(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(19) World Intellectual Property
`Organization
`International Bureau
`
`(43) International Publication Date
`15 January 2004 (15.01.2004)
`
`
`
`(10) International Publication Number
`
`WO 2004/005264 A2
`
`(51)
`
`C07D 233/64,
`International Patent Classification7:
`401/04, 403/04, 405/04, 409/04, 401/14, 405/14, 409/14,
`A61K 31/4178, A61P 31/20
`
`(21)
`
`International Application Number:
`PCT/EP2003/007286
`
`(22)
`
`International Filing Date:
`
`7 July 2003 (07.07.2003)
`
`(25)
`
`Filing Language:
`
`(26)
`
`Publication Language:
`
`English
`
`English
`
`(30)
`
`(71)
`
`(72)
`(75)
`
`Priority Data:
`020150967
`
`5 July 2002 (05.07.2002)
`
`EP
`
`Applicant (for all designated States except US): AXXIMA
`PHARMACEUTICALS AG
`[DE/DE]; Max—Leb—
`
`sche—Platz 32, 81377 Munich (DE).
`
`Inventors; and
`Inventors/Applicants (for US only): SALASSIDIS, Kon-
`stadinos [GR/DE]; Hauptstrasse 14c, 85386 Eching (DE).
`KURTENBACH, Alexander [DE/DE]; Leibelstrasse 14,
`82166 Graefelfing (DE). DAUB, Henrik [DE/DE]; Appen—
`zeller Strasse 116, 81475 Munich (DE). OBERT, Sabine
`[DE/DE]; Bellinzonastrasse 17, 81475 Munich (DE).
`
`(74)
`
`(81)
`
`(34)
`
`Agents: LEIDESCHER, Thomas et al.; Zimmermann &
`Partner, Postfach 330 920, 80069 Munich (DE).
`
`Designated States (national): AE, AG, AL, AM, AT, AU,
`AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CO, CR, CU,
`CZ, DE, DK, DM, DZ, EC, EE, ES, FI, GB, GD, GE, GH,
`GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC,
`LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW,
`MX, MZ, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RU, SC,
`SD, SE, SG, SK, SL, SY, TJ, TM, TN, TR, TT, TZ, UA,
`UG, US, UZ, VC, VN, YU, ZA, ZM, ZW.
`
`Designated States (regional): ARIPO patent (GH, GM,
`KE, LS, MW, MZ, SD, SL, SZ, TZ, UG, ZM, ZW),
`Eurasian patent (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM),
`European patent (AT, BE, BG, CH, CY, CZ, DE, DK, EE,
`ES, FI, FR, GB, GR, HU, IE, IT, LU, MC, NL, PT, RO,
`SE, SI, SK, TR), OAPI patent (BF, BJ, CF, CG, CI, CM,
`GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).
`
`Published:
`
`without international search report and to be republished
`upon receipt of that report
`
`For two—letter codes and other abbreviations, refer to the ”Guid—
`ance Notes on Codes and Abbreviations” appearing at the begin—
`ning of each regular issue of the PCT Gazette.
`
`(54) Title: IMIDAZOLE COMPOUNDS AND HUMAN CELLULAR PROTEINS CASEIN KINASE I ALPHA, DELTA AND
`EPSILON AS TARGETS FOR MEDICAL INTERVENTION AGAINST HEPA’I‘I’I‘IS C VIRUS INFECTIONS
`
`
`
`140
`
`120
`100
`
`%activity
`
`1
`
`Compound No. 39
`
`
`\\
`
`\
`
`10
`
`compound conc. (pM)
`
`*1
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`2004/005264A2|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||H
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`(57) Abstract: The present invention describes novel irnidazole compounds, which are particularly useful against Hepatitis C Virus
`infections and diseases associated therewith. Furthermore, the invention relates to the human cellular proteins casein kinase I alpha
`(0L), delta (8), and epsilon (8) as targets for medical intervention against Hepatitis C Virus (HCV) infections and diseases. In addition,
`the present invention refers to a method for the identification of compounds which are useful for the prophylaxis and/or treatment
`of infections and diseases caused by Hepatitis C Virus, methods for treating Hepatitis C Virus infections and diseases, as well as
`pharmaceutical compositions useful for the prophylaxis and/or treatment of Hepatitis C Virus infections and diseases. Moreover,
`O disclosed are antibodies, oligonucleotides and specific compounds which are effective for the detection, prophylaxis and/or treatment
`of infections and diseases caused by Hepatitis C Virus.
`In addition, the present invention describes solid supports useful for the
`B
`identification of compounds suitable for preventing and/or treating infections and diseases caused by said Hepatitis C Virus.
`
`

