Claims for Patent: 7,932,279

Summary for Patent: 7,932,279

Title:	Substituted tetrazole compounds and uses thereof
Abstract:	The present invention provides tetrazole compounds, and methods of preparation of these compounds. The present invention also relates to pharmaceutical compositions comprising the tetrazole compounds. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a compound of the present invention.
Inventor(s):	Yang; Rui-Yang (Lexington, MA), Ali; Syed M. (North Andover, MA), Ashwell; Mark A. (Carlisle, MA), Kelleher; Eugene (Wellesley, MA), Palma; Rocio (North Andover, MA), Westlund; Neil (Groton, MA)
Assignee:	ArQule, Inc. (Woburn, MA)
Application Number:	12/251,093
Patent Claims:	1. A compound of formula I, or pharmaceutically acceptable salts thereof ##STR00134## wherein: R.sub.1 is selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, and I; R.sub.2 is OH; R.sub.3 is selected from the group consisting of ##STR00135## R.sub.4 is selected from the group consisting of (C1-C6) alkyl, (C1-C6) substituted alkyl, (C3-C9) cycloalkyl, (C3-C9) substituted cycloalkyl; aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, --OR.sub.14, and ##STR00136## m is 1, or 2; n is 1, 2, or 3; R.sub.5 and R.sub.6 are independently selected from the group consisting of hydrogen, NO.sub.2, CN, --(C1-C6) alkyl, --(C1-C6) substituted alkyl, --(C3-C9) cycloalkyl, --(C3-C9) substituted cycloalkyl; --OR.sub.8, aryl, heteroaryl, heterocyclyl, --NR.sub.9R.sub.10, --C(.dbd.O)--WR.sub.11, --C(.dbd.O)--NR.sub.12R.sub.13, --S(.dbd.O)2R.sub.15; R.sub.7 is selected from --(C1-C6) alkyl, --(C1-C6) substituted alkyl, --(C3-C9) cycloalkyl, --(C3-C9) substituted cycloalkyl; --C(.dbd.O)--OR.sub.11, --C(.dbd.O)--NR.sub.12R.sub.13, --S(.dbd.O).sub.2R.sub.15; R.sub.8 is independently selected from the group consisting of (C1-C6) alkyl, (C1-C6) substituted alkyl, (C3-C9) cycloalkyl; and (C3-C9) substituted cycloalkyl; R.sub.9 and R.sub.10 are independently selected from the group consisting of Hydrogen, (C1-C6) alkyl, (C3-C9) cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclyl, and substituted heterocyclyl; W is independently O or S; each R.sub.11 is independently selected from the group consisting of (C1-C6) alkyl, (C1-C6) substituted alkyl, aryl, and heteroaryl; each R.sub.12 and each R.sub.13 are independently selected from the group consisting of Hydrogen, (C1-C6) alkyl, heteroaryl alkyl, and aryl; R.sub.14 is selected from the group consisting of (C1-C8) alkyl, (C1-C8) substituted alkyl, (C3-C9) cycloalkyl, (C3-C9) substituted cycloalkyl, aryl, heteroaryl, and heterocyclyl; and each R.sub.15 is independently selected from the group consisting of (C1-C6) alkyl, (C1-C6) substituted alkyl, and NR.sub.12R.sub.13. 2. The compound of claim 1 wherein R.sub.1 is hydrogen. 3. The compound of claim 1 wherein R.sub.5 is in ortho-, meta-, or para-position. 4. The compound of claim 1 wherein R.sub.5 is selected from the group consisting of methyl, ethyl, isopropyl, tert-butyl, phenyl, trifluoromethyl, methoxy, phenoxy, isopropyloxy, trifluoromethoxy, chloro, and fluoro. 5. The compound of claim 1 wherein R.sub.6 is hydrogen. 6. The compound of claim 3 wherein neither R.sub.5 nor R.sub.6 is hydrogen. 7. The compound of claim 1 wherein R.sub.3 is ##STR00137## 8. The compound of claim 1 wherein R.sub.4 is selected from the group consisting of ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, cyclobutyl, cyclohexyl, cyclopropylmethyl, 3-phenylpropyl, 4-fluorophenyl, 2-methoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 3-isopropoxypropyl, and tetrahydrofuran-2-ylmethyl. 