Abstract:
Novel 1-phenylakyl-3-phenylurea derivatives represented by the following formula (I): ##STR1## wherein R 1  is an alkyl group of 1 to 8 carbon atoms, an alkoxy group of 1 to 5 carbon atoms or a halogen atom, R 2  is an alkyl group of 1 to 15 carbon atoms, each of R 3  and R 4  is independently an alkyl group of 1 to 5 carbon atoms, m is an integer of 1 to 3, and n is 0 or 1, are provided. 
     The compounds are potent in reducing the cholesterol level in serum, and useful for treating hyperlipemia and atherosclerosis.

Description:
FIELD OF THE INVENTION 
     The present invention relates to 1-phenylalkyl-3-phenylurea derivatives which are potent in reducing a lipid level in blood and, therefore, useful as therapeutical medicines for hyperlipemia and atherosclerosis. 
     BACKGROUND OF THE INVENTION 
     Heretofore, it has been considered that hyperlipemia caused by metabolic error of lipids results in arteriosclerosis and is one of the major dangerous factors causing ischemic heart disease or cerebral embolism 
     Recently, it was revealed that an enzyme, acyl-CoA: cholesterol acyltransferase (ACAT) acts an important role at lipid metabolism, especially cholesterol metabolism. It was also reported that compounds having an inhibitory activity of the enzyme, ACAT, actually inhibit the absorption of cholesterol at intestine, reduce the level of cholesterol in blood, and inhibit the deposition of cholesterol on arterial wall, and accordingly, are useful as therapeutical medicines for atherosclerosis as well as hyperlipemia, as described in Japanese Patent Application Laying-Open (Kokai) No. 16761/88, No. 93569/89, No. 6455/90, No. 6456/90, and No. 457/90. 
     SUMMARY OF THE INVENTION 
     As a result of the extensive search for more potent compounds, the present inventors have found novel and useful 1-phenylalkyl-3-phenylurea derivatives which show an excellent lipid-reducing activity, and achieved the present invention. 
     Specifically, the present invention provides a 1-phenylalkyl-3-phenylurea derivative represented by the following formula (I): ##STR2## wherein R 1  is an alkyl group of 1 to 8 carbon atoms, an alkoxy group of 1 to 5 carbon atoms or a halogen atom, R 2  is an alkyl group of 1 to 15 carbon atoms, each of R 3  and R 4  is independently an alkyl group of 1 to 5 carbon atoms, m is an integer of 1 to 3, and n is 0 or 1. 
     The compounds according to the invention are potent in reducing the cholesterol level in blood owing to the ACAT inhibition, and accordingly, useful for treating hyperlipemia and/or atherosclerosis. 
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The 1-phenylalkyl-3-phenylurea derivative according to the present invention is represented by the above formula (I). 
     The examples of R 1  in the formula (I), i.e., an alkyl group of 1 to 8 carbon atoms, include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group, hexyl groups, heptyl groups, and octyl groups. 
     As the alkoxy group of 1 to 5 carbon atoms, there may be mentioned methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, n-pentoxy group, isopentoxy group, sec-pentoxy group, tert-pentoxy group, or neopentoxy group. Furthermore, as the halogen atom, there may be mentioned fluorine atom, chlorine atom, bromine atom, or iodine atom. 
     As the alkyl group of 1 to 15 carbon atoms of R 2 , there may be mentioned methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, neopentyl group, one of hexyl groups, one of heptyl groups, one of octyl groups, one of nonyl groups, one of decyl groups, one of undecyl groups, one of dodecyl groups, one of tridecyl groups, one of tetradecyl groups, or one of pentadecyl groups. 
     As the alkyl ethyl group of 1 to 5 carbon atoms of R 3  or R 4 , there may be mentioned methyl group, ethyl group, n-proply group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, sec-pentyl group, tert-pentyl group, or neopentyl group. 
     In the formula (I), R 2  may preferably be a normal alkyl group of 4 to 6 carbon atoms, and, in this case, more preferably, each of R 3  and R 4  is the same alkyl group of 1 to 3 carbon atoms. 
     The examples of the compounds according to the present invention are illustrated in the following Table. The compounds of the invention possesses at least one asymmetric carbon and may be racemic or optically pure. 
