# Patent

## Title
Pyrazolopyrimidines

## Abstract

The invention relates to prazolopyrimidines of the formula




    
    
        in which R1, R2, R3, R4, R5, and X are as defined in the disclosure,

to a process for preparing these compounds, and to their use for controlling unwanted microorganisms.

## Background
RELATED APPLICATIONS
The present patent application claims the right of priority under 35 U.S.C. 119 of German Patent Application 102004008807.1, filed Feb. 20, 2004.
BACKGROUND OF THE INVENTION
The invention relates to pyrazolopyrimidines, to a process for their preparation and to their use for controlling unwanted microorganisms.
It is already known that certain pyrazolopyrimidines have fungicidal properties (see, for example WO-A 02/048 151, WO-A 04/000 844 or FR-A 2 794 745).
However, since the ecological and economical demands made on modern fungicides are increasing constantly, for example with respect to activity spectrum, toxicity, selectivity, application rate, formation of residues and favourable manufacture, and there can furthermore be problems, for example, with resistance, there is a constant need to develop novel fungicides which, at least in some areas, have advantages over those of the prior art.
SUMMARY OF THE INVENTION
This invention now provides novel pyrazolopyrimidines of the formula (I),




and agrochemically active salts thereof,

in which

    R1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl or optionally substituted heterocyclyl, hydroxyl, optionally substituted alkoxy, amine, optionally substituted alkylamine or optionally substituted dialkylamine;
    R2 is hydrogen or alkyl;
    or
    R1 and R2 together with the nitrogen atom to which they are attached are an optionally substituted heterocyclic ring;
    R3 is optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aralkyl, halogen, an optionally substituted amino group, optionally substituted (C1-C8)-alkoxy, optionally substituted (C1-C8)-alkylthio, optionally substituted (C6-C10)-aryloxy, optionally substituted (C6-C10)-arylthio, optionally substituted heterocyclyloxy, optionally substituted (C6-C10)-aryl-(C1-C4)-alkoxy, optionally substituted (C6-C10)-aryl-(C1-C4)-alkylthio, optionally substituted heterocyclyl-(C1-C4)-alkoxy, or optionally substituted heterocyclyl-(C1-C4)-alkylthio, C(S)OR8, C(O)SR8 or C(S)SR8;
    R4 is CONR6R7, CONR7—N(R7)2, CO—NR7—OR7, COOR8, C(S)OR7, C(O)SR7, C(S)SR7,
    
        saturated partially or fully unsaturated or aromatic, optionally substituted 5- or 6-membered heterocyclyl,
        SR7, SOR7, SO2R7, SO3R7, SON(R7)2, SO2N(R7)2, P(O)(OR7)2, NR7OR7, —B(OR7)2, —(CR72)0-6—NR72 or —(CR72)0-6—NR7—NR72;
    
    
    R5 is H, halogen, optionally halogen-substituted alkyl or optionally halogen-substituted cycloalkyl, O—(C1-C4)-alkyl or S(O)0-2(C1-C4)-alkyl;
    X is halogen, cyano, hydroxyl, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted phenyl, optionally substituted alkylthio, optionally substituted alkylsulphinyl or optionally substituted alkylsulphonyl;
    R6 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl or optionally substituted cycloalkenyl, optionally substituted aryl and optionally substituted arylalkyl;
    R7 are identical or different and are H or R6, or two radicals R7 or one radical R7 and one radical R6 together form a cycle having 3 to 6 carbon atoms which is saturated or partially unsaturated and optionally contains 1 or 2 further nitrogen, sulphur or oxygen atoms, where oxygen atoms must not be adjacent to one another;
    R8 is H, a cation, for example an optionally alkyl- or aralkyl-substituted ammonium ion, substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl or optionally substituted aralkyl.




DETAILED DESCRIPTION OF THE INVENTION
Pyrazolopyrimidines of the formula (I) are highly suitable for controlling unwanted microorganisms. Especially, they have strong fungicidal activity and can be used both in crop protection and in the protection of materials.
The compounds of the formula (I) can be present both in pure form and as mixtures of different possible isomeric forms, in particular of stereoisomers, such as E and Z, threo and erythro and also optical isomers, such as R and S isomers or atropisomers, and, if appropriate, also of tautomers. The invention encompasses both the pure isomers and their mixtures.
Depending on the nature of the substituents defined above, the compounds of the formula (I) have acidic or basic properties and are capable of forming salts, if appropriate also inner salts. If the compounds of the formula (I) carry hydroxyl groups, carboxyl groups or other groups which induce acidic properties, these compounds can be reacted with bases to form salts. Suitable bases are, for example, hydroxides, carbonates, bicarbonates of the alkali metals and alkaline earth metals, in particular those of sodium, potassium, magnesium and calcium, furthermore ammonia, primary, secondary and tertiary amines having (C1-C4)-alkyl radicals or aralkyl radicals, mono-, di- and trialkanolamines of (C1-C4)-alkanols, choline and chlorocholine. If the compounds of the formula (I) carry amino groups, alkylamino groups or other groups which induce basic properties, these compounds can be reacted with acids to give salts. Suitable acids are, for example, mineral acids, such as hydrochloric acid, sulphuric acid and phosphoric acid, organic acids, such as acetic acid or oxalic acid, and acetic salts, such as NaHSO4 and KHSO4. The salts obtainable in this manner also have fungicidal properties.
The formula (I) provides a general definition of the pyrazolopyrimidines according to the invention.
Preference is given to compounds of the formula (I) in which R4 has one of the following meanings:

    a1: CONR6R7, CONR7—N(R7)2, CONR7—OR7, COOR8, CSOR7, COSR7 or CSSR7,
    a2: saturated, partially unsaturated or aromatic optionally substituted 5- or 6-membered heterocyclyl,
    a3: SR7, SOR7, SO2R7, SO3R7, SON(R7)2, or SO2N(R7)2,
    a4: P(O)—(OR7)2,
    a5: B(OR7)2 or
    a6: NR7OR7.


Preference is also given to compounds of the formula (I) in which R4 has one of the following meanings:

    a1, a1, a2, a3, a4, a5 
    a2, a1, a2, a3, a4, a6 
    a3, a1, a2, a3, a5, a6 
    a4, a1, a2, a3, a4, a5, a6 
    a5, a1, a3, a4, a5, a6 
    a6, a2, a3, a4, a5, a6 


Preference is furthermore given to compounds of the formula (I) in which

    b1) R3 represents optionally substituted aryl, or
    b2) R3 represents optionally substituted heterocyclyl, or
    b3) R3 represents optionally substituted alkyl, or
    b4) R3 represents optionally substituted alkenyl, or
    b5) R3 represents optionally substituted alkynyl, or
    b6) R3 represents optionally substituted cycloalkyl, or
    b7) R3 represents optionally substituted aralkyl, or
    b8) R3 represents an optionally substituted amino group, or
    b9) R3 represents optionally substituted (C1-C8)-alkylthio, or
    b10) R3 represents optionally substituted (C1-C8)-alkoxy.


Preference is also given to compounds of the formula (I) in which R3 has one of the following meanings:

    c1: b1, b2, b3, b4, b5, b6, b7, b8, b9 
    c2: b1, b2, b3, b4, b5, b6, b7, b8, b10 
    c3: b1, b2, b3, b4, b5, b6, b7, b9, b10 
    c4: b1, b2, b3, b4, b5, b6, b8, b9, b10 
    c5: b1, b2, b3, b4, b5, b7, b8, b9, b10 
    c6: b1, b2, b3, b4, b6, b7, b8, b9, b10 
    c7: b1, b2, b3, b5, b6, b7, b8, b9, b10 
    c8: b1, b2, b4, b5, b6, b7, b8, b9, b10 
    c9: b1, b3, b4, b5, b6, b7, b8, b9, b10 
    c10: b2, b3, b4, b5, b6, b7, b8, b9, b10 


Preference is furthermore given to those compounds of the formula (I) in which one or more groups have one of the preferred meanings given below, i.e.,

    R1 is hydrogen, alkyl having 1 to 10 carbon atoms which is unsubstituted or mono- to pentasubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, alkoxy having 1 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, mercapto, alkylthio having 1 to 4 carbon atoms, amino, mono- or dialkylamino having in each case 1 to 4 carbon atoms, or
    R1 is alkenyl having 2 to 10 carbon atoms which is unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, alkoxy having 1 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, mercapto, alkylthio having 1 to 4 carbon atoms, amino, mono- or dialkylamino having in each case 1 to 4 carbon atoms, or
    R1 is alkynyl having 2 to 10 carbon atoms which is unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, alkoxy having 1 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, mercapto, alkylthio having 1 to 4 carbon atoms, amino, mono- or dialkylamino having in each case 1 to 4 carbon atoms, or
    R1 is cycloalkyl having 3 to 10 carbon atoms which is unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of halogen and alkyl having 1 to 4 carbon atoms, or
    R1 is saturated or unsaturated heterocyclyl having 3 to 10 ring members and 1 to 3 heteroatoms, such as nitrogen, oxygen and/or sulphur, where the heterocyclyl is unsubstituted or mono- or polysubstituted by halogen, alkyl having 1 to 4 carbon atoms, cyano, nitro, cycloalkyl having 3 to 6 carbon atoms, hydroxyl, alkoxy having 1 to 4 carbon atoms and/or mercapto;
    R2 is hydrogen or alkyl having 1 to 6 carbon atoms;
    R1 and R2 together with the nitrogen atom to which they are attached are a saturated or unsaturated heterocyclic ring having 3 to 8 ring members, where the heterocycle optionally contains a further nitrogen, oxygen or sulphur atom as ring member and where the heterocycle may be unsubstituted or up to trisubstituted by fluorine, chlorine, bromine, alkyl having 1 to 4 carbon atoms, haloalkyl having 1 to 4 carbon atoms and 1 to 9 fluorine and/or chlorine atoms, hydroxyl, alkoxy having 1 to 4 carbon atoms, haloalkoxy having 1 to 4 carbon atoms and 1 to 9 fluorine and/or chlorine atoms, mercapto, thioalkyl having 1 to 4 carbon atoms and/or haloalkylthio having 1 to 4 carbon atoms and 1 to 9 fluorine and/or chlorine atoms;
    R3 is C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, C3-C8-cycloalkyl, phenyl-C1-C10-alkyl, where R3 is unsubstituted or partially or fully halogenated and/or optionally carries one to three radicals from the group RX, or C1-C10-haloalkyl which optionally carries one to three radicals from the group RX, and RX is cyano, nitro, hydroxyl, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-haloalkylthio, C1-C6-alkylsulphinyl, C1-C6-haloalkylsulphinyl, C1-C6-alkylsulphonyl, C1-C6-haloalkylsulphonyl, C1-C6-alkylamino, di-C1-C6-alkylamino, C2-C6-alkenyl, C2-C6-alkenyloxy, C2-C6-alkynyl, C3-C6-alkynyloxy and optionally halogenated oxy-C1-C4-alkyl-C1-C4-alkenoxy, oxy-C1-C4-alkenyl-C1-C4-alkoxy, oxy-C1-C4-alkyl-C1-C4-alkyloxy, or
    R3 is phenyl which may be mono- to tetrasubstituted by identical or different substituents from the group consisting of
    
        halogen, cyano, nitro, amino, hydroxyl, formyl, carboxyl, carboxyalkyl, carbamoyl, thiocarbamoyl;
        in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl having in each case 1 to 6 carbon atoms;
        in each case straight-chain or branched alkenyl or alkenyloxy having in each case 2 to 6 carbon atoms;
        in each case straight-chain or branched haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulphinyl or haloalkylsulphonyl having in each case 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms;
        in each case straight-chain or branched haloalkenyl or haloalkenyloxy having in each case 2 to 6 carbon atoms and 1 to 11 identical or different halogen atoms;
        in each case straight-chain or branched alkylamino, dialkylamino, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkylsulphonyloxy, hydroximinoalkyl or alkoximinoalkyl having in each case 1 to 6-carbon atoms in the individual alkyl moieties;
        cycloalkyl having 3 to 8 carbon atoms;
        1,3-propanediyl which is attached in the 2,3-position, 1,4-butanediyl, methylenedioxy (—O—CH2—O—) or 1,2-ethylenedioxy (—O—CH2—CH2—O—), where these radicals may be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, alkyl having 1 to 4 carbon atoms and haloalkyl having 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms;
    
    
    or
    R3 is saturated or fully or partially unsaturated or aromatic heterocyclyl having 3 to 8 ring members and 1 to 3 heteroatoms from the group consisting of nitrogen, oxygen and sulphur, where the heterocyclyl may be mono- or disubstituted by halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, haloalkoxy having 1 to 4 carbon atoms, haloalkylthio having 1 to 4 carbon atoms, hydroxyl, mercapto, cyano, nitro and/or cycloalkyl having 3 to 6 carbon atoms or/and carboxyalkyl;
    R3 is C1-C8-alkylamino, C2-C8-alkenylamino, C2-C8-alkynylamino, di-C1-C8-alkylamino, di-C2-C8-alkenylamino, di-C2-C8-alkynylamino, C2-C8-alkenyl-(C2-C8)-alkynylamino, C2-C6-alkynyl-(C1-C8)-alkylamino, C2-C8-alkenyl-(C1-C8)-alkylamino, C6-C10-arylamino, C6-C10-aryl-(C1-C8)-alkylamino, C6-C10-aryl-(C1-C4)-alkyl-(C1-C8)-alkylamino, heterocyclyl-(C1-C8)-alkylamino or heterocyclyl-(C1-C4)-alkyl-(C1-C8)-alkylamino;
    R4 is CONR6R7, CONR7—N(R7)2, CO—NR7—OR7, COOR8, CSOR7, COSR7, SR7, SOR7, SO2R7, SO3R7, SON(R7)2, SO2N(R7)2, P(O)—(OR7)2, B(OR7)2 or






    A, B, D, E, G are identical or different and are CR9, CR9R9, N, NR9, O or S, with the proviso that at least one such group is N, O or S and that oxygen atoms are not adjacent to one another;
    Y is C, CR9 or N;
    R9 is R7, halogen, NR72, OH, SR7 or OR7;
    R5 is H, halogen, (C1-C4)-alkyl which is unsubstituted or substituted by one or more halogen atoms, cyclopropyl which is unsubstituted or substituted by one or more halogen atoms, SCH3, SOCH3, SO2CH3 or OCH3;
    X is H, fluorine, chlorine, bromine, CN, hydroxyl, alkoxy having 1 to 4 carbon atoms or alkylthio having 1 to 4 carbon atoms;
    R6 is C1-C10-alkyl, C2-C10-alkenyl, C2-C11-alkynyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl, phenyl-C1-C10-alkyl, where R6 is unsubstituted or partially or fully halogenated and/or optionally carries one to three radicals from the group RX, or C1-C10-haloalkyl which optionally carries one to three radicals from the group RX, and RX is cyano, nitro, hydroxyl, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-haloalkylthio, C1-C6-alkylsulphinyl, C1-C6-haloalkylsulphinyl, C1-C6-alkylsulphonyl, C1-C6-haloalkylsulphonyl, C1-C6-alkylamino, di-C1-C6-alkylamino, C2-C6-alkenyl, C2-C6-alkenyloxy, C2-C6-alkynyl, C3-C6-alkynyloxy and optionally halogenated oxy-C1-C4-alkyl-C1-C4-alkenoxy, oxy-C1-C4-alkenyl-C1-C4-alkoxy, oxy-C1-C4-alkyl-C1-C4-alkyloxy and/or CONR6R7, CONR7OR7, COOR8, carboxy-(C1-C4)-alkyl;
    R7 is H or R6, or two radicals R7 or one radical R7 and one radical R8 together form a cycle having 3 to 6 carbon atoms which is saturated or partially unsaturated and optionally contains 1 or 2 further nitrogen, sulphur or oxygen atoms, where oxygen atoms may not be adjacent to one another;
    R8 is H, an alkali metal or alkaline earth metal, copper, NH4, mono-(C1-C10)-alkylammonium, di-(C1-C10)-alkylammonium, tri-(C1-C10)-alkylammonium, tetra-(C1-C10)-alkylammonium, cholinium, C2-C10-alkenyl, C2-C10-alkynyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl, where R8 is unsubstituted or partially or fully halogenated and/or optionally carries one to three radicals from the group RX, or C1-C10-haloalkyl which optionally carries one to three radicals from the group RX, or C1-C10-alkyl which is partially or fully halogenated and/or carries one to three radicals from the group Rx, and RX is cyano, nitro, hydroxyl, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-haloalkylthio, C1-C6-alkylsulphinyl, C1-C6-haloalkylsulphinyl, C1-C6-alkylsulphonyl, C1-C6-haloalkylsulphonyl, C1-C6-alkylamino, di-C1-C6-alkylamino, C2-C6-alkenyl, C2-C6-alkenyloxy, C2-C6-alkynyl, C3-C6-alkynyloxy and optionally halogenated oxy-C1-C4-alkyl-C1-C4-alkenoxy, oxy-C1-C4-alkenyl-C1-C4-alkoxy, oxy-C1-C4-alkyl-C1-C4-alkyloxy, CONR6R7, CONR7OR7, COOR8, carboxy-C1-C4)-alkyl.


Particular preference is given to those pyrazolopyrimidines of the formula (I) in which one or more of the groups have one of the particularly preferred meanings listed below, i.e.

    R1 is hydrogen or a radical of the formula






where # denotes the point of attachment (these radicals can be present both in optically pure form or as isomer mixtures);

    R2 is hydrogen, methyl, ethyl, propyl, or
    R1 and R2 together with the nitrogen atom to which they are attached are pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, 3,6-dihydro-1(2H)-pyridinyl or tetrahydro-1(2H)-pyridazinyl, where these radicals are unsubstituted or substituted by 1 to 3 fluorine atoms, 1 to 3 methyl groups and/or trifluoromethyl,
    or
    R1 and R2 together with the nitrogen atom to which they are attached are a radical of the formula






    
    
        in which
        R′ represents hydrogen or methyl,
        R′′ represents methyl, ethyl, fluorine, chlorine or trifluoromethyl,
        m represents the number 0, 1, 2 or 3, where R′′ represents identical or different radicals if m represents 2 or 3,
        R′′′ represents methyl, ethyl, fluorine, chlorine or trifluoromethyl
        and
        n represents the number 0, 1, 2 or 3, where R′′′ represents identical or different radicals if n represents 2 or 3;
    
    
    R3 is (C1-C8)-alkyl, (C1-C8)-cycloalkyl, where R3 is unsubstituted or substituted by one or more fluorine or chlorine atoms, benzyl or
    R3 is phenyl which may be mono- to trisubstituted by identical or different substituents from the group consisting of
    
        fluorine, chlorine, bromine, cyano, nitro, formyl, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, vinyl, ethynyl, allyl, propargyl, methoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, n- or i-propylthio, methylsulphinyl, ethylsulphinyl, methylsulphonyl, ethylsulphonyl, allyloxy, propargyloxy, trifluoromethyl, trifluoroethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, difluorochloromethylthio, trifluoromethylthio, trifluoromethylsulphinyl, trifluoromethylsulphonyl, trichloroethynyloxy, trifluoroethynyloxy, chloroallyloxy, iodopropargyloxy, methylamino, ethylamino, n- or i-propylamino, dimethylamino, diethylamino, acetyl, propionyl, acetyloxy, methoxycarbonyl, ethoxycarbonyl, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, ethoximinomethyl, methoximinoethyl, ethoximinoethyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or by
        1,3-propanediyl which is attached in the 2,3-position, 1,4-butanediyl, methylenedioxy (—O—CH2—O—) or 1,2-ethylenedioxy (—O—CH2—CH2—O—), where these radicals may be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, chlorine, methyl, ethyl, n-propyl, i-propyl, trifluoromethyl, carboxyl and carboxymethyl,
    
    
    R3 is pyridyl which is attached in the 2- or 4-position and which may be mono- to tetrasubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, hydroxyl, mercapto, nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
    R3 is pyrimidyl which is attached in the 2- or 4-position and which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
    R3 is thienyl which is attached in the 2- or 3-position and which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
    R3 is C1-C8-alkylamino or di-C1-C8-alkylamino, or
    R3 is thiazolyl which is attached in the 2-, 4- or 5-position and which may be mono- or disubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
    R3 is N-piperidinyl, N-tetrazolyl, N-pyrazolyl, N-imidazolyl, N-1,2,4-triazolyl, N-pyrrolyl or N-morpholinyl, each of which is unsubstituted or mono- or- if possible- polysubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl,
    R4 is CONR6R7, CONR7—N(R7)2, CO—NR7—OR7, COOR8, CSOR7, COSR7, pyrrolyl, imidazolyl, pyrazolyl, 1,3,4-triazolyl, thiazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazolyl, oxazolyl, tetrazolyl, oxadiazinyl, 4H-[1,2,4]-oxadiazin-3-yl, dioxazinyl, 5,6-dihydro-[1,4,2]-dioxazin-3-yl, pyridyl, where the heterocyclic radicals are optionally substituted by one or more radicals from the group consisting of C1-C4-alkyl and halogen, SR7, SOR7, SO2R7, SO3R7, SON(R7)2, SO2N(R7)2, P(O)—(OR7)2 or B(OR)2;
    R5 is H, Cl, F, CH3, —CH(CH3)2 or cyclopropyl; and
    X is H, F, Cl, CN, C1-C4-alkyl which is unsubstituted or substituted by one or more fluorine or chlorine atoms;
    R6 is (C1-C8)-alkyl, (C3-C6)-alkenyl, (C1-C8)-cycloalkyl, benzyl, CONR6R7, CONR7OR7, COOR8, carboxy-(C1-C4)-alkyl, cyano;
    R7 is H or R6; or two radicals R7 or one radical R6 and one radical R7 together form a cycle having 3 to 6 carbon atoms which is saturated or partially unsaturated and which optionally contains 1 or 2 further nitrogen, sulphur or oxygen atoms, where the oxygen atoms may not be adjacent to one another;
    R8 is H, Na, K, 1⁄2Ca, 1⁄2Mg, Cu, NH4, NH(CH3)3, N(CH3)4, HN(C2H5)3, N(C2H5)4, H2N(iC3H7)2, (C1-C4)-alkyl which is optionally fully or partially substituted by F and/or Cl, CONR6R7, CONR7OR7, COOR8, carboxy-(C1-C4)-alkyl(C1-C4)-alkoxy-(C1-C4)-alkyl, allyl, propargyl, cyclopropyl, benzyl, (CHRZ—CHRZ—O)m—(C1-C4)-alkyl, where RZ═H, CH3 and m=1 to 6.


Very particular preference is given to compounds of the formula (I) in which one or more of the groups have one of the very particularly preferred meanings listed below, i.e.

    R1 and R2 have the particularly preferred meanings listed above;
    R3 is (C1-C6)-alkyl, (C3-C6)-alkenyl, (C3-C6)-alkynyl, (C3-C8)-cycloalkyl, where R3 is unsubstituted or substituted by one or more fluorine or chlorine atoms and/or alkyl,
    or
    R3 is 2,4-, 2,5- or 2,6-disubstituted phenyl or 2-substituted phenyl or 2,4,6- or 2,4,5-trisubstituted phenyl having substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
    R3 is pyridyl which is attached in the 2- or 4-position and which may be mono- to tetrasubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
    R3 is pyrimidyl which is attached in the 4-position and which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl;
    R3 is thienyl which is attached in the 2- or 3-position and may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
    R4 is CONR6R7, CONR7—N(R7)2, CO—NR7—OR7, COOR8, 1H-pyrrolyl, 1H-imidazolyl, 1,3,4-oxadiazolyl, 1H-pyrazolyl, 1H-1,3,4-triazolyl, tetrazolyl, oxadiazinyl, 4H-[1,2,4]-oxadiazin-3-yl, dioxazinyl, 5,6-dihydro-[1,4,2]-dioxazin-3-yl, pyridyl, where the heterocyclic radicals are optionally substituted by one or more radicals from the group consisting of C1-C4-alkyl and halogen, SR7, SOR7, SO2R7, SO3R7, SON(R7)2, SO2N(R7)2, or P(O)—(OR7)2;
    R5 is H, —CH3, —CH(CH3)2, Cl or cyclopropyl; and
    X is fluorine, chlorine, (C1-C7)-alkyl or (C1-C3)-haloalkyl;
    R6 is (C1-C8)-alkyl, (C3-C6)-alkenyl, (C1-C8)-cycloalkyl, benzyl, carboxy-(C1-C4)-alkyl, CONR6R7, CONR7OR7, COOR8, cyano;
    R7 is H or R6, or two radicals R7 or one radical R6 and one radical R7 together form a cycle having 3 to 6 carbon atoms which is saturated or partially unsaturated and optionally contains 1 or 2 further nitrogen, sulphur or oxygen atoms, where oxygen atoms may not be adjacent to one another;
    R8 is H, Na, K, NH4, NH(Et)3, H2N(iPr)2, H2N(Bn2), H3N(Bn), (C1-C4)-alkyl which is fully or partially substituted by F and/or Cl and/or carboxy-(C1-C4)-alkyl, CONR6R7, CONR7OR7, COOR8, is (C1-C4)-alkoxy-(C1-C4)-alkyl, allyl, propargyl, cyclopropyl, benzyl, (CHRZ—CHRZ—O)m—(C1-C4)-alkyl where RZ═H, CH3 and m=1 to 6.


The radical definitions mentioned above may be combined with one another as desired. Moreover, individual definitions may not apply.
Compounds of the formula (I) in which R4 represents CONR6R7, CONR7—N(R2)2, CO—NR7—OR7 or COOR8 and X represents Cl can be prepared, for example, as shown in Scheme 1 starting with 3-aminopyrazole-4-carboxylic acid esters (II) which are known from the literature (see, for example, U.S. Pat. No. 3,515,715 and U.S. Pat. No. 3,634,391) and malonic acid esters (IIa) where R11═C1-C8-alkyl or aryl:




The intermediates of the formulae III, IV, V and VII are novel and also form part of the subject-matter of the invention.
The malonic acid ester (IIa) are known from the literature or can be prepared by processes known from literature (for example, CR3=heterocyclyl), U.S. Pat. No. 6,156,925 (R3=substituted phenyl), WO-A 03/009687 (CR3=substituted alkyl), Chem. Ber. 1956, 89, 996 (CR3=substituted cycloalkyl).
Malonic acid esters of the formula (IIa) where R3=(2-chloro- or -methyl)-thiophen-3-yl can also be prepared according to Scheme 1a below.




Analogously to the last two steps of the synthesis sequence, dimethyl 2-(2-chlorothiophen-3-yl)malonate can also be prepared from (2-chlorothiophen-3-yl)acetic acid.
The step-wise conversion of the starting materials (II) into the amine (V) can be carried out, for example, analogously to the process of WO 04/000 844.
The amines, hydrazines, hydroxylamines or alcohols used for the further conversion of the acid chlorides (VII) are known. They are commercially available or can be prepared by known processes which are familiar to the person skilled in the art, as described, for example, in Houben-Weyl, methoden der Organischen Chemie [methods of Organic Chemistry].
Compounds of the formula (I) in which X represents a cyano group can be prepared, for example, starting with intermediates (V), as shown in Scheme 2.




Compounds of the formula (I) in which X represents an optionally substituted alkyl or phenyl radical can be prepared from the esters (II), which are known from the literature, by reaction with β-keto esters, as shown in Scheme 3:







The synthesis of compounds of the formula (I) in which X represents a mercapto, sulphinyl or sulphonyl group is shown in Scheme 4 in an exemplary manner for compounds where X═S(O)0-2—CH3. Here, the cyanoalkenes can be prepared analogously to Compper et al., Chem. Ber. 1962, 95, 2861-70 or Chauhan et al., Tetrahedron 1976, 32, 1779-87.







Compounds of the formula (I) in which R4 represents a sulphonic acid or sulphonamide radical and X represents Cl can be prepared, for example as shown in Scheme 5, where the synthesis of the starting materials can be carried out, for example, as described in WO-A 02/048151.




Compounds of the formula (I) in which R4 represents a mercapto, sulphinyl or sulphonyl radical and X represents Cl can be prepared, for example, as shown in Scheme 6 for R4═(S(O)0-2—CH3, where the starting materials can be synthesized, for example, as described in WO-A 02/048151.




Compounds of the formula (I) in R6 represents an optionally substituted heterocyclyl group and X represents Cl can be prepared, for example, as shown in Scheme 7 for imidazole, where the starting material can be synthesized analogously to Kornfeld et al., J. Med. Chem. 1968, 11, 1028-31.




