GB2058061A

GB2058061A - 1,1,2-Triphenylpropane and -propene derivatives

Info

Publication number: GB2058061A
Application number: GB8026768A
Authority: GB
Original assignee: Egyt Gyogyszervegyeszeti Gyar
Current assignee: Egyt Gyogyszervegyeszeti Gyar
Priority date: 1979-08-15
Filing date: 1980-08-15
Publication date: 1981-04-08
Also published as: PL131227B1; YU42980B; BG35031A3; PL226254A1; GR69821B; SU1253426A3; FI74271C; YU43182B; BE884716A; SE450250B; CS241030B2; SU1097192A3; DD152536A5; NL8004542A; DK351780A; CH649758A5; JPH0234933B2; ATA419280A; YU206880A; ES8104782A1

Abstract

New 1,1,2-triphenylpropane and -propene derivatives of the general formula (I), <IMAGE> wherein A and B each stand for hydrogen or they form together a valence bond, X and Y are identical or different and stand for phenyl group or a phenyl group having a halogen, hydroxy methoxymethoxy, C1-6 alkoxy or benzyloxy substituent in the para position, R1 is a C1-6 alkyl, epoxyalkyl, azidoalkyl, methoxymethyl or benzyl group or a group of the general formula (II), <IMAGE> wherein R2 and R3 each represent hydrogen or a C1-6 alkyl, hydroxyalkyl or haloalkyl group, or R2 and R3 form together with the adjacent nitrogen atom an up to 8-membered heterocyclic group, an up to 6-membered heterocyclic group optionally containing further hetero atom(s), which heterocyclic groups optionally have a lower alkyl or hydroxyalkyl substituent, a guanidino group, an aminoguanidino group or a nitroguanidino group, with the proviso that if A and B form together a valence bond and X and Y each stand for phenyl or X is phenyl and Y is p-methoxyphenyl, R1 may not stand for a dimethylaminoethyl, diethylaminoethyl, pyrrolidinoethyl, a piperidinoethyl or morpholinoethyl group in the (Z) isomers, stereoisomers and isomeric mixtures thereof, and acid addition salts of the basic compounds of the general formula (I) exert oestrogenic or antioestrogenic effects and furthermore inhibit the growth of the mammary tumor induced by 7,12-dimethyl-benz(a)anthracene.

Description

SPECIFICATION New 1,1 2-triphenylpropane and -propene derivatives, a process for the preparation thereof and pharmaceutical compositions containing the new compounds The invention relates to new 1,1 2-triphenylpropane and and -propene derivatives, a process for the preparation thereof and pharmaceutical compositions which contain the new compounds.

It is known that some triphenylalkane derivatives possess oestrogenic properties [J. Grundy: Chem. Rev.

57,281(1957); P.R. Carter et al.: J. Chem. Soc. 1948, 150; N.P. Buu-Hoi et al.: Chim. Ther. 1969,327; W.J.

Middleton et al.: J. Med. Chem. 14, 1193 (1971); U.S. patent specification No. 3,712,929]. Analogous derivatives with a basic substituent on the phenyl ring possess primarily antioestrogenic effects [D.J. Collins et al.: J. Med. Chem. 14, 952 (1971)]. The two most important representatives of these compounds are 1 -[4-(2-diethylaminoethoxy)-phenyl]-1 ,2-diphenyl-2-chloroethylene (Clomifen) and (Z)-1 -[4-(2- dimethylaminoethoxy)-phenyl]-1 ,2-di-phenyl-1 -butene (Tamoxifen) - see F.P. Palopoli et al.: J. Med. Chem.

10, 84 (1966); G.R. Bedford et al.: Nature 212,733 (1966). Although both compounds show antioestrogenic (oestrogen-antagonizing and slight oestrogen-agonizing) activities, the former compound is applied primarily to induce ovulation [M. Murray et al.: J. Obstet.Gynaec.Br.Commonw. 78, 1108 (1971)] and in the treatment of oligospermy [J.F. Potts: J. Am. Med. Ass. 231,907 (1975)], whereas the main field of use of Tamoxifen is the treatment of mammary tumors [M.P. Cole et al.: Brit. J. Cancer 1971, 270]. Both compounds have, however, the disadvantage that upon prolonged treatment undesired side effects, such as eye damages [H.J. Silverman: Am. J. Optom. 49,335(1972); L.M. Roch et al.: Arch.Ophtalm. 77, 14(1967); M.J.

Kaiser-Kupfer et al.: Cancer Treatment Rep. 62,315 (1978)] liver damages [Martindale: The Extra Pharmacopoeia XXVII. 1392 (1977); The Pharmaceutical Press, London], and thrombosis [K. Nevasaarie et al.: Lancet, 946(1978)] appear.

The invention aims at providing new compounds which are superior in activity than the known ones, exert more specific effects and cause only minor undesired side effects.

The new compounds according to the invention exert various effects on the endocrinous system, and greatly inhibit the growth of mammary tumors induced experimentally by 7,1 2-dimethyl-benz(a)anthracene (DMBA).

The new 1,1,2-triphenyl propane and -propene derivatives according to the invention correspond to the general formula (I),

wherein A and B each stand for hydrogen or they form together a valence bond, X and Y are identical or different and stand for phenyl group or a phenyl group having a halogen, hydroxy, methoxy-methoxy, C16 alkoxy or benzyloxy substituent in the pare position, R1 is a C16 alkyl, epoxyalkyl, azidoalkyl, methoxymethyl or benzyl group or a group of the general formula (II),

wherein R2 and R3 each represent hydrogen or a C1 6 alkyl, hydroxyalkyl or haloalkyl group, or R2 and K3 torm together with the adjacent nitrogen atom an up to 8-membered heterocyclic group, an up to 6-membered heterocyclic group optionally containing further hetero atom(s), which heterocyclic groups optionally have a lower alkyl or hydroxyalkyl substituent, a guanidino group, an aminoguanidino group or a nitroguanidino group, with the proviso that: (a) if A and B form together a valence bond and X and Y each stand for phenyl or Xis phenyl and Y is p-methoxyphenyl, R1 may not stand for a dimethylaminoethyl, diethylaminoethyl, pyrrolidinoethyl, piperidinoethyl or morpholino-ethyl group in the (Z) isomers; (b) if A and B form together a valence bond and X and Y each stand for phenyl R' may not stand for methyl or ethyl;; (c) if A and B form together a valence bond and X andY each stand for phenyl, then in the case of (Z) isomers, R' may not stand for dimethylamino ethyl, diethylaminoethyl, morpholinoethyl or piperidinoethyl.

(d) if A and B form together a valence bond X stands for phenyl and Y stands for paramethoxyphenyl R' may not stand for methyl or pyrrolidinoethyl; (e) if A and B form together a valence bond X stands for paramethoxyphenyl, parafluorphenyl or paraethoxyphenyl, and Y stands for phenyl R' may not stand for methyl; (f) if A and B form together a valence bond Xis phenyl and Y is parahydroxyphenyl, R' may not stand for methyl; (g) if A and B form together a valence bond and X and Y each stand for paramethoxyphenyl, R' may not stand for methyl.

Stereoisomers and isomeric mixtures of the above compounds, furthermore acid addition salts of the basic compounds having the general formula (I) are also embraced by the scope of the invention.

The term "alkyl group", used either alone or in combination (such as alkoxy, azidoalkyl, epoxyalkyl, hydroxyalkyl or haloalkyl) refers to a straight-chained or branched saturated aliphatic hydrocarbyl group of 1 to 6, preferably 1 to 4 carbon atoms (such as methyl, ethyl, n-propyl, isopropyl, n-butyl sec.-butyl, etc.

preferably methyl or ethyl group). The term "halogen" embraces all the four halogens, i.e. fluorine, chlorine, bromine and iodine. If R2 and R3 form together with the adjacent nitrogen atom an optionally alkyl- or hydroxyalkyl-substituted heterocyclic group, this group may be preferably a pyrrolidino, piperidino, heptamethyleneimino, morpholino, piperazino or N-methylpiperazino group.

In a preferred subgroup of the compounds having the general formula (I) A and B together form a valence bond.

Those compounds of the general formula (I) are also preferred, in which A and B each stand for hydrogen or they form together a valence bond, X and Y are identical or different and stand for a phenyl or p-hydroxyphenyl group, and R1 represents a C14 hydroxyalkyl group, a C1 4 azidoalkyl group or a group of the general formula (II), wherein R2 and R3 each stand for hydrogen, a C1.4 alkyl group or a C1 4 hydroxyalkyl group or they form, together with the adjacent nitrogen atom, a piperazino, pyrrolidino, piperidino or morpholino group having optionally a C1.4 alkyl substituent.

Particularly preferred representatives of the compounds of the generalformula (1) are the following derivatives : threo-1-[4-(2,3-epoxypropoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propane, (E)-1,2-diphenyl3,3,3-trifluuro-1-[4-(2-/4methylpiperazino/-ethoxy)-phenyl]-propene, 1-[4-(2-dimethylamino-ethoxy)phenyl]-2-phenyl-3,3,3-trifluoro-1-[4-(hydroxyphenyl)-propen, 1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-/2hydroxyethylamino/-ethoxy)-phenyl]-propene, (E)-1-[4-(2-azidoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoropropene, 1-[4-(2-dimethylamino-ethoxy)-phenyl]-3,3,3-trifluoro-1,2-bis-(4-hydroxyphenyl)-propene and pharmaceutically acceptable acid addition salts thereof, and 1-[4-(2-dimethylamino-ethoxy)-phenyl]-3,3,3trifluoro-1 ,2-bis-(4-hydroxy-phenyl)-propene hydrochloride. The last two derivatives are particularly preferred.

The basic compounds of the general formula (I) form acid addition salts with mineral or organic acids, such as hydrochloric, hydrobromic, sulfuric, phosphoric, maleic, fumaric, lactic, methanesulfonic, ptoluenesulfonic, citric, etc. acids.

The compounds of the general formula (I) can be presented in the form of various stereoisomers, such as (Z) and (E) isomers, threo and erythro isomers, etc. All of the stereoisomers and mixtures thereof, furthermore their preparation as well as the pharmaceutical compositions which contain such isomers or isomeric mixtures are embraced by the scope of the invention.

The invention relates further to a process for the preparation of 1,1 ,2-triphenylpropane and-propene derivatives of the general formula (I), wherein A, B, X, Y and R1 are as defined above, stereoisomers and isomeric mixtures thereof, and acid addition salts of the basic compounds having the general formula (I).

These compounds are prepared according to the invention as follows: a) to prepare a compound of the general formula (I) in which A and B are as defined above, X and Y are identical or different and represent a phenyl group, a p-halophenyl group or a p-(C1.6 alkoxy)-phenyl group, R1 stands for azido-ethyl group or a group of the general formula (it), wherein R2 and R3 are as defined above, a phenoxyalkylhalide or sulfonate of the general formula (III),

wherein A and B are as defined above, Y and X are as defined in point a) and Z stands for halogen or a sulfonyloxy group, is reacted with an amine of the general formula R2R3NH, wherein R2 and R3 are as defined above, or with an alkali metal azide, and, if desired, the resulting azido derivative is reduced, and, if desired, a resulting amino derivative is converted into the respective guanidino, aminoguanidino or nitroguanidino derivative; or b) to prepare a compound of the general formula (I) in which A and B form together a valence bond, X and Y are identical or different and represent an unsubstituted phenyl group or a phenyl group which has a chloro, bromo, methoxymethoxy, C1 6 alkoxy or benzyloxy substituent in the para position, and R1 stands for a group of the general formula (II), wherein R2 and R3 each represent hydrogen or a Ca 6 alkyl group, or R2 and R3 form together with the adjacent nitrogen atom an up to 8-membered heterocyclic group or an up to 6-membered heterocyclic group optionally containing further hetero atom(s), which heterocyclic groups optionally have a lower alkyl or hydroxyalkyl substituent, a compound of the general formula (IV),

wherein A and B stand for hydrogen and X and Y are as defined in point b) above, is dehydrogenated and then reacted with an alcohol derivative of the general formula R1OM, wherein R1 is as defined in point b) and M stands for an alkali metal atom; or c) to prepare a compound of the general fomula (I) in which A and B are as defined above, X and Y are identical or different and represent an unsubstituted phenyl group or a phenyl group having a halogen or C1 6 alkoxy substituent in the para position and R1 stands for a C16 alkyl, epoxyalkyl, methoxymethyl or benzyl group or represents a group of the general formula (II), wherein R2 and R3 each stand for a C1.6 alkyl group or they form together with the adjacent nitrogen atom an up to 8-membered heterocyclic group or an up to 6-membered heterocyclic group optionally containing further hetero atom(s), which heterocyclic groups optionally have a lower alkyl substituent, a compound of the general formula (V),

wherein A and B are as defined above and X and Y are as defined in point c), is reacted with an R1-halide or an R1-sulfonate, wherein R1 is as defined in point c) above, in the presence of an acid binding agent; or d) to prepare a compound of the general formula (I) in which A and B form together a valence bond, X and/or Y stands for a p-hydroxyphenyl group and R1 is a group of the general formula (II), wherein R2 and R3 each represent hydrogen or a C16 alkyl group or they form together with the adjacent nitrogen atom an up to 8-membered heterocyclic group or an up to 6-membered heterocyclic group optionally containing further hetero atom(s), which heterocyclic groups optionally have a lower alkyl substituent, a compound of the general formula (IV), wherein A and B are as defined in point d) and X and/or Y is a p-(methoxymethoxy)phenyl group or a benzyloxyphenyl group, is reacted with an alcohol derivative of the general formula R1OM, wherein R1OM, wherein R1 is as defined in point d) and M is an alkali metal atom, and then the methoxymethoxy group or the benzyloxy group is subjected to an ether splitting reaction; or (e) to prepare a compound of the general formula (I) in which A and B form together a valence bond, X and Y are identical or different and stand for an unsubstituted phenyl group or a phenyl group which has a halo, methoxymethoxy, C1.6 alkoxy or benzyloxy substituent in the para position and R1 represents a C1.6 alkyl, epoxyalkyl, azidoethyl, methoxymethyl or benzyl group, a compound of the general formula (I), wherein A and B each stand for hydrogen and X, Y and R1 are as defined in point e), is dehydrogenated; or f) to prepare a compound of the general formula (I) in which R1 represents a group of the general formula (II) and in this latter formula R2 and/or R3 stands for a C16 halo-alkyl group, a compound of the general formula (I), wherein R1 is a group of the general formula (II) and in this latter formula R2 and/or R3 represents a C16 hydroxyalkyl group, is halogenated; and, if desired, the individual stereoisomers are separated from a resulting isomeric mixture, and, if desired, a basic compound of the general formula (I) is converted into its acid addition salt or liberated from its acid addition salt.

Process variant a) of the invention is performed preferably so that the starting substance of the general formula (III) is heated with an amine of the general formula R1R3NH in an inert solvent or diluent (such as alcohol, aqueous alcohol, acetone, etc.) in the presence of an acid binding agent (such as potassium carbonate or an excess of the amine reactant), or is reacted with an alkali metal azide in dimethylformamide or preferably in aqueous 2-methoxyethanol. If desired, a resulting azide derivative can be reduced in a manner known per se e.g. with an alkali metal hydride or with hydrogen in the presence of palladium-on-carbon catalyst.

In the starting substances of the general formula (III) Z is preferably a halogen atom (fluorine, chlorine, bromine or iodine), an alkylsulfonyloxy group (e.g. methylsulfonyloxy group) or an arylsulfonyloxy group (e.g. an optionally substituted phenylsulfonyloxy group, such as phenylsulfonyloxy, p-toluenesulfonyloxy or p-bromophenylsulfonyloxy group).

Process variant b) of the invention is performed preferably so that a compound of the general formula (IV), wherein A and B stand for hydrogen, is reacted with 1 to 3 molar equivalents of 2,3-dichloro-5,6-dicyano-1 4- benzoquinone in an inert solvent (e.g. benzene or dioxane) at the boiling point of the reaction mixture, and the resulting compound is reacted with an alcohol derivative of the general formula R1OM in a bipolar aprotic solvent (e.g. dimethyl acetamide, hexamethylphosphoric triamide, etc.) or preferably in an excess of the alcohol of the general formula R1OH. This latter reaction is performed preferably at 100 to 1600C.