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`WO 2004/005264
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`PCT/EP2003/007286
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`Imidazole Compounds and Human Cellular Proteins Casein Kinase I alpha, delta and
`
`epsilon as Targets for Medical Intervention against Hepatitis C Virus Infections
`
`Description
`
`10
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`15
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`20
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`3O
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`35
`
`The present
`
`invention relates to novel
`
`imidazole compounds. The present
`
`invention
`
`furthermore relates to the human cellular proteins casein kinase I alpha (or), delta (8), and
`
`epsilon (8) as targets for medical intervention against Hepatitis C Virus (HCV) infections and
`
`diseases. Furthermore, the present invention refers to a method for the identification of
`
`compounds which are useful for the prophylaxis and/or treatment of infections and diseases
`caused by Hepatitis C Virus, methods for treating Hepatitis C Virus infections and diseases,
`
`as well as pharmaceutical compositions useful for the prophylaxis and/or treatment of
`
`Hepatitis C Virus
`
`infections
`
`and
`
`diseases. Moreover,
`
`disclosed
`
`are
`
`antibodies,
`
`oligonucleotides and specific compounds which are effective for the detection, prophylaxis
`
`and/or treatment of infections and diseases caused by Hepatitis C Virus. In addition, the
`
`present invention describes solid supports usefiil for the identification of compounds suitable
`
`for preventing and/or treating infections and diseases caused by said Hepatitis C Virus.
`
`Hepatitis C Virus (HCV) infection is a major cause of chronic hepatitis, cirrhosis and
`
`hepatocellular carcinoma. The WHO estimates that approximately 3% of the world
`
`population, or 170 million people, have been infected with the Hepatitis C Virus. In the U.S.,
`
`an estimated 3.9 million Americans have been infected (CDC fact sheet Sept. 00). Over 80%
`
`of HOV—infected individuals develop chronic hepatitis, which is associated with disease states
`
`ranging from asymptomatic carrier states to repeated inflammation of the liver and serious
`
`chronic liver disease. Over the course of 20 years, more than 20% of the chronic HCV-
`
`patients are expected to be at risk to develop cirrhosis or progress to hepatocellular carcinoma.
`
`Liver failure from chronic hepatitis C is the leading indicator for liver transplantation.
`
`Excluding transplantation, the CDC estimates that medical and work-loss cost for HCV
`
`annually are around US—$ 600 million. HCV is transmitted primarily by blood and blood
`
`products. Due to routine screening of the blood supplies from mid-1992, new transfusion-
`
`related cases are exceedingly rare and have been surpassed by injection drug use as the
`
`highest risk factor for acquiring the Virus. There is also a sexual, however inefficient, route of
`
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`WO 2004/005264
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`PCT/EP2003/007286
`
`transmission, and a 6% rate of transmission from infected mothers to their children, which is
`
`higher in case of HIV co-infection. In a certain percentage of infections, the mode of
`
`transmission remains unknown. In spite of the significant decline in incidence in the 1990's,
`
`the number of deaths (estimated deaths annually at the moment: 8000 to 10,000 in US.) and
`
`severe disease due to HCV is anticipated to triple in the next 10 to 20 years. With respect to
`
`the above-mentioned statements see e.g. CDC fact sheet (accessed 12/ 12/00); Houghton M.
`
`Hepatitis C Viruses, in BN Fields, DM Knipe, PM Howley (ed.) Fields Virology, 1996,
`
`Lippencott-Raven Pub., Philadelphia; Rosen HR and Gretch DR, Molecular Medicine Today
`
`Vol. 5, 393, Sept. 1999; Science 285, 26, July 1999: News Focus: The scientific challenge of
`
`Hepatitis C; Wong JB et al., Am J Public Health, 90, 1562, Oct. 2000: Estimating future
`
`hepatitis C morbidity, mortality, and costs in the United States.
`
`According to the Consensus Statement from the EASL (European Association for the Study
`
`of the Liver) International Consensus Conference on Hepatitis C (February 26—28, 1999,
`
`Paris, France), combination therapy of alpha interferon and ribavirin is the recommended
`
`treatment for naive patients. Monotherapy with interferon has also been approved by the US.
`
`Food and Drug Administration (FDA), but the sustained response rate (HCV RNA remains
`
`undetectable in the serum for more than 6 months after end of therapy) is only 15 to 20%, in
`
`contrast to 35 to 45% with combination therapy. Interferons (Intron A, Schering-Plough;
`
`Roferon A, Hoffmann—LaRoche; Wellferon, Glaxo Wellcome; Infergen, Amgen) are injected
`
`subcutaneously three times a week, ribavirin (Rebetol, Schering—Plough) is an oral chug given
`
`twice a day. Recommended treatment duration is 6 to 12 months, depending on HCV
`
`genotype. Experimental forms of slow-release pegylated interferons (Pegasys, Hoffinann—
`
`LaRoche; PEG-Intron, Schering-Plough) have shown improvements in response rates (42 to
`
`82% in combination with ribavirin) and application (once-weekly injection) in recent clinical
`
`studies (Hepatology 32:4, Pt 2 of 2. Oct 2000; NEJM 343, 1673, Dec. 2000; NEJM 343,
`
`1666, Dec 2000). Common side effects of interferon therapy include: fatigue, muscle aches,
`
`head aches, nausea, fever, weight loss,
`
`irritability, depression, bone marrow suppression,
`
`reversible hair loss. The most common side effects of ribavirin are anemia, fatigue and
`
`irritability, itching, skin rash, nasal stuffiness, sinusitis, cough. More serious side effects of
`
`mono-and combination therapy occur in less than two percent of patients (NIDDK
`
`information: Chronic Hepatitis C: Current Disease Management, accessed 09. December
`
`1999). Some of the contraindications to interferon are psychosis or severe depression;
`
`neutropenia and/or thrombocytopenia; organ transplantation except liver; symptomatic heart
`
`l0
`
`15
`
`20
`
`25
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`30
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`WO 2004/005264
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`PCT/EP2003/007286
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`3
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`disease; decompensated cirrhosis; uncontrolled seizures. Contraindications to ribavirin are
`
`end-stage renal failure; anemia; hemoglobinopathies; severe heart disease; pregnancy; no
`
`reliable method of contraception (consensus statement EASL).
`
`Experimental
`
`treatments that are not new forms of interferon are Maxamine (histamine
`
`dihydrochloride, Maxim Pharmaceuticals), which will be combined with Interferon in phase
`
`III studies, VX-497 (Vertex Pharmaceuticals), an IMP dehydrogenase inhibitor, as a less toxic
`
`ribavirin substitute in phase II, and amantadine (Endo Labs), an approved influenza drug, as
`
`the third component in triple therapy (phase II). Inhibitors for HCV enzymes such as protease
`
`inhibitors, RNA polymerase inhibitors, helicase inhibitors as well as ribozymes and antisense
`
`RNAs are under preclinical development (Boehringer Ingelheim, Ribozyme Pharmaceuticals,
`
`Vertex Pharmaceuticals, Schering-Plough, Hoffmann-LaRoche, Irnmusol, Merck etc.). No
`
`vaccine is available for prevention or therapeutic use, but several companies are trying to
`
`develop conventional or DNA vaccines or
`
`immunostimulatory agents
`
`(e.g. Chiron,
`
`Merck/Vical, Epimmune, NABI, Innogenetics).
`
`In summary, the available treatment for chronic Hepatitis C is expensive, effective only in a
`
`certain percentage of patients and adverse side effects are not uncommon.
`
`It is therefore the object of the present invention to provide novel compounds for the
`
`prophylaxis and/or treatment of Hepatitis C Virus infections and diseases caused by such
`
`infections. Furthermore,
`
`it
`
`is the object of the present invention to provide targets for
`
`detection, medical intervention, prophylaxis and/or treatment of Hepatitis C Virus infections,
`
`including acute and chronic Hepatitis C, as well as methods for identifying compounds which
`
`can be used for the prophylaxis and/or treatment of Hepatitis C Virus infections. Moreover, it
`
`is the object of the present invention to provide agents and compounds detected by these
`
`methods for the prophylaxis and/or treatment of Hepatitis C Virus infections, including acute
`
`and chronic Hepatitis C, and methods for the prophylaxis and treatment of such infections and
`
`diseases, as well as pharmaceutical compositions which can be used for the prophylaxis
`
`and/or treatment of Hepatitis C Virus infections and diseases.
`
`This object is solved by the teaching of the independent claims. Further advantageous
`
`features, aspects and details of the invention are evident fiom the dependent claims, the
`
`description, the examples, and the drawings.
`
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`WO 2004/005264
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`PCT/EP2003/007286
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`According to one aspect, the present invention refers to novel compounds having the general
`
`formula (I):
`
`R4
`
`R3
`
`N
`
`1w
`N
`R2
`
`wherein:
`
`R1, R1,, and R1” represent independently of each other
`
`R7
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`/2’:
`
`

