WO2011023677A1 - Tetra-substituted heteroaryl compounds and their use as mdm2 and/or mdm4 modulators - Google Patents

Tetra-substituted heteroaryl compounds and their use as mdm2 and/or mdm4 modulators Download PDF

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WO2011023677A1
WO2011023677A1 PCT/EP2010/062300 EP2010062300W WO2011023677A1 WO 2011023677 A1 WO2011023677 A1 WO 2011023677A1 EP 2010062300 W EP2010062300 W EP 2010062300W WO 2011023677 A1 WO2011023677 A1 WO 2011023677A1
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Prior art keywords
alkyl
amino
carbonyl
phenyl
chloro
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PCT/EP2010/062300
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English (en)
French (fr)
Inventor
Guido Bold
Pascal Furet
François GESSIER
Joerg Kallen
Joanna Hergovich Lisztwan
Keiichi Masuya
Andrea Vaupel
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Novartis Ag
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Priority to MX2012002420A priority Critical patent/MX2012002420A/es
Priority to CA2771936A priority patent/CA2771936A1/en
Priority to IN1693DEN2012 priority patent/IN2012DN01693A/en
Priority to JP2012526033A priority patent/JP2013503129A/ja
Priority to US13/392,231 priority patent/US20120149661A1/en
Priority to EA201200321A priority patent/EA201200321A1/ru
Priority to CN2010800482502A priority patent/CN102574785A/zh
Priority to AU2010288534A priority patent/AU2010288534A1/en
Priority to BR112012008075A priority patent/BR112012008075A2/pt
Priority to EP10745635A priority patent/EP2470502A1/en
Publication of WO2011023677A1 publication Critical patent/WO2011023677A1/en

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Definitions

  • the present invention relates to tetra-substituted 5-membered heteroaryl compounds, capable of inhibiting the interaction between p53, or variants thereof, and MDM2 and/or MDM4, or variants thereof, respectively, especially binding to MDM2 and/or MDM4, or variants thereof, a process for the preparation of such compounds, pharmaceutical preparations comprising such compounds, uses and methods of use for such
  • p53 refers to all genes and/or proteins encoded thereof with the names TP53, p53, TP73, p73, TP63, TP73L, p63.
  • MDM2 refers to all genes and/or proteins encoded thereof with the names MDM2, Mdm2, HDM2, Hdm2.
  • M DM4 refers to all genes and/or proteins encoded thereof with the names MDM4, Mdm4, HDM4, Hdm4, MDMX, MdmX, HDMX, HdmX.
  • Protein p53 is known as a tumor suppressor protein which helps to control cellular integrity and prevents the proliferation of permanently damaged cells by initiating, among other responses, growth arrest or apoptosis (controlled cell death). p53 mediates its effects in that it is a transcription factor capable of regulating a number of genes that regulate e.g. cell cycle and apoptosis. Thus, p53 is an important cell cycle inhibitor. These activities are tightly controlled by MDM2, an important negative regulator of the p53 tumor supressor. "MDM2" (originally from the oncogene "murine double minute 2”) refers both to the name of the gene as well as the protein encoded by that gene.
  • MDM2 protein functions both as a E3 ubiquitin ligase that recognizes the N-terminal trans- activation domain (TAD) of the p53 tumor suppressor and thus mediates the ubiquitin- dependent degradation of p53, and as an inhibitor of p53 transcriptional activation.
  • TAD N-terminal trans- activation domain
  • MDM2 human double minute 2
  • MDM2 human tumor and proliferative disease types
  • MDM4 Another protein belonging to the MDM2 family is MDM4, also known as MDMX.
  • MDM2 in view of its mentioned effects, is capable to inhibit the activity of the tumor suppressor protein p53, thus leading to loss of p53's tumor suppressor activity and inhibiting regulatory mechanisms that impede cells from uncontrolled proliferation. As a consequence, uncontrolled proliferation can take place, leading to tumors, leukemias or other proliferative diseases.
  • the invention relates to heteroarylic compounds of the formula (I), containing between 1 to 2 nitrogen atoms, and/or tautomers and/or N- oxides and/or pharmaceutically acceptable salts and/or solvates thereof,
  • X 1 , X 3 and X 4 are independently C or N,
  • Y is C-H, N-H or N
  • rings A and B are independently selected from phenyl or pyridyl, wherein the Chlorine substituents are independently in the 3 or 4 position;
  • R 1 is selected from the group consisting of
  • C r C 7 -alkyl or C r C 7 -alkoxy groups are unsubstituted or substituted by 1-4 substituents selected from:
  • heterocyclic groups are unsubstituted or substituted by 1-4 substituents selected from:
  • R 4 is selected from the group consisting of
  • Ci-C 7 -alkyl or CrC 7 -alkoxy groups as part of substituents for R 4 as defined above are unsubstituted or substituted by 1-4 groups, independently selected from:
  • Ci-C 7 -alkoxy-carbonyl- C r C 7 -alkyl- oxo (O )
  • R' and R" are independently selected from the group consisting of:
  • heterocyclyl as part of substituents on R' or R" as defined above is unsubstituted or substituted by 1-4 groups, independently selected from:
  • n and m are independently 0 to 2.
  • alkyl refers to a fully saturated branched, including single or multiple branching, or unbranched hydrocarbon moiety having up to 20 carbon atoms. Unless otherwise provided, alkyl refers to hydrocarbon moieties having 1 to 16 carbon atoms, 1 to 10 carbon atoms, 1 to 7 carbon atoms, or 1 to 4 carbon atoms.
  • alkyl include, but are not limited to, methyl, ethyl, ⁇ -propyl, /so-propyl, n-butyl, sec-butyl, /so-butyl, terf-butyl, ⁇ -pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2,2- di methyl pentyl, 2,3-dimethylpentyl, n-heptyl, ⁇ -octyl, n-nonyl, n-decyl and the like.
  • alkyl groups have 1-7, more preferably 1-4 carbons.
  • halo-alkyl refers to an alkyl as defined herein, that is substituted by one or more halo groups as defined herein.
  • the halo-alkyl can be mono- halo-alkyl, di-halo-alkyl or poly-halo-alkyl including per-halo-alkyl.
  • a mono-halo-alkyl can have one iodo, bromo, chloro or fluoro within the alkyl group.
  • Di-halo-alky and poly-halo- alkyl groups can have two or more of the same halo atoms or a combination of different halo groups within the alkyl.
  • the poly-halo-alkyl contains up to 12, or 10, or 8, or 6, or 4, or 3, or 2 halo groups.
  • halo-alkyl include ftuoro- methyl, di-fluoro-methyl, tri-fluoro-methyl, chloro-methyl, di-chloro-methyl, tri-chloro- methyl, penta-fluoro-ethyl, hepta-fluoro-propyl, di-fluoro-chloro-methyl, di-chloro-fluoro- methyl, di-fluoro-ethyl, di-fluoro-propyl, di-chloro-ethyl and dichloro-propyl.
  • a per-halo- alkyl refers to an alkyl having all hydrogen atoms replaced with halo atoms.
  • alkylene refers to divalent alkyl group as defined herein above having 1 to 20 carbon atoms. It comprises 1 to 20 carbon atoms, Unless otherwise provided, alkylene refers to moieties having 1 to 16 carbon atoms, 1 to 10 carbon atoms, 1 to 7 carbon atoms, or 1 to 4 carbon atoms.
  • alkylene examples include, but are not limited to, methylene, ethylene, ⁇ -propylene, /so-propylene, n- butylene, sec-butylene, /so-butylene, terf-butylene, n-pentylene, isopentylene, neopentylene, ⁇ -hexy!ene, 3-methylhexylene, 2,2- dimethylpentylene, 2,3- dimethylpentylene, n-heptylene, ⁇ -octylene, /7-nonylene, /?-decylene and the like.
  • alkoxy refers to a!kyl-O-, wherein alkyl is defined herein above.
  • Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, terf-butoxy, pentyloxy, hexyloxy, cyclopropyloxy-, cyclohexyloxy- and the like.
  • alkoxy groups typically have 1-7, more preferably 1-4 carbons.
  • aryl refers to an aromatic hydrocarbon group having 6-20 carbon atoms in the ring portion. Typically, aryl is monocyclic, bicyclic or tricyclic aryl having 6-20 carbon atoms.
  • aryl refers to an aromatic substituent which can be a single aromatic ring, or multiple aromatic rings that are fused together. Non-limiting examples include phenyl or naphthyl. Aryl may be unsubstituted or substituted by 1-4 substituents, selected from the group selected from
  • N.N-di-d-Cy-alkyl-amino N,N-di-C 1 -C 7 -alkyl-annino- N-C r C 7 -alkyl-amino
  • heterocyclyl- one embodiment, where aryl substituents are or contain C r C 7 -alkyl, said alkyl is preferably Ci-C 4 -alkyl , and in apother embodiment C 1 -C 2 -BIkVl.
