Claims for Patent: 7,820,646

Summary for Patent: 7,820,646

Title:	Cyclized derivatives as Eg-5 inhibitors
Abstract:	The present invention relates to new substituted imidazole compounds have the following Formula (I) and to the pharmaceutically acceptable salts, esters, or prodrugs thereof, to compositions of the compounds together with pharmaceutically acceptable carriers, and to uses of the compounds: ##STR00001##
Inventor(s):	Boyce; Rustum (Singapore, SG), Martin; Eric (El Cerrito, CA), Wang; Weibo (Moraga, CA), Yang; Hong (Fremont, CA), Barsanti; Paul A. (Pleasant Hill, CA)
Assignee:	Novartis Vaccines and Diagnostics, Inc. (Emeryville, CA)
Application Number:	11/969,164
Patent Claims:	1. A compound of Formula (I): ##STR00135## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from the group consisting of alkyl and substituted alkyl; R.sup.2 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl; L is selected from the group consisting of a) --O--; b) --OCH.sub.2--, --CH.sub.2O--, --C(O)NR.sup.7--; c) --CH.sub.2OCH.sub.2--, --CH.sub.2NR.sup.7CH.sub.2--, --CH.sub.2CH.sub.2O--, --C(O)NR.sup.7CH.sub.2--, and --CH.sub.2CH.sub.2NR.sup.7--; R.sup.3 and R.sup.4 are independently selected from the group consisting of halo, alkyl, and substituted alkyl; R.sup.5 and R.sup.6 are independently selected from the group consisting of cyano, alkyl, substituted alkyl, alkoxy, substituted alkoxy, halo, and hydroxy; R.sup.7 is selected from the group consisting of hydrogen, alkyl, and --SO.sub.2alkyl; m is 0, 1, 2, or 3; n is 0, 1, 2, or 3; and p is 0 or 1. 2. A compound of claim 1 wherein R.sup.1 and R.sup.2 are alkyl. 3. A compound of claim 1 wherein R.sup.1 is alkyl and R.sup.2 is hydrogen. 4. A compound of claim 3 wherein R.sup.1 is selected from the group consisting of isopropyl, t-butyl, and propyl. 5. A compound of claim 1 wherein R.sup.4 is substituted alkyl. 6. A compound of claim 5 wherein R.sup.4 is alkyl substituted with 1 to 5 substituents selected from the group consisting of amino, substituted amino, halo, alkoxy, substituted alkoxy, and hydroxy. 7. A compound of claim 1 wherein R.sup.4 is selected from the group consisting of halo, --CH.sub.2NH.sub.2, --(CH.sub.2).sub.2NH.sub.2, --(CH.sub.2).sub.3NH.sub.2, and --CH.sub.2OH. 8. A compound of claim 1 wherein m is 0. 9. A compound of claim 1 wherein R.sup.6 is halo. 10. A compound of claim 1 wherein R.sup.6 and the phenyl ring to which it is attached is selected from the group consisting of phenyl, 3-bromophenyl, 3-chlorophenyl, 4-cyanophenyl, 2,5-difluorophenyl, 3-fluorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-methylphenyl, 2-trifluoromethylphenyl, and 3-trifluoromethylphenyl. 11. A compound of claim 1, wherein L and the atoms to which it is joined form a ring selected from the group consisting of ##STR00136## ##STR00137## ##STR00138## 12. A compound of claim 1 having Formula (Ia) or a pharmaceutically acceptable salt thereof: ##STR00139## 13. A compound of claim 1 having Formula (Ib)-(Id) or a pharmaceutically acceptable salt thereof: ##STR00140## 14. A compound of claim 1 having Formula (Ie)-(Ii) or a pharmaceutically acceptable salt thereof: ##STR00141## ##STR00142## 15. A compound that is (S)-5-(aminomethyl)-3-((R)-1-(1-benzyl-4-(2,5-difluorophenyl)-1H-imidazol- -2-yl)-2,2-dimethylpropyl)oxazolidin-2-one or a pharmaceutically acceptable salt thereof: ##STR00143## 16. A compound that is (R)-5-(aminomethyl)-3-((R)-1-(1-benzyl-4-(2,5-difluorophenyl)-1H-imidazol- -2-yl)-2,2-dimethylpropyl)oxazolidin-2-one or a pharmaceutically acceptable salt thereof: ##STR00144## 17. A compound claim 1 selected from: (5R)-5-(2-aminoethyl)-3-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-- dimethylpropyl]-1,3-oxazolidin-2-one; (5S)-5-(2-aminoethyl)-3-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-- dimethylpropyl]-1,3-oxazolidin-2-one; 5-(aminomethyl)-3-{(1R)-1-[1-benzyl-4-(3-chlorophenyl)-1H-imidazol-2-yl]-- 