Details for Patent: 7,612,092

Title:	Nitrogen-containing aromatic derivatives
Abstract:	Compounds represented by the following general formula: ##STR00001## [wherein A.sup.g is an optionally substituted 5- to 14-membered heterocyclic group, etc.; X.sup.g is --O--, --S--, etc.; Y.sup.g is an optionally substituted C.sub.6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group, etc.; and T.sup.g1 is a group represented by the following general formula: ##STR00002## (wherein E.sup.g is a single bond or --N(R.sup.g2)--, R.sup.g1 and R.sup.g2 each independently represent a hydrogen atom, an optionally substituted C.sub.1-6 alkyl group, etc. and Z.sup.g represents a C.sub.1-8 alkyl group, a C.sub.3-8 alicyclic hydrocarbon group, a C.sub.6-14 aryl group, etc.)], salts thereof or hydrates of the foregoing.
Inventor(s):	Funahashi; Yasuhiro (Nagoya, JP), Tsuruoka; Akihiko (Tsukuba, JP), Matsukura; Masayuki (Tsukuba, JP), Haneda; Toru (Ushiku, JP), Fukuda; Yoshio (Tsukuba, JP), Kamata; Junichi (Tsukuba, JP), Takahashi; Keiko (Ushiku, JP), Matsushima; Tomohiro (Ushiku, JP), Miyazaki; Kazuki (Tsukuba, JP), Nomoto; Ken-ichi (Tsukuba, JP), Watanabe; Tatsuo (Inzai, JP), Obaishi; Hiroshi (Tsukuba, JP), Yamaguchi; Atsumi (Tsukuba, JP), Suzuki; Sachi (Tsuchiura, JP), Nakamura; Katsuji (Tsukuba, JP), Mimura; Fusayo (Tsukuba, JP), Yamamoto; Yuji (Tsukuba, JP), Matsui; Junji (Toride, JP)
Assignee:	Eisai R & D Management Co., Ltd. (Tokyo, JP)
Filing Date:	Dec 02, 2005
Application Number:	11/293,785
Claims:	1. A method of treating cancer comprising administering a compound represented by the formula: ##STR01211## or a pharmacologically acceptable salt thereof; wherein: R.sup.1 and R.sup.2 are each independently a hydrogen atom, an optionally substituted C.sub.1-6 alkyl group, an optionally substituted C.sub.2-6 alkenyl group, an optionally substituted C.sub.2-6 alkynyl group, an optionally substituted C.sub.3-8 alicyclic hydrocarbon group, an optionally substituted C.sub.2-7 acyl group or an optionally substituted C.sub.2-7 alkoxycarbonyl group; Z.sup.12 is a hydrogen atom, an optionally substituted C.sub.1-6 alkyl group, an optionally substituted C.sub.2-6 alkenyl group, an optionally substituted C.sub.2-6 alkynyl group, an optionally substituted C.sub.3-8 alicyclic hydrocarbon group, an optionally substituted C.sub.6-14 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: ##STR01212## wherein Z.sup.31, Z.sup.33 and Z.sup.34 are each independently a methylene group, --CO--, --NH-- or --O--, and Z.sup.32 is a single bond, a methylene group, --CO--, --NH-- or --O--; and wherein Z.sup.12 is not pyrazolyl; Y.sup.a1 is a group represented by the formula: ##STR01213## wherein W.sup.31 and W.sup.32 are each independently an optionally substituted carbon atom or a nitrogen atom; R.sup.300 and R.sup.301 are each independently a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C.sub.1-6 alkyl group, an optionally substituted C.sub.3-8 alicyclic hydrocarbon group, an optionally substituted C.sub.1-6 alkoxy group, an optionally substituted C.sub.2-7 alkoxycarbonyl group, a formyl group, a group represented by the formula ##STR01214## wherein V.sup.300 and V.sup.301 are each independently a hydrogen atom or an optionally substituted C.sub.1-6 alkyl group, or an optionally substituted C.sub.2-7 acyl group; R.sup.a11 is a group represented by the formula --V.sup.a21--V.sup.a22--V.sup.a23, wherein: V.sup.a21 is an optionally substituted C.sub.1-6 alkylene group, a single bond or a group represented by the formula: ##STR01215## V.sup.a22 is a single bond, an oxygen atom, a sulfur atom, --CO--, --SO--, --SO.sub.2--, --CONR.sup.a14--, --SO.sub.2NR.sup.a14--, --NR.sup.a14SO.sub.2--, --NR.sup.a14CO-- or --NR.sup.a14--; wherein R.sup.a14 is a hydrogen atom, an optionally substituted C.sub.1-6 alkyl group or an optionally substituted C.sub.3-8 alicyclic hydrocarbon group; and V.sup.a23 is a hydrogen atom, an optionally substituted C.sub.1-6 alkyl group, an optionally substituted C.sub.2-6 alkenyl group, an optionally substituted C.sub.2-6 alkynyl group, an optionally substituted C.sub.3-8 alicyclic hydrocarbon group, an optionally substituted C.sub.6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group or an optionally substituted 5- to 14-membered aromatic heterocyclic group; and R.sup.a12 is a cyano group or a group represented by the formula: ##STR01216## wherein: V.sup.a11 is --CO-- or --SO.sub.2--; and V.sup.a12, V.sup.a13 and V.sup.a14 are each independently a hydrogen atom, an optionally substituted C.sub.1-6 alkyl group, an optionally substituted C.sub.2-6 alkenyl group, an optionally substituted C.sub.2-6 alkynyl group, an optionally substituted C.sub.3-8 alicyclic hydrocarbon group, an optionally substituted C.sub.6-14 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 that the compound is not: (1) a compound wherein R.sup.a12 is a group represented by the formula: ##STR01217## wherein: V.sup.a12 and V.sup.a13 are each independently a hydrogen atom, an optionally substituted C.sub.1-6 alkyl group, an optionally substituted C.sub.2-6 alkenyl group, an optionally substituted C.sub.2-6 alkynyl group, an optionally substituted C.sub.3-8 alicyclic hydrocarbon group, an optionally substituted C.sub.6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group or an optionally substituted 5- to 14-membered aromatic heterocyclic group; R.sup.1 and R.sup.2 are hydrogen atoms; and Z.sup.12 is a C.sub.6-14 aryl group, a 