According to process variant c) of the invention a phenol derivative of the general formula (V) is reacted with an R1-halide or an R1-sulfonate in a solvent or diluent, such as benzene, alcohol, etc., in the presence of an acid binding agent, such as an alkali metal hydroxide or an alkali metal carbonate. According to a preferred method the process is performed with an alkali metal salt of the starting phenol derivative, which also serves as acid binding agent.

Process variant d) of the invention is performed preferably as described above for process variant b). The resulting methoxymethoxy or benzyloxy derivative is treated then with an acid or reduced to effect the splitting of the ether group.

In process variant e) of the invention a compound of the general formula (I), wherein A and B each stand for hydrogen, is dehydrogenated. Dehydrogenation is performed preferably by reacting the starting substance with 2,3-dichloro-5,6-dicyano-1 ,4-benzoquinone in an inert solvent (e.g. benzene or dioxane) at the boiling point of the reaction mixture (see Org. Synth. Coll. Vol.5,428-431).

According to process variantf) of the invention a compound of the general formula (I), wherein R1 is a group of the general formula (II) and in this latter formula R2 and/or R3 stands for hydroxyalkyl, is reacted with a halogenating agent to obtain the respective derivative wherein R2 and/or R3 is a haloalkyl group.

Halogenation is performed in a manner known per se, utilizing conventional halogenating agents, such as thionyl chloride, etc.

The individual stereoisomers can be separated from their mixtures by methods known per se, such as fractional crystallization.

The basic compounds of the general formula (I) can be converted into their acid addition salts by reacting them with the appropriate acid in an inert solvent. Of the acid addition salts those formed with pharmaceutically acceptable acids are preferred. The bases can be liberated from the respective acid addition salts by treatment with a strong base.

The starting substances of the general formulae (III), (IV) and (V) are, with the exception of (Z)-1 ,2-diphenyl-3,3,3-trifluoro-1 -(44luorophenyl )-propene, (Z)-1 ,2-diphenyl-3,3,3-trifluoro-1 -(4- hydroxyphenyl)-propene and (E)-2-phenyl-3,3,3-trifluoro-1 -(4-hydroxyphenyl )-1 -(4-methoxyphenyl )propene, new compounds. The preparation of the new starting substances is described in detail in the examples.

The endocrinological and tumour-inhibitory effects of the new compounds according to the invention are demonstrated by the following tests. The compounds tested are listed below: 1 = threo-1 -[4-(2,3-epoxypropoxy)-phenyl]-1 ,2-diphenyl-3,3,3-trifl uoro-propane.

2 = 1 -[4-(2-3-epoxypropoxy)-phenyl]-1 ,2-diphenyl-3,3,3-trifluoro-propene, 3 = (E)-l ,2-diphenyl-3,3,3-trif uoro-1 -[4-(2-bis-/2-hydroxyethyl )-aminoi-ethoxy)-phenyl]-propene, 4 = (E)-1 ,2-diphenyl-3,3,3-trifluoro-1 -[4-(244-methylpiperazino/-ethoxy)-phenyl]-propene, 5 = 1-[4-(2-dimethylaminoethoxy)-phenyl]-2-phenyl-3,3,3-trifluoro-1-(4-methoxyphenyl)-propene, 6 = 1 -[4-(2-dimethylaminoethoxy)-phenyl]-2-phenyl-3,3,34rifiuorn-1 -(4-hydroxyphenyl)-propene, 7 = 1 ,2-diphenyl-3,3,3-trifluoro-1 -(4(2-;;2-hydrnxyethylaminoi-ethoxy)-phenyl]-prnpene, 8 = 1-[4-(2-dimethylaminoethoxy)-phenyl]-1-phenyl-3,3,3-trifluoro-2-(4-hydroxyphenyl)-propene, 9 = (E)-1,2-diphenyl-3,3,3-trifluoro-2-[4-(2-pyrrolidinoethoxy)-phenyl]-propene, 10 = (E)-l ,2-diphenyl-3,3,3-trifluoro-l -[4-(2-morpholinoethoxy)-phenyl]-propene 11 = (E)-l -[4-(2-diethylaminoethoxy)-phenyl]-l ,2-diphenyl-3,3,3-trifluoro-propene, 12 = (E)-l -[4-(2-azidoethoxy)-phenyl]-l ,2-diphenyl-3,3,3-trifluoro-propene, 13 = (E)-1 ,2-diphenyl-3,3,34rifiuorn-1 -[4-(2- )-a mino -ethoxy)-phenyl]-propene, 14 = 1 -[4-(2-dimethylaminoethoxy)-phenylj-3,3,3-trifluor-1 ,2-bis-(4-hydroxyphenyl)-propene hydroch loride, 15 = 1 -phenyl-2-(4-methoxyphenyl 1-1 -[4-(2-dimethylaminoethoxy)-phenyl]-3,3,34ruoro-prnpene, 16 = (E)-1 .2-diphenyl-3,3,3-trifluoro-1 -[4-(2- nitroguanidino -ethoxy)-phenyl]-propene.

The antioestrogenic effect was determined by the method of M.J.K. Harper et al. [J. Reprod. Fert. 13,101 (1967)]. 24 days old infantile female rats were treated with daily dosages of 5 9 kg of oestradiol for 3 days.

The test compound was also administered once a day orally for 3 days. On the 4th day the animals were sacrificed, and their uterus was removed and weighed. The data characteristic of the antioestrogenic activity (inhibition of the uterotropic effect of oestradiol) of some compounds according to the invention are listed in Table 1.

The antioestrogenic activity of some of the compounds listed in Table 1 reaches the activity of Clomifen or Tamoxifen, applied as reference substances. Compound No. 1 produces, however, only a slight inhibition when applied in an oral dosage of 1 mg, kg. The degree of inhibition still remains low (39%) when the dosage is increased to 10 mg kg.

TABLE 1 Determination of the antioestrogenic effect on infantile female rats Compound Dosage mg/kg/day tested 0.1 0.3 1.0 3.0 10.0 Clomifen -37.1 -67.7 -73.3 Tamoxifen -45.6 # 6.85 -55.2 # 2.5 -60.9 # 4.04 -70.9 # 4.52 -68.6 # 4.83 1 - 3.0 -39 2 -29 -24 -38 -78 -66 3 -14 -53 -59 -67 -73 4 -65.2 # 3.93 -71.9*1.81 -71.8*5.0 -72.2+5.5 5 -52.8+4.2 -52.2*6.12 -60.8*2.13 -68.2*3.32 -63.0*3.68 6 -37.0+5.3 -35.7 # 3.85 -48.4*8.61 -51.6*3.49 -61.0*3.9 7 -26.5 # 2.98 -49.2 # 2.1 -68.5 # 5.14 -60.4 # 2.5 - 51.0 # 8.1 8 -26 -29 -54 -61 14 -31 -32 -43 -50 -61 Remarks: The antioestrogenic (uterus weight lowering) effects of the compounds are given in per cents.

The tests were performed on groups of 5 to 10 animals.

The oestrogenic (uterotropic) effect was determined according to the method of R.J. Dorfman [Endocrinology 55,65 (1954)]. 24 days old female rats were treated with single daily oral dosages of the test compounds. On the 4th day the animals were sacrificed, and their uterus was removed and weighed. The data characteristic of the oestrogenic (uterotropic) effects of some of the compounds according to the invention are listed in Table 2. Ethynyloestradiol, a highly effective oestrogenic substance, and Clomifen and Tamoxifen, two known antioestrogenic agents, were also tested and their activity data are also presented.

The compounds listed in Table 2 possess generally weak oestrogenic properties, or, in the dosage range of 0.1 to 1.0 mg/kg, their activity is somewhat lower than that of Tamoxifen. The dosage-activity curve of Compound No. 1 is, however, somewhat steeper than those of the other compounds. Thus, in the lower dosage range (0.01 to 3.0 mg/kg) applied, the oestrogenic effect of Compound No. 1 is even weaker than the weak antagonistic effects of the antioestrogenic agents, whereas the maximum increase in uterine weight attainable at higher dose ranges (1 Omg/kg) with Compound No. 1 is higher than that attainable by the antioestrogenic agents.

TABLE 2 Determination of the uterotropic (oestrogenic) effect on infantile female rats Compound Dosage mg/kg/day p.o.

tested 0 0.01 0.03 0.1 0.3 1.0 3.0 10.0 20.0 Ethynyloestradiol 59.3 # 5.2 142.6 # 5.2 197.0 # 11.75 184.6 # 7.6 198.4 # 14.9 166.8 # 9.34 192.2 # 4.3 212.2 # 11.8 Temoxifen 41.5 # 1.36 75.6 # 3.76 79.0 # 2.67 102.3 # 4.35 96.2 # 4.04 108.3 # 6.97 113.0 # 6.97 110.1 # 4.5 101.0 Clomifen 41.5 # 1.36 107.3 # 6.48 103.3 # 6.38 94.4 # 2.35 1 41.5 # 1.36 49.2 # 3.48 52,2 # 2.67 65.8 # 5.7 72.0 # 4.6 118.2 # 9.9 130.6 # 11.2 142 # 10.47 138.0 2 59.3 # 5.2 84.5 # 4.33 87.5 # 8.7 90.8 # 3.4 95.0 # 3.14 101.2 # 4.3 107.0 # 2.19 128 # 5,.83 3 41.5 66 79 99 102 104 106 114 4 59.3 # 5.2 76.6 # 4.4 86.6 # 6.6 89.8 # 10.6 91.0 # 2.16 97.4 $4.43 100.8 # 0.7 110.8 # 6.18 7 59.3 # 5.2 72.0 # 2.7 73.7 # 4.5 89.6 # 5.0 96.0 # 5.8 101.0 # 1.9 99.4 # 4.07 112.2 # 8.0 8 59.3 # 5.2 83.9 # 4.7 79.5 # 5.4 78 # 3.4 92.2 # 1.6 95.8 # 3.67 102.8 # 3.2 106.0 # 3.4 14 38.0 # 2.9 59.0 1.7 74.0 # 4.3 77.0 # 6.1 79.0 # 2.3 78.0 # 1.2 Remarks : The tests were performed on group of 5 to 10 animals .

The weight of the uterus is given as mg/100 kg body weight.

The stimulating effect exerted on the secretion of luteinizing hormone (LH) was determined as follows: 24 days old infantile female rats were treated subcutaneously with the compounds to be tested on two consecutive days. Two hours after the second treatment the animals were bled and the luteinizing hormone (LH) level of the plasma was determined by radioimmune assay. When administered in subcutaneous dosages of 1 mglkg, the compounds tested provoke a considerable increase in the LH level of the plasma.

The results are summarized in Table 3.

TABLE 3 LH-level increasing effect on infantile female rats Compound tested Percentage change of the LH level in relation to the controls Tamoxifen 117 1 96 3 134 4 106 7 39 9 53 Remarks: The tests were performed on groups of 4 or 5 animals. Dosage: 2x 1 mg/kg s.c.

The effects of the new compounds exerted on hormone-dependent tumours were tested by the method of P. Griswold et al. [Cancer Research 26,2169 (1966)] on mammary cancer induced by 7,1 2-dimethyl- benz(a)anthracene (DMBA). The treatment was started when the weight of the tumor reached about 500 mg, and the animals were treated for 3 months with oral dosages of 20 mg/kg of the active agent, administered three times a week.

The size of the tumors was measured as described by the above authors as well as according to the method of V.C. Jordan et al. [Europ. J. Cancer 12,419(1976)], with a calliper gauge. The volume of the tumor was determined by the method of Griswold. The animals were kept under observation for 2 additional months after the termination of the treatment period, and the tumors were measured in this latter period as well.

A relative effectivity index was introduced to characterize the activities of the compounds tested. To calculate the relative effectivity index the number of animals showing a permanent or transitory cure or remission of various durations was determined and scored according to the following table: permanently cured 10 points temporarily cured 8 points durable remission 6 points short remission or unchanged state 4 points The changes in average tumor number appearing during the treatment period were evaluated according to the following scale: : no increase in tumor count in any of the animals 8 points the average number of tumors increases twofold 6 points higher increase in the average number of tumors 0 points The score numbers determined for the individual animals by the above two scales were added, and the result was expressed in percents related to the score number which corresponds to the maximum activity (permanent cure). This percentage value is the relative effectivity index.

The results of the test are listed in Table 4, where the figures in brackets have the following meanings: (1) permanently cured; (2) temporarily cured; (3) durable remission; (4) short remission; (5) un changed state.

TABLE 4 Effect on the mammary cancer of rats induced by DMBA Compound Activity Relative tested effectivity (1) (2) (3) (4) (5) index Untreated controls - - - - 25/25 0 Tamoxifen 2/5 1/5 - 1/5 1/5 70 1 4/5 1/5 - - - 96 3 1/5 1/5 - 3/5 - 65 4 - - 3/4 1/4 - 60 6 2/5 1/5 1/5 - 1/5 78 7 2/5 1/5 1/5 - 1/5 78 10 4/5 - - - 1/5 90 11 1/5 - 3/5 - 1/5 72 12 2/5 2/5 1/5 - - 85 13 1/5 1/5 1/5 2/5 - 67 15 2/5 - 2/5 - 1/5 70 16 - 1/4 3/4 - - 73 The invention relates further to pharmaceutical compositions which contain as active agent one or more compounds of the general formula (I) in the form of single isomers or mixtures of isomers, or acid addition salts of the basic compounds of the general formula (I) together with conventional inert, solid or liquid pharmaceutical carriers.These pharmaceutical compositions can be applied both in the human therapy and for veterinary purposes to influence the endocrine system. Some of the compounds of the general formula (I) can also be applied in the treatment of tumors, since they inhibit the growth of tumors induced experimentally by DMBA to a great extent. The pharmaceutical compositions can be presented preferably in the form of orally administerabie preparations (such as tablets, capsules, powder mixtures, solutions, suspensions, emulsions, elixirs, etc.) or as compositions for parenteral administration (e.g. injectable solutions or suspensions). These compositions may contain conventional inert, solid or liquid carriers (such as starch, lactose, magnesium stearate, silicon dioxide, magnesium carbonate, polyvinylpyrrolidone, water, etc.).The active agent content of the compositions varies generally between 0.05 and 98%. The pharmaceutical compositions may also contain conventional pharmaceutical additives or auxiliary agents, such as emulsifying, dispersing, wetting or disintegrating agents, buffers, etc.

The pharmaceutical compositions can be prepared by methods commonly applied in the pharmaceutical industry.

The daily dosage of the compounds according to the invention depends on various factors, such as the age and general health conditions of the patient, severity of the disorder, activity of the individual compounds, etc. The daily oral dosages vary generally within about 0.01 to 10 mg/kg body weight.

The above data are, however, only of informative character, since higher or lower dosages can also be applied, if necessary.

The invention is elucidated in detail with the aid of the following non-limiting Examples.

EXAMPLE 1 Preparation of erythro- and threo- 1,2-diphenyl-3,3,3-trifluoro- l-f4-(2-morpholinoethoxy)-phenylj-propane A mixture of 1.20 g (2.67 mmoles) of erythro-1 -[4-(2-bromoethoxy)-phenyl]-1 ,2-diphenyl-3,3,3-trifluoro- propane and 4.80 g of morpholine is heated to boiling, then cooled, diluted with 50 ml of ether and washed with water until neutral. The etheral solution is dried, evaporated to dryness, and the residue is crystallized from hexane. 1.02 g (83.6%) of erythro-1 ,2-diphenyl-3,3,3-trifluoro-1 -[4-(2-morpholino-ethoxy)-phenyl]- propane are obtained; m.p.: 112-115"C.

