Claims for Patent: 8,519,136

Summary for Patent: 8,519,136

Title:	Aminopyridine derivatives having aurora a selective inhibitory action
Abstract:	The present invention relates to a compound of formula I: wherein: R.sub.1 is a hydrogen atom, F, CN, etc.; R.sub.2 is CO, SO.sub.2, etc.; R.sub.3 is a phenyl which may be substituted; X.sub.1, X.sub.2, and X.sub.3 each independently CH, N, etc. provided, however, that among X.sub.1, X.sub.2 and X.sub.3, the number of nitrogen is 0 or 1; W is the following residue: wherein: W.sub.1, W.sub.2, and W.sub.3 each independently CH, N, etc., or a pharmaceutically acceptable salt or ester thereof. ##STR00001##
Inventor(s):	Kato; Tetsuya (Tsukuba, JP), Kawanishi; Nobuhiko (Moriya, JP), Mita; Takashi (Tsukuba, JP), Nonoshita; Katsumasa (Tsukuba, JP), Ohkubo; Mitsuru (Ushiku, JP)
Assignee:	MSD K.K. (Chiyoda-Ku, Tokyo, JP)
Application Number:	12/866,955
Patent Claims:	1. A compound which is: (a) 1-(3-chloro-2-fluorobenzoyl)-4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)met- hyl)piperidin-4-ol; (b) 5-(1-(2-fluoro-3-(trifluoromethyl)benzoyl)-4-((6-(1H-pyrazol-3-ylamino)py- ridin-2-yl)methyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; (c) 5-(1-(3-chloro-2-fluorobenzoyl)-4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)- methyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; (d) 5-(4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)-1-((2-(trifluoromethy- l)phenyl)sulfonyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; (e) 5-(1-(3-chloro-2-fluorobenzoyl)-4-((4-phenyl-6-(1H-pyrazol-3-ylamino)pyri- din-2-yl)methyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; or (f) 5-(4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)-1-(2,2,2-trifluoro-1-- (3-(trifluoromethyl)phenyl)ethyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one- ; or a pharmaceutically acceptable salt or ester thereof. 2. A pharmaceutical composition comprising, together with pharmaceutically acceptable carrier or diluent, at least one compound according to claim 1 as active ingredient. 3. A combined preparation for simultaneous, separate, or sequential administration in the treatment of cancer, comprising two separate preparations: (i) a preparation comprising, together with a pharmaceutically acceptable carrier or diluent, a compound according to claim 1; and (ii) a preparation comprising, together with a pharmaceutically acceptable carrier or diluent, one antitumor agent selected from the group consisting of antitumor alkylating agents, antitumor antimetabolites, antitumor antibiotics, plant-derived antitumor agents, antitumor platinum-complex compounds, antitumor campthotecin derivatives, antitumor tyrosine kinase inhibitors, monoclonal antibodies, interferons, biological response modifiers, and other antitumor agents or a pharmaceutically acceptable salt thereof, wherein: the antitumor alkylating agents are nitrogen mustard N-oxide, cyclophosphamide, ifosfamide, melphalan, busulfan, mitobronitol, carboquone, thiotepa, ranimustine, nimustine, temozolomide, and carmustine; the antitumor antimetabolites are methotrexate, 6-mercaptopurine riboside, mercaptopurine, 5-fluorouracil, tegafur, doxifluridine, carmofur, cytarabine, cytarabine ocfosfate, enocitabine, S-1, gemcitabine, fludarabine, and pemetrexed disodium; the antitumor antibiotics are actinomycin D, doxorubicin, daunorubicin, neocarzinostatin, bleomycin, peplomycin, mitomycin C, aclarubicin, pirarubicin, epirubicin, zinostatin stimalamer, idarubicin, sirolimus, and valrubicin; the plant-derived antitumor agents are vincristine, vinblastine, vindeshine, etoposide, sobuzoxane, docetaxel, paclitaxel, and vinorelbine; the antitumor platinum-complex compounds are cisplatin, carboplatin, nedaplatin, and oxaliplatin; the antitumor campthotecin derivatives are irinotecan, topotecan, and campthotecin; the antitumor tyrosine kinase inhibitors are gefitinib, imatinib, sorafenib, sunitinib, dasatinib, and erlotinib; the monoclonal antibodies are cetuximab, rituximab, bevacizumab, alemtuzumab, and trastuzumab; the interferons are interferon .alpha., interferon .alpha.-2a, interferon .alpha.-2b, interferon .beta., interferon .gamma.-1a, and interferon .gamma.