Claims
- 1. A method of treating hypocholesterolemia and atherosclerosis comprising administering to a patient an effective amount of a compound of the formula
- wherein R is phenyl (CH.sub.2).sub.n -- wherein n is zero and wherein the phenyl ring is substituted with two substituents in the 2- and 6-positions of the phenyl ring or with three substituents in the 2-, 4-, and 6-positions of the phenyl ring said substituents being selected from alkyl having 1 to 6 carbon atoms and which is straight or branched, alkoxy having from 1 to 6 carbon atoms and which is straight or branched, fluorine, chlorine, or bromine;
- wherein R.sub.1 is
- (a) hydrogen, or
- (b) alkyl having from 1 to 6 carbon atoms and is straight or branched;
- wherein R.sub.2 is
- (a) hydrogen;
- (b) a straight or branched hydrocarbon chain having from 1 to 20 carbon atoms and which is saturated or contains from 1 to 3 double bonds;
- (c) p-phenylmethoxybenzyl;
- (d) ##STR22## (e) --CH.sub.2 CH.sub.2 S(O).sub.0-2 CH.sub.3 ; or (f) phenyl, 1- or 2-naphthyl which is unsubstituted or is substituted with one or two substituents selected from alkyl having from 1 to 4 carbon atoms and which is straight or branched, alkoxy having from 1 to 4 carbon atoms, hydroxy, chlorine, fluorine, bromine, trifluoromethyl, or amino;
- (g) the group ##STR23## wherein t is zero to 4; w is zero to 4 with the proviso that the sum of t and w is not greater than 5; R.sub.11 and R.sub.12 are independently selected from hydrogen or alkyl having from 1 to 6 carbon atoms, or when R.sub.11 is hydrogen, R.sub.12 can be selected from the groups defined for R.sub.13 ; and R.sub.13 is phenyl, 1- or 2-naphthyl, or phenyl 1- or 2-naphthyl substituted with from one to three substituents selected from straight or branched alkyl having from 1 to 6 carbon atoms, straight or branched alkoxy having from 1 to 6 carbon atoms, phenoxy, hydroxy, fluorine, chlorine, bromine, nitro, hydroxymethyl, trifluoromethyl, --COOH, COOalkyl wherein alkyl has from 1 to 4 carbon atoms, and is straight or branched, --NR.sub.5 R.sub.6 wherein R.sub.5 and R.sub.6 are independently hydrogen or straight or branched alkyl of from 1 to 4 carbon atoms, or --CH.sub.2 NR.sub.5 R.sub.6 wherein R.sub.5 and R.sub.6 have the meanings defined above:
- (h) R.sub.1 and R.sub.2 taken together with the carbon atom to which they are attached form a saturated carbocyclic ring having from 3 to 7 carbon atoms;
- R.sub.3 is
- (a) hydrogen
- (b) a straight or branched hydrocarbon chain having from 1 to 20 carbon atoms and which is saturated or contains from 1 t 3 double bonds;
- (c) the group ##STR24## wherein q is zero to 3; r is zero to 2; s is 2 to 6; and Ar is phenyl,
- 1- or 2-naphthyl,
- phenyl or 1- or 2-naphthyl substituted with straight or branched alkyl of from 1 to 6 carbon atoms,
- straight or branched alkoxy of from 1 to 6 carbon atoms,
- hydroxy,
- benzyloxy,
- fluorine,
- chlorine,
- bromine,
- nitro,
- trifluoromethyl,
- --NH--COCH.sub.3,
- --CONH.sub.2,
- --COOH,
- --CH.sub.2 COOH,
- --CH.sub.2 CONH.sub.2,
- --NR.sub.7 R.sub.8 wherein
- R.sub.7 and R.sub.8 are independently hydrogen, alkyl of from 1 to 6 carbon atoms the terminal carbon of which optionally is substituted with an OR.sub.9 group where R.sub.9 is hydrogen, alkyl of from 1 to 6 carbon atoms, alkanoyl having from 2 to 5 carbon atoms, benzoyl, or R.sub.7 and R.sub.8 taken together with the nitrogen atom to which they are attached from a 5- or 6-membered ring optionally interrupted by an oxygen atom or --NR.sub.9 ; wherein R.sub.9 is as defined above;
- --CH.sub.2 NR.sub.7 R.sub.8 where R.sub.7 and R.sub.8 are as defined above;
- --CH.sub.2 OR.sub.9 where R.sub.9 is as defined above;
- --COO-alkyl where alkyl is from 1 to 6 carbons and is straight or branched and the terminal carbon of which optionally is substituted with an OR.sub.9 group or NR.sub.7 R.sub.8 where R.sub.7, R.sub.8, and R.sub.9 are as defined above;
- --NHCH.sub.2 COO-alkyl where alkyl is from 1 to 4 carbon atoms and is straight or branched;
- --SO.sub.2 NR.sub.7 R.sub.8 where R.sub.7 and R.sub.8 are as defined above;
- --SO.sub.2 OR.sub.9 where R.sub.9 is as defined above, or
- --NH--SO.sub.2 R.sub.10 where R.sub.10 is alkyl of 1 to 4 carbon atoms or phenyl;
- (d) the group ##STR25## wherein t, w, R.sub.11, R.sub.12, and R.sub.13 have the meanings defined hereinabove; or
- (e) 9-fluorenyl, 9-fluorenyl mono-substituted or di-substituted with chlorine, fluorine or bromine; or 9-fluorenyl mono-substituted on the 1-, 2-, or 4-position with straight or branched alkyl having from 1 to 6 carbon atoms, straight or branched alkoxy having from 1 to 6 carbon atoms, hydroxy, hydroxymethyl, --COOH, --COOalkyl wherein the alkyl group is straight or branched and has from 1 to 6 carbon atoms, or --CONR.sub.5 R.sub.6 wherein R.sub.5 and R.sub.6 have the meaning defined above;
- R.sub.4 is
- (a) hydrogen;
- (b) a straight or branched hydrocarbon chain having from 3 to 20 carbon atoms and which is saturated or contains from 1 to 3 double bonds;
- (c) the group ##STR26## wherein t, w, R.sub.11, R.sub.12, and R.sub.13 have the meanings defined hereinabove;
- (d) or R.sub.3 is hydrogen or a saturated straight hydrocarbon chain having from 1 to 4 carbon atoms and R.sub.4 is trityl;
- (e) 9-fluorenyl or 9-fluorenyl substituted with from 1 to 3 substituents selected from fluorine, chlorine, bromine, straight or branched alkyl having from 1 to 4 carbon atoms; --NHCO alkyl or --CO.sub.2 alkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched; or
- (f) phenyl or phenyl substituted with one or two substituents selected from straight or branched alkyl having from 1 to 4 carbon atoms, chlorine, bromine, fluorine, trifluoromethyl, hydroxy, straight or branched alkoxy having from 1 to 4 carbon atoms, amino or nitro; or a pharmaceutically acceptable salt thereof; with the provisos that each of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 is not hydrogen at the same time; each of R.sub.2, R.sub.3, and R.sub.4 is not at the same time a straight or branched hydrocarbon chain having from 1 to 20 carbon atoms and which is saturated or contains from 1 to 3 double bonds; and when each of R.sub.2 and R.sub.4 represents the group ##STR27## R.sub.12 does not have the same meaning as R.sub.13 ; and R.sub.12 and R.sub.13 are not a 9-fluorenyl substituent at the same time.
CROSS REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part of application Ser. No. 401,367 filed Aug. 31, 1989 now abandoned.
US Referenced Citations (7)
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
401367 |
Aug 1989 |
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