-dichloropyridin-4-yl)urea; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-(2-furylmethyl)urea; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-(4-cyanophenyl)urea; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-(3,4-difluorophenyl)urea; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-(3,5-dinitrophenyl)urea; N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dime- thylpropyl]-N'-phenylurea; (3R)--N-[(3S)-3-amino-4-hydroxybutyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imi- dazol-2-yl)-2,2-dimethylpropyl]-3-hydroxypyrrolidine-1-carboxamide; N-[(2S)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]piperazine-1-carboxamide; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]piperazine-1-carboxamide; (3R)--N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,- 2-dimethylpropyl]-3-hydroxypiperidine-1-carboxamide; (3S)--N-(3-aminopropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,- 2-dimethylpropyl]-3-hydroxypiperidine-1-carboxamide; N-[(3S)-3-amino-4-hydroxybutyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N',N'-dimethylurea; N-[(2S)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-phenylurea; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N',N'-dimethylurea; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-phenylurea; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-(2-methoxyethyl)urea; 4-acetyl-N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-- imidazol-2-yl)-2,2-dimethylpropyl]piperazine-1-carboxamide; (4R)--N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imi- dazol-2-yl)-2,2-dimethylpropyl]-4-hydroxyisoxazolidine-2-carboxamide; (3R)--N-(3-amino-2-fluoropropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol- -2-yl)-2,2-dimethylpropyl]-3-hydroxypiperidine-1-carboxamide; N-[(3S)-3-amino-4-hydroxybutyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-(2-methoxyethyl)urea; (3R)--N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imi- dazol-2-yl)-2,2-dimethylpropyl]-3-hydroxypyrrolidine-1-carboxamide; (3S)--N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imi- dazol-2-yl)-2,2-dimethylpropyl]-3-hydroxypyrrolidine-1-carboxamide; (3S)--N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imi- dazol-2-yl)-2,2-dimethylpropyl]-3-hydroxypiperidine-1-carboxamide; ethyl 4-({[(2S)-3-amino-2-fluoropropyl][(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2- -yl)-2,2-dimethylpropyl]amino}carbonyl)piperazine-1-carboxylate; ethyl 4-({[(2R)-3-amino-2-fluoropropyl][(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2- -yl)-2,2-dimethylpropyl]amino}carbonyl)piperazine-1-carboxylate; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-(ethylsulfonyl)piperazine-1-carboxamide; N-[(2S)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-hydroxypiperidine-1-carboxamide; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-hydroxypiperidine-1-carboxamide; N-(3-amino-2-fluoropropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)- -2,2-dimethylpropyl]-1,4'-bipiperidine-1'-carboxamide; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-1,4',-bipiperidine-1-carboxamide; N-(3-amino-2-fluoropropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)- -2,2-dimethylpropyl]-4-methylpiperazine-1-carboxamide; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-methylpiperazine-1-carboxamide; N-[(3S)-3-amino-4-hydroxybutyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-(2-hydroxyethyl)-N'-methylurea; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-(2-hydroxyethyl)-N'-methylurea; 1-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]tetrahy- dropyrimidin-2(1H)-one; N-[(2S)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-(2-hydroxyethyl)-N'-methylurea; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-(3,4-difluorophenyl)urea; N-[(2S)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-thien-3-ylurea; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-thien-3-ylurea; N-[(2S)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-morpholin-4-ylpiperidine-1-carboxamide; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-morpholin-4-ylpiperidine-1-carboxamide; N-(3-amino-2-fluoropropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)- -2,2-dimethylpropyl]morpholine-4-carboxamide; N-(3-amino-2-fluoropropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)- -2,2-dimethylpropyl]-4-(methylsulfonyl)piperazine-1-carboxamide; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-(methylsulfonyl)piperazine-1-carboxamide; N-(3-amino-2-fluoropropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)- -2,2-dimethylpropyl]-4-cyclohexylpiperazine-1-carboxamide; N-[(2S)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-(4-cyanophenyl)urea; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-(4-cyanophenyl)urea; N-[(2S)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-(propylsulfonyl)piperazine-1-carboxamide; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-(propylsulfonyl)piperazine-1-carboxamide; N-[(2S)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