Analysis: calculated for C27H28F3NO: C: 71.19%, H: 6.20 %, F: 12.51% N: 3.08%; found: C: 71.07%, H: 6.37%, F: 12.71%, N:2.97%, A mixture of 3.60 g (8 mmoles) of threo-1-[4-(2-bromo-ethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro- propane and 14 g of morpholine is heated to boiling, and thereafter one proceeds as described above. The resulting product is crystallized from hexane to obtain 2.85 g (78.3%) ofthreo-1 ,2-diphenyl-3,3,3-trif luoro-l [4-(2-morpholinoethoxy)-phenyl]-propane; m.p.: 88-91"C.

Analysis: calculated for C27H28F3NO2: C: 71.19%, H: 6.20%, F: 12.51%, N: 3.03% found: C: 71.24%, H: 6.44%, F: 12.45%, N: 3.03%.

The starting substances, erythro and threo-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro- propane, are prepared as follows: A solution of 456 9 (1.17 moles) of benzyl-triphenyl-phosphoniumchloride [G. Wittig: Chem. Ber. 87,1318 (1954)] in 1500 ml of dry ethanol is added to a solution of g (1.17 g.-atoms) of sodium in 500 ml of dry ethanol at 0-2"C. The resulting mixture is combined with a solution of 204 g (1.17 moles) of 2,2,2-trifluoroacetophenone in 100 ml of dry ethanol, and the mixture is allowed to stand overnight. The solution is evaporated, the residue is admixed with 800 ml of petroleum ether, filtered, and the filter cake is washed.The filtrate is evaporated, and the residue is distilled in vacuo. 268 g (92.5%) of 1,2-diphenyl-3,3,3trifluoro-propane are obtained; b.p.: 107-109 C/0.2 mm Hg, m.p.: 58-61 C.

Analysis: calculated for C15H11F3; C: 72.57% H: 4.47%, F: 22.96%; found C: 72.49% H: 4.23% F: 23.20% 268 g (1.08 moles) of the above product are hydrogenated at 200C for 6.8 hours in 4000 ml of acetic acid, in the presence of 20 g of a 10% palladium-on-carbon catalyst. The solution is evaporated and the residue is distilled in vacuo. 252 g (93.3%) of 1,2-diphenyl-3,3,34rifluoro-propane are obtained; b.p.: 94-96 C/0.1 mm Hg, nD = 1.5100.

Analysis: calculated for C15H13F3: C: 71.98% H: 5.26%, F: 22.75%; found C: 72.12% H: 5.44% F: 22.50%.

5 g (0.02 moles) of benzoyl peroxide are added to a solution of 250 g (1 mole) of the above product in 2500 ml of carbon tetrachloride, and then a solution of 176 g (1.1 moles) of bromine in 500 ml of carbon tetrachloride is added to the mixture at 500C within 30 minutes. The resulting mixture is boiled for 2 hours, then cooled, washed with sodium thiosulfate solution, sodium hydrocarbonate solution and then with water, dried and evaporated. The residue is crystallized from 1260 ml of ethanol to obtain 140 g (42.6%) of erythro-1-bromo-1 2 -diphenyl-3,3,3-trifluoro-propane ; m.p.: 164-165"C.

Analysis: calculated for C15H12BrF3: C: 54.73% H: 3.67% Br: 24.28% F: 17.32% found: C: 54.97% H: 3.93% Br. 23.98% F: 17.36% The mother liquor is evaporated to about one-third of its original volume. 130 g (39.5%) of threo0-1-bromo-1,2-diphenyl-3,3,3-trifluoro-propane separate ; m.p. : 91-94 C.

Analysis: calculated for C16H12BrF3: C: 54.73%, H: 3.67%%, Br: 24.28%, F: 17.32%; found: C: 54.86%, H: 3.82%, Br: 24.01%, F: 17.27%.

The NMR spectra of the compounds confirm the assigned structures.

270 g (0.82 mole) of an erythro-threo isomeric mixture obtained as described above are dissolved in 2500 ml of anisole, 110 g (0.83 mole) of anhydrous aluminium trichloride are added to the stirred solution at 6"C, and the mixture is allowed to stand at room temperature overnight. The reaction mixture is poured onto a mixture of 4 kg of crushed ice and 600 ml of 36% aqueous hydrochloric acid and extracted with 3 litres of chloroform. The organic solution is washed with aqueous sodium hydrocarbonate solution and then with water, dried and evaporated. The dry residue is crystallized from 750 ml of isopropanol, and the resulting crude product (162 g, 55%, m.p.: 121-126 C) is crystallized again from 1500 ml of isopropanol. 109 g (37%) of threo-1,2-diphenyl-3,3,3-trifluoro-1-(4-methoxyphenyl)propane are obtained; m.p.: 129-131 C.

Analysis: calculated for C22H19F3O: C: 74.14%, H: 5.37%, F: 16.00%; found: C: 74.08%, H: 5.47%, F: 15.75%, Spectral data: v CH 3050,3025,2995,2950, 2925, 2900, 2830 vc=c 1605,1580,1508, YAr 808,786,758, 702 5cH(Ar)2 = 4.60 (d), 1 H bCH(CF3) = 4.23(m), lH OOCH3 = 3.60 (s), 1 H OAr = 6.7-7.3 (m), 14H The mother liquor obtained in the first crystallization step is evaporated to dryness, the residue is admixed with 300 ml of hexane and filtered.The resulting crude product (96 g, 27%, m.p.: 89-101 C) is crystallized again from 960 ml of isopropanol to obtain 41.4 9 (14%) of erythro-1,2-dipehnyl-3,3,3-trifluoro-1 -(4methoxyphenyl)-propane; m.p.: 108-111"C.

Analysis: calculated for C22H19F3O: C: 74.14%, H: 5.37%, F: 16.00%; found: C: 74.23% H: 5.18%, F: 16.17%.

Spectral data: VCH 3090,3060,3025,3010, 2960,2940,2915,2840 vc=c 1658,1612,1590,1513,1500 YAr 808, 790, 762, 708 , 702 bcH(Ar)2 = 4.60 (d), 1 H # CH(CF3) = 4.23 (m), 1H 50CH3 = 3.60 (s), 3H bAr = 6.4-7.6 (m), 14H 100 g (0.28 mole) of threo-1,2-diphenyl-3,3,3-trifluoro-1-(4-methoxyphenyl)-propane are heated with 300 g of pyridine hydrochloride for 3 hours at 200-220"C. The mixture is cooled, diluted with 700 ml of chloroform, washed with water until neutral, dried and evaporated. The residue is crystallized from a 1:2 mixture of chloroform and hexane to obtain 85.7 9 (90%) of threo-1,2-diphenyl-3,3,3-trifluoro-1-(4-hydroxyphenyl)- propane ; m.p. : 123-125 C.

Analysis: calculated for C21H17F3O: C: 73.67%, H: 5.01%, F: 16.65%, found: C: 73.56%, H: 4.92%, F: 16.78%.

40 g (0.11 mole) of erythro-1 ,2-diphenyl-3,3,3-trifluoro-1 -(4-methoxyphenyl)-propane are reacted with 120 g of pyridine hydrochloride as described above. The resulting erythro-1,2-diphenyl-3,3,3-trifluoro-1-(4- hydroxyphenyl)-propane is crystallized from a 1:2 mixture of chloroform and hexane to obtain 32.5 9 (84.5%) of the product; m.p.: 114-1 17'C.

Analysis: calculated for C21H17F3O: C: 73.67%, H: 5.01%, F: 16.65%; found: C: 73.52%, H: 4.97%, F: 16.71%.

A mixture of 85.6 9 (0.25 mole) of threo-1,2-diphenyl-3,3,3-trifluoro-1-(4-hydroxyphenyl)-propane, 400 ml of 1 ,2-dibromoethane and 18.5 g (0.33 mole) of powdered potassium hydroxide is boiled under stirring. The reaction mixture is diluted with 1.5 litres of dichloromethane, washed with 10% aqueous hydrochloric acid and water, dried, and the solvent and the excess of 1,2-dibromoethane are distilled off in vacuo. The residue is crystallized from benzene to obtain 97.7 g (87%) of threo-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphenyl-3,3,3- trifluoro-propane ; m.p. : 144-151 C.

Analysis: calculated for C23H20BrF3O: C: 61.48%, H: 4.49%, Br: 17.78%, F: 12.68%; found: C: 61.55%, H: 4.57%, Br: 17.63%, F: 12.71%.

30 g (87.6 mmoles) of erythro-1,2-diphenyl-3,3,3-trifluoro-1-(4-hydroxyphenyl)-propane are reacted with 1,2-dibromoethane as described above. The resulting erythro-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphenyl- 3,3,3-trifluoro-propane is crystallized from benzene to obtain 27.9 g (71%) of the product; m.p.: 130-133"C.

Analysis: calculated for C23H20BrF3O: C: 61.48%, H: 4.49%, Br: 17.78%, F: 12.68%; found: C: 61.60%, H: 4.63%, Br: 17.60%, F: 12.77%.

EXAMPLE 2 Preparation of threo-1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-hydroxyethylaminol-ethoxy)-phenyl]-propane A mixture of 6.74 g (15 mmoles) of threo-1-[4-(2-bromoethoxy)-phenyl)-1,2-diphenyl-3,3,3-trifluoro- propane, prepared as described in Example 1,9.15 g (150 mmoles) of 2-aminoethanol and 15 ml of 2-methoxyethanol is boiled for 0.5 hours. The reaction mixture is cooled, diluted with 200 ml of chloroform, washed with water, dried and evaporated. The residue is crystallized from a 1:1 mixture of benzene and hexane to obtain 4.32 g (67%) of the desired compound; m.p.: 120-122"C.

Analysis: calculated for C25H26F3NO2: C: 69.90%, H: 6.10%, F: 13.27%, N: 3.26%; found: C: 69.71%, H: 6.15%, F: 13.17%, N: 3.35%.

EXAMPLE 3 Proparation of erythro-1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-bis-(2-hydroxyethyl)-aminol-ethoxy)-phenylpropane hydrochloride 8.98 g (20 mmoles) of erythro-1-[4-(2-bromoethoxy)-phenyl-1,2-diphenyl-3,3,3-trifluoro-propane, prepared as described in Example 1, are dissolved in 42 g (400 mmoles) of diethanolamine, and the solution is heated at 100-120"C for 0.5 hours. the reaction mixture is processed as described in Example 2, and the residue is crystallized from a 1:2 mixture of an isopropanol solution of hydrochloric acid and ether. 5.98 g (58.7%) of the desired compound are obtained; m.p.: 190-195 C.

Analysis: calculated for C27H31CIF3NO3: C: 63.59%, H: 6.13%, Cl: 6.95%, F: 11.18%, N: 2.75%; found: C: 63.41%, H: 6.29%, Cl: 7.08%, F: 10.98%, N: 2.80%.

EXAMPLE 4 Preparation of erythro- 1,2-diphenyl-3,3,3-trffluoro- 1-[4-(2-/bis (2-chloroethyl)-amino/-ethoxy)-phenyl]- propane hydrochloride A mixture of 2.04 g (4 mmoles) of erythro-1 ,2-diphenyl-3,3,3-trifluoro-1 -[4-(2-/bis (2-hydroxyethyl)-amino/ -ethoxy)-phenyl]-propane-hydrochloride, prepared as described in Example 3, 10 ml of chloroform and 3 ml (40 mmoles) of thionyl chloride is boiled for 2 hours. The excess of thionyl chloride is evaporated in vacuo, and the residue is crystallized from a 1:2 mixture of methanol and ether. 1.16 g (53%) of the desired compound are obtained; m.p.: 140-143"C.

Analysis: calculated for C27H29H29C13F3NO: C: 59.30%, H: 5.34%, Cl: 19.45%, F: 10.42%, N: 2.56%; found C: 59.16%, H: 5.53%, Cl: 19.32%, F: 10.60%, N: 2.62% EXAMPLE 5 Preparation of erythro-1-[4-(2-azidoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propane A solution of 3.25 g (50 mmoles) of sodium azide in 11 ml of water is added to a solution of 11.2 g (25 mmoles) of erythro-1-[4-(2-bromoethoxy)-phenyl]-1 2-diphenyl-3,3,3-trifiuorn-prnpane, prepared as described in Example 1, in 112 ml of 2-methoxyethanol, and the mixture Is boiled for one hour. The reaction mixture is evaporated to dryness, 30 ml toluene is added to the residue, and the mixture is evaporated again to remove the last traces of 2-methoxyethanol. The solid residue is triturated with water, filtered off and washed with water. The crude product is recrystallized twice from ethanol. 7.83 g (76%) of the desired compound are obtained; m.p.: 144-148"C.

Analysis: calculated for C23H20F3N3O: C: 67.14%, H: 4.90%, F: 13.85%, N: 10.21%; found: C: 67.35%, H: 5.15%, F: 13.94%, N: 10.06%.

EXAMPLE 6 Preparation of erythro- 7-[4-(2-aminoethoxy)-phenyl]- 1,2-diphenyl-3,3,3-trifluoro-propane 5.15 g (12.5 mmoles) of erythro-l -[4-(2-azidoethoxy)-phenyl]-l ,2-diphenyl-3,3,3-trifluoro-propane, prepared as described in Examples, are hydrogenated for about one hour in a mixture of 100 ml of methanol and 40 ml of tetrahydrofuran, in the presence of 0.6 g of a 5% palladium-on-carbon catalyst. The solution is evaporated and the residue is crystallized from hexane. 3.86 g (80.2%) of the desired compound are obtained ; m.p. : 125-127 C.

Analysis: calculated forC23H22F3NO: C: 71.67% H: 5.75%, F: 14.80%, F: 3.63%; found: C: 71.87%, H: 5.71%, F: 14.80%, N: 3.54%.

EXAMPLE 7 Preparation of (E)-1-[4-(2-azidoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene 9.83 g (22 mmoles ) of (E)-1-[4-(2-bromoethoxy)-phenyl-1,2-diphenyl-3,3,3-trifluoro-propene are dissolved in 100 ml of 2-methoxyethanol , a solution of 2.86 g (44 moles ) of sodium azide in 10 ml of wate ris added, and the mixture is boiled for one hour. The reaction mixture is processed as described in Examples, and the product is recrystallized twice from ethanol. 7.40 g (82%) of the desired compound are obtained ; m.p. : 73-75 C.

Analysis: calculated for C23H16F3N3O: C: 67.47%, H: 4.43%, F: 13.92%, N: 10.27%; found: C: 67.61%, H: 4.45%, F: 13.77%, N: 10.11%.

The starting substance, (E)-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene, is prepared as follows : 45.4 g (0.2 mole ) of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone [D. Walker et al. : J. Org. Chem. 30, 3240 (1965) ] are added to a solution of 44.7 g (0.1 mole ) of threo-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphenyl-3,3,3trifluoro-propane, prepared as described in Example 1 , in 225 ml of dry benzene, and the mixture is stirred and boiled for 30 hours. The reaction mixture is cooled and the separated 2,3-dichloro-5,6-dicyano-1 4- hydroquinone are filtered off. The filtrate is evaporated to dryness, the residue is admixed with 100 ml of chloroform, and the separated 2,3-dichloro-5,6-dicyano-1,4-benzoquinone is filtered off.The filtrate is diluted with 400 ml of chloroform, washed with a 10% aqueous sodium hydrocarbonate solution and then with water, dried and evaporated. The residue is crystallized from 220 ml of ethanol to obtain 34.4 g (77%) of a crude product melting at 110-118 c. This crude product, which is a 4:1 mixture of the E and Zisomers, is recrystallized from 200 ml of ethanol. 29.5 g (66%) of the Eisomer are obtained ; m.p. : 118-120 C.

Analysis: calculated for C23H18BrF3O: C: 61.67%, H: 4.06%, Br: 17.87%, F: 12.74%; found: C: 61.80%, H: 4.15%, Br: 17.59%, F: 12.90%.

Spectral data: vcH 3060,3020, 2920, 2900, 2850 vc=c 1590,1495 Ar 815, 822,758, 705 t)OCH2 = 4.08 (t), 2H # BrCH2 = 3.46 (t), 2H bAr = 6.4-7.4 (m),14H The mother liquor obtained above is evaporated, and the residue is recrystallized several times from ethanol. 2.14 g (4.8% ) of (Z)-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene are obtained : m.p. : 135-138 C.