6- to 14-membered heterocyclic group or a 6- to 14-membered aromatic heterocyclic group; or (2) a compound wherein R.sup.a12 is a group selected from the group consisting of the formulae: ##STR01218## wherein: V.sup.a11 is --CO-- or --SO.sub.2--; V.sup.a12, V.sup.a13 and V.sup.a14 are each independently a hydrogen atom, an optionally substituted C.sub.1-6 alkyl group, an optionally substituted C.sub.2-6 alkenyl group, an optionally substituted C.sub.2-6 alkynyl group, an optionally substituted C.sub.3-8 alicyclic hydrocarbon group, an optionally substituted C.sub.6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group or an optionally substituted 5- to 14-membered aromatic heterocyclic group; R.sup.2 is a hydrogen atom; and Z.sup.12 is (a) a C.sub.6-14 aryl group, (b) a 5- to 14-membered heterocyclic group, (c) a 5- to 14-membered aromatic heterocyclic group, (d) a C.sub.1-6 alkyl group substituted with a 5- to 10-membered heterocyclic group or a C.sub.5-10 alicyclic hydrocarbon group, (e) a C.sub.2-6 alkenyl group substituted with a 5- to 10-membered heterocyclic group or a C.sub.5-10 alicyclic hydrocarbon group, (f) a C.sub.2-6 alkynyl group substituted with a 5- to 10-membered heterocyclic group or a C.sub.5-10 alicyclic hydrocarbon group, or (g) a C.sub.3-8 alicyclic hydrocarbon group substituted with a 5- to 10-membered heterocyclic group or a C.sub.5-10 alicyclic hydrocarbon group, or a pharmacologically acceptable salt thereof. 2. The method according to claim 1, wherein R.sup.a11 is a methyl group, a 2-methoxyethyl group or a group represented by the formula: ##STR01219## wherein: R.sup.a53 is a methyl group, a cyclopropylmethyl group or a cyanomethyl group; R.sup.51 is a hydrogen atom, a fluorine atom or a hydroxyl group; and R.sup.a52 is a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinyl group, a dimethylamino group or a diethylamino group. 3. The method according to claim 1, wherein Z.sup.12 is a methyl group, an ethyl group, a cyclopropyl group, a 2-thiazolyl group or a 4-fluorophenyl group. 4. The method according to claim 1, wherein Y.sup.a1 is a group represented by the formula: ##STR01220## wherein R.sup.a61 is a hydrogen atom, a methyl group, a trifluoromethyl group, a chlorine atom or a fluorine atom. 5. The method according to claim 1, wherein R.sup.a12 is a cyano group or a group represented by the formula --CONHR.sup.a62, wherein R.sup.a62 is a hydrogen atom, an optionally substituted C.sub.1-6 alkyl group, an optionally substituted C.sub.3-8 alicyclic hydrocarbon group, an optionally substituted C.sub.1-6 alkoxy group or an optionally substituted C.sub.3-8 cycloalkoxy group. 6. The method according to claim 1, wherein the compound is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinoli- necarboxamide, or a pharmacologically acceptable salt thereof. 7. The method according to claim 1, wherein the compound is 4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarb- oxamide, or a pharmacologically acceptable salt thereof. 8. The method according to claim 1, wherein the compound is N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-me- thoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof. 9. The method according to claim 1, wherein the compound is N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-- 6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof. 10. The method according to claim 1, wherein cancer is pancreatic cancer, gastric cancer, colon cancer, breast cancer, prostate cancer, lung cancer, renal cancer, brain tumor, blood cancer or ovarian cancer. 11. The method according to claim 10, wherein R.sup.a11 is a methyl group, a 2-methoxyethyl group or a group represented by the formula: ##STR01221## wherein: R.sup.a53 is a methyl group, a cyclopropylmethyl group or a cyanomethyl group; R.sup.a51 is a hydrogen atom, a fluorine atom or a hydroxyl group; and R.sup.a52 is a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinyl group, a dimethylamino group or a diethylamino group. 12. The method according to claim 10, wherein Z.sup.12 is a methyl group, an ethyl group, a cyclopropyl group, a 2-thiazolyl group or a 4-fluorophenyl group. 13. The method according to claim 10, wherein Y.sup.a1 is a group represented by the formula: ##STR01222## wherein R.sup.a61 is a hydrogen atom, a methyl group, a trifluoromethyl group, a chlorine atom or a fluorine atom. 14. The method according to claim 10, wherein R.sup.a12 is a cyano group or a group represented by the formula --CONHR.sup.a62, wherein R.sup.a62 is a hydrogen atom, an optionally substituted C.sub.1-6 alkyl group, an optionally substituted C.sub.3-8 alicyclic hydrocarbon group, an optionally substituted C.sub.1-6 alkoxy group or an optionally substituted C.sub.3-8 cycloalkoxy group. 15. The method according to claim 10, wherein the compound is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinoli- necarboxamide, or a pharmacologically acceptable salt thereof. 16. The method according to claim 10, wherein the compound is 4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarb- oxamide, or a pharmacologically acceptable salt thereof. 17. The method according to claim 10, wherein the compound is N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-me- thoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof. 18. The method according to claim 10, wherein the compound is N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-- 6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof.