Novel imidazole derivatives as histamine receptor H.sub.3 antagonists and/or agonists, preparation thereof and therapeutical uses thereof. Chemical compounds for use as histamine receptor H.sub.3 agonists, partial agonists or antagonists, having general formula (Ia) or (Ib), the use thereof for making drugs, and methods for revealing the agonist, partial agonist or antagonist activity of such compounds in vivo, are disclosed. ##STR1##

The present invention relates to new imidazole derivatives, to their
 preparation and also to their therapeutic applications as chemical
 compounds which are histamine H.sub.3 receptor antagonists, agonists or
 partial agonists.
 Histamine, in a known manner, an aminated base derived from histidine by
 decarboxylation, causes smooth muscle contraction, a secondary hypotension
 and phenomena resembling anaphylactic shock (oedema, urticaria, etc.) in
 man and in animals.
 Histamine is also a chemical mediator released by some histaminergic cells.
 Hence the interest which exists, in particular in the medical field, in
 being able to control histamine release, in particular in the case of
 disease, is readily understood.
 This effect may be obtained by stimulation of the H.sub.3 receptors
 (presynaptic autoreceptors), whereas blockade of the latter induces, on
 the contrary, an increase in histamine release, in particular at the
 cerebral histaminic neurons (Nature, 1983, 302:832). Moreover, it has
 become apparent more recently that the H.sub.3 receptors also have a role
 as presynaptic heteroreceptors and, as such, they control, for example,
 the release of pro-inflammatory peptides in some tissues; their
 stimulation by H.sub.3 agonists will enable anti-inflammatory,
 anti-asthmatic and antimigraine effects to be produced and will make it
 possible to combat glaucoma, sleep-associated problems, Alzheimer's
 disease, schizophrenia, depression, hypertension, dysfunctions of a sexual
 nature, and the like.
 The H.sub.3 receptors have been defined pharmacologically by evaluating the
 effect of stimulating them on the release of endogenous histamine from
 slices of rat brain (Nature 1987, 327: 117-123). In addition, other models
 of studies of the effectors of the H.sub.3 receptor have been proposed
 since then (Physiol. Rev. 1991, 71: 1-51), but not all these models
 readily enable the effect of partial agonists of low intrinsic activity to
 be demonstrated, it being possible for the latter to be readily taken for
 antagonists. In point of fact, these partial agonists may be employed as
 medicinal products for indications similar to those of pure agonists, and
 not for indications for which antagonists are reserved. It is hence
 extremely important for the applications to make this distinction in a
 preclinical phase.
 Moreover, Patent Application WO 93/14070 describes imidazole compounds
 displaying histamine H.sub.3 receptor-antagonist properties, controlling
 the release and synthesis of histamine.
 It is the purpose of the present invention to select, from the family of
 imidazole compounds described in the said Patent Application WO 93/14070,
 groups of compounds or compounds which are noteworthy for their high
 activity with respect to histamine H.sub.3 receptors while being generally
 especially well suited as a result of their pharmacological properties to
 the preparation of medicinal products.
 Moreover, the inventors of the present invention have developed a sensitive
 biological test enabling an agonist displaying low intrinsic activity to
 be clearly differentiated from a pure antagonist. They have, as a result,
 identified partial agonists having strong biological activity in vivo from
 among compounds which, on the basis of their chemical structure and their
 traditional test, were predicted to be antagonists. They have also
 synthesized imidazole derivatives having a stronger H.sub.3 antagonist
 activity, in particular in vivo, than that of the compounds known
 hitherto, and this is likely to decrease the toxic effects or even the
 side-effects at the therapeutic doses, and accordingly to facilitate their
 clinical use.
 Hence the present invention relates to chemical compounds which are
 histamine H.sub.3 receptor agonists, partial agonists or antagonists,
 corresponding to the general formula:
 ##STR2##
 in which:
 the chain A represents an unbranched, branched or unsaturated alkyl group
 --(CH.sub.2).sub.n -- where n is an integer which can vary between 1 and 8
 and preferably between 1 and 4; an unbranched or branched alkene group
 comprising from 1 to 8 carbon atoms and preferably 1 to 4 carbon atoms; an
 unbranched or branched alkyne group comprising from 1 to 4 carbon atoms;
 the group X represents --OCONH--; --OCON(alkyl)-; --OCON(alkene)-; --OCO--;
 --OCSNH--; --CH.sub.2 --; --O--; --OCH.sub.2 CO--; --S--; --CO--; --CS--;
 amine; alkene;
 the chain B represents an unbranched, branched or unsaturated lower alkyl
 comprising from 1 to 8 carbon atoms and preferably 1 to 5 carbon atoms;
 --(CH.sub.2).sub.n (hetero atom)-- where the hetero atom is preferably a
 sulphur or oxygen atom; n being an integer which can vary between 0 and 5,
 preferably between 0 and 4;
 the group Y represents a phenyl group, unsubstituted or mono- or
 polysubstituted with one or more identical or different substituents
 selbcted from halogen atoms, OCF.sub.3, CHO, CF.sub.3, SO.sub.2
 N(alkyl).sub.2, SO.sub.2 N(CH.sub.3).sub.2, NO.sub.2, S(alkyl), S(aryl),
 SCH.sub.2 (phenyl), an unbranched or branched alkene, an unbranched or
 branched alkyne optionally substituted with a trialkylsilyl radical,
 --O(alkyl), --O(aryl), --CH.sub.2 CN, a ketone, an aldehyde, a sulphone,
 an acetal, an alcohol, a lower alkyl, --CH.dbd.CH--CHO,
 --C(alkyl).dbd.N--OH, --C(alkyl).dbd.N--O(alkyl) and other keto
 derivatives, --CH.dbd.NOH, --CH.dbd.NO(alkyl), and other aldehyde
 derivatives, --C(alkyl).dbd.NH--NH--CONH.sub.2, an O-phenyl or --OCH.sub.2
 (phenyl) group, --C(cycloalkyl).dbd.NOH, --C(cycloalkyl).dbd.N--O(alkyl),
 an optionally substituted heterocycle;
 a heterocycle comprising a sulphur hetero atom; a cycloalkyl; a bicyclic
 group and preferably a norbornyl group; a phenyl ring fused to a
 heterocycle comprising a nitrogen hetero atom or to a carbocycle or a
 heterocycle bearing a keto function; an unbranched or branched lower alkyl
 comprising from 1 to 8 carbon atoms; an unbranched or branched alkyne
 comprising from 1 to 8 carbon atoms and preferably 1 to 5 carbon atoms; a
 linear or branched alkyl mono- or polysubstituted with phenyl groups which
 are either unsubstituted or mono- or polysubstituted; a phenyl alkyl
 ketone in which the alkyl group is branched or unbranched or cyclic; a
 substituted or unsubstituted benzophenone; a substituted or unsubstituted,
 unbranched or branched or cyclic phenyl alcohol; an unbranched or branched
 alkene; a piperidyl group; a phenylcycloalkyl group; a polycyclic group,
 in particular a fluorenyl group, a naphthyl or polyhydronaphthyl group or
 an indanyl group; a phenol group; a ketone or keto derivative; a diphenyl
 group; a phenoxyphenyl group; a benzyloxyphenyl group;
 as well as their pharmaceutically acceptable salts, their hydrates, their
 hydrated salts, the polymorphic crystalline structures and the tautomeric
 forms of these compounds.
 The antagonist, the agonist or partial agonist activity of these compounds
 may be readily verified by biological test methods, in particular those
 defined in the present invention.
 The subject of the invention is also, by way of new compounds, those
 compounds of formulae Ia and Ib not known in the prior art, including
 Patent Application WO 93/14070.
 According to the invention, group X representing an amine is understood to
 mean a secondary or tertiary amine.
 The alkyl, alkene, alkyne, keto, aldehyde, cycloalkyl, S-alkyl, O-alkyl,
 phenyl alcohol and phenyl-cycloalkyl groups mentioned above as well as in
 the remainder of the description and the claims of the present patent
 comprise from 1 to 8 carbon atoms, and preferably 1 to 5.
 Likewise, keto derivatives are understood to mean any oxime, alkyloxime,
 hydrazone, acetal, aminal, ketal, thione, carbazone or semicarbazone group
 and the thio analogues of these derivatives.
 Likewise, by mono- or polysubstituted phenyl and/or benzophenone groups, it
 is understood to mean that these groups are substituted with one or more
 identical or different substituents selected from halogen atoms,
 OCF.sub.3, CHO, CF.sub.3, SO.sub.2 N(alkyl).sub.2, SO.sub.2
 N(CH.sub.3).sub.2, NO.sub.2, S(alkyl), S(aryl), SCH.sub.2 (phenyl), an
 unbranched or branched alkene, an unbranched or branched alkyne optionally
 substituted with a trialkylsilyl radical, --O(alkyl), --O(aryl),
 --CH.sub.2 CN, a ketone, an aldehyde, a sulphone, an acetal, an alcohol, a
 lower alkyl, --CH.dbd.CH--CHO, --C(alkyl).dbd.N--OH,
 --C(alkyl).dbd.N--O(alkyl) and other keto derivatives, --CH.dbd.NOH,
 --CH.dbd.NO(alkyl), and other aldehyde derivatives,
 --C(alkyl).dbd.NH--NH--CONH.sub.2, an O-phenyl or --OCH.sub.2 (phenyl)
 group, --C(cycloalkyl).dbd.NOH, --C(cycloalkyl).dbd.N--O(alkyl), an
 optionally substituted heterocycle.
 The keto substituent is preferably selected from a linear- or
 branched-chain aliphatic ketone, it being possible for the said chain to
 comprise from 1 to 8 carbon atoms and optionally to bear a hydroxyl group,
 a cycloalkyl ketone, an aryl alkyl ketone or aryl alkenyl ketone in which
 the aryl group is unsubstituted or mono- or polysubstituted, or a
 heteroaryl ketone in which the heteroaryl unit is preferably monocyclic.
 The acetal substituent preferably consists of an aliphatic acetal
 comprising from 1 to 8 carbon atoms and optionally bearing a hydroxyl
 radical.
 Group Y representing a ketone is understood to mean, in particular, a
 ketone substituted with an alkyl or aryl group, it being possible for
 these groups to be substituted or unsubstituted.
 As regards the heterocycles, these comprise from 1 to 3 hetero atoms,
 preferably sulphur, oxygen or nitrogen atoms.
 The heterocycle substituent is preferably selected from an oxadiazole or an
 imidazole.
 The present invention also relates to the addition salts formed by the
 compounds of formula Ia and Ib with pharmaceutically acceptable acids. The
 pharmaceutically acceptable salts comprise the non-toxic salts of
 inorganic or organic acids such as the hydrochloride, hydrobromide or
 maleate.
 The present invention also encompasses the hydrates of the compounds of
 formula Ia or Ib, the hydrated salts of these compounds and the
 polymorphic crystalline structures. It should, moreover, be noted that the
 structure of the compounds according to the invention as illustrated by
 the formulae Ia and Ib represents only one of the possible tautomeric
 forms of these compounds, and that the latter may occur in other
 tautomeric forms. Hence the present invention also encompasses all the
 possible tautomeric forms of the compounds in question, whether these
 tautomers occur in isolated form or in the form of mixtures.
 The compounds of formula Ia or Ib can exist in one or more isomeric forms,
 depending on the number of asymmetric centres in the molecule. Hence the
 invention relates both to all the optical isomers and to the racemic
 mixtures thereof and the corresponding diastereomers. The separation of
 the diastereoisomers and/or optical isomers may be performed according to
 methods known per se.
 A preferred group of compounds according to the present invention is the
 group composed of the chemical compounds in which the chain A is a
 (CH.sub.2).sub.3 group; X is an O or OCONH group; the chain B is a group
 (CH.sub.2).sub.n where n=0, 2 or 3; and Y is a cyclopentyl group,
 --CH(CH.sub.3).sub.2, --CH(phenyl).sub.2, --C(CH.sub.3).sub.3 or a phenyl
 group: p-substituted with --COC.sub.3 H.sub.7, --OCH.sub.2,
 --CO(cyclopropyl), --C(CH.sub.3).dbd.N--OH, --C(cyclopropyl).dbd.NOH,
 --C(CH.sub.3).dbd.NOCH.sub.3 or --C(cyclopropyl).dbd.N--OCH.sub.3, or
 m-substituted with --COCH.sub.3 or --CF.sub.3.
 A preferred group of compounds according to the invention is composed of
 the chemical compounds corresponding to the formula (Ib) in which Y
 represents a mono- or polysubstituted phenyl group.
 The present invention also relates to chemical compounds which are
 histamine H.sub.3 receptor agonists or partial agonists and which
 correspond to the general formula (Ib) in which:
 A represents --(CH.sub.2).sub.n -- where n is an integer which can vary
 between 1 and 8, preferably between 2 and 4, or --CH.sub.2 CH(CH.sub.3)--;
 X represents an oxygen atom; sulphur atom or --OCONH--; amine;
 Y represents a branched or unbranched lower alkyl optionally mono- or
 polysubstituted with phenyl groups; an aryl radical such as a phenyl group
 substituted with a lower alkyl, CF.sub.3, NO.sub.2, OCF.sub.3, an alcohol,
 an aldehyde, a ketone, --C(alkyl).dbd.N--OH;
 as well as their pharmaceutically acceptable salts, their hydrates, their
 hydrated salts, the polymorphic crystalline structures and the tautomeric
 forms of these compounds.
 Such compounds may be used for the purpose of manufacturing a medicinal
 product which acts as H.sub.3 receptor agonist or partial agonist,
 enabling the synthesis and/or release of histamine or of other
 neurotransmitters such as neuropeptides or noradrenaline in human or
 animal tissues to be inhibited by virtue of its action.
 The compounds which are partial agonists are of special interest in that
 they provide for a normalization of transmissions without maximum
 activation or complete blockade of the H.sub.3 receptor, as occurs,
 respectively, with complete agonists and with antagonists.
 The said compounds may also be used in the form of pharmaceutical
 composition comprising a therapeutically effective amount of such a
 chemical compound (or of several, combined or otherwise), in a
 pharmaceutically acceptable excipient, intended for an agonist or partial
 agonist action on the said histamine receptors.
 A preferred group of compounds which are agonists or partial agonists
 according to the present invention is the group composed of the chemical
 compounds in which: the chain A is a group (CH.sub.2).sub.n where n=2, 3
 or 4; X is an O, S or OCONH group; and Y is a --C(CH.sub.3).sub.3 or
 --CH(phenyl).sub.2 group or a phenyl group m-substituted with a
 --COCH.sub.3, --CF.sub.3, --OCF.sub.3 or --CH(CH.sub.3).sub.2 group.
 Among these, preferred compounds which are partial agonists according to
 the present invention correspond, in particular, to Examples 1, 3, 5, 6,
 7, 8, 10, 11, 12, 13, 14, 16, 17, 110, 111, 154 and 157 described below in
 the present description.
 The compound of Example 6 is especially preferred.
 Another preferred group of compounds which are agonists or partial agonists
 according to the present invention is the group composed of the compounds
 of formulae (Ib) in which A is --(CH.sub.2).sub.3 --, X is an amine group
 and Y represents a phenyl group which is substituted, especially
 meta-substituted, preferably with a CF.sub.3, COCH.sub.3 or C.sub.2
 H.sub.5 group.
 Among these, preferred compounds which are agonists correspond, in
 particular, to Examples 154 and 156, the compound of Example 154 being
 especially preferred.
 The subject of the present invention is also chemical compounds which are
 histamine H.sub.3 receptor antagonists, corresponding to the general
 formula (Ia) or (Ib) in which:
 the chain A represents an unbranched alkyl group --(CH.sub.2).sub.n --
 where n is an integer which can vary between 1 and 8, preferably between 1
 and 4; an unbranched alkene group comprising from 1 to 4 carbon atoms;
 the group X represents --OCONH--; --OCON(alkyl)-; --OCON(alkene)-; --OCO--;
 --OCSNH--; --CH.sub.2 --; --O--; --OCH.sub.2 CO--; --CO--; --S--; amine;
 alkene;
 the chain B represents an unbranched or branched lower alkyl comprising
 from 1 to 8 carbon atoms; --(CH.sub.2).sub.n (hetero atom)-, where the
 hetero atom is preferably an oxygen or sulphur atom (where n is an integer
 which can vary between 0 and 4);
 the group Y represents a phenyl group, unsubstituted or mono- or
