Claims for Patent: 8,268,848

Summary for Patent: 8,268,848

Title:	Cyclopropane compound
Abstract:	A cyclopropane compound represented by the following formula (A) or a pharmaceutically acceptable salt thereof has orexin receptor antagonism, and therefore has a potencial of usefulness for the treatment of sleep disorder for which orexin receptor antagonism is effective, for example, insomnia: ##STR00001## wherein Q represents --CH-- or a nitrogen atom, R.sub.1a and R.sub.1b each independently represent a C.sub.1-6 alkyl group and the like, R.sub.1c represents a hydrogen atom and the like, R.sub.2a, R.sub.2b, R.sub.2c and R.sub.2d each independently represent a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group and the like, R.sub.3a, R.sub.3b and R.sub.3c each independently represent a hydrogen atom, a halogen atom and the like, and R.sub.3d represents a hydrogen atom and the like.
Inventor(s):	Terauchi; Taro (Tsukuba, JP), Takemura; Ayumi (Tsukuba, JP), Doko; Takashi (Tokyo, JP), Yoshida; Yu (Tsukuba, JP), Tanaka; Toshiaki (Tsukuba, JP), Sorimachi; Keiichi (Tsukuba, JP), Naoe; Yoshimitsu (Tsukuba, JP), Beuckmann; Carsten (Tsukuba, JP), Kazuta; Yuji (Tsukuba, JP)
Assignee:	Eisai R&D Management Co., Ltd. (Tokyo, JP)
Application Number:	13/237,205
Patent Claims:	1. A compound represented by the following formula (A) or a pharmaceutically acceptable salt thereof: ##STR00429## wherein Q represents --CH-- or a nitrogen atom, when Q represents --CH--, R.sub.1a and R.sub.1b each independently represent a C.sub.1-6 alkyl group, a halo-C.sub.1-6 alkyl group or a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, R.sub.1c represents a hydrogen atom, R.sub.2a, R.sub.2b, R.sub.2c and R.sub.2d each independently represent a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group or a halo-C.sub.1-6 alkyl group, R.sub.3a and R.sub.3c each independently represent a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a halo-C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group, a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, a cyano group or a cyano-C.sub.1-6 alkyl group, R.sub.3b represents a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a halo-C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group or a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, and R.sub.3d represents a hydrogen atom or a fluorine atom, or when Q represents a nitrogen atom, R.sub.1a and R.sub.1b each independently represent a C.sub.1-6 alkyl group, a halo-C.sub.1-6 alkyl group, a hydroxy-C.sub.1-6 alkyl group or a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, R.sub.1c represents a hydrogen atom or a hydroxyl group, R.sub.2a, R.sub.2b, R.sub.2c and R.sub.2d each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group or a halo-C.sub.1-6 alkyl group, R.sub.3a represents a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group or a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, R.sub.3b represents a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group or a halo-C.sub.1-6 alkyl group, R.sub.3c represents a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a halo-C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group, or a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, and R.sub.3d represents a hydrogen atom. 2. The compound according to claim 1, which is represented by the following formula (B), or a pharmaceutically acceptable salt thereof: ##STR00430## wherein R.sub.1a and R.sub.1b each independently represent a C.sub.1-6 alkyl group, a halo-C.sub.1-6 alkyl group or a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, R.sub.1c represents a hydrogen atom, R.sub.2a, R.sub.2b, R.sub.2c and R.sub.2d each independently represent a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group or a halo-C.sub.1-6 alkyl group, R.sub.3a and R.sub.3c each independently represent a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a halo-C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group, a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, a cyano group or a cyano-C.sub.1-6 alkyl group, R.sub.3b represents a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a halo-C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group