Spectral data: Vch 3080,3060,3030,2935, 2870 ',c=c 1610,1510 VAr 832,770,715 # OCH2 = 4.28 (t), 2H bBrCH2 = 3.59 (t), 2H OAr = 6.8-7.4 (m), 14H EXAMPLE 8 Preparation of (E) -1-[4-(2-aminoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene 7.40 g (18 mmoles) of (E)-1-[4-(2-azidoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene, prepared as described in Example 7, are dissolved in 100 ml of methanol, 0.70 g of a 5% palladium-on-carbon catalyst are added, and the mixture is hydrogenated for about one hour. The catalyst is filtered off, the solution is evaporated, and the residue is crystallized from hexane. 3.63 g (52.3%) of the desired compound are obtained ; m.p. : 71-76 C.

Analysis: calculated for C23H20F3NO: C: 72.05% H: 5.26%, F: 14.87%, N: 3.65%; found: C: 72.36%, H: 5.30%, F: 14.88%, N: 3.52%.

EXAMPLE 9 Preparation of (E)- 1,2-diphenyl-3,3,3-trifluoro- 1-[4-(2-morpholinoethoxy-phenyl]-propene A mixture of 3.34 g (7.5 mmoles) of (E)-1-[4-(2-bromo-ethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro- propene, prepared as described in Example 7, and 13 g of morpholine is boiled for one hour. The reaction mixture is processed as described in Example 1, and the crude product is crystallized from hexane. 2.80 g (82.4%) of the desired compound are obtained; m.p.: 84-89 C.

Analysis: calculated for C27H26F3NO2: C: 71.51%, H: 5.78%, F: 12.57%, N: 3.09%, found: C: 71.80%, H: 5.98%, F: 12.70%, N: 3.28%.

EXAMPLE 10 Preparation of (E)-1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-(4-methylpiperazinol-ethoxy)-phenyl]-propene 4.0 g of N-methylpiperazine are added to a solution of 4.47 g (10 mmoles) of (E)-1-[4-(2-bromoethoxy)phenyli]-1,2-DIPHENYL-3,3,3-trifluoro-propene, prepared as described in Example 7, in 80 ml of dry ethanol, and the mixture is boiled for 6 hours. The reaction mixture is evaporated to dryness, and then one proceeds as described in Example 1. The product is crystallized from hexane. 3.45 g (74%) of the desired compound are obtained; m.p.: 94-97 C.

Analysis: calculated for C28H29F3N2O: C: 72.08%, H: 6.27%, F: 12.22%, N: 6.00%; found: C: 72.27%, H: 6.32%, F: 12.28%, N: 5.77%.

EXAMPLE 11 Preparation of (E)- 1,2-diphenyl-3,3,3-trifluoro- 1-[462-14z2-hydroxyethyl)-piperazinol-ethoxy)-phenylJ- propene A mixture of 1.79 g (4 mmoles) of (E)-l -[4-(2-bromo-ethoxy)-phenyl]-l ,2-diphenyl-3,3,3-trifluoro-propene, prepared as described in Example 7, and 10.4 g of 1-(2-hydroxyethyl)-piperazine is heated for one hour. The mixture is processed as described in Example 1, and the product is crystallized from hexane. 1.35 g (68%) of the desired compound are obtained; m.p.: 79-81 C.

Analysis: calculated for C29H3'F3N202: C: 70.14%, H: 6.29%, F: 11.48%, N: 5.64%; found: C: 70.15%, H: 5.65%, F: 11.36%, N: 5.48%.

EXAMPLE 12 Preparation of (E)~1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-(2-hydroxyethylaminol-ethoxy)-phenyl]-propene 6.719 (15 mmoles) of (E)-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene. prepared as described in Example 7, are dissolved in a mixture of 9.15 g of 2-amino-ethanol and 15 ml of 2-methoxyethanol. The solution is boiled for 30 minutes, and then the mixture is processed as described in Example 2. The product is crystallized from a 1:1 mixture of ethyl acetate and hexane. 5.29 g (83%) of the desired compound are obtained; m.p.: 96-98 C.

Analysis: calculated for C25H24F3NO2 : C: 70.24%, H: 5.66%, F: 13.33%, N: 3.28%; found: C: 70.42%, H 5.80%, F: 13.39%, N: 3.23%.

EXAMPLE 13 Preparation of (F)- 1,2-diphenyl-3,3,3-trifluoro- 1-[4-(2-bis(2-hydroxyethyl)-aminol-ethoxy)-phenyl]-propene A solution of 7.15 g (16 mmoles) of (E)-1-[4-(2-bromo-ethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro- propene, prepared as described in Example 7, in 16,8 g of diethanolamine is heated at 120-140"C for 0.5 hours, and then one proceeds as described in Example 2. The product is crystallized from a 1:1 mixture of ethyl acetate and hexane. 5.66 g (75%) of the desired compound are obtained; m.p.: 113.5-116 C.

Analysis: calculated for C27H28F3NO3: C: 68.78%, H: 5.99%, F: 12.09%, found: C: 68.75%, H: 5.78%, F: 12.13%.

EXAMPLE 14 Preparation of (E)-1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-chloroethyl)-aminol-ethoxy)~phenyl]-propene 3.6 ml (50 mmoles) of thionyl chloride are added to a solution of 2.36 g (5 mmoles) of (E)-1,2-diphenyl3,3,3-trifluoro-1-[4-(2-/bis (2-hydroxyethyl)-amino/-ethoxy)-phenyl]-propene. prepared as described in Example 13, in 12 ml of chloroform, and the mixture is boiled for2 hours. The excess of thionyl chloride is evaporated in vacuo, and the residue is crystallized from hexane. 1.90 g (74.7%) of the desired compound are obtained ; m.p. : 74-78 C.

Analysis: calculated for C27H26C12F3NO: C : 63 : 79%, H: 5.15%, Cl: 13.95%, F: 11.21%, N: 2.75%; found: C: 64.03%, H: 5.03%, Cl: 14.00%, F: 10.93%, N: 2.75%.

EXAMPLE 15 Preparation of 1-14-(2-azidoethoxy)-phenyll- 1-phenyl-3,3,3-trifluoro-2-(4fluorophenylJ-propene 11.63 g (25 mmoles) of 1 [4-(2-bromoethoxy)-phenyl]-1-phenyl-3,3,3-trifluoro-2-(4-fluorophenyl)-propene are converted into the azido derivative as described in Examples. The product is crystallized from ethanol to obtain 8.54 g (80%) of the desired compound; m.p.: 62-64 C Analysis: calculated for C23H14F4N3O; C: 64.63%, H: 4.01%, F: 17.78%, N: 9.83%; found : C 64.71 % H : 4.13%. F : 17.74 %, N : 9.63%.

1 -[4-(2-Bromoethoxy)-phenyl]-1 -phenyl-3,3,3-trifluoro-2-(4-fluorophenyl)-propene, applied as starting substance, is prepared by the method of Examples 1 and 7 as follows: 4'-Fluoro-2,2,2-trifluoroacetophenone [F.E. Herkes et al.: J. Org. Chem. 32 1311-18 (1967)] is reacted with benzyl-triphenyl-phosphonium chloride in the presence of an ethanol solution of sodium ethoxide.

1-Phenyl-3,3,3-trifluoro-2-(4-fíuorophenyl)-propene is obtained with a yield of 91%; b.p.:110-11 14"C/0.2 mm Hg, m.p.: 43-45"C.

Analysis: calculated for C15H10F4: C: 67.67%, H: 3.79%, F: 28.54%; found: C: 67.83% H: 3.90%, F: 28.33%.

This compound is hydrogenated in the presence of a palladium-on-carbon catalyst to obtain 1 -phenyl3,3,3-trifluoro-2-(4-fluorophenyl)-propane with a yield of 91.7% : b.p. : 100-104 C/0.2 mm Hg : nD20 = 1.4980.

Analysis: calculated for C15H12F4: C: 67.16%, H: 4.51%, F: 28.33%; found: C: 67.30%, H: 4.68%, F: 28.18%.

The above product is brominated in carbon tetrachloride, and the brominated compound is crystallized from ethanol . 1-Bromo-1-phenyl-3,3,3-trifluoro-2-(4-fluorophenyl)-propane is obtained with a yield of 48.2%; m.p.: 144-146 C.

Analysis: calculated forC15H11BrF4: C: 51.90%, H: 3.19%, Br: 23.02%, F: 21.89%; found: C: 51.70%, H: 3.18%, Br: 23.06%, F: 22.03%.

The brominated compound is reacted with anisole in the presence of aluminium trichloride. The resulting 1 -phenyl-3,3,3-trifl uoro-2-(4-fl uorophenyl)-1 -(4-methoxyphenyl )-propane (mixture of isomers) is crystallized from isopropanol. Yield: 79.8%; m.p.: 152-167 C.

Analysis: calculated for C22H16F4O: C. 70.58%, H: 4.85%, F: 20.30%; found: C: 70.80%, H: 4.78%, F: 20.40%.

The above compound is heated with pyridine hydrochloride, and the resulting 1-phenyl-3,3,3-trifluoro-2- (4-fluorophenyl)-1-(4-hydroxyphenyl)-propane is reacted directly, without purification, with 1,2dibromoethane in the presence of potassium hydroxide under heating. The resulting 1-[4-(2-bromoethoxy)phenyl]-1-phenyl-3,3,3-trifluoro-2-(4-fluorophenyl)-propane is crystallized from isopropanol; 15 to 20 ml of isopropanol are applied for 1 g of the crude product. The first fraction, which is a mixture of isomers, melts at 170-175 C.

Analysis: calculated for C23H19BrF4O: C: 59.11%, H: 4.10%, Br: 17.10%, F: 16.26%; found: C: 58.88%, H: 4.21%, Br: 16.96%, F: 16.50%.

The mother liquor is evaporated to dryness, and the solid is recrystallized from benzene. 5 ml of benzene are applied for 1 g of the solid. The resulting second fraction, which is a mixture of isomers, melts at 100-110 C.

Analysis: calculated for C23H19BrF4O: C: 59.11%, H: 4.10%, Br: 17.10%, F: 16.26%; found: C: 58.96%; H: 4.07%, Br: 17.05%, F: 16.32%.

The above two fractions are combined and boiled with 2,3-dichloro-5,6-dicyano-1 ,4-benzoquinone for 25 hours as described in Example 7. The product is crystallized from ethanol. 1-[4-(2-Bromoethoxy)-phenyl]-1- phenyl-3,3,3-trifluoro-2-(4-fluorophenyl)-propene is obtained with a yield of 66.5%; m.p.:115-11 15-118"C.

Analysis: calculated for C23H17BrF4O: C: 59.37% H: 3.68%, Br: 17.17%, F: 16.33%; found: C 59.48%, H: 3.87%, Br: 17.19%, F: 16.51%.

EXAMPLE 16 Preparation of l-[4-(2-aminoethoxy)-phenyl]- 1-phenyl-S,3,3-trifluoro-2-4-fluorophenyl)-propene A solution of 8.54 g (20 mmoles) of 1-[4-(2-azido-ethoxy)-phenyl]-1-phenyl-3,3,3-trifluoro-2-(4- fluorophenyl)-propene, prepared as described in Example 15, in 170 ml of methanol is hydrogenated for about one hour in the presence of 0.9 g of a 5% palladium-on-carbon catalyst. The solution is evaporated and the product is crystallized from hexane. 4.51 g (56.4%) of the desired compound are obtained: m.p.: 83-89 C.

Analysis: calculated for C23H19F4NO: C: 68.82%, H: 4.77%, F: 18.93%, N: 3.49%; found: C: 68.94%, H: 4.99%, F: 18.83%, N: 3.33%.

EXAMPLE 17 Preparation of 1-phenyl-3,3,3-trifluoro-2-(4-fluorophenyl)-1-[4-(2-morpholinoethoxy)-phenyl]-propene 3.25 g (7 mmoles) of 1-[4-(2-bromoethoxy)-phenyl]-1-phenyl-3,3,3-trifluoro-2-(4-fluorophenyl)-propene, prepared as described in Example 15, are reacted with morpholine as described in Example 1. The product is crystallized from hexane. 2.5 g (75.7%) of the desired compound are obtained; m.p.: 67.69 C.

Analysis: calculated for C27H25F4NO2: C: 68.78%, H: 5.35%, F: 16.12%, N: 2.97%; found: C: 68.62%, H: 5.94%, F: 16.40%, N: 3.14%.

EXAMPLE 18 Preparation of 2-phenyl-3,3,3-trifluoro- 1-r4fluorophenyl)- 1-[4-(2-morpholinoethoxy)-phenyl]-propene 3.25 g (7 mmoles) of 1-[4-(2-bromoethoxy)-phenyl]-2-phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-propene are reacted with morpholine as described in Example 1. The product is crystallized from hexane. 3.03 g (92%) of the desired compound are obtained; m.p.: 95-96"C.

Analysis: calculated for C27H25F4NO2: C: 68.78%, H: 5.35%, F: 16.12%, N: 2.97%, found: C: 68,96%, H: 5.83%, F: 15.98%, N: 3.00%.

1 -[4-(2-Bromoethoxy)-phenyl]-2-phenyl-3,3,3-trifluoro-1 -(4-fluorophenyl)-propene, applied as starting substance, is prepared according to the method of Example 1 as follows: 2,2,2-Trifluoroacetophenone is reacted with triphenyl-(4-fluorobenzyl)-phosphonium chloride [R.A. Jones: Australian J. Chem. 18,903-6(1965)] in ethanol in the presence of sodium ethoxide. 2-Phenyl-3,3,3-trifluoro- 1-(4-fluorophenyl)-propene is obtained with a yield of 90%; b.p.: 105-107 C/0.2 mm Hg, m.p.: 35-41"C.

Analysis: calculated for C15H10F4: C: 67.67%, H: 3.79%, F: 28.54%; found C: 67.58%, H: 3.95%, F: 28.50%.

The above product is hydrogenated with a palladium-on-carbon catalyst to obtain 2-phenyl-3,3,3-trifluoro 1-(4-fluorophenyl)-propanewith a yield of 94%; b.p.: 95-100"C/0.3 mm Hg.

Analysis: calculated for C15H12F4: C: 67.16% H: 4.51%, F: 28.33; found: C: 67.22%, H: 4.73%, F: 28.40%.

The obtained product is brominated in carbon tetrachloride, and the resulting 1-bromo-2-phenyl-3,3,3 trifluoro-1-(4-fluorophenyl)-propane is crystallized from ethanol. 3.5 ml of ethanol is applied for one 9 of the solid. The obtained first fraction, which is a mixture of isomers, melts at 143-145"C.

Analysis: calculated for C15H11BrF4: C: 51.90%, H: 3.19%, Br: 23.02%, F: 21.89%; found: 51.91%, H: 3.13%, Br: 22.92%, F: 22.06%.

The mother liquor is evaporated to about one-third of its original volume. The obtained second fraction, a mixture of isomers, melts at 69-76"C.

Analysis: calculated for C16H11BrF4: C: 51.90%, H: 3.19%, Br: 23.02%, F: 21.89%; found: C: 51.74%, H: 3.33%, Br: 23.08%, F: 22.02%, The total yield amounts to 76%.

The above fractions are combined and reacted with anisole in the presence of aluminium trichloride. The resulting 2-phenyl-3,3,3-trifluoro-1-(4-fluoropheyl)-1-(4-methoxyphenyl)-propane is crystallized from ethanol. 4 mg of ethanol are applied for 1 g of the solid. The first fraction, a mixture of isomers, melts at 120-127"C.

Analysis: calculated for C22H18F4O: C: 70.58%, H: 4.85%, F: 20.30%; found: C: 70.819b, H: 5.01%, F: 20.35%.

The mother liquor is concentrated to about one-sixth of its original volume. The resulting second fraction, a mixture of isomers, melts at 84-95C.