  • aryl preferably refers to unsubstituted phepyl or substituted phenyl, wherein the substituents for substituted phenyl are those as described above for "aryl”.
  • heteroaryl saturated (then also called saturated heterocydyl) or partially saturated ring or ring system, for example a A-, 5-, 6-, or 7-membered monocyclic, 7-, 8-, 9-, 10-, 1 1-, or 12-membered bicyclic or 10-, 11-, 12-, 13-, 14- or 15- membered tricyclic ring system and contains at least one heteroatom selected from N, O and S, where the N and S can also optionally be oxidized to various oxidation states.
  • the heteroatom selected from N, O and S, where the N and S can also optionally be oxidized to various oxidation states.
  • heterocycles include oxiranyl, azirinyl, aziridinyl, 1 ,2-oxathioianyl, thienyl, furanyl, tetrahydrofuryl, pyranyl, tetrahydropyranyl, thiopyranyl, thianthrenyl, isobenzo- furanyl, benzofuranyl, chromenyl, 2H-pyrrolyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolidinyl, benzimidazolyl, pyrazolyl, pyrazinyl, pyrazolidinyl, thiazolyl, isothiazolyl, dithiazolyl, oxazolyl, oxadiazolyi, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, piperidinyl, piperazinyl, pyrid
  • the term "heterocydyl-" refers preferably to 5-membered monocyclic unsaturated or partially saturated ring systems. Examples include, but are not limited to pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, oxadiazolyi, isoxazolyl, triazolyl, tetrazolyl.
  • the term "heterocydyl-” refers preferably to 5- to 6-membered monocyclic saturated or partially saturated ring systems. Examples include, but are not limited to pyrrolidinyl, piperazinyl, piperidinyl and morpholinyl.
  • heterocyclydyl- refers preferably to 5- to 6-membered monocyclic saturated or partially saturated ring systems. Examples include, but are not limited to pyrrolinyl, piperidinyl.
  • heteroaryl- refers preferably to 5- to 12-membered mono- or bicyclic unsaturated ring systems. Examples include, but are not limited to pyridyl, benzo- thiophenyl, thiophenyl, indolyl.
  • heterocyclyl- refers preferrably to 5- to 6-membered monocyclic unsaturated or partially saturated ring systems. Examples include, but are not limited oxadiazolyl, dihydroimidazolyl, pyridyl.
  • heterocyclyl- refers preferably to 5-membered monocyclic unsaturated ring systems. Examples include, but are not limited to oxathazolyl. As group in a substituent for R' and R", the term “heterocyclyl-” refers preferrably to 5- to 6- membered monocyclic saturated, unsaturated or partially saturated ring systems.
  • Examples include, but are not limited to pyrrolidinyl, piperazjnyl, piperidinyl, morpholinyl, pyridyl.
  • cycloalkyl refers to saturated or partially unsaturated monocyclic, bicyclic or tricyclic hydrocarbon groups of 3-12 carbon atoms. Unless otherwise provided, cycloalkyl refers to cyclic hydrocarbon groups having between 3 and 10 ring carbon atoms or between 3 and 7 ring carbon atoms, each of which are unsubstituted or substituted by one, or two, or three, or more substituents independently selected from the group of substituents described for "aryl”.
  • Exemplary monocyclic hydrocarbon groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl and cyclohexenyl.
  • bicyclic hydrocarbon groups include bornyl, indyl, hexahydroindyl, tetrahydronaphthyl, decahydronaphthyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptenyl, 6,6- dimethylbicyclo[3.1.1]heptyl, 2,6,6-trimethylbicyclo[3.1.1]heptyl, bicyclo[2.2.2]octy.
  • Exemplary tricyclic hydrocarbon groups include adamantyl.
  • cycloalkyl preferably refers to cyclopropyl, cyclopentyl, cycloheptyl or cyclohexyl.
  • oxy refers to an -O- linking group.
  • a pharmaceutically acceptable) salt thereof especially means that a compound of the formula (I) may be present as such or in mixture with its N-oxide, as tautomer (e.g. due to keto-enol, lactam-lactim, amide-imidic acid or enamine-imine tautomerism) or in (e.g. equivalency reaction caused) mixture with its tautomer, or as a salt of the compound of the formula (I) and/or any of these forms or mixtures of two or more of such forms.
  • tautomer e.g. due to keto-enol, lactam-lactim, amide-imidic acid or enamine-imine tautomerism
  • equivalency reaction caused mixture with its tautomer
  • the invention provides a compound of the formula (I), wherein the total number of nitrogen atoms represented by X 1 , X 3 , X 4 and Y is 2.
  • the invention provides a compound of the formula (I) according to the formula (Ia)
  • the invention provides a compound of the formula (I) according to the formula (Ib)
  • the invention provides a compound of the formula (I) according to the formula (Ic)
  • the invention provides a compound of the formula (I) according to the formula (Id)
  • the invention provides a compound of the formula (I) according to the formula (Ie)
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein
  • both rings A and B are phenyl, wherein the Chlorine substituents are independently in the 3 or 4 position.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein
  • ring A is pyridyl and ring B is phenyl, wherein the chlorine substituents are independently in the 3 or 4 position.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein
  • ring A is phenyl and ring B is pyridyl, wherein the chlorine substituents are independently in the 3 or 4 position.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein
  • ring A is phenyl, wherein the Chlorine substituent is in the 3 position and ring B is phenyl, wherein the Chlorine substituent is in the 4 position.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein
  • ring A is phenyl, wherein the Chlorine substituent is in the 4 position and ring B is phenyl, wherein the Chlorine substituent is in the 3 position.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein
  • ring A is phenyl, wherein the Chlorine substituent is in the 3 position and ring B is phenyl, wherein the Chlorine substituent is in the 3 position.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein
  • both rings A and B are pyridyl, wherein the Chlorine substituents are independently in the 3 or 4 position.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein rings A are selected from a group as shown for R 2 in Table 1.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein rings B are selected from a group as shown for R 3 in Table 1.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R 1 is selected from the group consisting of
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R 1 is selected from the group consisting of
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R 1 is selected from the group consisting of
  • N N-(Ji-C 1 -C 7 -alkyl-amino- Ci-Cy-alkoxy-carbonyl-amino- C ⁇ -C ⁇ -alkyl-carbonyl-amino- phosphonyl- Ci-C 7 -alkyl-phosphonyl- di-CrC 7 -alkyl-phosphonyl- benzyloxycarbonyl
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R 1 is selected from the group consisting of
  • R 1 when R 1 is heterocyclyl-, said heterocycle is selected from tetrazolyl, oxadiazolyl, imidazolyl, oxadiazolonyl, oxazolyl, pyrrolyl, pyrazolyl or dihydrotriazolethionyl, wherein said heterocyclyl is optionally substituted by 1 or 2 groups independently selected from methyl, ethyl, amino and methylamino, and when the heterocyclyl group is pyrazolyl or oxadiazolyl, said heterocyclyl may also be optionally substituted by N-d-Ca-alkylamino-carbonyl, CrCs-alkyl-carbonyl, carboxy, C 1 -C 3 - alkoxy- CrCs-alkyl-amino, trimethylsilyl-ethoxy-methyl or benzylamino.
  • R 1 aminooxadiazolyl In another preferred embodiment, R 1 aminooxadiazolyl.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R 1 selected from a group as shown in Table 1.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R 4 is selected from the group consisting of
  • N.N-di-Cr ⁇ -alkyl-hydrazino-carbonyl-C T Cralkyl-amino- N.N-di-Ct- ⁇ -alkyl-N'-Ct- ⁇ -alkyl-hydrazino-carbonyl-Ci-C T -alkyl-amino- CrC ⁇ alkyl-carbonyl-hydrazino-carbonyl-C ⁇ -alkyl-amino- d-C ⁇ alkyl-carbonyl-N-C ⁇ -alkyl-N'-C ⁇ Cralkyl-hydrazino-carbonyl-CrC T -alkyl- amino- hydrazino-carbonyl-Ci-C 7 -alkyl-N-(C 1 -C 7 -alkyl)-amino- N-C 1 -C 7 -alkyl-hydrazino-carbonyl-C r C 7 -alkyl-N-(C 1 -C
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R 4 is selected from the group consisting of substituted d-alkyl- C 2 -C 7 -alkyl- aryl- heteroaryl- heterocyclyl- C 3 -C 10 -cycloalkyl- aryl-C r C 7 -a!kyl- heterocyclyl-C i -C 7 -alkyl- C 3 -Cio-cycloalkyl-CrC 7 -alkyl- unsubstituted or substituted by 1 -2 substituents selected from hydroxy-
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R" is selected from the group consisting of
  • N.N-di-Ci-Cy-alkyl-aminocarbonyl C ⁇ C ⁇ alkyl-amino- amino-heterocyclyl-C r C 7 -alkyl-amino-phenyl- formyl- carboxy-Cr -alkyl-amino
  • R 4 is Cs-CnrCycloalkyl-CVCr-alkyl-, said C 3 -C 10 -cycloalkyl-
  • CrCr-alkyl- is cyclopropylmethyk
  • R 4 is selected from
  • phenyl said phenyl being optionally substituted by one or two substituents independently selected from methyl, amino and halo,
  • pyridyl said pyridyl being optionally substituted by methyl
  • Ci-C 5 -alkyl Ci-C 5 -alkyl
  • indolyl said indolyl being optionally substituted by methyl and cycloheptyl.