 polysubstituted with one or more identical or different substituents
 selected from halogen atoms, a linear or branched alkyl, CF.sub.3,
 SO.sub.2 N(alkyl).sub.2, S(alkyl), S(aryl), SCH.sub.2 (phenyl), SO.sub.2
 N(CH.sub.3).sub.2, SCH.sub.3, an unbranched or branched alkene, an
 unbranched or branched alkyne optionally substituted with a trialkylsilyl
 radical, OCH.sub.3, NO.sub.2, OCF.sub.3, a ketone, an alcohol, a sulphone,
 an acetal, CH.sub.2 CN, an aldehyde, --(alkyl)C.dbd.NOH,
 --CH.dbd.N--O(alkyl), --(alkyl)C.dbd.NO(alkyl),
 --C(alkyl).dbd.N--NHCONH.sub.2, --CH.dbd.CH--CHO, --O(alkyl), --O(aryl),
 --CH.dbd.NOH; --OCH.sub.2 (phenyl), optionally substituted heterocycle;
 a heterocycle comprising a sulphur hetero atom; a cycloalkyl; a bicyclic
 group, preferably a norbornyl group; a phenyl ring fused to a heterocycle
 comprising a nitrogen hetero atom or to a carbocycle or to a heterocycle
 bearing a keto function; an unbranched or branched alkyl comprising from 1
 to 8 carbon atoms; an alkyl polysubstituted with phenyl groups which are
 either unsubstituted or mono- or polysubstituted; a phenyl alkyl ketone in
 which the alkyl group is branched or unbranched or cyclic; a substituted
 or unsubstituted benzophenone; a substituted or unsubstituted, unbranched
 or branched or cyclic phenyl alcohol; an unbranched or branched alkyne; an
 unbranched or branched alkene; a piperidyl group; a phenylcycloalkyl; a
 polycyclic group, in particular a fluorenyl group, a naphthyl or
 polyhydronaphthyl group or an indanyl group; a phenol group; a ketone or
 keto derivative; a diphenyl group; a phenoxyphenyl group; a
 benzyloxyphenyl group;
 as well as their pharmaceutically acceptable salts, their hydrates, their
 hydrated salts, the polymorphic crystalline structures and the tautomeric
 forms of these compounds.
 Such compounds may be used for the purpose of manufacturing a medicinal
 product which acts as histamine H.sub.3 receptor antagonist, enabling the
 synthesis and/or release of histamine or of other neurotransmitters such
 as neuropeptides or noradrenaline in human or animal tissues to be
 promoted by virtue of its action.
 The said compounds may also be used in the form of pharmaceutical
 composition comprising a therapeutically effective amount of such a
 chemical compound (or of several, combined or otherwise), in a
 pharmaceutically acceptable excipient, intended for an antagonist action
 on the said histamine receptors.
 A preferred group of compounds which are antagonists according to the
 present invention is the group composed of the chemical compounds in which
 the chain A is a --(CH.sub.2).sub.3 -- group; X is an O or OCONH group;
 the chain B is a --(CH.sub.2).sub.2 -- or --(CH.sub.2).sub.3 -- group; and
 Y is a cyclopentyl group or a phenyl group p-substituted with
 --CO(cyclopropyl), --COC.sub.3 H.sub.7, --OCH.sub.3, --CHOH(cyclopropyl),
 --C(CH.sub.3).dbd.N--OH, --C(cyclopropyl).dbd.N--OH,
 --C(CH.sub.3).dbd.N--OCH.sub.3 or --C(cyclopropyl).dbd.N--OCH.sub.3.
 Another preferred group of compounds which are antagonists is composed of
 the chemical compounds corresponding to the formula (Ib) in which Y
 represents a phenyl group at least monosubstituted with a ketone, an
 oxime, an acetal, a sulphone, an optionally substituted oxadiazole group
 or an unsaturated aliphatic group, in particular a linear or branched
 alkyne group optionally substituted with a trialkylsilyl radical.
 Among these compounds, those for which Y represents a phenyl group
 disubstituted with, as the other substituent, a group preferably selected
 from halogen atoms and a lower alkyl group are preferred.
 Yet another preferred group of compounds which are antagonists is composed
 of the chemical compounds corresponding to the formula (Ib) in which Y
 represents a phenyl group fused to a carbocycle bearing a keto function.
 Yet another preferred group of compounds which are antagonists is composed
 of the chemical compounds corresponding to the formula (Ib) in which Y
 represents a phenyl group fused to a heterocycle bearing a keto function.
 Among the compounds of which the above mentioned groups are composed, those
 in which A represents a --(CH.sub.2).sub.3 -- group and X represents --O--
 are especially preferred.
 Among these compounds, preferred compounds which are antagonists according
 to the present invention correspond, in particular, to Examples 30, 68,
 78, 81, 82, 85, 88, 92, 93, 95, 112, 115, 122, 125, 126, 127, 128, 129,
 134, 135, 136, 138, 139, 141, 142, 143, 144, 145, 146, 147, 149, 16G, 163,
 166, 174, 175 and 176.
 The compound of Example 81 is especially preferred.
 The compounds of Examples 25, 107 and 108 are not preferred.
 The examples which are given in Table I below, without implied limitation,
 illustrate the present invention.
 The compounds of Examples 1 to 20, 110, 111 and 154 to 159 are agonists or
 partial agonists for the said receptors, and Examples 21 to 109, 112 to
 153 and 160 to 183 are antagonists for the said receptors.
 TABLE I
 Example Chain A X Chain B Y
 1 (CH.sub.2).sub.3 OCONH /
 --C(CH.sub.3).sub.3
 2 (CH.sub.2).sub.3 OCONH /
 ##STR3##
 3 (CH.sub.2).sub.3 OCONH /
 ##STR4##
 4 (CH.sub.2).sub.2 OCONH /
 ##STR5##
 5 (CH.sub.2).sub.3 O / --(CH.sub.2).sub.2
 --CH(CH.sub.3).sub.2
 6 (CH.sub.2).sub.3 O / --(CH.sub.2).sub.2
 --C(CH.sub.3).sub.3
 7 (CH.sub.2).sub.3 O / --(CH.sub.2).sub.3
 --CH(CH.sub.3).sub.2
 8 (CH.sub.2).sub.3 O /
 ##STR6##
 9 (CH.sub.2).sub.3 O /
 ##STR7##
 10 (CH.sub.2).sub.2 S /
 ##STR8##
 11 (CH.sub.2).sub.3 O /
 ##STR9##
 12 (CH.sub.2).sub.3 O /
 ##STR10##
 13 (CH.sub.2).sub.3 O /
 ##STR11##
 14 (CH.sub.2).sub.3 O /
 ##STR12##
 15 (CH.sub.2).sub.3 O /
 ##STR13##
 16 (CH.sub.2).sub.4 O /
 ##STR14##
 17 (CH.sub.2).sub.4 O /
 ##STR15##
 18 (CH.sub.2).sub.3 O /
 ##STR16##
 19 (CH.sub.2).sub.3 O /
 ##STR17##
 20 (CH.sub.2).sub.3 O /
 ##STR18##
 21 (CH.sub.2).sub.3 O /
 ##STR19##
 22 (CH.sub.2).sub.3 O /
 ##STR20##
 23 (CH.sub.2).sub.3 O /
 ##STR21##
 24 (CH.sub.2).sub.3 O /
 ##STR22##
 25 (CH.sub.2).sub.3 O /
 ##STR23##
 26 (CH.sub.2).sub.3 O /
 ##STR24##
 27 (CH.sub.2).sub.3 O /
 ##STR25##
 28 (CH.sub.2).sub.3 OCONH /
 --(CH.sub.2).sub.2 CH.sub.3
 29 (CH.sub.2).sub.3 OCONH /
 --(CH.sub.2).sub.3 CH.sub.3
 30 (CH.sub.2).sub.3 OCONH /
 --(CH.sub.2).sub.4 CH.sub.3
 31 (CH.sub.2).sub.3 OCONH /
 --(CH.sub.2).sub.5 CH.sub.3
 32 (CH.sub.2).sub.3 OCONH /
 --(CH.sub.2).sub.6 CH.sub.3
 33 (CH.sub.2).sub.3 OCONH /
 --(CH.sub.2).sub.7 CH.sub.3
 34 (CH.sub.2).sub.3 OCONH /
 ##STR26##
 35 (CH.sub.2).sub.3 OCONH /
 ##STR27##
 36 (CH.sub.2).sub.3 OCONH / --(CH.sub.2).sub.2
 CH(CH.sub.3).sub.2
 37 (CH.sub.2).sub.3 OCONH /
 ##STR28##
 38 (CH.sub.2).sub.3 OCONH /
 ##STR29##
 39 (CH.sub.2).sub.3 ##STR30## /
 --(CH.sub.2).sub.2 CH.sub.3
 40 (CH.sub.2).sub.3 ##STR31## / --CH.sub.2
 --CH.dbd.CH.sub.2
 41 (CH.sub.2).sub.3 OCO /
 ##STR32##
 42 (CH.sub.2).sub.3 OCONH /
 ##STR33##
 43 (CH.sub.2).sub.2 OCONH CH.sub.2
 ##STR34##
 44 (CH.sub.2).sub.3 OCONH CH.sub.2 --CH--CH.sub.3
 ##STR35##
 45 (CH.sub.2).sub.3 OCONH CH.sub.2
 ##STR36##
 46 (CH.sub.2).sub.3 OCONH /
 ##STR37##
 47 (CH.sub.2).sub.3 OCONH /
 ##STR38##
 48 (CH.sub.2).sub.3 OCONH CH.sub.2
 ##STR39##
 49 (CH.sub.2).sub.3 OCSNH /
 ##STR40##
 50 (CH.sub.2).sub.2 CO /
 ##STR41##
 51 CH.dbd.CH--CH.sub.2 CH.sub.2 /
 ##STR42##
 52 (CH.sub.2).sub.2 CH.sub.2 CH.sub.2
 ##STR43##
 53 CH.sub.2 O CH.sub.2
 ##STR44##
 54 CH.sub.2 O CH.sub.2
 ##STR45##
 55 (CH.sub.2).sub.3 O (CH.sub.2).sub.3
 ##STR46##
 56 (CH.sub.2).sub.3 O CH.sub.2
 ##STR47##
 57 (CH.sub.2).sub.3 O CH.sub.2
 ##STR48##
 58 (CH.sub.2).sub.3 O (CH.sub.2).sub.3
 ##STR49##
 59 (CH.sub.2).sub.3 O CH.sub.2
 ##STR50##
 60 (CH.sub.2).sub.3 O (CH.sub.2).sub.3
 ##STR51##
 61 (CH.sub.2).sub.3 O (CH.sub.2).sub.2
 ##STR52##
 62 (CH.sub.2).sub.3 O (CH.sub.2).sub.3
 ##STR53##
 63 (CH.sub.2).sub.3 O (CH.sub.2).sub.2
 ##STR54##
 64 (CH.sub.2).sub.3 O /
 (CH.sub.2).sub.6 --CH.sub.3
 65 (CH.sub.2).sub.3 O / CH.sub.2
 --CH(CH.sub.3).sub.2
 66 (CH.sub.2).sub.3 O (CH.sub.2).sub.2
 ##STR55##
 67 (CH.sub.2).sub.3 O /
 (CH.sub.2).sub.3 --C.tbd.CH
 68 (CH.sub.2).sub.3 O (CH.sub.2).sub.2 O
 ##STR56##
 69 (CH.sub.2).sub.3 O CH.sub.2
 ##STR57##
 70 CH.dbd.CHCH.sub.2 O (CH.sub.2).sub.3
 ##STR58##
 71 (CH.sub.2).sub.3 O /
 ##STR59##
 72 (CH.sub.2).sub.3 O /
 ##STR60##
 73 (CH.sub.2).sub.3 O /
 ##STR61##
 74 (CH.sub.2).sub.3 OCH.sub.2 CO /
 ##STR62##
 75 (CH.sub.2).sub.3 OCH.sub.2 CO /
 ##STR63##
 76 (CH.sub.2).sub.3 O /
 ##STR64##
 77 (CH.sub.2).sub.3 O /
 ##STR65##
 78 (CH.sub.2).sub.3 O /
 ##STR66##
 79 (CH.sub.2).sub.3 O /
 ##STR67##
 80 (CH.sub.2).sub.3 O /
 ##STR68##
 81 (CH.sub.2).sub.3 O /
 ##STR69##
 82 (CH.sub.2).sub.3 O /
 ##STR70##
 83 (CH.sub.2).sub.3 O /
 ##STR71##
 84 (CH.sub.2).sub.3 O /
 ##STR72##
 85 (CH.sub.2).sub.3 O /
 ##STR73##
 86 (CH.sub.2).sub.3 O /
 ##STR74##
 87 (CH.sub.2).sub.3 O /
 ##STR75##
 88 (CH.sub.2).sub.3 O /
 ##STR76##
 89 (CH.sub.2).sub.3 O /
 ##STR77##
 90 (CH.sub.2).sub.3 O /
 ##STR78##
 91 (CH.sub.2).sub.3 O /
 ##STR79##
 92 (CH.sub.2).sub.3 O /
 ##STR80##
 93 (CH.sub.2).sub.3 O /
 ##STR81##
 94 (CH.sub.2).sub.3 O /
 ##STR82##
 95 (CH.sub.2).sub.3 O /
 ##STR83##
 96 (CH.sub.2).sub.3 OCONH /
 ##STR84##
 97 (CH.sub.2).sub.3 OCONH /
 ##STR85##
 98 (CH.sub.2).sub.3 O /
 --(CH.sub.2).sub.2 CO CH.sub.3
 99 (CH.sub.2).sub.3 O (CH.sub.2).sub.2 O
 CH.sub.3
 100 (CH.sub.2).sub.3 O (CH.sub.2).sub.3
 ##STR86##
 101 (CH.sub.2).sub.3 OCONH /
 --CH(CH.sub.3).sub.2
 102 (CH.sub.2).sub.3 OCONH /
 ##STR87##
 103 (CH.sub.2).sub.2 CH.sub.2 (CH.sub.2.sub.5
 CH.sub.3
 104 (CH.sub.2).sub.3 O /
 ##STR88##
 105 (CH.sub.2).sub.3 O /
 ##STR89##
 106 (CH.sub.2).sub.2 O /
 ##STR90##
 107 (CH.sub.2).sub.3 O /
 ##STR91##
 108 (CH.sub.2).sub.3 O /
 ##STR92##
 109 (CH.sub.2).sub.3 O /
 ##STR93##
 110 (CH.sub.2).sub.3 OCONH / --C(CH.sub.3).sub.2
 --C.sub.2 H.sub.5
 111 (CH.sub.2).sub.3 OCONH CH.sub.2
 --C(CH.sub.3).sub.3
 112 (CH.sub.2).sub.3 OCONH CH.sub.2
 --CH.dbd.CH.sub.2
 113 (CH.sub.2).sub.3 OCONH /
 ##STR94##
 114 (CH.sub.2).sub.3 OCONH /
 ##STR95##
 115 (CH.sub.2).sub.3 OCONH /
 ##STR96##
 116 (CH.sub.2).sub.2 O /
 --C(CH.sub.3).sub.3
 117 (CH.sub.2).sub.3 O /
 --C(CH.sub.3).sub.3
 118 (CH.sub.2).sub.3 O CH.sub.2
 --CH.dbd.CH.sub.2
 119 (CH.sub.2).sub.3 O (CH.sub.2).sub.3
 --CH.dbd.CH.sub.2
 120 (CH.sub.2).sub.3 O CH.sub.2
 --C.tbd.CH
 121 (CH.sub.2).sub.3 O /
 ##STR97##
 122 (CH.sub.2).sub.3 O /
 ##STR98##
 123 (CH.sub.2).sub.3 O /
 ##STR99##
 124 (CH.sub.2).sub.3 O /
 ##STR100##
 125 (CH.sub.2).sub.3 O (CH.sub.2).sub.3
 ##STR101##
 126 (CH.sub.2).sub.2 O /
 ##STR102##
 127 (CH.sub.2).sub.3 O /
 ##STR103##
 128 (CH.sub.2).sub.3 O /
 ##STR104##
 129 (CH.sub.2).sub.3 O /
 ##STR105##
 130 (CH.sub.2).sub.3 O /
 ##STR106##
 131 (CH.sub.2).sub.3 O /
 ##STR107##
 132 (CH.sub.2).sub.3 O /
 ##STR108##
 133 (CH.sub.2).sub.3 O /
 ##STR109##
 134 (CH.sub.2).sub.3 O /
 ##STR110##
 135 (CH.sub.2).sub.3 O /
 ##STR111##
 136 (CH.sub.2).sub.3 O /
 ##STR112##
 137 (CH.sub.2).sub.3 O /
 ##STR113##
 138 (CH.sub.2).sub.3 O /
 ##STR114##
 139 (CH.sub.2).sub.3 O /
 ##STR115##
 140 (CH.sub.2).sub.3 O /
 ##STR116##
 141 (CH.sub.2).sub.3 O /
 ##STR117##
 142 (CH.sub.2).sub.3 O /
 ##STR118##
 143 (CH.sub.2).sub.3 O /
 ##STR119##
 144 (CH.sub.2).sub.3 O /
 ##STR120##
 145 (CH.sub.2).sub.3 O /
 ##STR121##
 146 (CH.sub.2).sub.3 O /
 ##STR122##
 147 (CH.sub.2).sub.3 O /
 ##STR123##
 148 (CH.sub.2).sub.3 O /
 ##STR124##
 149 (CH.sub.2).sub.3 O /
 ##STR125##
 150 (CH.sub.2).sub.3 O /
 ##STR126##
 151 (CH.sub.2).sub.3 O /
 ##STR127##
 152 (CH.sub.2).sub.3 O /
 ##STR128##
 153 (CH.sub.2).sub.3 O /
 ##STR129##
 ##STR130##
 Example Chain A X Chain B with
 R:
 154 (CH.sub.2).sub.3 NH /
 3-CF.sub.3
 155 (CH.sub.2).sub.3
 156 (CH.sub.2).sub.3 NH / 3-C.sub.2
 H.sub.5
 157 (CH.sub.2).sub.2 S /
 3-COCH.sub.3
 158 (CH.sub.2).sub.3 O /
 ##STR131##
 159 ##STR132## S /
 3-CF.sub.3
 160 (CH.sub.2).sub.2 O /
 4-CH.sub.3
 161 (CH.sub.2).sub.2 O /
 4-COC.sub.2 H.sub.5
 162 (CH.sub.2).sub.3 O /
 ##STR133##
 163 (CH.sub.2).sub.3 O / 4-C.sub.2
 H.sub.5
 164 (CH.sub.2).sub.3 O /
 ##STR134##
 165 (CH.sub.2).sub.3 O / 4-SO.sub.2
 N(CH.sub.3).sub.2
 166 (CH.sub.2).sub.3 O /
 4-SCH.sub.3
 167 (CH.sub.2).sub.3 O /
 4-SCH.sub.2 Ph
 168 (CH.sub.2).sub.3 S /
 3-COCH.sub.3
 169 (CH.sub.2).sub.3 NH / 4-C.sub.2
 H.sub.5
 170 (CH.sub.2).sub.3 NH /
 4-Cl
 Example Chain A X Chain B Y
 171 (CH.sub.2).sub.3 O /
 ##STR135##
 172 (C.sub.2).sub.3 O /
 ##STR136##
 173 (CH.sub.2).sub.3 O /
 ##STR137##
 174 (CH.sub.2).sub.3 O /
 CH.sub.3
 175 (CH.sub.2).sub.3 O CH.sub.2
 CH.sub.3
 176 (CH.sub.2).sub.3 O (CH.sub.2).sub.2
 CH.sub.3
 177 (CH.sub.2).sub.3 O /
 ##STR138##
 178 (CH.sub.2).sub.3 O CH.sub.2
 ##STR139##
 179 (CH.sub.2).sub.3 CH.sub.2 (CH.sub.2).sub.2
 ##STR140##
 180 (CH.sub.2).sub.3 OCONH /
 ##STR141##
 181 (CH.sub.2).sub.3 OCONH CHC(CH.sub.3).sub.3 --CH.sub.2
 ##STR142##
 182 (CH.sub.2).sub.3 OCONH CH (C.sub.2
 H.sub.5).sub.2
 183 (CH.sub.2).sub.2 CH.dbd.CH (CH.sub.2).sub.2
 ##STR143##
 The different routes or method of synthesis of the compounds in Table I are
 detailed below.
 Methods of Synthesis of Compounds having a Structural Component
 ##STR144##
 Synthesis of 1-(triphenylmethyl)-4-(3-hydroxypropyl)-imidazole
 In a reaction flask equipped for hydrogenation, 10 g of urocanic acid (72.4
 mmol) are dissolved in 200 ml of water. 1 g of Pd/C (10%) are added and
 hydrogenation is performed at 50.degree. C. for 4 hours. The catalyst is
 filtered off and the water evaporated off, giving
 3-(4-imidazolyl)propionic acid which appears in the form of a white powder
 (8.8 g; 86%); m.p.: 209-211.degree. C. (3-Imidazol-4-yl)propionic acid (6
 g, 42 mmol) is dissolved in absolute ethanol (204 ml), and a catalytic
 amount of concentrated sulphuric acid (2 ml) is added. The resulting
 mixture is heated to reflux for 16 hours. The solvent is evaporated off,
 which gives an oily residue which is dissolved in 45 ml of water. The
 solution is neutralized with sodium hydrogencarbonate, and
 4-(3-carboethoxypropyl)-1H-imidazole is extracted with ethyl acetate; an
 oil (5.1 g; 72%) is obtained. The 4-(3-carboethoxypropyl)-1H-imidazole
 (5.4 g, 32 mmol) is dissolved in 4 ml of anhydrous dimethylformamide. 3.4
 g of triethylamine (33.6 mmol) and 9.3 g of triphenylmethyl chloride (33.6
 mmol) are added, and the mixture is stirred at room temperature under
 nitrogen for 4 hours. The mixture is poured onto crushed ice (60 g), which
 gives a white precipitate which is recrystallized from diethyl ether (9.2
 g; 70%), giving 1-(triphenylmethyl)-4-(3-carboethoxypropyl)-1H-imidazole;
 m.p.: 134.degree. C.
 The above ester (7.5 g; 18.3 mmol), dissolved in freshly distilled THF (75
 ml), is added dropwise to a solution of 0.8 g of lithium aluminium hydride
 (21 mmol) in freshly distilled THF (45 ml) in the cold and with stirring.
 Stirring is continued at room temperature for 12 hours, and the lithium
 aluminium hydride is then decomposed by adding saturated sodium sulphate
 solution dropwise. The resulting complex is filtered off, and the THF is
 dried over magnesium sulphate, giving an oil which is reduced in ethyl
 acetate to give 1-(triphenylmethyl)-4-(3-hydroxypropyl)-1H-imidazole in
 the form of a white powder (5.8 g; 87%); m.p.: 130.degree. C.
 ##STR145##
 Method A
 4-(3-(3-Trifluoromethylphenoxy)propyl)-1H-imidazole oxalate
 300 mg of 1-(triphenylmethyl)-4-(3-hydroxypropyl)-1H-imidazole (0.81 mmol)
 are dissolved in 8 ml of freshly distilled THF. 277 mg of
 triphenylphosphine (1.06 mmol) and 145 mg m-trifluoromethylphenol are
 added thereto, and the resulting mixture is cooled and stirred for 5
 minutes under nitrogen. Diethyl azodicarboxylate (184 mg; 1.06 mmol),
 dissolved in freshly distilled THF (4 ml), is added gradually to the
 reaction mixture and while stirring continuously at room temperature for
 12 hours. After removal of the solvent in vacuo, column chromatography
 (SiO.sub.2 ; first eluent: petroleum spirit; second eluent: petroleum
 spirit/diethyl ether (50:50)) performed on the crude reaction mixture
 gives a white powder which is reduced in petroleum ether to give an oil of
 1-(triphenylmethyl)-4-[3-(trifluoromethylphenoxy)-propyl]-1H-imidazole.