Analysis: calculated for C22H18F4O: C: 70.58%, H: 4.85%, F: 20.30%; found: C: 70.72%, H: 4.92%, F: 20.18%.

The total yield amounts to 78.8%.

The above fractions (mixtures of isomers) are combined and heated with pyridine hydrochloride. The resulting crude 2-phenyl-3,3,3-trifl uoro-1 -(4-fluorophenyl)-1 -(4-hydroxyphenyl)-propane is reacted directly, without purification, with 1,2-dibromoethane in the presence of potassium hydroxide. The resulting 1-[4-(2-bromoethoxy)-phenyl]-2-phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-propane is crystallized from ethanol. 4 ml of ethanol are applied for 1 g of the solid. The first fraction, a mixture of isomers, melts at 119-123 C.

Analysis: calculated for C23H19BrF4O: C: 59.11%, H: 4.10%, Br. 72-74 C. F: 16.26%; found: C: 59.30%, H: 4.16%, Br: 17.03% F: 16.26%.

The mother liquor is evaporated to about one-half of its original volume. The obtained second fraction, a mixture of isomers, melts at H : 4.10%, Analysis: calculated for C2sH19BrF4O: C: 59.11%, C : 59.20%, Br: 17.10%, F: 16.26%; found: C: 59.27%, H: 4.30%, Br: 17.13%, F: 16.36%.

The above fractions (mixtures of isomers) are combined and reacted with 2,3-dichloro-5,6-dicyano-1 4- benzoquinone in benzene under boiling, as described in Example 7. The reaction mixture is processed as described in Example 7, and the product is crystallized from isopropanol. 1-[4-(2-bromoethoxy)-phenyl]-2- phenyl-3,3,3-trifluoro-1-(4-fluorophenyi)-propene is obtained with a yield of 58.4%; m.p.: 142-144"C.

Analysis: calculated for C23H17BrF4O: C: 59.37%, H: 3.68%, Br: 17.17%, F: 16.33%; found: BR.17.10% H: 3.90%, Br: 17.36%, F: 16.20%.

EXAMPLE 19 Preparation of 1-[24-(2-dimethylamino-ethoxy)-phenyl]-1-phenyl-3,3,3-trifluoro-2-(4-methoxyphenyl)~ propene 0.39 g (0.017 g.-atom) of sodium are dissolved in 3.12 g (35 mmoles) of 2-dimethylamino-ethanol. 3.15 g (8.5 mmoles) of 1 - phenyl]-3,3,3-trifluoro-1-(4-fluorophenyl)-2-(4-methoxyphenyl)-propene are added to the solution, and the mixture is heated at 150-155 C for one hour. The reaction mixture is cooled, diluted with 200 ml of ether, washed with water until neutral, dried and evaporated. The residue is dissolved in 30 ml of hexane, the solution is filtered, and the filtrate is evaporated. 3.39 g (90%) of 1-[4-(2-dimethylamino-ethoxy) phenyl]-1-phenyl-3,3,3-trifluoro-2-(4-methoxyphenyl)-propene are obtained as a resinous substance; the product is a 3:4 mixture of the (Z) and (E) isomers.

Analysis: calculated for C26H26F3NO2: C: 70.73%, H: 5.94%, F: 12.91%, N: 3.17%; found: C: 70.65%, H: 6.07%, F: 13.05%, N: 3.26%.

1-Phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-2-(4-emthoxyphenyl)-propane, applied as starting substance, is prepared according to the method of Example 1 as follows: 4'-Methoxy-2,2,2-trifluoroacetophenone [R. Fuchs: J. Org. Chem. 22, 993-994 (1957)1 is is reacted with triphenyl-(4-fluorobenzyl)-phosphonium chloride (see Example 18) in ethanol in the presence of sodium ethoxide. 3,3,3-Trifluoro-1-(4-fluorophenyl)-2-(4-methoxyphenylo)-propene is obtained with a yield of 87%; b.p.: 138-142 C/0.5 mm Hg.

Analysis: calculated for C16H12F4O: C: 64.86% H: 4.08%, F: 25.65%; found: C: 65.03 %, H: 4.27 %, F: 25.40 %.

The above compound is hydrogenated in the presence of a palladium-on-carbon catalyst to obtain 3,3,3-trifiuoro-1-(4-fluorophenyl)-2-(4-methoxyphenyl)-propane with a yield of 93%; b.p. 134-136 C/0.4 mm Hg, nD = 1.5070.

Analysis: calculated for C16H14F4O: C: 64.43%, H: 4.73%, F: 25.48%; found: C: 64.60%, H: 4.85%, F: 25.35%.

The above compound is brominated in carbon tetra-chloride, and the product is crystallized from hexane. 1-Bromo-3,3,3-trifluoro-1-(4-fluorophenyl)-2-(4-methoxyphenyl)-propane (mixture of isomers) is obtained with a yield of 49%; m.p.: 73-94 C.

Analysis: calculated for C16H13BrF4O: C: 50.95%, H: 3.47 %, Br: 21.19%, F: 20.15 %; foud : C : 50.82 %, $H : 3.60%, Br : 21.11 % F : 20.30%.

The above compound is reacted with benzene in the presence of aluminium trichloride, and the resulting 1-phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-2-(4-methoxyphenyl)-propane is crystallized from isopropanol. 5 ml of isopropanol are applied for 1 g of the solid. The first fraction, a mixture of isomers, melts at 126-1 450C.

Analysis: calculated for C22H18F4O : C : 70.58%, H : 4.85%, F : 20.30% found : C : 70.77%, H : 4.67 %, F : 20.45 %.

The mother liquor is evaporated to one-fifth of its original volume. The resulting second fraction, a mixture of isomers, melts at 102-11 0'C.

Analysis: calculated for C22H18F4O: C : 70.58%. H : 4.85%, F : 20.30% : found : C : 70.65%, H : 4.80%, F : 20.51%.

The above two fractions are combined and reacted with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone as described in Example 7 for 120 hours under boiling. The product is crystallized from isopropanol.

1-Phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-2-(4-emthoxyphenyl)-propene is obtained with a yield of 62 %; m.p. ; 113-120 C.

Analysis: calculated for C22H'6F4O: C : 70.96 %, H : 4.33 % F : 20.41% ; found: C: 71.17 %, H: 4.48%, F: 20.70%.

EXAMPLE 20 Preparation of 1-[4-(2-diemthylamio-ethoxy)-phenyl]-2-phenyl-3,3,3-trifluoro- 1-(4-methoxyphenyl)- propene 0.46 g (0.02 g.-atom) of sodium are dissolved in 4.5 g (50 mmoles) of 2-dimethylamino-ethanol. 3.72 g (10 mmoles) of 2-phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-1-(4-methoxyphenyl)-propene are added to the solution, the mixture is heated at 150-155 C for one hour, and then processed as described in Example 19.

3.95 g (89.6 %) of 1-[4-(2-dimethylamino-ethoxy)-phenyl)-2-phenyl-3,3,3-trifluoro-1-(4-methoxyphenyl)~ propene are obtained as a resinous substance; the product is a 9:1 mixture of the (Z) and (E) isomers.

Analysis: calculated for C26H26F3NO2: C : 70.73%, H : 5.94 %, F : 12.91%, N : 3.17 % ; found : C : 70.50%, H : 6.11 %, F : 12.73%, N : 2.91 %.

2-Phenyl-3,3,3-trifluoro-1-[4-fluorophenyl)-1-(4-methoxyphenyl)-propene, applied as starting substance, is prepared as follows: 2-Phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-1-(4-methoxyphenyl)-propane, prepared as described in Example 18, is reacted with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone under boiling for 8 hours as described in Example 7. The reaction mixture is processed, and the product is crystallized from ethanol. 2-Phenyl-3,3,3 trifluoro-1 -(4-fluorophenyl)-1 -(4-methoxyphenyl)-propene is obtained with a yield of 51 %; m.p.: 52-56 C.

Analysis: calculated for C22H16F4O: C : 70.96%, H : 4.33 %, F : 20.41% ; foud : C : 71.22%, H : 4.51 %, F : 20.54 % .

EXAMPLE 21 Preparation of 1-[4-(2-dimethylamino-ethoxy)-phenyl]-1-phenyl-3,3,3-trifluoro-2-[4-hydroxyphenyl)-propene hydrochloride 0.76 9(1.62 mmoles) of 1-[4-(2-dimethylamino-ethoxy)-phenyl]-1-phenyl-3,3,3-trifluoro-2-[4-(methoxy methoxy)-phenyl]-propene are dissolved in 8 ml of a 1% methanolic hydrochloric acid. The solution is heated for 0.5 hour, then evaporated, and the product is crystallized from isopropanol. 0.56 g (74 %) of the desired compound is obtained; m.p.: 196-220 C.

Analysis: calculated for C25H2sCIF3NO2: C: 64.72%, H: 5.43%, Cl: 7.64%, F: 12.29%, N: 3.02%; found: C: 64.51%, H: 5.31%, CI: 7.49%, F: 12.51%, N: 2.84%.

1-[4-(2-Dimethylamino-ethoxy)-phenyl]-1-phenyl-3,3,3-trifluoro-2-[4-(methoxy-methoxy)-phenylpropene, applied as starting substance, is prepared as follows: A mixture of 18.72 g (50 mmoles) of 1-phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-2-(4-methoxyphenyl)- propane, prepared as described in Example 19, and 56 g of pyridine hydrochloride is heated at 200 C for 3 hours, and then processed as described in Example 1. The resulting crude 1-phenyl-3,3,3-trifluoro-1-(4- fluorophenyl)-2-(4-hydroxyphenyl)-propane is dissolved in 70 ml of benzene, then 6.44 g (80 mmoles) of chloromethylether and 6 g (300 mmoles) of powdered sodium hydroxide are added, and the mixture is boiled for one hour. The reaction mixture is diluted with 100 ml of benzene, washed until neutral with a 20% aqueous ammonium chloride solution, dried and evaporated.The residue is crystallized from isopropanol.

12.54 g (62 %) of 1 -phenyl-3,3,3-trifl uoro-1 -(4-fluorophenyl)-2-[4-(methoxy-methoxy)-phenyl]-propane are obtained ; m.p. : 96.5-99 C.

Analysis: calculated for C23H20F402: C: 68.31 %, H: 4.99 %, F: 18.79 %; found ; C 68.45 %, H : 5.07 %, F : 18.73%.

12.13 g (30 mmoles) of the above compound are boiled with 13.62 g (60 mmoles) of 2,3-dichloro-5,6dicyano-1,4-benzoquinone in benzene for 120 hours. The reaction mixture is processed as described in Example 7, and the product is crystallized from isopropanol. 3.38 g (28 %) of 1-phenyl-3,3,3-trifluoro-1-(4- fluorophenyl)-2-[4-(methoxy-methoxy)-phenyl]-propene are obtained ; m.p. : 85-88 C.

Analysis: calculated for C23H18F402: C: 68.65%, H: 4.51 %, F: 18.89%; found: C: 68,78%, H: 4.65%, F: 18.81 %, 0.09 g (0.004 g-atoms) of sodium are dissolved in 0.89 g (10 mmoles) of 2-dimethylamino-ethanol. 0.80 g (2 mmoles) of the above compound are added, and the mixture is reacted as described in Example 19.0.76 g (80.6%) of 1-[4-(2-dimethylamino-ethoxy)-phenyl]-1-phenyl-3,3,3-trifluoro-2-[4-(methoxy-methoxy)-phenyl]propene is obtained as a resinous substance, which can be utilized in the subsequent step without purification.

EXAMPLE 22 Preparation of 1-[4-z2-dimethylamino-ethoxy)-phenyl7-2-phenyl-3,3,3-trifluoro- l-(4-h ydroxyphenyl)-propene 2.06 g (4.56 mmoles) of 1-(4-benzyloxyphenyl)-1-[4-(2-dimethylamino-ethoxy)-phenyl]-2-phenyl-3,3,3trifluoroprpene are dissolved in 45 ml of acetic acid and hydrogenated in the presence of 0.5 g of a 10% palladium-on-carbon catalyst. The solution is evaporated and the residue is crystallized from ether. 0.77 g (39.5 %) of the desired compound is obtained; m.p.: 149-155 C.

Analysis: calculated for C25H24F3NO2: C: 70.24%, H: 5.66%, F: 13.33%, N: 3.28%; found : C : 69.92 %, H : 6.12 %, F : 13.285 , N : 3.38 %.

1-(Benzyloxy-phenyl)-1-[4-(2-dimethylamino-ethoxy)-phenyl]-2-phenyl-3,3,3-trifluoro-propene, applied as starting substance, is prepared as follows: 2-Phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-1-(4-methoxyphenyl)-propane, prepared as described in Example 18, is reacted with pyridine hydrochloride as described in Example 1, and the resulting 2-phenyl-3,3,3 trifluoro-1-(4-fluorophenyl)-1-(4-hydroxyphenyl)-propane is reacted with benzyl chloride in ethanol solution, in the presence of sodium hydroxide. The product is crystallized from ethanol. 1-(4-Benzyloxy-phenyl)-2- phenyl-3,3,3-trifluoro-1 -(4-fluorophenyl)-propane is obtained with a yield of 64 %; m.p.: 104-125 C.

Analysis: calculated for C28H22F4O: C : 74.65 %, H : 4.92%, F : 16.87 % ; found : C : 74.82 %, H : 4.68 % , F : 16.92 %.

This compound is reacted with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone for 8 hours as described in Example 7. The obtained productis crystallized from ethanol. 1-(4-Benzyloxyphenyl)-2-phenyl-3,3,3trifluoro-1-(4-fluorophenyl)-propene is obtained with a yield of 24.5 % ; m.p. : 111-114 C.

Analysis: calculated for C28H20F4O: C:74.99%, H:4.50%, F: 16.94%; found : C : 75.17 % H : 4.81 %, F : 16.91 %.

This compound is reacted with a solution of 2-dimethylamino-ethanol and sodium as described in Example 19. The resulting 1-(4-benzyloxyphenyl)-1-[4-(2-dimethylaminoethoxy)-phenyl]-2-phenyl-3,3,3- trifluoro-propene can be applied in the subsequent step without purification.

EXAMPLE 23 Preparation of threo- 1.2-diphenyl-3,3,3-trifluoro- 7-[4-lmethoxy-methoxy)-phenyl]-propane 2 g (50 mmoles) of sodium hydroxide and 4 g (50 mmoles) of chloromethyl ether are added to a solution of 10.26 g (30 mmoles) of threo-1,2-diphenyl-3,3,3-trifluoro-1-(4-hydroxyphenyl)-propane, prepared as described in Example 1, in 40 ml of benzene, and the mixture is boiled for one hour. The reaction mixture is diluted with 100 ml of benzene, washed with a 20% aqueous ammonium chloride solution, dried and evaporated. The residue is crystallized from isopropanol. 7.45 g (64.2%) of the desired compound are obtained ; m.p. : 100-103 C.

Analysis: calculated for C23H21F302: C : 71.49%, H : 5.48 %, F : 14.75% ; found : C : 71.72 %, H : 5.71 %, F : 14.91 %.

EXAMPLE 24 Preparation of threo-1-[4-(2,3-epoxypropoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propane 0.48 g (12 mmoles) of sodium hydroxide and 9.2 g (100 mmoles) of 1,2-epoxy-3-chloropropane are added to a solution of 3.42 g (10 mmoles) of threo-1 ,2-diphenyl-3,3,3-trifluoro-1 -(4-hydroxyphenyl)-propane, prepared as described in Example 1, in 40 ml of ethanol, and the mixture is boiled for one hour. The reaction mixture is evaporated, n-butanol is added to the residue, and the mixture is again evaporated.

The residue is diluted with 30 ml of dichloromethane, washed with water, dried and evaporated. The residue is crystallized from methanol. 2.85 g (71.6 %) of the desired compound are obtained; m.p.: 113-116 C.