  • R is phenyl or cyclohexyl.
  • R 4 is as disclosed herein with the proviso that R 4 is not phenyl directly substituted with at least one alkoxy substituent.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R 4 selected from a group as shown in Table 1.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R 1 and R" are independently selected from the group consisting of heterocyclyl-heterocyclyl-carbonyl- d-Cy-alkyl- hydroxy-
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R' and R" are independently selected from the group consisting of hydroxy- C r C 7 -alkoxy- halogen- halo-C r C 7 -alkyl- cyano- formyl- C r C 7 -alkyl- amino-carbonyl- N-C r C 7 -alkyl-amino-carbonyl- N, N-di-C-i -Cz-alkyl-amino-carbonyl-
  • R' and/or R" are or contain a C r C 7 -alkyl or C r C 7 -alkoxy group
  • said C r C 7 -alkyl and/or CVCr-alkoxy groups are preferably a C r C 4 -alkyl or a CrC 4 -alkoxy group.
  • R 1 and/or R" are heterocyclyl-heterocyclyl-carbonyl- C r C 7 -alkyl-
  • said heterocyclyl-heterocyclyl-carbonyl-Ci-tValkyl- is piperazinyl-piperidinyl- carbonyl-methyl-, wherein said piperazinyl is optionally methyl substituted.
  • R' and/or R" are heterocyclyl-C 1 -C 7 -alkyl-
  • said heterocyclyl-CrCy-alkyl- is piperazinyl- Ci-C 7 -alkyl-, wherein said piperazinyl is optionally methyl substituted.
  • said heterocyclyl-carbonyl-CrC ⁇ -alkyl- is azetidinyl-carbonyl-methyl, wherein said azetidinyl is optionally substituted by one or two methyl substituents.
  • R' and/or R" are heterocyclyl-C r C 7 -alkyl-aminocarbonyl
  • said heterocyclyl is morphoiinyl or piperazinyl, wherein said piperazinyl is optionally methyl substituted.
  • R' and/or R" are heterocyclyl-CrC T -alkyl-amino-carbonyl- Ci-C T -alkyl-
  • said heterocyclyl-C r C 7 -alkyl-amino-carbony!-C 1 -C 7 -a!kyl- is pyridyl-methyl- amino-carbonyl-methyk
  • R' and/or R" are aryl-C 1 -C 7 -alky!-amino-carbonyl-C 1 -C 7 - aikyl-
  • said aryl-CrC ⁇ alkyl-amino-carbonyl-CIVCValkyl- is phenyi-methyl-aminocarbonyl- methyl-, wherein said phenyl is optionally substituted with a methyl or methoxy group.
  • R' and/or R" are heterocyclyl
  • said heterocyclyl is oxatriazolyl
  • R' and/or R" are C 1 -C 7 -alkyl-carbonyl-amino-C r C 7 -alkyi-
  • said C 1 -C 7 -alkyl-carbonyl-amino-C 1 -C 7 -alkyl- is methyl-carbonyl-amino-methyl-.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R' and R" are independently selected from the group consisting of
  • R' and /or R" are selected from at least one of the group consisting of
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R' and /or R" are fluoro, and optionally another R' and/or R" substituent is present as defined herein.
  • the invention provides a compound of the formula (I) and/or a tautomer and/or an N-oxide and/or a pharmaceutically acceptable salt and/or a solvate thereof, wherein R" is selected from the group consisting of
  • ring A is 3-chloro-4-fluoro-phenyl.
  • Example 3 1 -(S-chloro ⁇ -methyl-phenyO-S-tS-chloro-phenyO ⁇ - ⁇ -dimethyl-phenylJ-i H- imidazole-4-nitrile
  • Example 6 1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-(3,4-dimethyl-phenyl)-
  • Example 9 1 -(3-Chloro-2-fluoro-phenyl)-2-(3-chloro-phenyl)-5-phenyl-1 H-pyrrole-3- carboxylic acid ethyl ester
  • Example 11 1 ,5-Bis-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 12 1 ,5-Bis-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4-carboxylic acid
  • Example 13 1 ,5-Bis-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4-carboxylic acid (2- morpholin-4-yl-ethyl)-amide
  • Example 15 1 ,5-Bis-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4-carboxylic acid (3- dimethylamino-propyl)-methyl-amide
  • Example 17 6-[5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-4-(2H-tetrazol-
  • Example 20 5-[1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-(3,4-dimethyl- phenyl)-1 H-imidazoM-yl]-2-methyl-2H-tetrazole
  • Example 32 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazole-4-carboxylic acid (2-hydroxy-ethyl)-amide
  • Example 36 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- car boxy lie acid ethyl ester
  • Example 37 1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxyiic acid
  • Example 38 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid amide
  • Example 39 1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid methylamide
  • Example 40 1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid hydroxyamide
  • Example 41 1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1H-imidazole-4- carboxylic acid dimethylamide
  • Example 45 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazole-4-carboxylic acid (2-hydroxy-ethyl)-amide
  • Example 47 i-tS-Chloro ⁇ -methyl-phenyl ⁇ -tS-chloro-phenyl ⁇ -m-tolyM H-imidazole ⁇ - carboxylic acid ethyl ester
  • Example 48 i-t ⁇ -Chloro ⁇ -methyl-phenylJ- ⁇ -tS-chloro-phenylJ ⁇ -m-tolyl-i H-imidazole-4- carboxylic acid
  • Example 50 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-m-tolyl-1 H-imidazole-4- carboxylic acid amide
  • Example 51 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-m-tolyl-1 H-imidazole-4- carboxyltc acid ethoxy-amide
  • Example 54 i-t ⁇ -Chloro ⁇ -methyl-phenylJ- ⁇ -tS-chloro-phenylJ ⁇ -m-tolyl-i H-imidazole-4- carboxylic acid hydroxyamide
  • Example 58 1 -( ⁇ -Chloro-2-methyl-phenyl)- ⁇ -(3-chloro-phenyl)-2-p-tolyl-1 H-imidazo!e-4- carboxylic acid ethyl ester
  • Example 60 1 -(5-Chloro-2-methyl-phenyl)-5-(2,5-dichloro-phenyl)-2-m-tolyl-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 61 1 -(5-Chloro-2-methyl-phenyl)-5-(2,5-dichloro-phenyl)-2-m-tolyl-1 H- imidazole-4-carboxylic acid
  • Example 62 5-(3-Chloro-2-fluoro-pheny!)-1-(5-chloro-2-methyl-phenyl)-2-m-tolyl-1H- imidazole-4-carboxylic acid ethyl ester
  • Example 63 5-(3-Chloro-2-fluoro-phenyl)-1-(5-chloro-2-methyl-phenyl)-2-m-tolyl-1 H- imidazole-4-carboxylic acid
  • Example 65 S- ⁇ -Chloro ⁇ -methoxy-phenyO-i-fS-chloro ⁇ -methyl ⁇ henyl ⁇ -m-tolyM H- imidazole-4-carboxylic acid
  • Example 70 N-[5-(5-Chloro-2-methoxy-phenyl)-1-(5-chloro-2-methyl-phenyl)-2-m-tolyl-
  • Example 72 1-(5-Chloro-2-methyl-phenyl)-5-(3,4-dichloro-phenyl)-2-m-tolyl-1 H- imidazole-4-carboxylic acid
  • Example 74 2- ⁇ 4-Chloro-2-[5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-4-(2H-tetrazol-5- yl)-imidazol-1-yl]-phenyl ⁇ -N-[2-(4-methyl-piperazin-1-yl)-ethyl]-acetamide
  • Example 77 1-(3-Chloro-2-fluoro-phenyl)-5-(3,4-dichloro-phenyl)-2-m-tolyl-1 H-imidazole- 4-carboxylic acid ethyl ester
  • Example 78 1-(3-Chloro-2-fluoro-phenyl)-5-(3,4-dichloro-phenyl)-2-m-tolyl-1 H-imidazole-
  • Example 79 1-(3-Chloro-phenyl)-5-(3,5-dichloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid ethyl ester
  • Example 80 1-(3-Chloro-phenyl)-5-(3,5-dichloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid
  • Example 81 1 -(3-Chloro-phenyl)-5-(3,5-dichloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid methylamide