 The latter (210 mg; 0.41 mmol) is heated at 70.degree. C. for 3 hours in
 THF (5 ml) and 2N HCl (12 ml). The THF is removed under reduced pressure
 and Ph.sub.3 COH is extracted with diethyl ether. The aqueous phase is
 neutralized with potassium carbonate and the product is extracted into
 diethyl ether or chloroform. This solution is dried and evaporated, giving
 an oil which is dissolved in 2-propanol. Oxalic acid (1.5 equivalents) is
 added and the abovementioned product (on addition of diethyl ether) in the
 form of the oxalate, m.p.: 204-208.degree. C.
 The appropriate substituted phenols to be used in method A are obtained on
 the market, except for the following compounds which are synthesized (but
 which are known compounds):
 3-propanoylphenol (m.p.: 78-80.degree. C.) for Example 18 (lit. T.
 Geoffrey, P. Bruneau, G. C. Crawley, M. P. Edwards, S. J. Foster, J. M.
 Girodeau, J. F. Kingston and R. M. McMillan, J. Med. Chem. 1991, 34, 2176)
 3-(1-hydroxypropyl)phenol (m.p.: 106-108) for Example 19 (lit. Geoffrey et
 al., vide supra)
 3-propylphenol (b.p.: 125.degree. C. at 24 mm Hg) for Example 20 (lit. C.
 F. Carvalho and M. V. Sargent, J. Chem. Soc. Perk. Trans. 1. 1984,
 1621-1627)
 ##STR146##
 Method B
 4-[2-(3-Trifluoromethylphenyl)thioethyl]-1H-imidazole oxalate
 0.18 g (4.5 mmol) of sodium hydride (60% suspension in mineral oil) is
 added gradually to a cold solution of 3-trifluoromethylthiophenol (1.6;
 8.9 mmol) in dimethylformamide. The mixture is stirred under nitrogen at
 room temperature for 1 hour. 0.15 g of 4-(2-chloroethyl)-1H-imidazole
 (0.89 mmol) and 0.010 g of tetrabutylammonium iodide are added and the
 mixture is stirred at 80.degree. C. for 1 hour. The solvent is evaporated
 off and the oily residue is reduced with diethyl ether and then filtered.
 The product is then extracted from the filtrate with dilute HCl. The
 aqueous phase is washed again with diethyl ether and then alkalized with
 potassium carbonate, the product is extracted with chloroform to give an
 oil which is subjected to column chromatography (SiO.sub.2 ; first eluent:
 chloroform; second eluent: chloroform/methanol (97:3)), and the product is
 then converted to an oxalate salt; m.p.: 158-160.degree. C.
 ##STR147##
 Method C
 4-[4-(3-Ethanoylphenoxy)butyl]-1H-imidazole oxalate
 2.87 g of 3-ethanoylphenol (21 mmol) in anhydrous DMF (30 ml) is cooled to
 5.degree. C. (ice bath) under an argon atmosphere, and 0.37 g of sodium
 hydride (60% suspension in mineral oil; 9.25 mmol) are then added. The
 mixture is stirred at 5.degree. C. for 10 minutes and then at 20.degree.
 C. for 2 hours. 0.70 g of
 2-(t-butyldimethylsilyl)-5-(4-chlorobutyl)-1-(dimethylsulphamoyl)imidazole
 (1.85 mmol) (synthesized as described by R. C. Vollinga, W. M. P. B. Menge
 and H. Timmerman, Rec., Trav., Chem. Pays-Bas, 1993, 112, 123-125) and 45
 mg of tetrabutylammonium iodide are added and the mixture is heated at
 80.degree. C. under argon for 3 days, then cooled to 20.degree. C. and
 diluted with diethyl ether until the solution becomes cloudy. The
 resulting solid is filtered off and the filtrate evaporated to dryness in
 vacuo, giving a dark orange oil. The latter is subjected to column
 chromatography (SiO.sub.2 ; using an ethyl acetate/methanol mixture in the
 ratio 9:1) to give
 1-(N,N-dimethyl-sulphamoyl)-5-[4(3-ethanoylphenoxy)butyl]imidazole in the
 form of a yellow oil.
 This oil (0.408 g, 1.17 mmol) is heated. under reflux in 30 ml of 2M HCl
 for 12 hours, then cooled, washed with diethyl ether, alkalized with
 potassium carbonate and extracted (3.times.50 ml) with chloroform. The
 combined chloroform extracts are dried (MgSO.sub.4) and evaporated, giving
 the free base in the form of a yellow oil (0.28 g), which is converted to
 oxalate salt in ethanol (10 ml) using 1.5 molar equivalents of oxalic acid
 (in 10 ml ethanol). The resulting solid is collected, reduced with EtOH
 and recrystallized from EtOH, giving the desired product. M.p.:
 168-170.degree. C.
 ##STR148##
 Method D
 Preparation of 4-[3-(3-hydroxyphenoxy)propyl]-1H-imidazole oxalate
 A mixture of resorcinol monoacetate (0.41 g, 2.71 mmol),
 1-(triphenylaethyl-4-(3-hydroxypropyl)-1H-imidazole (1 g; 2.71 mmol) and
 triphenylphospine (1.06 g, 4.07 mmol, 1.5 equivalents) in anhydrous THF
 (30 ml) is cooled and stirred for 10 minutes under nitrogen.
 0.71 g of diethyl azodicarboxylate (4.07 mmol, 1.5 equiv.), dissolved in 10
 ml of freshly distilled THF, is added gradually to the reaction mixture,
 and continuous stirring is maintained for 16 hours at 20.degree. C. After
 removal of the solvent under reduced pressure, the resulting oil is
 subjected to column chromatography (SiO.sub.2 ; ethyl acetate/hexane,
 3:7), giving a yellow oil. This oil (0.5 g; 9.96 mmol) in ethanol (15 ml)
 and 5% potassium hydroxide (10 ml) are heated under reflux for 30 min. The
 mixture is acidified with 2N HCl (cooled on an ice bath) and extracted
 with chloroform: the organic extract is dried and the solvent removed
 under reduced pressure, leaving an oil. This oil is purified by column
 chromatography (SiO.sub.2 ; chloroform), then dissolved in 8 ml of THF and
 heated at 80.degree. C. for 5 hours in 2N HCl (12 ml). After cooling, the
 THF is removed under reduced pressure and Ph.sub.3 COH is extracted with
 diethyl ether. The aqueous phase is neutralized with potassium carbonate
 solution and the product is extracted with chloroform (3.times.100 ml).
 The combined chloroform extracts are dried (MgSO.sub.4) and evaporated
 under reduced pressure to give an oil, which is dissolved in 2-propanol (2
 ml) and converted to oxalate using 1.5 equivalents of oxalic acid and
 precipitating the product by adding diethyl ether; m.p.: 138-140.degree.
 C.
 ##STR149##
 Method E
 4-{3-[3-(2-Penten-3-yl)phenoxy]propyl}-1H-imidazole trifluoroacetate
 3-(3-Hydroxy-3-pentanyl)phenol, m.p. 78-80.degree. C., is synthesized as
 described by M. Satomura in Japanese Patent No. 04 82867 A2 (Chem. Abstr.,
 1992, 117, 130911).
 A mixture of this phenol (0.3 g, 1.66 mmol),
 1-(triphenylmethyl)-4-(3-hydroxypropyl)imidazole (0.61 g, 1.66 mmol) and
 triphenylphosphine (0.65 g; 2.5 mmol; 1.5 equiv.) in 30 ml of anhydrous
 THF is cooled and stirred for 10 minutes under nitrogen. 0.57 g of diethyl
 azodicarboxylate (2.5 mmol; 1.5 equiv.), dissolved in 10 ml of freshly
 distilled THF, is added slowly to the reaction mixture and stirred
 continuously at room temperature for 16 hours. After removal of the
 solvent under reduced pressure, the resulting oil is purified by column
 chromatography (SiO.sub.2 ; eluent: ethyl acetate/hexane 3:7).
 The purified oil is dissolved in THF (8 ml) and heated with 2N HCl at
 80.degree. C. for 5 hours.
 After cooling, the THF is removed under reduced pressure and Ph.sub.3 COH
 is extracted with diethyl ether. The aqueous phase is neutralized with
 potassium carbonate solution and the product is extracted into chloroform
 (3.times.100 ml). The combined chloroform extracts are dried and
 evaporated under reduced pressure to give an oil. This oil in 2 ml of
 2-propanol is converted to oxalate and precipitated with diethyl ether.
 The solid product is collected and purified by preparative HPLC to give
 the trifluoroacetate salt in the form of white crystals, m.p.:
 169-171.degree. C. from 2-propanol.
 .sup.1 H NMR and HPLC show that the compound contains 2 isomers (E/Z) in
 the ratio 4:1.
 ##STR150##
 Method F
 6 ml of 1.5M n-butyllithium in THF at -78.degree. C. are added slowly to 2
 g of a solution, cooled and stirred under nitrogen at -78.degree. C., of
 2-(tert-butyldimethylsilyl)-1-(dimethylsulphamoyl)imidazole (6.92 mmol) in
 20 ml of anhydrous THF. The mixture is then allowed to warm to 0.degree.
 C. A solution of ethylene oxide (3 g; 0.068 mol; 10 equiv.) in 10 ml of
 anhydrous THF is added slowly at 0.degree. C., and the mixture is stirred
 overnight at room temperature. The reaction mixture is poured into 50 ml
 of water and the THF is evacuated under reduced pressure. The product is
 extracted with CHCl.sub.3 (3.times.150 ml), dried (Na.sub.2 SO.sub.4) and
 concentrated in vacuo, leaving a brown oil. The latter is purified by
 means of a chromatography column (silica gel) using diethyl
 ether/40-60.degree. C. petroleum ether (1:1) as eluent, giving the doubly
 protected hydroxyethyl compound (1.2 g; 52% yield).
 A solution of
 2-(tert-butyldimethylsilyl)-1-(dimethylsulphamoyl)-5-(2-hydroxyethyl)imida
 zole (0.7 g, 2.10 mmol), triphenylphosphine (0.82 g, 3.15 mmol) and
 3-propanoylphenol (0.32 g, 2.10 mmol) in 20 ml of anhydrous THF is cooled
 and stirred under nitrogen at 0.degree. C. A solution of diethyl
 azodicarboxylate (DEAD) (0.55 g, 3.15 mmol) in 10 ml of anhydrous THF is
 then added dropwise at 0.degree. C., and the mixture is stirred at
 0.degree. C. for 10 minutes and then removed under reduced pressure and
 the resulting oil is purified on a chromatography column (silica gel)
 using an ethyl acetate/hexane (3:7) eluent to give
 2-(tert-butyldimethylsilyl)-1-(dimethyl-sulphamoyl)-5-[3-(3-propanoylpheno
 xyethyl]imidazole.
 The above compound (0.3 g; 6.72.times.10.sup.-4) is heated at 80.degree. C.
 with 2N HCl (12 ml) for 4 h. After cooling, the THF is removed under
 reduced pressure. The aqueous phase is washed with diethyl ether
 (3.times.100 ml), then alkalized with potassium carbonate and extracted
 (3.times.) with chloroform. The combined chloroform extracts are dried
 (MgSO.sub.4) and then evaporated, giving an oil, which is dissolved in
 2-propanol (2 ml) and treated with an excess of oxalic acid (1.5 equiv.)
 in 2-propanol (2 ml). The product is precipitated by adding diethyl ether,
 collected by filtration and washed with diethyl ether. Crystallization
 from ethanol gives pure 4-[2-(3-propanolphenoxy)ethyl]-1H-imidazole oxale.
 M.p.: 148-150.degree. C.
 ##STR151##
 TA=RT
 2N HCl [remove hyphen]
 Method of Synthesis of Compounds having a Structural Component
 ##STR152##
 with A=--(CH.sub.2).sub.3 -- and X=--NH--
 Method G
 4-[3-(3-Trifluoromethylphenylamino)propyl]-1H-imidazole oxalate
 A mixture of 1 g (2.72 mmol) of
 1-(triphenylmethyl)-4-[3-hydroxypropyl]imidazole, 0.55 g (4.07 mmol; 1.5
 equivalents) of morpholine oxide and 1.36 g of powdered 4 .ANG. molecular
 sieve in an anhydrous mixture of acetonitrile and dichloromethane (10:4)
 is stirred at room temperature under nitrogen. 0.047 g (0.135 mmol; 5 mol
 %) of tetrapropylammonium perruthenate (VII) is added in a single portion
 and the mixture is stirred at room temperature for 48 hours. The reaction
 mixture is filtered through silica gel (preloaded with ethyl acetate) and
 the filtrate is evaporated under reduced pressure. The oil obtained is
 purified by chromatography on a column of silica gel with diethyl ether as
 eluent to yield 3-(1-triphenylmethyl-4-imidazolyl)propionaldehyde.
 0.5 g (1.36 mmol) of the above aldehyde is heated with 0.22 g (1.36 mmol)
 of 3-trifluoromethylaniline in 50 ml of anhydrous toluene at 50.degree. C.
 for 30 minutes. The solvent is driven off under reduced pressure to leave
 0.6 g (86%) of an oil, which is dissolved in methanol, cooled to 0.degree.
 C. and then treated with 1.06 g (0.027 mol; 20 equivalents) of sodium
 borohydride added slowly at 0.degree. C. The mixture is stirred at room
 temperature overnight, the solvent is then driven off under reduced
 pressure, 20 ml of water are added and the mixture is extracted with
 chloroform. The chloroform extracts are dried (MgSO.sub.4) and the solvent
 is evaporated off under reduced pressure to leave an oil, which is
 purified by chromatography on a column of silica gel (eluent: diethyl
 ether) to yield 0.4 g of
 1-triphenylmethyl-4-[3-(3-trifluoromethylphenylamino)propyl]imidazole in
 the form of a colourless oil. The latter (0.35 g; 6.85 mmol) in 8 ml of
 tetrahydrofuran and 12 ml of 2M HCl is heated at 80.degree. C. for 5
 hours. The tetrahydrofuran is evaporated off under reduced pressure and
 Ph.sub.3 COH is extracted with diethyl ether. The aqueous layer is
 neutralized with potassium carbonate and the product is extracted into
 chloroform. The chloroform solution is dried and evaporated to yield a
 brown oil, which is purified by chromatography on a column of silica gel
 with an ethyl acetate/methanol (5:1) mixture as eluent. The oil obtained
 is dissolved in 4 ml of 2-propanol and treated with a solution of 1.5
 equivalents of oxalic acid in 3 ml of 2-propanol, and the mixture is
 cooled for 4 hours. The precipitate which is formed on addition of diethyl
 ether is collected and washed with ether to yield the desired oxalate in
 the form of a white solid, m.p. 150-151.degree. C.
 ##STR153##
 Method of Synthesis of Compounds having a Structural Component
 ##STR154##
 with A=--CH.sub.2 --CH(CH.sub.3)-- and X=--S--
 Method H
 4-[2-(3-Trifluoromethylphenylthio)propyl]-1H-imidazole oxalate
 5.426 g (18.7 mmol) of
 1-(N,N-dimethylsulphamoyl)-2-tert-butyldimothylsilylimidazole are
 dissolved in 100 ml of freshly distilled THF under nitrogen and cooled to
 -78.degree. C., and a solution of n-butyl-lithium in hexane (2.5M; 15 ml;
 37.5 mmol) is added dropwise over a period of 10 min. The mixture is
 stirred for 30 min at -78.degree. C. The solution is warmed to 0.degree.
 C. with rapid stirring, and a solution of 3.0 ml (2.49 g; 42.9 mmol) of
 propylene oxide in 20 ml of freshly distilled THF is added dropwise over a
 period of 15 min. The mixture is stirred for 18 hours with heating at
 20.degree. C., and the mixture is then hydrolysed by adding 100 ml of
 saturated NH.sub.4 Cl solution. The THF is removed under reduced pressure
 and the mixture obtained is extracted three times with 100 ml of
 dichloromethane. The organic layers are combined, dried (MgSO.sub.4) and
 evaporated under reduced pressure to yield an oil, which is subjected to
 column chromatography with diethyl ether as eluent to yield
 1-(N,N-dimethylsulphamoyl)-2-tert-butyldimethylsilyl-5-(2-hydroxypropyl)im
 idazole in the form of a viscous yellow oil.
 The above oil (11.28 g; 32.5 mmol) is dissolved in 50 ml of anhydrous
 carbon tetrachloride, and 9.18 g (35.0 mmol) of anhydrous
 triphenylphosphine in 50 ml of anhydrous carbon tetrachloride are added.
 The mixture is stirred under a nitrogen atmosphere at 50.degree. C. and
 then brought to reflux for 16 hours. The solvent is evaporated off in
 vacuo, and the solid obtained is subjected to column chromatography with
 dichloromethane on silica gel to yield
 1-(N,N-dimethylsulphamoyl)-2-tert-butyldimethylsilyl-5-(2-chloropropyl)imi
 dazole in the form of a pale yellow oil which solidifies, m.p.
 51-53.degree. C.
 3-Trifluoromethylthiophenol (0.298 g; 1.67 mmol) is dissolved in 20 ml of
 anhydrous DMF and cooled to 0.degree. C. under a nitrogen atmosphere, and
 NaH (60% dispersion in mineral oil; 0.0393 g; 1.638 mmol) is added in
 small portions. The reaction mixture is stirred at 0.degree. C. for 15 min
 and then at 20.degree. C. for a further 1.5 h, and 0.293 g (0.80 mmol) of
 1-(N,N-dimethylsulphamoyl)-2-tert-butyldimethylsilyl-5-(2-chloropropyl)
 imidazole dissolved in 5 ml of DMF and 10 mg of n-Bu.sub.4 NI are added
 and the mixture is heated at 80.degree. C. for 3 days. The solvent is
 driven off under reduced pressure to yield a brown oil, which is treated
 with 100 ml of water and extracted 3 times with 40 ml of dichloromethane.
 The extracts are dried (MgSO.sub.4) and concentrated, and the oil obtained
 is subjected to column chromatography using 2:1 and 1:1 petroleum
 spirit/ethyl acetate, then dissolved in 10 ml of 2M HCl and heated at
 100.degree. C. under reflux for 3 hours. The reaction mixture is then
 alkalized by adding 10% NaOH (pH approximately 11) and is extracted 3
 times with 40 ml of dichloromethane. The extracts are dried (MgSO.sub.4)
 and evaporated to form a clear oil, which is subjected to column
 chromatography with ethyl acetate as eluent and converted to the oxalate
 of the desired product in 2-propanol, m.p. 166-168.degree. C.
 ##STR155##
 Synthesis of the Compounds 1 to 7 and 28 to 183 and Summary for the
 Compounds 8 to 27