Analysis: calculated for C24H21F302: C : 72.35% , H : 5.31%, F : 14.31 % ; found: C:72.26%, H: 5.14%, F : 14.47%.

EXAMPLE 25 Preaparation of erythro-1-[4-(2,3-epoxypropxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propane 4.28 g (12.5 mmoles) of erythro-1,2-diphenyl-3,3,3-trifluoro-1-(4-hydroxyphene, prepared as described in Example 1, are reacted with 1,2-epoxy-3-chloropropane in the presence of sodium hydroxide as described in Example 24. The product is recrystallized twice from methanol. 2.18 g (44 %) of the desired compound are obtained; m.p.: 115-118 C.

Analysis: calculated for C24H21F3O2 : C: 72,35%, H: 5.31 %, F: 14.31 %; found ; C : 72.18 %, H : 5.46%, $F : 14.37 %.

EXAMPLE 26 Preparation of (E)-1-[4-(2,3-epxoypropoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene 0.29 g (12 mmoles) of sodium hydride are added to a solution of 3.40 g (10 mmoles) of (E)-1,2-diphenyl3,3,3-trifluoro-1 -(4-hydroxyphenyl)-propene in 30 ml of dry benzene, and the mixture is stirred for 0.5 hours.

Thereafter 1.39 g (15 mmoles) of 1,2-epoxy-3-chloropropane are introduced, and the mixture is heated for 5 hours. The reaction mixture is diluted with 70 ml of benzene, washed with water, dried, evaporated, and the residue is crystallized from methanol. 2.46 g (62 %) of the desired compound are obtained; m.p.: 73.5-76 C.

Analysis: calculated for C24H19F3O: C : 72.72%, H : 4.83%, F : 14.38% ; found : C : 72.89%, H : 4.88%, F : 14.61 %.

(E)-1,2-Diphenyl-3,3,3-trifluoro-1-(4-hydroxyphenyl)-proene applied as starting substance, is prepared as follows: 2.2 g (55 moles) of sodium hydroxide and 6.9 g (55 mmoles) of benzyl chloride are added to a solution of 15.4g (45 moles) of 1,2-diphenyl-3,3,3-trifluoro-1-(4-hydroxyphenyl)-propane, prepared as described in Example 1, in 75 ml of ethanol, and the resulting mixture is boiled for one hour. The reaction mixture is diluted with 300 ml of water, neutralized with an 1 n aqueous solution of hydrochloric acid, and extracted with 200 ml of chloroform. The organic phase is washed with water, dried and evaporated. The residue is crystallized from ethanol. 17 g (86.6 %) of the product are obtained; m.p.: 94-118 C.

Analysis: calculated for C28H23F3O: C : 77.76%, H : 5.36 %, E : 13.18 % ; found : C : 77.95%, H : 5.44 %, F : 13.42 %.

A mixture of 16.42 g (38 mmoles) of the above product, 17.25 g (76 mmoles) of 2,3-dichloro-5,6-dicyano1,4-benzoquinone and 80 ml of benzene is boiled for 2 hours, and then it is processed as described in Example 7. The product is crystallized from ethanol. 6.21 g (38 %) of (E)-1 -(4-benzyioxyphenyl)-1,2-diphenyl- 3,3,3-trifluoro-propene are obtained ; m.p. : 128-129 C.

Analysis: calculated for C28H21F3O : C: 78.13%, H: 4.92%, F: 13.24%; found : C : 78.34%, H: 5.10%, F : 13.24 %.

The NMR spectrum of the product confirms the structure.

6.02 g (14 mmoles) of the above product are hydrogenated in a 1:1 mixture of methanol and tetrahydrofuran in the presence of a 5% palladium-on-carbon catalyst. The solution is evaporated and the residue is crystallized from a 1:2 mixture of chloroform and hexane. 3.50 g (73.5 %) of (E)-1 ,2-diphenyl-3,3,3- trifluoro-1-(4-hydroxyphenyl)-propene are obtained ; m.p. : 113-120 C.

Analysis: calculated for C21H15F3O: C : 74.11 %, H: 4.44%, F: 16.75%; found : C : 74.17 %, H : 4.85%, F : 16.53%.

EXAMPLE 27 Preparation of 1-[4-(2,3-epoxypropoxy)-phenyl]-1-phenyl-3,3-trifluoro-2-(4-chlorophenyl)-propane 0.8 g (20 mmoles) of sodium hydroxide and 14.8 g (160 mmoles) of 1,2-epoxy-3-chloropropane are added to a solution of 6.03 g (16 mmoles) of 1-phenyl-3,3,3-trifluoro-1-(4-hydroxyphenyl)-2-(4-chlorophenyl)- propane in 60 ml of methanol. The mixture is boiled for 2 hours and then processed as described in Example 25. The product is crystallized from methanol. 4.44 g (64 %) of the desired compound are obtained; m.p.: 141-144 C.

Analysis: calculated for C24H20ClF302: C: 66.59 %, H : 4.86%, Cl : 8.19 %, F : 13.17 %; found: C: 66.71 %, H: 5.05%, Cl: 8.35%, F: 13.29%.

1-Phenyl-3,3,3-trifluoro-1-(4-hydroxyphenyl)-2-(4-chlorophenyl)-propane , applied as starting substance, is prepared by the method of Example 1 as follows: 4'-Chloro-2,2,2-trifluoroacetophenone [R. Fuchs, J. Org. Chem. 22, 993-994(1957)1 is s reacted with benzyl-triphenyl-phosphonium chloride in the presence of an ethanolic solution of sodium ethoxide. The product is crystallized from hexane. 1-Phenyl-3,3,3-trifluoro-2-(4-chlorophenyl)-propene is obtained with a yield of 68% ; m.p. : 63-66 C.

Analysis: calculated for C15H10ClF3 : C : 63.735 , H : 3.57% , Cl : 12.54 % , F : 20.16% ; found : C : 63.91%, H : 3,81 %, Cl : 12.37% , F : 20.03%.

The above product is hydrogenated in acetic acid in the presence of a 10% palladium-on-carbon catalyst to obtain 1-phenyl-3,3,3-trifluoro-2-(4-chlorophenyl)-propane with a yield of 86%, b.p. : 118-120 C/0.4 mm Hg, nD20= 1.5230.

Analysis: calculated for C15H12CIF3: C : 63.28% , H : 4.25 %, Cl : 12.45 %, F : 20.02% ; found : C : 63.51 %, H : 4,.40%, Cl : 12.38 %, F : 19.93 %.

The above product is brominated in carbon tetrachloride, and the bromine derivative is crystallized from hexane. 1-Bromo-1-phenyl-3,3,3-trifluoro-2-(4-chlorophenyl)-propane is obtained with a yield of 45.3% ; m.p. : 143-146 C.

Analysis: calculated for C15H11 BrCIF3: C: 49.55%, H: 3.05%, Br: 21.98%, CI: 9.75%, F: 15.68%; found: C: 49.68%, H: 3.15%, Br: 22.03%, Cl: 9.71%, F: 15.53%.

The above product is reacted with anisole in the presence of aluminium trichloride, and the resulting 1-phenyl-3,3,3-trifluoro-2(4-chlorophenyl)-1-(4-methoxyphenyl)-propane is crystallized from isopropanol.

Yield : 665 : m.p. 164-171 C.

Analysis: calculated for C22H18CIF3O: C : 67.61 %, H : 4.64 % , Cl : 9.07 %, F : 14.58 % ; found C : 67.75% , H : 4.70 %, Cl : 9.01 %, F : 14.45 %.

The above product is reacted with pyridine hydrochloride to obtain 1-phenyl-3,3,3-trifluoro-1-(4- hydroxyphenyl)-2-(4-chlorophenyl)-propane, which is utilized in the subsequent step without purification.

EXAMPLE 28 Preparation of threo- I-4-12-dimethylamino-ethoxyl-phenyl]- 7,2-diphenyl-3,3,3-trifluoro-propane hydrochloride A mixture of 6.84 g (20 mmoles ) of threo-1,2-diphenyl-3,3,3-trifluoro-1-(4-hydroxyphenyl)-propane, prepared as described in Example 1.06 g (24 mmoles) of sodium hydride and 60 ml of dry xylene is stirred for 0.5 hours. 7.2 ml of a 4.16 molar xylene solution of 2-dimethylaminoethyl chloride (=30 mmoles )are introduced, and the reaction mixture is heated for 2 hours. The mixture is evaporated, the residue is admixed with 10 ml of a 9.36% methanolic hydroxhloric acid, and the solvent is evaporated. The residue is erystallized from isopropanol. 5.76 g (64 % ) of the desired compound are obtained ; m.p. : 229-231 C.

Analysis: calculated for C25H27CIF3NO C: 66.74%, H: 6.05%, Cl: 7.88%, F: 12.67%, N: 3.11%; found: C: 66.47%, H: 6.03%, Cl: 7.96%, F: 12.86%, N: 3.00%.

EXAMPLE 29 Preparation of threo-1,2-diphenyl-3,3,3-trifluoro-1[4-(2-morpholinoethoxy)-phenyl]-propane 3,42 g (10 mmoles) of threo-1,2-diphenyl-3,3,3-trifluoro-1-(4-hydroxyphenyl)-propane, prepared as described in Example 1, are reacted in xylene with sodium hydride and then with 2-chloroethyl-morpholine as described in Example 28. The product is crstallized from hexane. 3.12 g (68.5%) of the desired compound are obtained ; m.p. : 87-89 C.

Analysis: calculated for C27H28F3NO2: C : 71.19%, H : 6.20 %, F : 12.51 %, N : 3,08 % ; found : C : 71.415, H : 6.48%, F : 12.35%, N : 3,01 %.

EXAMPLE 30 Preparation of fE)- 1,2-diphenyl-3,3,3-trifluoro- 1-[4-(2-pyrrolidinoethoxy)-phenyl]-propene 2.72 g (8 mmoles) of (E)-1,2-diphenyl-3,3,3-trifluoro-1-(4-hydroxyphenyl)-propene, prepared as described in Example 26, are reacted in xylene with sodium hydride and then with 2-chloroethyl-pyrrolidine as described in Example 26. The product is crystallized from hexane. 2.15 g (61.4 %) of the desired compound are obtained; m.p.: 84.6-86 C.

Analysis: calculated for C27H26F3NO: C : 74.12 % , H : 5.99% , F : 13.03 %, N : 3.20 5 ; found: C: 74.40%, H: 6.11 %, F: 13.15%, N: 3.15%.

EXAMPLE 31 Preparation of 12-[4-(2-dimethylamino-ethoxy)-phenyl]-3,3,3-trifluoro-1,2-bis-(4-methoxyphenyl)-propene 0.46 g (0.02 g.-atoms) of sodium are dissolved in 3.56 g (40 mmoles ) of 2-dimethylamino-ethanol, 4.02 g (10 mmoles) of 1-(4-fluorophenyl)-3,3,3-trifluoro-1,2-bis-(4-methoxyphenyl)-propene are added, and the mixture is heated at 1700C for one hour. The reaction mixture is cooled, diluted with 200 ml of ether, washed with water until neutral, dried and then evaporated. The residue is recrystallized from 45 ml of hexane. 3.43 g (73%) of the desired compound are obtained :m.p. : 77-79 C, Analysis : calculated for C17H28F3NO3 ; C:68.92%, H : 5.78%, F : 12.11 %, N : 2.98 % ; found : C:68.97%, H : 5.855, F : 12.10%, N : 2.99%.

1-(4-Fluorophenyl)-3,3,3-trifluoro-1,2-bis (4-methoxyphenyl)-propene, applied as starting substance, is prepared as follows: 20 g (0.15 mole) of anhydrous aluminium trichloride are added to a solution of 56.6 g (0.15 mole) of 1-bromo-3,3,3-trifluoro-1-(4-fluorophenyl)-2-(4-methoxyphenyl)-propane, prepared as described in Example 19, in 570 ml of anisol at 6 C under stirring. The reaction mixture is allowed to stand at room temperature overnight, then it is poured into a mixture of 600 g of crushed ice and 100 ml of a 36% aqueous hydrochloric acid, and the resulting mixture is extracted with 500 ml of chloroform. The organic solution is washed with aqueous sodium hydrocarbonate solution and water, dried, and the solvent is evaporated.The dry residue is crystallized from 240 ml of isopropanol to obtain 34.6 g (57 %) of 1-(4-fluorophenyl)-3,3,3-trifluoro-1,2-bis (4-methoxyphenyl)-propane ; m.p. : 132-135 C.

Analysis: calculated for C23H20F402: C : 68.31 %, H : 4.99 %, F : 18.79% ; found: C: 68.45%, H: 5.14 F: 18.63%; 13.62 g (60 mmoles) of 2,3-dichloro-5,6-dicyano-1 ,4-benzoquinone are added to a solution of 12.13 g (30 mmoles) of the above product in 60 ml of dry benzene, and the mixture is stirred and boiled for 16 hours.

Thereafter one proceeds as described in Example 7. The crude product is crystallized from 40 ml of isopropanol to obtain 8.75 g (72.5 %) of 1-(4-fluorophenyl)-3,3,3-trifluoro-1,2-bis (4-methoxyphenyl)propane; m.p.: 75-77wC.

Analysis: calculated for C23H18F402: C: 68.65% H: 4.51 %, F: 18.89%; found : c : 69.07 %, H : 4.67 %, F : 19.03% EXAMPLE 32 Preparation of 144-(2-dirneTh y/arnino-eThoxy)-phen Vl]-3,3,3-trifluoro- 1,2-bis (4-h ydroxyphen yl)-propene- hydrochloride 10 ml of a 9% methanolic hydrochloric acid are added to a solution of 4.0 g (7.47 mmoles) of 1 -[4.(2-dimethylaminoethoxy)-phenyl]-3,3,3-trifluoro-1 ,2-bis-(4.methoxymethoxyphenyl)-propene in 40 ml of methanol, and the mixture is boiled for one hour. The solution is evaporated to dryness, and the residue is crystallized from ethanol. 2.67 g (74.4 %) of the desired compound are obtained; m.p.: 256-262 C.

Analysis: calculated for C25H25CIF3NO3: C: 62.57%, H: 5.25%, Cl: 7.39%, F: 11.88%, N: 2.92%; found: C: 62.61%, H: 5.52%, Cl: 7.62%, F: 11.69%, N: 2.81%.

1-[4-(2-Dimethylamino-ethoxy)-phenyl]-3,3,3-trifluoro-1,2-bis (4-methoxymethoxy-phenyl)-propene, applied as starting substance, is prepared as follows: A mixture of 18.72 g (48 mmoles of 1-(4-fluorophenyl)-3,3,3-trifluoro-1,2-bis-(4-methoxyphenyl)-propane, prepared as described in Example 31 and 76 g of pyridine hydrochloride is heated at 200-210 C for 3 hours.

The mixture is cooled , diluted with 200 ml of chloroform and washed with water until neutral . The solution is dried and evaporated. The resulting 17.7 g of 1-(4-fluorophenyl)-3,3,3-trifluoro-1,2-bis-(4-hydrxoyphenyl)propane are dissolved as such, without puriflcation , In 200 ml of benzend. 11.1 g (138 mmoles) of chloromethyl ether and 10 g (275 mmoles) of powdered sodium hydroxide are added to the solution, and the mixture is boiled for one hour. The mixture is diluted with 100 ml of benzene, washed with a 20% aqueous ammonium chloride solution until neutral, dried and evaporated. The residue is crystallized from isopropanol. 15.63 g (73 %) of 1-(4-fluorophenyl)-3,3,3-trifluoro-1,2-bis-(4-methoxy-methoxy-phenyl)- propane are obtained ; m.p. : 106-107 C.

Analysis: calculated for C25H24F4O4: C : 64.65% , H : 5.21 %, F : 16.36 % ; found: C: 64.60%, H: 5.52 %, F: 16.47 %.

5.86 g (26 mmoles) of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone are added to a solution of 6.0 g (12.9 mmoles) of 1-(4-fluorophenyl)-3,3,3-trifluoro-1,2-bis-(4-methoxy-methoxy-phenyl)-propane in 30 ml of dry benzene. The mixture is boiled for 28 hours and then processed as described in Example 7. The product is crystallized from isopropanol. 4.42 g (74 %) of the desired compound are obtained; m.p.: 43-74 C.