The processes according to the invention for preparing the compounds of the formula (I) are preferably carried out using one or more reaction auxiliaries.
Suitable reaction auxiliaries are, if appropriate, the customary inorganic or organic bases or acid acceptors. These preferably include alkali metal or alkaline earth metal acetates, amides, carbonates, bicarbonates, hydrides, hydroxides or alkoxides, such as, for example, sodium acetate, potassium acetate or calcium acetate, lithium amide, sodium amide, potassium amide or calcium amide, sodium carbonate, potassium carbonate or calcium carbonate, sodium bicarbonate, potassium bicarbonate or calcium bicarbonate, lithium hydride, sodium hydride, potassium hydride or calcium hydride, lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, sodium methoxide, ethoxide, n- or i-propoxide, n-, i-, s- or t-butoxide or potassium methoxide, ethoxide, n- or i-propoxide, n-, i-, s- or t-butoxide; furthermore also basic organic nitrogen compounds, such as, for example, trimethylamine, triethylamine, tripropylamine, tributyl-amine, ethyldiisopropylamine, N,N-dimethylcyclohexylamine, dicyclohexylamine, ethyldicyclohexylamine, N,N-dimethylaniline, N,N-dimethyl-benzylamine, pyridine, 2-methyl-, 3-methyl-, 4-methyl-, 2,4-dimethyl-, 2,6-dimethyl-, 3,4-dimethyl- and 3,5-dimethylpyridine, 5-ethyl-2-methyl-pyridine, 4-dimethylaminopyridine, N-methylpiperidine, 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).
The processes according to the invention are preferably carried out using one or more diluents. Suitable diluents are virtually all inert organic solvents. These preferably include aliphatic and aromatic, optionally halogenated hydrocarbons, such as pentane, hexane, heptane, cyclohexane, petroleum ether, benzine, ligroin, benzene, toluene, xylene, methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, chlorobenzene and o-dichlorobenzene, ethers, such as diethyl ether and dibutyl ether, glycol dimethyl ether and diglycol dimethyl ether, tetrahydrofuran and di-oxane, ketones, such as acetone, methyl ethyl ketone, methyl isopropyl ketone or methyl isobutyl ketone, esters, such as methyl acetate or ethyl acetate, nitriles, such as, for example, acetonitrile or propionitrile, amides, such as, for example, dimethylformamide, dimethylacetamide and N-methylpyrrolidone, and also dimethyl sulphoxide, tetramethylene sulphone and hexamethylphosphoric triamide.
The reaction temperatures in the processes according to the invention can be varied within a relatively wide range. In general, the processes are carried out at temperatures between 0° C. and 250° C., preferably at temperatures between 10° C. and 185° C.
The processes according to the invention are generally carried out under atmospheric pressure. However, it is also possible to operate under elevated or reduced pressure.
For carrying out the processes according to the invention, the starting materials required in each case are generally employed in approximately equimolar amounts. However, it is also possible to use a relatively large excess of one of the components employed in each case. Work-up in the processes according to the invention is in each case carried out by customary methods (cf. the Preparation Examples).
The compounds according to the invention have potent microbicidal activity and can be employed for controlling unwanted microorganisms, such as fungi and bacteria, in crop protection and in the protection of materials.
Fungicides can be employed in crop protection for controlling Plasmodiophoromycetes, Oomycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes and Deuteromycetes.
Bactericides can be employed in crop protection for controlling Pseudomonadaceae, Rhizobiaceae, Enterobacteriaceae, Corynebacteriaceae and Streptomycetaceae.
Some pathogens causing fungal and bacterial diseases which come under the generic names listed above may be mentioned as examples, but not by way of limitation:

    Xanthomonas species, such as, for example, Xanthomonas campestris pv. oryzae; 
    Pseudomonas species, such as, for example, Pseudomonas syringae pv. lachrymans; 
    Erwinia species, such as, for example, Erwinia amylovora; 
    Pythium species, such as, for example, Pythium ultimum; 
    Phytophthora species, such as, for example, Phytophthora infestans; 
    Pseudoperonospora species, such as, for example, Pseudoperonospora humuli or Pseudoperonospora cubensis; 
    Plasmopara species, such as, for example, Plasmopara viticola; 
    Bremia species, such as, for example, Bremia lactucae; 
    Peronospora species, such as, for example, Peronospora pisi or P. brassicae; 
    Erysiphe species, such as, for example, Erysiphe graminis; 
    Sphaerotheca species, such as, for example, Sphaerotheca fuliginea; 
    Podosphaera species, such as, for example, Podosphaera leucotricha; 
    Venturia species, such as, for example, Venturia inaequalis; 
    Pyrenophora species, such as, for example, Pyrenophora teres or P. graminea (conidia form: Drechslera, syn: Helminthosporium);
    Cochliobolus species, such as, for example, Cochliobolus sativus (conidia form: Drechslera, syn: Helminthosporium);
    Uromyces species, such as, for example, Uromyces appendiculatus; 
    Puccinia species, such as, for example, Puccinia recondita; 
    Sclerotinia species, such as, for example, Sclerotinia sclerotiorum; 
    Tilletia species, such as, for example, Tilletia caries; 
    Ustilago species, such as, for example, Ustilago nuda or Ustilago avenae; 
    Pellicularia species, such as, for example, Pellicularia sasakii; 
    Pyricularia species, such as, for example, Pyricularia oryzae; 
    Fusarium species, such as, for example, Fusarium culmorum; 
    Botrytis species, such as, for example, Botrytis cinerea; 
    Septoria species, such as, for example, Septoria nodorum; 
    Leptosphaeria species, such as, for example, Leptosphaeria nodorum; 
    Cercospora species, such as, for example, Cercospora canescens; 
    Alternaria species, such as, for example, Alternaria brassicae; and
    Pseudocercosporella species, such as, for example, Pseudocercosporella herpotrichoides. 


The active compounds according to the invention also show a strong invigorating action in plants. Accordingly, they are suitable for mobilizing the internal defences of the plant against attack by unwanted microorganisms.
In the present context, plant-invigorating (resistance-inducing) compounds are to be understood as meaning substances which are capable of stimulating the defence system of plants such that, when the treated plants are subsequently inoculated with unwanted microorganisms, they display substantial resistance to these microorganisms.
In the present case, unwanted microorganisms are to be understood as meaning phytopathogenic fungi, bacteria and viruses. The compounds according to the invention can thus be used to protect plants within a certain period of time after treatment against attack by the pathogens mentioned. The period of time for which this protection is achieved generally extends for 1 to 10 days, preferably 1 to 7 days, from the treatment of the plants with the active compounds.
The fact that the active compounds are well tolerated by plants at the concentrations required for controlling plant diseases permits the treatment of above-ground parts of plants, of propagation stock and seeds, and of the soil.
The active compounds according to the invention can be employed with particularly good results for controlling cereal diseases, such as, for example, against Erysiphe species, and of diseases in viticulture and in the cultivation of fruit and vegetables, such as, for example, against Botrytis, Venturia, Sphaerotheca and Podosphaeva species.
The active compounds according to the invention are also suitable for increasing the yield of crops. In addition, they show reduced toxicity and are well tolerated by plants.
If appropriate, the active compounds according to the invention can, at certain concentrations and application rates, also be employed as herbicides, for regulating plant growth and for controlling animal pests. If appropriate, they can also be used as intermediates or precursors in the synthesis of other active compounds.
According to the invention, it is possible to treat all plants and parts of plants. Plants are to be understood here as meaning all plants and plant populations, such as desired and undesired wild plants or crop plants (including naturally occurring crop plants). Crop plants can be plants which can be obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, including the transgenic plants and including plant cultivars which can or cannot be protected by plant breeders' certificates. Parts of plants are to be understood as meaning all above-ground and below-ground parts and organs of plants, such as shoot, leaf, flower and root, examples which may be mentioned being leaves, needles, stems, trunks, flowers, fruit-bodies, fruits and seeds and also roots, tubers and rhizomes. Parts of plants also include harvested material and vegetative and generative propagation material, for example seedlings, tubers, rhizomes, cuttings and seeds.
The treatment of the plants and parts of plants according to the invention with the active compounds is carried out directly or by action on their environment, habitat or storage area according to customary treatment methods, for example by dipping, spraying, evaporating, atomizing, broadcasting, brushing-on and, in the case of propagation material, in particular in the case of seeds, furthermore by one- or multilayer coating.
In the protection of materials, the compounds according to the invention can be employed for protecting industrial materials against infection with, and destruction by, unwanted microorganisms.
Industrial materials in the present context are understood as meaning non-living materials which have been prepared for use in industry. For example, industrial materials which are intended to be protected by active compounds according to the invention from microbial change or destruction can be tackifiers, sizes, paper and board, textiles, leather, wood, paints and plastic articles, cooling lubricants and other materials which can be infected with, or destroyed by, microorganisms. Parts of production plants, for example cooling-water circuits, which may be impaired by the proliferation of microorganisms may also be mentioned within the scope of the materials to be protected. Industrial materials which may be mentioned within the scope of the present invention are preferably tackifiers, sizes, paper and board, leather, wood, paints, cooling lubricants and heat-transfer liquids, particularly preferably wood.
Microorganisms capable of degrading or changing the industrial materials which may be mentioned are, for example, bacteria, fungi, yeasts, algae and slime organisms. The active compounds according to the invention preferably act against fungi, in particular moulds, wood-discolouring and wood-destroying fungi (Basidiomycetes) and against slime organisms and algae.
Microorganisms of the following genera may be mentioned as examples:

    Alternaria, such as Altemaria tenuis, 
    Aspergillus, such as Aspergillus niger, 
    Chaetomium, such as Chaetomium globosum, 
    Coniophora, such as Coniophora puetana, 
    Lentinus, such as Lentinus tigrinus, 
    Penicillium, such as Penicillium glaucum, 
    Polyporus, such as Polyporus versicolor, 
    Aureobasidium, such as Aureobasidium pullulans, 
    Sclerophoma, such as Sclerophoma pityophila, 
    Trichoderma, such as Trichoderma viride, 
    Escherichia, such as Escherichia coli, 
    Pseudomonas, such as Pseudomonas aeruginosa, and
    Staphylococcus, such as Staphylococcus aureus. 


Depending on their particular physical and/or chemical properties, the active compounds can be converted into the customary formulations, such as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols and microencapsulations in polymeric substances and in coating compositions for seeds, and ULV cool and warm fogging formulations.
These formulations are produced in a known manner, for example by mixing the active compounds with extenders, that is liquid solvents, liquefied gases under pressure, and/or solid carriers, optionally with the use of surfactants, that is emulsifiers and/or dispersants, and/or foam formers. If the extender used is water, it is also possible to employ, for example, organic solvents as auxiliary solvents. Essentially, suitable liquid solvents are: aromatics such as xylene, toluene or alkylnaphthalenes, chloroinated aromatics or chloroinated aliphatic hydrocarbons such as chlorobenzenes, chloroethylenes or methylene chloride, aliphatic hydrocarbons such as cyclohexane or paraffins, for example petroleum fractions, alcohols such as butanol or glycol and their ethers and esters, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents such as dimethylformamide or dimethyl sulphoxide, or else water. Liquefied gaseous extenders or carriers are to be understood as meaning liquids which are gaseous at standard temperature and under atmospheric pressure, for example aerosol propellants such as halogenated hydrocarbons, or else butane, propane, nitrogen and carbon dioxide. Suitable solid carriers are: for example ground natural minerals such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic minerals such as finely divided silica, alumina and silicates. Suitable solid carriers for granules are: for example crushed and fractionated natural rocks such as calcite, pumice, marble, sepiolite and dolomite, or else synthetic granules of inorganic and organic meals, and granules of organic material such as sawdust, coconut shells, maize cobs and tobacco stalks. Suitable emulsifiers and/or foam formers are: for example nonionic and anionic emulsifiers, such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, for example alkylaryl polyglycol ethers, alkylsulphonates, alkyl sulphates, arylsulphonates, or else protein hydrolysates. Suitable dispersants are: for example lignosulphite waste liquors and methylcellulose.
Tackifiers such as carboxymethylcellulose, natural and synthetic polymers in the form of powders, granules or latices, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, or else natural phospholipids such as cephalins and lecithins and synthetic phospholipids can be used in the formulations. Other possible additives are mineral and vegetable oils.
It is possible to use colorants such as inorganic pigments, for example iron oxide, titanium oxide and Prussian Blue, and organic dyestuffs such as alizarin dyestuffs, azo dyestuffs and metal phthalocyanine dyestuffs, and trace nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.
The formulations generally comprise between 0.1 and 95 percent by weight of active compound, preferably between 0.5 and 90%.
The active compounds according to the invention can, as such or in their formulations, also be used in a mixture with known fungicides, bactericides, acaricides, nematicides or insecticides, to broaden, for example, the activity spectrum or to prevent development of resistance. In many cases, synergistic effects are obtained, i.e. the activity of the mixture is greater than the activity of the individual components.
Suitable mixing components are, for example, the following compounds:
Fungicides:
2-phenylphenol; 8-hydroxyquinoline sulphate; acibenzolar-S-methyl; aldimorph; amidoflumet; ampropylfos; ampropylfos-potassium; andoprim; anilazine; azaconazole; azoxystrobin; benalaxyl; benalaxyl-M, benodanil; benomyl; benthiavalicarb-isopropyl; benzamacril; benzamacril-isobutyl; bilanafos; binapacryl; biphenyl; bitertanol; blasticidin-S; boscalid; bromuconazole; bupirimate; buthiobate; butylamine; calcium polysulphide; capsimycin; captafol; captan; carbendazim; carboxin; carpropamid; carvone; chinomethionat; chlobenthiazone; chlorofenazole; chloroneb; chlorothalonil; chlozolinate; clozylacon; cyazofamid; cyflufenamid; cymoxanil; cyproconazole; cyprodinil; cyprofuram; Dagger G; debacarb; dichlofluanid; dichlone; dichlorophen; diclocymet; diclomezine; dicloran; diethofencarb; difenoconazole; diflumetorim; dimethirimol; dimethomorph; dimoxystrobin; diniconazole; diniconazole-M; dinocap; diphenylamine; dipyrithione; ditalimfos; dithianon; dodine; drazoxolon; edifenphos; epoxiconazole; ethaboxam; ethirimol; etridiazole; famoxadone; fenamidone; fenapanil; fenarimol; fenbuconazole; fenfuram; fenhexamid; fenitropan; fenoxanil; fenpiclonil; fenpropidin; fenpropimorph; ferbam; fluazinam; flubenzimine; fludioxonil; flumetover; flumorph; fluoromide; fluoxastrobin; fluquinconazole; flurprimidol; flusilazole; flusulphamide; flutolanil; flutriafol; folpet; fosetyl-A1; fosetyl-sodium; fuberidazole; furalaxyl; furametpyr; furcarbanil; furmecyclox; guazatine; hexachlorobenzene; hexaconazole; hymexazole; imazalil; imibenconazole; iminoctadine triacetate; iminoctadine tris(albesilate); iodocarb; ipconazole; iprobenfos; iprodione; iprovalicarb; irumamycin; isoprothiolane; isovaledione; kasugamycin; kresoxim-methyl; mancozeb; maneb; meferimzone; mepanipyrim; mepronil; metalaxyl; metalaxyl-M; metconazole; methasulphocarb; methfuroxam; metiram; metominostrobin; metsulphovax; mildiomycin; myclobutanil; myclozolin; natamycin; nicobifen; nitrothal-isopropyl; noviflumuron; nuarimol; ofurace; orysastrobin; oxadixyl; oxolinic acid; oxpoconazole; oxycarboxin; oxyfenthiin; paclobutrazole; pefurazoate; penconazole; pencycuron; phosdiphen; phthalide; picoxystrobin; piperalin; polyoxins; polyoxorim; probenazole; prochloroaz; procymidone; propamocarb; propanosine-sodium; propiconazole; propineb; proquinazid; pro-thioconazole; pyraclostrobin; pyrazophos; pyrifenox; pyrimethanil; pyroquilon; pyroxyfur; pyrrolenitrine; quinconazole; quinoxyfen; quintozene; simeconazole; spiroxamine; sulphur; tebuconazole; tecloftalam; tecnazene; tetcyclacis; tetraconazole; thiabendazole; thicyofen; thifluzamide; thiophanate-methyl; thiram; tioxymid; tolclofos-methyl; tolylfluanid; triadimefon; triadimenol; triazbutil; triazoxide; tricyclamide; tricyclazole; tridemorph; trifloxystrobin; triflumizole; triforine; triticonazole; uniconazole; validamycin A; vinclozolin; zineb; ziram; zoxamide; (2S)-N-[2-[4-[[3-(4-chlorophenyl)-2-propynyl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulphonyl)amino]butanamide; 1-(1-naphthalenyl)-1H-pyrrole-2,5-dione; 2,3,5,6-tetrachloro-4-(methylsulphonyl)pyridine; 2-amino-4-methyl-N-phenyl-5-thiazolecarboxamide; 2-chloro-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-3-pyridinecarboxamide; 3,4,5-trichloro-2,6-pyridinedicarbonitrile; actinovate; cis-1-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)cycloheptanol; methyl 1-(2,3-dihydro-2,2-dimethyl-1H-inden-1-yl)-1H-imidazole-5-carboxylate; monopotassium carbonate; N-(6-methoxy-3-pyridinyl)-cyclopropanecarboxamide; N-butyl-8-(1,1-dimethylethyl)-1-oxaspiro[4.5]decane-3-amine; sodium tetrathiocarbonate;
and copper salts and preparations, such as Bordeaux mixture; copper hydroxide; copper naphthenate; copper oxychloride; copper sulphate; cufraneb; copper oxide; mancopper; oxine-copper.
Bactericides:
bronopol, dichlorophen, nitrapyrin, nickel dimethyldithiocarbamate, kasugamycin, octhilinone, furancarboxylic acid, oxytetracyclin, probenazole, streptomycin, tecloftalam, copper sulphate and other copper preparations.
Insecticides/Acaricides/Nematicides:
1. Acetylcholinesterase (AChE) Inhibitors
1.1 carbamates (for example alanycarb, aldicarb, aldoxycarb, allyxycarb, aminocarb, azamethi-phos, bendiocarb, benfuracarb, bufencarb, butacarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, chloethocarb, coumaphos, cyanofenphos, cyanophos, dimetilan, ethiofencarb, fenobucarb, fenothiocarb, formetanate, furathiocarb, isoprocarb, metam-sodium, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, promecarb, propoxur, thiodicarb, thiofanox, triazamate, trimethacarb, XMC, xylylcarb)
1.2 organophosphates (for example acephate, azamethiphos, azinphos (-methyl, -ethyl), bromophos-ethyl, bromfenvinfos (-methyl), butathiofos, cadusafos, carbophenothion, chloroethoxyfos, chlorofenvinphos, chloromephos, chloropyrifos (-methyl/-ethyl), coumaphos, cyanofenphos, cyanophos, chlorofenvinphos, demeton-s-methyl, demeton-s-methylsulphon, dialifos, diazinon, dichlofenthion, dichlorovos/DDVP, dicrotophos, dimethoate, dimethylvinphos, dioxabenzofos, disulfoton, EPN, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion, fensulfothion, fenthion, flupyrazofos, fonofos, formothion, fosmethilan, fosthiazate, heptenophos, iodofenphos, iprobenfos, isazofos, isofenphos, isopropyl o-salicylate, isoxathion, malathion, mecarbam, methacrifos, methamidophos, methidathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, parathion (-methyl/-ethyl), phenthoate, phorate, phosalone, phosmet, phosphamidon, phosphocarb, phoxim, pirimiphos (-methyl/-ethyl), profenofos, propaphos, propetamphos, prothiofos, prothoate, pyraclofos, pyridaphenthion, pyridathion, quinalphos, sebufos, sulfotep, sulprofos, tebupirimfos, temephos, terbufos, tetrachlorovinphos, thiometon, triazophos, triclorfon, vamidothion)
2. Sodium Channel Modulators/Blockers of Voltage-dependent Sodium Channels
2.1 pyrethroids (for example acrinathrin, allethrin (d-cis-trans, d-trans), beta-cyfluthrin, bifenthrin, bioallethrin, bioallethrin-5-cyclopentyl-isomer, bioethanomethrin, biopermethrin, bioresmethrin, chlovaporthrin, cis-cypermethrin, cis-resmethrin, cis-permethrin, clocythrin, cycloprothrin, cyflu-thrin, cyhalothrin, cypermethrin (alpha-, beta-, theta-, zeta-), cyphenothrin, DDT, deltamethrin, empenthrin (1R-isomer), esfenvalerate, etofenprox, fenfluthrin, fenpropathrin, fenpyrithrin, fen-valerate, flubrocythrinate, flucythrinate, flufenprox, flumethrin, fluvalinate, fubfenprox, gamma-cyhalothrin, imiprothrin, kadethrin, lambda-cyhalothrin, metofluthrin, permethrin (cis-, trans-), phenothrin (1R-trans isomer), prallethrin, profluthrin, protrifenbute, pyresmethrin, resmethrin, RU 15525, silafluofen, tau-fluvalinate, tefluthrin, terallethrin, tetramethrin (1R-isomer), tralomethrin, transfluthrin, ZXI 8901, pyrethrins (pyrethrum))
2.2 oxadiazines (for example indoxacarb)
3. Acetylcholine Receptor Agonists/Antagonists
3.1 chloronicotinyls/neonicotinoids (for example acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, nithiazine, thiacloprid, thiamethoxam)
3.2 nicotine, bensultap, cartap
4. Acetylcholine Receptor Modulators
4.1 spinosyns (for example spinosad)
5. Antagonists of GABA-controlled Chloride Channels
5.1 cyclodiene organochlorines (for example camphechloro, chlorodane, endosulfan, gamma-HCH, HCH, heptachloro, lindane, methoxychloro
5.2 fiproles (for example acetoprole, ethiprole, fipronil, vaniliprole)
6. Chloride Channel Activators
6.1 mectins (for example abamectin, avermectin, emamectin, emamectin-benzoate, ivermectin, milbemectin, milbemycin)
7. Juvenile-hormone Mimetics
(for example diofenolan, epofenonane, fenoxycarb, hydroprene, kinoprene, methoprene, pyriproxifen, triprene)
8. Ecdyson Agonists/Disruptors
8.1 diacylhydrazines (for example chromafenozide, halofenozide, methoxyfenozide, tebufenozide)
9. Chitin Biosynthesis Inhibitors
9.1 benzoylureas (for example bistrifluron, chlofluazuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, penfluron, teflubenzuron, triflumuron)
9.2 buprofezin
9.3 cyromazine
10. Inhibitors of Oxidative Phosphorylation, ATP Disruptors
10.1 diafenthiuron
10.2 organotins (for example azocyclotin, cyhexatin, fenbutatin-oxide)
11. Decouplers of Oxidative Phosphorylation Acting by Interrupting the H-proton Gradient
11.1 pyrroles (for example chlorofenapyr)
11.2 dinitrophenols (for example binapacryl, dinobuton, dinocap, DNOC)
12. Site-I Electron Transport Inhibitors
12.1 METIs (for example fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, tolfenpyrad)
12.2 hydramethylnone
12.3 dicofol
13. Site-II Electron Transport Inhibitors
13.1 rotenone
14. Site-III Electron Transport Inhibitors
14.1 acequinocyl, fluacrypyrim
15. Microbial disruptors of the insect gut membrane
Bacillus thuringiensis strains
16. Inhibitors of Fat Synthesis
16.1 tetronic acids (for example spirodiclofen, spiromesifen)
16.2 tetramic acids [for example 3-(2,5-dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4.5]dec-3-en-4-yl ethyl carbonate (alias: carbonic acid, 3-(2,5-dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4.5]dec-3-en-4-yl ethyl ester, CAS Reg. No.: 382608-10-8) and carbonic acid, cis-3-(2,5-dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4.5]dec-3-en-4-yl ethyl ester (CAS Reg. No.: 203313-25-1)]
17. Carboxamides
(for example flonicamid)
18. Octopaminergic Agonists
(for example amitraz)
19. Inhibitors of Magnesium-stimulated ATPase
(for example propargite)
20. Phthalamides
(for example N2-[1,1-dimethyl-2-(methylsulphonyl)ethyl]-3-iodo-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide (CAS Reg. No.: 272451-65-7), flubendiamide)
21. Nereistoxin Analogues
(for example thiocyclam hydrogen oxalate, thiosultap-sodium)
22. Biologicals, Hormones or Pheromones
(for example azadirachtin, Bacillus spec., Beauveria spec., Codlemone, Metarrhizium spec., Paecilomyces spec., Thuringiensin, Verticillium spec.)
23. Active Compounds with Unknown or Unspecific Mechanisms of Action
23.1 fumigants (for example aluminium phosphide, methyl bromide, sulphuryl fluoroide)
23.2 selective antifeedants (for example cryolite, flonicamid, pymetrozine)
23.3 mite growth inhibitors (for example clofentezine, etoxazole, hexythiazox)
23.4 amidoflumet, benclothiaz, benzoximate, bifenazate, bromopropylate, buprofezin, chinomethi-onat, chlorodimeform, chlorobenzilate, chloropicrin, clothiazoben, cycloprene, cyflumetofen, di-cyclanil, fenoxacrim, fentrifanil, flubenzimine, flufenerim, flutenzin, gossyplure, hydramethylnone, japonilure, metoxadiazone, petroleum, piperonyl butoxide, potassium oleate, pyrafluprole, pyridalyl, pyriprole, sulfluramid, tetradifon, tetrasul, triarathene, verbutin,
furthermore the compound 3-methylphenyl propylcarbamate (Tsumacide Z), the compound 3-(5-chloro-3-pyridinyl)-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octane-3-carbonitrile (CAS Reg. No. 185982-80-3) and the corresponding 3-endo-isomer (CAS Reg. No. 185984-60-5) (cf. WO 96/37494, WO 98/25923), and preparations which comprise insecticidally active plant extracts, nematodes, fungi or viruses.
A mixture with other known active compounds, such as herbicides, or with fertilizers and growth regulators, safeners and/or semiochemicals is also possible.
In addition, the compounds of the formula (I) according to the invention also have very good antimycotic activity. They have a very broad antimycotic activity spectrum in particular against dermatophytes and yeasts, moulds and diphasic fungi (for example against Candida species such as Candida albicans, Candida glabrata) and Epidermophyton floccosum, Aspergillus species such as Aspergillus niger and Aspergillus fumigatus, Trichophyton species such as Trichophyton mentagrophytes, Microsporon species such as Microsporon canis and audouinii. The list of these fungi does by no means limit the mycotic spectrum which can be covered, but is only for illustration.
The active compounds can be used as such, in the form of their formulations or the use forms prepared therefrom, such as ready-to-use solutions, suspensions, wettable powders, pastes, soluble powders, dusts and granules. Application is carried out in a customary manner, for example by watering, spraying, atomizing, broadcasting, dusting, foaming, spreading, etc. It is furthermore possible to apply the active compounds by the ultra-low volume method, or to inject the active compound preparation or the active compound itself into the soil. It is also possible to treat the seeds of the plants.
When using the active compounds according to the invention as fungicides, the application rates can be varied within a relatively wide range, depending on the kind of application. For the treatment of parts of plants, the active compound application rates are generally between 0.1 and 10 000 g/ha, preferably between 10 and 1000 g/ha. For seed dressing, the active compound application rates are generally between 0.001 and 50 g per kilogram of seed, preferably between 0.01 and 10 g per kilogram of seed. For the treatment of the soil, the active compound application rates are generally between 0.1 and 10 000 g/ha, preferably between 1 and 5 000 g/ha.
As already mentioned above, it is possible to treat all plants and their parts according to the invention. In a preferred embodiment, wild plant species and plant cultivars, or those obtained by conventional biological breeding, such as crossing or protoplast fusion, and parts thereof, are treated. In a further preferred embodiment, transgenic plants and plant cultivars obtained by genetic engineering, if appropriate in combination with conventional methods (Genetically Modified Organisms), and parts thereof, are treated. The term “parts” or “parts of plants” or “plant parts” has been explained above.
Particularly preferably, plants of the plant cultivars which are in each case commercially available or in use are treated according to the invention. Plant cultivars are to be understood as meaning plants having new properties (“traits”) and which have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques. They can be cultivars, varieties, bio- or genotypes.
Depending on the plant species or plant cultivars, their location and growth conditions (soils, climate, vegetation period, diet), the treatment according to the invention may also result in superadditive (“synergistic”) effects. Thus, for example, reduced application rates and/or a widening of the activity spectrum and/or an increase in the activity of the substances and compositions which can be used according to the invention, better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering performance, easier harvesting, accelerated maturation, higher harvest yields, better quality and/or a higher nutritional value of the harvested products, better storage stability and/or processability of the harvested products are possible which exceed the effects which were actually to be expected.
The transgenic plants or plant cultivars (i.e. those obtained by genetic engineering) which are preferably to be treated according to the invention include all plants which, in the genetic modification, received genetic material which imparted particularly advantageous useful properties (“traits”) to these plants. Examples of such properties are better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering performance, easier harvesting, accelerated maturation, higher harvest yields, better quality and/or a higher nutritional value of the harvested products, better storage stability and/or processability of the harvested products. Further and particularly emphasized examples of such properties are a better defence of the plants against animal and microbial pests, such as against insects, mites, phytopathogenic fungi, bacteria and/or viruses, and also increased tolerance of the plants to certain herbicidally active compounds. Examples of transgenic plants which may be mentioned are the important crop plants, such as cereals (wheat, rice), maize, soya beans, potatoes, cotton, tobacco, oilseed rape and also fruit plants (with the fruits apples, pears, citrus fruits and grapes), and particular emphasis is given to maize, soya beans, potatoes, cotton, tobacco and oilseed rape. Traits that are particularly emphasized are increased defence of the plants against insects, arachnids, nematodes and slugs and snails by toxins formed in the plants, in particular those formed in the plants by the genetic material from Bacillus thuringiensis (for example by the genes CryIA(a), CryIA(b), CryIA(c), CryIIA, CryIIIA, CryIIIB2, Cry9c, Cry2Ab, Cry3Bb and CryIF and also combinations thereof) (hereinbelow referred to as “Bt plants”). Traits that are also particularly emphasized are the increased defence of the plants against fungi, bacteria and viruses by systemic acquired resistance (SAR), systemin, phytoalexins, elicitors and resistance genes and correspondingly expressed proteins and toxins. Traits that are furthermore particularly emphasized are the increased tolerance of the plants to certain herbicidally active compounds, for example imidazolinones, sulphonylureas, glyphosate or phosphinotricin (for example the “PAT” gene). The genes which impart the desired traits in question can also be present in combination with one another in the transgenic plants. Examples of “Bt plants” which may be mentioned are maize varieties, cotton varieties, soya bean varieties and potato varieties which are sold under the trade names YIELD GARD® (for example maize, cotton, soya beans), KnockOut® (for example maize), StarLink® (for example maize), Bollgard® (cotton), Nucoton® (cotton) and NewLeaf® (potato). Examples of herbicide-tolerant plants which may be mentioned are maize varieties, cotton varieties and soya bean varieties which are sold under the trade names Roundup Ready® (tolerance to glyphosate, for example maize, cotton, soya bean), Liberty Link® (tolerance to phosphinotricin, for example oilseed rape), IMI® (tolerance to imidazolinones) and STS® (tolerance to sulphonylureas, for example maize). Herbicide-resistant plants (plants bred in a conventional manner for herbicide tolerance) which may be mentioned also include the varieties sold under the name Clearfield® (for example maize). Of course, these statements also apply to plant cultivars which have these genetic traits or genetic traits still to be developed, and which will be developed and/or marketed in the future.
The plants listed can be treated according to the invention in a particularly advantageous manner with the compounds of the general formula (I) or the active compound mixtures according to the invention. The preferred ranges stated above for the active compounds or mixtures also apply to the treatment of these plants. Particular emphasis is given to the treatment of plants with the compounds or mixtures specifically mentioned in the present text.
The compounds of the formula (I) according to the invention are furthermore suitable for suppressing the growth of tumour cells in humans and mammals. This is based on an interaction of the compounds according to the invention with tubulin and microtubuli and by promoting microtubuli polymerization.
For this purpose, it is possible to administer an effective amount of one or more compounds of the formula (I) or pharmaceutically acceptable salts thereof.
The preparation and the use of the active compounds according to the invention is illustrated in the examples below.
EXAMPLES
Example I
5-chloro-6-(2-chloro-4-fluorophenyl)-7-(4-methylpiperidin-1-yl)-3-methylmercapto-pyrazolo [2,3-a]pyrimidine