EXAMPLES OF COMPOUNDS ACCORDING TO THE PRESENT INVENTION
 The compounds 1 to 20, 110, 111 and 154 to 159 are agonists or partial
 agonists.
 The compounds 21-109, 112-153 and 160-182 are antagonists.
 EXAMPLE 1
 N-t-Butyl-3-(1H-imidazol-4-yl)propyl carbamate
 5 mmol of 3-(1H-imidazol-4-yl)propanol.HCl and of 5 mmol t-butyl isocyanate
 in 10 ml of anhydrous acetonitrile are refluxed for 1 to 3 h. The solvent
 is evaporated off and the residue then purified by rotatory chromatography
 (eluent: chloroform/methanol (99:1-90:10), ammoniacal atmosphere). After
 removal of the solvent under reduced pressure, the residue is crystallized
 as hydrogen maleate from diethyl ether and ethanol.

EF: C.sub.20 H.sub.21 N.sub.3 O.sub.2.C.sub.4 H.sub.4 O.sub.4 (451.5)
 CHN analysis Calculated C 63.9 H 5.58 N 9.31
 Found C 63.7 H 5.77 N 9.13
 Yield: 40% M.p.: 150-152.degree. C.
 EXAMPLE 5
 3-(1H-Imidazol-4-yl)propyl 3-methylbutyl ether
 5 mmol of sodium 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanolate, 5 mmol
 of 3-methylbutane bromide and 0.5 mmol of 15-crown-15 (1, 4, 7, 10,
 13-pentaoxacyclopentadecane) dissolved in 10 ml of anhydrous toluene are
 refluxed for 24 hours. The solvent is then evaporated off, and the residue
 dissolved in 10 ml THF and 30 ml 2N HCl and then heated at 70.degree. C.
 for 2 hours. The THF is evaporated off under reduced pressure and
 triphenylmethanol is extracted with diethyl ether. The aqueous phase is
 neutralized with potassium carbonate and the product is extracted with
 diethyl ether. The organic extract is dried and evaporated, giving rise to
 an oil, which is crystallized as hydrogen maleate from diethyl ether and
 ethanol.

EF: C.sub.13 H.sub.15 N.sub.3 OS .multidot. C.sub.4 H.sub.4 O.sub.4 (377.4)
 CHN analysis Calculated C 54.1 H 5.07 N 11.1
 Found C 53.7 H 5.12 N 11.1
 Yield: 55% M.p.: 129-131.degree. C.
 EXAMPLE 50
 3-(1H-Imidazol-4-yl)-1-(4-methylphenyl)propanone
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanoic acid methyl ester
 are dissolved at 0.degree. C. in 10 ml of thionyl chloride. After 1 hour
 of stirring at room temperature, the solvent is evacuated under reduced
 pressure. The residue is dissolved in toluene and added to a solution of
 15 mmol of AlCl.sub.3 in 20 ml of toluene. After 30 minutes at 0.degree.
 C., the reaction is refluxed for 5 hours. The toluene is evaporated off
 and the residue is hydrolysed with water. Extraction with diethyl ether
 followed by concentration gives an oil, which is heated in 30 ml 2N HCl
 and 10 ml of THF.
 The THF is evaporated off under reduced pressure and triphenylmethanol is
 extracted with diethyl ether. The aqueous phase is alkalized using
 ammonia, and the crude product is extracted with diethyl ether and
 purified by rotatory chromatography (eluent: chloroform/methanol
 (99:1-90:10), ammoniacal atmosphere). After evacuation of the solvent
 under reduced pressure, the product is recrystallized as hydrogen maleate
 from diethyl ether and ethanol.

EF: C.sub.13 H.sub.14 N.sub.2 .multidot. C.sub.4 H.sub.4 O.sub.4 (330.4)
 CHN analysis Calculated C 61.8 H 5.49 N 8.48
 Found C 61.8 H 5.52 N 8.50
 Yield: 35% M.p.: 121.degree. C.
 EXAMPLE 51
 3-(1H-Imidazol-4-yl)-4-phenyl-1-butene
 10 mmol of 3-phenylpropyltriphenylphosphonium bromide, 10 mmol of
 (1-triphenylmethyl-1H-imidazol-4-yl)methanal (J. L. Kelley, C. A. Miller,
 E. W. Mc Lean, J. Med. Chem. 1977, 20, 721) and 12 mmol of potassium of
 t-butanolate are stirred for 24 hours in 50 ml THF. The solvent is
 evaporated off under reduced pressure, hydrolysed with water and extracted
 using chloroform. The concentrated organic extract is heated from reflux
 in 30 ml 2N HCl and 30 ml of acetone for 1 hour. The solvent is evaporated
 off under reduced pressure and triphenylmethanol is extracted using
 diethyl ether. The aqueous phase is alkalized using ammonia and the crude
 product is extracted using diethyl ether. The aqueous phase is alkalized
 using diethyl ether and crystallized as hydrogen maleate from diethyl
 ether and ethanol.

EF: C.sub.13 H.sub.14 N.sub.2 .multidot. C.sub.4 H.sub.4 O.sub.4 (314.3)
 CHN analysis Calculated C 65.0 H 5.77 N 8.91
 Found C 65.0 H 5.74 N 8.81
 Yield: 40% M.p.: 114.degree. C.
 EXAMPLE 52
 3-(1H-Imidazol-4-yl)-4-pheylbutane
 3 mmol of (1H-imidazol-4-yl)-4-phenyl-1-butene (Example 51) are dissolved
 in 50 ml of methanol. 70 mg Pd/C (10%) are added, and reduction is carried
 out for 12 hours at a pressure of 10 bar under hydrogen.
 The solution is filtered and purified by rotatory chromatography. The
 product is crystallized as hydrogen maleate from diethyl ether and
 ethanol.

EF: C.sub.15 H.sub.17 N.sub.2 OF .multidot. C.sub.4 H.sub.4 O.sub.4 (376.4)
 CHN analysis Calculated C 60.6 H 5.62 N 7.44
 Found C 60.4 H 5.55 N 7.69
 Yield: 20% M.p.: 130-132.degree. C.
 EXAMPLE 71
 3-(1H-Imidazol-4-yl)propyl diphenylmethyl ether
 5 mmol of 3-(1H-imidazol-4-yl)propanol.HCl and 5 mmol of diphenylmethane
 chloride in 50 ml of acetonitrile are refluxed for 4-5 hours, the solvent
 is evaporated off and the residue purified by rotatory chromatography
 (eluent: chloroform/methanol (90-99:10-1), ammoniacal atmosphere). After
 evacuation of the solvent under reduced pressure the residue is
 crystallized as hydrogen maleate from diethyl ether and ethanol.

EF: C.sub.19 H.sub.18 N.sub.2 OF.sub.2 .multidot. C.sub.4 H.sub.4 O.sub.4
 (444.4)
 CHN analysis Calculated C 62.2 H 4.98 N 6.30
 Found C 61.9 H 4.98 N 6.29
 Yield: 40% M.p.: 107-109.degree. C.
 EXAMPLE 74
 2-(3-(1H-Imidazol-4-yl)propyloxy)-1-phenylethanone
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol and 5 mmol of
 2-bromo-1-phenylethanone are stirred for 72 hours in methylene chloride.
 The solvent is evaporated off under reduced pressure and the residue is
 refluxed for 1 hour in 30 ml of 2N HCl and 30 ml of acetone. The solvent
 is evaporated off under reduced pressure and triphenylmethanol is
 extracted using diethyl ether. The aqueous phase is alkalized with
 ammonia, and the crude product is extracted with diethyl ether, purified
 by rotatory chromatography and crystallized as hydrogen maleate from
 diethyl ether and ethanol.

EF: C.sub.14 H.sub.15 N.sub.3 O.sub.4 .multidot. C.sub.4 H.sub.4 O.sub.4
 .multidot. H.sub.2 O (423.4)
 CHN analysis Calculated C 51.1 H 5.00 N 9.92
 Found C 51.4 H 4.73 N 10.1
 Yield: 35% M.p.: 117-118.degree. C.
 EXAMPLE 76
 4-(4-(3-(1H-Imidazol-4-yl)propyloxy)phenyl)-2-butanone
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol, 6 mmol of
 triphenylphosphine and 5 mmol of 4-(4-hydroxyphenyl)-2-butanone are
 dissolved under nitrogen in the cold. 6 mmol of diethyl azodicarboxylate,
 dissolved in 4 ml of THF, are added and the reaction mixture is stirred at
 room temperature for 48 hours. After evacuation of the solvent under
 reduced pressure and column chromatography (eluent: ethyl acetate), the
 residue is dissolved in 10 ml THF and 30 ml of 2N HCl and heated to
 70.degree. C. for 2 hours. The solvent is evaporated off under reduced
 pressure and triphenylmethanol is extracted using diethyl ether. The
 aqueous phase is neutralized with potassium carbonate and the product
 extracted with diethyl ether. The ethereal solution is dried and
 evaporated to obtain an oil, which is crystallized as hydrogen maleate
 from diethyl ether and ethanol.

EF: C.sub.16 H.sub.20 N.sub.2 O.sub.2 .multidot. C.sub.4 H.sub.4 O.sub.4
 .multidot. 0 .multidot. 5H.sub.2 O (397.4)
 CHN analysis Calculated C 60.4 H 6.34 N 7.05
 Found C 60.5 H 6.03 N 7.03
 Yield: 85% M.p.: 95.degree. C.
 EXAMPLE 81
 Cyclopropyl 4-(3-(1H-imidazol-4-yl)propyloxy)phenyl ketone
 Method 1:
 5 mmol of sodium 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanolate, 10 mmol
 of 4-chloro-4'-fluorobutyrophenone and 30 mmol of NaH (60% suspension in
 mineral oil) are heated for 48 h in toluene under reflux. The reaction
 mixture is treated as described in Example 5. Yield: 40%.
 Method 2:
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol and 6 mmol of
 cyclopropyl 4-hydroxyphenyl ketone are treated as described in Example 76.
 Yield 80%.
 Method 3:
 5 mmol of sodium 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanolate, 10 mmol
 of cyclopropyl 4-fluorophenyl ketone and 10 mmol of NaH (60% suspension in
 mineral oil) are heated for 4 hours in toluene under reflux. The reaction
 mixture is then treated as described in Example 5. Yield 40%.

EF: C.sub.19 H.sub.17 N.sub.2 O.sub.2 F .multidot. C.sub.4 H.sub.4 O.sub.4
 (440.4)
 CHN analysis Calculated C 62.7 H 4.81 N 6.36
 Found C 62.6 H 4.83 N 6.43
 Yield: 80% M.p.: 125-127.degree. C.
 EXAMPLE 87
 (4-(3-(1H-imidazol-4-yl)propyloxy)phenyl)methanol
 2 mnol of (4-(3-(1H-imidazol-4-yl)propyloxy)phenyl)-carbaldehyde (Example
 77) are placed in a suspension of 0.5 mmol LiAlH.sub.4 in 10 ml anhydrous
 THF, and the reaction mixture is then refluxed for 1 hour. 5 ml of 2N NaOH
 are added, and the organic phase is separated, washed with water and dried
 with sodium carbonate.
 After removal of the solvent under reduced pressure, the residue is
 crystallized as hydrogen maleate from diethyl ether and ethanol.