`

`WO 2004/005264
`
`PCT/EP2003/007286
`
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`
`

`

`WO 2004/005264
`
`PCT/EP2003/007286
`
`——N
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`

`WO 2004/005264
`
`PCT/EP2003/007286
`
`R2'
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`WO 2004/005264
`
`PCT/EP2003/007286
`
`-\NN
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`WO 2004/005264
`
`PCT/EP2003/007286
`
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`R2, R2,, and R2” represent independently of each other —H, —CH3, —C2H5, —CH=CH2, —
`
`CECH, —c3H7, —cyclo—C3H5, —CH(CH3)2, —CH2—CH=CH2, —C(CH3)=CH2, —CH=CH—
`
`CH3, —CEC—CH3, ~CH2—CECH, —C4H9, —cyclo—C4H7, —CH2—CH(CH3)2, —CH(CH3)—
`
`CZHS, —C(CH3)3, —C5H11, —cyclo—C5H9,
`
`4361—113,
`
`~cyclo—C6H11, —Ph, —C(R5)3, n
`
`C(RS’)3, —CR5(R5’)2, —CR5(R5’)R5”, —C2(R5)5,
`
`~CH2—C(R5)3, —CH2—C(R5’)3, —CH2—
`
`CR5(R5’)2,
`
`~CH2—CR5(R5’)R5”, —03(R5)7, —CzH4—C(R5)3,
`
`~C7H15, —cyclo—C7H13,
`
`——
`
`CHgPh, —C3H17, —cyclo—CgH15, —C7_H4Ph, —CH=CH—Ph, —CEC—Ph;
`
`R3 and R4 represent independently of each other —R1’, —R1”, —R6, ~R6’, —OR2’, —OR2”,
`
`—SR2’, —SR2”;
`
`10
`
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`
`R5, R5, and R5” represent independently of each other —F, —Cl, —Br, —I, —CN;
`
`

`

`
`
`WO 2004/005264
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`
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`
`PCT/EP2003/007286
`
`R6 and R6, represent independently of each other
`
`~R2’,
`
`~R2”, —C2H4—-CH=CH2,
`
`—
`
`CH=CH—C2H5,
`
`~~CH=C(CH3)2, ——CH2—CH=CH—CH3, —CH=CH—CH=CH2,
`
`——C2H4-—
`
`CECH, —CEC—C2H5, —CH2—CEC—CH3, —CEC—CH=CH2, —CH=CH—CECH, —CEC—
`
`CECH,
`
`~C2H4—CH(CH3)2, —CH(CH3)—C3H7, —CH2—CH(CH3)—CZH5, —CH(CH3)—
`
`CH(CH3)2, —C(CH3)2—C2H5,
`
`~CH2—C(CH3)3, —C3H6—CH=CH2, —CH=CH—C3H7,
`
`—
`
`C2H4—CH=CH—CH3,
`
`—CH2—CH=CH—C2H5,
`
`—CH2~CH=CH——CH=CH2,
`
`—CH=CH—
`
`CH=CH~CH3,
`
`—CH=CH—CH2—CH=CH2,
`
`—C(CH3)=CH—CH=CH2,
`
`~CH=C(CH3)—
`
`CH=CH2, —CH=CH—C(CH3)=CH2, —CH2—CH=C(CH3)2, —C(CH3)=C(CH3)2, —C3H6~
`
`CECH, —CEC—C3H7, —C2H4—CEC—CH3, —CH2—CEC—C2H5, —CH2—CEC—CH=CH2, —
`
`CHZ—CH=CH—CECH,
`
`~CH2—CEC—CECH, —CEC—CH=CH—CH3, —CH=CH—CEC—CH3,
`
`—CEC—CEC-CH3, —CEC~CH2—CH=CH2, —CH=CH—CH2—CECH, —CEC—CH2—CECH, —
`
`C(CH3)=CH—CH=CH2, —CH=C(CH3)—CH=CH2, —CH=CH—C(CH3)=CH2, —C(CH3)=CH—
`
`CECH,
`
`—CH=C(CH3)—CECH,
`
`—CEC—C(CH3)=CH2,
`
`~C3H6—CH(CH3)2,
`
`4:21-14—
`
`CH(CH3)—C2H5,
`
`~CH(CI—I3)—C4H9, —CH2—CH(CH3)~C3H7, —CH(CH3)—CH2—CH(CH3)2,
`
`—CH(CH3)—CH(CH3)—C2H5,
`
`—CH2—CH(CH3)—CH(CH3)2,
`
`—CH2—C(CH3)2—C2H5,
`
`—
`
`C(CH3)2—C3H7,
`
`~C(CH3)2—CH(CH3)2, —CgH4—C(CH3)3, —CH(CH3)—C(CH3)3, —C4Hg—
`
`CH=CH2, —CH=CH—C4H9, —C3H6—CH=CH—CH3, —CH2—CH=CH—C3H7,
`
`—C2H4—
`
`CH=CH—CgH5, —CH2—C(CH3)=C(CH3)2, —C2H4—CH=C(CH3)2, —C4Hg—CECH, —CEC—
`
`C4H9, —C3H6—CEC—CH3, —CH2—-CEC—C3H7,
`
`*CZH4—CEC—C2H5, —o—C6H4—R2, —o—
`
`CGH4—R2’, ~m—C6H4—R2, —m~ch4—R2’, —p—C5H4—R2, —p~ch4—R2’, —o—CH2—C6H4—R2,
`
`m CH2 C6H4 R2,
`m CH2 06m RT, —p—CH2—06H4—R2,
`
`—o~CH2—C6H4—R2’,
`
`4%
`
`CHz—C6H4—R2’;
`
`R7 and R7: represent independently of each other
`
`OCN, —NCO, —SCN, ~NCS, —COCN, 430018, ~COOR2”,
`
`~R5’, —R5”, ~I-I, —N02, —N0, —N3, —
`
`(:0 R”,
`00 R2”,
`
`CONRZ’RZ”, —NR2’R2”, —NR6R6’, —N@R2’R2”R6’, —SOR2’, —s0R2”, —sozR2’, —
`
`sozRT’, —so3R2’, $03112”, —NHco—R2’, —NHCO—R2”, ~NHCOO—R2’, —NHCOO—
`
`R2”, —OCONR2’R2”, —OCONR"’R6’, —OCOR2’, —OCOR2", —NH——soz—R2’, —NH—SOZ—
`
`R2”, —soz—NR2’R2”, —soz—NR6R6’, —NH—Co—NH—R2’, —NH——CO—-NH—R2”, —NH—CS—
`
`NH—RZ’, —NH—Cs—NH—R2”, —0R2’, —0R2”, ~SR2’, —SRZ”;
`
`R8 and R8, represent independently of each other ~R7, —R7,, —R6’, —R6”;
`
`and pharmaceutically acceptable salts thereof.
`
`10
`
`15
`
`20
`
`25
`
`30
`
`