2-methylpropyl}-1,3-oxazolidin-2-one; (5S)-5-(aminomethyl)-3-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]-1,3-oxazinan-2-one; (5R)-5-(aminomethyl)-3-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]-1,3-oxazinan-2-one; (6S)-6-(aminomethyl)-4-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]morpholin-3-one; (6R)-6-(aminomethyl)-4-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]morpholin-3-one; (6R)-6-(aminomethyl)-4-{(1R)-1-[1-benzyl-4-(3-chlorophenyl)-1H-imidazol-2- -yl]-2-methylpropyl}morpholin-3-one; (6S)-6-(aminomethyl)-4-{(1R)-1-[1-benzyl-4-(3-chlorophenyl)-1H-imidazol-2- -yl]-2-methylpropyl}morpholin-3-one; (6R)-6-(2-aminoethyl)-4-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-- dimethylpropyl]morpholin-3-one; (6S)-6-(2-aminoethyl)-4-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-- dimethylpropyl]morpholin-3-one; (6S)-6-(2-aminoethyl)-4-{(1R)-1-[1-benzyl-4-(3-chlorophenyl)-1H-imidazol-- 2-yl]-2-methylpropyl}morpholin-3-one; (6R)-6-(2-aminoethyl)-4-{(1R)-1-[1-benzyl-4-(3-fluorophenyl)-1H-imidazol-- 2-yl]-2-methylpropyl}morpholin-3-one; (2S,6R)-6-(aminomethyl)-4-{(1R)-1-[1-benzyl-4-(3-fluorophenyl)-1H-imidazo- l-2-yl]-2,2-dimethylpropyl}-2-methylmorpholin-3-one; (2R,6R)-6-(aminomethyl)-4-{(1R)-1-[1-benzyl-4-(3-fluorophenyl)-1H-imidazo- l-2-yl]-2,2-dimethylpropyl}-2-methylmorpholin-3-one; (5R)-5-(aminomethyl)-1-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]piperazine-2,3-dione; (5S)-5-(aminomethyl)-1-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]piperazine-2,3-dione; (5R)-5-(aminomethyl)-1-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]-4-methylpiperazine-2,3-dione; (2S)-4-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]-2- -(hydroxymethyl)-1,4-diazepan-5-one; (2R)-2-(aminomethyl)-4-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]-1,4-diazepan-5-one; (2R)-2-(aminomethyl)-4-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]-1-(methylsulfonyl)-1,4-diazepan-5-one; (2S)-2-(aminomethyl)-4-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]-1,4-oxazepan-5-one; (2R)-2-(aminomethyl)-4-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]-1,4-oxazepan-5-one; (6S)-6-(aminomethyl)-4-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]-1,4-oxazepan-3-one; (6R)-6-(aminomethyl)-4-{(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl}-1,4-oxazepan-3-one; (6R)-6-(aminomethyl)-4-{(1R)-1-[1-(3,5-difluorobenzyl)-4-(3-fluorophenyl)- -1H-imidazol-2-yl]-2,2-dimethylpropyl}-1,4-oxazepan-3-one; (6R)-6-(aminomethyl)-4-{(1R)-1-[1-benzyl-4-(3-fluorophenyl)-1H-imidazol-2- -yl]-2,2-dimethylpropyl}-1,4-oxazepan-3-one; (6R)-6-(aminomethyl)-4-{(1R)-1-[1-(3-fluorobenzyl)-4-(3-fluorophenyl)-1H-- imidazol-2-yl]-2,2-dimethylpropyl}-1,4-oxazepan-3-one; (6S)-6-(aminomethyl)-4-{(1R)-1-[1-(3-fluorobenzyl)-4-(3-fluorophenyl)-1H-- imidazol-2-yl]-2,2-dimethylpropyl}-1,4-oxazepan-3-one; (6S)-6-(aminomethyl)-1-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-d- imethylpropyl]-1,4-diazepane-2,3-dione; (6R)-1-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]-6- -fluoro-1,4-diazepan-2-one; or (6S)-1-[(1R)-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-2,2-dimethylpropyl]-6- -fluoro-1,4-diazepan-2-one; or a pharmaceutically acceptable salt thereof. 18. A pharmaceutical composition comprising a therapeutically effective amount of a compound of any one of claims 1 to 17 and a pharmaceutically acceptable carrier. 19. The composition of claim 18 further comprising at least one additional agent for the treatment of cancer. 20. The composition of claim 19, wherein the additional 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.

Details for Patent 7,820,646

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2027-01-05
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2027-01-05
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2027-01-05
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2027-01-05
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2027-01-05