or a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, and R.sub.3d represents a hydrogen atom or a fluorine atom. 3. The compound according to claim 1, which is represented by the following formula (C), or a pharmaceutically acceptable salt thereof: ##STR00431## wherein R.sub.1a represents a C.sub.1-6 alkyl group or a hydroxy-C.sub.1-6 alkyl group, R.sub.1b represents a C.sub.1-6 alkyl group, a halo-C.sub.1-6 alkyl group, a hydroxy-C.sub.1-6 alkyl group or a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, R.sub.1c represents a hydrogen atom or a hydroxyl group, R.sub.2a, R.sub.2b, R.sub.2c and R.sub.2d each independently represent a hydrogen atom, a halogen atom, a hydroxyl group, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group or a halo-C.sub.1-6 alkyl group, R.sub.3a represents a substituent selected from a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group and a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, R.sub.3b represents a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group or a halo-C.sub.1-6 alkyl group, R.sub.3c represents a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a halo-C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group or a C.sub.1-6 alkoxy-C.sub.1-6 alkyl group, and R.sub.3d represents a hydrogen atom. 4. The compound according to claim 3, or a pharmaceutically acceptable salt thereof, wherein R.sub.1a represents a methyl group, R.sub.1b represents a methyl group, an ethyl group, a hydroxymethyl group, a methoxymethyl group or a methoxyethyl group, and R.sub.1c represents a hydrogen atom. 5. A compound, which is selected from the following compounds, or a pharmaceutically acceptable salt thereof: 1) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoropyridin-2-- yl)-2-phenylcyclopropanecarboxamide, 2) (1R,2S)-N-(5-chloropyridin-2-yl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]meth- yl}-2-phenylcyclopropanecarboxamide, 3) (1R,2S)-N-[3-(dimethylamino)phenyl]-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]m- ethyl}-2-phenylcyclopropanecarboxamide, 4) (1R,2S)-N-(3-chlorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2p- henylcyclopropanecarboxamide, 5) (1R,2S)-N-(3-cyano-4-fluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]me- thyl}-2-phenylcyclopropanecarboxamide, 6) (1R,2S)-N-(3-chloro-4-fluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]m- ethyl}-2-phenylcyclopropanecarboxamide, 7) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(3-methoxyphenyl)-2- -phenylcyclopropanecarboxamide, 8) (1R,2S)-N-[3-(cyanomethyl)phenyl]-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]met- hyl}-2-phenylcyclopropanecarboxamide, 9) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-phenyl-N-[3-(triflu- oromethyl)phenyl]cyclopropanecarboxamide, 10) (1R,2S)-N-(5-chloro-4-methylpyridin-2-yl)-2-{[(2,4-dimethylpyrimidin-5-yl- )oxy]methyl}-2-phenylcyclopropanecarboxamide, 11) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methylp- yridin-2-yl)-2-phenylcyclopropanecarboxamide, 12) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-[5-fluoro-4-(methox- ymethyl)pyridin-2-yl]-2-phenylcyclopropanecarboxamide, 13) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methoxy- pyridin-2-yl)-2-phenylcyclopropanecarboxamide, 14) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methylp- yridin-2-yl) -2-(3-fluorophenyl)cyclopropanecarboxamide, 15) (1R,2S)-N-(3,4-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-2-(3-fluorophenyl)cyclopropanecarboxamide, 16) (1R,2S)-N-(4-chloropyridin-2-yl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]meth- yl}-2-(3-fluorophenyl)cyclopropanecarboxamide, 17) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methoxy- methylpyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide, 18) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-- (4-fluorophenyl)cyclopropanecarboxamide, 19) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-- phenylcyclopropanecarboxamide, 20) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methoxy- pyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide, 21) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-- (5-fluoropyridin-2-yl)cyclopropanecarboxamide, 