EF: C.sub.16 H.sub.20 N.sub.2 O.sub.2 .multidot. C.sub.4 H.sub.4 O.sub.4
 .multidot. H.sub.2 O (406.4)
 CHN analysis Calculated C 59.1 H 6.45 N 6.89
 Found C 59.2 H 6.23 N 7.30
 Yield: 78% M.p.: 87.degree. C.
 EXAMPLE 92
 (4-(3-(1H-Imidazol-4-yl)propyloxy)phenyl)ethanone oxime
 1.2 mmol of (4-(3-(1H-imidazol-4-yl)propyloxy)phenyl)ethanone (Example 78),
 2.4 mmol of hydroxylamine hydrochloride and 4.8 mmol of NaOH are heated
 under reflux in 10 ml of water and 10 ml of ethanol for 7 hours. The
 mixture is concentrated under reduced pressure and alkalized with
 saturated K.sub.2 CO.sub.3 solution, and the crude product is filtered off
 and washed with water. The product is crystallized as hydrogen maleate
 from diethyl ether and ethanol.

EF: C.sub.12 H.sub.22 N.sub.2 .multidot. C.sub.2 H.sub.2 O.sub.4 .multidot.
 H.sub.2 O (284.4)
 CHN analysis Calculated C 59.1 H 8.51 N 9.85
 Found C 59.1 H 8.39 N 9.79
 Yield: 10% M.p.: 137-138.degree. C.
 EXAMPLE 104
 3-(4-(3-(1H-Imidazol-4-yl)propyloxy)phenyl)propenal
 5 mmol of
 (4-(3-(1-triphenylmethyl-1H-imidazol-4-yl)propyloxy)phenyl)carbaldehyde
 (intermediate of Example 77) and 5 mmol of ethinylmagnesium bromide are
 dissolved in 20 ml of THF and refluxed for 1 h. The solvent is evaporated
 off and the residue heated for 2 h in 50 ml of 2N HCl. The lipophilic
 by-products are extracted with diethyl ether. The aqueous phase is
 alkalized with ammonia, and the crude product is extracted with diethyl
 ether and purified by rotatory chromatography (eluent: chloroform/methanol
 (99:1-90:10), ammoniacal atmosphere). After removal of the solvent under
 reduced pressure, the product is recrystallized as hydrogen maleate from
 diethyl ether and ethanol.

EF: C.sub.13 H.sub.15 N.sub.3 O.sub.2 .multidot. C.sub.2 H.sub.2 O.sub.4
 CHN analysis Calculated C 53.7 H 5.50 N 12.5
 Found C 53.7 H 5.11 N 12.5
 M.p.: 120-122.degree. C.
 Preparation of 4-[3-(3-hydroxyiminamethylenephenoxy)propyl]-1H-imidazole
 oxalate
 A mixture of hydroxylamine hydrochloride (0.5:7.24 mmol) and sodium acetate
 (1 g; 0.012 mmol) in 10 ml of water is stirred for 10 min. A solution of
 4-[3-(3-formylphenoxy)propyl]-1H-imidazole (0.25 g; 1.08 mmol) in 3 ml of
 ethanol is then added slowly and the mixture is heated at 80.degree. C.
 for 2 hours. The solvent is removed under reduced pressure, leaving a
 white residue which is extracted with chloroform (3.times.100 ml). The
 combined chloroform extracts are dried (MgSO.sub.4) and evaporated under
 reduced pressure, leaving an oil (0.11 g). The latter is dissolved in
 2-propanol (3 ml) and treated with an excess of oxalic acid (1.5 equiv.)
 in 2 ml of 2-propanol. The product, which is precipitated by adding
 diethyl ether, is filtered off and washed with diethyl ether, and has a
 melting point of 120-122.degree. C.
 EXAMPLE 108
 4-[3-(3-Formylphenoxy)propyl]-1H-imidazole
 The procedure is as described in synthesis route A.
 Salt form: oxalate
 Crystallization solvent: EtOH

EF: C.sub.19 H.sub.20 N.sub.2 O.sub.2 .multidot. 0 .multidot. 85H.sub.2 O
 CHN analysis Calculated C 70.9 H 6.73 N 8.70
 Found C 70.9 H 6.44 N 8.55
 M.p.: 135-137.degree. C.
 EXAMPLE 110
 3-(1H-Imidazol-4-yl)propyl N-(2-methyl-2-butyl)carbamate
 5 mmol of 2,2-dimethylbutyric acid, 5 mmol of triethylamine and 5 mmol of
 diphenyl phosphorazidate in 30 ml of anhydrous acetonitrile are stirred at
 20.degree. C. for 45 minutes and are then brought to reflux for 30
 minutes. 6 mmol of 3-(1H-imidazol-4-yl)propanol.HCl are added and are
 brought to reflux for 40 hours. The mixture is evaporated and the residue
 dissolved in diethyl ether. The solution is washed successively with 30 ml
 of 5% aqueous citric acid, 30 ml of H.sub.2 O and 30 ml of saturated
 aqueous NaHCO.sub.3. The organic layer is evaporated and the residue is
 purified by rotatory chromatography (eluent: chloroform/methanol
 (99:1-90:10)). After removal of the solvent under reduced pressure, the
 residue is crystallized in the form of hydrogen oxalate in diethyl ether
 and ethanol.

C.sub.9 H.sub.16 N.sub.2 O .multidot. 0 .multidot. 8C.sub.2 H.sub.2 O.sub.4
 (240.3)
 CHN analysis Calculated C 53.0 H 7.38 N 11.7
 Found C 53.1 H 7.38 N 11.6
 Yield: 15% M.p.: 168.degree. C.
 EXAMPLE 117
 1,1-Dimethylethyl 3-(1H-imidazol-4-yl)propyl ether
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol and 10 mmol of
 tert-butyl trichloroacetimidate are treated as described in Example 116.
 The title compound is crystallized in the form of the hydrogen maleate in
 ethanol and diethyl ether.

C.sub.9 H.sub.14 N.sub.2 O .multidot. 0 .multidot. 8C.sub.2 H.sub.2 O.sub.4
 (238.3)
 CHN analysis Calculated C 53.4 H 6.60 N 11.8
 Found C 53.3 H 6.61 N 11.6
 Yield: 20% M.p.: 158-159.degree. C.
 EXAMPLE 119
 3-(1H-Iinidazol-4-yl)propyl 4-pentenyl ether
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol and 5 mmol of
 5-bromo-1-pentene are treated as described in Example 5. The title
 compound is crystallized in the form of the hydrogen oxalate from ethanol
 and diethyl ether.

C.sub.9 H.sub.12 N.sub.2 O .multidot. 0 .multidot. 75C.sub.2 H.sub.2
 O.sub.4 (231.7)
 CHN analysis Calculated C 54.4 H 5.87 N 12.1
 Found C 54.2 H 5.85 N 12.0
 Yield: 20% M.p.: 148.degree. C.
 EXAMPLE 121
 4-Butylphenyl 3-(1H-imidazol-4-yl)propyl ether
 0.8 mmol of cyclopropyl 4-(3-(1H-imidazol-4-yl)propyloxy)phenyl ketone
 (Example 61), 4 mmol of hydrazine hydrate and 3.2 mmol of KOH in 30 ml of
 triethylene glycol are brought to reflux for 2 hours. The solvent is
 evaporated off under reduced pressure, and the crude product is extracted
 with dichloromethane and purified by rotatory chromatography
 (eluent:dichloromethane/methanol (99:1)-(90:10), ammoniacal atmosphere).
 The product is crystallized in the form of hydrogen maleate from diethyl
 ether and ethanol.

C.sub.16 H.sub.22 N.sub.2 O .multidot. 0 .multidot. 75C.sub.2 H.sub.2
 O.sub.4 (325.9)
 CHN analysis Calculated C 64.5 H 7.27 N 8.60
 Found C 64.2 H 7.54 N 8.41
 Yield: 20% M.p.: 193.degree. C.
 EXAMPLE 122
 4-(1-Ethynyl)phenyl 3-(1H-imidazol-4-yl)propyl ether
 10 mmol of 3-(1H-imidazol-4-yl)propanol are reacted with 12 mmol of
 di-tert-butyl dicarbonate in 20 ml of acetonitrile, 5 ml of triethylamine
 and 5 ml of H.sub.2 O in the presence of 1 mmol of
 4-(N,N-dimethylamino)pyridine at room temperature for 2 hours. Evaporation
 of the solvent and final purification by column chromatography
 (eluent:dichloromethane/methanol, 90:10) yield
 4-(3-hydroxypropyl)-1H-imidazole-1-carboxylic acid tert-butyl ester in the
 form of an oil.
 4-(2-(Trimethylsilyl)-1-ethynyl)phenol is prepared from 4-iodoanisole
 according to Sonogashira K. et al., Tetrahedron Lett. 1975, 50, 4467 and
 Feutrill, G. I. et al., ibid, 1970, 16, 1327.
 5 mmol of the latter compound are reacted with 5 mmol of the former as
 described in Example 56.

C.sub.16 H.sub.20 N.sub.2 O.sub.3 .multidot. C.sub.4 H.sub.4 O.sub.4
 (404.4)
 CHN analysis Calculated C 59.4 H 5.98 N 6.93
 Found C 59.1 H 6.08 N 7.01
 Yield: 20% M.p.: 107.degree. C.
 EXAMPLE 131
 4-Hydroxy-(4-(3-(1H-imidazol-4-yl)propyloxy)phenyl)butanone ethylene acetal
 1.3 mmol of cyclopropyl 4-(3-(1H-imidazol-4-yl)propyloxy)phenyl ketone
 (Example 61) and a catalytic amount of 4-toluenesulphonic acid in 15 ml of
 ethylene glycol are brought to reflux for 5 hours. The solvent is
 evaporated off under reduced pressure, and the residue is dissolved in 10
 ml of H.sub.2 O and alkalized with ammonia. The crude product is extracted
 with dichloromethane and purified by rotatory chromatography (eluent:
 dichloromethane/methanol (99:1-90:10), ammoniacal atmosphere). The product
 is crystallized in the form of hydrogen maleate from diethyl ether and
 ethanol.

C.sub.17 H.sub.16 N.sub.2 O.sub.2 S .multidot. C.sub.2 H.sub.2 O.sub.4
 (402.4)
 CHN analysis Calculated C 56.7 H 4.51 N 6.96
 Found C 56.8 H 4.57 N 6.97
 Yield: 10% M.p.: 174.degree. C.
 EXAMPLE 138
 (4-(3-(1H-Imidazol-4-yl)propyloxy)phenyl)carbaldehyde oxime
 1.2 mmol of (4-(3-(1H-imidazol-4-yl)propyloxy)phenyl)carbaldehyde (Example
 57) and 2.4 mmol of hydroxylamine hydrochloride in 20 ml of anhydrous
 ethanol are heated to reflux for 3 hours. The mixture is concentrated
 under reduced pressure and alkalized with saturated K.sub.2 CO.sub.3
 solution and the crude product is isolated and washed with water. The
 product is crystallized in the form of the hydrogen maleate from diethyl
 ether and ethanol.

C.sub.18 H.sub.25 N.sub.3 O.sub.2 .multidot. 0 .multidot. 25H.sub.2 O
 (324.4)
 CHN analysis Calculated C 66.6 H 8.08 N 13.0
 Found C 66.4 H 7.81 N 12.8
 Yield: 80% M.p.: 138.degree. C.
 EXAMPLE 143
 Cyclopropyl 4-(3-(1H-imidazol-4-yl)propyloxy)phenyl ketone oxime
 1.2 mmol of cyclopropyl 4-(3-(1H-imidazol-4-yl)propyloxy)phenyl ketone
 (Example 61) and 2.4 mmol of hydroxylamine hydrochloride in 20 ml of
 anhydrous ethanol are heated at 60.degree. C. for 5 hours. The mixture is
 treated as described in Example 138, but isolated in the form of the free
 base.

C.sub.13 H.sub.14 F.sub.3 N.sub.3 .multidot. 1 .multidot. 5C.sub.2 H.sub.2
 O.sub.4
 CHN analysis Calculated C 47.18 H 3.76 N 9.96
 Found C 47.08 H 4.15 N 10.17
 EXAMPLE 155
 4-[3-(4-Ethanoylphenylamino)propyl]-1H-imidazole oxalate
 A mixture of 4 g (0.029 mol) of 3-aminoacetophenone and 2.47 ml (0.044 mol;
 1.5 equivalents) of ethylene glycol and a small amount of
 4-toluenesulphonic acid in 60 ml of anhydrous benzene are heated to reflux
 with azeotropic removal of water for 4 hours. The solution is left to
 cool, washed successively with 20% aqueous sodium carbonate and water and
 then dried (MgSO.sub.4). The solvent is evaporated off under reduced
 pressure to leave a yellow oil, which is purified by chromatography on a
 column of silica gel using a diethyl ether/petroleum ether (1:1) mixture
 as eluent, and then crystallized in hexane to yield
 3-(2-methyl-1,3-dioxolan-2-yl)aniline, m.p. 75-77.degree. C.
 The latter (0.096 g; 1.64 mmol) is heated with 0.6 g (1.64 mmol) of
 3-[1-(triphenylmethyl)-4-imidazolyl]-propionaldehyde in 50 ml of anhydrous
 toluene at 50.degree. C. for 30 minutes. The solvent is removed under
 reduced pressure to leave an oil, which is reduced with 0.064 g (0.016
 mol) of sodium borohydride in methanol as described for Example 154 to
 yield
 N-{3-[1-(triphenylmethyl)-4-imidazolyl]propyl}-3-(2-methyl-1,3-dioxolan-2-
 yl)aniline in the form of a colourless oil. The latter (0.5 g; 0.95 mmol)
 is heated with 12 ml of 2M HCl in 8 ml of tetrahydrofuran at 80.degree. C.
 for 5 hours. The tetrahydrofuran is evaporated off under reduced pressure
 and Ph.sub.3 COH is extracted into diethyl ether. The aqueous layer is
 neutralized with potassium carbonate and the product is extracted into
 chloroform. The chloroform solution is dried and evaporated to yield a
 brown oil, which is purified by chromatography on a column of silica gel
 (eluent: ethyl acetate/methanol, 5:1), and then treated with oxalic acid
 in 2-propanol as described for Example 154 to yield the desired oxalate,
 m.p. 152-154.degree. C., after recrystallization in ethanol.