     
         ______________________________________ ##STR3##(R.sup.1).sub.m     n      R.sup.2    R.sup.3 R.sup.4______________________________________2-CH.sub.3     0n-C.sub.4 H.sub.9           C.sub.2 H.sub.5                               C.sub.2 H.sub.52-CH.sub.3     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-CH.sub.3     0n-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.52-CH.sub.3     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-CH.sub.3     0i-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.52-CH.sub.3     0i-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-CH.sub.3     0n-C.sub.6 H.sub.13     C.sub.2 H.sub.5            C.sub.2 H.sub.52-CH.sub.3     0n-C.sub.6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-CH.sub. 3     0i-C.sub.6 H.sub.13     C.sub.2 H.sub.5            C.sub.2 H.sub.52-CH.sub.3     0i-C.sub.6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-C.sub.2 H.sub.5     0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5            C.sub.2 H.sub.52-C.sub.2 H.sub.5     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-C.sub.2 H.sub.5     0n-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.52-C.sub.2 H.sub.5     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-C.sub.2 H.sub.5     0i-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.52-C.sub.2 H.sub.5     0i-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-C.sub.2 H.sub.5     0n-C.sub.6 H.sub.13     C.sub.2 H.sub.5            C.sub.2 H.sub.52-C.sub.2 H.sub.5     0n-C.sub.6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-C.sub.2 H.sub.5     0i-C.sub.6 H.sub.13     C.sub.2 H.sub.5            C.sub.2 H.sub.52-C.sub.2 H.sub.5     0i-C.sub. 6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-n-C.sub.3 H.sub.7     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-n-C.sub.3 H.sub.7     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-n-C.sub.3 H.sub.7     0i-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-i-C.sub.3 H.sub.7     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-i-C.sub.3 H.sub.7     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-n-C.sub.4 H.sub.9     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-CH.sub.3     0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5            C.sub.2 H.sub.53-CH.sub.3     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-CH.sub.3     0n-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.53-CH.sub.3     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-CH.sub.3     0n-C.sub.6 H.sub.13     C.sub.2 H.sub.5            C.sub.2 H.sub.53-CH.sub.3     0n-C.sub.6 H.sub. 13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-CH.sub.3     0i-C.sub.6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-C.sub.2 H.sub.5     0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5            C.sub.2 H.sub.53-C.sub.2 H.sub.5     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-C.sub.2 H.sub.5     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-C.sub.2 H.sub.5     0i-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-n-C.sub.3 H.sub.7     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-i-C.sub.3 H.sub.7     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-n-C.sub.4 H.sub.9     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-n-C.sub.7 H.sub.11     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-CH.sub.3     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-CH.sub.3     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-C.sub.2 H.sub.5     0n-C.sub.4 H.sub. 9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-n-C.sub.3 H.sub.7     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-i-C.sub.3 H.sub.7     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-n-C.sub.4 H.sub.9     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-n-C.sub.5 H.sub.11     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-n-C.sub.7 H.sub.11     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diCH.sub.3     0      CH.sub.3   CH.sub.3                               CH.sub.32,3-diCH.sub.3     0      C.sub.2 H.sub.5i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diCH.sub.3     0n-C.sub.3 H.sub.7     C.sub.2 H.sub.5            C.sub.2 H.sub.52,3-diCH.sub.3     0n-C.sub.3 H.sub.7i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diCH.sub.3     0i-C.sub.3 H.sub.7i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diCH.sub.3     0n-C.sub.4 H.sub.9     CH.sub.3            CH.sub.32,3-diCH.sub.3     0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5            C.sub.2 H.sub.52,3-diCH.sub. 3     0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5n-C.sub.3 H.sub.72,3-diCH.sub.3     0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5i-C.sub.3 H.sub.72,3-diCH.sub.3     0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5sec-C.sub.4 H.sub.92,3-diCH.sub.3     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diCH.sub.3     0n-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.52,3-diCH.sub.3     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diCH.sub.3     0i-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.52,3-diCH.sub.3     0i-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73,4-diCH.sub.3     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3,4-triCH.sub.3     0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5            C.sub.2 H.sub.52,3,4-triCH.sub.3     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3,4-triCH.sub.3     0n-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.52,3,4-triCH.sub.3     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub. 7i-C.sub.3 H.sub.72-OCH.sub.3     0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5            C.sub.2 H.sub.52-OCH.sub.3     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-OCH.sub.3     0n-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.52-OCH.sub.3     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-OCH.sub.3     0n-C.sub.6 H.sub.13     C.sub.2 H.sub.5            C.sub.2 H.sub.52-OCH.sub.3     