With stirring, 1.06 g of aluminium trichloride were initially added to 1 g of 5-chloro-6-(2-chloro-4-fluorophenyl)-7-(4-methylpiperidin-1-yl)pyrazolo[2,3-a]pyrimidine, the preparation of which is described, for example, in WO 02/048151, in 50 ml of dichloromethane, and 0.99 g of methyl methylthiosulphonate was then added dropwise. After 15 h of stirring at room temperature, the mixture was poured into ice-water and hydrochloric acid was added. The organic phase was separated off, and the aqueous phase was extracted two more times with in each case 15 ml of ethyl acetate. The combined organic phases were dried with sodium sulphate, and the solvent was removed under reduced pressure. The residue was chromatographed on silica gel using cyclohexane/ethyl acetate 4:1. This gave 0.65 g of an orange oil, logPs=5.73.
Example II
5-chloro-6-(2-chloro-4-fluorophenyl)-7-(4-methylpiperidin-1-yl)-3-methylsulphonyl-pyrazolo[2,3-a]pyrimidine




0.5 g of the compound obtained above was initially charged in 50 ml of dichloromethane. At room temperature, 0.58 g of 3-chloroperoxybenzoic acid was added, and the mixture was stirred at room temperature for another 24 h. The mixture was slightly concentrated using a rotary evaporator, and water and diethyl ether were then added and the mixture was made alkaline using aqueous ammonia. The mixture was extracted three times with diethyl ether, the combined organic phases were washed twice with aqueous ammonia and dried with sodium sulphate and the solvents were removed under reduced pressure. The residue was chromatographed on silica gel using cyclohexane/ethyl acetate 4:1. This gave 80 mg of a light-yellow solid, logPs=4.20.
Example III
5-chloro-6-(2-chloro-4-fluorophenyl)-7-(4-methylpiperidin-1-yl)pyrazolo[2,3-a]pyrimidine-3-sulphonic acid




1 g of 5-chloro-6-(2-chloro-4-fluorophenyl)-7-(4-methylpiperidin-1-yl)pyrazalo[2,3-a]pyrimidine, the preparation of which is described, for example, in WO 02/048151, was initially charged in 20 ml of acetic anhydride, and 0.388 g of conc. sulphuric acid was added with ice-cooling. After 15 h of stirring at room temperature, the mixture was concentrated under reduced pressure and the residue was added to ice-water. The aqueous phase was extracted once with a little ethyl acetate, and the organic phase was discarded. The aqueous phase was filtered off with suction, and the residue was air-dried. This gave 80 mg of a pink solid, logPs=2.48.
Example IV




At room temperature, 0.185 g (1.46 mmol) of oxalyl chloride was added over a period of 5 minutes to 0.2 g (0.485 mmol) of 5-chloro-6-(2-chloro-6-fluorophenyl)-7-{[(1R)-1,2-dimethylpropyl]amino}pyrazolo[1,5-a]pyrimidine-3-carboxylic acid. The mixture was stirred for 30 minutes, until the evolution of gas had ceased. The reaction mixture was concentrated under reduced pressure and taken up in 5 ml of dichloromethane. At 25° C., the solution obtained in this manner was, over a period of 10 minutes, added dropwise to a mixture of 0.057 g (0.973 mmol) of isopropylamine and 5 ml of pyridine. The mixture was stirred at 25° C. for another 2 hours. 10 ml of dilute 1 N hydrochloric acid and 10 ml of dichloromethane was then added to the reaction mixture. The organic phase was dried over sodium sulphate and then concentrated under reduced pressure. The residue was chromatographed on silica gel using a mixture of cyclohexane: ethyl acetate=5:1. This gave 0.145 g of 5-chloro-6-(2-chloro-6-fluorophenyl)-7-{[(1R)-1,2-dimethylpropyl]amino}-N-isopropylpyrazolo[1,5-a]pyrimidine-3-carboxamide (logPs=4.72; content by HPLC: 93%).
Example V




At room temperature, 2 g (4.7 mmol) of methyl 5-chloro-6-(2-chloro-6-fluorophenyl)-7-{[(1R)-1,2-dimethylpropyl]amino}pyrazolo[1,5-a]pyrimidine-3-carboxylate were mixed with a mixture of 50 ml of ethanol and 25 ml (25 mmol) of an aqueous 1 N solution of sodium hydroxide. The mixture was then stirred at 50° C. for 3 hours. The reaction mixture was concentrated under reduced pressure. 10 ml of dilute 1 N hydrochloric acid and 10 ml of dichloromethane were then added to the residue. The organic phase was dried over sodium sulphate and then concentrated under reduced pressure. This gave 1.7 g of 5-chloro-6-(2-chloro-6-fluorophenyl)-7-{[(1R)-1,2-dimethylpropyl]amino}pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (logPs=3.24; content by HPLC: 92%).
Example VI




At 0° C., 0.50 g (1.23 mmol) of nitrile (described in WO-A 04/000 844) was stirred into 5 ml of conc. sulphuric acid and stirring at 0° C. was continued for 5 h, and the mixture was then stirred at RT for another 2 h. The mixture was stirred into ice and the resulting precipitate was filtered off with suction, washed thoroughly with water and dried.
Yield 0.48 g (80%), m.p. 190-2° C.
HPLC: logP=3.88




0.42 g (0.99 mmol) of amide in 25 ml of toluene was heated to 90° C., 0.21 g (1.58 mmol) of chlorocarbonylsulphenyl chloride was then added and the mixture was stirred at 90° C. for another 4 h. After the evolution of HCl had ended, the mixture was concentrated under reduced pressure and the residue was titrated thoroughly with petroleum ether and dried.
Yield 0.38 g (65%), m.p. 205-7° C. (decomp.)
HPLC: logP=5.38
Example VII




0.50 g (1.18 mmol) of the amide intermediate from Example VI a and 0.23 g (1.53 mmol) of chloroacetaldehyde diethyl acetal in 10 ml of ethanol were heated at the boil under reflux for 15 h. A further 0.23 g (1.53 mmol) of acetal was added, and the mixture was heated for another 15 h. The mixture was concentrated under reduced pressure, and the residue was purified on a silica gel cartridge (mobile phase: petroleum ether/MTBE 4:1).
Yield 0.14 g (19%)
HPLC: logP=4.72
Example VIII




At RT, 0.5 g (1.13 mmol) of the appropriate acid chloride was dissolved in 15 ml of acetonitrile. 0.12 g (1.69 mmol) of hydroxylamine hydrochloride was added at RT, followed by 0.31 g (2.25 mmol) of potassium carbonate, also at RT. The mixture was stirred at RT for 1 hour, introduced into water, acidified and taken up in methylene chloride. The organic phase was washed with water, dried with sodium sulphate and concentrated under reduced pressure.
Yield 0.45 g (76%)
HPLC: logP=3.51




0.4 g (0.91 mmol) of hydroxamic acid was dissolved in 4 ml of methanol, and 0.30 g (1.36 mmol) of ethylene glycol bismesylate, followed by 0.13 g (0.91 mmol) of potassium carbonate dissolved in 1 ml of water, was added. The mixture was stirred at 60° C. for 30 min and then cooled to RT and introduced into a mixture of ice-water and dilute hydrochloric acid. The product was taken up in methylene chloride and the organic phase was extracted with water, dried with sodium sulphate and concentrated under reduced pressure. The oil that remained was chromatographed over a silica gel cartridge (mobile phase: petroleum ether/MTBE 4:1).
HPLC: logP=4.43
Examples IX and X




At RT, 0.4 g (0.99 mmol) of nitrile (described in WO-A 04/000 844) was dissolved in 25 ml of ethanol, and 0.10 g (1.48 mmol) of hydroxylammonium chloride and 0.8 g of Amberlyst A-21 were added. At RT, the mixture was shaken in a shaker overnight. To bring the reaction to completion, a further 0.04 g (0.59 mmol) of hydroxylammonium chloride and 0.2 g of Amberlyst A-21 were added, and the mixture was again shaken at RT overnight. After the Amberlyst A-21 had been filtered off with suction, the mother liquor was then concentrated under reduced pressure and the residue was purified on a silica gel cartridge (mobile phase: petroleum ether/MTBE 4:1).
Yield 0.24 g (55%), m.p. 233-6° C.
HPLC: logP=2.47




At RT, a suspension of 2.20 g (5.00 mmol) of amidoxime and 1.40 g (25.00 mmol) of powdered potassium hydroxide in 60 ml of acetonitrile was added to 1.09 g (5.00 mmol) of ethylene glycol bismesylate in 40 ml of acetonitrile, and the mixture was heated at the boil under reflux for 24 h. After cooling to RT, the mixture was poured into water, adjusted to pH 3 to 4 using dilute hydrochloric acid and extracted with ethyl acetate, and the organic phase was washed with water, dried with sodium sulphate and concentrated under reduced pressure. The residue was chromatographed on a silica gel cartridge (mobile phase: cyclohexane/ethyl acetate, gradient 9:1, 3:1, 1:1).
Fraction 1: Ex. X, yield 0.17 g (7%), (atropisomer “A”)
HPLC: logP=4.87
Fraction 2: Ex. X, yield 0.18 g (8%), (atropisomer “B”)
HPLC: logP=4.90
Fraction 3: Ex. IX, yield 0.03 g (1%)
HPLC: logP=3.23
Example XI


    a) analogously to Example IXa:






Yield 21.6 g (88%)
HPLC: logP=2.41

    b) analogously to Example IX b:






Yield 0.19 g (9%)
HPLC: logP=2.84
Example XII


    a)






With stirring, a mixture of 10 g (0.046 mol) of diethyl sec-butylmalonate, 6.5 g (0.046 mol) of methyl 5-amino-1H-pyrazole-3-carboxylate and 9.4 g (0.051 mol) of tri-n-butylamine was heated at 180° C. for 6 hours. During this time, the ethanol released during the reaction was continuously distilled off. The reaction mixture was then concentred under reduced pressure. This gave 12.2 g (100% of theory) of methyl 5,7-dihydroxy-6-(sec-butyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylate. The product was used for further syntheses without additional purification.

    b)






At room temperature, 5.5 g (0.026 mol) of phosphorus pentachloride were added with stirring to a mixture of 12.2 g (0.046 mol) of methyl 5,7-dihydroxy-6-(sec-butyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylate and 63.1 g (0.412 mol) of phosphorus oxychloride. The reaction mixture was heated at 110° C. for 3 hours and then concentrated under reduced pressure. The residue that remained was dissolved in dichloromethane. The solution formed was initially washed with ice-water and then dried over sodium sulphate and concentrated under reduced pressure. The residue that remained was chromatographed on silica gel using petroleum ether:tert-butyl methyl ether=2:1. This gave 4.6 g (29.1% of theory) of methyl 5,7-dichloro-6-(sec-butyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylate (content according to HPLC: 88%).
HPLC: logP=3.13

    c)






1.0 g (0.003 mol) of methyl 5,7-dichloro-6-(sec-butyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylate and 0.92 g (0.003 mol) of potassium fluoroide in 10 ml of acetonitrile were stirred at 60° C. for 3 hours. 0.75 g (0.007 mol) of (S)-trifluoromethylisopropylamine were then added, and the mixture was stirred at 80° C. for 5 hours. The mixture was then allowed to cool to room temperature, acidified by addition of hydrochloric acid and extracted with dichloromethane. The combined organic phases were dried over sodium sulphate and then concentrated under reduced pressure. The residue that remained was chromatographed on silica gel using cyclohexane:ethyl acetate=8:2. This gave 0.4 g (31.3% of theory) of methyl 5-chloro-6-(sec-butyl)-7-[(S)-3-trifluoroisopropylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylate.
HPLC: logP=3.76

    d)






0.3 g (0.001 mol) of methyl 5-chloro-6-(sec-butyl)-7-[(S)-3-trifluoroisopropylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylate was dissolved in 4.5 ml of dioxane. 0.63 g (0.0016 mol) of sodium hydroxide in 8 ml of an aqueous solution was added at room temperature, and the reaction mixture was then stirred for 100 hours. The mixture was then poured into water, acidified with hydrochloric acid and extracted with ethyl acetate. The organic phase was dried over sodium sulphate and concentrated under reduced pressure. The residue was chromatographed on silica gel using cyclohexane:ethyl acetate=8:2. This gave 0.15 g of 5-chloro-6-(sec-butyl)-7-[(S)-3-trifluoroisopropylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylic acid.
HPLC: logP=2.88.
The following compounds were prepared analogously:
Example XIII


    a)






methyl 5-chloro-6-(sec-butyl)-7-[(R)-3-methyl-2-butylamino][1,5-a]pyrimidine-3-carboxylate
HPLC: logP=4.49 b)




5-chloro-6-(sec-butyl)-7-[(S)-3-trifluoroisopropylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylic acid
HPLC: logP=3.52
Example XIV


    a)






methyl 5-chloro-6-(sec-butyl)-7-[(S)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylate
HPLC: logP=4.49

    b)






5-chloro-6-(sec-butyl)-7-[(S)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylic acid HPLC: logP=3.52
Example XV


    a)






With stirring, a mixture of 14.15 g (0.071 mol) of dimethyl cyclopentylmalonate (WO2004/006926), 10 g (0.071 mol) of methyl 5-amino-1H-pyrazole-3-carboxylate and 14.4 g (0.078 mol) of tri-n-butylamine was heated at 180° C. for 6 hours. The methanol released during the reaction was continuously distilled off. The reaction mixture was then concentrated under reduced pressure. This gave 19.7 g (100% of theory) of methyl 5,7-dihydroxy-6-cyclopentylpyrazolo[1,5-a]pyrimidine-3-carboxylate. The product was used for further syntheses without additional purification.

    b)






At room temperature, 8.4 g (0.04 mol) of phosphorus pentachloride were added with stirring to a mixture of 19.6 g (0.071 mol) of methyl 5,7-dihydroxy-6-cyclopentylpyrazolo[1,5-a]pyrimidine-3-carboxylate and 96.5 g (0.629 mol) of phosphorus oxychloride. The reaction mixture was heated at 110° C. for 3 hours and then concentrated under reduced pressure. The residue that remained was dissolved in dichloromethane. The solution formed was initially washed with ice-water and then dried over sodium sulphate and concentrated under reduced pressure. The residue that remained was chromatographed on silica gel using petroleum ether:tert-butyl methyl ether=2:1. This gave 4.5 g (20% of theory) of methyl 5,7-dichloro-6-cyclopentylpyrazolo[1,5-a]pyrimidine-3-carboxylate (content according to HPLC: 98%).
HPLC: logP=3.31

    c)






0.33 g (0.004 mol) of (R)-3-methyl-2-butylamine and 0.4 g (0.004 mol) of triethylamine were initially charged in dichloroethane. At 0° C., 1.0 g (0.003 mol) of methyl 5,7-dichloro-6-cyclopentylpyrazolo[1,5-a]pyrimidine-3-carboxylate was added. The mixture was then stirred at room temperature for 12 hours. The mixture was then acidified by addition of hydrochloric acid and extracted with diethyl ether. The organic phase was dried over sodium sulphate and then concentrated under reduced pressure. The residue was titrated with a mixture of diethyl ether and petroleum ether. This gave 0.1 g of 5-chloro-6-cyclopentyl-7-[(R)-3-methyl-2-butylamino]-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid.
HPLC: logP=4.72
The following compounds were prepared analogously:




methyl 5-chloro-6-cyclopentyl-7-[(S)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylate
HPLC: logP=4.72




methyl 5-chloro-6-cyclopentyl-7-[(S)-3-trifluoroisopropylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylate
HPLC: logP=3.89

    d)






0.5 g (0.001 mol) of methyl 5-chloro-6-cyclopentyl-7-[(R)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxlate was initially charged in 8 ml of dioxane. At room temperature, 0.63 g (0.016 mol) of potassium hydroxide in 8 ml of an aqueous solution was added, and the reaction mixture was then stirred for 1 hour. The mixture was then poured into water, acidified with hydrochloric acid and extracted with diethyl ether. The organic phase was dried over sodium sulphate and concentrated under reduced pressure. The residue was titrated with a mixture of diethyl ether and petroleum ether, filtered off with suction and dried. This gave 0.1 g of 5-chloro-6-cyclopentyl-7-[(R)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylic acid.
HPLC: logP=3.7
The following compounds were obtained analogously:
Example XVI




HPLC: logP=3.7
Example XVII




5-chloro-6-cyclopentyl-7-[(S)-3-trifluoroisopropylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylic acid
HPLC: logP=3.06
Example XVIII


    a)






methyl 5-chloro-6-cyclopentyl-7-[(R)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylate
HPLC: logP=4.99

    b)






5-Chloro-6-cyclopentyl-7-[(R)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylic acid
HPLC: logP=3.93
Example XIX


    a)






25 g (0.164 mol) of 3-amino-4-brombenzonitrile were initially charged in 230 ml of 48% strength hydrobromic acid. At from 0° C. to at most 5° C., 11.3 g (0.164 mol) of sodium nitrite, dissolved in water, were added dropwise. After the addition had ended, excess nitrous acid was destroyed by addition of urea. With stirring at 0° C., the solution was added dropwise to solution of 31.26 g (0.218 mol) of copper(I) bromide and 500 ml of 48% strength hydrobromic acid. The reaction mixture was then heated at 100° C. After the evolution of nitrogen had ceased, the mixture was cooled to room temperature and extracted with ethyl acetate. The organic phase was washed with aqueous sodium hydroxide solution, dried and concentrated. This gave 21.6 g of 3-chloro-4-bromobenzonitrile.
HPLC: logP=2.82

    b)






7.6 g (0.191 mol) of 60% strength sodium hydride in paraffin oil were initially charged in 300 ml of dioxane. At from 55° C. to 60° C., 22.9 g (0.173 mol) of diethyl malonate were added dropwise, and the mixture was stirred at 50° C. for 1-2 hours. 9.9-g (0.069 mol) of copper(1) bromide were added. At 80° C., 15 g (0.069 mol) of 3-chloro-4-bromobenzonitrile were then added dropwise, and the mixture was subsequently stirred at 100° C. for 14 hours. The reaction mixture was then cooled and acidified by dropwise addition of concentrated hydrochloric acid at from 15° C. to 20° C. Water was added, the mixture was extracted with dichloromethane, the organic phase was dried over sodium sulphate and the solvent was removed. The residue was distilled at 1 mbar, giving 17.5 g of dimethyl(2-chloro-4-cyanophenyl)malonate.
HPLC: logP=2.34

    c)






With stirring, a mixture of 10 g (0.037 mol) of dimethyl(2-chloro-4-cyanophenyl)malonate, 5.2 g (0.037 mol) of methyl 5-amino-1H-pyrazole-3-carboxylate and 7.6 g (0.041 mol) of tri-n-butyl-amine was heated at 180° C. for 6 hours. The methanol released during the reaction was continuously distilled off. The reaction mixture was then concentrated under reduced pressure. This gave 12.8 g (100% of theory) of methyl 5,7-dihydroxy-6-(2-chloro-4-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate. The product was used for further syntheses without additional purification.

    d)






At room temperature, 4.4 g (0.021 mol) of phosphorus pentachloride were added with stirring to a mixture of 12.8 g (0. 037 mol) of methyl 5,7-dihydroxy-6-(2-chloro-4-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate and 50.5 g (0.329 mol) of phosphorus oxychloride. The reaction mixture was heated at 1 10° C. for 3 hours and then concentrated under reduced pressure. The residue that remained was dissolved in dichloromethane. The solution formed was initially washed with ice-water and then dried over sodium sulphate and concentrated under reduced pressure. The residue that remained was chromatographed on silica gel using petroleum ether:tert-butyl methyl ether=2:1. The product was then titrated with diethyl ether and filtered off with suction. This gave 2.2 g of methyl 5,7-dichloro-6-(2-chloro-4-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate.
HPLC: logP=2.85

    e)






0.274 g (0.003 mol) of (R)-3-methyl-2-butylamine and 0.318 g (0.003 mol) of triethylamine were initially charged in dichloroethane. At 0° C., 1.0 g (0.003 mol) of methyl 5,7-dichloro-6-(2-chloro-4-cyanophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate was added. The mixture was then stirred at room temperature for 12 hours. The mixture was then acidified by addition of hydrochloric acid and extracted with dichloromethane. The organic phase was dried over sodium sulphate and then concentrated under reduced pressure. The residue that remained was chromatographed on silica gel using tert-butyl methyl ether:petroleum ether=1:1. This gave 0.4 g of methyl 5-chloro-6-(2-chloro-4-cyanophenyl)-7-[(R)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylate as atropisomer A.
HPLC: logP=3.64
A further 0.4 g of methyl 5-chloro-6-(2-chloro-4-cyanophenyl)-7-[(R)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylate was obtained as atropisomer B.
HPLC: logP=3.74
The following compounds were obtained analogously:




methyl 5-chloro-6-(2-chloro-4-cyanophenyl)-7-[(S)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylate, atropisomer A
HPLC: logP=3.72
methyl 5-chloro-6-(2-chloro-4-cyanophenyl)-7-[(S)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylate, atropisomer B
HPLC: logP=3.74




methyl 5-chloro-6-(2-chloro-4-cyanophenyl)-7-[(S)-trifluoroisopropylamino]pyrazolo-[1,5-a]pyrimidine-3-carboxylate
HPLC: logP=3.32 atropisomer A
HPLC: logP=3.37 atropisomer B

    f)






0.35 g (0.001 mol) of atropisomer A of methyl 5-chloro-6-(2-chloro-4-cyanophenyl)-7-[(R)-3-methyl-2-butylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylate were dissolved in 4.6 ml of dioxane. 0.37 g (0.009 mol) of potassium hydroxide in 4.6 ml of aqueous solution was added at room temperature, and the reaction mixture was then stirred for 12 hours. The mixture was then poured into water and acidified with hydrochloric acid. 0.15 g of product was filtered off. The product was chromatographed on silica gel using ethyl acetate:cyclohexane:acetic acid=40:10:1, which gave the atropisomer A of 5-chloro-6-(2-chloro-4-cyanophenyl)-7-[(R)-3-methyl-2-butyl-amino]pyrazolo[1,5-a]pyrimidine-3-carboxylic acid.
HPLC: logP=2.90
Also obtained was
Example XX




the Atropisomer A of 5-chloro-6-(2-chloro-4-aminocarbonylphenyl)-7-[(R)-3-methyl-2-butyl-amino]pyrazolo[1,5-a]pyrimidine-3-carboxylic acid
HPLC: logP=1.96
The following compound was obtained analogously:
Atropisomer B of 5-chloro-6-(2-chloro-4-cyanophenyl)-7-[(R)-3-methyl-2-butylamino]-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid
HPLC: logP=2.92
Example XXI




Atropisomer A of 5-chloro-6-(2-chloro-4-cyanophenyl)-7-[(S)-3-methyl-2-butylamino]-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid
HPLC: logP=2.90
Atropisomer B of 5-chloro-6-(2-chloro-4-cyanophenyl)-7-[(S)-3-methyl-2-butylamino]-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid
HPLC: logP=2.91
Example XXII




5-chloro-6-(2-chloro-4-cyanophenyl)-7-[(S)-trifluoroisopropylamino]pyrazolo[1,5-a]pyrimidine-3-carboxylic acid
HPLC: logP=2.63 atropisomer B
Example XXIII


    a)






0.220 g (0.577 mol) of 5-chloro-6-(2-chloro-4-fluorophenyl)-N-(1,2,2-trimethylpropyl)-pyrazolo[1,5-a]pyrimidin-7-amine (which can be prepared according to processes from WO 2004 000844) was initially charged in 2 ml of DMF. At room temperature, a solution of 0.103 g (0.577 mmol) of N-bromosuccinimide was added dropwise with stirring, over a period of a few minutes. The mixture was stirred for another 30 minutes. The reaction mixture was then poured into water. The solid was subsequently filtered off with suction and dried. This gave 0.150 g (55% of theory) of 3-bromo-5-chloro-6-(2-chloro-4-fluorophenyl)-N-(1,2,2-trimethylpropyl)pyrazolo[1,5-a]pyrimidin-7-amine (content according to HPLC: 98%).
HPLC: logP=5.78

    b)






At −78° C., 0.200 g (0.435 mmol) of 3-bromo-5-chloro-6-(2-chloro-4-fluorophenyl)-N-(1,2,2-trimethylpropyl)pyrazolo[1,5-a]pyrimidin-7-amine was initially charged in 10 ml of tetrahydrofuran. At −78° C., 0.54 ml (0.869 mmol) of a 1.6 molar solution of n-butyllithium in hexane was slowly added dropwise. After 30 minutes, 0.082 g (0.478 mmol) of diethyl chlorophosphate, dissolved in 1 ml of THF, was added dropwise. After a further 30 minutes of stirring at −78° C., the mixture was poured into a mixture of 3 ml of 1 N HCl solution and 3 ml of dichloromethane. The phases were separated and the organic phase was then dried over sodium sulphate and subsequently concentrated under reduced pressure. The residue that remained was chromatographed on silica gel using cyclohexane:ethyl acetate=3:1, 1:1. This gave 0.050 g (20% of theory) of diethyl {5-chloro-6-(2-chloro-4-fluorophenyl)-7-[(1,2,2-trimethylpropyl)-amino]pyrazolo[1,5-a]pyrimidin-3-yl}phosphonate (content according to HPLC: 91%).
HPLC: logP=4.48
Example XXIV