  • Example 82 1-(3-Chloro-2-fluoro-phenyl)-5-(5-chtoro-2-methoxy-phenyl)-2-m-tolyl-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 83 i- ⁇ -Chloro ⁇ -fluoro-phenylJ-S-tS-chloro ⁇ -methoxy-phenylJ ⁇ -m-tolyl-I H- imidazole-4-carboxylic acid
  • Example 84 1-(3-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-methoxy-phenyl)-2-m-tolyl-1 H- imidazole-4-carboxylic acid amide
  • Example 87 1 -(3-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-2-m-tolyl-1 H-imidazole-4- carboxylic acid ethyl ester
  • Example 88 1-(3-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-2-m-tolyl-1H-imidazole-4- carboxylic acid
  • Example 92 I .S-Bis- ⁇ -chloro-phenylJ ⁇ -isobutyl-I H-imidazole ⁇ -carboxylic acid ethyl ester
  • Example 96 1 ,5-Bis-(3-chloro-phenyl)-2-isobutyl-1 H-imidazole-4-carboxylic acid (2- morpholin-4-yl-ethyl)-amide
  • Example 99 5-(3-Chloro-2-fluoro-phenyl)-1-(3-chloro-phenyl)-2-isobutyl-1 H-imidazole-4- carboxylic acid methylamide
  • Example 100 5-(3-Chloro-2-fluoro-phenyl)-1-(3-chloro-phenyl)-2-isobutyl-1H-imidazole-
  • Example 102 N-tert-Butyl-2- ⁇ 4-chloro-2-[5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-4-(2H- tetrazol-5-yl)-imidazol-1-yl]-phenyl ⁇ -acetamide
  • Example 104 2- ⁇ 4-Chloro-2-[5-(3-chloro-4-fluoro-phenyl)-2-cyclohexy!-4-(2H-tetrazol-5- yl)-irnidazol-1-yl]-phenyl ⁇ -N-pyridin-2-ylrnethyl-acetamide
  • Example 105 3- ⁇ 2-[4-Carbamoyl-5-(3-chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro- phenyl)-1 H-imidazol-2-yl]-pheny!amino ⁇ -propionic acid tert-butyl ester
  • Example 106 5-(3-Chloro-2-fluoro-phenyl)-1-(3-chloro-phenyl)-2-phenyl-1H-imidazole-4- carboxyljc acid ethyl ester
  • Example 110 1,5-Bis-(3-chloro-phenyl)-2-(2-fluoro-phenyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 112 1,5-Bis-(3-chloro-phenyl)-2-(2-fluoro-phe ⁇ yl)-1H-imidazole-4-carboxylic acid amide
  • Example 113 1 ,5-Bis-(3-chloro-phenyl)-2-(2-fluoro-phenyl)-1 H-imidazole-4-carboxylic acid methylamide
  • Example 114 3- ⁇ 2-[4-Carbamoyl-5-(3-chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro- phenyl)-1 H-imidazol-2-yl]-phe ⁇ ylamino ⁇ -propionic acid
  • Example 116 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2- ⁇ 2-[2-(2,2- dimethoxy-ethylcarbamoyl)-ethylamino]-phenyl ⁇ -1 H-imidazole-4-carboxylic acid amide
  • Example 117 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2- ⁇ 2-[2-(methyl- pyridin-3-ylmethyl-carbamoyl)-ethylamino]-phenyl ⁇ -1 H-imidazole-4-carboxylic acid amide
  • Example 118 2-Benzyl-1 ,5-bis-(3-chloro-phenyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 122 2-(2-Chloro-phenyl)-1 ,5-bis-(3-chloro-phenyl)-1 H-imidazole-4-carboxylic acid
  • Example 129 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-pyridin-3-yl-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 130 1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-pyridin-3-yl-1 H- imidazole-4-carboxylic acid
  • Example 134 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-pyridin-2-yl-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 135 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-pyridin-2-yl-1H- imidazole-4-carboxylic acid
  • Example 136 1-(3-Chloro-4-fluoro-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid ethyl ester
  • Example 137 1-(3-Chloro-4-fluoro-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxyiic acid
  • Example 138 1-(3-Chloro-4-fluoro-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid methylamide
  • Example 139 1-(3-Chloro-4-fluoro-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid amide
  • Example 140 1-(3-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-methoxy-phenyl)-2-phenyl-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 141 1-(3-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-methoxy-phenyl)-2-phenyl-1 H- imidazole-4-carboxylic acid
  • Example 142 1-(3-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-hydroxy-phenyl)-2-phenyl-1 H- imidazole-4-carboxylic acid
  • Example 143 1-(3-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-methoxy-phenyl)-2-phenyl-1H- imidazole-4-carboxylic acid amide
  • Example 144 1-(3-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-methoxy-phenyl)-2-phenyl-1 H- imidazole-4-carbonitrile
  • Example 150 5-(5-Chloro-2-hydroxy-phenyl)-1-(5-chloro-2-methyl-phenyl)-2-(6-methyl- pyridin-2-yl)-1 H-imidazole-4-carboxylic acid
  • Example 151 5-(5-Chloro-2-methoxy-phenyl)-1-(5-chloro-2-methyl-phenyl)-2-(6-methyl- pyridin-2-yl)-1 H-imidazole-4-carbonitrile
  • Example 153 2-[2-(2-Carbamoyl-ethylamino)-phenyl]-5-(3-chloro-4-fluoro-phenyl)-1-(3- chloro-2-fluoro-phenyl)-1 H-imidazole-4-carboxylic acid amide
  • Example 154 5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-[2-(2- hydrazinocarbonyl-ethylamino)-phenyl]-1 H-imidazole-4-carboxylic acid amide
  • Example 155 1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-(6-methyl-pyridin-2-yl)-
  • Example 156 1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-(6-methyl-pyridin-2-yl)-
  • Example 158 1 -(5-Chloro-2-methyl-phenyl)-5-(3,4-dichloro-phenyl)-2-(6-methyl-pyridin-
  • Example 159 1-(5-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-2-m-tolyl-1 H-imidazole-4- carboxylic acid ethyl ester
  • Example 160 1-(5-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-2-m-tolyl-1 H-imidazole-4- carboxylic acid
  • Example 161 1-(5-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-methoxy-phenyl)-2-m-tolyl-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 162 1-(5-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-methoxy-phenyl)-2-m-tolyl-1 H- imidazole-4-carboxylic acid
  • Example 163 1-(5-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-methoxy-phenyl)-2-m-tolyl-1 H- imidazole-4-carboxylic acid amide
  • Example 164 1-(5-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-methoxy-phenyl)-2-m-tolyl-1 H- imidazoie-4-carbonitrile
  • Example 165 1-(5-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-hydroxy-phenyl)-2-m-tolyl-1 H- imidazole-4-carbonitrile
  • Example 166 5-(3-Chloro-4-fluoro-phenyl)-1-(5-chloro-2-fluoro-phenyl)-2-m-tolyl-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 168 1-(3-Chloro-phenyl)-5-(3,4-dichloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid ethyl ester
  • Example 170 1-(3-Chloro-phenyl)-5-(3,4-dichloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid methylamide
  • Example 171 1-(3-Chloro-2-fluoro-phe ⁇ yl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazoie-4- carboxylic acid ethyl ester
  • Example 172 1-(3-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazoie-4- carboxylic acid
  • Example 173 1-(3-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid methylamide
  • Example 175 1-(3-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid hydroxyamide
  • Example 176 1- ⁇ 3-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- carbonitrile
  • Example 180 5-(5-Chloro-2-methoxy-phenyl)-1-(5-chloro-2-methyl-phenyl)-2-(3,4- dimethyl-phenyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 181 5-(5-Chloro-2-methoxy-phenyl)-1-(5-chloro-2-methyl-phenyl)-2-(3,4- dimethyl-phenyl)-1 H-imidazole-4-carboxylic acid