22) (1R,2S)-N-(5-cyanopyridin-2-yl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methy- l}-2-(3-fluorophenyl)cyclopropanecarboxamide, 23) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(4-fluorophenyl)-N-- (5-fluoropyridin-2-yl)cyclopropanecarboxamide, 24) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methoxy- pyridin-2-yl)-2-(4-fluorophenyl)cyclopropanecarboxamide, 25) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methoxy- methylpyridin-2-yl)-2-(4-fluorophenyl)cyclopropanecarboxamide, 26) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methylp- yridin-2-yl)-2-(4-fluorophenyl)cyclopropanecarboxamide, 27) (1R,2S)-2-(3-cyanophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(- 5-fluoro-4-methylpyridin-2-yl)cyclopropanecarboxamide, 28) (1R,2S)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoropyridi- n-2-yl)-2-phenylcyclopropanecarboxamide, 29) (1R,2S)-N-(5-cyanopyridin-2-yl)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]m- ethyl}-2-phenylcyclopropanecarboxamide, 30) (1R,2S)-N-(5-chloropyridin-2-yl)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]- methyl}-2-phenylcyclopropanecarboxamide, 31) (1R,2S)-2-(3,5-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-N-(5-fluoro-4-methylpyridin-2-yl)cyclopropanecarboxamide, 32) (1R,2S)-2-(3,5-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-N-(4-fluorophenyl)cyclopropanecarboxamide, 33) (1R,2S)-2-(3,5-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-N-(pyridin-2-yl)cyclopropanecarboxamide, 34) (1R,2S)-N-(5-chloropyridin-2-yl)-2-(3,5-difluorophenyl)-2-{[(2,4-dimethyl- pyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 35) (1R,2S)-2-(3,5-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide, 36) (1R,2S)-N-(3,4-difluorophenyl)-2-(3,5-difluorophenyl)-2-{[(2,4-dimethylpy- rimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 37) (1R,2S)-N-(2,4-difluorophenyl)-2-(3,5-difluorophenyl)-2-{[(2,4-dimethylpy- rimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 38) (1R,2S)-N-(5-cyanopyridin-2-yl)-2-(3,5-difluorophenyl)-2-{[(2,4-dimethylp- yrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 39) (1R,2S)-2-(3,5-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-N-(5-fluoro-4-methoxypyridin-2-yl)cyclopropanecarboxamide, 40) (1R,2S)-N-(5-chloropyridin-2-yl)-2-{[(4-(methoxymethyl)-2-methylpyrimidin- -5-yl)oxy]methyl}-2-phenylcyclopropanecarboxamide, 41) (1R,2S)-N-(5-cyanopyridin-2-yl)-2-{[(4-(methoxymethyl)-2-methylpyrimidin-- 5-yl)oxy]methyl}-2-phenylcyclopropanecarboxamide, 42) (1R,2S)-N-(5-fluoropyridin-2-yl)-2-{[(4-(methoxymethyl)-2-methylpyrimidin- -5-yl)oxy]methyl}-2-phenylcyclopropanecarboxamide, 43) (1R,2S)-N-(5-fluoro-4-methylpyridin-2-yl)-2-{[(4-methoxymethyl-2-methylpy- rimidin-5-yl)oxy]methyl}-2-phenylcyclopropanecarboxamide, 44) (1R,2S)-N-(4-fluorophenyl)-2-{[(4-methoxymethyl-2-methylpyrimidin-5-yl)ox- y]methyl}-2-phenylcyclopropanecarboxamide, 45) (1R,2S)-N-(3,4-difluorophenyl)-2-{[(4-methoxymethyl-2-methylpyrimidin-5-y- l)oxy]methyl}-2-phenylcyclopropanecarboxamide, 46) (1R,2S)-2-(3,4-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-N-(5-fluoro-4-methylpyridin-2-yl)cyclopropanecarboxamide, 47) (1R,2S)-2-(3,4-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-N-(4-fluorophenyl)cyclopropanecarboxamide, 48) (1R,2S)-2-(3,4-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-N-(pyridin-2-yl)cyclopropanecarboxamide, 49) (1R,2S)-N-(5-cyanopyridin-2-yl)-2-(3,4-difluorophenyl)-2-{[(2,4-dimethylp- yrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 50) (1R,2S)-N-(5-chloropyridin-2-yl)-2-(3,4-difluorophenyl)-2-{[(2,4-dimethyl- pyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 51) (1R,2S)-2-(3,4-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide, 52) (1R,2S)-N,2-bis(3,4-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]m- ethyl}cyclopropanecarboxamide, 53) (1R,2S)-2-(3,4-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-N-(5-fluoro-4-methoxypyridin-2-yl)cyclopropanecarboxamide, 54) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoropyridin-2-- yl)-2-(3-methoxyphenyl)cyclopropanecarboxamide, 55) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methylp- yridin-2-yl)-2-(3-methoxyphenyl)cyclopropanecarboxamide, 