Claims for Patent: 7,601,746

Summary for Patent: 7,601,746

Title:	Compounds exhibiting thrombopoietin receptor agonism
Abstract:	A compound represented by the general formula (I): ##STR00001## wherein R.sup.1 is a hydrogen atom, a halogen atom, or the like; R.sup.2, R.sup.3, and R.sup.4 are each independently a hydrogen atom, a halogen atom, C1-C15 alkyl optionally substituted with one or more C1-C12 alkyloxy or the like, or the like; R.sup.5 is a hydrogen atom or the like; R.sup.6 and R.sup.7 are a hydrogen atom or the like; R.sup.8 is C1-C3 alkyl or the like; R.sup.9 is a hydrogen atom or the like), a prodrug, a pharmaceutically acceptable salt, or solvate thereof.
Inventor(s):	Takayama; Masami (Osaka, JP), Yoshida; Yutaka (Osaka, JP)
Assignee:	Shionogi & Co., Ltd. (Osaka, JP)
Application Number:	10/567,993
Patent Claims:	1. A compound represented by the general formula (I): ##STR00016## wherein R.sup.1 is a hydrogen atom, halogen atom, C1-C6 alkyl, or C1-C12 alkyloxy; R.sup.2, R.sup.3, and R.sup.4 are each independently a hydrogen atom, a halogen atom, C1-C15 alkyl optionally substituted with one or two substituent(s) selected from substituent group A, C2-C15 alkenyl optionally substituted with one or two substituent(s) selected from substituent group A, C2-C15 alkynyl optionally substituted with one or two substituent(s) selected from substituent group A, C3-C8 cycloalkyl, C1-C15 alkyloxy optionally substituted with one or two substituent(s) selected from substituent group A, or phenyl optionally substituted with one or two substituent(s) selected from substituent group A; R.sup.5 is a hydrogen atom, a halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy; R.sup.6 is a hydrogen atom, a halogen atom, or C1-C3 alkyl; R.sup.7 is a halogen atom or C1-C3 alkyl; R.sup.8 is a halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy; R.sup.9 is a hydrogen atom or C1-C6 alkyl; or R.sup.1 and R.sup.5 are taken together with the adjacent carbon atoms may form a 5 to 8 membered ring which may contain a heteroatom and/or an unsaturated bond, wherein the ring may be substituted with one or two C1-C8 alkyl; provided that when R.sup.2 and R.sup.3 are a chlorine atom, R.sup.6 is not a hydrogen atom; substituent group A consists of halogen atom, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, naphthyl, pyridyl, oxolanyl, cyano, C1-C12 alkyloxy, C2-C12 alkenyloxy, C2-C12 alkynyloxy, C3-C8 cycloalkyl-C1-C8 alkyloxy, phenyl-C1-C8 alkyloxy, naphthyl-C1-C8 alkyloxy, C1-C8 alkyloxy-C1-C8 alkyloxy, (C1-C8 alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy, di(C1-C8 alkyloxy)C1-C8 alkyloxy, oxolanyl-C1-C8 alkyloxy, haloC1-C8 alkyloxy, C3-C8 cycloalkyloxy, amino optionally substituted with C1-C8 alkyl, C1-C8 alkylthio, and C1-C8 alkylthio-C1-C8 alkyloxy; a pharmaceutically acceptable salt, or solvate thereof. 2. A compound of claim 1, wherein both of R.sup.6 and R.sup.7 are fluorine atom or chlorine atom, a pharmaceutically acceptable salt, or solvate thereof. 3. A compound of claim 1, wherein R.sup.5 is a hydrogen atom or C1-C3 alkyloxy, a pharmaceutically acceptable salt, or solvate thereof. 4. A compound of claim 1, wherein R.sup.8 is methyl or methyloxy, a pharmaceutically acceptable salt, or solvate thereof. 5. A compound of any one of claims 1 to 4, wherein R.sup.2 is C1-C15 alkyl optionally substituted with one or two substituent(s) selected from substituent group A, C2-C15 alkynyl optionally substituted with one or two substituent(s) selected from substituent group A, or C1-C15 alkyloxy optionally substituted with one or two substituent(s) selected from substituent group A, a pharmaceutically acceptable salt, or solvate thereof. 6. A compound of any one of claims 1 to 4, wherein R.sup.2 is C1-C12 alkyl optionally substituted with one or two C1-C8 alkyloxy, and both of R.sup.3 and R.sup.4 are a hydrogen atom, a pharmaceutically acceptable salt, or solvate thereof. 7. A compound represented by the general formula (II): ##STR00017## wherein R.sup.A is a hydrogen atom, C1-C12 alkyloxy, C1-C8 alkyloxy-C1-C8 alkyloxy or (C1-C8 alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy; R.sup.B is C1-C14 alkyl optionally substituted with one or two substituent(s) selected from substituent group B, C2-C14 alkynyl optionally substituted with one or two substituent(s) selected from substituent group B, C3-C8 cycloalkyl, C1-C14 alkyloxy optionally substituted with one or two substituent(s) selected from substituent group B, phenyl, or naphthyl; R.sup.C is a hydrogen atom, halogen atom, C1-C6 alkyl, or C1-C12 alkyloxy; R.sup.D is a hydrogen atom, halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy; R.sup.6 and R.sup.7 are each independently halogen atom or C1-C3 alkyl; R.sup.8 is halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy; substituent group B consists of halogen atom, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, naphthyl, pyridyl, oxolanyl, cyano, C1-C8 alkyloxy, C2-C8 alkenyloxy, C2-C8 alkynyloxy, C3-C8 cycloalkyl-C1-C8 alkyloxy, phenyl-C1-C8 alkyloxy, naphthyl-C1-C8 alkyloxy, C1-C8 alkyloxy-C1-C8 alkyloxy, (C1-C8 alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy, di(C1-C8 alkyloxy)C1-C8 alkyloxy, oxolanyl-C1-C8 alkyloxy, haloC1-C8 alkyloxy, C3-C8 cycloalkyloxy, amino optionally substituted with C1-C8 alkyl, C1-C8 alkylthio, and C1-C8 alkylthio-C1-C8 alkyloxy; a pharmaceutically acceptable salt, or solvate thereof. 