Analysis: calculated for C25H22F404: C: 64.93 %, H: 4.80 %, F: 16.43 %; found: C: 64.67 %, H: 4.98 %, F: 16.49%.

3.0 g (6.5 mmoles) of the above product are added to a solution of 0.35 g (0.015 g.-atoms) of sodium in 2.67 g (30 mmoles ) of dimethylamino-ethanol, and the mixture is treated as described in Example 19.3.97 g (100 %) of 1-[4-(2-dimethylamino-ethoxy)-phenyl]-3,3,3-trifluoro-1,2-bis-(4-methoxy-methoxy)-phenyl-propene are obtained as a resinous substance. This product is utilized in the subsequent step without purification EXAMPLE 33 Preparation of2-phenyl-3,3,3-trifluoro- 1-{4-hydroxy-phenyl)- 1-[4-(2-morpholinoethoxy)-phenyl]-propene 10 ml of a 9% methanolic hydrochloric acid are added to a solution of 3.08 g (6 mmoles) of 2-phenyl-3,3,3-trifluoro-1-[4-(2-morpholinoethoxy)~phenyl]-1-(4-methoxymethoxy-phenyl)-propene in 40 ml of methanol, and the mixture is boiled for one hour.The solution is rendered alkaline with 1.5 ml of a 10 n sodium hydroxide solution and then evaporated. The residue is dissolved in 400 ml of ether, the solution is washed with water until neutral, dried and evaporated. The residue is crystallized from acetone. 2.23 g (73.6 %) of the desired compound are obtained : m.p. : 154-157 C.

Analysis: calculated for C27H26F3NO3: C: 69.07%, H: 5.58%, F: 12.14%, N: 2.98%; found : C : 69.37%, H : 5.82 %, F : 12.04 %, N : 2.87%.

2-Phenyl-3,3,3-trifluoro-1-(4-methoxymethoxy-phenyl)-1-[4-(2-morpholinoethoxy)-phenyl]-propene, applied as starting substance, is prepared as follows : 9.6 g (120 mmoles ) of chloromethyl ether and 8.4 hg (210 mmoles )of powdered sodium hydroxide are added to a solution of 27.7 g (76 mmoles ) of 2-phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-1-(4-hydroxyphenyl)propane in 100 ml of benzene , prepared as described in Example 22, and the mixture si bolied for one hour The reaction mixture is diluted with 150 ml of benzene, washed with a 20% aqueous ammonium chloride solution until neutral, dried and evaporated. The residue is dissolved in benzene and passed through a chromatographic column filled with 650 g of silica gel.The first eluate fractions are combined and evaporated to obtain 20.66 g (66.6 %) of 2-phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-1-(4-methoxymethoxy- phenyl)-propane, which is applied in the subsequent step without purification.

22.7 g (100 mmoles) of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone are added to a solution of 19.70 g (48.7 mmoles) of the above product in 100 ml of dry benzene. The mixture is boiled for 17 hours and then - processed as described in Example 7. The product is crystallized from isopropanol. 7.20 g (36.7 %) of 2-phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-1-(4-methoxy-methoxy-phenyl)-propene are obtained; m.p.: 6668 C.

Analysis: calculated for C23H18F402: C: 68.65 %, H: 4.51 %, F: 18.89 %; found : C : 68.50%, H : 4,73 % , F : 19.01%.

0.28 g (0.021 g.-atoms) of sodium are dissolved in 4.72 g (36 mmoles) of (2-hydroxyethyl)-morphollne, 2.40 g (6 mmoles) of the above product are added, and the mixture is heated at 150 C for one hour. The mixture is cooled, diluted with 100 ml of ether, washed with water until neutral and dried. 3.08 g (100 %) of 2-phenyl-3,3,3-trifluoro-1 -(4-methoxymethoxy-phenyl)-1 -[4-(2-morpholi noethoxy)-phenyl]-propene are obtained as a resinous substance. This product is utilized in the subsequent step without purification.

EXAMPLE 34 Preparation of2-phenyl-3,3,3-trifluoro- 1-(4-hydroxy-phenyl)- 1-[4-(2-methylamino-ethoxy)-phenyyl]-propene hydrochloride 1.5 ml of a 9% methanolic hydrochloric acid are added to a solution of 1.50 g (3.28 mmoles) of 2-phenyl-3,3,3-trifluoro-1 -[4-(2-methylam inoethoxy)-phenyl]-1 -(4-methoxymethoxy-phenyl)-propene in 15 ml of methanol, and the mixture is boiled for one hour. The solution is evaporated to dryness, and the residue is crystallized from isopropanol. 1.06 g (71.6 %) of the desired compound are obtained; m.p.: 213-218 C.

Analysis: calculated for C24H23CIF3NO2: C: 64.07%, H: 5.15%, Cl: 7.88%, F: 12.67%, N: 3.11%; found: C: 64.74%, H: 5.53%, Cl: 8.01%, F: 12.45%, N: 3.03% 2-Phenyl-3,3,3-trifluoro-1 -[4-(2-methylam inoethoxy)-phenyl]-1 -(4-methoxymethoxy-phenyl)-propene, applied as starting substance, is prepared as follows: 0.28 g (0.012 g.-atoms) of sodium are dissolved in 2.70 g (36 mmoles) of N-methylamino-ethanol, 2.36 g (5.86 mmoles) of 2-phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-1-(4-methoxymethoxy-phenyl)-propene, prepared as described in Example 33, are added, and the mixture is heated at 1500C for one hour. The mixture is cooled, diluted with 100 ml of ether, washed with water until neutral, dried and evaporated.The residue is crystallized from hexane. 1.94 g (72.4 %) of 2-phenyl-3,3,3-trifluoro-1-[4-(2-methylaminoethoxy)-phenyl]-1- (4-methoxymethoxy-phenyl)-propene are obtained; m.p.: 87-90 C.

Analysis: calculated for C26H26F3NO3: C : 69.25%, H : 5.73 %, F : 12.46%, N : 3.06 % ; found : C : 70.08%, H : 5.65 %, F : 12.66%, N : 3.16 % .

EXAMPLE 35 Preparation of (E)-1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-heptamethyleneimino-ethoxy)~phenyl]-propene 2.32 g (20 mmoles) of heptamethyleneimine are added to a solution of 4.47 g (10 mmoles) of (E)-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene, prepared as described in Example 7, in 30 ml of ethanol, and the mixture is boiled for 5 hours. The reaction mixture is evaporated to dryness.

Thereafter one proceeds as described in Example 1, and crystallizes the product from hexane. 3.22 g (67 %) of the desired compound are obtained; m.p.: 73-77 C.

Analysis: calculated for C30H32F3NO: C : 75.13 %, H : 6.73 %, F : 11.88%, N : 2.92% ; found : C : 75.11 %, H : 6.75 %, F : 11.88%, N : 2.98 %.

EXAMPLE 36 Preparation of (E)-1-[4-(2-diethylaminoethoxy)-phenyl)-1,2-diphenyl-3,3,3-trifluoro-propene picrate 5.37 g (12 mmoles) of (E)-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphonyl-3,3,3-trifluoro-propene, prepared as described in Example 7, are boiled with 8.8 g of diethylamine for 5 hours. The reaction mixture is diluted with 50 ml of benzene, washed with water until neutral, dried and evaporated. The residue is dissolved in 20 ml of 95% ethanol, and a solution of 3.22 g (14 mmoles) of picric acid in 32 ml of 95% ethanol is added. The separated crystals are filtered off, washed with ethanol and ether. 6.46 g (80.4 %) of the desired compound are obtained; m.p.: 131-135 C.

Analysis: calculated for C33H31F3N4O8: C: 59.28 %, H: 4.67 %, F: 8.52 %, N : 8.40 % ; found: C: 59,55%, H:4,78%, F:8,73%, N:8,35%.

EXAMPLE 37 Preparation of (E)-1-[4-(2-dimethylaminoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene sulfate 0.03 ml (0.55 mmole) of 98% sulfuric acid are added to a solution of 0.205 g (0.5 mmole) of (E)-l -[4-(2-dimethylaminoethoxy)-phenyl]-l ,2-diphenyl-3,3,3-trif luoro-propene in 1.5 ml of isopropanol. The separated crystals are filtered off, washed with ether, and the crude product is recrystallized from isopropanol. 0.22 g (84.6%) of the desired compound are obtained; m.p.: 150-153 C.

Analysis: calculated for C2sH26F3NO5S: C : 58.93%, H: 5.14%, F: 11.19%, N : 2.75% , S: 6.29%; found: C: 59.07%, H: 5.30%, F: 11.29%, N: 2.70%, S: 6.46%.

(E)-l -[4-(2-Dimethylaminoethoxy)-phenyl]-l ,2-diphenyl-3,3,3-trif luoro-propene, applied as starting subst ance, is prepared as follows: 10 ml of a 40% aqueous solution of dimethylamine are added to a solution of 5.37 g (12 mmoles) of (E)-1-[4-(2-bromoethxoy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene, prepared as described in Example 7, in 10 ml of ethanol. The mixture is allowed to stand for 3-4 days, then evaporated, the residue is diluted with 50 ml of benzene, the resulting solution is washed with water until neutral, dried and evaporated. The residue is crystallized from hexane. 4.26 g (86.2 %) of (E)-1-[4-(2-dimethylaminoethoxy)-phenyl]-1,2- diphenyl-3,3,3-trifluoro-propene are obtained; m.p.: 90-91 C.

Analysis: calculated for C25H24F3NO: C: 72.98 %, H: 5.88 %, F: 13.85 %, N: 3.40 %; found: C: 72.80%, H: 5.51 %, F: 14.01 %, N: 3.53 %.

EXAMPLE 38 Preparation of (E)-1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-(4-(2-hydroxyethyl)-piperazinol-ethoxy)-phenyl]propene mesylate A solution of 0.2 g (2 mmoles) of methanesulfonic acid in 2 ml of isopropanol is added to a solution of 0.50 g (1 mmole) of (E)-1 ,2-diphenyl-3,3,3-trifluoro-1 -[4-(2-/4-(2-hydroxyethyl)-piperazino/-ethoxy)-phenyl]- propene, prepared as described in Example 11, in 1 ml of isopropanol. The separated crystals are filtered off and washed with ether. 0.58 g (96.7 %) of the desired compound are obtained; m.p.: 203-209 C.

Analysis : calculated for C31H39F3N2O8S2.

C: 54.06%, H: 5.71%, F: 8.28%, N: 4.07%, S: 9.31%; found: C: 53.71%, H: 5.90%, F: 8.42%, N: 3.81%, S: 9.03%.

EXAMPLE 39 Preparation of (E)-1-[4-(2-aminoethoxy)-phenyl-1,2-diphenyl-3,3,3-trifluoro-propene tosylate A solution of 0.20 g (1 mmole) of p-toluenesulfonic acid in 1 ml of isopropanol is added to a solution of 0.30 g (0.8 mmoles) of (E)-1-[4-(2-aminoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene, prepared as described in Example 8, in 0.5 ml of isopropanol. The separated crystals are filtered off and washed with ether.

0.37 g (84%) of the desired ocmpound are obtained : m.p. : 162-163 C.

Analysis: calculated for C30H28F3NO4S: C: 64.85%, H: 5.08%, F: 10.26%, N: 2.52%, S: 5.77%; found: C: 64.98%, H: 5.03%, F: 10.53%, N: 2.23% S: 5.93%.

EXAMPLE 40 Preparation of {E)- 1,2-diphenyl-3,3,3-trifluoro- 1-[4-(2-12-hydroxyethylaminol-ethoxy)-phenyl]-propene citrate A solution of 0.13 g (0.6 mmole) of citric acid hydrate in 0.8 ml of acetone is added to a solution of 0.21 g (0.5 mmole) of (E)-1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-2-hydroxy-ethylamino/-ethoxy)-pheny]-propene, prepared as described in Example 12, in 0.2 ml of acetone. The mixture is cooled, the separated crystals are filtered off and washed with acetone. 0.18 g (58%) of the desired compound is obtained; m.p.: 127-129 C.

Analysis: calculated for C31H32F3NO9: C: 60.09%, H: 5.21%, F: 9.20%, N: 2.26%; EXAMPLE 41 Preparation of (E)-1,2-diphenyl-3,3,3-trifluoro-1-1[4-(2-hexylamino-ethoxy)~phenyl]-propene tosylate 2.23 g (5 mmoles) of (E)-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene, prepared as described in Example 7, are dissolved in a mixture of 5.0 g (50 mmoles) of n-hexylamine and 10 ml of 2-methoxyethanol. The mixture is boiled for 30 minutes, then evaporated, and the residue is passed through a chromatographic column filled with 50 g of silica gel. The column is eluted with benzene. The fractions which are chromatographically uniform are combined and evaporated, the residue is dissolved in 5 ml of isopropanol, and a solution of 1.20 g (6 mmoles) of p-toluenesulfonic acid in 6 ml of isopropanol is added.

The separated crystals are filtered off and washed with ether. 2.14 g (91.8 %) of the desired compound are obtained ; m.p. : 151-153 C.

Analysis: calculated for C36H40F3NO4S: C: 67.58%, H: 6.30%, F: 8.91%, N: 2.19%, S: 5.01%; found: C: 67.61%, H: 6.55%, F: 9.08%, N: 2.39%, S: 5.15%.

EXAMPLE 42 Preparation of fE)- 1,2-diphenyl-3,3,3-trifluoro- 1-[4f2-13-hydroxy-propylaminol-ethoxy)-phenyll-propene 2.23 g (5 mmoles) of (E)-1-[4-(2-bromoethoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propene, prepared as described in Example 7, are dissolved in a mixture of 3.80 g of 1-amino-3-propanol and 10 ml of 2-methoxyethanol. The mixture is boiled for 30 minutes and then processed as described in Example 2. The mixture is crystallized from a 1:1 mixture of ethyl acetate and hexane. 1.77 g (80.5 %) of the desired compound are obtained; m.p.: 97-99 C.

Analysis: calculated for C26H26F3NO2: C : 70.73%, H : 5.94 %, F : 12.91%, N : 3.17% ; found: C: 70.71 %, H: 5.94%, F: 12.83%, N: 3.23%.

EXAMPLE 43 Preparation of (E)-1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-nitroguanidino-ethoxy)-phenyl]-propene A solution of 3.83 g (10 mmoles) of (E)-l -[4-(2-aminoethoxy)-phenyl]-l ,2-diphenyl-3,3.3-trifluoro-propene, prepared as described in Example 8, and 1.22 g (9 mmoles) of 2-methyl-1-nitro-2-isothiourea [L. Fishbein et al.: J. Am. Chem. Soc. 76, 1877(1954] in 25 ml of ethanol is boiled for one hour. The reaction mixture is evaporated and the residue is crystallized from methanol. 2.78 g (66 %) of the desired compound are obtained ; m.p. : 112-116 c (decomposition).

Analysis: calculated for C24H21F3N403: C : 61.27%, H : 4.50 %, F : 12.125 , N : 11.91 found: C: 61.21 %, H : 4.80%. F: 12.27%, N: 11.62%.

EXAMPLE 44 Preparation of (Z)-1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-/2-hydroxyethylaminol-ethoxy)-phenyl]-propenefumarate 0.59 g (1.17 mmoles) of (Z)-1 -[4-(2-bromoethoxy)-phenyl]-l ,2-diphenyl-3,3,3-trifluoro-propene, prepared as described in Example 7, are dissolved in a mixture of 1.34 g of 2-aminoethanol and 1.5 ml of 2-methoxyethanol. The solution is boiled for 30 minutes and then processed as described in Example 2. The crude product is crystallized from a 1:3 mixture of ethyl acetate and hexane. 0.35 g (70 %) of the base form of the desired compound are obtained; m.p.: 81-83 C. The free base is dissolved in 1.5 ml of ethanol, and an ethanol solution of 0.12 g (1 mmole) of fumaric acid is added.The separated crystals are filtered off and washed with ether. 0.28 g (62.2 %) of the desired compound are obtained; m.p.: 168-172 C.