C.sub.13 H.sub.14 N.sub.2 OS .multidot. 0 .multidot. 95C.sub.2 H.sub.2
 O.sub.4 .multidot. 0 .multidot. 1C.sub.3 H.sub.7 OH:
 CHN analysis Calculated C 54.03 H 4.98 N 8.29
 Found C 54.25 H 4.99 N 7.83
 EXAMPLE 158
 4-[3-(3-(1-Hydroxyiminoethyl)phenoxy)propyl]-1H-imidazole oxalate
 A solution of 0.125 g (1.81 mmol) of hydroxylamine hydrochloride and 0.5 g
 (0.006 mol) of sodium acetate in 10 ml of water is stirred for 10 minutes,
 and a solution of 0.125 g (0.512 mmol) of
 4-[3-(3-ethanoylphenoxy)propyl]-1H-imidazole in 3 ml of ethanol is then
 added slowly. The mixture is stirred at room temperature for 1 hour and
 then heated at 80.degree. C. for 2 hours. After cooling, the solvent is
 removed under reduced pressure and the white residue obtained is extracted
 with chloroform. The chloroform is dried (MgSO.sub.4) and then evaporated.
 The oil obtained is dissolved in 4 ml of 2-propanol and treated with 1.3
 equivalents of oxalic acid in 3 ml of 2-propanol. The addition of diethyl
 ether yields the product, which is separated by filtration, washed with
 ether and recrystallized in a 2-propanol/diethyl ether mixture, m.p.
 149-151.degree. C.

C.sub.14 H.sub.17 N.sub.3 O.sub.2 .multidot. C.sub.2 H.sub.2 O.sub.4 :
 CHN analysis Calculated C 55.01 H 5.45 N 12.03
 Found C 54.87 H 5.01 N 12.16
 EXAMPLE 159
 4-[2-(3-Trifluoromethylphenylthio)propyl]-1H-imidazole oxalate
 5.426 g (18.7 mmol) of
 1-(N,N-dimethylsulphamoyl)-2-tert-butyldimethylsilylimidazole are
 dissolved in 100 ml of freshly distilled THF under nitrogen and cooled to
 -78.degree. C., and a solution of n-butyl-lithium in hexane (2.5M; 15 ml;
 37.5 mmol) is added dropwise over a period of 10 min. The mixture is
 stirred for 30 min at -78.degree. C. The solution is warmed to 0.degree.
 C. with rapid stirring, and a solution of 3.0 ml (2.49 g; 42.9 mmol) of
 propylene oxide in 20 ml of freshly distilled THF is added dropwise over a
 period of 15 min. The mixture is stirred for 18 hours with heating at
 20.degree. C., and the mixture is then hydrolysed by adding 100 ml of
 saturated NH.sub.4 Cl solution. The THF is removed under reduced pressure
 and the mixture obtained is extracted three times with 100 ml of
 dichloromethane. The organic layers are combined, dried (MgSO.sub.4) and
 evaporated under reduced pressure to yield an oil, which is subjected to
 column chromatography with diethyl ether as eluent to yield
 1-(N,N-dimethylsulphamoyl)-2-tert-butyldimethylsilyl-5-(2-hydroxypropyl)im
 idazole in the form of a viscous yellow oil.
 The above oil (11.28 g; 32.5 mmol) is dissolved in 50 ml of anhydrous
 carbon tetrachloride, and 9.18 g (35.0 mmol) of anhydrous
 triphenylphosphine in 50 ml of anhydrous carbon tetrachloride are added.
 The mixture is stirred under a nitrogen atmosphere at 50.degree. C. and
 then brought to reflux for 16 hours. The solvent is evaporated off in
 vacuo, and the solid obtained is subjected to column chromatography with
 dichloromethane on silica gel to yield
 1-(N,N-dimethylsulphamoyl)-2-tert-butyldimethylsilyl-5-(2-chloropropyl)imi
 dazole in the form of a pale yellow oil which solidifies, m.p.
 51-53.degree. C.
 3-Trifluoromethylthiophenol (0.298 g; 1.67 mmol) is dissolved in 20 ml of
 anhydrous DMF and cooled to 0.degree. C. under a nitrogen atmosphere, and
 NaH (60% dispersion in mineral oil; 0.0393 g; 1.638 mmol) is added in
 small portions. The reaction mixture is stirred at 0.degree. C. for 15 min
 and then at 20.degree. C. for a further 1.5 h, and 0.293 g (0.80 mmol) of
 1-(N,N-dimethylsulphamoyl)-2-tert-butyldimethylsilyl-5-(2-chloropropyl)
 imidazole dissolved in 5 ml of DMF and 10 mg of n-Bu.sub.4 NI are added
 and the mixture is heated at 80.degree. C. for 3 days. The solvent is
 driven off under reduced pressure to yield a brown oil, which is treated
 with 100 ml of water and extracted 3 times with 40 ml of dichloromethane.
 The extracts are dried (MgSO.sub.4) and concentrated, and the oil obtained
 is subjected to column chromatography using 2:1 and 1:1 petroleum
 spirit/ethyl acetate, then dissolved in 10 ml of 2M HCl and heated at
 100.degree. C. under reflux for 3 hours. The reaction mixture is then
 alkalized by adding 10% NaOH (pH approximately 11) and is extracted 3
 times with 40 ml of dichloromethane. The extracts are dried (MgSO.sub.4)
 and evaporated to form a clear oil, which is subjected to column
 chromatography with ethyl acetate as eluent and converted to the oxalate
 of the desired product in 2-propanol, m.p. 166-168.degree. C.

C.sub.13 H.sub.13 F.sub.3 N.sub.2 S .multidot. C.sub.2 H.sub.2 O.sub.4 :
 CHN analysis Calculated C 47.87 H 4.02 N 7.44
 Found C 47.43 H 4.04 N 7.22
 EXAMPLE 160
 4-[2-(4-Methylphenoxy)ethyl]-1H-imidazole oxalate
 (Similar to method A)
 A mixture of 0.18 g (1.68 mmol) of p-cresol, 0.60 g (1.69 mmol) of
 1-(triphenylmethyl)-4-(2-hydroxyethyl)imidazole and 0.44 g (1.69 mmol) of
 triphenylphosphine in 20 ml of anhydrous tetrahydrofuran is cooled and
 stirred for 10 minutes under nitrogen. 0.66 g (3.44 mmol) of diethyl
 azodicarboxylate, dissolved in 10 ml of freshly distilled THF, is added
 slowly to the reaction mixture, and stirring is continued at room
 temperature for 16 hours. After removal of the solvent in vacuo, column
 chromatography of the crude reaction mixture on silica gel (eluent:
 hexane/ethyl acetate, 2:1) yields 0.45 g (60%) of product in the form of a
 colourless oil. The latter is heated at 80.degree. C. for 5 hours in 8 ml
 of THF and 1.3 equivalents of 2M hydrochloric acid. After cooling, the THF
 is driven off under reduced pressure and Ph.sub.3 COH is extracted with 3
 30-ml portions of diethyl ether. The aqueous layer is neutralized with
 potassium carbonate and the product is extracted into 3 30-ml portions of
 chloroform. The combined chloroform layers are dried (MgSO.sub.4) and
 evaporated under reduced pressure to yield an oil, which is treated with a
 propanolic solution of oxalic acid to yield the product, m.p.
 188-189.degree. C., which is dried in vacuo.

C.sub.14 H.sub.18 N.sub.2 O .multidot. 0 .multidot. 8C.sub.2 H.sub.2
 O.sub.4 :
 CHN analysis Calculated C 61.97 H 6.53 N 9.27
 Found C 62.16 H 6.39 N 9.38
 EXAMPLE 164
 4-[3-(4-Imidazol-1-ylphenoxy)propyl]-1H-imidazole trifluoroacetate
 In a manner similar to Example 160, 0.5 g (1.36 mmol) of
 1-(triphenylmethyl)-4-(3-hydroxypropyl)imidazole is treated with 0.27 g
 (1.70 mmol) of 4-(1-imidazolyl)phenol to yield the abovementioned compound
 in the form of the oxalate salt. The latter is impure, and it is hence
 subjected to preparative high pressure liquid chromatography on Kromasil
 C.sub.18 using 0.1% trifluoacetic acid and 0.1% trifluoroacetic acid in
 methanol in a 4:1 ratio. The product obtained is the hydrated
 trifluoroacetate, m.p. 259.degree. C. (decomposition).

C.sub.14 H.sub.19 N.sub.3 O.sub.3 S .multidot. 0 .multidot. 85C.sub.2
 H.sub.2 O.sub.4 :
 CHN analysis Calculated C 48.86 H 5.41 N 10.89
 Found C 48.81 H 5.67 N 10.81
 EXAMPLE 166
 4-[3-(4-Thiomethylphenoxy)propyl]-1H-imidazole oxalate
 In a manner similar to Example 160, 0.50 g (1.35 mmol) of
 1-(triphenylmethyl)-4-(3-hydroxypropyl)imidazole is treated with 0.19 g
 (1.35 mmol) of 4-thiomethylphenol to yield the abovementioned oxalate,
 which has an m.p. of 202-204.degree. C. after recrystallization in
 ethanol.

C.sub.19 H.sub.20 N.sub.2 OS .multidot. HCl:
 CHN analysis Calculated C 63.32 H 5.87 N 7.77
 Found C 63.73 H 5.77 N 8.13
 EXAMPLE 168
 4-[3-(3-Acetylphenylthio)propyl]-1H-imidazole oxalate
 (Similar to method C)
 3-Acetylthiophenol (0.256 g; 1.68 mmol) is dissolved in 20 ml of anhydrous
 dimethylformamide and cooled to below 4.degree. C. under a nitrogen
 atmosphere, and 0.067 g (1.68 mmol) of sodium hydride is added in small
 portions at below 4.degree. C. The mixture is stirred at 4.degree. C. for
 15 min and then at 20.degree. C. for 1.5 h.
 2-tert-Butyldimethylsilyl-5-(3-chloropropyl)-1-(N,N-dimethylsulphamoyl)imi
 dazole (Vollinga, R. C., Menge, W. M. P. B. and Timmerman, H. Rec. trav.
 chim. Pays-Bas. 1993, 112, 123-125) (0.283 g; 0.84 mmol) in 10 ml of
 dimethylformamide and 10 mg of tetra-n-butylammonium iodide as catalyst
 are added, and the mixture is heated at 80.degree. C. for 3 days. The
 solvent is removed under reduced pressure, and the reaction mixture is
 halted with 100 ml of water and extracted 3 times with 40 ml of
 dichloromethane; the extracts are dried (MgSO.sub.4) and concentrated to
 an oil, which is purified by column chromatography by using a petroleum
 spirit/ethyl acetate (60:40) mixture to yield
 1-(N,N-dimethylsulphamoyl)-4-[3-(3-acetylphenylthio)propyl]imidazole. The
 latter is heated in 15 ml of 2M HCl under reflux for 5 h. The reaction is
 left to cool, then alkalized with 10% aqueous sodium hydroxide to pH 10
 and extracted 3 times with 50 ml of dichloromethane. The extracts are
 dried (MgSO.sub.4) and concentrated to an oil, which is purified by column
 chromatography with a 95:5 ethyl acetate/methanol mixture. The oily
 product is converted to the oxalate in ethanol to yield a white
 crystalline solid, m.p. 122-124.degree. C.

C.sub.14 H.sub.16 N.sub.2 OS .multidot. 1 .multidot. 2C.sub.2 H.sub.2
 O.sub.4 :
 CHN analysis Calculated C 54.14 H 5.10 N 7.79
 Found C 54.57 H 5.21 N 7.41
 EXAMPLE 169
 4-[3-(4-Ethylphenylamino)propyl]-1H-imidazole oxalate
 In a manner similar to Example 154, 4-ethyl-aniline is converted to the
 abovementioned compound, which has an m.p. of 154-156.degree. C. after
 crystallization in ethanol.

C.sub.14 H.sub.19 N.sub.3 .multidot. 1 .multidot. 85C.sub.2 H.sub.2 O.sub.4
 :
 CHN analysis Calculated C 53.70 H 5.74 N 10.61
 Found C 53.74 H 5.98 N 10.56
 EXAMPLE 170
 4-[3-(4-Chlorophenylamino)propyl]-1H-imidazole oxalate
 In a manner similar to Example 154, 4-chloroaniline is converted to the
 abovementioned compound, which has an m.p. of 130-134.degree. C. after
 crystallization in ethanol.

C.sub.12 H.sub.14 ClN.sub.3 .multidot. 2 .multidot. 2C.sub.2 H.sub.2
 O.sub.4 :
 CHN analysis Calculated C 45.41 H 4.28 N 9.69
 Found C 45.48 H 4.40 N 9.80
 EXAMPLE 171
 3-(1H-Imidazol-4-yl)propyl 4-(2-(trimethylsilyl)-1-ethynyl)phenyl ether
 5 mmol of 4-(3-hydroxypropyl)-1H-imidazole-1-carboxylic acid tert-butyl
 ester and 5 mmol of 4-(2-(trimethylsilyl)-1-ethynyl)phenol (for the
 preparation see the literature mentioned in Example 122) are treated as
 described in Example 122.

C.sub.7 H.sub.12 N.sub.2 O .multidot. C.sub.2 H.sub.2 O.sub.4 (230.7)
 CHN analysis Calculated C 47.0 H 6.13 N 12.2
 Found C 47.1 H 6.01 N 12.1
 Yield: 40% M.p.: 139.degree. C.
 EXAMPLE 175
 Ethyl 3-(1H-imidazol-4-yl)propyl ether
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol and 5 mmol of
 bromoethane are treated as described in Example 5. The title compound is
 crystallized in the form of hydrogen oxalate from ethanol and diethyl
 ether.