0n-C.sub.6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-OCH.sub.3     0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5            C.sub.2 H.sub.53-OCH.sub.3     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-OCH.sub.3     0n-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.53-OCH.sub.3     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-OCH.sub.3     0n-C.sub.6 H.sub.13     C.sub.2 H.sub.5            C.sub.2 H.sub.53-OCH.sub.3     0n-C.sub.6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-OCH.sub.3     0i-C.sub.6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-OCH.sub.3     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-OCH.sub.3     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub.4 H.sub.9n-C.sub.3 H.sub.7n-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.52,3-diOCH.sub.3     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0sec-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0i-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub.6 H.sub.13     C.sub.2 H.sub.5            C.sub.2 H.sub.52,3-diOCH.sub.3     0n-C.sub.7 H.sub.15i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub.8 H.sub.17i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub.9 H.sub.19i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub. 10 H.sub.21i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub.11 H.sub.23i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub.12 H.sub.25i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub.13 H.sub.27i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub.14 H.sub.29i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72,3-diOCH.sub.3     0n-C.sub.15 H.sub.31i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73,4-diOCH.sub.3     0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5            C.sub.2 H.sub.53,4-diOCH.sub.3     0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73,4-diOCH.sub.3     0n-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.53,4-diOCH.sub.3     0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73,4-diOCH.sub.3     0i-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.53,4-diOCH.sub.3     0i-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73,4-diOCH.sub.3     0n-C.sub.6 H.sub.13     C.sub.2 H.sub.5            C.sub.2 H.sub.53,4-diOCH.sub. 3     0n-C.sub.6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73,4-diOCH.sub.3     0i-C.sub.6 H.sub.13     C.sub.2 H.sub.5            C.sub.2 H.sub.53,4-diOCH.sub.3     0i-C.sub.6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-F       0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-F       0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-F       0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-F       0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-F       0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-F       0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-Cl      0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5            C.sub.2 H.sub.52-Cl      0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-Cl      0n-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.52-Cl      0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-Cl      0n-C.sub.6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-Cl      0n-C.sub.4 H.sub.9     C.sub.2 H.sub.5            C.sub.2 H.sub.53-Cl      0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-Cl      0n-C.sub.5 H.sub.11     C.sub.2 H.sub.5            C.sub.2 H.sub.53-Cl      0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-Cl      0n-C.sub.6 H.sub.13     C.sub.2 H.sub.5            C.sub.2 H.sub.53-Cl      0n-C.sub.6 H.sub.13i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-Cl      0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-Cl      0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-Br      0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-Br      0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-Br      0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-Br      0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-Br      0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-Br      0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-I       0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-I       0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-I       0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-I       0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-I       0n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-I       0n-C.sub.5 H.sub.11i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-CH.sub.3     1n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-CH.sub.3     1n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-CH.sub.3     1n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.72-Cl      1n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.73-Cl      1n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.74-Cl      1n-C.sub.4 H.sub.9i-C.sub.3 H.sub.7i-C.sub.3 H.sub.7______________________________________ 
    
     It should be, however, understood that the present invention is not limited to the above examples. 
     The compounds of the present invention may be prepared, for example, according to the processes described below. ##STR4## wherein, R 1 , R 2 , R 3 , R 4 , m and n are the same as defined above. 
     According to Method A, the compound (I) of the invention is prepared by condensing a phenylalkylamine derivative of the formula (II) with a phenyl isocyanate derivative of the formula (III) at a temperature range of 0° C. to 150° C. in an inert solvent such as benzene, toluene, xylene, hexane, heptane, diethyl ether, tetrahydrofuran (THF), dioxane, or N,N-dimethylformamide. ##STR5## wherein, R 1 , R 2 , R 3 , R 4 , m and n are the same as defined above. 
     According to method B, the compound (I) of the invention is prepared by reacting a phenylalkyl isocyanate of the formula (IV) with an aniline derivative of the formula (V) in a similar manner to method A. ##STR6## wherein, R 1 , R 2 , R 3 , R 4 , m and n are the same as defined above. 