At 100° C., 0.430 g (0.831 mmol) of diethyl {5-chloro-6-(2-chloro-4-fluorophenyl)-7-[(1,2,2-trimethylpropyl)amino]pyrazolo[1,5-a]pyrimidin-3-yl}phosphonate was stirred for 3 hours in 2 ml of a concentrated solution of hydrochloric acid (36% strength in water). The mixture was then allowed to cool to room temperature and poured into a mixture of 5 ml of water and 5 ml of ethyl acetate. The combined organic phases were dried over sodium sulphate and then concentrated under reduced pressure. The residue that remained was chromatographed on silica gel using toluene:acetone=10:1, 1:1 and then dichloromethane:methanol=9:1. This gave 0.040 g (9% of theory) of ethyl hydrogen {5-chloro-6-(2-chloro-4-fluorophenyl)-7-[(1,2,2-trimethylpropyl)-amino]pyrazolo[1,5-a]pyrimidin-3-yl}phosphonate (content according to HPLC: 85%).
HPLC: logP=3.01
Example XXV


    a)






methyl 7-(1,2-dimethylpropylamino)-5-methoxy-6-(3-methylthiophen-2-yl)pyrazolo[1,5-a]-pyrimidine-3-carboxylate
0.17 g (3 mmol) of sodium methoxide was dissolved in 10 ml of methanol, and 0.79 g (2 mmol) of methyl 7-(1,2-dimethylpropylamino)-5-chloro-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]-pyrimidine-3-carboxylate was added. The mixture was stirred at 22° C. for 16 hours. 10 ml of water were then added, the methanol was distilled off and 10 ml of dichloromethane were added to the residue. The organic phase was separated off, dried over sodium sulphate and concentrated under reduced pressure. This gave 0.35 g of methyl 7-(1,2-dimethylpropylamino)-5-methoxy-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]pyrimidine-3-carboxylate (logPs=4.60; content according to HPLC: 96%).

    b)






7-(1,2-dimethylpropylamino)-5-methoxy-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]pyrimidine-3-carboxylic acid
At room temperature, 0.2 g (0.55 mmol) of methyl 7-(1,2-dimethylpropylamino)-5-methoxy-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]pyrimidine-3-carboxylate was mixed with a mixture of 5 ml of 1,4-dioxane and 2.5 ml (2.5 mmol) of a 1 N sodium hydroxide solution. The mixture was then stirred at 22° C. for 16 hours. 5 ml of water and 3 ml of 1 N hydrochloric acid were added to the reaction mixture. The precipitate formed was filtered off, washed with water and dried. This gave 0.2 g of 7-(1,2-dimethylpropylamino)-5-methoxy-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]-pyrimidine-3-carboxylic acid (logPs=3.65; content according to HPLC: 96%).
Example XXVI


    a)






5-chloro-7-(1,2-dimethylpropylamino)-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]pyrimidine-3-carbonyl chloride
At room temperature, 6.6 g (56 mmol) of thionyl chloride were added to 10.6 g (28 mmol) of 5-chloro-7-(1,2-dimethylpropylamino)-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]pyrimidine-3-carbxylic acid in 120 ml of toluene, and the mixture was stirred under reflux for 3 hours. The reaction mixture was then concentrated under reduced pressure. This gave 11.0 g of 5-chloro-7-(1,2-dimethylpropylamino)-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]pyrimidine-3-carbonyl chloride, which was reacted directly.

    b)






5-chloro-7-(1,2-dimethylpropylamino)-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide
At room temperature, 15 ml of concentrated aqueous ammonia were added to 4.0 g (10 mmol) of 5-chloro-7-(1,2-dimethylpropylamino)-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]pyrimidine-3-carbonyl chloride in 30 ml of tetrahydrofuran. The mixture was stirred at 22° C. for 16 hours, and 50 ml of ethyl acetate were then added. The organic phase was separated off, dried over sodium sulphate and concentrated under reduced pressure. This gave 3.0 g of 5-chloro-7-(1,2-dimethyl-propylamino)-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide (logPs=3.5; content according to HPLC: 94%)

    c)






5-[5-Chloro-7-(1,2-dimethylpropylamino)-6-(3-methylthiophen-2-yl)pyrazolo[1,5-α]pyrimidin-3-yl]-[1,3,4]oxathiazol-2-one
1.5 g (4.0 mmol) of 5-chloro-7-(1,2-dimethylpropylamino)-6-(3-methylthiophen-2-yl)pyrazolo-[1,5-α]pyrimidine-3-carboxamide were dissolved in 60 ml of toluene, and 0.8 g (6.4 mmol) of chlorocarbonylsulphenyl chloride was added at 90° C. The mixture was stirred at 90° C. for 4 hours and then concentrated under reduced pressure. The residue that remained was chromatographed on silica gel using a mixture of cyclohexane:ethyl acetate=1:1. Two titrations with diisopropyl ether gave, after drying, 0.13 g of 5-[5-chloro-7-(1,2-dimethylpropylamino)-6-(3-methylthiophen-2-yl)-pyrazolo[1,5-α]pyrimidin-3-yl]-[1,3,4]oxathiazol-2-one as a crystalline solid (logPs=5.0; content according to HPLC: 94%).
Example XXVII




[5-Chloro-6-(3-methylthiophen-2-yl)-3-oxazol-2-ylpyrazolo[1,5-α]pyrimidin-7-yl](1,2-dimethyl-propyl)amine
0.95 g (2.5 mmol) of 5-chloro-7-(1,2-dimethylpropylamino)-6-(3-methylthiophen-2-yl)pyrazolo-[1,5-α]pyrimidine-3-carboxamide was dissolved in 25 ml of ethanol, and 1.0 g (6.5 mmol) of chloroacetaldehyde diethyl acetal was added. The mixture was stirred for 3 hours at 120° C. and 15 bar in a microwave oven (200 W). The reaction mixture was then concentrated under reduced pressure, and the residue that remained was chromatographed on silica gel using a mixture of cyclohexane:ethyl acetate=1:1. This gave 0.3 g of [5-chloro-6-(3-methylthiophen-2-yl)-3-oxazol-2-yl-pyrazolo[1,5-α]pyrimidin-7-yl](1,2-dimethylpropyl)amine (logPs=4.3; content according to HPLC: 98%)
Example XXVIII




0.476 g of chlorosulphonic acid in 5 ml of dichloromethane was added to 0.847 g of 5-chloro-6-(2-chloro-4-fluorophenyl)-7-(1,2,2-trimethylpropylamino)pyrazolo[1,5-a]pyrimidine, the preparation of which is described, for example, in WO 02/048151, and the mixture was then stirred at room temperature for 16 h. 0.810 g of thionyl chloride was then added, and the mixture was heated under reflux for 24 hours. After cooling to 0° C., ammonia was introduced, stirring at room temperature was continued for 72 h and the mixture was filtered off with suction. The filtrate was concentrated and purified chromatographically on silica gel using cyclohexane/ethyl acetate 3:1.
logPs: 3.65 If methylamine is introduced instead of ammonia, N-methyl-5-chloro-6-(2-chloro-4-fluorophenyl)-7-(1,2,2-trimethylpropylamino)pyrazolo[1,5-a]pyrimidine-3-sulphonamide, logPs: 4.09, is obtained correspondingly




Example XXIX
a) Thiosemicarbazone of 5-chloro-6-(2-chloro-4-fluorophenyl)-7-(1,2-dimethyl-propylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde




0.231 g of thiosemicarbazide, 18 ml of ethanol and a drop of acetic acid are added to 1 g of 5-chloro-6-(2-chloro-4-fluorophenyl)-7-(1,2-dimethylpropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde, the preparation of which is described, for example, in LeA36087, and the mixture is stirred under reflux for 15 h. After cooling, the mixture is filtered. Yellow solid.
logPs: 3.75
b) cyclization of the thiosemicarbazone




A solution of 1.625 g of iron(III) chloride in 10 ml of ethanol is added dropwise to a solution of 0.4 g of the thiosemicarbazone (prepared as above) in 50 ml of ethanol. The resulting solution is heated under reflux for 4 h. After cooling, water is added and the mixture is extracted 3 times with chloroform. The organic phases are separated off, dried and concentrated, giving a solid which is purified on silica gel using dichloromethane/ethyl acetate 5:1.
logPs: 3.57
Example XXX
Aa) 3-aminopyrazole-4-carbohydrazide




15 g of methyl 3-aminopyrazole-4-carboxylate (prepared, for example, according to J. Med. Chem. 1996, 39, 3019-3029) were introduced into 53.2 g of hydrazine hydrate, and the mixture was stirred under reflux for 24 h. The mixture was then evaporated to dryness, the residue was taken up in a little ice-water and the product was filtered off with suction. The crude product was reacted further without further purification.
Ab) N-(1-dimethylaminoethylidene)-5-amino-1H-pyrazole-4-carbohydrazide




2.914 g of the above crude product were initially charged in 10 ml of acetonitrile and heated to reflux temperature. 3.3 g of dimethylacetamide dimethyl acetal (dissolved in a little acetonitrile) were then added dropwise, and the mixture was stirred under reflux for a further 20 h. After cooling, the mixture was concentrated to half of its original volume and cooled, and the product was filtered off with suction. The product was used further without further purification.

    Ac) 4-(5-Methyl-[1,3,4]oxadiazol-2-yl)-2H-pyrazol-3-ylamine






4.43 g of the product obtained as above were dissolved in 20 ml of ethanol, and 1.1 ml of acetic acid were added. After 3 h of stirring under reflux, the mixture was concentrated and the residue that remained was titrated with a little cold water, filtered off with suction and dried. The crude product obtained was used for the subsequent steps without further purification.
Ba) 3-Ethoxy-2-(5-methyl-1H-[1,2,4]triazol-3-yl)acrylonitrile




7 g of 3-methyl-1,2,4-triazol-5-ylacetonitrile and 8.494 g of triethyl orthoformate were stirred under reflux for 5.5 h and then concentrated under reduced pressure. The resulting crude product was immediately reacted further.
Bb) 4-(5-Methyl-1H-[1,2,4]triazol-3-yl)-2H-pyrazol-3-ylamine




10 g of the crude product described above were initially charged in 40 ml of ethanol, and 2.128 g of hydrazine hydrate were added dropwise. After 15 h of stirring under reflux, the mixture was concentrated and the residue was titrated with a little ice-water, filtered off with suction and dried. The brown solid obtained was reacted further without further purification.
Ca) 3-Ethoxy-2-pyridin-2-ylacrylonitrile




5 g of pyridin-2-ylacetonitrile, 6.27 g of triethyl orthoformate and 8.64 g of acetic anhydride were stirred under reflux for 5.5 h and then concentrated under reduced pressure. The crude product obtained was directly used further.
Cb) 4-Pyridin-2-yl-2H-pyrazol-3-ylamine




3.42 g of hydrazine hydrate were added to 11.9 g of the crude product obtained above, and the mixture was stirred under reflux for 15 h. The mixture was then concentrated under reduced pressure. The product obtained in this manner was then reacted further without further purification.
D) 6-(2-Chloro-4-fluorophenyl)-3-(5-methyl-[1,3,4]oxadiazol-2-yl)pyrazolo[1,5-a]pyrimidine-5,7-diol




0.789 g of dimethyl 2-chloro-4-fluorophenylmalonate and 0.79 ml of tributyalmine were added to 0.5 g of the 4-(5-methyl-[1,3,4]oxadiazol-2-yl)-2H-pyrazol-3-ylamine obtained under Ac), and the mixture was stirred at 185° C. for 3 h. Concentration gave a glass-like substance.
logPs: 0.67
The following compounds were obtained in the same manner: (Examples XXXI, XXXII)

    
    
        from the product obtained under Bb): 6-(2-chloro-4-fluorophenyl)-3-(5-methyl-[1,3,4]triazol-2-yl)pyrazolo[1,5-a]pyrimidine-5,7-diol, logPs=0.51
    
    






    
    
         from the product obtained under Cb): 6-(2-chloro-4-fluorophenyl)-3-pyridin-2-ylpyrazolo[1,5-a]pyrimidine-5,7-diol, logPs=0.91
    
    






Example XXXIII




1.09 g of 6-(2-chloro-4-fluorophenyl)-3-(5-methyl-[1,3,4]oxadiazol-2-yl)pyrazolo[1,5-a]pyrimidine-5,7-diol were initially charged in 2.81 ml of phosphoryl chloride and stirred under reflux for 30 min and then cooled to 0° C., and 0.441 g of dimethylformamide was added carefully. Stirring was continued at room temperature for 15 h and then under reflux for another 2 h. After cooling, the mixture was poured onto ice and extracted three times with ethyl acetate. The organic phases were removed and concentrated. The crude product was converted without further purification into the end products.
The following compounds were obtained in the same manner:
Examples XXXIV, XXXV
5,7-Dichloro-6-(2-chloro-4-fluorophenyl)-3-(5-methyl-[1,3,4]triazol-2-yl)pyrazolo[1,5-a]pyrimidine




5,7-Dichloro-6-(2-chloro-4-fluorophenyl)-3-pyridin-2-ylpyrazolo[1,5-a]pyrimidine




Example XXXVI




0.36 g of the 5,7-dichloro-6-(2-chloro-4-fluorophenyl)-3-(5-methyl-[1,3,4]oxadiazol-2-yl)pyrazolo[1,5-a]pyrimidine described above was initially charged in 40 ml of acetonitrile, and 110 mg of potassium carbonate and 6 mg of 18-crown-6 were added. The mixture was stirred at room temperature for 15 min, and 0.075 g of 3-methylbutyl-2-amine, dissolved in a little acetonitrile, was added over a period of 15 min. After 20 h of stirring at room temperature, 1 ml of water was added, stirring was continued for a further 1 h and the mixture was concentrated. The residue was titrated with cold water and filtered off with suction. Silica gel chromatography using ethyl acetate gave a beige solid.
logPs: 3.94
The following compounds were obtained in the same manner:
Examples XXXVII, XXXVIII
5,7-Dichloro-6-(2-chloro-4-fluorophenyl)-3-(5-methyl-[1,3,4]triazol-2-yl)pyrazolo[1,5-a]-pyrimidine gave, after silica gel chromatography using ethyl acetate, [5-chloro-6-(2-chloro-4-fluorophenyl)-3-(5-methyl-[1,3,4]triazol-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl](1,2-dimethylpropyl)-amine, logPs: 2.91




5,7-Dichloro-6-(2-chloro-4-fluorophenyl)-3-pyridin-2-ylpyrazolol[1,5-a]pyrimidine gave, after silica gel chromatography using cyclohexane/ethyl acetate 4:1, [5-chloro-6-(2-chloro-4-fluorophenyl)-3-pyridin-2-ylpyrazolo[1,5-a]pyrimidin-7-yl](1,2-dimethylpropyl)amine, logps: 3.54




The compounds of the formula (I-a) listed in Table 1 below are/were obtained analogously to the methods described above.







TABLE 1













 














R1 or







Ex. No.
—R1+R2—
R2
R3
X
R4
log p
















1
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
CO—NH—CH3


2
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
CON(CH3)2


3
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
CO—NH-i-propyl
5.09


4
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
CO-morpholin-1-yl
3.82


5
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COOH
3.54


6
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COO-propen-3-yl
5.14


7
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COO-benzyl
5.67


8
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COO—CH2—CH2—OCH3
4.44


9
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
SO3H


10
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
SO2CH3


11
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
CO—NH—CH3


12
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
CON(CH3)2


13
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
CO—NH-i-propyl


14
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
CO-morpholin-1-yl
3.78


15
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COOH
3.48


16
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COO-propen-3-yl


17
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COO-benzyl


18
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COO—CH2—CH2—OCH3
4.37


19
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
SO3H


20
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
SO2CH3


21
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CO—NH—CH3
4.3


22
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CON(CH3)2


23
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CO—NH-i-propyl
5.28


24
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CO-morpholin-1-yl
4.09


25
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COOH
3.77


26
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COO-propen-3-yl
5.28


27
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COO-benzyl
5.78


28
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COO—CH2—CH2—OCH3
4.64


29
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
SO3H


30
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
SO2CH3


31
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
CO—NH—CH3
4.26


32
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
CON(CH3)2


33
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
CO—NH-i-propyl


34
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
CO-morpholin-1-yl
3.94


35
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
COOH
3.67


36
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
COO-propen-3-yl
5.27


37
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
COO-benzyl


38
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.59


39
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
SO3H


40
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
SO2CH3


41
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
CO—NH—CH3


42
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
CON(CH3)2


43
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
CO—NH-i-propyl


44
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
CO-morpholin-1-yl


45
(R) CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
COOH
2.53


46
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
COO-propen-3-yl


47
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
COO-benzyl


48
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
COO—CH2—CH2—OCH3


49
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
SO3H


50
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
SO2CH3


51
(S) CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
CO—NH—CH3
3.22


52
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
CON(CH3)2


53
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
CO—NH-i-propyl


54
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
CO-morpholin-1-yl


55
(S) CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
COOH
2.8


56
(S) CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
COO-propen-3-yl
4.17


57
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
COO-benzyl


58
(S) CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
COO—CH2—CH2—OCH3
3.54


59
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
SO3H


60
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
SO2CH3


61
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
CO—NH—CH3


62
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
CON(CH3)2


63
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
CO—NH-i-propyl


64
(S) CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
CO-morpholin-1-yl
3.01


65
(S) CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
COOH
2.74


66
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
COO-propen-3-yl


67
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
COO-benzyl


68
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
COO—CH2—CH2—OCH3


69
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
SO3H


70
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
SO2CH3


71
(S) CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
CO—NH—CH3
3.33


72
(S) CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
CON(CH3)2
3.96


73
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
CO—NH-i-propyl


74
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
CO-morpholin-1-yl


75
(S) CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
COOH
2.98


76
(S) CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
COO-propen-3-yl
4.31


77
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
COO-benzyl


78
(S) CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
COO—CH2—CH2—OCH3
3.72


79
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
SO3H


80
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
SO2CH3


81
(S) CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
CO—NH—CH3
3.25


82
CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
CON(CH3)2


83
CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
CO—NH-i-propyl


84
CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
CO-morpholin-1-yl


85
(S) CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
COOH
2.86


86
(S) CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
COO-propen-3-yl
4.21


87
CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
COO-benzyl


88
(S) CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
3.59


89
CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
SO3H


90
CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
SO2CH3


91
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
CO—NH—CH3


92
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
CON(CH3)2


93
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
CO—NH-i-propyl


94
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
CO-morpholin-1-yl


95
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
COOH


96
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
COO-propen-3-yl


97
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
COO-benzyl


98
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
COO—CH2—CH2—OCH3


99
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
SO3H


100
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
SO2CH3


101
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
CO—NH—CH3


102
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
CON(CH3)2


103
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
CO—NH-i-propyl
4.72


104
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
CO-morpholin-1-yl
3.49


105
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
COOH
3.24


106
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
COO-propen-3-yl
4.75


107
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
COO-benzyl
5.3


108
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
COO—CH2—CH2—OCH3
4.07


109
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
SO3H


110
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
SO2CH3


111
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
CO—NH—CH3


112
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
CON(CH3)2


113
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
CO—NH-i-propyl


114
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
CO-morpholin-1-yl
3.47


115
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
COOH
3.21


116
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
COO-propen-3-yl


117
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
COO-benzyl


118
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
COO—CH2—CH2—OCH3
4.08


119
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
SO3H


120
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
SO2CH3


121
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
CO—NH—CH3
3.95


122
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
CON(CH3)2
3.77


123
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
CO—NH-i-propyl


124
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
CO-morpholin-1-yl
3.76


125
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
COOH
3.45


126
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
COO-propen-3-yl
4.92


127
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
COO-benzyl
5.44


128
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
COO—CH2—CH2—OCH3
4.27


129
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
SO3H
2.19


130
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
SO2CH3


131
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
CO—NH—CH3
3.9


132
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
CON(CH3)2


133
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
CO—NH-i-propyl


134
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
CO-morpholin-1-yl


135
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
COOH
3.35


136
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
COO-propen-3-yl
4.89


137
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
COO-benzyl


138
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.21


139
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
SO3H


140
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
SO2CH3


141
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
CO—NH—CH3


142
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
CON(CH3)2


143
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
CO—NH-i-propyl


144
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
CO-morpholin-1-yl


145
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
COOH


146
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
COO-propen-3-yl


147
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
COO-benzyl


148
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
COO—CH2—CH2—OCH3


149
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
SO3H


150
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
SO2CH3












151
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
CO—NH—CH3


152
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
CON(CH3)2


153
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
CO—NH-i-propyl


154
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
CO-morpholin-1 -yl


155
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
COOH
3.63


156
—CH2—CH2—CH(CH3)—CH2—CH2—
2-2-Cl-6-F-phenyl
Cl
COO-propen-3-yl


157
—CH2—CH2—CH(CH3)—CH2—CH2—
2-2-Cl-6-F-phenyl
Cl
COO-benzyl


158
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
COO—CH2—CH2—OCH3
4.55


159
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
SO3H


160
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
SO2CH3


161
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
CO—NH—CH3


162
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
CON(CH3)2


163
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
CO—NH-i-propyl


164
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
CO-morpholin-1 -yl


165
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
COOH
3.54


166
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
COO-propen-3-yl


167
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
COO-benzyl


168
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
COO—CH2—CH2—OCH3
4.43


169
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
SO3H


170
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
SO2CH3


171
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
CO—NH—CH3


172
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
CON(CH3)2


173
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
CO—NH-i-propyl


174
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
CO-morpholin-1-yl


175
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
COOH
3.79


176
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
COO-propen-3-yl


177
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
COO-benzyl


178
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
COO—CH2—CH2—OCH3


179
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
SO3H
2.48


180
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
SO2CH3


181
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
Cl
CO—NH—CH3
4.1


182
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
Cl
CON(CH3)2


183
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
Cl
CO—NH-i-propyl


184
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
Cl
CO-morpholin-1-yl


185
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
Cl
COOH
3.69


186
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
Cl
COO-propen-3-yl
5.32


187
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
Cl
COO-benzyl


188
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.61


189
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
Cl
SO3H


190
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
Cl
SO2CH3


191
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
Cl
CO—NH—CH3


192
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
Cl
CON(CH3)2


193
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
Cl
CO—NH-i-propyl


194
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
Cl
CO-morpholin-1 -yl


195
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
Cl
COOH


196
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
Cl
COO-propen-3-yl


197
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
Cl
COO-benzyl


198
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
Cl
COO—CH2—CH2—OCH3


199
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
Cl
SO3H


200
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
Cl
SO2CH3













201
2-butyl
H
2,4-dichloro,5-CH3-phenyl
Cl
COOH
4


202
2-butyl
H
2,5-Cl-phenyl
Cl
COOH
3.4


203
2-butyl
H
2,5-Me-phenyl
Cl
COOH
3.52


204
2-butyl
H
2-Cl,4-methylphenyl
Cl
COO−K+


205
2-butyl
H
2-Cl,4-methylphenyl
Cl
COO−Na+


206
2-butyl
H
2-Cl,4-methylphenyl
Cl
COOH
3.41


207
2-butyl
H
2-Cl,5-Br-phenyl
Cl
COOH
3.48


208
2-butyl
H
2-Cl,5-F-phenyl
Cl
COOH
3.06


209
2-butyl
H
2-Cl,5-methoxy-phenyl
Cl
COOH
3.1


210
2-butyl
H
2-Cl-5-Me-phenyl
Cl
COOH
3.38


211
2-butyl
H
2-F,4-Cl-phenyl
Cl
COOH
3.33


212
2-butyl
H
2-F-phenyl
Cl
COOH
2.82


213
2-butyl
H
3,4-methylenedioxy-phenyl
Cl
COOH
2.69


214
C2H5
H
2,5-F-phenyl
Cl
COOH
2.25


215
(S) CH(CH3)(CF3)
H
2,4-Cl-phenyl
Cl
COOH
3.34


216
(S) CH(CH3)(CF3)
H
2,4-difluoro-,6-Cl-phenyl
Cl
CONCH3OCH3
3.3*


217
(S) CH(CH3)(CF3)
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.08*


218
(S) CH(CH3)(CF3)
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
3.68*


219
(S) CH(CH3)(CF3)
H
2,4-difluoro-,6-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
3.76*


220
(S) CH(CH3)(CF3)
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH2COOCH3
3.73*


221
(S) CH(CH3)(CF3)
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOH
2.95


222
(S) CH(CH3)(CF3)
H
2,5-F-phenyl
Cl
COOH
2.69


223
(S) CH(CH3)(CF3)
H
2,5-Me-phenyl
Cl
COOH
3.33


224
(S) CH(CH3)(CF3)
H
2-butyl
Cl
COOH
2.88


225
(S) CH(CH3)(CF3)
H
2-Cl,4-methylphenyl
Cl
COO−Na+


226
(S) CH(CH3)(CF3)
H
2-Cl,4-methylphenyl
Cl
COOH
3.2


227
(S) CH(CH3)(CF3)
H
2-Cl,5-F-phenyl
Cl
COOH
2.89


228
(S) CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
COOC2H5
4.14


229
(S) CH(CH3)(CF3)
H
2-Cl-5-Me-phenyl
Cl
COOH


230
(S) CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
COOC2H5
3.99


231
(S) CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
COOCH2CF3
4.3


232
(S) CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
COOC2H5
4.02


233
(S) CH(CH3)(CF3)
H
2-methyl-4-F-phenyl
Cl
COOH
3.03


234
(S) CH(CH3)(CF3)
H
3-Me-thien-2-yl
Cl
COOH
2.95


235
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
CONCH3OCH3
3.97*


236
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
CONHCH(CH3)COOCH3
4.54**


237
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
CONHCH2COOCH3
4.05**


238
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COO−K+


239
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COO−Na+


240
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COOCH(CH3)COOCH3
4.69*


241
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
(R)
4.25**







COOCH(CH3)CONHCH3



242
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.36*


243
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COOCH2CONCH3OCH3
4.04**


244
(R) CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COOCH2COOCH3
4.31*


245
CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
2-pyridyl
4.51


246
CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
3-Me-1,2,4-triazol-5-yl
3.92


247
CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
5-Me-oxadiazol-2-yl
4.78


248
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
CON(CH3)2
4.63**


249
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
CONCH3OCH3
4.75*


250
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
CONH(CH2)2OCH3
5.05**


251
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
CONHCH(CH3)COOCH3
5.22**


252
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
CONHCH2CN
4.7**


253
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
CONHCH2COOCH3
4.85**


254
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
CO—NH—CH3
4.51**


255
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
COO−K+


256
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
COO−Na+


257
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
COO(CH2)2O(CH2)2O(CH2)2OCH3
4.97**


258
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
COO-2-carboxymethylphenyl
5.83**


259
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
COOCH(CH3)COOCH3
5.48**


260
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
5.04**


261
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
5.22*


262
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
COOCH2CONCH3OCH3
4.76**


263
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
COOCH2COOCH3
5.1**


264
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
COOH
4.26


265
(R) CH(CH3)—C(CH3)3
H
2,4-Cl-phenyl
Cl
COOphenyl
6.12**


266
(R) CH(CH3)—C(CH3)3
H
2,4-dichloro,5-CH3-phenyl
Cl
COOH
4.67


267
(R) CH(CH3)—C(CH3)3
H
2,4-difluoro-,6-Cl-phenyl
Cl
CONCH3OCH3
4.19*


268
(R) CH(CH3)—C(CH3)3
H
2,4-difluoro-,6-Cl-phenyl
Cl
CONHCH(CH3)COOCH3
4.77**


269
(R) CH(CH3)—C(CH3)3
H
2,4-difluoro-,6-Cl-phenyl
Cl
CONHCH2COOCH3
4.29**


270
(R) CH(CH3)—C(CH3)3
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.95*


271
(R) CH(CH3)—C(CH3)3
H
2,4-difluoro-,6-Cl-phenyl
Cl
(R)
4.46**







COOCH(CH3)CONHCH3


272
(R) CH(CH3)—C(CH3)3
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.6*


273
(R) CH(CH3)—C(CH3)3
H
2,4-difluoro-,6-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.64*


274
(R) CH(CH3)—C(CH3)3
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH2CONCH3OCH3
4.27**


275
(R) CH(CH3)—C(CH3)3
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH2COOCH3
4.61*


276
(R) CH(CH3)—C(CH3)3
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOH
3.73


277
(R) CH(CH3)—C(CH3)3
H
2,4-F-phenyl
Cl
CONH(CH2)2OCH3
4.2**


278
(R) CH(CH3)—C(CH3)3
H
2,4-F-phenyl
Cl
CO—NH-morpholin-1-yl
3.76**


279
(R) CH(CH3)—C(CH3)3
H
2,4-F-phenyl
Cl
COO−Na+


280
(R) CH(CH3)—C(CH3)3
H
2,4-F-phenyl
Cl
COO−K+


281
(R) CH(CH3)—C(CH3)3
H
2,4-F-phenyl
Cl
COOH
3.55


282
(R) CH(CH3)—C(CH3)3
H
2,5-Cl-phenyl
Cl
COOH
4.06


283
(R) CH(CH3)—C(CH3)3
H
2,5-dimethylthien-3-yl
Cl
COO−Na+
4


284
(R) CH(CH3)—C(CH3)3
H
2,5-dimethylthien-3-yl
Cl
COOH
4.15


285
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
CO-morpholin-1-yl
3.69


286
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
CON(CH3)2
3.72


287
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
CONCH3OCH3
3.86


288
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
CONHC(CH3)2—C≡CH
4.99


289
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
CO—NH—CH3
3.86


290
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
CONHCHMeCH2OCH3
4.48


291
(R) OH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
COO−K+
3.36


292
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
COO−Na+
3.36


293
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
COO−NH4
3.37


294
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
COO−NH2[CH(CH3)2]2+


295
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.08


296
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
COO—CH2—CH2—OCH3
4.24


297
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
COOH
3.37


298
(R) CH(CH3)—C(CH3)3
H
2,5-F-phenyl
Cl
COO-propen-3-yl
4.88


299
(R) CH(CH3)—C(CH3)3
H
2,5-Me-phenyl
Cl
CONHOH
3.88


300
(R) CH(CH3)—C(CH3)3
H
2,5-Me-phenyl
Cl
COO−NH4+
4.18


301
(R) CH(CH3)—C(CH3)3
H
2,5-Me-phenyl
Cl
COO−K+
4.18


302
(R) CH(CH3)—C(CH3)3
H
2,5-Me-phenyl
Cl
COO−Na+
4.18


303
(R) CH(CH3)—C(CH3)3
H
2,5-Me-phenyl
Cl
COOH
4.18


304
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
CONCH3OCH3
4.4*


305
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
CONHCH(CH3)COOCH3
5.01**


