KR20010086091A - Heterocyclic carboxamide-containing thiourea inhibitors of herpes viruses containing a substituted phenylenediamine group - Google Patents

Abstract

Having the formula (I); A compound effective to treat a disease associated with a Herns virus, including human cytomegalovirus, Houghs simplex virus, Epstein-Barr virus, Varicella-Zoster virus, human Herns virus-6 and 7, and Kaposi Hough virus :

Formula I

Wherein R ₁ -R ₅ is selected from hydrogen or substituents; R ₉ -R ₁₂ are independently hydrogen or substituents; Provided that at least one of R < _9-12 > is not hydrogen; G is monocyclic heteroaryl; X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J; J is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl.

Description

[0001] HETEROCYCLIC CARBOXAMIDE-CONTAINING THIOREA INHIBITORS OF HERPES VIRUSES CONTAINING A SUBSTITUTED PHENYLENEDIAMINE GROUP OF HERPES VIRUS CONTAINING SUBSTITUTED Phenylenediamine Groups [0002]

Eight kinds of viruses that are members of the Houghs virus class have been identified (Roizman, B. 1996. Herpesviridae, 2221-2230. In BN Fields, DM Knipe, and PM Howley (ed.), Fields Virology, 3rd ed. Lippincott-Raven Publishers, Philadelphia, Pa.). Each member of this class is characterized by a transmembrane virus containing a proteinaceous envelope and a nucleocapsid, the latter containing a relatively large double-stranded DNA genome of the virus (i.e., approximately 80-250 kb). Members of the human alpha Huffs virus subclass are neurotrophic and include Huffs simplex virus type 1 (HSV-1) and type 2 (HSV-2), and Varicella-Zoster virus (VZV). Human Beta Herns viruses are cytomegalovirus (HCMV), human HERPES virus 6 (HHV-6) and human HERP virus 7 (HHV-7). Gamma Herns viruses are fragile and include Epstein-Barr virus (EBV) and Kaposi's Huffs virus (HHV-8). Each of these HERPV viruses was infected with pneumocystis carotenoids from the pancreas of the pancreas, including the pancreas of HSC-1 and HSV-2 [Whitley, RJ 1996. Herpes Simplex Viruses, p. 2297-2342, In BNFields, DM Knipe, and PM Howley (ed. , Fields Virology, 3rd ed., Lippincott-Raven Publishers, Philadelphia, Pa.); (VZV [Arvin, A. 1996. Varicella-Zoster Virus, p. 2547-2585. In BN Fields, DM Knipe, and PM Hawley (eds.), Fields Virology, 3rd ed., Lippincott- Raven Publishers, Philadelphia, Pa.); Epstein-Barr Virus, pp. 2397-2446. In BN Fields, DM Knipe, and PM Howley (ed.), Fields Virology, 3rd ed., Lippincott -Raven Publishers, Philadelphia, Pa.); Pneumonia and retinitis (HCMV [(Britt, WJ, and Alford, CA 1996. Cytomegalovirus, p. 2493-2523. In BN Fields, DM Knipe, and PM Howley (ed.), Fields Virology, 3rd ed., Lippincott-Raven Publishers , Philadelphia, Pa.); HHV-6 (Pellet, PE, and Black, JB 1996. Human Herpesvirus 6, p. 2587-2608, In BN Fields, DM Knipe, and PM Howley Fields Virology, 3rd ed. Lippincott-Raven Publishers, Philadelphia, PA] and HHV-7 [Frenkel, N., and Roffman, E. 1996. Human Herpesvirus 7, p. 2609-2622. In BN Fields, DMKnipe, and Philadelphia, Pa.) And Kaposi's sarcoma (HHV-8 [Neipel, F., Albrecht, JC, and Fleckenstein, B. 1997. Cell- 71: 4187-92, 1997). [0004] HCMV is considered in more detail in the following paragraphs: [0005] 1. After tea infections, In HSV, the resumed virus is transferred to the infant at birth and is then transferred to the infant at birth. In the case of HSV, the resumed virus is transferred to the infant at birth , Skin or eye infections, central nervous system infections, or metastatic infections (i.e., multiple organs or systems). Shingles is a clinical sign of resumption of VZV activity. Treatment of HSV and VZV is generally performed using antiviral drugs such as acroclover (Glaxo Wellcome), moxibustion clover (Roche) and Asta, and targets virus-encoded DNA polymerases.

