	US 7,612,092 B2
	Nitrogen-containing aromatic derivatives
Yasuhiro Funahashi, Nagoya (Japan); Akihiko Tsuruoka, Tsukuba (Japan); Masayuki Matsukura, Tsukuba (Japan); Toru Haneda, Ushiku (Japan); Yoshio Fukuda, Tsukuba (Japan); Junichi Kamata, Tsukuba (Japan); Keiko Takahashi, Ushiku (Japan); Tomohiro Matsushima, Ushiku (Japan); Kazuki Miyazaki, Tsukuba (Japan); Ken-ichi Nomoto, Tsukuba (Japan); Tatsuo Watanabe, Inzai (Japan); Hiroshi Obaishi, Tsukuba (Japan); Atsumi Yamaguchi, Tsukuba (Japan); Sachi Suzuki, Tsuchiura (Japan); Katsuji Nakamura, Tsukuba (Japan); Fusayo Mimura, Tsukuba (Japan); Yuji Yamamoto, Tsukuba (Japan); and Junji Matsui, Toride (Japan)
Assigned to Eisai R & D Management Co., Ltd., Tokyo (Japan)
Filed on Dec. 02, 2005, as Appl. No. 11/293,785.
Application 11/293785 is a division of application No. 10/420466, filed on Apr. 18, 2003, granted, now 7,253,286.
Application 10/420466 is a continuation in part of application No. PCT/JP01/09221, filed on Oct. 19, 2001.
Claims priority of application No. 2000-320420 (JP), filed on Oct. 20, 2000; application No. 2000-386195 (JP), filed on Dec. 20, 2000; and application No. 2001-046685 (JP), filed on Feb. 22, 2001.
Prior Publication US 2006/0247259 A1, Nov. 02, 2006
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/47 (2006.01)

U.S. Cl. 514—312 [546/153; 546/155]

18 Claims

1. A method of treating cancer comprising administering a compound represented by the formula:

or a pharmacologically acceptable salt thereof;

wherein:

R¹and R²are each independently a hydrogen atom, an optionally substituted C_1-6alkyl group, an optionally substituted C_2-6alkenyl group, an optionally substituted C_2-6alkynyl group, an optionally substituted C_3-8alicyclic hydrocarbon group, an optionally substituted C_2-7acyl group or an optionally substituted C_2-7alkoxycarbonyl group;

Z¹²is a hydrogen atom, an optionally substituted C_1-6alkyl group, an optionally substituted C_2-6alkenyl group, an optionally substituted C_2-6alkynyl group, an optionally substituted C_3-8alicyclic hydrocarbon group, an optionally substituted C_6-14aryl 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, Z³³and Z³⁴are each independently a methylene group, —CO—, —NH— or —O—, and Z³²is a single bond, a methylene group, —CO—, —NH— or —O—; and

wherein Z¹²is not pyrazolyl;

Y^a1is a group represented by the formula:

wherein W³¹and W³²are each independently an optionally substituted carbon atom or a nitrogen atom;

R³⁰⁰and R³⁰¹are each independently a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C_1-6alkyl group, an optionally substituted C_3-8alicyclic hydrocarbon group, an optionally substituted C_1-6alkoxy group, an optionally substituted C_2-7alkoxycarbonyl group, a formyl group, a group represented by the formula

wherein V³⁰⁰and V³⁰¹are each independently a hydrogen atom or an optionally substituted C_1-6alkyl group, or an optionally substituted C_2-7acyl group;

R^a11is a group represented by the formula —V^a21—V^a22—V^a23, wherein:

V^a21is an optionally substituted C_1-6alkylene group, a single bond or a group represented by the formula:

V^a22is a single bond, an oxygen atom, a sulfur atom, —CO—, —SO—, —SO₂—, —CONR^a14—, —SO₂NR^a14—, —NR^a14SO₂—, —NR^a14CO— or —NR^a14—;

wherein R^a14is a hydrogen atom, an optionally substituted C_1-6alkyl group or an optionally substituted C_3-8alicyclic hydrocarbon group; and

V^a23is a hydrogen atom, an optionally substituted C_1-6alkyl group, an optionally substituted C_2-6alkenyl group, an optionally substituted C_2-6alkynyl group, an optionally substituted C_3-8alicyclic hydrocarbon group, an optionally substituted C_6-14aryl group, an optionally substituted 5- to 14-membered heterocyclic group or an optionally substituted 5- to 14-membered aromatic heterocyclic group; and

R^a12is a cyano group or a group represented by the formula:

wherein:

V^a11is —CO— or —SO₂—; and

V^a12, V^a13and V^a14are each independently a hydrogen atom, an optionally substituted C_1-6alkyl group, an optionally substituted C_2-6alkenyl group, an optionally substituted C_2-6alkynyl group, an optionally substituted C_3-8alicyclic hydrocarbon group, an optionally substituted C_6-14aryl 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^a12is a group represented by the formula:

wherein:

V^a12and V^a13are each independently a hydrogen atom, an optionally substituted C_1-6alkyl group, an optionally substituted C_2-6alkenyl group, an optionally substituted C_2-6alkynyl group, an optionally substituted C_3-8alicyclic hydrocarbon group, an optionally substituted C_6-14aryl group, an optionally substituted 5- to 14-membered heterocyclic group or an optionally substituted 5- to 14-membered aromatic heterocyclic group;

R¹and R²are hydrogen atoms; and

Z¹²is a C_6-14aryl group, a 6- to 14-membered heterocyclic group or a 6- to 14-membered aromatic heterocyclic group; or

(2) a compound wherein R^a12is a group selected from the group consisting of the formulae:

wherein:

V^a11is —CO— or —SO₂—;

R²is a hydrogen atom; and

Z¹²is (a) a C_6-14aryl group, (b) a 5- to 14-membered heterocyclic group, (c) a 5- to 14-membered aromatic heterocyclic group, (d) a C_1-6alkyl group substituted with a 5- to 10-membered heterocyclic group or a C_5-10alicyclic hydrocarbon group, (e) a C_2-6alkenyl group substituted with a 5- to 10-membered heterocyclic group or a C_5-10alicyclic hydrocarbon group, (f) a C_2-6alkynyl group substituted with a 5- to 10-membered heterocyclic group or a C_5-10alicyclic hydrocarbon group, or (g) a C_3-8alicyclic hydrocarbon group substituted with a 5- to 10-membered heterocyclic group or a C_5-10alicyclic hydrocarbon group,

or a pharmacologically acceptable salt thereof.