`

`WO 2004/005264
`
`PCT/EP2003/007286
`
`11
`
`The above-mentioned imidazole compounds according to general formula (I) as well as their
`
`pharmaceutically acceptable salts are particularly useful as agents against Hepatitis C Virus
`
`infections and diseases associated with such infections.
`
`According to a preferred embodiment, in the general formula (1) R1, R1,, and R1” represent
`
`independently of each other
`
`R7
`
`R6
`
`R8.
`
`R8
`
`5
`
`R7
`
`R7'
`
`R8'
`
`R8
`
`5
`
`R8'
`
`R8'
`
`R6
`
`R6'
`
`R8'
`
`R8
`
`5
`
`R3
`
`R8
`
`i
`
`5
`
`R8
`
`—@< M3: MK
`
`7
`
`R8
`
`S
`
`a
`
`N
`
`S
`
`\
`
`/ 3
`
`8
`
`I
`
`R8
`
`8'
`
`5
`
`R8
`
`R8'
`
`l
`
`RS'
`
`a
`
`8
`
`R8'
`
`3
`
`R8
`
`O
`
`«
`
`N
`
`O
`
`\
`
`8
`
`1
`
`R8
`
`R8'
`
`5
`
`R8
`
`H
`
`\N
`
`4
`
`N
`
`H
`
`\N
`
`\
`
`/
`
`H
`
`/ N
`
`R8'
`
`1
`
`/ 0
`
`R8'
`
`5
`
`R8
`
`R8
`
`5
`
`10
`
`

`

`WO 2004/005264
`
`_
`
`12
`
`PCT/EP2003/007286
`
`R8'
`
`R8'
`
`! C0 ’
`
`R8
`
`R8'
`
`,
`
`R8
`
`R8'
`
`5
`
`R8
`
`R8'
`
`’
`
`R8
`
`/
`
`N \
`
`R8
`
`R8'
`
`,
`
`R8'
`
`1
`
`R8
`
`R8'
`
`1
`
`R8
`
`YN
`N\
`
`/N
`
`\
`
`R8,
`
`!
`
`R8
`
`R8'
`
`,
`
`R8
`
`R8'
`
`5
`
`R8
`
`/N
`IN
`
`/ \
`
`N
`
`5
`
`3‘:
`
`R8'
`
`R8
`
`i
`
`N_
`
`WEB/i
`
`R8'
`
`R8
`
`,
`
`_N R8'
`
`’Q/i
`
`R8
`
`,
`
`_ R8'
`N
`
`\
`
`R8
`
`,
`
`

`

`WO 2004/005264
`
`PCT/EP2003/007286
`
`13
`
`—yR8'
`RS'
`N=N
`NM \
`
`R8
`
`,
`
`__N
`{fig
`
`Rs'
`
`R8
`
`,
`
`,
`
`R8
`
`N\N
`_</ J\
`N
`/
`H
`
`R8
`
`’
`
`I1
`N
`_<\
`N
`
`R8'
`
`R8
`
`/—‘\
`—N
`N
`\__/
`
`,
`
`R8'
`
`R8'
`
`—N
`
`N—Rz'
`
`--—N
`
`O
`
`—N
`
`R8'
`
`8
`R a
`
`R8'
`
`R8
`
`R8'
`N=<
`——<\
`N
`N“<
`R8
`
`/
`
`’
`
`R2'
`
`.
`/ N/
`__|{J_R8 ’
`
`R8
`
`R2
`\
`N\ N
`\
`
`8.
`R ’
`
`R8
`
`R8'
`
`N—RZ'
`a
`
`R8
`
`R8
`
`\N
`\N
`N/l\R8'
`I
`
`\
`
`’
`
`5
`
`R2
`\
`N
`
`_< %L_ 8‘
`\N
`R ’
`
`R8
`
`R8'
`
`a
`R8
`
`-
`
`R8
`
`’
`
`R2'
`
`/ N/
`
`N
`
`R8
`
`R8'
`
`/ N
`Nj
`
`R8
`
`’
`
`

`

`
`
`WO 2004/005264
`
`PCT/EP2003/007286
`
`/ O—z
`
`and R2,, R6, R6,, R7, R7,, R8, R8, have the meanings as defined above.
`
`Specifically, R1, R1,, and R1” represent independently of each other
`1.,\‘A A
`ln— n— A-
`
`

`

`WO 2004/005264
`
`PCT/EP2003/007286
`
`15
`
`:18.7Rmw
`
`N/\\N
`
`R-
`owOm
`
`
`

`

`— R81
`
`N
`\
`NAIR" .
`
`_N Rs'
`«K
`
`R8
`
`,
`
`,
`
`a
`
`"—N
`
`H\
`
`_<\
`
`N
`
`R8'
`
`R8
`
`R8
`
`R8
`
`a
`
`N—_—N
`\
`
`Rs'
`
`R8
`
`,
`
`R8'
`
`——yR8'
`\
`N
`
`R8
`
`——N‘
`
`::N——R2'
`
`——N
`
`:0
`
`R8'
`
`R8
`
`R8'
`
`i
`
`R8
`
`WO 2004/005264
`
`_
`
`16
`
`PCT/EP2003/007286
`
`N —
`
`R8,
`
`%\3X 41
`N
`R8
`,
`
`_ N
`
`N
`
`R8!
`
`R8
`
`R8
`
`R8'
`
`N—RZ'
`
`y
`
`R8
`
`R8
`\
`N\N
`\N/lk
`
`,
`
`R8
`
`R‘
`N
`——<\
`
`N
`
`R8
`
`8
`R ,
`
`8
`\
`
`8'
`R ’
`
`5
`
`R2'
`
`N/
`
`R8"
`
`R2
`
`N/
`/ _[il__R8 ’
`
`_</\
`N
`
`R8
`
`R8'
`/ Nil
`
`N1
`R2
`
`o
`\
`
`R8
`
`R2\
`“\N
`\
`
`R8
`
`s
`R a
`
`R8 ’
`
`8'
`R ,
`
`_
`
`/N\
`N
`
`8'
`R ,
`
`