306
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
CONHCH2COOCH3
4.47**


307
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COO−K+


308
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COO−Na+


309
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH(CH3)COOCH3
5.19*


310
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
(R)
4.69**







COOCH(CH3)CONHCH3


311
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.73*


312
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.88*


313
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH2COOCH3
4.79*


314
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-phenyl
Cl
COOH
3.95


315
(R) CH(CH3)—C(CH3)3
H
2,6-difluoro,4-methylphenyl
Cl
COOH
3.75**


316
CH(CH3)—C(CH3)3
H
2,6-F-phenyl
Cl
CON(CH3)2
3.66


317
CH(CH3)—C(CH3)3
H
2,6-F-phenyl
Cl
COO(CH2)2O(CH2)2O(CH2)2OCH3
4.05


318
CH(CH3)—C(CH3)3
H
2,6-F-phenyl
Cl
COOCH(CH3)COOCH3
4.58


319
CH(CH3)—C(CH3)3
H
2,6-F-phenyl
Cl
COOCH2CH2CH2CH3
5.68


320
CH(CH3)—C(CH3)3
H
2,6-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.14


321
CH(CH3)—C(CH3)3
H
2,6-F-phenyl
Cl
COO—CH2—CH2—OCH3
4.23


322
CH(CH3)—C(CH3)3
H
2,6-F-phenyl
Cl
COOCH2COOCH3
4.2


323
CH(CH3)—C(CH3)3
H
2,6-F-phenyl
Cl
COOH
3.35


324
(R) CH(CH3)—C(CH3)3
H
2-Cl,4-MeO-phenyl
Cl
COO−Na+


325
(R) CH(CH3)—C(CH3)3
H
2-Cl,4-MeO-phenyl
Cl
COOH
3.57


326
(R) CH(CH3)—C(CH3)3
H
2-Cl,4-methylphenyl
Cl
CONH(CH2)2OCH3
4.82**


327
(R) CH(CH3)—C(CH3)3
H
2-Cl,4-methylphenyl
Cl
CO—NH-morpholin-1-yl
4.41**


328
(R) CH(CH3)—C(CH3)3
H
2-C1,4-methylphenyl
Cl
COO−K+


329
(R) CH(CH3)—C(CH3)3
H
2-Cl,4-methylphenyl
Cl
COO−Na+


330
(R) CH(CH3)—C(CH3)3
H
2-Cl,4-methylphenyl
Cl
COOH
4.04


331
(S) CH(CH3)—C(CH3)3
H
2-Cl,4-methylphenyl
Cl
COOH
4.07


332
(R) CH(CH3)—C(CH3)3
H
2-Cl,5-Br-phenyl
Cl
COOH
4.15


333
(R) CH(CH3)—C(CH3)3
H
2-Cl,5-F-phenyl
Cl
COO−K+


334
(R) CH(CH3)—C(CH3)3
H
2-Cl,5-F-phenyl
Cl
COO−Na+


335
(R) CH(CH3)—C(CH3)3
H
2-Cl,5-F-phenyl
Cl
COO−NH4+


336
(R) CH(CH3)—C(CH3)3
H
2-Cl,5-F-phenyl
Cl
COO−NH2[CH(CH3)2]2+


337
(R) CH(CH3)—C(CH3)3
H
2-Cl,5-F-phenyl
Cl
COOH
3.68


338
(R) CH(CH3)—C(CH3)3
H
2-Cl,5-methoxy-phenyl
Cl
COOH
3.72


339
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
1,3,4-oxathiazol-2-on-5-yl
5.38


340
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
2-pyridyl
4.02


341
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
3-Me-1,2,4-triazol-5-yl
3.48


342
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
5-amino-thiadiazol-2-yl
3.91


343
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
5-Me-oxadiazol-2-yl
4.24


344
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
OCH2C
CCNCH2Cy3
6.26


345
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONCH3OCH3
4.27


346
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONH(CH2)2OCH3
4.45


347
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONH(CH2)2OCO(CH3)
4.39**


348
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONHC(CH3)2—C≡CH
5.44


349
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONHC(CH3)2CN
5.02


350
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONH—CH(CH3)CONHCH_S
3.75


351
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONHCH(CH3)COOCH3
4.8


352
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONHCH2CH2OH
3.53**


353
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONHCH2CN
4.24


354
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONHCH2COOCH3
4.34


355
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONHCHMeCH2OCH3
4.9


356
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONHOH
3.51**


357
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COO−K+


358
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COO(CH2)2O(CH2)2O(CH2)2OCH3
4.53


359
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COOC2H5
5.15


360
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COOC2H5
5.63


361
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COOCH(CH3)COOCH3
5.01


362
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
(R)
4.47







COOCH(CH3)CONHCH3


363
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.57


364
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COOCH2CONCH3OCH3
4.28


365
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COOCH2COOCH3
4.59


366
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
dioxazin-3-yl
4.43


367
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
O-i-propyl
N(C≡N)CH(CH3)2
6.35


368
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
-n-butoxy
N(C≡N)CH2CH2CH2CH3
7.11


369
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
-O-n-propyl
N(C≡N)CH2CH2CH3
6.46


370
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
—O—C2H5
N(C≡N)Et
5.71


371
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
—NH2


372
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
oxadiazin-3-yl
4.9


373
(R) CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
oxazol-2-yl
4.72


374
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
PO(OEt)2
4.48**


375
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
PO(OH)OEt
3.01**


376
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
SO2NCH(CH3)2
4.73


377
(R) CH(CH3)—C(CH3)3
H
2-Cl-5-Me-phenyl
Cl
COOH
4.05


378
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
CONCH3OCH3
4.02*


379
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
CONHCH(CH3)COOCH3
4.59**


380
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
CONHCH2COOCH3
4.11**


381
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COOC2H5
4.99


382
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COOCH(CH3)COOCH3
4.87*


383
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
(R)
4.34**







COOCH(CH3)CONHCH3


384
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.41*


385
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COOCH2COOCH3
4.46*


386
(R) CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COO-i-propyl
5.45


387
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
CONCH3OCH3
4.14*


388
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
CONHCH(CH3)COOCH3
4.64**


389
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
CONHCH2COOCH3
4.25**


390
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
COOC2H5
5.11


391
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.92*


392
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
COOCH2CF3
5.37


393
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.51*


394
(R) CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
COOCH2COOCH3
4.53*


395
(R) CH(CH3)—C(CH3)3
H
2-F,4-Cl-phenyl
Cl
COO−K+


396
(R) CH(CH3)—C(CH3)3
H
2-F,4-Cl-phenyl
Cl
COO−Na+


397
(R) CH(CH3)—C(CH3)3
H
2-F,4-Cl-phenyl
Cl
COO−NH4+


398
(R) CH(CH3)—C(CH3)3
H
2-F,4-Cl-phenyl
Cl
COO−NH2[CH(CH3)2]2+


399
(R) CH(CH3)—C(CH3)3
H
2-F,4-Cl-phenyl
Cl
COOH
3.93


400
(R) CH(CH3)—C(CH3)3
H
2-F-phenyl
Cl
COOH
3.43


401
CH(CH3)—C(CH3)3
H
2-Me-phenyl
Cl
CONH(CH2)2OCH3
4.5


402
CH(CH3)—C(CH3)3
H
2-Me-phenyl
Cl
COOCH(CH3)COOCH3
5.04


403
CH(CH3)—C(CH3)3
H
2-Me-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.59


404
CH(CH3)—C(CH3)3
H
2-Me-phenyl
Cl
COO—CH2—CH2—OCH3
4.67


405
CH(CH3)—C(CH3)3
H
2-Me-phenyl
Cl
COOCH2COOCH3
4.64


406
CH(CH3)—C(CH3)3
H
2-Me-phenyl
Cl
COOH
3.83


407
(R) CH(CH3)—C(CH3)3
H
3,4-methylenedioxy-phenyl
Cl
COOH
3.22


408
(R) CH(CH3)—C(CH3)3
H
3-Cl-thien-2-yl
Cl
COO−Na+


409
(R) CH(CH3)—C(CH3)3
H
3-Cl-thien-2-yl
Cl
COOH
3.62


410
(R) CH(CH3)—C(CH3)3
H
3-Me-thien-2-yl
Cl
COOH
3.68


411
CH(CH3)—C(CH3)3
H
4-chlorobenzyl
Cl
COOC2H5


412
(S) CH(CH3)—C(CH3)3
H
4-chlorobenzyl
Cl
COOC2H5


413
(R) CH(CH3)—C(CH3)3
H
4-chlorobenzyl
Cl
COOC2H5


414
CH(CH3)—C(CH3)3
H
4-chlorobenzyl
Cl
COOH


415
(S) CH(CH3)—C(CH3)3
H
4-chlorobenzyl
Cl
COOH


416
(R) CH(CH3)—C(CH3)3
H
4-chlorobenzyl
Cl
COOH


417
(R) CH(CH3)—C(CH3)3
H
5-F-pyrimidin-4-yl
Cl
COOH
2.35


418
CH(CH3)—C(CH3)3
H
phenyl
Cl
3-Me-1,2,4-triazol-5-yl
3.25


419
CH(CH3)—C(CH3)3
H
phenyl
Cl
5-Me-oxadiazyl-2-yl
4.03


420
CH(CH3)—C(CH3)3
H
phenyl
Cl
COOH
3.6


421
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
CONCH3OCH3
3.67


422
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
CONHCH(CH3)COOCH3
4.22**


423
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
CONHCH2COOCH3
3.76**


424
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
COO−K+


425
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
COO−Na+


426
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
COOCH(CH3)COOCH3
4.39


427
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
(R)
3.9**







COOCH(CH3)CONHCH3


428
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
COOCH2CH2OCH2CH2OCH3
3.96


429
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
COOCH2CONCH3OCH3
3.73**


430
(R) CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
COOCH2COOCH3
4.05*


431
CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
2-pyridyl
4.02


432
CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
3-Me-1,2,4-triazol-5-yl
3.6


433
CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
5-Me-oxadiazyl-2-yl
4.42


434
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
CON(CH3)2
4.3**


435
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
CONCH3OCH3
4.38*


436
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
CONH(CH2)2OCH3
4.7**


437
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
CONHCH(CH3)COOCH3
5.15**


438
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
CONHCH2CN
4.38**


439
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
CONHCH2COOCH3
4.52**


440
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
CO—NH—CH3
4.52**


441
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
COO−Na+


442
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
COO−NH2[CH(CH3)2]2+


443
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
COO(CH2)2O(CH2)2O(CH2)2OCH3
4.62**


444
CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
COOC2H5
5.71


445
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
COOCH(CH3)COOCH3
5.15*


446
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
(R)
4.62**







COOCH(CH3)CONHCH3


447
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.89*


448
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.78*


449
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
COOCH2CONCH3OCH3
4.43**


450
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
COOCH2COOCH3
4.77*


451
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
COOH
3.93


452
(R) CH(CH3)—CH(CH3)2
H
2,4-Cl-phenyl
Cl
COOphenyl
5.75**


453
(R) CH(CH3)—CH(CH3)2
H
2,4-dichloro,5-CH3-phenyl
Cl
COOH
4.32


454
(R) CH(CH3)—CH(CH3)2
H
2,4-difluoro-,6-Cl-phenyl
Cl
CONCH3OCH3
3.86*


455
(R) CH(CH3)—CH(CH3)2
H
2,4-difluoro-,6-Cl-phenyl
Cl
CONHCH(CH3)COOCH3
4.48**


456
(R) CH(CH3)—CH(CH3)2
H
2,4-difluoro-,6-Cl-phenyl
Cl
CONHCH2COOCH3
4.01**


457
(R) CH(CH3)—CH(CH3)2
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.64*


458
(R) CH(CH3)—CH(CH3)2
H
2,4-difluoro-,6-Cl-phenyl
Cl
(R)
4.12**







COOCH(CH3)CONHCH3


459
(R) CH(CH3)—CH(CH3)2
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.22*


460
(R) CH(CH3)—CH(CH3)2
H
2,4-difluoro-,6-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.31*


461
(R) CH(CH3)—CH(CH3)2
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH2CONCH3OCH3
3.96**


462
(R) CH(CH3)—CH(CH3)2
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH2COOCH3
4.26*


463
(R) CH(CH3)—CH(CH3)2
H
2,4-difluoro-,6-Cl-phenyl
Cl
COOH
3.46


464
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
CON(CH3)2
3.55**


465
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
CONH(CH2)2OCH3
3.85**


466
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
CONHCH(CH3)CH2OH
3.41**


467
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
CONH—CH(CH3)CONHCH_S
3.29**


468
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
CONHCH(CH3)COOCH3
4.26**


469
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
CONHCH2CN
3.68**


470
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
CO—NH—CH3
3.68**


471
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
CO—NH-morpholin-1-yl
3.46**


472
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COO−Na+


473
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COO−K+


474
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COO(CH2)2O-(4-
4.84**







carboxymethylphenyl)


475
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COO(CH2)2O(CH2)2O(CH2)2OCH3
3.89**


476
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COO-2-
4.74**







carboxymethylphenyl


477
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COOC2H5
4.47**


478
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COOCH(CH2OCH3)2
4.22**


479
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COOCH(CH3)COOCH3
4.37


480
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
(R)
3.91**







COOCH(CH3)CONHCH3


481
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COOCH2—C≡CH
4.23**


482
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COOCH2CF3
4.79**


483
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COO—CH2—CH2—OCH3
4


484
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COOCH2CONCH3OCH3
3.71**


485
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COOCH2COOCH3
4**


486
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COOH
3.28


487
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COO-i-propyl
4.89**


488
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COOphenyl
4.98**


489
(R) CH(CH3)—CH(CH3)2
H
2,5-Cl-phenyl
Cl
COOH
3.72


490
(R) CH(CH3)—CH(CH3)2
H
2,5-dimethylthien-3-yl
Cl
COO−Na+


491
(R) CH(CH3)—CH(CH3)2
H
2,5-dimethylthien-3-yl
Cl
COO−K+


492
(R) CH(CH3)—CH(CH3)2
H
2,5-dimethylthien-3-yl
Cl
COOH
3.82


493
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
CO-morpholin-1-yl
3.39


494
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
CON(CH3)2
3.43


495
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
CONHCHMeCH2OCH3
4.19


496
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
CONHOH


497
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
COO−K+
3.06


498
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
COO−Na+
3.06


499
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
COO−NH4+
3.06


500
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
COO−NH2[CH(CH3)2]2+


501
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
COOC2H5
4.37


502
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
COOCH(CH3)COOCH3
4.29


503
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
3.84


504
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
COO—CH2—CH2—OCH3
3.91


505
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
COOH
3.06


506
(R) CH(CH3)—CH(CH3)2
H
2,5-F-phenyl
Cl
COO-propen-3-yl
4.53


507
(R) CH(CH3)—CH(CH3)2
H
2,5-Me-phenyl
Cl
CONHOH
3.55


508
(R) CH(CH3)—CH(CH3)2
H
2,5-Me-phenyl
Cl
COO−K+
3.85


509
(R) CH(CH3)—CH(CH3)2
H
2,5-Me-phenyl
Cl
COO−NH4+
3.85


510
(R) CH(CH3)—CH(CH3)2
H
2,5-Me-phenyl
Cl
COO−Na+
3.85


511
(R) CH(CH3)—CH(CH3)2
H
2,5-Me-phenyl
Cl
COOH
3.85


512
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
CONCH3OCH3
4.1*


513
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
CONHCH(CH3)COOCH3
4.68**


514
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
CONHCH2COOCH3
4.17**


515
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
COO−K+


516
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
COO−Na+


517
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.77*


518
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
(R)
4.34**







COOCH(CH3)CONHCH3


519
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.37*


520
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.44*


521
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH2CONCH3OCH3
4.1**


522
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH2COOCH3
4.39*


523
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-Cl-phenyl
Cl
COOH
3.61


524
(R) CH(CH3)—CH(CH3)2
H
2,6-difluoro,4-
Cl
COOH
3.43**





methylphenyl


525
CH(CH3)—CH(CH3)2
H
2,6-F-phenyl
Cl
COOH
3.08


526
(R) CH(CH3)—CH(CH3)2
H
2-butyl
Cl
COOH
3.54


527
(S) CH(CH3)—CH(CH3)2
H
2-butyl
Cl
COOH
3.52


528
(R) CH(CH3)—CH(CH3)2
H
2-Cl,4-MeO-phenyl
Cl
COO−Na+


529
(R) CH(CH3)—CH(CH3)2
H
2-Cl,4-MeO-phenyl
Cl
COOH
3.31


530
(R) CH(CH3)—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COO−K+


531
(R) CH(CH3)—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COO−Na+


532
(R) CH(CH3)—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.51


533
(R) CH(CH3)—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COO—CH2—CH2—OCH3
4.59


534
(R) CH(CH3)—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COOH
3.72


535
(R) CH(CH3)—CH(CH3)2
H
2-Cl,5-Br-phenyl
Cl
COOH
3.82


536
(R) CH(CH3)—CH(CH3)2
H
2-Cl,5-F-phenyl
Cl
COOH
3.36


537
(R) CH(CH3)—CH(CH3)2
H
2-Cl,5-methoxy-phenyl
Cl
COOH
3.4


538
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
2-pyridyl
3.54


539
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
3-Me-1,2,4-triazol-5-yl
3.23


540
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
5-amino-thiadiazol-2-yl
3.57


541
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
5-Me-oxadiazyl-2-yl
3.94


542
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
OCH2Cy3
CCNCH2Cy3
5.95


543
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
CONCH3OCH3
3.95


544
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
CONHCH(CH3)COOCH3
4.41**


545
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
CONHCH2COOCH3
4.05**


546
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
COOC2H5
4.75


547
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
COOC2H5
5.23


548
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
COOCH(CH3)COOCH3
4.65


549
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
(R)
4.13**







COOCH(CH3)CONHCH3


550
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
COOCH2CF3
5.01


551
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.24


552
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
COOCH2CONCH3OCH3
3.99**


553
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
O-i-propyl
N(C≡N)CH(CH3)2
6.02


554
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
-n-butoxy
N(C≡N)CH2CH2CH2CH3
6.83


555
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
-O-n-propyl
N(C≡N)CH2CH2CH3
6.12


556
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
OCH2Cybutyl
N(C≡N)CH2Cybutyl
7.16


557
(R) CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
—O—C2H5
N(C≡N)Et
5.38


558
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
—NO2
4.28


559
(R) CH(CH3)—CH(CH3)2
H
2-Cl-5-Me-phenyl
Cl
COOH
3.71


560
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
CONCH3OCH3
3.66*


561
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
COOC2H5
4.58


562
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
COOCH(CH3)COOCH3
4.46*


563
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.03*


564
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
COOCH2COOCH3
4.08*


565
(R) CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
COO-i-propyl
5.03


566
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
CONCH3OCH3
3.77*


567
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
CONH(CH2)2CH3
4.78


568
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
CONHCH(CH3)COOCH3
4.49**


569
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
CONHCH2COOCH3
3.92**


570
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
COOC2H5
4.71


571
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.56*


572
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
(R)
4.17**







COOCH(CH3)CONHCH3


573
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
COOCH2CF3
5.01


574
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.13*


575
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
COOCH2CONCH3OCH3
3.88**


576
(R) CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
COOCH2COOCH3
4.18*


577
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
—NH2
2.54


578
(R) CH(CH3)—CH(CH3)2
H
2-F,4-Cl-phenyl
Cl
COOH
3.64


579
(R) CH(CH3)—CH(CH3)2
H
2-F-phenyl
Cl
COO−Na+


580
(R) CH(CH3)—CH(CH3)2
H
2-F-phenyl
Cl
COOH
3.13


581
(R) CH(CH3)—CH(CH3)2
H
2-Me-cyclopentyl
Cl
COOH
3.93


582
CH(CH3)—CH(CH3)2
H
2-Me-phenyl
Cl
COOC2H5
3.8


583
CH(CH3)—CH(CH3)2
H
2-Me-phenyl
Cl
COO—CH2—CH2—OCH3
4.32


584
CH(CH3)—CH(CH3)2
H
2-Me-phenyl
Cl
COOH
3.53


585
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
CONH-2-pyrimidinyl
6.61


586
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
CONHCH2COOEt
4.3


587
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO−Na+
1.78


588
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO−K+
1.78


589
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO−NH(CH2CH3)3+
1.77


590
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)2C(CH3)3
6.18


591
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)2—C≡CH
4.6


592
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)2CF3
4.95


593
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)2CH(CH3)2
5.91


594
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)2CH2Br
5.18


595
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)2CH2Cl
5.04


596
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)2CH2F
4.64


597
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)2CHCH2
5.18


598
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)2OC(CH3)3
5.19


599
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)2OCH2?
4.57


600
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)3OCH3
4.6


601
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)4CH3
5.96


602
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)5CH3
6.37


603
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO(CH2)9CH3
7.36


604
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO-2-carboxymethylphenyl
4.94


605
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO-4-iPrPh
6.12


606
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOC(CH3)2—C≡CH
4.81


607
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOC(CH3)2CH2OCH3
5.21


608
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOC2H5
4.69


609
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH(CH3)C(CH3)3
6.24


610
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH(CH3)CF3
5.35


611
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH(CH3)CH(CH3)2
5.91


612
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH(CH3)CH2CH3
5.53


613
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH(CH3)CH2CHCH2
5.56


614
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH(CH3)CH2OCH3
4.66


615
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH(CH3)cyclohexyl
6.87


616
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH(Et)-4-MePh
6.53


617
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH2C(CH3)3
5.56


618
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH2—C≡CH
5.17


619
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH2CF3
4.98


620
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH2CH2Br
4.87


621
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH2CH2CH2CH3
5.55


622
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH2CH2CH3
5.15


623
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO—CH2—CH2—OCH3
4.21


624
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH2CHCHCH3
4.42


625
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH2Cl
4.72


626
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH2F
4.32


627
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCH(CH3)CH═CH2
5.25


628
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOCyhexyl
6.05


629
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOH
3.45


630
(S) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOH
3.45


631
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COO-i-propyl
5.11


632
(R) CH(CH3)—CH(CH3)2
H
2-methyl-4-F-phenyl
Cl
COOphenyl
5.2


633
CH(CH3)—CH(CH3)2
H
2-methyl-5-(4-Cl)-phenyl
Cl
COOH
4.92


634
(R) CH(CH3)—CH(CH3)2
H
3,4-methylendioxy-phenyl
Cl
COOH
2.96


635
(R) CH(CH3)—CH(CH3)2
H
3-Cl-thien-2-yl
Cl
COO−Na+


636
(R) CH(CH3)—CH(CH3)2
H
3-Cl-thien-2-yl
Cl
COOH
3.3


637
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
1,3,4-oxathiazol-2-on-5-yl
4.98


638
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
CON(CH3)COCHNH2CH3
3.41**


639
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
CONH(CH2)2OCH3
4.1**


640
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
CONH2
3.49


641
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
CONHCH(CH3)COOCH3
4.46**


642
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
CO—NH-morpholin-1-yl
3.63**


643
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
COO−K+


644
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
COO−Na+


645
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
—O—CH3
COO−Na+


646
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
COOCH(CH3)COOCH3
4.6


647
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
COOCH2CH2OCH2CH2OCH3
4.11


648
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
COO—CH2—CH2—OCH3
4.17


649
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
—O—CH3
COOH
3.65


650
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
oxazol-2-yl
4.27


651
(R) CH(CH3)—CH(CH3)2
H
5-F-pyrimidin-4-yl
Cl
COOH
2.06


652
(R) CH(CH3)—CH(CH3)2
H
cyclopentyl
Cl
COOH
3.7


653
(S) CH(CH3)—CH(CH3)2
H
cyclopentyl
Cl
COOH
3.7


654
CH(CH3)—CH(CH3)2
H
phenyl
Cl
2-pyridyl
3.03


655
CH(CH3)—CH(CH3)2
H
phenyl
Cl
3-Me-1,2,4-triazol-5-yl
2.91


656
CH(CH3)—CH(CH3)2
H
phenyl
Cl
5-Me-oxadiazol-2-yl
3.7


657
CH(CH3)—CH(CH3)2
H
phenyl
Cl
COOC2H5
4.98


658
CH(CH3)—CH(CH3)2
H
phenyl
Cl
COOCH(CH3)COOEt
4.76


659
CH(CH3)—CH(CH3)2
H
phenyl
Cl
COO—CH2—CH2—OCH3
6.61


660
CH(CH3)—CH(CH3)2
H
phenyl
Cl
COOH
3.29


661
CH(CH3)—CH2—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COOH
4.12


662
CH(CH3)—CH2—CH(CH3)2
H
3-Me-thien-2-yl
Cl
COOH
3.75


663
CH2—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
CONCH3OCH3
3.8*


664
CH2—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COO−K+


665
CH2—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COO−Na+


666
CH2—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COOCH(CH3)COOCH3
4.45*


667
CH2—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.04*


668
CH2—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COO—CH2—CH2—OCH3
4.12*


669
CH2—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COOCH2COOCH3
4.44*


670
CH2—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
COOH
3.31


671
CH2—C(CH3)3
H
2,4-Cl-phenyl
Cl
CONCH3OCH3
4.51*


672
CH2—C(CH3)3
H
2,4-Cl-phenyl
Cl
COO−K


673
CH2—C(CH3)3
H
2,4-Cl-phenyl
Cl
COO−Na+


674
CH2—C(CH3)3
H
2,4-Cl-phenyl
Cl
COOCH(CH3)COOCH3
5.27*


675
CH2—C(CH3)3
H
2,4-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.82*


676
CH2—C(CH3)3
H
2,4-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.9*


677
CH2—C(CH3)3
H
2,4-Cl-phenyl
Cl
COOCH2COOCH3
4.88*


678
CH2—C(CH3)3
H
2,4-Cl-phenyl
Cl
COOH
4.05


679
CH2—C(CH3)3
H
2,4-F-phenyl
Cl
COO−K+


680
CH2—C(CH3)3
H
2,4-F-phenyl
Cl
COO−Na+


681
CH2—C(CH3)3
H
2,4-F-phenyl
Cl
COOH
3.33


682
CH2—C(CH3)3
H
2,5-Me-phenyl
Cl
COOH
3.9


683
CH2—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
CONCH3OCH3
4.21*


684
CH2—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COO−K+


685
CH2—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COO−Na+


686
CH2—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.85*


687
CH2—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.45*


688
CH2—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.96*


689
CH2—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH2COOCH3
4.46*


690
CH2—C(CH3)3
H
2,6-difluoro,4-Cl-phenyl
Cl
COOH
3.71


691
CH2—C(CH3)3
H
2-Cl,4-methylphenyl
Cl
COO−Na


692
CH2—C(CH3)3
H
2-Cl,4-methylphenyl
Cl
COOH
3.84


693
CH2—C(CH3)3
H
2-Cl,5-F-phenyl
Cl
COOH
3.53


694
CH2—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
CONCH3OCH3
4.03*


695
CH2—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COO−K+


696
CH2—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COO−Na+


697
CH2—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COOCH(CH3)COOCH3
4.77*


698
CH2—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.41*


699
CH2—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COO—CH2—CH2—OCH3
4.46*


700
CH2—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COOCH2COOCH3
4.42*


701
CH2—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
COOH
3.61


702
CH2—C(CH3)3
H
2-Cl-5-Me-phenyl
Cl
COOH
3.8


703
CH2—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
CONCH3OCH3
3.9*


704
CH2—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COOCH(CH3)COOCH3
4.59*


705
CH2—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.16*


706
CH2—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COO—CH2—CH2—OCH3
4.25*


707
CH2—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COOCH2COOCH3
4.2*


708
CH2—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
COOH
3.39


709
CH2—C(CH3)3
H
2-Cl-phenyl
Cl
CONCH3OCH3
3.89*


710
CH2—C(CH3)3
H
2-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.69*


711
CH2—C(CH3)3
H
2-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.25*


712
CH2—C(CH3)3
H
2-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.37*


713
CH2—C(CH3)3
H
2-Cl-phenyl
Cl
COOCH2COOCH3
4.24*


714
CH2—C(CH3)3
H
2-Cl-phenyl
Cl
COOH
3.5


715
CH2—C(CH3)3
H
2-F,4-Cl-phenyl
Cl
COOH
3.69


716
CH2—C(CH3)3
H
3-Me-thien-2-yl
Cl
COOH
3.47


717
CH2—CH2—CH(CH3)2
H
2,4-F-phenyl
Cl
COO−K+


718
CH2—CH2—CH(CH3)2
H
2,4-F-phenyl
Cl
COO−Na+


719
CH2—CH2—CH(CH3)2
H
2,4-F-phenyl
Cl
COOH
3.29


720
CH2—CH2—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COO−Na+


721
CH2—CH2—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COO−K+


722
CH2—CH2—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COOH
3.81


723
CH2—CH2—CH(CH3)2
H
3-Me-thien-2-yl
Cl
COOH
3.47












724
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
CONCH3OCH3
3.99*


725
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
COOCH(CH3)COOCH3
4.76*


726
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.36*


727
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
Cl
COOCH2COOCH3
4.41*


728
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-Cl-phenyl
Cl
2-pyridyl
4.34