56) (1R,2S)-N-(3,4-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-2-(3-methoxyphenyl)cyclopropanecarboxamide, 57) (1R,2S)-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)-2-[(4-methoxymethyl-2- -methylpyrimidin-5-yl)oxymethyl]cyclopropanecarboxamide, 58) (1R,2S)-2-(3-fluorophenyl)-N-(4-fluorophenyl)-2-{[(4-methoxymethyl-2-meth- ylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 59) (1R,2S)-2-(3-fluorophenyl)-2-{[(4-methoxymethyl-2-methylpyrimidin-5-yl)ox- y]methyl}-N-(pyridin-2-yl)cyclopropanecarboxamide, 60) (1R,2S)-N-(3,4-difluorophenyl)-2-(3-fluorophenyl)-2-{[(4-methoxymethyl-2-- methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 61) (1R,2S)-N,2-bis(3-fluorophenyl)-2-{[(4-methoxymethyl-2-methylpyrimidin-5-- yl)oxy]methyl}cyclopropanecarboxamide, 62) (1R,2S)-N-(2,4-difluorophenyl)-2-(3-fluorophenyl)-2-{[(4-methoxymethyl-2-- methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 63) (1R,2S)-N-(2,5-difluorophenyl)-2-(3-fluorophenyl)-2-{[(4-methoxymethyl-2-- methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 64) (1R,2S)-N-(5-chloropyridin-2-yl)-2-(3-fluorophenyl)-2-{[(4-methoxymethyl-- 2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 65) (1R,2S)-N-(5-fluoro-4-methylpyridin-2-yl)-2-(3-fluorophenyl)-2-{[(4-metho- xymethyl-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 66) (1R,2S)-2-(3-fluorophenyl)-2-{[(4-methoxymethyl-2-methylpyrimidin-5-yl)ox- y]methyl}-N-[5-(trifluoromethyl)pyridin-2-yl]cyclopropanecarboxamide, 67) (1R,2S)-2-(4-fluorophenyl)-N-(5-fluoropyridin-2-yl)-2-{[(4-methoxymethyl-- 2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 68) (1R,2S)-N,2-bis(4-fluorophenyl)-2-{[(4-methoxymethyl-2-methylpyrimidin-5-- yl)oxy]methyl}cyclopropanecarboxamide, 69) (1R,2S)-N-(5-chloropyridin-2-yl)-2-(4-fluorophenyl)-2-{[(4-methoxymethyl-- 2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 70) (1R,2S)-N-(5-fluoro-4-methylpyridin-2-yl)-2-(4-fluorophenyl)-2-{[(4-metho- xymethyl-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 71) (1R,2S)-N-(3,4-difluorophenyl)-2-(4-fluorophenyl)-2-{[(4-methoxymethyl-2-- methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 72) (1R,2S)-2-(3,4-difluorophenyl)-2-{[(4-methoxymethyl-2-methylpyrimidin-5-y- l)oxy]methyl}-N-(pyridin-2-yl)cyclopropanecarboxamide, 73) (1R,2S)-2-(3,4-difluorophenyl)-N-(5-fluoro-4-methylpyridin-2-yl)-2-{[(4-m- ethoxymethyl-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 74) (1R,2S)-N,2-bis(3,4-difluorophenyl)-2-{[(4-methoxymethyl-2-methylpyri- midin-5-yl)oxy]methyl}cyclopropanecarboxamide, 75) (1R,2S)-N-(2,4-difluorophenyl)-2-(3,4-difluorophenyl)-2-{[(4-methoxymethy- l-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 76) (1R,2S)-2-(3,5-difluorophenyl)-2-{[(4-methoxymethyl-2-methylpyrimidin-5-y- l)oxy]methyl}-N-(pyridin-2-yl)cyclopropanecarboxamide, 77) (1R,2S)-2-(3,5-difluorophenyl)-N-(4-fluorophenyl)-2-{[(4-methoxymethyl-2-- methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 78) (1R,2S)-N-(3,4-difluorophenyl)-2-(3,5-difluorophenyl)-2-{[(4-methoxymethy- l-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 79) (1R,2S)-2-(3-chlorophenyl)-2-{[(4-methoxymethyl-2-methylpyrimidin-5-yl)ox- y]methyl}-N-(pyridin-2-yl)cyclopropanecarboxamide, 80) (1R,2S)-2-(3-chlorophenyl)-N-(5-fluoro-4-methylpyridin-2-yl)-2-{[(4-metho- xymethyl-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 81) (1R,2S)-N-(5-fluoro-4-methylpyridin-2-yl)-2-(3-fluorophenyl)-2-{[(4-metho- xyethyl-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 82) (1R,2S)-2-(3-fluoro-5-methoxyphenyl)-N-(4-fluorophenyl)-2-{[(4-methoxymet- hyl-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 83) (1R,2S)-N-(3,4-difluorophenyl)-2-(3-fluoro-5-methoxyphenyl)-2-{[(4-methox- ymethyl-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 84) (1R,2S)-2-(3-fluoro-5-methoxyphenyl)-N-(5-fluoropyridin-2-yl)-2-[(4-metho- xymethyl-2-methylpyrimidin-5-yl)oxymethyl]cyclopropanecarboxamide, 85) (1R,2S)-2-(3-fluoro-5-methoxyphenyl)-N-(5-fluoro-4-methylpyridin-2-yl)-2-- {[(4-methoxymethyl-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxami- de, 86) (1R,2S)-2-(3-fluoro-5-methoxyphenyl)-2-[(4-methoxymethyl-2-methylp- yrimidin-5-yl)oxymethyl]-N-(pyridin-2-yl)cyclopropanecarboxamide, 