8. A compound of claim 7, wherein both of R.sup.6 and R.sup.7 are fluorine atom or chlorine atom, a pharmaceutically acceptable salt, or solvate thereof. 9. A compound of claim 7, wherein R.sup.8 is methyl or methyloxy, a pharmaceutically acceptable salt, or solvate thereof. 10. A compound of claim 7, wherein R.sup.C is fluorine atom or C1-C3 alkyloxy, a pharmaceutically acceptable salt, or solvate thereof. 11. A compound of any one of claims 7 to 10, wherein R.sup.A is C1-C8 alkyloxy; R.sup.B is C1-C11 alkyl optionally substituted with one or two substituent(s) selected from substituent group B, or C2-C11 alkynyl optionally substituted with one or two substituent(s) selected from substituent group B, a pharmaceutically acceptable salt, or solvate thereof. 12. A compound of claim 7, wherein R.sup.C is fluorine atom or C1-C3 alkyloxy, R.sup.D is a hydrogen atom or C1-C3 alkyloxy, both of R.sup.6 and R.sup.7 are fluorine atom or chlorine atom, R.sup.8 is methyl or methyloxy, R.sup.A is C1-C3 alkyloxy, R.sup.B is C8-C12 alkyl optionally substituted with one or two substituent(s) selected from substituent group B, a pharmaceutically acceptable salt, or solvate thereof. 13. A compound represented by the general formula (II-A): ##STR00018## wherein R.sup.C is a hydrogen atom, a halogen atom, C1-C6 alkyl, or C1-C12 alkyloxy; R.sup.D is a hydrogen atom, a halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy; R.sup.F is C1-C14 alkyl optionally substituted with one or two substituent(s) selected from substituent group D, C2-C14 alkenyl optionally substituted with one or two substituent(s) selected from substituent group D, C2-C14 alkynyl optionally substituted with one or two substituent(s) selected from substituent group D, C1-C14 alkyloxy optionally substituted with one or two substituent(s) selected from substituent group C, C3-C8 cycloalkyl, or phenyl optionally substituted with one or two substituent(s) selected from substituent group D; R.sup.6 and R.sup.7 are each independently halogen atom or C1-C3 alkyl; R.sup.8 is halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy; substituent group D consists of halogen atom, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, naphthyl, pyridyl, oxolanyl, cyano, C1-C8 alkyloxy, C2-C8 alkenyloxy, C2-C8 alkynyloxy, C3-C8 cycloalkyl-C1-C8 alkyloxy, phenyl-C1-C8 alkyloxy, naphthyl-C1-C8 alkyloxy, C1-C8 alkyloxy-C1-C8 alkyloxy, (C1-C8 alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy, di(C1-C8 alkyloxy)C1-C8 alkyloxy, oxolanyl-C1-C8 alkyloxy, haloC1-C8 alkyloxy, C3-C8 cycloalkyloxy, amino optionally substituted with C1-C8 alkyl, C1-C8 alkylthio, and C1-C8 alkylthio-C1-C8 alkyloxy; a pharmaceutically acceptable salt, or solvate thereof. 14. A compound of claim 13, wherein both of R.sup.6 and R.sup.7 are fluorine atom or chlorine atom, a pharmaceutically acceptable salt, or solvate thereof. 15. A compound of claim 13, wherein R.sup.8 is methyl or methyloxy, a pharmaceutically acceptable salt, or solvate thereof. 16. A compound of claim 13, wherein R.sup.C is fluorine atom or C1-C3 alkyloxy, a pharmaceutically acceptable salt, or solvate thereof. 17. A compound of any one of claims 13 to 16, wherein R.sup.F is C1-C14 alkyl optionally substituted with one or two substituent(s) selected from substituent group D, C2-C14 alkynyl optionally substituted with one or two substituent(s) selected from substituent group D, or C1-C14 alkyloxy optionally substituted with one or two substituent(s) selected from substituent group D, a pharmaceutically acceptable salt, or solvate thereof. 18. A pharmaceutical composition containing a compound as an active ingredient, a pharmaceutically acceptable salt, or solvate thereof of any one of claims 1 to 4, 7 to 10, or 13 to 16. 19. A pharmaceutical composition containing a compound as an active ingredient, a pharmaceutically acceptable salt, or solvate thereof of any one of claims 1 to 4, 7 to 10, or 13 to 16 in an amount effective for exhibiting thrombopoietin receptor agonism. 20. A pharmaceutical composition containing a compound as an active ingredient, a pharmaceutically acceptable salt, or solvate thereof of any one of claims 1 to 4, 7 to 10, or 13 to 16 in an amount effective for modifying platelet production. 21. A method for treating or preventing hemopathy in a mammal, including a human, in need thereof, comprising administering to said mammal a compound, a pharmaceutically acceptable salt, or solvate thereof of any one of claims 1 to 4, 7 to 10, or 13 to 16 in an amount effective amount for modifying platelet production. 22. A compound of claim 1, wherein the compound is ##STR00019## or a pharmaceutically acceptable saft thereof. 23. A compound of claim 1, wherein the compound is ##STR00020## or a pharmaceutically acceptable salt thereof. 24. A compound of claim 1, wherein the compound is ##STR00021## or a pharmaceutically acceptable salt thereof.