729
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-Cl-phenyl
Cl
3-Me-1,2,4-triazol-5-yl
3.91


730
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-Cl-phenyl
Cl
5-Me-oxadiazol-2-yl
4.82


731
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-Cl-phenyl
Cl
COOC2H5
6.31


732
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-difluoro-,6-Cl-phenyl
Cl
CONCH3OCH3
4.26*


733
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH(CH3)COOCH3
5.04*


734
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.63*


735
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-difluoro-,6-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.73*


736
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-difluoro-,6-Cl-phenyl
Cl
COOCH2COOCH3
4.64*


737
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-difluoro-,6-Cl-phenyl
Cl
COOH
3.77


738
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-F-phenyl
Cl
COO−Na+


739
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-F-phenyl
Cl
COOH
3.56


740
—CH2—CH2—CH(CH3)—CH2—CH2—
2,5-dimethylthien-3-yl
Cl
COOH
4.15


741
—CH2—CH2—CH(CH3)—CH2—CH2—
2,5-F-phenyl
Cl
COOH
3.48


742
—CH2—CH2—CH(CH3)—CH2—CH2—
2,5-Me-phenyl
Cl
COOH
4.1


743
—CH2—CH2—CH(CH3)—CH2—CH2—
2,6-F-phenyl
Cl
COOCH(CH3)COOCH3
4.63


744
—CH2—CH2—CH(CH3)—CH2—CH2—
2,6-F-phenyl
Cl
COO—CH2—CH2—OCH3
4.27


745
—CH2—CH2—CH(CH3)—CH2—CH2—
2,6-F-phenyl
Cl
COOCH2COOCH3
4.24


746
—CH2—CH2—CH(CH3)—CH2—CH2—
2,6-F-phenyl
Cl
COOH
3.39


747
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl,4-MeO-phenyl
Cl
COO−K+


748
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl,4-MeO-phenyl
Cl
COO−Na+


749
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl,4-MeO-phenyl
Cl
COOH
3.6


750
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl,4-methylphenyl
Cl
COO−Na+


751
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl,4-methylphenyl
Cl
COOH
4.12


752
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl,4-methylphenyl
—OH
COOH


753
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl,5-F-phenyl
Cl
COOH
3.71


754
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
2-pyridyl
3.8


755
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
3-Me-1,2,4-triazol-5-yl
3.49


756
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
5-amino-thiadiazol-2-yl


757
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
5-Me-oxadiazyl-2-yl
4.35


758
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
COOC2H5
5.78


759
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
—NO2
4.69


760
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
SO2OCH2CH2OCH2CH2OMe
4.56


761
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
SO2OEt
4.86


762
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
SO2OiPr
5.09


763
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
SO3—NH4+
2.26


764
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-5-Me-phenyl
Cl
COOH
4.06


765
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
CONCH3OCH3
4.08*


766
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
COOCH(CH3)COOCH3
4.89*


767
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.45*


768
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
Cl
COOCH2COOCH3
4.48*


769
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
Cl
COOC2H5
5.15


770
—CH2—CH2—CH(CH3)—CH2—CH2—
2-F-phenyl
Cl
COOH
3.45


771
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Me-phenyl
Cl
CONH(CH2)2OCH3
4.33


772
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Me-phenyl
Cl
COOCH(CH3)COOCH3
4.98


773
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Me-phenyl
Cl
COO—CH2—CH2—OCH3
4.6


774
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Me-phenyl
Cl
COOH
3.76


775
—CH2—CH2—CH(CH3)—CH2—CH2—
3-Me-thien-2-yl
Cl
COOH
3.62


776
—CH2—CH2—CH(CH3)—CH2—CH2—
phenyl
Cl
3-Me-1,2,4-triazol-5-yl
3.15


777
—CH2—CH2—CH(CH3)—CH2—CH2—
phenyl
Cl
5-Me-oxadiazol-2-yl
4.01


778
—CH2—CH2—CH(CH3)—CH2—CH2—
phenyl
Cl
COOC2H5
5.45


779
—CH2—CH2—CH(CH3)—CH2—CH2—
phenyl
Cl
COOH
3.56


780
—CH2—CH2—CH2—CH(CH3)—
2,4-Cl-phenyl
Cl
2-pyridyl
3.57


781
—CH2—CH2—CH2—CH(CH3)—
2,4-Cl-phenyl
Cl
5-Me-oxadiazol-2-yl
4.2


782
—CH2—CH2—CH2—CH(CH3)—
2,6-F-phenyl
Cl
COOH
2.91


783
—CH2—CH2—CH2—CH(CH3)—
2-Cl,4-methylphenyl
Cl
COO−K+


784
—CH2—CH2—CH2—CH(CH3)—
2-Cl,4-methylphenyl
Cl
COO−Na+


785
—CH2—CH2—CH2—CH(CH3)—
2-Cl,4-methylphenyl
Cl
COOH
3.59


786
—CH2—CH2—CH2—CH(CH3)—
2-Cl,5-Br-phenyl
Cl
COOH
3.59


787
—CH2—CH2—CH2—CH(CH3)—
2-Cl,5-methoxy-phenyl
Cl
COOH
3.21


788
—CH2—CH2—CH2—CH(CH3)—
2-Cl-4-F-phenyl
Cl
2-pyridyl
3.15


789
—CH2—CH2—CH2—CH(CH3)—
2-Cl-4-F-phenyl
Cl
3-Me-1,2,4-triazol-5-yl
2.9


790
—CH2—CH2—CH2—CH(CH3)—
2-Cl-4-F-phenyl
Cl
5-Me-oxadiazol-2-yl
3.77


791
—CH2—CH2—CH2—CH(CH3)—
2-Cl-4-F-phenyl
Cl
COOC2H5
5.08


792
—CH2—CH2—CH2—CH(CH3)—
2-Cl-4-F-phenyl
Cl
SO3H
2.01


793
—CH2—CH2—CH2—CH(CH3)—
2-F-phenyl
Cl
COOH
2.93


794
—CH2—CH2—CH2—CH(CH3)—
2-Me-phenyl
Cl
COOH
3.2


795
—CH2—CH2—CH2—CH(CH3)—
phenyl
Cl
5-Me-oxadiazol-2-yl
3.42


796
—CH2—CH2—CH2—CH(CH3)—
phenyl
Cl
COOC2H5
4.7


797
—CH2—CH2—O—CH2—CH2—
2-Cl,5-NO2-phenyl
Cl
—NO2
2.91













798
CH3
H
2,5-F-phenyl
Cl
COOH
2.05


799
CH3
H
2-methyl-4-F-phenyl
Cl
COOH
2.22


800
cyclopentyl
H
2-Cl,4-methylphenyl
Cl
COO−Na+


801
cyclopentyl
H
2-Cl,4-methylphenyl
Cl
COOH
3.59


802
cyclopentyl
H
2-F-phenyl
Cl
COOH
2.98


803
cyclopropylmethyl
H
2,4-F-phenyl
Cl
COOH
2.77


804
cyclopropylmethyl
H
2-Cl,4-methylphenyl
Cl
COOH
3.18


805
cyclopropylmethyl
H
3-Me-thien-2-yl
Cl
COOH
2.83


806
H
H
2-Cl-4-F-phenyl
Cl
SO2NH2
1.89


807
i-butyl
H
2,4,6-trifluorophenyl
Cl
CONCH3OCH3
3.31*


808
i-butyl
H
2,4,6-trifluorophenyl
Cl
COO−K+


809
i-butyl
H
2,4,6-trifluorophenyl
Cl
COO−Na+


810
i-butyl
H
2,4,6-trifluorophenyl
Cl
COOCH(CH3)COOCH3
4.1*


811
i-butyl
H
2,4,6-trifluorophenyl
Cl
COOCH2CH2OCH2CH2OCH3
3.64*


812
i-butyl
H
2,4,6-trifluorophenyl
Cl
COO—CH2—CH2—OCH3
3.7*


813
i-butyl
H
2,4,6-trifluorophenyl
Cl
COOCH2COOCH3
3.69*


814
i-butyl
H
2,4,6-trifluorophenyl
Cl
COOH
2.97


815
i-butyl
H
2,4-Cl-phenyl
Cl
CONCH3OCH3
4.04*


816
i-butyl
H
2,4-Cl-phenyl
Cl
COO−K+


817
i-butyl
H
2,4-Cl-phenyl
Cl
COO−Na+


818
i-butyl
H
2,4-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.77*


819
i-butyl
H
2,4-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.37*


820
i-butyl
H
2,4-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.47*


821
i-butyl
H
2,4-Cl-phenyl
Cl
COOCH2COOCH3
4.45*


822
i-butyl
H
2,4-Cl-phenyl
Cl
COOH
3.65


823
i-butyl
H
2,4-F-phenyl
Cl
COOH
2.97


824
i-butyl
H
2,6-difluoro,4-Cl-phenyl
Cl
CONCH3OCH3
3.78*


825
i-butyl
H
2,6-difluoro,4-Cl-phenyl
Cl
COO−K+


826
i-butyl
H
2,6-difluoro,4-Cl-phenyl
Cl
COO−Na+


827
i-butyl
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.43*


828
i-butyl
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
4.03*


829
i-butyl
H
2,6-difluoro,4-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.1*


830
i-butyl
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH2COOCH3
4.44*


831
i-butyl
H
2,6-difluoro,4-Cl-phenyl
Cl
COCH
3.35


832
i-butyl
H
2-Cl,4-methylphenyl
Cl
COO−Na+


833
i-butyl
H
2-Cl,4-methylphenyl
Cl
COOH
3.44


834
i-butyl
H
2-Cl-4-F-phenyl
Cl
CONCH3OCH3
3.59*


835
i-butyl
H
2-Cl-4-F-phenyl
Cl
COO−K+


836
i-butyl
H
2-Cl-4-F-phenyl
Cl
COO−Na+


837
i-butyl
H
2-Cl-4-F-phenyl
Cl
COOCH(CH3)COOCH3
4.33*


838
i-butyl
H
2-Cl-4-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
3.9*


839
i-butyl
H
2-Cl-4-F-phenyl
Cl
COO—CH2—CH2—OCH3
3.97*


840
i-butyl
H
2-Cl-4-F-phenyl
Cl
COOCH2COOCH3
3.95*


841
i-butyl
H
2-Cl-4-F-phenyl
Cl
COOH
3.24


842
i-butyl
H
2-Cl-6-F-phenyl
Cl
COOH
3.01


843
i-butyl
H
2-Cl-phenyl
Cl
CONCH3OCH3
3.43*


844
i-butyl
H
2-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.22*


845
i-butyl
H
2-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
3.79*


846
i-butyl
H
2-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
3.85*


847
i-butyl
H
2-Cl-phenyl
Cl
COOCH2COOCH3
3.84*


848
i-butyl
H
2-Cl-phenyl
Cl
COOH
3.1


849
i-butyl
H
3-Me-thien-2-yl
Cl
COO−Na+


850
i-butyl
H
3-Me-thien-2-yl
Cl
COOH
3.09


851
i-propyl
H
2,4,6-Me-phenyl
Cl
COOH
3.39


852
i-propyl
H
2,4,6-trifluorophenyl
Cl
CONCH3OCH3
3.03*


853
i-propyl
H
2,4,6-trifluorophenyl
Cl
COO−K+


854
i-propyl
H
2,4,6-trifluorophenyl
Cl
COO−Na+


855
i-propyl
H
2,4,6-trifluorophenyl
Cl
COOCH(CH3)COOCH3
3.81*


856
i-propyl
H
2,4,6-trifluorophenyl
Cl
COOCH2CH2OCH2CH2OCH3
3.36*


857
i-propyl
H
2,4,6-trifluorophenyl
Cl
COOCH2COOCH3
3.37*


858
i-propyl
H
2,4,6-trifluorophenyl
Cl
COOH
2.69


859
i-propyl
H
2,4-Cl-phenyl
Cl
CONCH3OCH3
3.68*


860
i-propyl
H
2,4-Cl-phenyl
Cl
COO−K+


861
i-propyl
H
2,4-Cl-phenyl
Cl
COO−Na+


862
i-propyl
H
2,4-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.42*


863
i-propyl
H
2,4-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
3.99*


864
i-propyl
H
2,4-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
4.05*


865
i-propyl
H
2,4-Cl-phenyl
Cl
COOCH2COOCH3
4.04*


866
i-propyl
H
2,4-Cl-phenyl
Cl
COOH
3.3


867
i-propyl
H
2,4-dichloro,5-CH3-phenyl
Cl
COOH
3.64


868
i-propyl
H
2,5-Me-phenyl
Cl
COOH
3.18


869
i-propyl
H
2,6-difluoro,4-Cl-phenyl
Cl
CONCH3OCH3
3.36*


870
i-propyl
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH(CH3)COOCH3
4.13*


871
i-propyl
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
3.71*


872
i-propyl
H
2,6-difluoro,4-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
3.78*


873
i-propyl
H
2,6-difluoro,4-Cl-phenyl
Cl
COOCH2COOCH3
3.77*


874
i-propyl
H
2-Cl,4-methylphenyl
Cl
COOH
3.1


875
i-propyl
H
2-Cl,5-Br-phenyl
Cl
COOH
3.17


876
i-propyl
H
2-Cl,5-F-phenyl
Cl
COOH
2.78


877
i-propyl
H
2-Cl-4-F-phenyl
Cl
CONCH3OCH3
3.31*


878
i-propyl
H
2-Cl-4-F-phenyl
Cl
COOCH(CH3)COOCH3
3.98*


879
i-propyl
H
2-Cl-4-F-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
3.56*


880
i-propyl
H
2-Cl-4-F-phenyl
Cl
COO—CH2—CH2—OCH3
3.61*


881
i-propyl
H
2-Cl-4-F-phenyl
Cl
COOCH2COOCH3
3.62*


882
i-propyl
H
2-Cl-4-F-phenyl
Cl
COOH
2.91


883
i-propyl
H
2-Cl-4-F-phenyl
Cl
SO2NCH(CH3)2
3.75


884
i-propyl
H
2-Cl-5-Me-phenyl
Cl
COOH
3.09


885
i-propyl
H
2-Cl-6-F-phenyl
Cl
COOH
2.7


886
i-propyl
H
2-Cl-phenyl
Cl
CONCH3OCH3
3.07*


887
i-propyl
H
2-Cl-phenyl
Cl
COOCH(CH3)COOCH3
3.85*


888
i-propyl
H
2-Cl-phenyl
Cl
COOCH2CH2OCH2CH2OCH3
3.41*


889
i-propyl
H
2-Cl-phenyl
Cl
COO—CH2—CH2—OCH3
3.46*


890
i-propyl
H
2-Cl-phenyl
Cl
COOCH2COOCH3
3.49*


891
i-propyl
H
2-Cl-phenyl
Cl
COOH
2.77


892
i-propyl
H
2-F,4-Cl-phenyl
Cl
COOH
3.29


893
i-propyl
H
3-Me-thien-2-yl
Cl
COOH
2.74


894
sec-butyl
H
2,5-Cl-phenyl
Cl
COO−Na+
3.41


895
sec-butyl
H
2,5-Cl-phenyl
Cl
COOH
3.41


896
sec-butyl
H
2-Cl,5-Br-phenyl
Cl
COOH
3.48


897
sec-butyl
H
2-Cl,5-F-phenyl
Cl
COO−Na+
3.07


898
sec-butyl
H
2-Cl,5-F-phenyl
Cl
COOH
3.07


899
sec-butyl
H
2-Cl-5-Me-phenyl
Cl
COO−Na+
3.38


900
sec-butyl
H
2-Cl-5-Me-phenyl
Cl
COOH
3.38


901
sec-butyl
H
2-F,4-Cl-phenyl
Cl
COO−Na+
3.34


902
sec-butyl
H
2-F,4-Cl-phenyl
Cl
COOH
3.34


903
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
CH3
CO—NH—CH3


904
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
CH3
CON(CH3)2


905
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
CH3
CO—NH-i-propyl


906
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
CH3
CO-morpholin-1-yl


907
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
CH3
COOH


908
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
CH3
COO-propen-3-yl


909
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
CH3
COO-benzyl


910
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
CH3
COO—CH2—CH2—OCH3


911
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
CH3
SO3H


912
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
CH3
SO2CH3


913
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
CO—NH—CH3


914
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
CON(CH3)2


915
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
CO—NH-i-propyl


916
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
CO-morpholin-1-yl


917
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
COOH


918
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
COO-propen-3-yl


919
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
COO-benzyl


920
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
COO—CH2—CH2—OCH3


921
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
SO3H


922
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
SO2CH3


923
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
CO—NH—CH3


924
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
CON(CH3)2


925
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
CO—NH-i-propyl


926
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
CO-morpholin-1-yl


927
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
COOH


928
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
COO-propen-3-yl


929
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
COO-benzyl


930
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
COO—CH2—CH2—OCH3


931
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
SO3H


932
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
SO2CH3


933
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
CO—NH—CH3


934
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
CON(CH3)2


935
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
CO—NH-i-propyl


936
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
CO-morpholin-1-yl


937
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
COOH


938
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
COO-propen-3-yl


939
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
COO-benzyl


940
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
COO—CH2—CH2—OCH3


941
CH(CH3)—C(CH3)3
H
2-Oi-phenyl
CH3
SO3H


942
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
SO2CH3


943
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
CO—-NH—CH3


944
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
CON(CH3)2


945
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
CO—NH-i-propyl


946
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
CO-morpholin-1-yl


947
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
COOH


948
CH(CH3)—C(CH3)3
H.
5-Cl-pyrimidin-4-yl
CH3
COO-propen-3-yl


949
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
COO-benzyl


950
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
COO—CH2—CH2—OCH3


951
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
SO3H


952
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
SO2CH3


953
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
CH3
CO—NH—CH3


954
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
CH3
CON(CH3)2


955
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
CH3
CO—NH-i-propyl


956
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
CH3
CO-morpholin-1-yl


957
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
CH3
COOH


958
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
CH3
COO-propen-3-yl


959
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
CH3
COO-benzyl


960
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
CH3
COO—CH2—CH2—OCH3


961
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
CH3
SO3H


962
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
CH3
SO2CH3


963
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
CO—NH—CH3


964
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
CON(CH3)2


965
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
CO—NH-i-propyl


966
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
CO-morpholin-1-yl


967
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
COOH


968
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
COO-propen-3-yl


969
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
COO-benzyl


970
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
COO—CH2—CH2—OCH3


971
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
SO3H


972
CH(CH3)(0F3)
H
2,4,6-trifluorophenyl
CH3
SO2CH3


973
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
CO—NH—CH3


974
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
CON(CH3)2


975
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
CO—NH-i-propyl


976
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
CO-morpholin-1-yl


977
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
COOH


978
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
COO-propen-3-yl


979
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
COO-benzyl


980
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
COO—CH2—CH2—OCH3


981
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
SO3H


982
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
SO2CH3


983
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
CO—NH—CH3


984
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
CON(CH3)2


985
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
CO—NH-i-propyl


986
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
CO-morpholin-1-yl


987
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
COOH


988
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
COO-propen-3-yl


989
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
COO-benzyl


990
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
COO—CH2—CH2—OCH3


991
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
SO3H


992
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
SO2CH3


993
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
CO—NH—CH3


994
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
CON(CH3)2


995
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
CO—NH-i-propyl


996
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
CO-morpholin-1-yl


997
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
COOH


998
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
COO-propen-3-yl


999
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
COO-benzyl


1000
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
COO—CH2—CH2—OCH3


1001
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
SO3H


1002
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
SO2CH3


1003
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
CH3
CO—NH—CH3


1004
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
CH3
CON(CH3)2


1005
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
CH3
CO—NH-i-propyl


1006
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
CH3
CO-morpholin-1-yl


1007
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
CH3
COOH


1008
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
CH3
COO-propen-3-yl


1009
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
CH3
COO-benzyl


1010
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
CH3
COO—CH2—CH2—OCH3


1011
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
CH3
SO3H


1012
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
CH3
SO2CH3


1013
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
CO—NH—CH3


1014
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
CON(CH3)2


1015
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
CO—NH-i-propyl


1016
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
CO-morpholin-1-yl


1017
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
COOH


1018
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
COO-propen-3-yl


1019
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
COO-benzyl


1020
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
COO—CH2—CH2—OCH3


1021
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
SO3H


1022
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
SO2CH3


1023
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
CO—NH—CH3


1024
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
CON(CH3)2


1025
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
CO—NH-i-propyl


1026
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
CO-morpholin-1-yl


1027
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
COOH


1028
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
COO-propen-3-yl


1029
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
COO-benzyl


1030
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
COO—CH2—CH2—OCH3


1031
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
SO3H


1032
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
SO2CH3


1033
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
CO—NH—CH3


1034
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
CON(CH3)2


1035
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
CO—NH-i-propyl


1036
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
CO-morpholin-1-yl


1037
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
COOH


1038
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
COO-propen-3-yl


1039
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
COO-benzyl


1040
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
COO—CH2—CH2—OCH3


1041
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
SO3H


1042
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
SO2CH3


1043
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
CO—NH—CH3


1044
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
CON(CH3)2


1045
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
CO—NH-i-propyl


1046
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
CO-morpholin-1-yl


1047
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
COOH


1048
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
COO-propen-3-yl


1049
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
COO-benzyl


1050
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
COO—CH2—CH2—OCH3


1051
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
SO3H


1052
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
SO2CH3












1053
—CH2—CH2—CH(CH3)—CH2—CH3—
2-Cl-6-F-phenyl
CH3
CO—NH—CH3


1054
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
CH3
CON(CH3)2


1055
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
CH3
CO—NH-i-propyl


1056
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
CH3
CO-morpholin-1-yl


1057
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
CH3
COOH


1058
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
CH3
COO-propen-3-yl


1059
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
CH3
COO-benzyl


1060
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
CH3
COO—CH2—CH2—OCH3


1061
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
CH3
SO3H


1062
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
CH3
SO2CH3


1063
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
CH3
CO—NH—CH3


1064
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
CH3
CON(CH3)2


1065
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
CH3
CO—NH-i-propyl


1066
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
CH3
CO-morpholin-1 -yl


1067
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
CH3
COOH


1068
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
CH3
COO-propen-3-yl


1069
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
CH3
COO-benzyl


1070
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
CH3 
COO—CH2—CH2—OCH3


1071
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
CH3
SO3H


1072
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
CH3
SO2CH3


1073
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
CO—NH—CH3


1074
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
CON(CH3)2


1075
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
CO—NH-i-propyl


1076
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
CO-morpholin-1-yl


1077
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
COOH


1078
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
COO-propen-3-yl


1079
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
COO-benzyl


1080
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
COO—CH2—CH2—OCH3


1081
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
SO3H


1082
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
SO2CH3


1083
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
CH3
CO—NH—CH3


1084
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
CH3
CON(CH3)2


1085
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
CH3
CO—NH-i-propyl


1086
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
CH3
CO-morpholin-1-yl


1087
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
CH3
COOH


1088
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
CH3
COO-propen-3-yl


1089
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
CH3
COO-benzyl


1090
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
CH3
COO—CH2—CH2—OCH3


1091
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
CH3
SO3H


1092
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
CH3
SO2CH3


1093
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
CH3
CO—NH—CH3


1094
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
CH3
CON(CH3)2


1095
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
CH3
CO—NH-i-propyl


1096
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
CH3
CO-morpholin-1 -yl


1097
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
CH3
COOH


1098
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
CH3
COO-propen-3-yl


1099
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
CH3
COO-benzyl


1100
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
CH3
COO—CH2—CH2—OCH3


1101
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
CH3
SO3H


1102
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
CH3
SO2CH3













1103
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
CO—NH—CH3


1104
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
CON(CH3)2


1105
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
CO—NH-i-propyl


1106
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
CO-morpholin-1-yl


1107
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
COOH


1108
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
COO-propen-3-yl


1109
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
COO-benzyl


1110
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
COO—CH2—CH2—OCH3


1111
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
SO3H


1112
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
SO2CH3


1113
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
SCH3
CO—NH—CH3


1114
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
SCH3
CON(CH3)2


1115
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
SCH3
CO—NH-i-propyl


1116
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
SCH3
CO-morpholin-1-yl


1117
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
SCH3
COOH


1118
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
SCH3
COO-propen-3-yl


1119
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
SCH3
COO-benzyl


1120
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
SCH3
COO—CH2—CH2—OCH3


1121
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
SCH3
SO3H


1122
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
SCH3
SO2CH3


1123
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
SCH3
CO—NH—CH3


1124
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
SCH3
CON(CH3)2


1125
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
SCH3
CO—NH-i-propyl


1126
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
SCH3
CO-morpholin-1-yl


1127
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
SCH3
COOH


1128
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
SCH3
COO-propen-3-yl


1129
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
SCH3
COO-benzyl


1130
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
SCH3
COO—CH2—CH2—OCH3


1131
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
SCH3
SO3H


1132
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
SCH3
SO2CH3


1133
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
SCH3
CO—NH—CH3


1134
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
SCH3
CON(CH3)2


1135
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
SCH3
CO—NH-i-propyl


1136
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
SCH3
CO-morpholin-1-yl


1137
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
SCH3
COOH


1138
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
SCH3
COO-propen-3-yl


1139
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
SCH3
COO-benzyl


1140
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
SCH3
COO—CH2—CH2—OCH3


1141
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
SCH3
SO3H


1142
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
SCH3
SO2CH3


1143
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
SCH3
CO—NH—CH3


1144
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
SCH3
CON(CH3)2


1145
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
SCH3
CO—NH-i-propyl


1146
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
SCH3
CO-morpholin-1-yl


1147
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
SCH3
COOH


1148
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
SCH3
COO-propen-3-yl


1149
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
SCH3
COO-benzyl


1150
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
SCH3
COO—CH2—CH2—OCH3


1151
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
SCH3
SO3H


1152
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
SCH3
SO2CH3


1153
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
CO—NH—CH3


1154
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
CON(CH3)2


1155
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
CO—NH-i-propyl


1156
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
CO-morpholin-1-yl


1157
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
COOH


1158
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
COO-propen-3-yl


1159
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
COO-benzyl


1160
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
COO—CH2—CH2—OCH3


1161
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
SO3H


1162
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
SO2CH3


1163
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
SCH3
CO—NH—CH3


1164
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
SCH3
CON(CH3)2


1165
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
SCH3
CO—NH-i-propyl


1166
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
SCH3
CO-morpholin-1-yl


1167
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
SCH3
COCH


1168
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
SCH3
COO-propen-3-yl


1169
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
SCH3
COO-benzyl


1170
CH(CH3)(CF3)
H
2,46-trifluorophenyl
SCH3
COO—CH2—CH2—OCH3


1171
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
SCH3
SO3H


1172
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
SCH3
SO2CH3


1173
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
SCH3
CO—NH—CH3


1174
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
SCH3
CON(CH3)2


1175
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
SCH3
CO—NH-i-propyl


1176
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
SCH3
CO-morpholin-1-yl


1177
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
SCH3
COOH


1178
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
SCH3
COO-propen-3-yl


1179
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
SCH3
COO-benzyl


1180
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
SCH3
COO—CH2—CH2—OCH3


1181
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
SCH3
SO3H


1182
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
SCH3
SO2CH3


1183
CH(CH3)(CF3)
H
2-Cl-phenyl
SCH3
CO—NH—CH3


1184
CH(CH3)(CF3)
H
2-Cl-phenyl
SCH3
CON(CH3)2


1185
CH(CH3)(CF3)
H
2-Cl-phenyl
SCH3
CO—NH-i-propyl


1186
CH(CH3)(CF3)
H
2-Cl-phenyl
SCH3
CO-morpholin-1-yl


1187
CH(CH3)(CF3)
H
2-Cl-phenyl
SCH3
COOH


1188
CH(CH3)(CF3)
H
2-Cl-phenyl
SCH3
COO-propen-3-yl


1189
CH(CH3)(CF3)
H
2-Cl-phenyl
SCH3
COO-benzyl


1190
CH(CH3)(CF3)
H
2-Cl-phenyl
SCH3
COO—CH2—CH2—OCH3


1191
CH(CH3)(CF3)
H
2-Cl-phenyl
SCH3
SO3H


1192
CH(CH3)(CF3)
H
2-Cl-phenyl
SCH3
SO2CH3


1193
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
SCH3
CO—NH—CH3


1194
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
SCH3
CON(CH3)2


1195
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
SCH3
CO—NH-i-propyl


1196
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
SCH3
CO-morpholin-1-yl