9. The compound of claim 1 wherein R.sub.4 is ##STR00138## 10. The compound of claim 5 wherein m is 1, or 2; and n is 1, 2, or 3. 11. The compound of claim 5 wherein m 2 and n is 2. 12. The compound of claim 5 wherein R.sub.7 is hydrogen, or ethyl. 13. The compound of claim 1 wherein the compound is selected from the group consisting of Methyl 2',4'-dihydroxy-5'-[1-(3-methoxypropyl)-1H-tetrazol-5-yl]biphenyl-3-carbo- xylate, Methyl 5'-(1-butyl-1H-tetrazol-5-yl)-2',4'-dihydroxybiphenyl-3-carboxylate, tert-Butyl 4-[5-(4,6-dihydroxy-5'-isopropyl-2'-methoxybiphenyl-3-yl)-1H-tetrazol-1-y- l]piperidine-1-carboxylate, 5'-Isopropyl-2'-methoxy-5-(1-piperidin-4-yl-1H-tetrazol-5-yl)biphenyl-2,4- -diol, 5'-Isopropyl -2'-methoxy-5-[1-(2-methoxyethyl) -1H-tetrazol-5-yl]biphenyl-2,4-diol, 5-[1-(3-Ethoxypropyl)-1H-tetrazol-5-yl]-5'-isopropyl-2'-methoxybiphenyl-2- ,4-diol, 5-(1-Ethyl-1H-tetrazol-5-yl)-5'-isopropyl-2'-methoxybiphenyl-2,4-- diol, 5-[1-(3-Isopropoxypropyl)-1H-tetrazol-5-yl]-5'-isopropyl-2'-methoxyb- iphenyl-2,4-diol, 5'-Isopropyl-2'-methoxy-5-[1-(3-phenylpropyl)-1H-tetrazol-5-yl]biphenyl-2- ,4-diol, 5'-Isopropyl-2'-methoxy-5-[1-(tetrahydrofuran-2-ylmethyl)-1H-tetr- azol-5-yl]biphenyl-2,4-diol, 5-(1-Butyl-1H-tetrazol-5-yl)-5'-isopropyl-2'-methoxybiphenyl-2,4-diol, 3-[5-(4,6-Dihydroxy-5'-isopropyl-2'-methoxybiphenyl-3-yl)-1H-tetrazol-1-y- l]dihydrofuran-2(3H)-one, 5-(1-Cyclopropyl-1H-tetrazol-5-yl)-5'-isopropyl-2'-methoxybiphenyl-2,4-di- ol, 5-(1-Cyclobutyl-1H-tetrazol-5-yl)-5'-isopropyl-2'-methoxybiphenyl-2,4-- diol, 5'-Isopropyl-5-(1-isopropyl-1H-tetrazol-5-yl)-2'-methoxybiphenyl-2,4- -diol, 5-[1-(4-Fluorophenyl)-1H-tetrazol-5-yl]-5'-isopropyl-2'-methoxybiph- enyl-2,4-diol, 5-(1-Cyclohexyl-1H-tetrazol-5-yl)-5'-isopropyl-2'-methoxybiphenyl-2,4-dio- l, 5-[1-(Cyclopropylmethyl)-1H-tetrazol-5-yl]-5'-isopropyl-2'-methoxybiphe- nyl-2,4-diol, 5'-Isopropyl-2'-methoxy-5-(1-propyl-1H-tetrazol-5-yl)biphenyl-2,4-diol, 5-(1-Isobutyl-1H-tetrazol-5-yl)-5'-isopropyl-2'-methoxybiphenyl-2,4-diol, and 5-[1-(1-Ethylpiperidin-4-yl)-1H-tetrazol-5-yl]-5'-isopropyl-2'-methox- ybiphenyl-2,4-diol. 14. A pharmaceutical composition comprising a compound of claim 1 in combination with a pharmaceutically acceptable carrier or excipient. 15. The pharmaceutical composition of claim 14 further comprising a second chemotherapeutic agent, wherein said second chemotherapeutic agent is selected from the group consisting of tamoxifen, raloxifene, anastrozole, exemestane, letrozole, cisplatin, carboplatin, paclitaxel, cyclophosphamide, lovastatin, minosine, gemcitabine, araC, 5-fluorouracil, methotrexate, docetaxel, goserelin, vincristin, vinblastin, nocodazole, teniposide, etoposide, epothilone, navelbine, camptothecin, daunonibicin, dactinomycin, mitoxantrone, amsacrine, doxorubicin, epirubicin, idarubicin imatanib, gefitinib, erlotinib, sorafenib, sunitinib malate, trastuzumab, rituximab, cetuximab, and bevacizumab.

Details for Patent 7,932,279

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2027-10-12
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2027-10-12
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2027-10-12
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2027-10-12
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2027-10-12