87) (1R,2S)-2-(3-fluoro-5-methoxyphenyl)-N-(3-fluorophenyl)-2-{[(4-methoxymet- hyl-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 88) (1R,2S)-2-(4-fluoro-3-methoxyphenyl)-N-(5-fluoro-4-methylpyridin-2-yl)-2-- {[(4-methoxymethyl-2-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxami- de, 89) (1R,2S)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]methyl}-2-(3-fluor- ophenyl)-N-(pyridin-2-yl)cyclopropanecarboxamide, 90) (1R,2S)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl- )-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide, 91) (1R,2S)-N-(5-cyanopyridin-2-yl)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]m- ethyl}-2-(3-fluorophenyl)cyclopropanecarboxamide, 92) (1R,2S)-N-(5-chloropyridin-2-yl)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]- methyl}-2-(3-fluorophenyl)cyclopropanecarboxamide, 93) (1R,2S)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-met- hylpyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide, 94) (1R,2S)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]methyl}-2-(4-fluorophenyl- )-N-(pyridin-2-yl)cyclopropanecarboxamide, 95) (1R,2S)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]methyl}-2-(4-fluorophenyl- )-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide, 96) (1R,2S)-N-(4-chloropyridin-2-yl)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]- methyl}-2-(4-fluorophenyl)cyclopropanecarboxamide, 97) (1R,2S)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-met- hylpyridin-2-yl)-2-(4-fluorophenyl)cyclopropanecarboxamide, 98) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluoro-5-methoxy- phenyl)-N-(5-fluoro-4-methylpyrimidin-2-yl)cyclopropanecarboxamide, 99) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoropyridin-2-- yl)-2-(3-trifluoromethylphenyl)cyclopropanecarboxamide, 100) (1R,2S)-2-(4-bromophenyl)-N-(5-chloropyridin-2-yl)-2-{[(2,4-dimethylpyrim- idin-5-yl)oxy]methyl}cyclopropanecarboxamide, 101) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoromethylpyri- din-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide, 102) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoropyridin-2-- yl)-2-(3-iodophenyl)cyclopropanecarboxamide, 103) (1R,2S)-N-(5-fluoropyridin-2-yl)-2-{[(4-hydroxymethyl-2-methylpyrimidin-5- -yl)oxy]methyl}-2-(3-fluorophenyl)cyclopropanecarboxamide, 104) (1R,2S)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl- )-N-(4-fluorophenyl)cyclopropanecarboxamide, 105) (1R,2S)-2-{[(4-fluoromethyl-2-methylpyrimidin-5-yl)oxy]methyl}-2-(3-fluor- ophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide, 106) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluoro-4-hydroxy- phenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide, 107) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluoro-4-methoxy- phenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide, 108) (1R,2S)-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)-2-{[(2-hydroxymethyl-- 4-methylpyrimidin-5-yl)oxy]methyl}cyclopropanecarboxamide, 109) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2[5-fluoro-2-hydroxyp- henyll-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide, 110) (1R,2S)-2-{[(2,4-dimethyl-6-oxo-1,6-dihydropyrimidin-5-yl)oxy]methyl}-2-(- 3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide, 111) (1R,2S)-N-(2-cyanopyridin-4-yl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methy- l}-2-phenylcyclopropanecarboxamide, 112) (1R,2S)-2-[N-(2,4-dimethylpyrimidin-5-yl)methylaminomethyl]-N-(5-fluoropy- ridin-2-yl)-2-(3-fluorophenyl) cyclopropanecarboxamide, 113) (1R,2S)-N-(5-chloro-4-methylpyridin-2-yl)-2[N-(2,4-dimethylpyrimidin-5-yl- )methylaminomethyl]-2-(3-fluorophenyl) cyclopropanecarboxamide, 114) (1R,2S)-N-(3,4-fluoropyridin-2-yl)-2-[N-(2,4-dimethylpyrimidin-5-yl)methy- laminomethyl]-2-(3-fluorophenyl) cyclopropanecarboxamide, 115) (1R,2S)-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)-2-[N-(2-methyl-4-trif- luoromethylpyrimidin-5-yl)methylaminomethyl] cyclopropanecarboxamide, and 116) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(6-fluoro-5-me- thoxypyridin-3-yl)-2-phenylcyclopropanecarboxamide. 