1197
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
SCH3
COOH


1198
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
SCH3
COO-propen-3-yl


1199
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
SCH3
COO-benzyl


1200
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
SCH3
COO—CH2—CH2—OCH3


1201
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
SCH3
SO3H


1202
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
SCH3
SO2CH3


1203
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
CO—NH—CH3


1204
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
CON(CH3)2


1205
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
CO—NH-i-propyl


1206
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
CO-morpholin-1-yl


1207
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
COOH


1208
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
COO-propen-3-yl


1209
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
COO-benzyl


1210
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
COO—CH2—CH2—OCH3


1211
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
SO3H


1212
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
SO2CH3


1213
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
SCH3
CO—NH—CH3


1214
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
SCH3
CON(CH3)2


1215
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
SCH3
CO—NH-i-propyl


1216
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
SCH3
CO-morpholin-1 -yl


1217
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
SCH3
COOH


1218
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
SCH3
COO-propen-3-yl


1219
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
SCH3
COO-benzyl


1220
CH(CH3)—CH(CH3)2
H
2,4,6-trifiuorophenyl
SCH3
COO—CH2—CH2—OCH3


1221
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
SCH3
SO3H


1222
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
SCH3
SO2CH3


1223
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
SCH3
CO—NH—CH3


1224
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
SCH3
CON(CH3)2


1225
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
SCH3
CO—NH-i-propyl


1226
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
SCH3
CO-morpholin-1-yl


1227
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
SCH3
COOH


1228
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
SCH3
COO-propen-3-yl


1229
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
SCH3
COO-benzyl


1230
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
SCH3
COO—CH2—CH2—OCH3


1231
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
SCH3
SO3H


1232
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
SCH3
SO2CH3


1233
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
SCH3
CO—NH—CH3


1234
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
SCH3
CON(CH3)2


1235
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
SCH3
CO—NH-i-propyl


1236
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
SCH3
CO-morpholin-1-yl


1237
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
SCH3
COOH


1238
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
SCH3
COO-propen-3-yl


1239
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
SCH3
COO-benzyl


1240
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
SCH3
COO—CH2—CH2—OCH3


1241
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
SCH3
SO3H


1242
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
SCH3
SO2CH3


1243
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
SCH3
CO—NH—CH3


1244
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
SCH3
CON(CH3)2


1245
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
SCH3
CO—NH-i-propyl


1246
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
SCH3
CO-morpholin-1-yl


1247
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
SCH3
COOH


1248
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
SCH3
COO-propen-3-yl


1249
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
SCH3
COO-benzyl


1250
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
SCH3
COO—CH2—CH2—OCH3


1251
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
SCH3
SO3H


1252
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
SCH3
SO2CH3












1253
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
SCH3
CO—NH—CH3


1254
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
SCH3
CON(CH3)2


1255
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
SCH3
CO—NH-i-propyl


1256
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
SCH3
CO-morpholin-1-yl


1257
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
SCH3
COOH


1258
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
SCH3
COO-propen-3-yl


1259
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
SCH3
COO-benzyl


1260
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
SCH3
COO—CH2—CH2—OCH3


1261
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
SCH3
SO3H


1262
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-6-F-phenyl
SCH3
SO2CH3


1263
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
SCH3
CO—NH—CH3


1264
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
SCH3
CON(CH3)2


1265
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
SCH3
CO—NH-i-propyl


1266
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
SCH3
CO-morpholin-1-yl


1267
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
SCH3
COOH


1268
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
SCH3
COO-propen-3-yl


1269
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
SCH3
COO-benzyl


1270
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
SCH3
COO—CH2—CH2—OCH3


1271
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
SCH3
SO3H


1272
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4,6-trifluorophenyl
SCH3
SO2CH3


1273
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
SCH3
CO—NH—CH3


1274
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
SCH3
CON(CH3)2


1275
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
SCH3
CO—NH-i-propyl


1276
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
SCH3
CO-morpholin-1-yl


1277
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
SCH3
COOH


1278
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
SCH3
COO-propen-3-yl


1279
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
SCH3
COO-benzyl


1280
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
SCH3
COO—CH2—CH2—OCH3


1281
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
SCH3
SO3H


1282
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
SCH3
SO2CH3


1283
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
SCH3
CO—NH—CH3


1284
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
SCH3
CON(CH3)2


1285
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
SCH3
CO—NH-i-propyl


1286
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
SCH3
CO-morpholin-1-yl


1287
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
SCH3
COOH


1288
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
SCH3
COO-propen-3-yl


1289
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
SCH3
COO-benzyl


1290
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
SCH3
COO—CH2—CH2—OCH3


1291
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
SCH3
SO3H


1292
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-phenyl
SCH3
SO2CH3


1293
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
SCH3
CO—NH—CH3


1294
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
SCH3
CON(CH3)2


1295
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
SCH3
CO—NH-i-propyl


1296
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
SCH3
CO-morpholin-1-yl


1297
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
SCH3
COOH


1298
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
SCH3
COO-propen-3-yl


1299
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
SCH3
COO-benzyl


1300
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
SCH3
COO—CH2—CH2—OCH3


1301
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
SCH3
SO3H


1302
—CH2—CH2—CH(CH3)—CH2—CH2—
5-Cl-pyrimidin-4-yl
SCH3
SO2CH3


1303
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
SO2NH2
3.66


1304
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
SCH3
5.73


1305
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
SO2NHCH3


1306
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
SO2NH2


1307
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
CH3
SCH3


1308
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl-4-F-phenyl
Cl
SO2NHCH3













1309
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
SO2NH2


1310
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
SCH3


1311
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
Cl
SO2NHCH3


1312
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
SO2NH2


1313
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
SCH3


1314
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
Cl
SO2NHCH3


1315
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
SO2NH2


1316
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
SCH3


1317
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
Cl
SO2NHCH3


1318
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
SO2NH2


1319
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
SCH3


1320
CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
SCH3
SO2NHCH3


1321
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
SO2NH2


1322
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
SCH3


1323
CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
SCH3
SO2NHCH3


1324
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
SO2NH2


1325
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
SCH3


1326
CH(CH3)(CF3)
H
2-Cl-6-F-phenyl
SCH3
SO2NHCH3


1327
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
SO2NH2


1328
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
SCH3


1329
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
Cl
SO2NHCH3


1330
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
SO2NH2


1331
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
SCH3


1332
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
Cl
SO2NHCH3


1333
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
SO2NH2


1334
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
SCH3


1335
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
Cl
SO2NHCH3


1336
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
SO2NH2


1337
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
SCH3


1338
CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
CH3
SO2NHCH3


1339
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
SO2NH2


1340
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
SCH3


1341
CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
CH3
SO2NHCH3


1342
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
SO2NH2


1343
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
SCH3


1344
CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
CH3
SO2NHCH3


1345
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
SO2NH2


1346
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
SCH3


1347
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
Cl
SO2NHCH3


1348
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
SO2NH2


1349
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
SCH3


1350
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
Cl
SO2NHCH3


1351
CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
SO2NH2


1352
CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
SCH3


1353
CH(CH3)(CF3)
H
2-Cl-phenyl
Cl
SO2NHCH3


1354
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
SO2NH2


1355
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
SCH3


1356
CH(CH3)—CH(CH3)2
H
2-Cl-phenyl
CH3
SO2NHCH3


1357
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
SO2NH2


1358
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
SCH3


1359
CH(CH3)—C(CH3)3
H
2-Cl-phenyl
CH3
SO2NHCH3


1360
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
SO2NH2


1361
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
SCH3


1362
CH(CH3)(CF3)
H
2-Cl-phenyl
CH3
SO2NHCH3


1363
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
SO2NH2
3.39


1364
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
SCH3


1365
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
SO2NHCH3


1366
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
SO2NH2
3.63


1367
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
SCH3


1368
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
SO2NHCH3
4.09


1369
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
SO2NH2


1370
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
SCH3


1371
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
Cl
SO2NHCH3


1372
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
SO2NH2


1373
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
SCH3


1374
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
CH3
SO2NHCH3


1375
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
SO2NH2


1376
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
SCH3


1377
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
CH3
SO2NHCH3


1378
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
SO2NH2


1379
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
SCH3


1380
CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
CH3
SO2NHCH3


1381
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
SO2NH2


1382
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
SCH3


1383
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
Cl
SO2NHCH3


1384
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
SO2NH2


1385
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
SCH3


1386
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
Cl
SO2NHCH3


1387
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
SO2NH2


1388
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
SCH3


1389
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
Cl
SO2NHCH3


1390
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
SO2NH2


1391
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
SCH3


1392
CH(CH3)—CH(CH3)2
H
5-Cl-pyrimidin-4-yl
CH3
SO2NHCH3


1393
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
SO2NH2


1394
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
SCH3


1395
CH(CH3)—C(CH3)3
H
5-Cl-pyrimidin-4-yl
CH3
SO2NHCH3


1396
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
SO2NH2


1397
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
SCH3


1398
CH(CH3)(CF3)
H
5-Cl-pyrimidin-4-yl
CH3
SO2NHCH3


1399
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
SO2NH2
3.66


1400
CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
Cl
SO2NH2
3.39


1401
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
Cl
SO2NHCH3
4.09


1402
CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
NHCH3
SO2NHCH3
3.86





The logP values were determined in accordance with EEC Directive 79/831 Annex V.A8 by HPLC (gradient method, acetonitrile/0.1% aqueous phosphoric acid).


**These logP values were determined in accordance with EEC Directive 79/831 Annex V.A8 by HPLC (gradient method, acetonitrile/0.1% aqueous formic acid).






Table 2 shows the melting points of selected compounds of the formula (I):
















 













Ex.
R1 or







No.
-R1 + R2-
R2
R3
X
R4
m.p.
















204
2-butyl
H
2-Cl,4-methylphenyl
Cl
COO−K+
189-193








dec


205
2-butyl
H
2-Cl,4-methylphenyl
Cl
COO−Na+
>280


279
(R) CH(CH3)—C(CH3)3
H
2,4-F-phenyl
Cl
COO−Na+
266-271° C.


280
(R) CH(CH3)—C(CH3)3
H
2,4-F-phenyl
Cl
COO−K+
245-247° C.


283
(R) CH(CH3)—C(CH3)3
H
2,5-dimethylthien-3-yl
Cl
COO−Na+
269-270








dec


324
(R) CH(CH3)—C(CH3)3
H
2-Cl,4-MeO-phenyl
Cl
COO−Na+
250-255° C.


328
(R) CH(CH3)—C(CH3)3
H
2-Cl,4-methylphenyl
Cl
COO−K+
220–222








dec


329
(R) CH(CH3)—C(CH3)3
H
2-Cl,4-methylphenyl
Cl
COO−Na+
238-241








dec


414
CH(CH3)—C(CH3)3
H
4-chlorobenzyl
Cl
COOH
208-209


415
(S) CH(CH3)—C(CH3)3
H
4-chlorobenzyl
Cl
COOH
100-107


416
(R) CH(CH3)—C(CH3)3
H
4-chlorobenzyl
Cl
COOH
183-186


472
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COO−Na+
268-272° C.


473
(R) CH(CH3)—CH(CH3)2
H
2,4-F-phenyl
Cl
COO−K+
247-251° C.


490
(R) CH(CH3)—CH(CH3)2
H
2,5-dimethylthien-3-yl
Cl
COO−Na+
280-281








dec


491
(R) CH(CH3)—CH(CH3)2
H
2,5-dimethylthien-3-yl
Cl
COO−K+
207-211








dec


528
(R) CH(CH3)—CH(CH3)2
H
2-Cl,4-MeO-phenyl
Cl
COO−Na+
290-300° C.


530
(R) CH(CH3)—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COO−K+
204-205








dec.


531
(R) CH(CH3)—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COO−Na+
194-196


635
(R) CH(CH3)—CH(CH3)2
H
3-Cl-thien-2-yl
Cl
COO−Na+
285-287








dec.


644
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
Cl
COO−Na+
270-273








dec.


645
(R) CH(CH3)—CH(CH3)2
H
3-Me-thien-2-yl
—O—CH3
COO−Na+
258-259








dec.


679
CH2—C(CH3)3
H
2,4-F-phenyl
ClCOO−K+
~245° C.


680
CH2—C(CH3)3
H
2,4-F-phenyl
ClCOO−Na+
245.8° C


691
CH2—C(CH3)3
H
2-Cl,4-methylphenyl
Cl
COO−Na+
214-217








dec


717
CH2—CH2—CH(CH3)2
H
2,4-F-phenyl
Cl
COO−K+
220-225° C.


718
CH2—CH2—CH(CH3)2
H
2,4-F-phenyl
Cl
COO−Na+
252.6° C.


720
CH2—CH2—CH(CH3)2
H
2-Cl,4-methylphenyl
Cl
COO−Na+
220–225








dec.












738
—CH2—CH2—CH(CH3)—CH2—CH2—
2,4-F-phenyl
Cl
COO−Na+
285-290° C.


747
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl,4-MeO-phenyl
Cl
COO−K+
~250° C.


748
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl,4-MeO-phenyl
Cl
COO−Na+
215.3° C.


752
—CH2—CH2—CH(CH3)—CH2—CH2—
2-Cl,4-methylphenyl
—OH
COOH
218-221


783
—CH2—CH2—CH2—CH(CH3)—
2-Cl,4-methylphenyl
Cl
COO−K+
236-239


784
—CH2—CH2—CH2—CH(CH3)—
2-Cl,4-methylphenyl
Cl
COO−N+
265-266













800
cyclopentyl
H
2-Cl,4-methylphenyl
Cl
COO−Na+
248-251


832
i-butyl
H
2-Cl,4-methylphenyl
Cl
COO−Na+
248-252








dec









Preparation of the Starting Materials:





In an apparatus fitted with a Vigreux column, 198 g (1998 mmol) of methyl cyanoacetate, 296 g (1998 mmol) of triethyl orthoformate and 440 g (4310 mmol) of acetic anhydride were heated at reflux. Volatile components were distilled off, until a overhead temperature of 120° C. had been reached. After cooling, the mixture was fractionated under reduced pressure. This gave 5 g of methyl (2E/Z)-2-cyano-3-ethoxyacrylate (fraction 1: 65-100° C., 0.2 mbar, purity according to GCMS 88%) and a further 209 g of methyl (2E/Z)-2-cyano-3-ethoxyacrylate (fraction 2: 105-108° C., 0.2 mbar, purity according to GCMS>99%).




100 g (645 mol) of methyl (2E/Z)-2-cyano-3-ethoxyacrylate were initially charged in 481 ml of ethanol. With cooling (exothermic reaction!), 31 ml (645 mmol) of an 85% strength hydrazine hydrate solution were then added dropwise at room temperature over a period of 45 minutes. The mixture was stirred at 75° C. for another 12 hours. The hot mixture was filtered off, and the organic phase was concentrated under reduced pressure. This gave 64 g of methyl 5-amino-1H-pyrazole-4-carboxylate (logPs=−0.07; content according to HPLC: 86%).




At room temperature, 15 g (57.5 mmol) of dimethyl(2-chloro-6-fluorophenyl)malonate were mixed with 9.4 g (57.5 mmol) of methyl 5-amino-1H-pyrazole-4-carboxylate and 15 ml (63.3 mmol) of tri-n-butylamine. The mixture was then stirred at 185° C. for 8 hours, during which time methanol was distilled off. After cooling, excess tri-n-butylamine was carefully decanted off. Concentration under reduced pressure gave 27 g of methyl 6-(2-chloro-6-fluorophenyl)-5,7-dihydroxypyrazolo[1,5-a]pyrimidine-3-carboxylate (logPs=0.55; content according to HPLC: 83%).




At room temperature, 27 g (80 mmol) of methyl 6-(2-chloro-6-fluorophenyl)-5,7-dihydroxypyrazolo[1,5-a]pyrimidine-3-carboxylate were mixed with 75 ml (800 mmol) of phosphorus oxychloride and 8.3 g (40 mmol) of phosphorus pentachloride. The mixture was then stirred at 115° C. for 4 hours. Excess phosphorus oxychloride was distilled off under reduced pressure. With cooling, 50 ml of dichloromethane and 20 ml of water were then added carefully to the residue. The organic phase was dried over sodium sulphate and then concentrated under reduced pressure. The residue was chromatographed on silica gel using a mixture of cyclohexane:ethyl acetate=gradient: 9:1, 5:1 and 3:1. This gave 10 g of methyl 5,7-dichloro-6-(2-chloro-6-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (logPs=3.17; content according to HPLC:>99%).




At room temperature, 2 g (5.33 mmol) of methyl 5,7-dichloro-6-(2-chloro-6-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate in 20 ml of acetonitrile were mixed with 0.51 g (5.87 mmol) of 2-R-methyl-2-butylamine. 1.11 g (8.00 mmol) of potassium carbonate were added. The mixture was then stirred at 25° C. for 12 hours. 10 ml of dilute 1 N hydrochloric acid and 10 ml of dichloromethane were added to the reaction mixture. The organic phase was dried over sodium sulphate and then concentrated under reduced pressure. This gave 2.1 g of methyl 5-chloro-6-(2-chloro-6-fluorophenyl)-7-{[(1R)-1,2-dimethylpropyl]amino}pyrazolo[1,5-a]pyrimidine-3-carboxylate (logPs=4.12 and 4.15; content according to HPLC: 99%) as a mixture of the atropisomers.
The following intermediates were prepared analogously:
















 










R1
R2
R3
log P













CH(CH3)—C(CH3)3
H
5-F-pyrimidin-4-yl
3.15


CH(CH3)—CH(CH3)2
H
2-Cl-6-F-phenyl
4.12









(CH2—CH2—CHCH3—CH2—CH2)
2-Cl-6-F-phenyl
4.61










CH(CH3)—C(CH3)3
H
2-Cl-6-F-phenyl
4.51


CH(CH3)—C(CH3)3
H
2,4,6-trifluorophenyl
4.93


CH(CH3)—CH(CH3)2
H
2,4,6-trifluorophenyl
4.05


CH(CH3)(CF3)
H
2,4,6-trifluorophenyl
3.53


CH(CH3)(CF3)
H
2-Cl-4-F-phenyl
3.75


CH(CH3)—CH(CH3)2
H
2-Cl-4-F-phenyl
4.31


CH(CH3)—C(CH3)3
H
2-Cl-4-F-phenyl
4.68


CH(CH3)—CH(CH3)2
H
2-Ci-phenyl
4.21


CH(CH3)—C(CH3)3
H
2-Ci-phenyl
4.61









Dimethyl 2-(3-methylthiophen-2-yl)malonate




Aluminium trichloride (163 g, 1.222 mol) was initially charged in 540 ml of dichloromethane, the mixture was cooled to 0° C. and 112 ml (150 g, 1.222 mol) of methyl oxalyl chloride were added dropwise at this temperature. The mixture was then stirred at this temperature for another 10 min, 3-methylthiophene was added dropwise, again at 0° C., and, after warming to room temperature, the reaction mixture was stirred at this temperature overnight. Hydrolysis was carried out by pouring the mixture into 2 l of ice-water, and the organic phase was separated off, washed with sodium bicarbonate solution and dried over sodium sulphate, giving, after removal of the drying agent by filtration and concentration using a rotary evaporator, 119.5 g of methyl(3-methylthiophen-2-yl)-oxoacetate. Yield: 57%. 1H-NMR (DMSO): δ=8.09 (d, 1H), 7.19 (d, 1H), 7.67 (dd, 1H), 3.90 (s, 3H), 2.49 (s, 3H).




112.5 ml (116 g, 2.312 mol) of hydrazine hydrate were added slowly to a solution of 90 g (0.489 mol) of methyl(3-methylthiophen-2-yl)oxoacetate in 260 ml of diethylene glycol, and the mixture was heated under reflux for 30 min. After cooling to 3040° C., 82 g (1.246 mol) of potassium hydroxide were added a little at a time, which was accompanied by a temperature increase to 70-80° C. with simultaneous evolution of nitrogen. The mixture was then slowly heated to reflux and stirred at this temperature for a total of 5 h. After cooling to room temperature, the mixture was poured into 2 l of water, adjusted to pH=1 using 250 ml of semi-concentrated hydrochloric acid and extracted with ethyl acetate. The organic phase was dried over magnesium sulphate and filtered off and the solvent was removed, which gave 50 g of (3-methylthiophen-2-yl)acetic acid. Yield: 66%. 1H-NMR (DMSO): δ=7.25 (d, 1H), 6.84 (d, 2H), 3.67 (s, 2H), 2.11 (s, 3H).




5 ml of concentrated sulphuric acid were added to a solution of 50 g (0.32 mol) of (3-methyl-thiophen-2-yl)acetic acid in 500 ml of methanol, and the mixture was heated under reflux for 8 h. The solvent was then removed using a rotary evaporator, and water and dichloromethane were added to the residue. Phase-separation and another extraction of the aqueous phase with dichloromethane gave, after drying of the organic phase over sodium sulphate, filtration and concentration using a rotary evaporator, 42.5 g of methyl(3-methylthiophen-2-yl)acetate. Yield: 70%. 1H-NMR (DMSO): δ=7.30 (d, 1H), 6.87 (d, 1H), 3.82 (s, 2H), 3.65 (s, 3H), 2.13 (s, 3H).




Under argon, 14.7 g of sodium hydride (60% in mineral oil) were added to 311 ml (332 g, 3.685 mol) of dimethyl carbonate, and the mixture was heated at 80° C. At this temperature, a solution of 41 g (0.217 mol) of methyl(3-methylthiophen-2-yl)acetate in 50 ml of toluene was slowly added dropwise, and the mixture was stirred under reflux overnight. For work-up, the mixture was diluted with about 200 ml of methanol and poured into ice-water and acidified with dilute hydrochloric acid. Extraction with dichloromethane, drying of the organic phase over sodium sulphate, filtration and removal of the solvent gave 43.6 g of dimethyl 2-(3-methylthiophen-2-yl)malonate. Yield: 88%. 1H-NMR (DMSO): δ=7.42 (d, 1H), 6.89 (d, 1H), 5.27 (s, 1H), 3.69 (s, 6H), 2.15 (s, 3H).
Spectroscopic data of the intermediates, which were prepared in an analogous manner:











Structure
1H—NMR (DMSO)











δ = 8.30 (d, 1 H), 7.36 (d, 1 H), 3.92 (s, 3 H)


 






δ = 7.54 (d, 1 H), 7.02 (d, 1 H), 3.78 (s, 2 H)


 






δ = 7.57 (d, 1 H), 7.04 (d, 1 H), 3.90 (s, 2 H), 3.66 (s, 3 H)


 






δ = 7.71 (d, 1 H), 7.08 (d, 1 H), 5.25 (s, 1 H), 3.73 (s, 6 H)


 






δ = 7.42 (d, 1 H), 7.00 (d, 1 H), 3.66 (s, 2 H), 3.63 (s, 3 H)


 






δ = 7.49 (d, 1 H), 7.05 (d, 1 H), 4.98 (s, 1 H), 3.70 (s, 6 H)









USE EXAMPLES
Example A
Podosphaera Test (Apple)/Protective
















Solvents:
24.5 parts by weight of acetone




24.5 parts by weight of dimethylacetamide



Emulsifier:
1 part by weight of alkylaryl polyglycol ether










To produce a suitable preparation of active compound, 1 part by weight of active compound was mixed with the stated amounts of solvents and emulsifier, and the concentrate was diluted with water to the desired concentration.
To test for protective activity, young plants are sprayed with the preparation of active compound at the stated application rate. After the spray coating has dried on, the plants are inoculated with an aqueous spore suspension of the apple mildew pathogen Podosphaera leucotricha. The plants are then placed in a greenhouse at about 23° C. and a relative atmospheric humidity of about 70%.
Evaluation was carried out 10 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.
In this test, the compounds according to the invention having the example numbers below exhibited, at an active compound concentration of 100 ppm, an efficacy of 70% or more.
8, 15, 25, 35, 65, 75, 105, 106, 108, 121, 125, 126, 127, 128, 135, 208, 211, 216, 217, 218, 219, 220, 221, 222, 223, 224, 226, 227, 233, 235, 238, 239, 240, 242, 244, 248, 249, 253, 255, 256, 257, 259, 261, 264, 267, 270, 272, 273, 275, 276, 280, 281, 286, 287, 289, 290, 291, 292, 293, 295, 296, 297, 298, 304, 307, 308, 311, 312, 313, 314, 323, 325, 330, 337, 345, 346, 351, 354, 356, 357, 363, 366, 373, 377, 378, 382, 384, 385, 391, 393, 394, 399, 409, 421, 424, 425, 428, 430, 435, 441, 442, 445, 447, 448, 450, 451, 454, 457, 459, 460, 462, 463, 472, 486, 494, 495, 496, 497, 498, 499, 501, 503, 504, 505, 506, 515, 516, 517, 519, 520, 522, 523, 529, 534, 536, 543, 550, 551, 559, 560, 561, 562, 563, 564, 570, 571, 574, 576, 587, 588, 589, 591, 597, 607, 608, 614, 619, 623, 629, 630, 631, 632, 636, 664, 665, 667, 668, 684, 687, 694, 695, 701, 705, 706, 707, 710, 711, 712, 713, 724, 732, 753, 757, 808, 810, 812, 814, 825, 826, 828, 836, 842, 844, 845, 846, 859, 866, 876
Example B
Venturia Test (Apple)/Protective
















Solvents:
24.5 parts by weight of acetone




24.5 parts by weight of dimethylacetamide



Emulsifier:
1 part by weight of alkylaryl polyglycol ether










To produce a suitable preparation of active compound, 1 part by weight of active compound was mixed with the stated amounts of solvents and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for protective activity, young plants are sprayed with the preparation of active compound at the stated application rate. After the spray coating has dried on, the plants are inoculated with an aqueous conidia suspension of the apple scab pathogen Venturia inaequalis and then remain in an incubation cabinet at about 20° C. and 100% relative atmospheric humidity for one day.
The plants are then placed in a greenhouse at about 21° C. and a relative atmospheric humidity of about 90%.
Evaluation is carried out 10 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.
In this test, the compounds according to the invention having the example numbers below exhibited, at an active compound concentration of 100 ppm, an efficacy of 70% or more.
5, 8, 15, 25, 35, 65, 75, 105, 106, 108, 115, 121, 124, 125, 126, 128, 135, 179, 203, 208, 210, 211, 213, 216, 217, 218, 219, 220, 221, 222, 224, 225, 226, 227, 233, 234, 235, 238, 239, 240, 242, 244, 248, 249, 250, 251, 253, 255, 256, 257, 258, 259, 261, 262, 263, 264, 267, 270, 272, 273, 275, 276, 279, 280, 281, 284, 285, 286, 287, 289, 290, 291, 292, 293, 295, 296, 297, 298, 303, 304, 307, 308, 309, 311, 312, 313, 314, 323, 324, 325, 330, 337, 345, 347, 349, 351, 352, 354, 356, 357, 363, 366, 373, 377, 378, 382, 384, 385, 387, 391, 393, 394, 399, 400, 406, 408, 409, 410, 417, 421, 424, 425, 426, 428, 430, 435, 441, 442, 445, 447, 448, 450, 451, 454, 457, 459, 460, 462, 463, 472, 473, 486, 490, 491, 492, 493, 495, 496, 497, 498, 499, 501, 503, 504, 505, 506, 508, 511, 512, 515, 516, 517, 519, 520, 522, 523, 528, 529, 531, 534, 536, 543, 550, 551, 559, 560, 561, 562, 563, 564, 566, 570, 571, 574, 576, 578, 579, 580, 587, 588, 589, 591, 597, 605, 607, 608, 614, 619, 623, 629, 630, 631, 632, 635, 636, 643, 644, 645, 662, 663, 664, 665, 666, 667, 668, 670, 671, 672, 673, 678, 681, 682, 683, 684, 685, 687, 690, 691, 692, 693, 694, 695, 696, 701, 702, 705, 706, 707, 708, 710, 711, 712, 713, 714, 716, 720, 722, 724, 732, 737, 738, 739, 753, 757, 764, 765, 777, 804, 807, 808, 809, 810, 812, 815, 816, 817, 822, 825, 826, 828, 831, 832, 833, 834, 835, 836, 842, 844, 845, 846, 849, 850, 851, 852, 853, 854, 858, 859, 860, 861, 866, 868, 874, 876, 884
Example C
Botrytis Test (Bean)/Protective
