HCMV is an opportunistic pathogen present everywhere that infects 50-90% of adult populations (Britt, WJ, and Alford, CA 1996. Cytomegalovirus, p. 2493-2523. In BN Fields, DM Knipe, and PM Howley , Fields Virology, 3rd ed., Lippincott-Raven Publishers, Philadelphia, Pa.). Primary infection of HCMV usually has no subjective symptoms, but heterozygous negative mononucleosis is observed. The virus is transferred horizontally by sexual contact, breast milk, and saliva. Uterine transmission of HCMV from pregnant women to the fetus occurs and is often the cause of serious clinical illness. HCMV survives in a latent state for the remainder of his / her lifetime in the infected human. Cell-mediated immunity plays an important role in regulating activity resumption from latency. Damaged cellular immunity resumes the activity of latent HCMV in positive sera.

HCMV disease is associated with defective or immature cell immunity. There are mainly three classes of people with HCMV disease (see Britt and Alford, 1996). (1) In immunocompromised (AIDS) patients, HCMV is one of the two most common pathogens causing clinical disease (the remainder being Pneumocystis ). Infection of the adrenal glands, lungs, GI tract, and other organs, including the central nervous system, is often reported, but the most common manifestation of HCMV in AIDS is retinitis. 90% of AIDS patients have active HCMV infection; 25-40% (approximately 85,000 patients in the US) have life-or-sight-threatening HCMV disease. HCMV is the cause of death of 10% of humans with AIDS. (2). HCMV activity resumption or reinfection is common in patients with renal, hepatic, cardiac, and genetically different allogeneic bone marrow transplants due to immune system inhibition to reduce the risk of graft rejection. Pneumonia is the most common HCMV disease in these patients and occurs in 70% of these transplant patients. (3) Congenital infection due to HCMV occurs in 1% of all newborns, about 40 K per year. Twenty-five percent of these infants show signs of HCMV disease between the ages of 0-3. HCMV disease is a progressive disease that causes mental retardation and neurodegeneration in childhood. Recent studies suggest that treatment with anti-HCMV drugs may reduce the mortality of these children.

Many antiviral drugs are currently on the market (Bron, D., R. Snoeck, and L. Lagneaux, 1996. New insights into the pathogenesis and treatment of cytomegalovirus. Exp. Opin. Invest. Drugs 5: 337-344; Crumpacker , 1996. Ganciclovir. New Eng. J. Med. 335: 721-729; Sachs, S., and F. Alrabiah. 1996. Novel herpes treatments: a review Exp. Opin. Invest. Drugs 5: 169-183 ). These include moxibustion clovers (Roche), nucleoside analogs with hematopoietic cytotoxicity; Astra, a pyrophosphate analog with renal toxicity; And try a forer (Gilead), nucleoside phosphonates with acute renal toxicity. Each of these drugs targets a virus-encoded DNA polymerase and is typically administered intravenously due to its low bioavailability, and as noted above, is a significant source of toxicity. Clinically occurring ganoderma clover-resistant mutants are often try-forvers and cross-resistant. Thus, it is safer (i. E., Less toxic) that oral bioavailability antiviral drugs are needed for new viral targets.

It is known that phenylthiourea has been utilized in various pharmaceutical fields. WO 97/40028 to Armistead et al. Teaches phenylurea and thiourea as inosine monophosphate dehydrogenase (IMPDH) enzyme inhibitors taught to play an important role in viral replication disorders such as Houghs.

WO 96/25157 to Widdowson et al. Teaches phenylurea and thiourea compounds of the following formula to treat diseases mediated by chemokines, interleukin-8.

U.S. Patent No. 5,593,993 to Morin, Jr., et al. Teaches certain phenylthiourea compounds to inhibit AIDS treatment and replication of HIV-related viruses.