  • Example 182 5-(5-Chloro-2-methoxy-phenyl)-1 -(5-chloro-2-methyl-phenyl)-2-(3,4- dimethyl-phenyl)-1 H-imidazole-4-carboxylic acid amide
  • Example 185 1-(5-Chloro-2-methyl-phe ⁇ yl)-5-(3,4-dichloro-phenyl)-2-(3,4-dimethyl- phenyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 186 1 -(5-Chloro-2-methyl-phenyl)-5-(3,4-dichloro-phenyl)-2-(3,4-dimethyl- phenyl)-1 H-imidazole-4-carboxylic acid
  • Example 188 5-(3-Chloro-4-fluoro-phenyl)-1 -(5-chloro-2-methyl-phenyl)-2-(3,4-dimethyl- phe ⁇ yl)-1 H-imidazole-4-carboxylic acid
  • Example 190 5- ⁇ 3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-phenyl-1H- imidazole-4-carboxylic acid
  • Example 191 i-fS-Chloro ⁇ -fluoro-phenyO-S-CS-chloro ⁇ -methoxy-phenyO ⁇ -f ⁇ -methyl- pyridin-2-yl)-1H-imidazole-4-carboxylic acid ethyl ester
  • Example 192 1 -(S-Chloro ⁇ -fluoro-phenyO-S-fS-chloro ⁇ -methoxy-phenyl ⁇ -f ⁇ -methyl- pyridin-2-yl)-1 H-imidazole-4-carboxylic acid
  • Example 195 2-[1-(3-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-methoxy-phenyl)-4-(2H- tetrazol-5-yl)-1 H-imidazol-2-yl]-6-methyl-pyridine
  • Example 196 1-(3-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-2-(6-methyl-pyridin-2-yl)-
  • Example 198 1 -(3-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-2-(6-methyl-pyridin-2-yl)-
  • Example 200 2-[1 -(3-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-4-(2H-tetrazol-5-yl)-1 H- imidazol-2-yl]-6-methyl-pyridine
  • Example 201 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-cyclohexyl-1H- imidazole-4-carboxylic acid ethyl ester
  • Example 202 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-cyclohexyl-1 H- imidazole-4-carboxylic acid lithium salt
  • Example 203 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-cyclohexyl-1 H- imidazole-4-carboxylic acid amide
  • Example 204 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-cyclohexyl-1 H- imidazole-4-carboxylic acid ethylamide
  • Example 205 2- ⁇ 2-[2-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-ethylamino]-phenyl ⁇ -5-(3-chloro-4- fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-1 H-imidazole-4-carboxylic acid amide
  • Example 206 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-[2-(2-methyl-
  • Example 207 2- ⁇ 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-[2-(2-methyl-
  • Example 210 1 -(3-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-methoxy-phenyl)-2-cyclohexyl-
  • Example 217 5-(3-Chloro-4-fluoro-phenyl)-1 -(5-chloro-2-methyl-phenyl)-2-cyclohexyl-
  • Example 220 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-cyclohexyl-1 H- imidazole-4-carboxylic acid
  • Example 224 2-[5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-thiophen-3- yl-1 H-imidazol-4-yl]-5-methyl-[1 ,3,4]oxadiazole
  • Example 226 5-[5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-thiophen-3- yl-1 H-imidazol-4-yl]-[1 ,3,4]oxadiazol-2-ylamine
  • Example 227 2-(2-Amino-phenyl)-5-(3-chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro- phenyl)-1 H-imidazole-4-carboxylic acid amide
  • Example 228 5-(3-Chloro-phenyl)-1-(4-chloro-phenyl)-2-(2,2-dimethyl-propyl)-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 231 5-(3-Chloro-phenyl)-1 -(4-chloro-phenyl)-2-(2,2-dimethyl-propyl)-1 H- imidazole-4-carboxylic acid (2-morpholin-4-yl-ethyl)-amide
  • Example 232 2-[2-(2-Amino-ethylamino)-phenyl]-5-(3-chloro-4-fluoro-phenyl)-1 -(3- ch!oro-2-f!uoro-phenyi)-1H-imidazole-4-carboxylic acid amide
  • Example 234 N-(2- ⁇ 2-E4-(N'-Acetyl-hydrazinocarbonyl)-5-(3-chloro-4-fluoro-phenyl)-1-(3- chloro ⁇ -fluoro-phenyO-IH-imidazol ⁇ -y ⁇ -phenylaminoJ-ethylJ-acetamide
  • Example 236 1 ,5-Bis-(3-chloro-phenyl)-2-(2,2-dimethyl-propyl)-1 H-imidazole-4- carboxylic acid ethyl ester
  • Example 237 1 ,5-Bis-(3-chloro-phenyl)-2-(2,2-dimethyl-propyl)-1 H-imidazole-4- carboxylic acid lithium salt
  • Example 238 1 ,5-Bis-(3-chloro-phenyl)-2-(2,2-dimethyl-propyl)-1 H-imidazole-4- carboxylic acid ethylamide
  • Example 240 1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-(2,2-dimethyl-propyl)-
  • Example 241 1-(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-(2,2-dimethyl-propyl)- 1 H-imidazole-4-carboxylic acid
  • Example 242 1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-(2,2-dimethyl-propyl)-
  • Example 243 1 -(5-Chloro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-(2,2-dimethyl-propyl)-
  • Example 244 5-(5-Chloro-2-methoxy-phenyl)-1-(5-chloro-2-methyl-phenyl)-2-(2,2- dimethyl-propyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 245 5-(5-Chloro-2-methoxy-phenyl)-1 -(5-chloro-2-methyl-phenyl)-2-(2,2- dimethyl-propyl)-1 H-imidazole-4-carboxylic acid
  • Example 248 5-(3-Chloro-4-fluoro-phenyl)-1 -(5-chloro-2-methyl-phenyl)-2-(2,2-dimethyl- propyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 250 5-(3-Chloro-4-fluoro-phenyl)-1 -(5-chloro-2-methyl-phenyl)-2-(2,2-dimethyl- propyl)-1 H-imidazole-4-carboxylic acid amide
  • Example 251 5-(3-Chloro-4-fluoro-phenyl)-1-(5-chloro-2-methyl-phenyl)-2-(2,2-dimethyl- propyl)-1 H-imidazole-4-carbonitrile
  • Example 253 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-(2,2-dimethyl- propyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 254 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-(2,2-dimethyl- propyl)-1 H-imidazole-4-carboxylic acid
  • Example 257 5-[5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-(2,2- dimethyl-propyl)-1 H-imidazol-4-yl]-2H-tetrazole
  • Example 258 5-(3-Chloro-4-f luoro-phenyl)- 1 -(3-chtoro-2-f luoro-phenyl)-2- cyclopentylmethyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 260 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2- cyclopentylmethyl-1 H-imidazole-4-carboxylic acid amide
  • Example 262 5-[5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2- cyclopentylmethyl-1 H-imidazol-4-yl]-2H-tetrazole
  • Example 263 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2- cyclohexylmethyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 265 ⁇ -tS-Chloro ⁇ -fluoro-phenyO-i-tS-chloro ⁇ -fluoro-phenyl) ⁇ - cyclohexylmethyl-1 H-imidazole-4-carboxylic acid
  • Example 266 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2- cyclohexylmethyl-1 H-imidazole-4-carboxylic acid amide
  • Example 268 ⁇ -E ⁇ - ⁇ -Chloro ⁇ -fluoro-phenylH-tS-chloro ⁇ -fluoro-phenyl) ⁇ - cydohexylmethyl-1H-imidazol-4-yl]-2H-tetrazole
  • Example 274 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-(3-hydroxy- phenyl)-1 H-imidazole-4-carboxylic acid
  • Example 277 5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-(1 H-indol-6-yl)- 1 H-imidazole-4-carboxylic acid amide
  • Example 278 5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-(1-methyl-1 H- indol-5-yl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 280 2-Benzo[b]thiophen-5-yl-5-(3-chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro- phenyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 281 2-Benzo[b]thiophen-5-yl-5-(3-chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro- phenyl)-1 H-imidazole-4-carboxylic acid