     This method is basically similar to Method B. Thus, the compound (I) of the invention is prepared by converting a phenylalkylcarboxylic acid derivative of the formula (VI) into a phenylalkyl isocyanate derivative of the formula (IV), followed by condensing the isocyanate derivative (IV) with an aniline derivative of the formula (V). The conversion of the phenylalkylcarboxylic acid derivative of the formula (VI) into the phenylalkyl isocyanate derivative of the formula (IV) may be achieved, for example, by treating the phenylalkylcarboxylic acid derivative with DPPA (diphenoxy phosphoryl azide) in the presence of an inert amine such as triethylamine at a temperature range of room temperature to 150° C. in an inert solvent such as benzene, toluene or xylene. ##STR7## wherein, R 3  and R 4  are the same as defined above. 
     Method D comprises the preparation of the compound (I) of the invention by converting a benzoic acid derivative of the formula (VII) into a phenyl isocyanate derivative of the formula (III) in an similar manner to Method C, followed by reacting the isocyanate derivative (III) with a phenylalkylamine derivative of the formula (II). ##STR8## wherein, R 1 , R 2 , R 3 , R 4 , m and n are the same as defined above, and X is a leaving group such as a halogen atom, aryloxy group or alkylthio group. 
     Method E comprises the preparation of the compound (I) of the invention by converting a phenylalkylamine derivative of the formula (II) into a reactive intermediate of the formula (VIII), followed by reacting the resulting intermediate with an aniline derivative of the formula (V) at a temperature range of 0° C. to 150° C. in an inert solvent such as benzene, diethyl ether, or ethyl acetate. As the reactive intermediate, there may be mentioned a phenylalkylcarbamoyl chloride of the formula (VIII) in which X is chlorine atom obtained by reacting a phenylalkylamine derivative (II) with phosgene, or an aryl phenylalkylcarbamate of the formula (VIII) in which X is an aryloxy group, obtained by reacting a phenylalkylamine derivative (II) with an aryl chloroformate. ##STR9## wherein, R 3 , R 4  and X are the same as defined above. 
     Method F comprises the preparation of the compound (I) of the invention by converting an aniline derivative of the formula (V) into a reactive intermediate of the formula (IX), followed by reacting the intermediate with a phenylalkylamine derivative of the formula (II) at a temperature range of 0° C. to 150° C. in an inert solvent such as benzene, diethyl ether, or ethyl acetate. As the reactive intermediate, there may be mentioned a phenylcarbamoyl chloride of the formula (IX) in which X is chlorine atom obtained by reacting an aniline derivative (V) with phosgene, or an aryl phenylcarbamate of the formula (IX) in which X is an aryloxy group, obtained by reacting an aniline derivative (V) with an aryl chloroformate. 
     The present invention also provides an acyl-CoA: cholesterol acyltransferase inhibitor comprising a 1-phenylalkyl-3-phenylurea derivative as defined hereinbefore as active ingredient. The inhibitor may be administrated, preferably, orally to a human patient. 
     The present invention further provides a pharmaceutical composition for treating hyperlipemia and atherosclerosis comprising a therapeutically effective amount of a 1-phenylalkyl-3-phenylurea derivative as defined hereinbefore, in admixture with a pharmaceutically acceptable carrier, diluent or a mixture thereof. The composition may be administrated, preferably, orally to a patient. 
     The formulation for the oral administration may be tablet, granule, powder, capsule, etc. The inhibitor or pharmaceutical composition may further include usual additives known in the art, for example, an excipient such as glucose, lactose, corn starch or mannitol, a binder such as hydroxypropyl cellulose (HPC) and carboxymethyl cellulose (CMC), a disintegrating agent such as starch or powdery gelatin, a lubricating agent such as talc or magnesium stearate. 
     The dose of the compound according to the present invention, in the case of oral administration, is from 1 mg to 1000 mg per day for an adult, which may vary depending on the body conditions and necessity of patients, degree of the disease to be treated, and the activity of the compound used. 
    
    
     EXAMPLES 
     The present invention is further illustrated in detail with reference to the following examples. It should be understood that the present invention is not limited solely to those examples. 
     EXAMPLE 1 
     Preparation of 1-(2-(3-methylphenyl)hexyl)-3-(2,6-diisopropylphenyl)urea 
     To 20 ml of n-hexane was added 1.81 g (9.5 mmol) of 2-(3-methylphenyl)hexylamine. An 18 ml of 0.52M hexane solution of 2,6-diisopropylphenyl isocyanate was added dropwise to the mixture under ice cooling. The resulting mixture was stirred overnight and the precipitated crystals were collected by filtration to give 1.87 g (50% yield) of 1-(2-(3-methylphenyl)hexyl)-3-(2,6-diisopropylphenyl)urea. 