`

`WO 2004/005264
`
`PCT/EP2003/007286
`
`/
`
`s
`
`R8
`
`R8,
`
`’
`
`1
`
`3
`NI
`<\
`
`R8'
`
`R8
`
`R8'
`
`374
`\ N
`
`I
`
`R8
`
`R8
`
`N74
`
`R8
`
`R8'
`
`/ m—z
`
`17
`
`/
`
`O
`
`R8
`
`R8,
`
`.
`
`NN
`
`_N\;€7R8’
`
`R8
`
`O
`N
`<\
`
`l
`
`R8'
`
`R8
`
`R8
`
`0%
`\ N
`
`I
`
`R8
`
`R8'
`
`S/N
`
`R8
`
`R8'
`
`/ O—Z
`
`R8'
`
`/N7/O
`1 M 5
`
`R8
`
`R8'
`
`“74
`5 M i
`
`R8
`
`R8
`
`074
`
`R8
`
`R8
`
`$2ER
`
`and R2,, R6, R6,, R7, R7,, R8, R8, have the meanings as defined above.
`
`Even more specifically, R1, R1,, and R1” represent independently of each other
`
`10
`
`

`

`WO 2004/005264
`
`PCT/EP2003/007286
`
`18
`
`R7
`
`.n- n— A-
`
`

`

`
`
`PCT/EP2003/007286
`
`/N\
`
`R8'
`
`,
`
`—N
`
`R8
`
`,
`
`R8
`
`R8 ,
`
`NN
`
`_N9€—R8
`
`R8
`
`’.
`
`,
`
`5
`
`19
`
`O
`\
`
`/
`
`R8
`
`o
`
`R8
`
`WO 2004/005264
`
`S
`\
`
`/
`
`R8
`
`s
`
`R8
`
`R8 ,
`
`R8 ’
`
`8
`—<\
`N
`
`I
`
`8
`
`R8
`
`R8'
`
`\ N
`
`R8
`
`1
`
`,
`
`R8
`
`N74
`\ S
`
`R8
`
`0
`-—<\
`N
`
`l
`
`R8'
`
`R8
`
`R8'
`
`|
`\ N
`
`R8
`
`a
`
`,
`
`and R2,, R6, R67, R7, R7,, R8, R87 have the meanings as defined above.
`
`10
`
`15
`
`According to a further preferred embodiment R2, R2,, and R2” represent independently of each
`
`other ~H, —CH3, —C2H5, —CH=CH2, —CECH, —C3H7, —cyclo—C3H5, ~CH(CH3)2, —
`
`CHz—CH=CH2, —C4H9, —cyclo—C4H7, —CH2—CH(CH3)2, —CH(CH3)——C2H5, —C(CH3)3,
`
`—CsH11, —cyclo——C5H9, 4361113, —cyclo—C5H11, —Ph, —C(R5)3, —C(R5’)3, —CR5(R5’)2, —
`
`CHgPh; and R5, R5, have the meanings as defined above.
`
`In addition, preferred are compounds wherein R5, R5, and R5” represent independently of each
`
`other —F, —Cl, —Br.
`
`Furthermore, preferred are compounds wherein R6 and R6, represent independently of each
`
`other 48’, —R2”, ~o—C6H4—R2, —o—C6H4—R2’, —m—C5H4—R2, —m-CGH4—R2’, —p~C6H4—
`
`R2, —p—C5H4—R2’, —o—CH2—C6H4—R2, —o—CH2—CGH4—R2’, —m CH2 06H4 R2, m CH2
`
`1nAnA
`
`11.
`
`.A-A—An
`
`

`

`
`
`WO 2004/005264
`
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`
`PCT/EP2003/007286
`
`CGHrRZ’, —p—CH2—C6H4—R2, —p—CH2—C6H4—R2,; and R2, RT, R2” have the meanings as
`
`defined above.
`
`Among those compounds, R6 and R6, specifically represent independently of each other ~H,
`
`—CH3,
`
`-—C2H5, —CH=CH2, —CECH, —C3H7, —cyclo~C3H5, —CH(CH3)2, —CH2—
`
`CH=CH2, —C4H9,
`
`~cyclo~C4H7, —CH2—CH(CH3)2, —CH(CH3)—C2H5, —C(CH3)3, —
`
`05H”, —cyclo—C5H9, 4:61;”, —cyclo—C5H11,
`
`-Ph, —C(R5)3, —C(R5’)3, —CR5(R55)2, —
`
`CHZPh, ——o—C6H4—CH3, —o—C6H4—C2H5, —m—CsH4—CH3, —m—C6H4—C2H5, —p—C6H4—
`
`CH3, —p—C6H4—C2H5,
`
`~o—CH2—CGH4—«CH3, —o—CH2—C6H4—CZH5, —m—CH2—C6H4—CH3,
`
`—m—CH2—C5H4~—CZH5, —p—CH2—CsH4—CH3, —p—CH2—CsH4—C2H5;
`
`and R5, R5, have the
`
`meanings as defined above.
`
`According to further preferred embodiment of formula (I), R7 and R77 represent independently
`
`of each other —F, 4:1, —Br, —H, —N02, —COOR2’, 4300112”, —co—R2’, —Co—R2”,
`
`—CONR2’R2”, —NR2’R2”, —NR6R6’, —s0R2’, —SOR2”, —s02R2’, —sozR2”, —so3R2’, —
`
`303112”, —NHCO—R2’, —NHCO—R2”, —OCOR2’, —OCOR2”, —0R2’, —0R2", —SR2’, —
`
`SR2”; and R2,, R2”, R6, R6, have the meanings as defined above.
`
`Preferred compounds falling under the general formula (1) above are
`
`(Compound 1)
`
`4—[5-(4—Fluoro-pheny1)-2-(4-isopropyl-phenyl)—3H—imidazole-4—yl]—
`pyridine,
`
`(Compound 2)
`
`3-[4-(4-F1uoro—phenyl)—5—pyridine—4—yl- lH—imidazole-Z—yl] —4-nitro—
`phenol,
`
`(Compound 3)
`
`4-[4-(4-Fluoro-pheny1)—5—pyridine-4-yl-lH-imidazole-Z-yl]-2-nitro-
`phenol,
`
`(Compound 4)
`
`4-[5-(4-Fluoro—phenyl)-2-(3 -trifluoromethyl-phenyl)—3H—imidazole—4-
`y1J-Py1‘idine,
`
`(Compound 5)
`
`2,6—Di-tert—butyl—4—[4-(4-fluoro—phenyl)-5-pyridine-4-yl)-1H—
`imidazole-2~yl] -phenol,
`
`(Compound 6)
`
`4—[2—(2,5-Bis—trifluoromethyl)-5—(4-fluoro—pheny1)~3H—imidazole-4—y1]—
`pyridine,
`
`(Compound 7)
`
`4-[5-(4-Fluoro-phenyl)-2—furan-2-y1-3H-imidazole—4-yl]-pyridine,
`
`(Compound 8)
`
`4-[5-(4—Fluoro-pheny1)-2-(2—methoxy—phenyl)-3H—imidazole-4—yl]—
`pyridine,
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`4o
`
`

