Claims for Patent: 7,253,286

Summary for Patent: 7,253,286

Title:	Nitrogen-containing aromatic derivatives
Abstract:	Compounds represented by the following general formula: [wherein Ag is an optionally substituted 5- to 14-membered heterocyclic group, etc.; Xg is -O-, -S-, etc.; Yg is an optionally substituted C6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group, etc.; and Tg1 is a group represented by the following general formula: (wherein Eg is a single bond or -N(Rg2)-, Rg1 and Rg2 each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, etc. and Zg represents a C1-8 alkyl group, a C3-8 alicyclic hydrocarbon group, a C6-14 aryl group, etc.)], salts thereof or hydrates of the foregoing.
Inventor(s):	Yasuhiro Funahashi, Akihiko Tsuruoka, Masayuki Matsukura, Toru Haneda, Yoshio Fukuda, Junichi Kamata, Keiko Takahashi, Tomohiro Matsushima, Kazuki Miyazaki, Ken-ichi Nomoto, Tatsuo Watanabe, Hiroshi Obaishi, Atsumi Yamaguchi, Sachi Suzuki, Katsuji Nakamura, Fusayo Mimura, Yuji Yamamoto, Junji Matsui, Kenji Matsui, Takako Yoshiba, Yasuyuki Suzuki, Itaru Arimoto
Assignee:	Eisai R&D Management Co Ltd
Application Number:	US10/420,466
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,253,286
Patent Claims:	1. A compound represented by the following general formula: wherein: R1 and R2 are each independently a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 alicyclic hydrocarbon group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; Z12 is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 alicyclic hydrocarbon group, an optionally substituted C6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group, an optionally substituted 5- to 14-membered aromatic heterocyclic group or a group represented by the formula: wherein Z31, Z33 and Z34 are each independently a methylene group, —CO—, —NH— or —O—, and Z32 is a single bond, a methylene group, —CO—, —NH— or —O—; and wherein Z12 is not pyrazolyl; Ya1 is a group represented by the formula: wherein W31 and W32 are each independently an optionally substituted carbon atom or a nitrogen atom; R300 and R301 are each independently a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 alicyclic hydrocarbon group, an optionally substituted C1-6 alkoxy group, an optionally substituted C2-7 alkoxycarbonyl group, a formyl group, a group represented by the formula wherein V300 and V301 are each independently a hydrogen atom or an optionally substituted C1-6 alkyl group, or an optionally substituted C2-7 acyl group; Ra11 is a group represented by the formula —Va21—Va22—Va23, wherein: Va21 is an optionally substituted C1-6 alkylene group, a single bond or a group represented by the formula: Va22 is a single bond, an oxygen atom, a sulfur atom, —CO—, —SO—, —SO2—, —CONRa14—, —SO2NRa14—, —NRa14SO2—, —NRa14CO— or —NRa14—; wherein Ra14 is a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 alicyclic hydrocarbon group; and Va23 is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 alicyclic hydrocarbon group, an optionally substituted C6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group or an optionally substituted 5- to 14-membered aromatic heterocyclic group; and Ra12 is a cyano group or a group represented by the formula: wherein: Va11 is —CO— or —SO2—; and Va12, Va13 and Va14 are each independently a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 alicyclic hydrocarbon group, an optionally substituted C6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group or an optionally substituted 5- to 14-membered aromatic heterocyclic group; with the exception of the following compounds (1) and (2): (1) a compound wherein Ra12 is a group represented by the formula: wherein: Va12 and Va13 are each independently a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 alicyclic hydrocarbon group, an optionally substituted C6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group or an optionally substituted 5- to 14-membered aromatic heterocyclic group; R1 and R2 are hydrogen atoms; and Z12 is a C6-14 aryl group, a 6- to 14-membered heterocyclic group or a 6- to 14-membered aromatic heterocyclic group; (2) a compound wherein Ra12 is a group selected from the group consisting of the formulae: wherein: Va11 is —CO— or —SO2—; Va12, Va13 and Va14 are each independently a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 alicyclic hydrocarbon group, an optionally substituted C6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group or an optionally