Accordingly, the object of the present invention is to provide a method for the treatment of hepatitis B virus, including human cytomegalovirus, Huffs simplex virus, Epstein-Barr virus, Varicella-Zoster virus, human Herns virus- Or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment and /

According to the present invention there is provided a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein:

In this formula,

R ₁ -R ₅ is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, 10 carbon atoms, cycloalkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, _{halogen, -CN, -NO 2, -CO 2} R 6, -COR 6, -OR 6, -SR 6 _{, -SOR 6, -SO 2 R 6} , -CONR 7 R 8, -NR 6 N (R 7 R 8), -N (R 7 R 8) or _{WY- (CH 2) n -Z (} R 1 - And at least one of R < ₅ > is not hydrogen; R ₂ and R ₃ or R ₃ and R ₄ together form a 3- to 7-membered heterocycloalkyl or a 3- to 7-membered heteroaryl;

R ₆ and R ₇ are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl;

R ₈ is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, 3 to 10 membered heterocycloalkyl, aryl or heteroaryl ,

R ₇ and R _{8 taken} together may form a 3- to 7-membered heterocycloalkyl;

R ₉ -R ₁₂ are independently hydrogen, alkyl of 1 to 4 carbon atoms, perhaloalkyl of 1 to 4 carbon atoms, halogen, alkoxy of 1 to 4 carbon atoms, or cyano, or R ₉ and R ₁₀ or R ₁₁ and R _{12 taken} together may form an aryl of 5 to 7 carbon atoms; Provided that at least one of R < _9-12 > is not hydrogen;

W is O, NR < ₆ > or absent;

Y is - (CO) - or - (CO ₂ ), or is absent;

Z is alkyl of 1 to 4 carbon _{atoms, -CN, -CO 2 R 6,} CO 6, -CONR 7 R 8, -OCOR 6, -NR 6 COR 7, -OCONR 6, -OR 6, -SR 6 , -SOR ₆ , -SO ₂ R ₆ , SR ₆ N (R ₇ R ₈ ), -N (R ₇ R ₈ ) or phenyl;

G is monocyclic heteroaryl;

X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J;

J is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl;

n is 1 to 6;

In some preferred embodiments of the invention, at least one of R ₁ -R ₅ is not hydrogen. In another preferred embodiment of the invention, R ₁ -R ₅ are independently hydrogen, alkyl of 1 to 6 carbon atoms, halogen, perhaloalkyl of 1 to 6 carbon atoms, OR ₆ or N (R ₇ R ₈ ) to be. Preferably, at least one to three of R &_lt; 1 > -R < ₅ > are not hydrogen. Most preferably, two of R < _{1 >} -R < ₅ > are not hydrogen. In preferred compounds of the invention, R ₃ and R ₅ or R ₄ and R ₅ are preferably independently halogen or CF ₃ .

In some preferred embodiments of the present invention, R ₉ -R ₁₂ is selected from halogen, methyl, methoxy and cyano.

In some embodiments of the invention G is preferably thiazolyl, thiadiazolyl, oxazolyl or furyl. More preferably, G is furan. G is preferably unsubstituted.

In some embodiments of the invention, X is a bond or C1-C4 alkyl. Preferably, when X is Ci-C4 alkyl, alkyl is straight chain alkyl.

Preferred compounds of the invention are the following compounds and their pharmaceutical salts:

2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2,5-dimethoxy-phenyl}

2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -3-trifluoromethyl-phenyl}

2-carboxylic acid {3-chloro-4- [3- (5-chloro-2,4-dimethoxy- phenyl) -thioureido] -phenyl}

2-carboxylic acid {5-chloro-4- [3- (5-chloro-2,4-dimethoxy- phenyl) -thioureido] -2-

2-carboxylic acid {5-chloro-4- [3- (5-chloro-2,4- dimethoxy- phenyl) -thioureido] -2-hydroxy- phenyl}

2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -3- cyano- phenyl}

2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -3-methyl- phenyl}

2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy-

2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -3-methoxy-phenyl}

2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2-trifluoromethyl- phenyl}

2-carboxylic acid {2-chloro-4- [3- (5-chloro-2,4-dimethoxy- phenyl) -thioureido] -phenyl}

2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2- cyano- phenyl}

Thioureido] -2 - [(furan-2-carbonyl) -amino] -benzoic acid,

2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2-phenylcarbamoyl-

2-carboxylic acid {2-benzoyl-4- [3- (5-chloro-2,4-dimethoxy- phenyl) -thioureido] -phenyl}

2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy- phenyl) -thioureido] -2-methyl- phenyl}

2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -naphthalen- 1- yl} -amide, and

Furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy-phenyl} -amide, and pharmaceutical salts thereof.

Alkyl, as used herein, refers to straight or branched chain lower alkyl of 1 to 6 carbon atoms. Typical alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl and hexyl.