  • Example 282 2-Benzo[b]thiophen-5-yl-5-(3-chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro- phenyl)-1 H-imidazole-4-carboxylic acid amide
  • Example 283 5- ⁇ 3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-(1 H-indol-3-yl)-
  • Example 284 5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-(1 H-indol-3-yl)-
  • Example 290 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-(3-chloro- phenyl)-1 H-imidazole-4-carboxylic acid
  • Example 294 2-(2-Amino-phenyl)-5-(3-chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro- phenyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 296 2-[2-(2-Acetylamino-ethylamino)-phenyl]-5-(3-chloro-4-fluoro-phenyl)-1 -(3- chloro-2-fluoro-phenyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 298 2-[2-(2-Acetylamino-ethylamino)-phenyl]-5-(3-chloro-4-fluoro-phenyl)-1-(3- chloro-2-fluoro-phenyl)-1 H-imidazole-4-carboxylic acid amide
  • Example 299 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-(5- hydroxymethyl-thiophen-3-yl)-1H-imidazole-4-carboxylic acid ethyl ester
  • Example 300 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-(5- hydroxymethyl-thiophen-3-yl)-1 H-imidazole-4-carboxylic acid
  • Example 301 S-p-Chloro ⁇ -fluoro-phenylJ-HS-chloro ⁇ -methyl-phenylJ ⁇ -m-tolyl-IH- imidazole-4-carboxylic acid ethyl ester
  • Example 305 5-(3-Chloro-4-fluoro-phenyl)-1-(5-chloro-2-methyl-phenyl)-2-(6-methoxy- pyridin-2-yl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 306 5-(3-Chloro-4-fluoro-phenyl)-1-(5-chloro-2-methyl-phenyl)-2-(6-methoxy- pyridin-2-yl)-1 H-imidazole-4-carboxylic acid
  • Example 307 1-(3-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-hydroxy-phenyl)-2-phenyl-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 308 N-(2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-1- (3-chloro-2-fluoro-phenyl)-1H-imidazol-2-yl]-phenylamino ⁇ -ethyl)-acetamide
  • Example 310 [5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-cyc!ohexyl-1 H- imidazol-4-yl]-phosphonic acid diethyl ester
  • Example 311 [5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-cyclohexyl-1 H- imidazol-4-yl]-phosphonic acid monoethyl ester
  • Example 312 [5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-cyclohexyl-1 H- imidazol-4-yl]-phosphonic acid
  • Example 315 [5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazol-4-yl]-phosphonic acid diethyl ester
  • Example 316 5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-m-tolyl-1 H- imidazole-4- ⁇ /H-methyl-sulfoximine
  • Example 317 [5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazol-4-yl]-phosphonic acid monoethyl ester
  • Example 320 5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazole-4-carboxylic acid hydrazide
  • Example 321 5-[5- ⁇ 3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazol-4-yl]-[1 ,3,4]oxadiazol-2-ylamine
  • Example 322 2-[5- ⁇ 3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazol-4-yl]-5-methyl-[1 ,3,4]oxadiazole
  • Example 325 5-(3-Chloro-phenyl)-1-(4-chloro-phenyi)-2-phenyl-1 H-imidazole-4- carboxylic acid ethyl ester
  • Example 328 5- ⁇ 3-Chloro-phenyl)-1 - ⁇ 4-chloro-phenyl)-2-phenyl-1 H-imidazoie-4- carboxylic acid (2-rnorpholin-4-yl-ethyl)-amide
  • Example 330 5- ⁇ 3-Chloro-phenyl)-1 - ⁇ 4-chlorophenyl)-2-phenyl-1 H-imidazole-4- carboxylic acid cyclopropylmethyl-amide
  • Example 331 5-[5- ⁇ 3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazol-4-yl]-3-methyl-[1 ,2,4]oxadiazole
  • Example 332 1 -[2- ⁇ Acetylamino-methyl)-5-chloro-phenyl]-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-1 H-imidazole-4-carboxylic acid
  • Example 334 5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-(6-methyl- pyridin-2-yl)-1 H-imidazole-4-carboxylic acid
  • Example 335 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-f luoro-phenyl)-2-(6-methyl- pyridin-2-yl)-1H-imidazole-4-carboxylic acid amide
  • Example 336 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-(6-methyl- pyridin-2-yl)-1H-imidazole-4-carbonitrile
  • Example 337 2-[5-(3-Chloro-4-fiuoro-phenyl)-1-(3-ch [ oro-2-fluoro-phenyl)-4-(2H-tetrazol-
  • Example 339 1 -(S-Chloro ⁇ -methyl-phenyO-S- ⁇ -chloro-phenylJ ⁇ -piperidin-S-yl-i H- imidazole-4-carboxylic acid ethyl ester
  • Example 340 1 -(5-Chioro-2-methyl-phenyl)-5-(3-chloro-phenyl)-2-piperidin-3-yl-1 H- imidazole-4-carboxylic acid
  • Example 341 HS-Chloro ⁇ -methyl-phenyO-S-tS-chioro-phenyl ⁇ -fi-methyl-piperidin-S- yl)-1 H-imidazoie-4-carboxylic acid ethyl ester
  • Example 342 1-(5-Chloro-2-methyl-phenyl)-5-(3-chioro-phenyl)-2-(1-methyl-piperidin-3- yl)-1 H-imidazole-4-carboxylic acid
  • Example 343 1 -[2-(Acetylamino-methyl)-5-chloro-phenyl]-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-1 H-imidazole-4-carboxylic acid amide
  • Example 344 ⁇ 5-[5-(3-Chloro-4-fiuoro-phenyl)-1 -(3-chloro-2-f!uoro-phenyl)-2-cyclohexyl- 1 H-imidazol-4-yl]-[1 ,3,4]oxadiazol-2-yl ⁇ -methyl-amine
  • Example 345 S-IS- ⁇ -Chtoro ⁇ -fluoro-phenylJ-i-fS-chloro ⁇ -fluoro-phenylJ ⁇ -phenyl-i H- imidazol-4-yl]-1 H-pyrazole-4-carboxylic acid ethylamide
  • Example 346 2-[3-(tert-Butyl-diphenyl-silanyloxy)-cyclohexyl]-5-(3-chloro-4-fiuoro- pheny!)-1-(5-chloro-2-methyl-phenyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 347 2-[3-(tert-Butyl-diphenyl-silanyloxy)-cyclohexyl]-5-(3-chloro-4-fiuoro- phenyl)-1 -(5-chloro-2-methyl-phenyl)-1 H-imidazole-4-carboxylic acid
  • Example 348 S-fS-Chloro ⁇ -fluoro-phenyO-i-fS-chloro ⁇ -methyl-phenyO ⁇ S-hydroxy- cyclohexyl)-1 H-imidazole-4-carboxylic acid
  • Example 349 2-[3-(tert-Butyl-diphenyl-silanyloxy)-cyclohexyl]-5-(3-chloro-4-fluoro- phenyl)-1-(3-chloro-2-fluoro-phenyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 350 2-[3-(tert-Butyl-diphenyl-silanyloxy)-cyclohexyl]-5-(3-chloro-4-fluoro- phenyl)-1 -(3-chloro-2-fluoro-phenyl)-1 H-imidazole-4-carboxylic acid
  • Example 351 2-[3-(tert-Butyl-diphenyl-silanyloxy)-cyclohexyl]-5-(3-chloro-4-fluoro- phenyl)-1-(3-chloro-2-fluoro-phenyl)-1 H-imidazole-4-carboxylic acid amide
  • Example 352 S-fS-Chloro ⁇ -fluoro-phenyO-i-fS-chloro ⁇ -fluoro-phenyO ⁇ -CS-hydroxy- cyclohexyl)-1 H-imidazole-4-carboxy!ic acid
  • Example 353 3-[5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-4-(2H-tetrazol-
  • Example 354 1-(3-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-formyl-phenyl)-2-phenyl-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 357 5-(5-Chloro-2-dimethylaminomethyl-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2- phenyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 358 5-(5-Chloro-2-dimethylaminomethyl-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2- phenyl-1 H-imidazole-4-carboxylic acid
  • Example 359 1 -(3-Chloro-2-fluoro-phenyl)-5-[5-chloro-2-(4-methyl-piperazin-1 -ylmethyl)- phenyl]-2-phenyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 360 1-(3-Chloro-2-fluoro-phenyl)-5-[5-chloro-2-(4-methyl-piperazin-1-ylmethyl)- phenyl]-2-phenyl-1 H-imidazole-4-carboxylic acid