Solvents:
24.5 parts by weight of acetone




24.5 parts by weight of dimethylacetamide



Emulsifier:
1 part by weight of alkylaryl polyglycol ether










To produce a suitable preparation of active compound, 1 part by weight of active compound was mixed with the stated amounts of solvents and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for protective activity, young plants are sprayed with the preparation of active compound at the stated application rate. After the spray coating has dried on, two small pieces of agar colonized by Botrytis cinerea are placed onto each leaf. The inoculated plants are placed in a dark chamber at about 20° C. and 100% relative atmospheric humidity.
The size of the infected areas on the leaves is evaluated 2 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.
In this test, the compounds according to the invention having the example numbers below exhibited, at an active compound concentration of 500 ppm, an efficacy of 70% or more.
5, 8, 15, 25, 35, 65, 75, 105, 106, 108, 115, 121, 122, 124, 125, 126, 128, 135, 179, 222, 223, 224, 226, 227, 233, 234, 235, 238, 239, 242, 244, 249, 255, 256, 264, 276, 281, 284, 285, 286, 287, 289, 290, 291, 292, 295, 296, 297, 298, 304, 307, 308, 312, 314, 325, 330, 337, 339, 345, 346, 349, 351, 354, 357, 363, 373, 377, 399, 400, 406, 409, 410, 417, 421, 424, 425, 426, 428, 435, 441, 442, 451, 463, 473, 486, 492, 493, 494, 495, 497, 498, 501, 503, 504, 505, 506, 511, 512, 515, 516, 519, 520, 523, 528, 531, 534, 536, 540, 543, 550, 551, 559, 561, 570, 580, 587, 588, 589, 605, 607, 608, 619, 623, 629, 630, 631, 632, 636, 651, 661, 662, 663, 664, 665, 667, 668, 670, 672, 673, 678, 683, 684, 685, 687, 688, 690, 692, 695, 696, 701, 708, 714, 716, 722, 737, 738, 739, 757, 777, 804, 807, 808, 809, 811, 812, 814, 816, 817, 822, 825, 826, 828, 829, 831, 833, 835, 836, 842, 850, 851, 853, 854, 858, 860, 861, 866, 874, 876, 884
Example D
Pyricularia Test (Rice)/Protective
















Solvent:
50 parts by weight of N,N-dimethylformamide



Emulsifier:
1 part by weight of alkylaryl polyglycol ether










To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water and the stated amount of emulsifier to the desired concentration.
To test for protective activity, young rice plants are sprayed with the preparation of active compound at the stated application rate. One day after the treatment, the plants are inoculated with an aqueous spore suspension of Pyricularia oryzae. The plants are then placed in a greenhouse at 100% relative atmospheric humidity and 25° C.
Evaluation is carried out 7 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.
In this test, the compounds according to the invention having the example numbers below exhibited, at an active compound concentration of 1000 ppm, an efficacy of 70% or more:
5, 15, 65, 75, 105, 115, 124, 125, 208, 210, 216, 218, 226, 233, 235, 239, 244, 249, 261, 267, 272, 273, 276, 281, 287, 292, 293, 297, 304, 307, 308, 311, 312, 314, 346, 409, 424, 425, 428, 435, 441, 450, 451, 459, 460, 462, 483, 486, 490, 492, 498, 499, 505, 511, 519, 520, 523, 526, 527, 529, 559, 578, 588, 589, 608, 623, 629, 630, 636, 648, 664, 667, 668, 672, 673, 678, 682, 684, 687, 688, 690, 693, 694, 701, 737, 739, 751, 764, 811, 825, 828, 829, 831, 841, 848, 851, 852, 854, 858, 872, 882, 885
Example E
Alternaria Test (Tomato)/Protective
















Solvent:
49 parts by weight of N,N-dimethylformamide



Emulsifier:
1 part by weight of alkylaryl polyglycol ether










To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for protective activity, young tomato plants are sprayed with the preparation of active compound at the stated application-rate. One day after the treatment, the plants are inoculated with a spore suspension of Alternaria solani and then remain at 100% relative humidity and 20° C. for 24 h. The plants then remain at 96% relative atmospheric humidity and a temperature of 20° C.
Evaluation is carried out 7 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.
In this test, the compounds according to the invention having the example numbers below exhibited, at an active compound concentration of 500 ppm, an efficacy of 70% or more.
5, 15, 25, 35, 65, 71, 75, 105, 106, 108, 115, 121, 122, 124, 125, 127, 128, 135, 201, 204, 206, 208, 210, 211, 215, 221, 224, 225, 230, 231, 234, 236, 237, 240, 243, 244, 254, 264, 266, 268, 269, 276, 279, 281, 285, 292, 293, 295, 303, 309, 311, 313, 316, 323, 324, 325, 330, 337, 339, 341, 343, 345, 347, 351, 352, 354, 357, 363, 373, 376, 377, 383, 389, 399, 400, 407, 408, 410, 421, 422, 423, 428, 430, 434, 437, 439, 440, 451, 453, 456, 463, 473, 479, 483, 486, 491, 494, 496, 497, 498, 499, 503, 505, 511, 517, 522, 525, 529, 531, 533, 534, 536, 539, 541, 544, 545, 546, 550, 551, 559, 561, 565, 569, 570, 573, 578, 579, 580, 582, 588, 589, 591, 595, 597, 598, 599, 600, 604, 606, 607, 610, 613, 614, 618, 619, 620, 624, 626, 629, 631, 634, 635, 644, 646, 647, 648, 661, 666, 674, 675, 676, 677, 678, 679, 681, 686, 690, 691, 692, 693, 697, 698, 699, 700, 701, 702, 703, 704, 709, 714, 715, 717, 720, 722, 725, 726, 727, 733, 734, 736, 737, 743, 745, 748, 749, 751, 753, 759, 764, 766, 767, 768, 770, 783, 784, 785, 789, 794, 795, 799, 800, 801, 804, 807, 810, 818, 819, 820, 821, 822, 823, 824, 827, 831, 833, 837, 838, 840, 841, 843, 847, 855, 856, 857, 862, 864, 865, 866, 867, 869, 871, 872, 873, 874, 877, 878, 880, 881, 882, 885, 886, 887, 888, 889
Example F
Fusarium nivale (var. majus) Test (Wheat)/Protective
















Solvent:
50 parts of weight of N,N-dimethylacetamide



Emulsifier:
1.0 part by weight of alkylaryl polyglycol ether










To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.
To test for protective activity, young plants are sprayed with the preparation of active compound at the stated application rate. After the spray coating has dried on, the plants are sprayed with a conidia suspension of Fusarium nivale (var. majus).
The plants are placed in a greenhouse under translucent incubation hoods at a temperature of about 15° C. and a relative atmospheric humidity of about 100%.
Evaluation is carried out 6 days after the inoculation. 0% means an efficacy which corresponds to that of the control, whereas an efficacy of 100% means that no infection is observed.
In this test, the compounds according to the invention having the example numbers below exhibited, at an active compound concentration of 1000 ppm, an efficacy of 70% or more:
25, 35, 126, 128, 214, 228, 232, 238, 242, 248, 250, 251, 252, 253, 255, 256, 257, 259, 260, 263, 264, 270, 275, 283, 289, 291, 296, 328, 330, 337, 345, 347, 349, 351, 353, 354, 356, 357, 361, 362, 363, 364, 365, 378, 382, 387, 392, 393, 394, 400, 408, 421, 428, 430, 442, 445, 447, 448, 454, 457, 463, 473, 491, 495, 497, 501, 503, 504, 506, 512, 515, 516, 528, 531, 533, 534, 536, 543, 546, 548, 551, 560, 562, 563, 566, 571, 574, 580, 598, 635, 643, 644, 663, 670, 683, 685, 692, 695, 696, 705, 711, 724, 732, 739, 765, 808, 809, 812, 814, 816, 817, 822, 834, 835, 836, 845, 859, 860, 861, 866.

## Claims

1. A compound of the formula (I)



in which
R1 is alkyl having 1 to 10 carbon atoms which is unsubstituted or mono- to pentasubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, alkoxy having 1 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, mercapto, alkylthio having 1 to 4 carbon atoms, amino, mono- or dialkylamino having in each case 1 to 4 carbon atoms, or
is alkenyl having 2 to 10 carbon atoms which is unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, alkoxy having 1 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, mercapto, alkylthio having 1 to 4 carbon atoms, amino, and mono- or dialkylamino having in each case 1 to 4 carbon atoms, or
is alkynyl having 2 to 10 carbon atoms which is unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, alkoxy having 1 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, mercapto, alkylthio having 1 to 4 carbon atoms, amino, and mono- or dialkylamino having in each case 1 to 4 carbon atoms, or
is cycloalkyl having 3 to 10 carbon atoms which is unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of halogen and alkyl having 1 to 4 carbon atoms, or
is saturated or unsaturated heterocyclyl having 3 to 10 ring members and 1 to 3 heteroatoms that are nitrogen, oxygen and/or sulphur, where the heterocyclyl is unsubstituted or mono- or polysubstituted by halogen, alkyl having 1 to 4 carbon atoms, cyano, nitro, cycloalkyl having 3 to 6 carbon atoms, hydroxyl, alkoxy having 1 to 4 carbon atoms and/or mercapto;

R2 is hydrogen or alkyl having 1 to 6 carbon atoms;
R3 is C1-C10-alkyl, C2-C10-alkenyl, C2-C10alkynyl, C3-C8-cycloalkyl, phenyl-C1-C10-alkyl, where R3 is unsubstituted or partially or fully halogenated and/or optionally carries one to three radicals from the group Rx, or C1-C10-haloalkyl which optionally carries one to three radicals from the group Rx, and Rx is cyano, nitro, hydroxyl, C1-C6-alkyl, C1,-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-haloalkylthio, C1-C6-alkylsulphinyl, C1-C6-haloalkylsulphinyl, C1-C6-alkylsulphonyl, C1-C6-haloalkylsulphonyl, C1-C6-alkylamino, di-C1-C6-alkylamino, C2-C6-alkenyl, C2-C6-alkenyloxy, C2-C6-alkynyl, C3-C6-alkynyloxy and optionally halogenated oxy-C1-C4-alkyl-C1-C4-alkenoxy, oxy-C1-C4-alkenyl-C1-C4-alkoxy, oxy-C1-C4-alkyl-C1-C4-alkyloxy, or
is phenyl which may be mono- to tetrasubstituted by identical or different substituents from the group consisting of
halogen, cyano, nitro, amino, hydroxyl, formyl, carboxyl, carboxyalkyl, carbamoyl, thiocarbamoyl;
in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl having in each case 1 to 6 carbon atoms;
in each case straight-chain or branched alkenyl or alkenyloxy having in each case 2 to 6 carbon atoms;
in each case straight-chain or branched haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulphinyl or haloalkylsulphonyl having in each case 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms;
in each case straight-chain or branched haloalkenyl or haloalkenyloxy having in each case 2 to 6 carbon atoms and 1 to 11 identical or different halogen atoms;
in each case straight-chain or branched alkylamino, dialkylamino, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkylsulphonyloxy, hydroximinoalkyl or alkoximinoalkyl having in each case 1 to 6 carbon atoms in the individual alkyl moieties;
cycloalkyl having 3 to 8 carbon atoms;
1,3-propanediyl which is attached in the 2,3-position, 1,4-butanediyl, methylenedioxy (—O—CH2—O—) or 1,2-ethylenedioxy (—O—CH2—CH2—O—), where these radicals may be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, alkyl having 1 to 4 carbon atoms and haloalkyl having 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms; or
is saturated or fully or partially unsaturated or aromatic heterocyclyl having 3 to 8 ring members and 1 to 3 heteroatoms from the group consisting of nitrogen, oxygen and sulphur, where the heterocyclyl may be mono- or disubstituted by halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, haloalkoxy having 1 to 4 carbon atoms, haloalkylthio having 1 to 4 carbon atoms, hydroxyl, mercapto, cyano, nitro and/or cycloalkyl having 3 to 6 carbon atoms and/or carboxyalkyl; or
is C1-C8-alkylamino, C2-C8-alkenylamino, C2-C8-alkynylamino, di-C2-C8-alkylamino, di-C2-C8-alkenylamino, di-C2-C8-alkynylamino, or C2-C8-alkenyl-(C2-C8)-alkynylamino, C2-C6-alkynyl-(C1-C8)-alkylamino, C2-C8-alkenyl-(C1-C8)-alkylamino, C6-C10-arylamino, C6-C10-aryl-(C1-C8)-alkylamino, C6-C10-aryl-(C1-C4)-alkyl-(C1-C8)-alkylamino, heterocyclyl-(C1-C8)-alkylamino or heterocyclyl-(C1-C4)-alkyl-(C1-C8)-alkylamino;

R4 is CONR6R7, CONR7—N(R7)2, CO—NR7—OR7, COOR8, CSOR7, COSR7, SR7, SOR7, SO2R7, SO3R7, SON(R7)2, SO2N(R7)2, or P(O)-(OR7)2, B(OR7)2 or





A, B, D, E, G are identical or different and are CR9, CR9R9, N, NR9, O or S, with the proviso that at least one group is N, O or S and that oxygen atoms are not adjacent to one another;

Y is C, CR9or N;
R9 is R7, halogen, NR72, OH, SR7 or OR7;
R5 is H, halogen, (C1-C4)-alkyl which is unsubstituted or substituted by one or more halogen atoms, cyclopropyl which is unsubstituted or substituted by one or more halogen atoms; SCH3, SOCH3, SO2CH3 or OCH3;
X is H, fluorine, chlorine, bromine, CN, hydroxyl, alkoxy having 1 to 4 carbon atoms or alkylthio having 1 to 4 carbon atoms;
R6 is C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl, phenyl-C1-C10-alkyl, where R6 is unsubstituted or partially or fully halogenated and/or optionally carries one to three radicals from the group Rx, or C1-C10-haloalkyl which optionally carries one to three radicals from the group Rx, and Rx is cyano, nitro, hydroxyl, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-haloalkylthio, C1-C6-alkylsulphinyl, C1-C6-haloalkylsulphinyl, C1-C6-alkylsulphonyl, C1-C6-haloalkylsulphonyl, C1-C6-alkylamino, di-C1-C6-alkylamino, C2-C6-alkenyl, C2-C6-alkenyloxy, C2-C6-alkynyl, C3-C6-alkynyloxy and optionally halogenated oxy-C1-C4-alkyl-C1-C4-alkenoxy, oxy-C1-C4-alkenyl-C1-C4-alkoxy, oxy-C1-C4-alkyl-C1-C4-alkyloxy, CONR6R7, CONR7OR7, COOR8, carboxy-(C1-C4)-alkyl;
R7 is H or R6, or two radicals R7 or one radical R7 and one radical R8 together form a cycle having 3 to 6 carbon atoms which is saturated or partially unsaturated and optionally contains 1 or 2 further nitrogen, sulphur or oxygen atoms, where the oxygen atoms may not be adjacent to one another; and
R8 is H, an alkali metal or alkaline earth metal, copper, NH4, mono-(C1-C10)-alkylammonium, di-(C1-C10)-alkylammonium, tri-(C1-C10)-alkylammonium tetra-(C1-C10)-alkylammonium, where the alkyl substituents of the ammonium ions are optionally substituted by aryl or hydroxyl, cholinium, C2-C10-alkenyl, C2-C10-alkynyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl, where R8 is unsubstituted or partially or fully halogenated and/or optionally carries one to three radicals from the group Rx, or C1-C10-haloalkyl which optionally carries one to three radicals from the group Rx, or C1-C10-alkyl which is partially or fully halogenated and/or carries one to three radicals from the group Rx, and Rx is cyano, nitro, hydroxyl, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-haloalkylthio, C1-C6-alkylsulphinyl, C1-C6-haloalkylsulphinyl, C1-C6-alkylsulphonyl, C1-C6-haloalkylsulphonyl, C1-C6-alkylamino, di-C1-C6-alkylamino, C2-C6-alkenyl, C2-C6-alkenyloxy, C2-C6-alkynyl, C3-C6-alkynyloxy and optionally halogenated oxy-C1-C4-alkyl-C1-C4-alkenoxy, oxy-C1-C4-alkenyl-C1-C4-alkoxy, oxy-C1-C4-alkyl-C1-C4-alkyloxy, CONR6R7, CONR7OR7, COOR8, carboxy-(C1-C4)-alkyl
or an agrochemically active salt thereof.

2. A compound of the formula (I) according to claim 1 in which
R1 is a radical of the formula




 where # denotes the point of attachment, and wherein said radicals can be present both in optically pure form and as isomer mixtures;
R2 is hydrogen, methyl, ethyl, propyl, or
R3 is (C1-C8)-alkyl, (C1-C8)-cycloalkyl, where R3 is unsubstituted or substituted by one or more fluorine or chlorine atoms, or benzyl or
is phenyl which may be mono- to trisubstituted by identical or different substituents from the group consisting of
fluorine, chlorine, bromine, cyano, nitro, formyl, methyl, ethyl, n- or i- propyl, n-, i-, s- or t-butyl, vinyl, ethynyl, allyl, propargyl, methoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, n- or i-propylthio, methylsulphinyl, ethylsulphinyl, methylsulphonyl, ethylsulphonyl, allyloxy, propargyloxy, trifluoromethyl, trifluoroethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, difluorochloromethylthio, trifluoromethylthio, trifluoromethylsulphinyl, trifluoromethylsuiphonyl, trichloroethynyloxy, trifluoroethynyloxy, chloroallyloxy, iodopropargyloxy, methylamino, ethylamino, n- or i- propylamino, dimethylamino, diethylamino, acetyl, propionyl, acetyloxy, methoxycarbonyl, ethoxycarbonyl, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, ethoximinomethyl, methoximinoethyl, ethoximinoethyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, or by
1,3-propanediyl which is attached in the 2,3-position, 1,4-butanediyl, methylenedioxy (—O—CH2—O—) or 1,2-ethylenedioxy (—O—CH2—CH2—O—), where these radicals may be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, chlorine, methyl, ethyl, n-propyl, i-propyl, trifluoromethyl, carboxyl and carboxymethyl; or

is pyridyl which is attached in the 2- or 4-position and which may be mono- to tetrasubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, hydroxyl, mercapto, nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
is pyrimidyl which is attached in the 2- or 4-position and which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
is thienyl which is attached in the 2- or 3-position and which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hyd roximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
is C1-C8-alkylamino or di-C1-C8-alkylamino, or
is thiazolyl which is attached in the 2-, 4- or 5-position and which may be mono- to disubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
is N-piperidinyl, N-tetrazolyl, N-pyrazolyl, N-imidazolyl, N-1,2,4-triazolyl, N-pyrrolyl or N-morpholinyl, each of which is unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl,

R4 is CONR6R7, CONR7—N(R7)2, CO—NR7—OR7, COOR8, CSOR7, COSR7, pyrrolyl, imidazolyl, pyrazolyl, 1,3,4-triazolyl, thiazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazolyl, oxazolyl, tetrazolyl, oxadiazinyl, 4H-[1,2,4]-oxadiazin-3-yl, dioxazinyl, 5,6-dihydro-[1,4,2]-dioxazin-3-yl, pyridyl, where the heterocyclic radicals are optionally substituted by one or more radicals from the group consisting of C1-C4-alkyl and halogen, SR7, SOR7, SO2R7, SO3R7, SON(R7)2, SO2N(R7)2, P(O)—(OR7)2 or B(OR7)2;
R5 is H, Cl, F, CH3, —CH(CH3)2 or cyclopropyl; and
X is H, F, Cl, CN, C1-C4-alkyl which is unsubstituted or substituted by one or more fluorine or chlorine atoms;
R6 is (C1-C8)-alkyl, (C3-C6)-alkenyl, (C1-C8)-cycloalkyl or benzyl, CONR6R7, CONR7OR7, COOR8, carboxy-(C1,-C4-alkyl, or cyano;
R7 is H or R6; or two radicals R7 or one radical R6 and one radical R7 together form a cycle having 3 to 6 carbon atoms, which is saturated or partially unsaturated and optionally contains 1 or 2 further nitrogen, sulphur or oxygen atoms, where oxygen atoms must not be adjacent to one another; and
R8 is H, Na, K, 1⁄2Ca, 1⁄2Mg, Cu, NH4, NH(CH3)3, N(CH3)4, HN(C2H5)3, N(C2H5)4, H2N(iC3H7)2, H2N(Bn)2, H3N(Bn), (C1-C4)-alkyl which is fully or partially substituted by F and/or Cl, CONR6R7, CONR7OR7, COOR8, carboxy-(C1-C4)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, allyl, propargyl, cyclopropyl, benzyl, (CHRz—CHRZ—O)m(C1-C4)alkyl where RZ is H or CH3 and m is 1 to 6.

3. A compound of the formula (I) according to claim 1 in which
R3 is (C1-C6)-alkyl, (C3-C6)-alkenyl, (C3-C6)-alkynyl, (C3-C8)-cycloalkyl, where R3 is unsubstituted or substituted by one or more fluorine or chlorine atoms and/or alkyl, or
is 2,4-, 2,5- or 2,6-disubstituted phenyl or 2-substituted phenyl or 2,4,6- or 2,4,5-trisubstituted phenyl having substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl or
is pyridyl which is attached in the 2- or 4-position and which may be mono- to tetrasubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl; or
is pyrimidyl which is attached in the 4-position and which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl; or
is thienyl which is attached in the 2- or 3-position and which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl;

R4 is CONR6R7, CONR7—N(R7)2, CO—NR7—OR7, COOR8, 1H-pyrrolyl, 1H-imidazolyl, 1,3,4-oxadiazolyl, 1 H-pyrazolyl, 1H-1,3,4-triazolyl, tetrazolyl, oxadiazinyl, 4H-[1,2,4]-oxadiazin-3-yl, dioxazinyl, 5,6-dihydro-[1,4,2]-dioxazin-3-yl, pyridyl, where the heterocyclic radicals are optionally substituted by one or more radicals from the group consisting of C1-C4-alkyl and halogen, SR7, SOR7, SO2R7, SO3R7, SON(R7)2, SO2N(R7)2, or P(O)—(OR7)2;
R5 is H, —CH3, —CH(CH3)2, Cl or cyclopropyl; and
X is fluorine, chlorine, (C1-C7)-alkyl or (C1-C3)-haloalkyl;
R6 is (C1-C8)-alkyl, (C3-C6)-alkenyl, (C1-C8)-cycloalkyl, benzyl, carboxy-(C1-C4)-alkyl, CONR6R7, CONR7OR7, COOR8, or cyano;
R7 is H or R6, or two radicals R7 or one radical R6 and one radical R7 together form a cycle having 3 to 6 carbon atoms, which is saturated or partially unsaturated and optionally contains 1 or 2 further nitrogen, sulphur or oxygen atoms, where the oxygen atoms must not be adjacent to one another; and
R8 is H, Na, K, NH4, H2N(iPr)t2, H2N(Bn)2, H3N(Bn), (C1-C4-alkyl which is fully or partially substituted by F and/or Cl and/or carboxy-(C1-C4)-alkyl, CONR6R7, CONR7OR7, COOR8, (C1-C4)-alkoxy-(C1-C4)-alkyl, allyl, propargyl, cyclopropyl, benzyl, (CHRZ—CHRZ—O)m-(C1C4)-alkyl where RZ is H, CH3 and m is 1 to 6.

4. A composition for controlling unwanted microorganisms comprising one or more compounds of the formula (I) according to claim 1 and one or more extenders and/or surfactants.

5. A composition according to claim 4 comprising one or more further agrochemically active compounds.

6. A method for controlling unwanted microorganisms comprising applying an effective amount of one or more compounds of the formula (I) according to claim 1 to the unwanted microorganisms and/or their habitats.

7. A process for preparing compositions for controlling unwanted microorganisms comprising mixing one or more compounds of the formula (I) according to claim 1 with one or more extenders and/or surfactants.

8. A process for preparing compounds of the formula (I) in which X is halogen and R4 represents CONR6R7, CONR7—N(R7)2, CONR7OR7 or COOR8, and R1, R2, R3, and R5 are as defined in formula (1) in claim 1 comprising
a) reacting a substituted 3-aminopyrazole derivative of the formula II




 and a malonic ester IIa





where R10 represents C1-C4-alkyl and R11 represents C1-C8-alkyl or aryl to give a dihydroxypyrazolopyrimidine III,





b) halogenating a dihydroxypyrazolopyrimidine III to give a halopyrazolopyrimidine IV,




c) reacting a dihydroxypyrazolopyrimidine IV with an amine to give a 7-aminopyrazolopyrimidine V,




d) hydrolyzing a 7-aminopyrazolopyrimidine V, to give a pyrazolopyrimidinecarboxylic acid VI,




e) reacting a pyrazolopyrimidinecarboxylic acid VI with a chlorinating agent to give a pyrazolopyrimidine acid chloride VII,




 and
f) (1) reacting a pyrazolopyrimidine acid chloride VII with an amine to give an amide of the formula (Ia)




 or
(2) reacting a pyrazolopyrimidine acid chloride VII with a hydrazine to give a hydrazide of the formula (Ib)





 or
(3) reacting a pyrazolopyrimidine acid chloride VII with a hydroxylamine to give a hydroxamide of the formula (Ic)





 or
(4) reacting a pyrazolopyrimidine acid chloride VII with an alcohol to give an ester of the formula (Id)

9. A compound selected from the group consisting of compounds of the formula III, IV, V and VII as follows:




wherein
R1 is alkyl having 1 to 10 carbon atoms which is unsubstituted or mono- to pentasubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, alkoxy having 1 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, mercapto, alkylthio having 1 to 4 carbon atoms, amino, mono- or dialkylamino having in each case 1 to 4 carbon atoms, or
is alkenyl having 2 to 10 carbon atoms which is unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, alkoxy having 1 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, mercapto, alkylthio having 1 to 4 carbon atoms, amino, and mono- or dialkylamino having in each case 1 to 4 carbon atoms, or
is alkynyl having 2 to 10 carbon atoms which is unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, hydroxyl, alkoxy having 1 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, mercapto, alkylthio having 1 to 4 carbon atoms, amino, and mono- or dialkylamino having in each case 1 to 4 carbon atoms, or
is cycloalkyl having 3 to 10 carbon atoms which is unsubstituted or mono- to trisubstituted by identical or different substituents from the group consisting of halogen and alkyl having 1 to 4 carbon atoms, or
is saturated or unsaturated heterocyclyl having 3 to 10 ring members and 1 to 3 heteroatoms that are nitrogen, oxygen and/or sulphur, where the heterocyclyl is unsubstituted or mono- or polysubstituted by halogen, alkyl having 1 to 4 carbon atoms, cyano, nitro, cycloalkyl having 3 to 6 carbon atoms, hydroxyl, alkoxy having 1 to 4 carbon atoms and/or mercapto;

R2 is hydrogen or alkyl having 1 to 6 carbon atoms;
R3 is (C1-C8)-alkyl, (C1-C8)-cycloalkyl, where R3 is unsubstituted or substituted by one or more fluorine or chlorine atoms, or benzyl or
is phenyl which may be mono- to trisubstituted by identical or different substituents from the group consisting of
fluorine, chlorine, bromine, cyano, nitro, formyl, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, vinyl, ethynyl, allyl, propargyl, methoxy, ethoxy, n- or i-propoxy, methylthio, ethylthio, n- or i-propylthio, methylsulphinyl, ethylsulphinyl, methylsulphonyl, ethylsulphonyl, allyloxy, propargyloxy, trifluoromethyl, trifluoroethyl, difluoromethoxy, trifluoromethoxy, difluorochloromethoxy, trifluoroethoxy, difluoromethylthio, difluorochloromethylthio, trifluoromethylthio, trifluoromethylsulphinyl, trifluoromethylsulphonyl, trichioroethynyloxy, trifluoroethynyloxy, chloroallyloxy, iodopropargyloxy, methylamino, ethylamino, n- or i-propylamino, dimethylamino, diethylamino, acetyl, propionyl, acetyloxy, methoxycarbonyl, ethoxycarbonyl, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, ethoximinomethyl, methoximinoethyl, ethoximinoethyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, or by
1,3-propanediyl which is attached in the 2,3-position, 1,4-butanediyl, methylenedioxy (—O—CH2—O—) or 1,2-ethylenedioxy (—O—CH2—CH2—O—), where these radicals may be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, chlorine, methyl, ethyl, n-propyl, -propyl, trifluoromethyl, carboxyl and carboxymethyl; or

is pyridyl which is attached in the 2- or 4-position and which may be mono- to tetrasubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, hydroxyl, mercapto, nitro, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
is pyrimidyl which is attached in the 2- or 4-position and which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
is thienyl which is attached in the 2- or 3-position and which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
is C1-C8-alkylamino or di- C1-C8-alkylamino, or
is thiazolyl which is attached in the 2-, 4- or 5-position and which may be mono- to disubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl, trifluoromethyl, carboxyl and carboxymethyl, or
is N-piperidinyl, N-tetrazolyl, N-pyrazolyl, N-imidazolyl, N-1,2,4-triazolyl, N-pyrrolyl or N-morpholinyl, each of which is unsubstituted or mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, hydroxyl, mercapto, methyl, ethyl, methoxy, methylthio, hydroximinomethyl, hydroximinoethyl, methoximinomethyl, methoximinoethyl and trifluoromethyl;

R5 is H, Cl, F, CH3, —CH(CH3)2 or cyclopropyl; and
R10 is C1-C4-alkyl.