     Melting point: 173°-174° C. 
     IR (KBr) cm -1  : 3340, 2970, 1635, 1575, 1460, 1250, 700 
     NMR (CDCl 3 ) δ: 0.80 (t, 3H), 0.96-1.25 (m, 16H), 1.50-1.68 (m, 2H), 2.21 (s, 3H), 2.53 (m, 1H), 3.02-3.12 (m, 3H), 3.56 (m, 1H), 3.93 (br. s, lH), 5.65 (s, 1H), 6.71 (m, 2H), 6.90 (d, 1H), 6.99-7.10 (m, 3H), 7.27 (t, 1H) 
     EXAMPLES 2-49 
     The compounds listed in Table 1-1, Table 1-2 and Table 1-3 were similarly prepared as described in Example 1. In the case that crystals were not precipitated from the reaction mixture during the operations similar to Example 1, the resulting crude products were purified by subjecting them to column chromatography over silica gel (eluent n-hexane/ethyl acetate =4/1) to give desired products. 
     In the tables, Me, Et, Pr, Bu, Pen, Hex, Hep, and Oct represent methy group, ethyl group, propyl group, pentyl group, hexyl group, heptyl group, and octyl group, respectively. 
     
                       TABLE 1-1______________________________________ ##STR10##Example                Yield MeltingNo.    (R.sup.1).sub.m          R.sup.2 (%)   point (°C.)                                IR(KBr)cm.sup.-1______________________________________2      2-Me    n-Pen   38    140-141 3300, 2950,                                1630, 1560                                1460, 1250, 7603      2-Me    n-Hex   54    123-124 3300, 2900,                                1630, 1560                                1450, 1250, 7504      3-Me    n-Pen   34    86-87   3320, 2950,                                1630, 1565                                1460, 1250, 7005      3-Me    n-Hex   24    amorphous                                3350, 2960,                                1635, 1570                                1470, 1260, 7106      3-OMe   n-Bu    60    amorphous                                3320, 2950,                                1635, 1560                                1460, 1250,                                1040, 7007      3-OMe   n-Pen   49    amorphous                                3320, 2940,                                1630, 1560                                1460, 1255,                                1045, 7008      3-OMe   n-Hex   55    amorphous                                3320, 2940,                                1630, 1570                                1460, 1260,                                1045, 700______________________________________ 
    
     
                       TABLE 1-2______________________________________ ##STR11##Example                Yield MeltingNo.    (R.sup.1).sub.m          R.sup.2 (%)   point (°C.)                                IR(KBr)cm.sup.-1______________________________________ 9     2-Me    n-Bu    50    121-123 3350, 2950,                                1630, 1565                                1460, 1250, 80010     2-Me    n-Pen   27    120-122 3300, 2920,                                1630, 1560                                1450, 1250, 75011     2-Me    n-Hex   51    amorphous                                3300, 2950,                                1630, 1560                                1460, 1250, 75012     3-Me    n-Pen   22    168-170 3300, 2960,                                1630, 1565                                1460, 1250, 70013     3-Me    n-Hex   42    160-162 3350, 2950,                                1630, 1565                                1460, 1260, 70014     3-Me    i-Hex   29    177-179 3300, 2950,                                1630, 1560                                1460, 1250, 70015     3-Et    n-Bu    34    159-160 3340, 2960,                                1630, 1570                                1460, 1250, 71016     3-Pr    n-Bu    37    140-141 3340, 2970,                                1630, 1570                                1460, 1250, 81017     3-Bu    n-Bu    31    110-112 3350, 2950,                                1630, 1560                                1460, 1250, 70018     3-Hep   n-Bu    63    oil     3330, 2950,                                1620, 1560                                1460, 1250, 70019     4-Me    n-Bu    48    198-200 3340, 2950,                                1630, 1565                                1460, 1250, 80020     4-Bu    n-Bu    71    136-137 3350, 2950,                                1630, 1570                                1460, 1250, 80021     3-Hep   n-Bu    67    oil     3330, 2950,                                1630, 1550                                1460, 1250, 80022     2,3-    n-Pen   76    107-110 3340, 2980,  diMe                          2950, 2900                                1640, 1570,                                1530, 1470                                126023     3,4-    n-Bu    38    174-175 3300, 2920,  diMe                          1630, 1560                                1450, 1250, 70024     