C.sub.8 H.sub.14 N.sub.2 O .multidot. 0 .multidot. 75C.sub.2 H.sub.2
 O.sub.4 (221.7)
 CHN analysis Calculated C 51.5 H 7.05 N 12.6
 Found C 51.4 H 6.85 N 12.7
 Yield: 20% M.p.: 167.degree. C.
 EXAMPLE 176
 3-(1H-Imidazol-4-yl)propyl propyl ether
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol and 5 mmol of
 bromopropane are treated as described in Example 5. The title compound is
 crystallized in the form of hydrogen oxalate from ethanol and diethyl
 ether.

C.sub.9 H.sub.16 N.sub.2 O .multidot. 0 .multidot. 75C.sub.2 H.sub.2
 O.sub.4 (235.8)
 CHN analysis Calculated C 53.5 H 7.48 N 11.9
 Found C 53.1 H 7.26 N 11.8
 Yield: 20% M.p.: 169.degree. C.
 EXAMPLE 177
 Cyclopropyl 3-(1H-imidazol-4-yl)propyl ether
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propyl.HCl chloride (see
 Example 174) and 30 mmol of sodium cyclopropanolate (prepared with sodium
 in cyclopropanol) in 20 ml of cyclopropanol are treated as described in
 Example 174. The title compound is crystallized in the form of hydrogen
 oxalate from ethanol and diethyl ether.

C.sub.9 H.sub.14 N.sub.2 O .multidot. C.sub.2 H.sub.2 O.sub.4 (256.3)
 CHN analysis Calculated C 51.6 H 6.29 N 10.9
 Found C 51.3 H 5.98 N 10.7
 Yield: 10% M.p.: 158.degree. C.
 EXAMPLE 178
 Cyclopropylmethyl 3-(1H-imidazol-4-yl)propyl ether
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol and 10 mmol of
 cyclopropylmethylsodium chloride are treated as described in Example 5.
 The title compound is crystallized in the form of hydrogen maleate from
 ethanol and diethyl ether.

C.sub.10 H.sub.16 N.sub.2 O .multidot. C.sub.4 H.sub.4 O.sub.4 (296.3)
 CHN analysis Calculated C 56.7 H 6.80 N 9.45
 Found C 56.7 H 6.70 N 9.38
 Yield: 10% M.p.: 85.degree. C.
 EXAMPLE 179
 1-(1H-Imidazol-4-yl)-6-phenyl hexane
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanal (prepared
 according to standard methods (Swern oxidation) with
 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol and oxalyl chloride in DMSO
 at -45.degree. C.) and 5 mmol of 3-phenylpropyltriphenylphosphonium
 bromide (prepared from triphenylphosphine and 3-phenylpropyl bromide in
 toluene under reflux for 12 h) are treated as described in Example 51. The
 1-(1H-imidazol-4-yl)-6-phenyl-3-hexene is hydrogenated as described in
 Example 52. The title compound is crystallized in the form of hydrogen
 oxalate in ethanol and diethyl ether.

C.sub.12 H.sub.21 N.sub.3 O.sub.2 .multidot. C.sub.4 H.sub.4 O.sub.4
 (355.4)
 CHN analysis Calculated C 54.1 H 7.09 N 11.8
 Found C 53.7 H 6.92 N 11.6
 Yield: 22% M.p.: 108.degree. C.
 EXAMPLE 183
 1-(1H-Inidazol-4-yl)-6-phenyl-3-hexene
 5 mmol of 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanal (prepared
 according to standard methods (Swern oxidation) with
 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanol and oxalyl chloride in DMSO
 at -45.degree. C.; see Examples 179 and 154) and 5 mmol of
 3-phenylpropyltriphenylphosphonium bromide (see Example 179) are treated
 as described in Example 51. The title compound is crystallized in the form
 of hydrogen oxalate in ethanol and diethyl ether.

C.sub.15 H.sub.18 N.sub.2 .multidot. 0 .multidot. 75C.sub.2 H.sub.2 O.sub.4
 (293.9)
 CHN analysis Calculated C 67.4 H 6.69 N 9.53
 Found C 67.3 H 6.92 N 9.69
 Yield: 30% M.p.: 140.degree. C.
 PHARMACOLOGICAL STUDY
 Antagonist Compounds
 The interaction of the compounds with the H.sub.3 receptor is demonstrated
 in vitro by measuring the release of [.sup.3 H]histamine synthesized from
 [.sup.3 H]histidine by synaptosomes of rat cerebral cortex (Garbarg et
 al., J. Pharmacol. Exp. Ther. 1992, 263: 304).
 The H.sub.3 antagonist power of the compounds is evaluated by the
 progressive reversal of the inhibition of the release of [.sup.3
 H]histamine by (R)- -methylhistamine, a selective H.sub.3 agonist (Arrang
 et al., Nature, 1987, 327: 117-123).
 The antagonist effects of the compounds in vivo are evaluated by measuring
 the changes in the levels of cerebral tele-methylhistamine in mice
 (Garbarg et al., J. Neurochem. 1989, 53: 1724). After a variable lapse of
 time following administration of the compound, the effect of an H.sub.3
 antagonist is demonstrated by the rise in the level of cerebral
 tele-methylhistamine which it induces. Results are collated in Tables II
 and III below:
 TABLE II
 APENT DISSOCIATION CONSTANTS (Ki) OF
 VARIOUS DERIVATIVES OF THE INVENTION AS HISTAMINE
 ANTAGONISTS AT THE H.sub.3 RECEPTORS.
 Example No. Ki (nM)
 21 45
 64 16
 56 22
 30 8
 61 0.5
 93 25
 115 44
 149 44
 166 3
 TABLE III
 EFFECTS OF ANTAGONIST COMPOUNDS ON THE
 LEVEL OF CEREBRAL TELE-METHYLHISTAMINE.
 Change in the level of cerebral
 tele-methylhistamine
 H.sub.3 antagonists (relative to controls)
 81 +72%
 21 +79%
 67 +73%
 78 +68%
 30 +67%
 39 +84%
 112 +98%
 140 +84%
 160 +95%
 These various compounds were administered at a dose of 10 mg/kg p.o., and
 the mice sacrificed 90 min later. The reference compound was thioperamide
 which, under the same conditions, induces changes of +75% to +100% on
 average.
 This property of H.sub.3 antagonists which are active systemically makes
 the compounds of the invention useful derivatives in human and veterinary
 medicine. Their therapeutic applications relate, in particular, to the
 central nervous system (including as psychostimulants). The compounds
 which are histamine H.sub.3 receptor antagonists of formula Ia or Ib are
 advantageously used as active principle of medicinal products having
 psychotropic and wakefulness-, attention-, memory- and mood-activating
 actions, in the treatment of conditions such as Alzheimer's disease and
 other cognitive disorders of the elderly, and depressive or even simply
 asthenic states. Their nootropic effects may be turned to good account in
 order to stimulate alertness or the learning capacity of healthy subjects.
 Their positive effects on the regulation of the activity of the balance
 centres will be turned to good account in the treatment of vertigo. They
 may also be used as active principle of medicinal products intended for
 the treatment of balancing disorders and vertigo, in particular Meniere's
 disease, especially in the elderly. They may be usefully combined with
 treatments with other psychiatric agents such as neuroleptics in order to
 increase their activity and decrease their side-effects. The therapeutic
 applications also relate to the peripheral organs, in particular as
 stimulants of secretion and of gastrointestinal motor function.
 Hence the present invention also relates to pharmaceutical compositions
 which contain as active principle a therapeutically effective amount of
 one of the antagonist compounds of formula Ia or Ib.
 The pharmaceutical composition according to the invention is administrable
 to man via the oral, perlingual, nasal, dermal, transdermal, ophthalmic,
 vaginal, percutaneous, topical, rectal and parenteral routes, the active
 principle being combined with a therapeutically appropriate excipient or
 vehicle.
 Each single dose advantageously contains 0.03 to 3 mg/kg.
 The subject of the invention is also the use of the derivatives according
 to the invention for the preparation of H.sub.3 antagonist medicinal
 products according to the abovementioned procedures.
 Agonist or Partial Agonist Compounds
 The interaction of the compounds with the H.sub.3 receptor is demonstrated
 in vitro by measuring the release of [.sup.3 H]histamine synthesized from
 [.sup.3 H]histidine by the synaptosomes of rat cerebral cortex.
 The H.sub.3 agonist effect of the compounds is demonstrated by the
 inhibition of release of [.sup.3 H]histamine which they induce reversibly
 in the presence of a H.sub.3 antagonist such as thioperamide. The partial
 agonist effect of the compounds is evaluated by comparison of the maximum
 inhibition which they induce relative to the maximum inhibition induced by
 exogenous histamine or [R]-.alpha.-methylhistamine; the ratio of these two
 values giving the intrinsic activity of the compound with respect to the
 system.
 The effect of a partial agonist in vivo is characterized by the fact that
 the maximum reduction in the level of tele-methylhistamine which it
 induces at high dose is smaller than the reduction induced by a reference
 H.sub.3 agonist.
 However, for some partial agonist compounds displaying a low or even
 moderate intrinsic activity (.ltoreq.10% of that of histamine), the in
 vitro test does not enable the agonist effect to be demonstrated readily.
 In contrast, we have discovered that measurement of the activity of the
 cerebral histaminic neurons in vivo, reflected by the level of
 tele-methylhistamine, a characteristic metabolite of released histamine,
 constitutes a more sensitive test of agonist activity. In effect,
 compounds displaying an intrinsic activity .ltoreq.25% in vitro cause, in
 vivo, a maximum or virtually maximum fall in the level of the
 tele-methylhistamine. Another sensitive test of H.sub.3 agonist activity,
 in this instance in relation to peripheral organs, consists in measuring
 the plasma extravasation induced in rats under the influence of capsaicin
 (90 .mu.g/kg i.v.) and determined by measuring the tissue level of Evans
 blue, a dye administered at the same time as capsaicin, namely 5 min
 before infusion and sacrifice (Saria et al., Naunyn-Schmiedeberg's Arch.
 Pharmacol. 1983, 324: 212). Thus, in these two tests, the compound of
 Example 2 induces a response akin to that of (R)-.alpha.-methylhistamine,
 while, in vitro, its intrinsic agonist activity is in the region of 20%
 and it hence behaves essentially as an antagonist.
 The results are collated in Tables IV and V below:
 TABLE IV
 50% EFFECTIVE CONCENTRATIONS (EC.sub.50)
 OF TIAL AGONISTS
 Example No. EC.sub.50 (nM) Intrinsic activity
 8 100 40%
 5 130 20%
 2 100 20%
 TABLE V
 EFFECTS OF TIAL AGONIST COMPOUNDS ON THE LEVEL OF
 CEREBRAL TELE-METHYLHISTAMINE
 Change in the level of cerebral tele-
 H.sub.3 agonists methylhistamine (relative to controls)
 8 -41%
 5 -52%
 2 -30%
 111 -34%
 157 -38%
 These various compounds were administered at a dose of 10 mg/kg p.o. and
 the mice sacrificed 90 min later. The reference compound was Imetit which,
 under the same conditions, induces changes of -45% to -60% on average.
 This property of H.sub.3 agonists which are active systemically makes the
 compounds of the invention useful derivatives in human and veterinary
 medicine.
 H.sub.3 receptor agonists and partial agonists, through their cerebral
 effects, mainly exert sedative, tranquillizing, antistress and analgesic
 activity, indicating their use as mild sedative psychotropics, in
 particular in various psychosomatic disorders.
 H.sub.3 agonists and partial agonists are also indicated in the treatment
 of migraine states and other headaches.
 Through their peripheral effects, H.sub.3 receptor agonists and partial
 agonists will be mainly indicated in the treatment of respiratory,
 allergic or inflammatory conditions (asthma, bronchitis, rhinitis,
 tracheitis, and the like), cardiac conditions (myocardial dysfunction and
 infarction), gastrointestinal conditions as a result of their
 antisecretory and anti-inflammatory actions (gastric and duodenal ulcers,
 ulcerative colitis, Crohn's disease, irritable bowel, faecal incontinence,
 and the like), conditions of the urogenital system (cystitis, metritis,
 premenstrual syndrome, prostatic inflammations, urinary incontinence,
 genital disorders) and conditions of the cutaneous system (urticaria,
 itching). The anti-inflammatory and analgesic effect may usefully be
 turned to good account in the treatment of arthritis and other rheumatic
 conditions, conjunctivitis and other ocular inflammations, and
 sialorrhoea.
 Compounds which are histamine H.sub.3 receptor agonists or partial agonists
 are advantageously used as active principle of medicinal products, in
 particular having mild sedative, antisecretory, anti-inflammatory,
 sleep-regulating and anticonvulsant effects, regulatory effects on
 hypothalamohypophyseal secretion, anti-depressant effects, modulatory
 effects on cerebral circulation, modulatory effects on the immune system,
 and anti-allergic and antimigraine effects.
 Hence the present invention also relates to pharmaceutical compositions
 which contain as active principle a therapeutically effective amount of
 one of the agonist or partial agonist compounds of formula (Ib).
 The pharmaceutical composition according to the invention is administrable
 to man via the oral, perlingual, dermal, transdermal, ophthalmic, vaginal,
 percutaneous, topical, nasal, rectal and parenteral routes, the active
 principle being combined with a therapeutically appropriate excipient or
 vehicle.
 The agonist or partial agonist compounds of the present invention are
 active at single doses of between 0.1 and 10 mg/kg via the oral route in
 rodents, corresponding to doses of between 0.03 and 3 mg/kg in man. For
 local applications, for example in the form of ointments or eyewashes, the
 active concentrations will be between 10.sup.-8 M and 10.sup.-5 M.
 The subject of the invention is also the use of the derivatives according
 to the invention for the preparation of H.sup.3 agonist medicinal products
 according to the abovementioned procedures.