`

`
`
`WO 2004/005264
`
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`
`PCT/EP2003/007286
`
`(Compound 9)
`
`4— [5 -(4-Fluoro—pheny1)—2-(5-methy1—furan—2—y1)-3H—imidazole—4—yl] —
`pyridine,
`
`(Compound 10)
`
`4-[5-(4-F1uoro-pheny1)—2—(3-methoxy—pheny1)~3H-imidazole-4—y1]—
`pyridine,
`
`(Compound 11)
`
`4- [5 —(4—Fluoro—pheny1)-2-p—toly1-3H—imidazole-4-y1] -pyridine,
`
`(Compound 12)
`
`4—[5-(4-F1uoro—pheny1)-2-(4—methoxy—pheny1)-3H~imidazole—4-yl]-
`pyridine,
`
`(Compound 13)
`
`4- [5-(4-F1uoro~phenyl)—2-(2-chloro-phenyl)-3H-imidazole-4—yl] -
`pyridine,
`
`(Compound 14)
`
`4-[5-(4-Fluoro~pheny1)-2-(2,4,6—trimethy1—pheny1)-3H—imidazole-4—y1]-
`pyridine,
`
`(Compound 15)
`
`4-[5-(4-F1uoro~pheny1)—2 -(2,4-dichloro-phenyl)—3H-imidazole-4-y1] —
`pyridine,
`
`(Compound 16)
`
`4—[5—(4—F1uoro—pheny1)—2-(2,3—dichloro—pheny1)-3H—imidazole—4-yl]—
`pyridine,
`
`(Compound 17)
`
`4-[4—(4-F1uoro—pheny1)—5-pyridine-4-yl)-1H—imidazole-2-yl] —2-
`methoxy—phenol,
`
`(Compound 1 8)
`
`4—[5-(4-F1uoro-pheny1)-2-(2—nitro-pheny1)-3H—imidazole—4—yl]—
`pyridine,
`
`(Compound 19)
`
`4-[4-(4-F1uoro—pheny1)—5-pyridine-4—yl-1H—imidazole-2-yl] -benzene-
`1,2—diol,
`
`(Compound 20)
`
`4—[4-(4—F1uoro-pheny1)—5-pyridine—4-yl-1H—imidazole—2-y1] —phenol,
`
`(Compound 2 1 )
`
`4-[2-(4,5-Dimethoxy—2-nitro-pheny1)—5-(4—fluoro—pheny1)—3H-
`imidazole-4—y1]—pyridine,
`
`(Compound 22)
`
`4—[5-(4—F1uoro-pheny1)—2-(3 -ohloro-pheny1)—3H-imidazole—4—y1]—
`pyridine,
`
`(Compound 23)
`
`4— [5-(4-F1uoro-phenyl)-2-(3 -bromo-phenyl)-3H—imidazole-4—yl] —
`pyridine,
`
`(Compound 24)
`
`4-[5-(4—F1uoro-pheny1)—2-(3 -nitro-pheny1)-3H—imidazole-4-y1] -
`pyridine,
`
`(Compound 25)
`
`4-[5-(4-F1uoro-pheny1)-2-(4-nitro-phenyl)—3H-imidazole-4-yl]-
`pyridine,
`
`(Compound 26)
`
`4— [5 -(4-F1uoro-pheny1)-2-naphtalene-1 -y1-3H—imidazole—4—y1]-pyridine,
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`4o
`
`45
`
`50
`
`

