Quinoline derivatives and quinazoline derivatives inhibiting autophosphorylation of macrophage colony stimulating factor receptor

A compound of formula (Ic) or a pharmaceutically acceptable salt thereof:

• wherein
• R41 represents a hydrogen atom, a fluorine atom at 2-position, a fluorine atom at 3-position, a chlorine atom at 2-position, a chlorine atom at 3-position, methyl at 2- and 3-positions, methyl at 2- and 5-positions, methoxy at 2-position, methoxy at 3-position, methyl at 2-position, or trifluoromethyl at 2-position,
• R42 represents methyl,
• R43 represents a fluorine atom at 4-position, a bromine atom at 3-position, a bromine atom at 4-position, methoxy at 2-position, methoxy at 3-position, methoxy at 4-position, a chlorine atom at 4-position, methyl at 4-position, or nitro at 4-position.

A compound of formula (Id) or a pharmaceutically acceptable salt thereof:

• wherein
• X represents CH or N,
• R51 represents a hydrogen atom, a fluorine atom at 2-position, a fluorine atom at 3-position, methoxy at 2-position, methoxy at 3-position, or methyl at 2- and 5-positions,
• R52 represents methyl,
• R53 represents imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, or isothiazolyl in which one or two hydrogen atoms on the groups are optionally substituted by a halogen atom or C1-4 alkyl, and
• R54 and R55 which may be the same or different, represent a hydrogen atom or C1-6 alkyl in which the alkyl group is optionally substituted by hydroxyl;
• a halogen atom;
• —OR wherein R56 represents C1-4 alkyl;
• —NR57R58 wherein R57 and R58, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl or —OR59 wherein R59 represents C1-4 alkyl;
• or a saturated or unsaturated three- to seven-membered carbocyclic or heterocyclic group in which the carbocyclic and heterocyclic groups are optionally substituted by one or two halogen atoms or C1-4 alkyl.

A compound of formula (Ie) or a pharmaceutically acceptable salt ef-sel*ate thereof:

• wherein
• R601 represents a hydrogen atom, a fluorine atom at 2-position, a fluorine atom at 3-position, a chlorine atom at 2-position, a chlorine atom at 3-position, methyl at 2- and 3-positions, methyl at 2- and 5-positions, methoxy at 2-position, methoxy at 3-position, methyl at 2-position, or trifluoromethyl at 2-position,
• R602 represents methyl,
• X represents N or CH,
• R604 and R605, which may be the same or different, represent a hydrogen atom or C1-6 alkyl in which the alkyl group is optionally substituted by hydroxyl;
• a halogen atom;
• —OR606 wherein R606 represents C1-4 alkyl;
• —NR607R608 , wherein R607 and R608, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl or —OR609 wherein R609 represents C1-4 alkyl;
• or a saturated or unsaturated three- to seven-membered carbocyclic or heterocyclic group in which the carbocyclic and heterocyclic groups are optionally substituted by one or two halogen atoms or C1-4 alkyl, and
• R611, R612, R613, R614, and R615, which may be the same or different, represent a hydrogen atom;
• C1-6 alkyl;
• —OR616 wherein R616 represents C1-4 alkyl;
• a halogen atom;
• nitro;
• or —NNR617R618 wherein R617 and R618, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl, —OR619 wherein R619 represents C1-4 alkyl or NR620R621 wherein R620 and R621, which may be the same or different, represent a hydrogen atom or C1-4 alkyl.

A compound of formula (If) or a pharmaceutically acceptable salt thereof:

• wherein
• X represents CH or N,
• R701 represents a hydrogen atom, a fluorine atom at 2-position, a fluorine atom at 3-position, methoxy at 2-position, methoxy at 3-position, or methyl at 2- and 5-positions,
• R702 represents C1-4 alkyl,
• R703 represents imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, or isothiazolyl in which one or two hydrogen atoms on the groups are optionally substituted by a halogen atom or C1-4 alkyl, and
• R704 and R705, which may be the same or different, represent a hydrogen atom;
• hydroxyl;
• nitro;
• cyano;
• a halogen atom;
• —NR706R707 wherein R706 and R707, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl, OR708 wherein R708 represents C1-4 alkyl, or —NR709R710 wherein R709 and R710, which may be the same or different, represent a hydrogen atom or alkyl;
• CONR711R712 wherein R711 and R712, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl, —OR713 wherein R713 represents C1-4 or —NR714R715 wherein R714andR715,which may be the same or different, represent a hydrogen atom or C1-4 alkyl;
• COOR716 wherein R716 represents a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl, —OR717 wherein R717 represents C1-4 alkyl, or —NR718R719 wherein R718 and R719, which may be the same or different, represent a hydrogen atom or C1-4 alkyl;
• C1-6 alkyl;
• C2-6 alkenyl;
• C2-6 alkynyl;
• or C1-6 alkoxy, in which the alkyl, alkenyl, alkynyl, and alkoxy groups are optionally substituted by hydroxyl, a halogen atom, —OR720 in which R720 represents C1-4 alkyl, —NR721R722 wherein R721 and R722, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl or —OR723 wherein R723 represents C1-4 alkyl, or a saturated or unsaturated three- to seven-membered carbocyclic or heterocyclic group in which the carbocyclic and heterocyclic groups are optionally substituted by one or two halogen atoms or C1-4 alkyl.