  • Example 361 5-(5-Chloro-2-dimethylaminomethyl-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2- phenyl-1 H-imidazole-4-carboxylic acid amide
  • Example 362 1 -(3-Chloro-2-fluoro-phenyl)-5-[5-chloro-2-(4-methyl-piperazin-1 -ylmethyl)- phenyl]-2-phenyl-1 H-imidazole-4-carboxylic acid amide
  • Example 363 1 -(3-Chloro-2-fluoro-phenyl)-5-[5-chloro-2-(4-methyl-piperazin-1 -ylmethyl)- phenyl]-2-phenyl-1H-imidazole-4-carbonitrile
  • Example 364 1 - ⁇ 4-Chloro-2-[3-(3-chloro-2-fluoro-phenyl)-2-phenyl-5-(2H-tetrazol-5-yl)-
  • Example 365 1-(3-Chloro-2-fluoro-phenyl)-5-(5-chloro-2-formyl-phenyl)-2-cyclohexyl-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 366 5-(5-Chloro-2-dimethylaminomethyl-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2- cyclohexyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 368 1-(3-Chloro-2-fluoro-phenyl)-5-[5-chloro-2-(4-methyl-piperazin-1-ylmethyl)- phenyl]-2-cyclohexyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 369 1 -(3-Chloro-2-f luoro-phenyl)-5-[5-chloro-2-(4-methyl-piperazin-1 -ylmethyl)- phenyl]-2-cyclohexyl-1 H-imidazole-4-carboxylic acid
  • Example 370 1-(3-Chloro-2-fluoro-phenyl)-5-[5-chloro-2-(4-methyl-piperazin-1-ylmethyl)- phenyl]-2-cyclohexyl-1 H-imidazole-4-carboxylic acid amide
  • Example 371 1-(2-Carboxymethyl-5-chloro-phenyl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 372 1-(2-tert-Butoxycarbonylmethyl-5-chloro-phenyl)-5-(3-chloro-4-f!uoro- phenyl)-2-cyclohexy!-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 373 1-(2-Carboxymethyl-5-chloro-phenyl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-1 H-imidazole-4-carboxylic acid
  • Example 374 1 -(2-Carbamoylmethyl-5-chloro-phenyl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 375 5-(3-Chloro-4-fluoro-phenyl)-1 -(5-chloro-2-methylcarbamoylmethyl- phenyl)-2-cyclohexyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 376 1 -(2-Carbamoylmethyl-5-chloro-phenyl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-1 H-imidazole-4-carboxylic acid
  • Example 377 5-(3-Chloro-4-fluoro-phenyl)-1 -( ⁇ -chloro ⁇ -methylcarbamoylmethyl- phenyl)-2-cyclohexyl-1 H-imidazole-4-carboxylic acid
  • Example 381 3-[5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazol-4-yl]-1 -(2-trimethylsilanyl-ethoxymethyl)-1 H-pyrazole-4-carboxylic acid
  • Example 382 3-[5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazol-4-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-1 H-pyrazole-4-carboxylic acid methyl ester
  • Example 383 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-piperidin-1 - ylmethyl-1 H-imidazole-4-carboxylic acid
  • Example 384 5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-pyrrolidin-1 - ylmethyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 387 5- ⁇ 3-Chloro-5-[3-(3-chloro-2-fluoro-phenyl)-2-phenyl-5-(2H-tetrazol-5-yl)- 3H-imidazol-4-yl]-phenyl ⁇ -[1 ,2,3,4]oxatriazole
  • Example 388 5-(3-Chloro-4-fluoro-phenyl)-1-(5-chloro-2-methyl-phenyl)-2-(3-chloro- phenyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 389 S-tS-Chloro ⁇ -fluoro-phenylJ-i-fS-chloro ⁇ -methyl-phenylJ ⁇ -fS-chloro- phenyl)-1 H-imidazole-4-carboxylic acid
  • Example 390 1 -(5-Chloro-2-methoxy-pyridin-3-yl)-5-(3-chloro-phenyl)-2-phenyl-1 H- imidazole-4-carboxylic acid ethyl ester
  • Example 391 1 -(5-Chloro-2-methoxy-pyridin-3-yl)-5-(3-chloro-phenyl)-2-phenyl-1 H- imidazole-4-carboxylic acid
  • Example 392 1 -(S-Chloro ⁇ -methoxy-pyridin-S-ylJ-S-tS-chloro-phenylJ ⁇ -phenyl-i H- imidazole-4-carboxylic acid amide
  • Example 395 1 -(6-Carboxymethyl-3-chloro-2-fluoro-phenyl)-5-(3-chloro-4-fluoro-phenyl)-
  • Example 396 1-(6-tert-Butoxycarbonylmethyl-3-chloro-2-fluoro-phenyl)-5-(3-chloro-4- fluoro-phenyl)-2-cyclohexyl-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 398 1 -(6-Carboxymethyl-3-chloro-2-f luoro-phenyl)-5-(3-chloro-4-f luoro-phenyl)- 2-cyclohexyl-1 H-imidazole-4-carboxylic acid
  • Example 400 ⁇ 2-[4-Carbamoyl-5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-imidazol-1 -yl]-4- chloro-3-fluoro-phenyl ⁇ -acetic acid methyl ester
  • Example 401 ⁇ 2-[4-Carbamoyl-5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-imidazol-1 -yl]-4- chloro-3-fluoro-phenyl ⁇ -acetic acid
  • Example 402 N'- ⁇ 5-[5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-f luoro-phenyl)-2- cyclohexyl-1 H-imidazol-4-yl]-[1 ,3,4]oxadiazol-2-yl ⁇ -N,N-dimethyl-ethane-1 ,2-diamine
  • Example 403 ⁇ 5-[5-(3-Chloro-4-fl ⁇ oro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-cyclohexyl- 1 H-imidazol-4-yl]-[1 ,3,4]oxadiazol-2-yl ⁇ -(3-methoxy-propyl)-arnine
  • Example 404 Benzyl- ⁇ 5-[5-(3-chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2- cyclohexyl-1 H-imidazol-4-yl]-[1 ,3,4]oxadiazol-2-yl ⁇ -amine
  • Example 405 ⁇ 4-Chloro-2-[5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-4- hydrazinocarbonyl-imidazol-i-ylJ-S-fluoiO-phenylJ-acetic acid tert-butyl ester
  • Example 406 1-(5-Chloro-2-methyl-phenyl)-5-(2-chloro-pyridin-4-yl)-2-(3,4-dimethyl- phenyl)-1 H-imidazole-4-carboxylic acid ethyl ester
  • Example 407 1 -(5-Chloro-2-methyl-phenyl)-5-(2-chloro-pyridtn-4-yl)-2-(3,4-dimethyl- phenyl)-1 H-imidazole-4-carboxylic acid
  • Example 408 1 -(5-Chloro-2-methyl-phenyl)-2-(3-chloro-phenyl)-5-phenyl-1 H-pyrrole-3- carboxylic acid ethyl ester
  • Example 409 i-fS-Chloro ⁇ -methyl-phenylJ ⁇ -fS-chloro-phenyO-S-phenyl-IH-pyrrole-S- carboxylic acid
  • Example 410 4-(3-Chloro-2-fluoro-phenyl)-3-(3-chloro-phenyl)-5-phenyl-1 H-pyrrole-2- carboxylic acid methyl ester
  • Example 411 1-(3-Chloro-2-fluoro-phenyl)-2-(3-chloro-phenyl)-5-(3-nitro-phenyl)-1 H- pyrrole-3-carboxylic acid ethyl ester
  • Example 412 5-(3-Amino-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-(3-chloro-phenyl)-1 H- pyrrole-3-carboxylic acid ethyl ester
  • Example 414 1-(3-Chloro-2-fluoro-phenyl)-2-(3-chloro-phenyl)-5-(3-dimethylamino- phenyl)-1 H-pyrrole-3-carboxylic acid ethyl ester
  • Example 415 i-tS-Chloro ⁇ -fluoro-phenyl ⁇ -tS-chloro-phenylJ-S-fS-dimethylamino- phenyl)-1 H-pyrrole-3-carboxylic acid
  • Example 416 1-[5-Chloro-2-(2-hydroxy-ethyl)-phenyl]-2-(3-chioro-phenyl)-5-phenyl-1H- pyrrole-3-carboxylic acid
  • Example 417 2-(3-Chloro-4-fluoro-phenyl)-1-[5-chloro-2-(2-hydroxy-ethyl)-phenyl]-5- phenyl-1 H-pyrrole-3-carboxylic acid ethyl ester
  • Example 419 1-(2-Carboxymethyl-5-chloro-phenyl)-2-(3-chloro-4-fluoro-phenyl)-5- phenyl-1 H-pyrrole-3-carboxylic acid ethyl ester
  • Example 421 1-(5-Chloro-2-methylcarbamoylmethyl-phenyl)-2-(3-chloro-phenyl)-5- phenyl-1 H-pyrrole-3-carboxylic acid
  • Example 422 1-(2-Carbamoylmethyl-5-chloro-phenyl)-2-(3-chioro-phenyl)-5-phenyl-1 H- pyrrole-3-carboxylic acid ethyl ester
  • Example 423 1-(2-Carbamoylmethyl-5-chloro-phenyl)-2-(3-chioro-phenyl)-5-phenyl-1 H- pyrrole-3-carboxylic acid
  • Example 424 1-(2-Carbamoylmethyl-5-chloro-phenyl)-2-(3-chloro-4-fluoro-phenyl)-5- phenyl-1 H-pyrrole-3-carboxylic acid
  • Example 425 2-(3-Ch!oro-4-fluoro-phenyl)-1-[5-ch!oro-2-(2-hydroxy-ethyl)-phenyl]-5- phenyl-1 H-pyrrole-3-carboxy ⁇ c acid amide