2,3,4-  n-Bu    22    144-146 3300, 2950,  triMe                         1630, 1560                                1460, 1250, 80025     2-OMe   n-Bu    44    138-139 3300, 2960,                                1630, 1560                                1460, 1240, 75026     2-OMe   n-Pen   44    134-136 3290, 2970,                                1640, 1550                                1460, 1240, 75027     2-OMe   n-Hex   48    153-154 3250, 2950,                                1640, 1550                                1460, 1240, 75028     3-OMe   n-Bu    55    159-161 3320, 2940,                                1640, 1550                                1460, 1255,                                1045, 70029     3-OMe   n-Pen   32    163-165 3320, 2940,                                1635, 1565                                1460, 1260,                                1050, 70030     3-OMe   n-Hex   53    131-133 3320, 2940,                                1630, 1570                                1460, 1260,                                1045, 70031     3-OMe   i-Hex   41    148-150 3330, 2960,                                1630, 1565                                1460, 1260,                                1050, 70032     2,3-    n-Bu    70    138-139 3450, 2950,  diOMe                         2880, 1645                                1550, 1480, 127033     2,3-    n-Pen   47    152-154 3300, 2950,  diOMe                         1630, 1560                                1470, 1270, 75034     3,4-    n-Bu    72    131-133 3330, 2970,  diOMe                         1635, 1570                                1520, 1465,                                1260, 103035     3,4-    n-Pen   16    amorphous                                3350, 2950,  diOMe                         1620, 1550                                1460, 1240, 80036     3,4-    n-Hex   19    amorphous                                3350, 2950,  diOMe                         1630, 1560                                1460, 1250, 80037     2-Cl    n-Bu    10    118-119 3320, 2950,                                1640, 1560                                1460, 1250, 75038     2-Cl    n-Pen   11    149-150 3300, 2920,                                1630, 1560                                1460, 1250, 70039     2-Cl    n-Hex   13    131-132 3300, 2920,                                1630, 1560                                1460, 1250, 75040     3-Cl    n-Bu    30    186-188 3350, 2970,                                1630, 1570                                1460, 1250, 780, 70041     3-Cl    n-Pen   59    178-180 3320, 2990,                                1630, 1570                                1460, 1250, 69042     3-Cl    n-Hex   40    161-164 3320, 2950,                                1630, 1560                                1460, 1240, 75043     4-Cl    n-Bu    65    223-224 3350, 2980,                                1635, 1575                                1500, 1280,                                1015, 830______________________________________ 
    
     
                       TABLE 1-3______________________________________ ##STR12##Example               Yield Melting pointNo.    (R.sup.1).sub.m          R.sup.2                 (%)   (°C.)                                IR(KBr)cm.sup.-1______________________________________44     2-Me    n-Bu   32    122-124  3330, 2950,                                1630, 1560                                1460, 1250, 74045     3-Me    n-Bu   43    155-156  3330, 2950,                                1630, 1560                                1460, 1250, 70046     4-Me    n-Bu   43    amorphous                                3300, 2950,                                1630, 1560                                1460, 1250, 80047     2-Cl    n-Bu   42    162-164  3300, 2950,                                1630, 1560                                1460, 1250, 75048     3-Cl    n-Bu   28    140-142  3300, 2930,                                1630, 1560                                1460, 1250, 70049     4-Cl    n-Bu   29    170-171  3330, 2950,                                1630, 1560                                1460, 1250, 800______________________________________ 
    
     EXAMPLE 50 
     Preparation of (+)-1-(2-(2,3-dimethoxyphenyl)heptyl)-3-(2,6-diisopropylpehyl)urea 
     To 0.65 g (2.6 mmol) of (+)-2-(2,3-dimethoxyphenyl)-heptylamine was added dropwise a 5.2 ml of 0.502M toluene solution of 2,6-diisopropylphenyl isocyanate at room temperature and the whole was stirred overnight. The reaction mixture was concentrated and the resulting residue was crystallized from methanol. The crystals were collected by filtration and washed with n-hexane to give 0.512 g (43.5% yield) of (+)-1-(2-(2,3-dimethoxyphenyl)heptyl)-3-(2,6-diisopropylpheyl)urea. 
     Melting point: 113°-115° C. 