A compound of formula (Ig) or a pharmaceutically acceptable salt thereof:

• wherein
• X represents CH or N,
• R801 represents a hydrogen atom, a fluorine atom at 2-position, a fluorine atom at 3-position, a chlorine atom at 2-position, a chlorine atom at 3-position, methyl at 2- and 3-positions, methyl at 2- and 5-positions, methoxy at 2-position, methoxy at 3-position, methyl at 2-position, or trifluoromethyl at 2-position,
• R802 represents C1-4 alkyl,
• R804 and R805, which may be the same or different, represent a hydrogen atom;
• hydroxyl;
• nitro;
• cyano;
• a halogen atom;
• —NR806R807 wherein R806 and R807, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl, —OR808 wherein R808 represents C1-4 alkyl, or NR809R810 wherein R809 and R810, which may be the same or different, represent a hydrogen atom or alkyl;
• CONR R811R810 wherein R811 and R812, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl, —OR813 wherein R813 represents C1-4 alkyl, or —NR814R815 wherein R814 and R815, which may be the same or different, represent a hydrogen atom or C1-4 alkyl;
• —OOR 6 wherein R816 represents a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl, —OR817 wherein R817 represents C1-4 alkyl, or —NR818R819 wherein R818 and R819, which may be the same or different, represent a hydrogen atom or C1-4 alkyl;
• C1-6 alkyl;
• C2-6 alkenyl;
• C2-6 alkynyl;
• or C1-6 alkoxy, in which the alkyl, alkenyl, alkynyl, and alkoxy groups are optionally substituted by hydroxyl, a halogen atom, —OR820 in which R820 represents C1-4 alkyl, —NR821 R822 wherein R821 and R822, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl or —OR823 wherein R823 represents C1-4 alkyl, or a saturated or unsaturated three- to seven-membered carbocyclic or heterocyclic group in which the carbocyclic and heterocyclic groups are optionally substituted by one or two halogen atoms or C1-4 alkyl, and
• R831, R832, R833, R834, and R835, which may be the same or different, represent a hydrogen atom;
• hydroxyl;
• C1-6 alkyl;
• R836 wherein R836 represents C1-4 alkyl;
• a halogen atom;
• nitro;
• or —NR837 R838 wherein R837 and R838, which maybe the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl, —OR839 wherein R839 represents C1-4 alkyl, or —NR840R841 wherein R831, and R832, which may be the same or different, represent a hydrogen atom or C1-4 alkyl.

A method for treating osteoporosis or bone metastasis of a malignant tumor-comprising:

• administering a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof to a mammal in need thereof,
• wherein formula I is:
• wherein
• X represents CH or N;
• Z represents O or S;
• R1, R2, and R3, which may be the same or different, represent a hydrogen atom;
• a halogen atom;
• hydroxyl;
• cyano;
• C1-6 alkyl;
• C1-6 alkoxy;
• C2-6 alkenyl;
• C2-6 alkynyl;
• nitro;
• —NR106R107 wherein R106 and R107, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl, —OR108 wherein R108 represents C1-4 alkyl, or —NR109R110 wherein R109 and R110, which may be the same or different, represent a hydrogen atom or C1-4 alkyl;
• —CONR111R112 wherein R111 and R112, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl, —OR113 wherein R113 represents C1-4 alkyl, or —NR114R115 wherein R114 and R115, which maybe the same or different, represent a hydrogen atom or C1-4 alkyl;
• or —COOR116 wherein R116 represents a hydrogen atom or alkyl in which the alkyl group is optionally substituted by hydroxyl, —OR117 wherein R117 represents C1-4 alkyl, or —NR118R119 wherein R118 and R119, which maybe the same or different, represent a hydrogen atom or C1-4 alkyl in which the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, and C2-6 alkynyl groups are optionally substituted by a halogen atom;
• hydroxyl;
• C1-4 alkyl;
• C1-4 alkoxy;
• C1-4 alkoxycarbonyl;
• amino in which one or two hydrogen atoms on the amino group each are optionally substituted by C1-4 alkyl optionally substituted by hydroxyl or C1-4 alkoxy;
• group R15R16N—C(═O)—O— wherein R15 and R16, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl or C1-4 alkoxy;
• or group R17—(S)m— wherein R17 represents a saturated or unsaturated three- to seven-membered carbocyclic or heterocyclic group optionally substituted by a halogen atom or C1-4 alkyl and m is 0 (zero) or 1,
• R4 represents a hydrogen atom,
• R5, R6, R7, and R8, which may be the same or different, represent a hydrogen atom, a halogen atom, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, trifluoromethyl, nitro, or amino,
• R19 and R0, which may be the same or different, represent a hydrogen atom, C1-6 alkyl, or C1-4 alkylcarbonyl, and
• any one of R11 and R12 represents a hydrogen atom while the other represents C1-4 alkyl, and R13 represents a saturated or unsaturated three- to seven-membered carbocyclic or heterocyclic group or a saturated or unsaturated nine- to twelve-membered bicylic carbocyclic group in which the carbocyclic and heterocyclic groups are optionally substituted by a halogen atom;
• hydroxyl;
• C1-4 alkyl;
• C1-4 alkoxy;
• C1-4 alkylthio;
• trifluoromethyl;
• nitro;
• or —NR137R138 wherein R137 and R138, which may be the same or different, represent a hydrogen atom or C1-4 alkyl in which the alkyl group is optionally substituted by hydroxyl, —OR139 wherein R139 represents C1-4 alkyl, or —NR140R141 wherein R140 and R141, which may be the same or different, represent a hydrogen atom or C1-4 alkyl, or
• R11 represents a hydrogen atom, and R12 and R13 may combine with a carbon atom attached thereto to form a saturated or unsaturated nine- to twelve-membered bicyclic carbocyclic group.