  • Example 426 4-(5-Chloro-2-methoxy-phenyl)-5-(3-chloro-phenyl)-1 -phenyl-1 H-pyrazole-
  • Example 428 5-(3-Chloro-phenyl)-4-(3,4-dichloro-phenyl)-1 -phenyl-1 H-pyrazole-3- carboxylic acid
  • Example 429 4-(3-Chloro-4-fluoro-phenyl)-5-(3-chloro-pheny!)-1 -phenyl-1 H-pyrazole-3- carboxylic acid
  • Example 431 4-(5-Chloro-2-methoxy-phenyl)-5-(3-chloro-phenyl)-1 -m-tolyl-1 H-pyrazole-
  • Example 434 4-(3-Chloro-4-fluoro-phenyl)-5-(3-chloro-phenyl)-1 -m-tolyl-1 H-pyrazole-3- carboxylic acid
  • Example 435 1 -[5-(3-Chloro-4-fluoro-phenyl)-4-(3-chloro-2-f l ⁇ oro-phenyl)-3-m-tolyl- pyrazol-1 -yl]-2-hydroxy-ethanone
  • Example 436 2-[5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-pheny!-1 H- imidazol-4-yl]-4-methyl-oxazole
  • Example 443 [5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazol-4-yl]-acetonitrile
  • Example 444 5-[5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fiuoro-phenyl)-2-phenyl-1 H- imidazol-4-ylmethyl]-2H-tetrazole
  • Example 448 1 -[3-(3-Chloro-4-fluoro-phenyl)-4-(3-chloro-2-fluoro-phenyl)-5-m-tolyl- pyrazol-1 -yl]-2-hydroxy-ethanone
  • Example 449 1 -(5-Chloro-2-oxo-1 ,2 r dihydro-pyridin-3-yl)-5-(3-chloro-phenyl)-2-phenyl-
  • Example 451 1 -(3-Chloro-2-fluoro-phenyl)-5-(3-chloro -phenyl)-2-phenyl-1 -H-imidazole-
  • Example 452 1-(3-Chloro-2-f!uoro-phenyl)-5-(3-chloro -phenyl)-2-phenyl-1-H-imidazole-
  • Example 453 1-(3-Chloro-2-fluoro-phenyl)-5-(3-chloro-phenyl)-2-phenyl-1 H-imidazole-4- sulfonic acid methylamide
  • Example 454 1-(3-Chloro-2-fluoro-phenyl)-5-(3-chloro-4-fluoro-phenyl)-2-phenyl-4-(1 H- pyrrol-2-yl)-1-H-imidazole
  • Example 455 1 -(2-tert-Butoxycarbonylmethyl-5-chloro-phenyl)-5-(3-ch loro-4-fluoro- phenyl)-2-cyc!ohexyl-1 H-imidazole-4-carboxylic acid
  • Example 456 ⁇ 2-[4-Carbamoyl-5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-imidazol-1-yl]-4- chloro-phenyl ⁇ -acetic acid tert-butyl ester
  • Example 457 ⁇ 2-[4-Carbamoyl-5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-imidazol-1 -y!]-4- chloro-pheny! ⁇ -acetic acid
  • Example 458 1 -(2-Carbamoylmethyl-5-chloro-phenyl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-1 H-imidazole-4-carboxylic acid amide
  • Example 459 ⁇ 4-Chloro-2-[5-(3-chloro-4-fluoro-phenyl)-4-cyano-2-cyclohexyl-imidazol-1 - yl]-phenyl ⁇ -acetic acid tert-butyl ester
  • Example 460 ⁇ 4-Chloro-2-[5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-4-(2H-tetrazol-5-yl)- imidazol-1-yl]-phenyl ⁇ -acetic acid tert-butyl ester
  • Example 461 ⁇ 4-chloro-2-[5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-4-(2H-tetrazol-5-yl)- imidazol-1-yi]-phenyi ⁇ -acetic acid
  • Example 462 2- ⁇ 4-Ch!oro-2-[5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-4-(2H-tetrazol-5- yl)-imidazol-1-yl]-phenyl ⁇ -N-(4-methoxy-benzyl)-acetamide
  • Example 466 3-[5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-phenyl)-2-phenyl-1 H- imidazo!-4-y!]-5-methyl-[1 ,2,4]oxadiazole
  • Example 467 ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-3-fluoro-phenyl ⁇ -acetic acid tert-butyl ester
  • Example 468 ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1 -ylJ ⁇ -chloro-S-fluoro-phenylJ-acetic acid
  • Example 469 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-3-fluoro-phenyl ⁇ -N-methyl-acetamide
  • Example 470 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-3-fluoro-phenyl ⁇ -N-tert-butyl-acetamide
  • Example 471 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazo!-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-3-fluoro-phenyl ⁇ -N-ethyl-N-phenethyl-acetamide
  • Example 472 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-3-fluoro-phenyl ⁇ -N-(2,2-dimethoxy-ethyl)-acetamide
  • Example 473 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4
  • Example 475 ⁇ 4-Chloro-2-[5-(3-chloro-4-fluoro-phenyl)-2-cydohexyl-4-(5-methyl- [1 ,3,4]oxadiazol-2-yl)-imidazol-1-yl]-phenyl ⁇ -acetic acid
  • Example 476 2- ⁇ 4-Chloro-2-[5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-4-(5-methyl- [1 ,3,4]oxadiazol-2-yl)-imidazol-1 -yl]-phenyl ⁇ -1 -piperidin-1 -yl-ethanone
  • Example 477 2- ⁇ 4-Chloro-2-[5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl-4-(5-methyl- [1 ,3,4]oxadiazol-2-yl)-imidazol-1-yl]-phenyl ⁇ -N-methyl-N-pyridin-3-ylmethyl-acetamide
  • Example 478 ⁇ 4-Chloro-2-[5-(3-chloro-4-fluoro-phenyl)-2-cyclohexyl]-4- hydrazinocarbonyl-imidazol-1-yl]-phenyl ⁇ -acetic acid tert-butyl ester
  • Example 479 ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-2-fluoro-phenyl)-2- (cyclohexyl)-imidazol-1-yl]-4-chloro-phenyl ⁇ -actic acid tert butylester
  • Example 480 ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-2-fluoro-phenyl)-2- (cyclohexyl)-imidazol-1-yl]-4-chloro-phenyl ⁇ actic acid
  • Example 481 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-phenyl ⁇ -N-methyl-N-pyridin-3-ylmethyl-acetamide
  • Example 482 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-phenyl ⁇ -N-methyl-acetamide
  • Example 483 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-phenyl ⁇ -N-tert-butyl-acetamide
  • Example 484 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-phenyl ⁇ -1-mo ⁇ holin-4-yl-ethanone
  • Example 490 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-phenyl ⁇ -N-(3-methoxy-propyl)-acetamide
  • Example 491 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-phenyl ⁇ -N-pyridin-4-ylmethyl-acetamide
  • Example 492 2-(2-[4-(5-Amino-[1,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-phenyl ⁇ -N-(4,4-dimethyl-pentyl)-acetamide
  • Example 493 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-phenyl ⁇ -N-cyclohexylmethyl-acetamide
  • Example 494 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-phenyl ⁇ -N-(3-hydraxy-2,2-dimethyl-propyl)-acetamide
  • Example 495 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-phenyl ⁇ -1-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]- ethanone
  • Example 496 2- ⁇ 2-[4-(5-Amino-[1 ,3,4]oxadiazol-2-yl)-5-(3-chloro-4-fluoro-phenyl)-2- cyclohexyl-imidazol-1-yl]-4-chloro-phenyl ⁇ -N-(2-phenylamino-ethyl)-acetamide
  • Example 497 2-[5-(3-Chloro-4-fluoro-phenyl)-1 -(3-chloro-2-fluoro-phenyl)-2-cyclohexyl- 1 H-imidazol-4-yl]-5-methyl-[1 ,3,4]oxadiazole
  • Example 498 5-[5-(3-Chloro-4-fluoro-phenyl)-1-(3-chloro-2-fluoro-pheny!)-2-cyclohexyl-

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CN102503930A (zh) * 2011-10-28 2012-06-20 浙江大学 3,4,5,-三取代氨基噻吩类化合物及其制备和用途
US8569341B2 (en) 2010-06-04 2013-10-29 Amgen Inc. Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer
US8846657B2 (en) 2012-12-20 2014-09-30 Merck Sharp & Dohme Corp. Substituted imidazopyridines as HDM2 inhibitors
US8859723B2 (en) 2010-08-13 2014-10-14 Aileron Therapeutics, Inc. Peptidomimetic macrocycles
US8859776B2 (en) 2009-10-14 2014-10-14 Merck Sharp & Dohme Corp. Substituted piperidines that increase p53 activity and the uses thereof
US8889632B2 (en) 2007-01-31 2014-11-18 Dana-Farber Cancer Institute, Inc. Stabilized p53 peptides and uses thereof
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