     IR (KBr) cm -1  : 3410, 3210, 2950, 1640, 1550, 1470, 1270, 1060, 800 
     NMR (CDCl 3 ) δ: 0.80 (t, 3H), 1.08-1.24 (m, 16H), 1.50-1.61 (m, 2H), 3.09-3.27 (m, 4H), 3.40-3.57 (m, 1H), 3.56 (s, 3H), 3.80 (s, 3H), 4.24 (br. s, 1H), 5.55 (s, 1H), 6.59 (d, 1H), 6.71 (d, 1H), 6.90 (t, 1H), 7.13 (d, 2H), 7.29 (t, 1H) 
     Optical rotation: [α] D   24  =+0.64 (c=2.67, methanol) 
     EXAMPLE 51 
     Preparation of (-)-1-(2-(2,3-dimethoxyphenyl)heptyl)-3-(2,6-diisopropylpheyl)urea 
     The title compound was prepared in a similar manner to Example 50 using (-)-2-(2,3-dimethoxypehnyl)heptylamine instead of (+)-2-(2,3-dimethoxyphenyl)heptylamine. Yield: 64%. 
     Melting point: 115°-116° C. 
     IR (KBr) cm -1  : 3410, 3210, 2950, 1640, 1550, 1470, 1270, 1060, 800 
     NMR (CDCl 3 ) δ: 0.80 (t, 3H), 1.08-1.24 (m, 16H), 1.50-1.61 (m, 2H), 3.09-3.27 (m, 4H), 3.40-3.57 (m, 1H), 3.56 (s, 3H), 3.80 (s, 3H), 4.24 (br. s, 1H), 5.55 (s, 1H), 6.59 (d, 1H), 6.71 (d, 1H), 6.90 (t, 1H), 7.13 (d, 2H), 7.29 (t, 1H) 
     Optical rotation: [α] D   24  =-0.83 (c=2.64, methanol) 
     TEST EXAMPLE 1 
     The effect of reducing a lipid level in blood by the action of the compounds according to the present invention was determined as follows: 
     Male golden Syrian hamsters weighing from 80 to 100 g were randomly divided into groups. The hamsters were first fed standard laboratory diets (solid feed MF-1 for mouse/rat/hamster, manufactured by Oriental Yeast Industries, KK) for 3 days. Then, they were fed the experimental diet containing 1% cholesterol and 0.5% cholic acid (manufactured by Oriental Yeast Industries, KK), ad libitum. At the same time, the compounds of the invention formulated in a shown dose (0.1-10 mg/10 ml water/kg) were administrated to the animals orally once a day at a determined time for 5 days. Water was administrated orally to the hamsters of control group in an amount of 10 ml per 1 kg of body weight. After five days of administrating the compounds, the animals were anesthetized with Pentobarbital Na (Nembutal injection, manufactured by Dainabbot) and three hours after the final administration of the test compound, a blood sample was taken from abdominal cava. The serum was separated from the sample by centrifuging. 
     The cholesterol level in the serum was determined by using a blood cholesterol measuring kit, Determina-TC5 manufactured by Kyowa Medix Co. The results are represented by percent inhibition (%) of cholesterol level in serum relative to that of the control group, and shown in the following Table 2. 
     
                       TABLE 2______________________________________Compound  Percent inhibition of cholesterol in serum (%)(Example No.)     5 mg/kg      1 mg/kg  0.1 mg/kg______________________________________ 9                     1912                     4315                     3619                     3624                     3929                     3632                     4333                              2436                     2640                     3849         33.sup.2)50                              1851                              25Comparative     5Example 1.sup.1)______________________________________ .sup.1) 1-(3,3-dimethyl-2-phenylbutyl)-3-(2,6-diisopropyl-phenyl)urea described in Japanese Patent Application LayingOpen (Kokai) No. 6456/90 .sup.2) 10 mg/kg 
    
     TEST EXAMPLE 2 
     The ACAT inhibitory action of the compounds according to the present invention was measured as follows: 
     ACAT activity in the hamster microsomes was determined by measuring the rate of radio-active cholesteryl-[ 14  C] oleate formation from cholesterol and radio-labelled oleoyl coenzyme A ( 14  C) with or without test compound. 
     Calculations of IC 50  value were made using data of the percent inhibition at each compound concentration. The results are shown in the following Table 3. 
     
                       TABLE 3______________________________________Compound     ACAT inhibitory activity(Example No.)        IC.sub.50 (nM)______________________________________ 9           4.912           2633           1640           31______________________________________