`

`
`
`WO 2004/005264
`
`22
`
`PCT/EP2003/007286
`
`(Compound 27)
`
`4-[2-(3,5—Bis-trifluoromethy1—pheny1)-5—(4—fluoro-pheny1)— 3H-
`imidazole—4—y1]—pyridine,
`
`(Compound 28)
`
`{4—[4—(4—F1uoro-pheny1)—5—pyridine—4-y1~ 1H—imidazole-2-y1]-pheny1}-
`dimethyl-amine
`
`(Compound 29)
`
`4-[5 -(4-Fluoro-phenyl)—2-(3 ,4-dichloro-pheny1)-3H—imidazole—4-y1] —
`pyridine,
`
`(Compound 30)
`
`4-[5-(4-Fluoro-pheny1)-2-(4-trifluoromethyl-pheny1)-3H—imidazole-4—
`y1]-pyridine,
`
`(Compound 3 1)
`
`4—[4-(4-F1uoro-pheny1)—5-pyridine—4-yl— 1H—in1idazole—2-y1]—2, 6—
`dimethyl-phenol,
`
`(Compound 32)
`
`4-[5-(4-F1uoro—phenyl)-2-(4-methy1sulfanyl-pheny1)-3H—imidazole-4-
`IVE-pyridine,
`
`(Compound 33)
`
`3-[4—(4-F1uoro~pheny1)—5-pyridine—4-y1—1H-imidazole—2-yl]-1H—indole,
`
`(Compound 34)
`
`4-[5—(4-Fluoro—pheny1)—2—(4—chloro~pheny1)~3H—imidazole-4—yl]—
`pyridine,
`
`(Compound 35)
`
`4—[5-(4-F1uor0~phenyl)-2-thiophene-2-y1—3H—imidazole-4-y1] —pyridine
`
`(Compound 36)
`
`4-[5-(4-F1uoro—pheny1)—2-(4-bromo-pheny1)-3H—imidazole—4-y1]-
`pyridine,
`
`(Compound 37)
`
`4- [2-(3 ,4—Dimethoxy—pheny1)—5-(4-fluoro -phenyl)-3H—imidazole-4-y1] -
`pyridine,
`
`(Compound 3 8)
`
`4-[5-(4-Fluoro-phenyl)-2-(4—methanesu1finy1-pheny1)—3H—imidazole-4—
`yl] -Py1‘idine,
`
`(Compound 39)
`
`4—[5—(3 -Iodo-pheny1)-2-(4-methanesulfinyl-phenyl)-3H—imidazole—4—
`y1]-pyridine,
`
`(Compound 40)
`
`6-(4—F1uoro-pheny1)-5-pyridine-4-yl-3 ,7-dihydro ~2H-imidazole-
`[2,1 -b]thiazole,
`
`(Compound 41)
`
`4-[5-Ethyl-2—(4-methoxy—phenyl)-1H-imidazole-4—y1]—pyridine,
`
`(Compound 42)
`
`4-[2,5 ~Bis-(4-chloro-phenyl)-1H—imidazole—4-yl] -pyridine,
`
`(Compound 43)
`
`4-[2-(4-Bromo-phenyl)—5-(4—chloro-phenyl)— 1H—imidazole-4-yl] -
`pyridine,
`
`(Compound 44)
`
`4—[2—(2—Ch10ro—pheny1)-5-(4—chloro-pheny1)—1H—imidazole—4-y1]—
`pyridine,
`
`10
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`15
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`20
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`25
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`30
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`35
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`40
`
`45
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`50
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`(Compound 45)
`
`4- [2-(3 -Bromo-pheny1)—5-(4-chloro-pheny1)-1H—imidazole—4-y1]—
`pyridine,
`
`(Compound 46)
`
`4- [5-(4—Chloro-pheny1)-2-(2,3 —dichloro-pheny1)-1H—imidazole-4-y1] —
`pyridine,
`
`(Compound 47)
`
`3 —[5-(4-Chloro-pheny1)—4-pyridine-4-yl-1H-imidazole—2—yl]-4-nitro—
`phenol,
`
`(Compound 48)
`
`4-[5-(4-Chloro-pheny1)-2-(4—fluoro—phenyl)-1H—imidazole—4—yl]—
`pyridine,
`
`(Compound 49)
`
`4-[5-(4-Chloro-pheny1)-2-naphtalene-1 -y1— 1H—imidazole-4—y1] -
`pyridine,
`
`(Compound 50)
`
`4- [2-(3 —Chloro-pheny1)—5-(4-chloro-pheny1)-1H—imidazole-4—yl]-
`pyridine,
`
`(Compound 51)
`
`4—[5-(4-Chloro-pheny1)—2-(3 —methoxy—pheny1)— 1H—imidazole-4-yl] —
`pyridine,
`
`(Compound 52)
`
`4-[5-(4-Chloro-phenyl)—2-(2—methoxy—phenyl)— 1H—imidazole—4-yl] -
`pyridine,
`
`(Compound 53)
`
`4—[5-(4-Chloro-pheny1)—4—pyridine-4-yl- 1H-imidazole-2-yl] -benzene—
`1 ,3-diol,
`
`(Compound 54)
`
`4—[5-(4—Chloro—phenyl)-4-pyridine-4—yl- 1H-imidazole-2-yl]-2-
`metho‘xy-phenol,
`
`(Compound 55)
`
`4—[2—(3~Bromo-pheny1)—5—(3-trifluoromethy1—pheny1)- 1H—imidazole—4—
`le-pyridine,
`
`(Compound 56)
`
`4-[2-(4-Trifluoromethyl-phenyl)—5~(3—t1ifluoromethy1-phenyl)— 1H-
`imidazole-4—y1]—pyridine,
`
`(Compound 57)
`
`4-[2-(4-Bromo—phenyl)—5-(3—trifluoromethy1—pheny1)— 1H—imidazole—4-
`y11-pyridine,
`
`(Compound 58)
`
`4—[5-(3~Iodo-phenyl)—2-(4—trifluor0methyl-phenyl)— 1H—imidazole—4-
`y1]-pyridine,
`
`(Compound 59)
`
`4—[5-(4-Chloro—phenyl)-2-(4~isopropyl—pheny1)—1H—imidazole-4-yl]—
`pyridine,
`
`(Compound 60)
`
`4-[5—(4-Ch]oro-pheny1)-4-pyridine-4-y1—1H—imidazole-2-yl]—2,6—
`dimethyl—phenol,
`
`(Compound 61)
`
`4—[5—(4-Chloro-pheny1)—2-(2,4—Dichloro pheny1)—1H—imidazole—4—yl]—
`pyridine,
`
`10
`
`15
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`20
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`25
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`30
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`35
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`4O
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`45
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`50
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`(Compound 62)
`
`4- [5-(4-Chloro-phenyl) -4-pyridine-4-y1— 1 H-imidazole—2-yl] -
`benzonitrile,
`
`(Compound 63)
`
`4- [5-(4-Chloro-phenyl)-4-pyridine—4-y1-1H—imidazole—2-yl] -phenol,
`
`(Compound 64)
`
`2,6-Di-tert-buty1—4- [5—(4-chloro-pheny1)—4-pyridine-4-y1- lH-imidazole—
`2-y1] -phenol
`
`(Compound 65)
`
`4— [5—(4-Chloro-phenyl)-2—(3 ,4—dimethoxy—phenyl)— 1H—imidazole—4—yl] -
`pyridine,
`
`(Compound 66)
`
`4-[5-(4-Chloro—phenyl)—2-(3 -nitro-phenyl)-1H—imidazole-4-y1]-
`pyridine,
`
`(Compound 67)
`
`4-[5-(4-Chloro—phenyl)-2-(3,4-Dichloro phenyl)-1H—imidazole-4-y1]—
`pyridine,
`
`(Compound 68)
`
`4-[5~(4-Chloro-phenyl)-2-(4-methoxy—phenyl)—1H-imidazole—4-yl]—
`pyridine,
`
`(Compound 69)
`
`4— [5—(4—Chloro—pheny1)-4—pyridine—4-y1— 1H—imidazole-2-yl] —2,6-
`diisopropyI-phenol,
`
`(Compound 70)
`
`N— {4-[5—(4-Chloro-pheny1)—4-pyridine—4-yl-1H-imidazole—2-yl]—
`acetamide,
`
`(Compound 71 )
`
`4-[2-(3,4-Dichloro-pheny1)—5-(3-trifluoromethy1-phenyl)- 1H—
`imidazole-4—yl]—pyridine,
`
`(Compound 72)
`
`4— [2-(4—Chloro-phenyl) -5—(3 —trifluoromethyl—phenyl)— 1H—imidazole-4-
`y1]-pyridine,
`
`(Compound 73)
`
`4-[4-Pyridine-4—yl-5—(3 —trifluoromethy1—phenyl)-lH-imidazole-Z—yl]—
`phenol,
`
`(Compound 74)
`
`4- [4—Pyridine—4—yl—5-(3 -trifluoromethy1-pheny1)-lH-imidazole-Z-yl] -2-
`methoxy—phenol,
`
`(Compound 75)
`
`4-[2—(3 -Chloro-phenyl)—5-(3 -trifluoromethy1—phenyl)-1H—imidazole-4-
`y1]-pyridine,
`
`(Compound 76)
`
`4- [2-(4-Methylsu1fany1-pheny1)—5—(3 -trifluoromethy1—phenyl)—1H-
`imidazole-4—y1]—pyridine,
`
`(Compound 77)
`
`3 - [4-Pyridine—4—yl-5—(3 -trifluoromethyl-pheny1)—IH—imidazole—Z—yl]-
`phenol,
`
`(Compound 78)
`
`4—[2—(3-Bromo-phenyl)—5—(3—iodo-phenyl)—1H—imidazole—4—y1]—
`pyridine,
`
`10
`
`15
`
`20
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`25
`
`3O
`
`35
`
`40
`
`45
`
`50
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`