6. A compound, which is selected from the following compounds, or a pharmaceutically acceptable salt thereof: 1) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoropyridin-2-- yl)-2-phenylcyclopropanecarboxamide, 11) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methylp- yridin-2-yl)-2-phenylcyclopropanecarboxamide, 14) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-methylp- yridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide, 21) (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-- (5-fluoropyridin-2-yl)cyclopropanecarboxamide, 31) (1R,2S)-2-(3,5-difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl- }-N-(5-fluoro-4-methylpyridin-2-yl)cyclopropanecarboxamide, and 89) (1R,2S)-2-{[(4-ethyl-2-methylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl- )-N-(pyridin-2-yl)cyclopropanecarboxamide. 7. (1R,2S)-2-{[(2,4-Dimethylpyrimidin-5-yl)oxy]methyl}-N-(5-fluoro-4-meth- ylpyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide represented by the following formula or a pharmaceutically acceptable salt thereof: ##STR00432## 8. (1R,2S)-2-{[(2,4-Dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)- -N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide represented by the following formula or a pharmaceutically acceptable salt thereof: ##STR00433## 9. (1R,2S)-2-(3,5-Difluorophenyl)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]met- hyl}-N-(5-fluoro-4-methylpyridin-2-yl)cyclopropanecarboxamide represented by the following formula or a pharmaceutically acceptable salt thereof: ##STR00434## 10. A pharmaceutical composition comprising, as an active ingredient, the compound according to claim 2 or a pharmaceutically acceptable salt thereof. 11. A method for treating sleep disorder for which orexin receptor antagonism is effective, which comprises administering the compound according to claim 2 or a pharmaceutically acceptable salt thereof into a subject in need thereof. 12. The method according to claim 11, wherein said sleep disorder is insomnia. 13. A pharmaceutical composition comprising, as an active ingredient, the compound according to claim 3 or a pharmaceutically acceptable salt thereof. 14. A method for treating sleep disorder for which orexin receptor antagonism is effective, which comprises administering the compound according to claim 3 or a pharmaceutically acceptable salt thereof into a subject in need thereof. 15. The method according to claim 14, wherein said sleep disorder is insomnia. 16. A pharmaceutical composition comprising, as an active ingredient, the compound according to claim 5 or a pharmaceutically acceptable salt thereof. 17. A method for treating sleep disorder for which orexin receptor antagonism is effective, which comprises administering the compound according to claim 5 or a pharmaceutically acceptable salt thereof into a subject in need thereof. 18. The method according to claim 17, wherein said sleep disorder is insomnia. 19. A pharmaceutical composition comprising, as an active ingredient, the compound according to claim 7 or a pharmaceutically acceptable salt thereof. 20. A method for treating sleep disorder for which orexin receptor antagonism is effective, which comprises administering the compound according to claim 7 or a pharmaceutically acceptable salt thereof into a subject in need thereof. 21. The method according to claim 20, wherein said sleep disorder is insomnia. 22. A pharmaceutical composition comprising, as an active ingredient, the compound according to claim 8 or a pharmaceutically acceptable salt thereof. 23. A method for treating sleep disorder for which orexin receptor antagonism is effective, which comprises administering the compound according to claim 8 or a pharmaceutically acceptable salt thereof into a subject in need thereof. 24. The method according to claim 23, wherein said sleep disorder is insomnia. 25. A pharmaceutical composition comprising, as an active ingredient, the compound according to claim 9 or a pharmaceutically acceptable salt thereof. 26. A method for treating sleep disorder for which orexin receptor antagonism is effective, which comprises administering the compound according to claim 9 or a pharmaceutically acceptable salt thereof into a subject in need thereof. 27. The method according to claim 26, wherein said sleep disorder is insomnia.