-(isopropylsulfonyl)piperazine-1-carboxamide; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-(isopropylsulfonyl)piperazine-1-carboxamide; N-[(2S)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-(cyclopropylsulfonyl)piperazine-1-carboxamide; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-(cyclopropylsulfonyl)piperazine-1-carboxamide; N-[(2S)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-(butylsulfonyl)piperazine-1-carboxamide; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-(butylsulfonyl)piperazine-1-carboxamide; N-[(3S)-3-amino-4-hydroxybutyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-1,4'-bipiperidine-1-carboxamide; N-[(3S)-3-amino-4-hydroxybutyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-(4-cyanophenyl)urea; N-[(3S)-3-amino-4-hydroxybutyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-(3,4-difluorophenyl)urea; N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]-N-{[(3- S)-3-fluoropyrrolidin-3-yl]methyl}-1,4'-bipiperidine-1'-carboxamide; N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]-N-{[(3- R)-3-fluoropyrrolidin-3-yl]methyl}-1,4'-bipiperidine-1'-carboxamide; N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]-N-{[(2- S,3S)-2-(hydroxymethyl)pyrrolidin-3-yl]methyl}-1,4'-bipiperidine-1'-carbox- amide; N-(3-amino-2-fluoropropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol- -2-yl)-2,2-dimethylpropyl]-N'-tetrahydro-2H-pyran-4-ylurea; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-N'-tetrahydro-2H-pyran-4-ylurea; N-(3-amino-2-fluoropropyl)-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)- -2,2-dimethylpropyl]-4-(dimethylamino)piperidine-1-carboxamide; N-[(2R)-3-amino-2-fluoropropyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-- 2-yl)-2,2-dimethylpropyl]-4-(dimethylamino)piperidine-1-carboxamide; N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]-N-{[(3- R,4R)-4-hydroxypyrrolidin-3-yl]methyl}-1,4'-bipiperidine-1'-carboxamide; N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]-N-{[(3- S,4S)-4-hydroxypyrrolidin-3-yl]methyl}-1,4'-bipiperidine-1'-carboxamide; N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]-N-[(3-- fluoropyrrolidin-3-yl)methyl]-4-(methylsulfonyl)piperazine-1-carboxamide; N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]-N-{[(3- S)-3-fluoropyrrolidin-3-yl]methyl}-4-(methylsulfonyl)piperazine-1-carboxam- ide; N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]-N-- {[(3R)-3-fluoropyrrolidin-3-yl]methyl}-4-(methylsulfonyl)piperazine-1-carb- oxamide; N-[(3R)-3-amino-4-hydroxybutyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-i- midazol-2-yl)-2,2-dimethylpropyl]-4-(methylsulfonyl)piperazine-1-carboxami- de; N-[(3S)-3-amino-4-hydroxybutyl]-N-[(1R)-1-(1-benzyl-4-phenyl-1H-imidaz- ol-2-yl)-2,2-dimethylpropyl]-4-(methylsulfonyl)piperazine-1-carboxamide; 1-((R)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-benzyl-4-(3-fluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-3,3-dimethyl-urea; 1-((S)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-benzyl-4-(3-fluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-3,3-dimethyl-urea; 1,1-Dioxo-1-thiomorpholine-4-carboxylic acid ((R)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(3-fluoro-phenyl)-1H-imid- azol-2-yl]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid ((R)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(3-fluoro-phenyl)-1H-imid- azol-2-yl]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(3-fluoro-phenyl)-1H-imid- azol-2-yl]-2,2-dimethyl-propyl}-amide; 4-Methanesulfonyl-piperidine-1-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(3-fluoro-phenyl)-1H-imid- azol-2-yl]-2,2-dimethyl-propyl}-amide; 1-((S)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-- phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3-methyl-urea; 1-((R)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-- phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3-methyl-urea; 1,1-Dioxo-1-thiomorpholine-4-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(3-fluoro-phenyl)-1H-imid- azol-2-yl]-2,2-dimethyl-propyl}-amide; 4-Methanesulfonyl-piperidine-1-carboxylic acid ((R)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(3-fluoro-phenyl)-1H-imid- azol-2-yl]-2,2-dimethyl-propyl}-amide; 1-((R)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-- phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-urea; 1-(3-Amino-3-methyl-butyl)-1-{(R)-1-[1-benzyl-4-(3-fluoro-phenyl)-1H-imid- azol-2-yl]-2,2-dimethyl-propyl}-3-methyl-urea; 1-(3-Amino-3-methyl-butyl)-1-{(R)-1-[1-benzyl-4-(3-fluoro-phenyl)-1H-imid- azol-2-yl]-2,2-dimethyl-propyl}-3,3-dimethyl-urea; 1-((S)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-- phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-urea; 4-Methyl-piperazine-1-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-phen- yl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 4-Methyl-piperazine-1-carboxylic acid ((R)-3-amino-4-fluoro-butyl)-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-phen- yl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1-(3-Amino-3-methyl-butyl)-1-{(R)-1-[1-benzyl-4-(3-fluoro-phenyl)-1H-imid- azol-2-yl]-2,2-dimethyl-propyl}-urea; Morpholine-4-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-phen- yl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid ((R)-3-amino-4-fluoro-butyl)-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro- -phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1-((S)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-- phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3,3-dim ethyl-urea; 1-((R)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-- phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3,3-dimethyl-urea; Pyrrolidine-1-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-phen- yl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Pyrrolidine-1-carboxylic acid ((R)-3-amino-4-fluoro-butyl)-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro- -phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid ((S)-3-amino-2-fluoro-propyl)-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-phe- nyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Pyrrolidine-1-carboxylic acid ((S)-3-amino-2-fluoro-propyl)-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-phe- nyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1-((S)-3-Amino-4-methoxy-butyl)-1-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro- -phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3-methyl-urea; Pyrrolidine-1-carboxylic acid ((S)-3-amino-4-methoxy-butyl)-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-phe- nyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid ((S)-3-amino-4-methoxy-butyl)-{(R) ---[1-(3-fluoro-benzyl)-4-(3-fluoro-phenyl)-1H-imidazol-2-yl]-2,2-dimethy- l-propyl}-amide; 1,1-Dioxo-1-thiomorpholine-4-carboxylic acid ((S)-3-amino-2-fluoro-propyl)-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro-phe- nyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1-((S)-3-Amino-2-fluoro-propyl)-1-{(R)-1-[1-(3-fluoro-benzyl)-4-(3-fluoro- -phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-urea; 1-(3-Amino-propyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol- -2-yl]-2,2-dimethyl-propyl}-3-methyl-urea; 1-(3-Amino-propyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol- -2-yl]-2,2-dimethyl-propyl}-3,3-dimethyl-urea; 1-(3-Amino-propyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol- -2-yl]-2,2-dimethyl-propyl}-3-(3,5-dimethyl-isoxazol-4-yl)-urea; Pyrrolidine-1-carboxylic acid (3-amino-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol-2-y- l]-2,2-dimethyl-propyl}-amide; Isoxazolidine-2-carboxylic acid (3-amino-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol-2-y- l]-2,2-dimethyl-propyl}-amide; 4-Methanesulfonyl-piperazine-1-carboxylic acid (3-amino-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazo- l-2-yl]-2,2-dimethyl-propyl}-amide; 4-Methanesulfonyl-piperidine-1-carboxylic acid (3-amino-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol-2-y- l]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid (3-amino-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol-2-y- l]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid ((S)-3-amino-4-methoxy-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H- -imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1-((S)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)- -1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3-methyl-urea; Morpholine-4-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1,1-Dioxo-1-thiomorpholine-4-carboxylic acid (3-amino-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol-2-y- l]-2,2-dimethyl-propyl}-amide; Pyrrolidine-1-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1-((S)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)- -1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3,3-dimethyl-urea; 4-Methanesulfonyl-piperazine-1-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1-((S)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)- -1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3-(3,5-di-methyl-isoxazol-4-yl)-ur- ea; 1,1-Dioxo-1-thiomorpholine-4-carboxylic acid ((S)-3-amino-2-fluoro-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H- -imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Isoxazolidine-2-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl- )-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Thiomorpholine-4-carboxylic acid (3-amino-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol-2-y- l]-2,2-dimethyl-propyl}-amide; Isoxazolidine-2-carboxylic acid ((S)-3-amino-2-fluoro-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H- -imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Pyrrolidine-1-carboxylic acid ((S)-3-amino-2-fluoro-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H- -imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid ((S)-3-amino-2-fluoro-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H- -imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1,1-Dioxo-1-thiomorpholine-4-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1-Oxo-1-thiomorpholine-4-carboxylic acid (3-amino-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol-2-y- l]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid ((S)-3-amino-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol-- 2-yl]-2,2-dimethyl-propyl}-amide; 4-Methanesulfonyl-piperazine-1-carboxylic acid ((S)-3-amino-2-fluoro-propyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H- -imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid ((R)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,3,5-trifluoro-phenyl)-- 1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,3,5-trifluoro-phenyl)-- 1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Morpholine-4-carboxylic acid ((R)-3-amino-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol-- 2-yl]-2,2-dimethyl-propyl}-amide; (2R,6S)-2,6-Dimethyl-morpholine-4-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 4-Isopropyl-piperazine-1-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1-((S)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)- -1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3-isopropyl-urea; 1-((S)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)- -1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3-cyclopropylmethyl-urea; 1-((S)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)- -1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3-(tetrahydro-pyran-4-yl)-urea; Morpholine-4-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(S)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 4-(3-((S)-3-Amino-4-fluoro-butyl)-3-{(R)-1-[1-benzyl-4-(2,5-difluoro-phen- yl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-ureido)-piperidine-1-carboxylic acid ethyl ester; (2S,6R)-2,6-Dimethyl-morpholine-4-carboxylic acid ((R)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; (S)-3-Hydroxy-pyrrolidine-1-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; (R)-3-Hydroxy-pyrrolidine-1-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; 1-((S)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)- -1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3-cyclopropyl-urea; (S)-2-Hydrazinocarbonyl-pyrrolidine-1-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; (S)-1-((3-Amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-- 1H-imidazol-2-yl]-2,2-dimethyl-propyl}-carbamoyl)-pyrrolidine-2-carboxylic acid methyl ester; 1-((R)-3-Amino-4-fluoro-butyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)- -1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3-methyl-urea; 1-((S)-3-Amino-4-methoxy-butyl)-1-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl- )-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-3-methyl-urea; Morpholine-4-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-(3-hydroxy-benzyl)-4-(2,3,5-triflu- oro-phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; (2S,6R)-2,6-Dimethyl-morpholine-4-carboxylic acid ((S)-3-amino-4-fluoro-butyl)-{(R)-1-[1-(3-hydroxy-benzyl)-4-(2,3,5-triflu- oro-phenyl)-1H-imidazol-2-yl]-2,2-dimethyl-propyl}-amide; Pyrrolidine-1-carboxylic acid ((R)-3-amino-4-fluoro-butyl)-{(R)-1-[1-benzyl-4-(2,5-difluoro-phenyl)-1H-- imidazol-2-yl]-2,2-dimethyl-propyl}-amide; N-[(3S)-3-amino-4-fluorobutyl]-N-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)- -1H-imidazol-2-yl]-2,2-dimethylpropyl}-N'-hydroxyurea; N-[(3R)-3-amino-4-fluorobutyl]-N-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)- -1H-imidazol-2-yl]-2,2-dimethylpropyl}-N'-hydroxyurea; 1-{(R)-1-[1-Benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol-2-yl]-2,2-dimethyl- -propyl}-1-[(S)-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-4-fluoro-butyl]-3-- methyl-urea; and N--[(S)-3-(1-{(R)-1-[1-Benzyl-4-(2,5-difluoro-phenyl)-1H-imidazol-2-yl]-2- ,2-dimethyl-propyl}-3-methyl-ureido)-1-fluoromethyl-propyl]-N'-methyl-phth- alamide, or a pharmaceutically acceptable salt or ester thereof. 20. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier. 21. The composition of claim 20 further comprising at least one agent for the treatment of cancer. 22. The composition of claim 21, wherein the agent for the treatment of cancer is selected from the group consisting of irinotecan, topotecan, gemcitabine, imatinib, trastuzumab, 5-fluorouracil, leucovorin, carboplatin, cisplatin, docetaxel, paclitaxel, tezacitabine, cyclophosphamide, vinca alkaloids, anthracyclines, rituximab, and trastuzumab. 23. The compound of claim 1, wherein A.sup.2 is phenyl, 3-fluorophenyl or 3-hydroxyphenyl.

Details for Patent 7,626,040

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2025-08-09
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2025-08-09
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2025-08-09
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2025-08-09
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2025-08-09
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2025-08-09