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`
`(Compound 79)
`
`4—[5-(3-Iodo-phenyl)-4-pyridin-4-y1—lH—imidazole-Z-yl]-2,6—dimethyl-
`phenol,
`
`(Compound 80)
`
`4-[2-(4—Bromo-phenyl)—5-(3-iodo-pheny1)—1H—imidazole—4—yl]—
`pyridine,
`
`(Compound 81)
`
`4-[2-(3 —Chlor0—phenyl)-5-(3 —i0d0-pheny1)— 1H-imidazole-4-y1]—
`pyridine,
`
`(Compound 82)
`
`4—[2-(4—F1uoro—pheny1)—5-(3 -iodo-pheny1)— 1H~imidazole—4—y1] -pyridine,
`
`(Compound 83)
`
`4- [2-Naphta1ene- 1 -y1-5 —pheny1~ 1H-imidazole-4-y1] -pyridine,
`
`(Compound 84)
`
`4-(5 -Pheny1—2-styry1- 1H-imidazole—4—y1]-pyridine,
`
`(Compound 85)
`
`4- [5 -Pheny1-2-(4—trifluoromethy1—phenyl)- 1H—imidazole-4—yl] pyridine,
`
`(Compound 86)
`
`2-Nitro—4—(5-pheny1-4—pyridine—4-yl-1H-imidazole-2-y1)—phenol,
`
`(Compound 87)
`
`4-[2-(3 ~Bromo-pheny1)—5-phenyl— 1H-imidazole-4-y1] -pyridine,
`
`(Compound 88)
`
`2,6-Dimethy1—4—(5 —phenyl-4-pyn'dine-4—y1— 1H-imidazole-Z-yl)-phenol,
`
`(Compound 89)
`
`4- [2-(3,4—Bis—benzyloxy—phenyl)-5-phenyl-1H—imidazole-4-yl]-
`pyridine,
`
`(Compound 90)
`
`4-[2-(3 ,4—Dimethoxy—phenyl)-5—pheny1—1H—imidazole-4—yl] -pyridine,
`
`(Compound 91)
`
`4-[2-(3 —Nitro-pheny1)—5-phenyl— 1H—imidazole-4-y1]-pyridine,
`
`(Compound 92)
`
`4-[2-(4—Chloro-phenyl)-5-pheny1—1H—imidazole—4—y1]—pyridine,
`
`(Compound 93)
`
`2-(5-Phenyl-4—pyridine—4—y1— 1H—imidazole-Z-yl)—benzene—1 ,4-diol,
`
`(Compound 94)
`
`4—(5 -Pheny1—4—pyridine-4-y1- 1H—imidazole-Z—yl)—phenol,
`
`(Compound 95)
`
`3—(5-Phenyl-4-pyridine-4—yl- 1H—imidazole-Z—yl)-phenol,
`
`(Compound 96)
`
`4-[2-(4—Bromo-phenyl)—5-pheny1—1H—imidazole-4—y1]-pyridine,
`
`(Compound 97)
`
`2—Methoxy—4—(5 -pheny1—4-pyridine-4—y1— lH—imidazole-Z-yl)—phenol,
`
`(Compound 98)
`
`4- [2-(4—Isopropyl-pheny1)—5-pheny1- 1H—imidazole-4—y1]-pyridine,
`
`(Compound 99)
`
`4-[2—(2,3—Dichloro—pheny1)—5—phenyl- lH—imidazole—4—y1]—pyridine,
`
`(Compound 100)
`
`4-[2-(2,4-Dichloro-phenyl)-5—pheny1—1H—imidazole-4-yl]-pyridine,
`
`(Compound 101)
`
`4-[2-(4—Methy1sulfanyl—phenyl)-5 -pheny1—1H—imidazole—4-y1]-pyridine,
`
`(Compound 1 02)
`
`4-[2-(2—Ch10ro-pheny1)—5-pheny1—1H—imidazole—4—yl] -pyridine,
`
`10
`
`15
`
`20
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`25
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`3O
`
`35
`
`40
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`45
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`50
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`(Compound 103)
`
`4- [2-(4-Methoxy—pheny1)—5 -pheny1— 1H—imidazole-4—yl] -pyridine,
`
`(Compound 104)
`
`4- [2-(3 -Methoxy-pheny1)-5 -pheny1- 1H-imidazole-4-yl] -pyridine,
`
`(Compound 105)
`
`4-[2—(2-Methoxy—pheny1)—5—pheny1-1H—imidazole-4—y1]—pyridine,
`
`(Compound 106)
`
`4-[2—(3-Ch10ro-pheny1)—5—phenyl—1H—imidazole-4—yl]-pyridine,
`
`(Compound 107)
`
`2,6-Di-tert—butyl-4—(5-pheny1-4-pyridine-4-yl-1H—imidazole-2-yl)-
`phenol,
`
`(Compound 108)
`
`4—(5 —Phenyl-4—pyridine-4-y1- 1H-imidazole-Z~y1)-benzonitrile,
`
`(Compound 109)
`
`N-[4-(5-Phenyl-4-pyridine-4—y1—lH-imidazole-Z ~y1)-pheny1] -acetamide,
`
`(Compound 1 1 0)
`
`4- {2-[2-(2-Methoxy-pheny1)-viny1]-5-phenyl—1H—imidazole-4-yl} —
`pyridine,
`
`(Compound 11 1)
`
`4— [5 —(3 -Iodo—pheny1)-4-pyridine-4-y1— 1H—imidazole-2-yl] -phen01,
`
`(Compound 1 12)
`
`4-[2-(2,3 -Dichloro—pheny1)—5-(3 -iodo-pheny1)-1H—imidazole-4-yl]—
`pyridine,
`
`(Compound 1 13)
`
`4-[5-(4-Chloro-phenyl)-2-(4-methy1su1fany1-pheny1)— 1H-imidazole~4—
`y1]-pyridine,
`
`(Compound 114)
`
`4—[5—(4-Chloro~phenyl)—4—pyridine—4-yl- 1H—imidazole-2—y1]—dimethyl
`amine,
`
`(Compound 1 15)
`
`(Compound 1 16)
`
`4-[5 -(3 -I0do-pheny1)—2-(5 -methy1—furan-2-y1)— 1H—imidazole-4-yl] —
`pyridine,
`4- [4-(4-F1uoro-phenyl)—5 ~pyridine-4-y1-1H—imidazole-2—y1]-
`
`benzylamine,
`
`(Compound 1 17)
`
`4— [5 -(3 —Iodo—pheny1)—2—(4-methylsulfanylpheny1)— 1H—imidazole—4—y1] -
`
`pyridine,
`
`(Compound 1 1 8)
`
`4- [2-(4-Methanesu1finyl~phenyl)—5—phenyl-3H—imidazole-4—y1] -
`
`pyridine,
`
`(Compound 1 1 9)
`
`4-[5 -(4-F1uo