substituted 5- to 14-membered aromatic heterocyclic group; R2 is a hydrogen atom; and Z12 is (a) a C6-14 aryl group, (b) a 5- to 14-membered heterocyclic group, (c) a 5- to 14-membered aromatic heterocyclic group, (d) a C1.6 alkyl group substituted with a 5- to 10-membered heterocyclic group or a C5-10 alicyclic hydrocarbon group, (e) a C2-6 alkenyl group substituted with a 5- to 10-membered heterocyclic group or a C5-10 alicyclic hydrocarbon group, (f) a C2-6 alkynyl group substituted with a 5- to 10-membered heterocyclic group or a C5-10 alicyclic hydrocarbon group, or (g) a C3-8 alicyclic hydrocarbon group substituted with a 5- to 10-membered heterocyclic group or a C5-10 alicyclic hydrocarbon group, or a pharmacologically acceptable salt or hydrate thereof. 2. The compound according to claim 1, a pharmacologically acceptable salt or hydrate thereof, wherein Ra11 is a methyl group, a 2-methoxyethyl group or a group represented by the formula: wherein: Ra53 is a methyl group, a cyclopropylmethyl group or a cyanomethyl group; Ra51 is a hydrogen atom, a fluorine atom or a hydroxyl group; and Ra52 is a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinyl group, a dimethylamino group or a diethylamino group. 3. The compound according to either of claims 1 or 2, a pharmacologically acceptable salt or hydrate thereof, wherein Z12 is a methyl group, an ethyl group, a cyclopropyl group, a 2-thiazolyl group or a 4-fluorophenyl group. 4. The compound according to any one of claims 1 to 3, a pharmacologically acceptable salt or hydrate thereof, wherein Ya1 is a group represented by the formula: wherein Ra61 is a hydrogen atom, a methyl group, a trifluoromethyl group, a chlorine atom or a fluorine atom. 5. The compound according to any one of claims 1 to 4, a salt or hydrate thereof, wherein Ra12 is a cyano group or a group represented by the formula —CONHRa62, wherein Ra62 is a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 is alicyclic hydrocarbon group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group. 6. The compound according to claim 1, a pharmacologically acceptable salt or hydrate thereof, wherein said compound is a compound selected from: N-(4-(6-cyano-7-(3-(4-pyridyl)propoxy)-4-quinolyl)oxyphenyl)-N′-(4-methoxyphenyl)urea, N-(4-(6-cyano-7-(2-(1,2,3-triazol-2-yl)ethoxy)-4-quinolyl)oxyphenyl)-N′-(4-fluorophenyl)urea, N-(4-(6-cyano-7-(2-(1,2,3-triazol-1-yl)ethoxy)-4-quinolyl)oxyphenyl)-N′-(4-fluorophenyl)urea, N-(4-(6-cyano-7-(2-(1,2,3-triazol-2-yl)ethoxy)-4-quinolyl)oxyphenyl)-N′-(2,4-difluorophenyl)urea, N-(4-(6-cyano-7-(2-(1,2,3-triazol-1-yl)ethoxy)-4-quinolyl)oxyphenyl)-N′-(2,4-difluorophenyl)urea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxyphenyl)-N′-(4-fluorophenyl)urea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxyphenyl)-N′-(1,3-thiazol-2-yl)urea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxyphenyl)-N′-(3-cyanophenyl)urea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxyphenyl)-N′-cyclopropylurea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(1,3-thiazol-2-yl)urea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-cyclopropylurea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxyphenyl)-N′-cyclopropylmethylurea, N-(4-(6-cyano-7-(3-(morpholin-4-yl)propoxy)quinolin-4-yloxy)-2-fluorophenyl)-N′-(2,4-difluorophenyl)urea, N-(4-(6-cyano-7-(3-(diethylamino)propoxy)-4-quinolyloxy)phenyl)-N′-(4-fluorophenyl)urea, N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(4-fluorophenyl)urea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(3-(methylsulfonyl)phenyl)urea, N-(4-(6-cyano-7-(3-(diethylamino)propoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(2,4-difluorophenyl)urea, N-(4-(6-cyano-7-(3-(1-(4-ethylpiperazino))propoxy)-4-quinolyl)oxyphenyl)-N′-(4-methoxyphenyl)urea, N-(4-(6-cyano-7-(3-cyanopropoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(2,4-difluorophenyl)urea, N-(4-(6-cyano-7-(2-(methylsulfonyl)ethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(2,4-difluorophenyl)urea, N-(4-(6-cyano-7-(2-(methylsulfonyl)ethoxy)-4-quinolyl)oxyphenyl)-N′-(4-fluorophenyl)urea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxyphenyl)-N′-phenylurea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(2,4-difluorophenyl)urea, N-(4-(6-cyano-7-(3-methoxycarbonylpropoxy)-4-quinolyl)oxyphenyl)-N′-(4-methoxyphenyl)urea, N-(4-(6-cyano-7-(3-carboxypropoxy)-4-quinolyl)oxyphenyl)-N′-(4-methoxyphenyl)urea, N-(4-(6-cyano-7-(2-(2-hydroxyethoxy)ethoxy)-4-quinolyl)oxyphenyl)-N′-(4-methoxyphenyl)urea, N-(4-(6-cyano-7-(3-(diethylamino)propoxy)-4-quinolyloxy)phenyl)-N′-(3-(methylsulfonyl)phenyl)urea, N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(3-(methylsulfonyl)phenyl)urea, N-(4-(6-cyano-7-(3-(diethylamino)propoxy)-4-quinolyloxy)phenyl)-N′-phenylurea, N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-phenylurea, N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N′-(2-oxo -1,2,3,4-tetrahydro-6-quinolyl)urea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxyphenyl)-N′-(3-acetamidophenyl)urea, N-(4-(6-cyano-7-benzyloxy-4-quinolyl)oxy-2-fluorophenyl)-N′-(2,4-difluorophenyl)urea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea, N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-phenylurea, 4-(4-((4-fluoroanilino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide, 7-(2-methoxyethoxy)-4-(4-((1,3-thiazol-2-ylamino)carbonyl)aminophenoxy)-6-quinolinecarboxamide, 4-(4-((anilinocarbonyl)amino)-3-fluorophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide, 4-(4-((4-fluoroanilino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, 4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide, 7-methoxy-4-(4-((1,3-thiazol-2-ylamino)carbonyl)aminophenoxy)-6-quinolinecarboxamide, 4-(4-((2,4-difluoroanilino)carbonyl)amino-3-fluorophenoxy)-7-methoxy-6-quinolinecarboxamide, 4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, 4-(5-((anilinocarbonyl)amino)-2-pyridyloxy)-7-methoxy-6-quinolinecarboxamide, 4-(4-(anilinocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, 4-(4-(anilinocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide, 4-(4-((2,4-difluoroanilino)carbonyl)amino-3-fluorophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide, 4-(4-((4-fluoroanilino)carbonyl)amino-3-fluorophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide, 7-(2-methoxyethoxy)-4-(4-((1,3-thiazol-2-ylamino)carbonyl)amino-3-fluorophenoxy)-6-quinolinecarboxamide; and 4-(4-((4-fluoroanilino)carbonyl)amino-3-fluorophenoxy)-7-methoxy-6-quinolinecarboxamide. 7. The compound according to claim 1, a pharmacologically acceptable salt or hydrate thereof, wherein said compound is a compound selected from N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N′-(4-fluorophenyl)urea, N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N′-cyclopropylurea, N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea, N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N′-(4-fluorophenyl)urea, N-{4-[6-cyano-7-(2-hydroxy-3-pyrrolidin-1-yl-propoxy)-quinolin-4-yloxy]-2-methylphenyl}-N′-cyclopropyl-urea, 4-(4-(4-fluoroanilino)carbonyl)-4-methylaminophenoxy)-7-methoxy-6-quinolinecarboxamide, 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2methoxy-6-quinolinecarboxamide, N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino) phenoxy)-7-methoxy-6-quinolinecarboxamide, N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy -6-quinolinecarboxamide, N6-(2-pyridyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide, N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide, N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide, N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide, and N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide. 8. The compound according to claim 1, a pharmacologically acceptable salt or hydrate thereof, wherein said compound is a compound selected from 4-(3-chloro-4-(cyclopropylaminocarbonyl) aminophenoxy)-7-methoxy-6-quinolinecarboxamide, 4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide, 4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, and N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-mcthoxy-6-quinolinecarboxamide. 9. A pharmaceutical composition comprising a compound according to claim 1, and a pharmaceutically acceptable carrier. 10. A pharmaceutical composition comprising a compound according to claim 1 in an amount effective to inhibit angiogenesis. 11. A compound having the formula 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt or hydrate thereof. 12. A compound having the formula 4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt or hydrate thereof. 13. A compound having the formula N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt or hydrate thereof. 14. A compound having the formula 4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt or hydrate thereof. 15. A compound having the formula N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt or hydrate thereof.