Analysis: calculated for C29H28F3NO6: C : 64.08%, H : 5.19 %, F : 10.49 %, N : 2.58% ; found : C : 64.40%, H : 5.32%, F : 10.65%, N : 2.85 %.

EXAMPLE 45 Preparation of threo-1,2-diphenyl-3,3,3-trifluoro-1-(4-propoxyphenyl)-propane 0.80 g (20 mmoles) of powdered sodium hydroxide and 6.8 g (40 mmoles) of n-propyl iodide are added to a solution of 3.42 g (10 mmoles) of threo-l ,2-diphenyl-3,3,3-trifluoro-l -(4-hydroxyphenyl)-propane, prepared as described in Example 1, in 35 ml of dry benzene, and the mixture is boiled for 4 hours. The mixture is diluted with 50 ml of benzene, washed with water until neutral, dried and evaporated. The residue is crystallized from isopropanol. 3.32 g (85.5 %) of the desired compound are obtained; m.p.: 77-80 C.

Analysis: calculated forC24H23F3O: C : 74.98%, H : 6.03%, F : 14.83% ; found: C: 75.01 %, H: 6.20 %, F: 14.95% .

EXAMPLE 46 Preparation of threo- 1-[4-(3,4-epoxy)-2-hydroxyl-butoxy)-phenyl]-1,2-diphenyl-3,3,3-trifluoro-propane A mixture of 3.42 g (10 mmoles) of threo-l ,2-diphenyl-3,3,3-trifluoro-l -(4-hydroxyphenyl)-propane, prepared as described in Example 1, and 17 ml of DL-diepoxybutane is heated at 100 C for 0.5 hours. The reaction mixture is evaporated, the residue is diluted with 300 ml of ether, washed with water, dried and evaporated. The residue is crystallized from isopropanol.The obtained substance, weighing 3.22 g (75.2 %; m.p.: 121-126 C), is subjected to chromatography in a 3:2 mixture of hexane and acetone, and the chromatographically uniform product is crystallized from isopropanol. 1.90 g (44.4%) of the desired compound are obtained; m.p.: 130-133 C.

Analysis: calculated for C25H23F3O3 : C : 70.08%, H : 5.41 5, F : 13.30% found: C: 70.30%, H: 5.74%, F: 13.09%.

EXAMPLE 47 Preparation ofpharmaceutical compositions a) Tablets Tablets for oral administration, each containing 10 mg of the active agent, are prepared in a manner known per se. The composition of one tablet is as follows: (E)-1 ,2-Diphenyl-3,3,3-trifluoro-1 -[4-(2-/2-hydroxy-ethylamino/ ethoxy)-phenyl]-propane (calculated as free base) 10.0 mg Maize starch 49.6 mg Lactose 109.0 mg Pelyvinylpyrrolidone 5.4 mg Magnesium stearate 1.0 mg Colloidal silicon dioxide 5.0 mg Average weight: 180.0 mg b) Capsules Hard gelatine capsules, each containing 10 mg of the active agent, are prepared in a manner known per se.The composition of one capsule is as fellows: threo-l -[4-(2,3-Epoxypropoxy)-phenyl]-1,2-diphenyl- 3,3,3-trifluoro-propane 10.0 mg Maize starch 84.0 mg Magnesium stearate 1.0 mg Colloidal silicon dioxide 5.0 mg

Claims

1. 1,1 ,2-Triphenylpropane and-propene derivatives of the general formulae (I),

wherein A and B each stand for hydrogen or they form together as a valence bond, X and Y are identical or different and stand for phenyl group or a phenyl group having a halogen, hydroxy, methoxy-methoxy, C1.6 alkoxy or benzyloxy substituent in the para position, R1 is a C16 alkyl, epoxyalkyl, azidoalkyl, methoxymethyl or benzyl group or a group of the general formula (II),

wherein R2 and R3 each represent hydrogen or a C1.6 alkyl, hydroxyalkyl or haloalkyl group, or R2 and R3 form together with the adjacent nitrogen atom an up to 8-membered heterocyclic group, an up to 6-membered heterocyclic group optionally containing further hetero atom(s), which heterocyclic groups optionally have a C1-C6 alkyl or hydroxyalkyl substituent, a guanidino group, an aminoguanidino group or a nitroguanidino group, with the proviso that (a) if A and B form together a valance bond that (a) and X and Y each stand for phenyl or X is phenyl and Y is p-methoxyphenyl, R1 may not stand for a dimethylaminoethyl, diethylaminoethyl, pyrrolidinoethyl, piperidinoethyl or morpholinoethyl group in the case ofthe (Z) isomers, (b) if A and B form together a valence bond and X and Y each stand for phenyl R' may not stand for methyl or ethyl; (c) if A and B form together a valence bond and X and Y each stand for phenyl, then in the case of (Z) isomers, R' may not stand for dimethylamino ethyl, diethylaminoethyl, morpholinoethyl or piperidinoethyl.

(d) if A and B form together a valence bond X stands for phenyl and Y stands for paramethoxyphenyl R' may not stand for methyl or pyrrolidinoethyl; (e) if A and B form together a valence bond X stands for paramethoxyphenyl, parafluorphenyl or paraethoxyphenyl, and Y stands for phenyl R' may not stand for methyl; (f) if A and B form together a valence bond Xis phenyl and Y is parahydroxyphenyl, R' may not stand for methyl; (g) if A and B form together a valence bond and X and Y each stand for paramethoxyphenyl, R' may not stand for methyl, stereoisomers and isomeric mixtures thereof, and acid addition salts of the basic compounds having the general formula (I).

2. A compound as claimed in claim 1 in which A and B form together a valence bond.

3. A compound as claimed in claim 1 in which A and B form together a valence bond or each of them represents hydrogen, X and Y are identical or different and stand for phenyl or p-hydroxyphenyl and R1 is a C1 4 epoxyalkyl group, a C1 4 azidoalkyl group or a group of the general formula (it), wherein R2 and R3 each stand for hydrogen, a C1 4 alkyl group or a C1 4 hydroxyalkyl group or they form together with the adjacent nitrogen atom a piperazino, pyrrolidino, piperidino or morpholino group having optionally a C14 alkyl su bstituent.

4. Threo-1 -[4-(2,3-Epoxypropoxy)-phenyl]-1 ,2-diphenyl-3,3,34rifluoro-propane.

5. (E)-1 ,2-Diphenyl-3,3,3-trifluoro-1 -[4-(2-/4-methyl-piperazino/ethoxy)-phenyl]-propene.

6. 1 -[4-(2-Dimethylam inoethoxy)-phenyl]-2-phenyl-3,3,3-trifluoro-1 -(4-hydroxyphenyl )-propene.

7. 1,2-Diphenyl-3,3,3-trifluoro-1-[4-(2-/2-hydroxyethylaminol-ethoxy)-phenyl]-propene.

8. (E)-l -[4-(2-Azidoethoxy)-phenyl]-l ,2-diphenyl-3,3,3-trif luoro-propene.

9. 1-[4-(2-Dimethylaminoethoxy)-phenyl]-3,3,3-trifluoro-1 ,2-bis-(4-hydroxyphenyl)-propene.

10. 1 -[4-(2-Dimethyla minoethoxy)-phenyl]-3,3,3-trifluoro-1 ,2-bis-(4-hyroxyphenyl)-propene hydrochloride.

11. A process for the preparation of a 1,1 ,2-triphenylpropane or -propene derivative of the general formula (I),

wherein A and B each stand for hydrogen or they form together a valence bond, X and Y are identical or different and stand for phenyl group or a phenyl group having a halogen, hydroxy, methoxy-methoxy, C1-6 alkoxy or benzyloxy substituent in the para position, R1 is a C1 6 alkyl, epoxyalkyl, azidoalkyl, methoxymethyl or benzyl group or a group of the general formula (it),

wherein R2 and R3 each stand for hydrogen or a C1 6 alkyl, hydroxyalkyl or haloalkyl group, or R2 and R3 form together with the adjacent nitrogen atom an up to 8-membered heterocyclic group, an up to 6-membered heterocyclic group optionally containing further hetero atom(s), which heterocyclic groups optionally have a C1 6 alkyl or hydroxyalkyl substituent, a guanidino group, an aminoguanidino group or a nitroguanidino group, with the proviso that (a) if A and B form together a valence bond and X and Y each stand for phenyl or Xis phenyl and Y is p-methoxyphenyl, R1 may not stand for a dimethylaminoethyl, diethylaminoethyl, pyrrolidinoethyl, piperidinoethyl or morpholinoethyl group in the case ofthe (Z) isomers, and stereoisomers and isomeric mixtures thereof, furthermore acid addition salts of the basic compounds having the general formula (I), characterized in that a) to prepare a compound of the general formula (I) in which A and B are as defined above, X and Y are identical or different and represent a phenyl group, a p-halophenyl group or a p-(C1.6 alkoxy)-phenyl group, R1 stands for azidoethyl group or a group of the general formula (II), wherein R2 and R3 are as defined above, a phenoxyalkylhalide or -sulfonate of the general formula (III),

wherein A and B are as defined above, X and Y are as defined in point a) and Z stands for halogen or a sulfonyloxy group, is reacted with an amine of the general formula R2R3NH, wherein R2 and B3 are as defined above, or with an alkali metal azide, and, if desired, the resulting azido derivative is reduced, and, if desired, a resulting amino derivative is converted into the respective guanidino, aminoguanidino or nitroguanidino derivative; or (b) to prepare a compound of the general formula (I) in which A and B form together a valence bond, X and Y are identical or different and represent an unsubstituted phenyl group or a phenyl group which has a chloro, bromo, methoxymethoxy, C16 alkoxy or benzyloxy substituent in the para position, and R1 stands for a group of the general formula (II), wherein R2 and B3 form together with the adjacent nitrogen atom an up to 8-membered heterocyclic group or an up to 6-membered heterocyclic group optionally containing further hetero atom(s), which heterocyclic groups optionally have a lower alkyl or hydroxyalkyl substituent, a compound of the general formula (IV),

wherein Aand B stand for hydrogen and X and Y are as defined in point b) above, is dehydrogenated and then reacted with an alcohol derivative of the general formula R1OM, wherein R1 is as defined in point b) and M stands for an alkali metal atom; or c) to prepare a compound of the general formula (I) in which A and B are as defined above, X and Y are identical or different and represent an unsubstituted phenyl group or a phenyl group having a halogen or C16 alkoxy substituent in the para position and R1 stands for a C1.6 alkyl, epoxyalkyl, methoxymethyl or benzyl group or represents a group of the general formula (II), wherein R2 and B3 each stand for a C1.6 alkyl group or they form together with the adjacent nitrogen atom an up to 8-membered heterocyclic group or an up to 6-membered heterocyclic group optionally containing further hetero atom(s), which heterocyclic groups optionally have a C16 alkyl substituent, a compound of the general formula (V),

wherein A and B are as defined above and X and Y are as defined in point c), is reacted with an R1-halide or an R1-sulfonate, wherein R1 is as defined in point c) above, in the presence of an acid binding agent; or d) to prepare a compound of the general formula (I) in which A and B form together a valence bond, X and/or Y stands for a p-hydroxyphenyl group and R1 is a group of the general formula (II), wherein B2 and B3 each represent hydrogen or a C16 alkyl group or they form together with the adjacent nitrogen atom an up to 8-membered heterocyclic group or an up to 6-membered heterocyclic group optionally containing further hetero atom(s), which heterocyclic groups optionally have a C1 6 alkyl substituent, a compound of the general formula (IV), wherein A and B are as defined in point d) and X and/or Y is a p-(methoxymethoxy)phenyl group or a benzyloxyphenyl group, is reacted with an alcohol derivative of the general formula R1OM, wherein R1 is as defined in point d) and M is an alkali metal atom, and then the methoxymethoxy group or the benzyloxy group is subjected to an ether splitting reaction; or e) to prepare a compound of the general formula (I) in which A and B form together a valence bond, X and Y are identical or different and stand for an unsubstituted phenyl group or a phenyl group which has a halo, methoxymethoxy, C1.6 alkoxy or benzyloxy substituent in the para position and R1 represents a C1 6 alkyl, epoxyalkyl, azidoethyl, methoxy-methyl or benzyl group, a compound of the general formula (I), wherein A and B each stand for hydrogen and X, Y and R1 are as defined in point e), is dehydrogenated; or f) to prepare a compound of the general formula (I) in which R1 represents a group of the general formula (II) and in this latter formula R2 and/or R3 stands for a C1 6 haloalkyl group, a compound of the general formula (I), wherein R1 is a group of the general formula (II) and in this latter formula R2 and/or R3 represents a C1 6 hydroxyalkyl group, is halogenated; and, if desired, the individual stereoisomers are separated from a resulting isomeric mixture, and, if desired, a basic compound of the general formula (I) is converted into its acid addition salt or liberated from its acid addition salt.

12. A process as claimed in claim 11 for the preparation ofthreo-1 -[4-(2,3-epoxypropoxy)-phenyl]-1 ,2- diphenyl-3,3,3-trifluoro-propane, characterized in that the appropriate starting substances are applied.

13. A process as claimed in claim 11 for the preparation of (E)-l ,2-diphenyl-3,3,3-trifluoro-l -[4-(2-/ 4-methylpiperazino/-ethoxy)-phenyl]-propene, characterized in that the appropriate starting substances are applied.

14. A process as claimed in claim 11 for the preparation of 1 -[4-(2-dimethylaminoethoxy)-phenyl]-2phenyl-3,3,3-trifluoro-1 -(4-hydroxyphenyl )-propene, characterized in that the appropriate starting substances are applied.

15. A process as claimed in claim 11 for the preparation of 1,2-diphenyl-3,3,3-trifluoro-1-[4-(2-/ 2-hydroxyethylamino/-ethoxy)-phenyl]-propene, characterized in that the appropriate starting substances are applied.

16. A process as claimed in claim 11 for the preparation of (E)-1 -[4-(2-azidoethoxy)-phenyl]-1 ,2-diphenyl- 3,3,3-trifluoro-propene, characterized in that the appropriate starting substances are applied.

17. A process as claimed in claim 11 for the preparation of 1 -[4-(2-dimethylaminoethoxy)-phenyl]-3,3,3- trifluoro-1,2-bis (4-hydroxyphenyl)-propene, characterized in that the appropriate starting substances are applied.

18. A process as claimed in claim 11 for the preparation of 1 -[4-(2-dimethylaminoethoxy)-phenyl]-3,3,3 trifluoro-1 ,2-bis-(4-hydroxyphenyl )-propene hydrochloride, characterized in that the appropriate starting substances are applied.

19. A pharmaceutical composition which contains as active ingredient at least one compound of the general formula (I), wherein A, B, X, Y and R1 are as defined in claim 1, or a stereoisomer or an isomeric mixture thereof or a pharmaceutically acceptable acid addition salt of a basic compound of the general formula (I) together with a conventional inert, solid or liquid pharmaceutical carrier.

20. A process for the preparation of a pharmaceutical composition as claimed in claim 19, characterized in that a compound of the general formula (I), wherein A, B, X, Y and R1 are as defined in claim 1, or a stereoisomer or an isomeric mixture thereof or a pharmaceutically acceptable acid addition salt of a basic compound of the general formula (I) is converted into a pharmaceutical composition in a manner known per se, utilizing a conventional inert, solid or liquid pharmaceutical carrier.

21. A compound as claimed in any of claims 1 to 10 substantially as hereinbefore described, with specific reference to any one of the Examples 1 to 46.

22. A process as claimed in any of claims 11 to 18 substantially as hereinbefore described, with specific reference to any one of the Examples 1 to 46.

23. A composition as claimed in claim 19 substantially as hereinbefore described, with specific reference to Example 47.

24. A process as claimed in claim 20 substantially as herein before described, with specific reference to Example 47.