-n1, the biological response modifiers are krestin, lentinan, sizofuran, picibanil, or ubenimex, and the other antitumor agents are mitoxantrone, L-asparaginase, procarbazine, dacarbazine, hydroxycarbamide, pentostatin, tretinoin, alefacept, darbepoetin alfa, anastrozole, exemestane, bicalutamide, leuprorelin, flutamide, fulvestrant, pegaptanib octasodium, denileukin diftitox, aldesleukin, thyrotropin alfa, arsenic trioxide, bortezomib, capecitabine, and goserelin. 4. The combined preparation according to claim 3 wherein one of or both of the two separate preparations is/are oral preparation(s). 5. The combined preparation according to claim 3 which is further combined with at least one preparation comprising, together with a pharmaceutically acceptable carrier or diluent, an antitumor agent selected from the group consisting of antitumor alkylating agents, antitumor antimetabolites, antitumor antibiotics, plant-derived antitumor agents, antitumor platinum-complex compounds, antitumor campthotecin derivatives, antitumor tyrosine kinase inhibitors, monoclonal antibodies, interferons, biological response modifiers, and other antitumor agents, wherein the definition of each antitumor agent is the same as defined in claim 3, or a pharmaceutically acceptable salt thereof. 6. The combined preparation according to claim 3 wherein: among the combined preparation, (i) one is a preparation which comprises, together with a pharmaceutically acceptable carrier or diluent, (a) 1-(3-chloro-2-fluorobenzoyl)-4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)met- hyl)piperidin-4-ol; (b) 5-(1-(2-fluoro-3-(trifluoromethyl)benzoyl)-4-((6-(1H-pyrazol-3-ylamino)py- ridin-2-yl)methyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; (c) 5-(1-(3-chloro-2-fluorobenzoyl)-4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)- methyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; (d) 5-(4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)-1-((2-(trifluoromethy- l)phenyl)sulfonyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; (e) 5-(1-(3-chloro-2-fluorobenzoyl)-4-((4-phenyl-6-(1H-pyrazol-3-ylamino)pyri- din-2-yl)methyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; or (f) 5-(4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)-1-(2,2,2-trifluoro-1-- (3-(trifluoromethyl)phenyl)ethyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one- ; or a pharmaceutically acceptable salt or ester thereof; and (ii) the other is a preparation which comprises, together with a pharmaceutically acceptable carrier or diluent, paclitaxel or docetaxel. 7. A pharmaceutical composition comprising, together with a pharmaceutically acceptable carrier or diluent, a compound according to claim 1, or a pharmaceutically acceptable salt thereof; and an antitumor agent selected from the group consisting of antitumor alkylating agents, antitumor antimetabolites, antitumor antibiotics, plant-derived antitumor agents, antitumor platinum-complex compounds, antitumor campthotecin derivatives, antitumor tyrosine kinase inhibitors, monoclonal antibodies, biological response modifiers, and other antitumor agents, wherein the definition of each antitumor agent is the same as defined in claim 3, or a pharmaceutically acceptable salt thereof. 8. The pharmaceutical composition according to claim 7, wherein a compound according to claim 1 is the following: (a) 1-(3-chloro-2-fluorobenzoyl)-4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)met- hyl)piperidin-4-ol; (b) 5-(1-(2-fluoro-3-(trifluoromethyl)benzoyl)-4-((6-(1H-pyrazol-3-ylamino)py- ridin-2-yl)methyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; (c) 5-(1-(3-chloro-2-fluorobenzoyl)-4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)- methyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; (d) 5-(4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)-1-((2-(trifluoromethy- l)phenyl)sulfonyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; (e) 5-(1-(3-chloro-2-fluorobenzoyl)-4-((4-phenyl-6-(1H-pyrazol-3-ylamino)pyri- din-2-yl)methyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one; or (f) 5-(4-((6-(1H-pyrazol-3-ylamino)pyridin-2-yl)methyl)-1-(2,2,2-trifluoro-1-- (3-(trifluoromethyl)phenyl)ethyl)piperidin-4-yl)-1,3,4-oxadiazol-2(3H)-one- ; or a pharmaceutically acceptable salt or ester thereof; and the antitumor agent is paclitaxel or docetaxel.

Details for Patent 8,519,136

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genzyme Corporation	THYROGEN	thyrotropin alfa	For Injection	020898	11/30/1998		2039-02-26
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2039-02-26
Clinigen, Inc.	PROLEUKIN	aldesleukin	For Injection	103293	05/05/1992		2039-02-26