Alkenyl as used herein refers to straight or branched chain lower alkyl of 2 to 6 carbon atoms containing at least one carbon-carbon double bond. The alkenyl includes a vinyl group.

Alkynyl as used herein refers to straight or branched chain lower alkyl of 2 to 6 carbon atoms containing at least one carbon-carbon triple bond.

The alkyl, alkenyl and alkynyl groups of the present invention may be optionally substituted.

Cycloalkyl refers to a saturated mono or bicyclic ring system of 3 to 10 carbon atoms. Typical cycloalkyl groups include cyclopentyl, cyclohexyl and cycloheptyl. The cycloalkyl group of the present invention may be substituted or unsubstituted.

Heterocycloalkyl refers to a saturated mono- or bicyclic ring system of 3 to 10 members having 1 to 3 heteroatoms selected from N, S and O, and includes aziridinyl, azetidinyl, imidazolidinyl, mor But are not limited to, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, The heterocycloalkyl group of the present invention may be substituted or unsubstituted.

Aryl as used herein refers to an aromatic mono or bicyclic ring of 5 to 10 carbon atoms. Typical aryl groups include phenyl, naphthyl, and biphenyl. The aryl group of the present invention may be substituted or unsubstituted.

Heteroaryl as used herein refers to a 5-10 membered aromatic mono or bicyclic ring having 1 to 3 heteroatoms selected from N, S, or O, and includes thiazolyl, thiadiazolyl, oxazolyl, furyl, But are not limited to, indolyl, benzothiazolyl, benzotriazolyl, benzodioxyl, indazolyl, and benzofuryl. Preferred heteroaryls are selected from quinolyl, isoquinolyl, naphthalenyl, benzofuranyl, benzothienyl, indolyl, pyridyl, pyrazinyl, thienyl, furyl, pyrrolyl, isoxazolyl, oxazolyl, isothiazolyl , Thiazolyl, pyrazolyl, triazolyl, thiadiazolyl, and imidazolyl. The heteroaryl group of the present invention may be substituted or unsubstituted.

Perhaloalkyl refers to an alkyl group of one to six carbon atoms wherein three or more hydrogens are substituted with a halogen.

The phenyl used herein refers to a six membered aromatic ring.

Halogen used herein refers to chlorine, bromine, iodine, and fluorine.

Unless otherwise specified, the substituents may be unsubstituted and have 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms, heterocycloalkyl of 1 to 6 members, perhalo of 1 to 6 carbon atoms, Alkyl, alkylamino, dialkylamino, aryl, or heteroaryl.

The carbon number refers to the number of carbon atoms in the carbon backbone and does not include carbon atoms present in substituents such as alkyl or alkoxy substituents.

Where terms are used in combination, the definitions of each individual part of the combination shall apply unless otherwise specified. For example, alkylcycloalkyl is an alkyl-cycloalkyl group, wherein the alkyl and cycloalkyl are as previously defined.

Pharmaceutically acceptable salts include those of the above formula and pharmaceutically acceptable salts such as phosphoric acid, sulfuric acid, hydrochloric acid, hydrobromic acid, citric acid, maleic acid, succinic acid, fumaric acid, acetic acid, lactic acid, nitric acid, sulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, Is an acid addition salt that may be formed from an acceptable acid.

The compounds of the present invention contain chiral centers and provide various stereoisomeric forms of compounds such as racemic mixtures and individual optical isomers. In some preferred embodiments of the present invention, the compounds of the present invention are substantially pure optical isomers. Substantially pure refers to a composition containing at least 75% of the desired isomer and may include only 25% of the undesired isomer. In a more preferred embodiment, the pure optical isomer has 90% or more of the desired isomer. In some preferred embodiments, when the target is VZV, the (S) isomer is preferred. The individual isomers may be prepared by direct preparation, by asymmetric or stereospecific synthesis, or by conventional separation of the optical isomers from the racemic mixture.

The skilled artisan can prepare the compounds of the present invention by organic synthesis by the methods described below using readily available preparations and starting materials, unless otherwise indicated. The compounds of the present invention are prepared according to the following scheme.

The novel compounds of the present invention are prepared according to the following reaction schemes.

Method 31 and 34. In the case of suitably substituted amine in a suitable solvent, such as a pure solvent or in tetrahydrofuran, acetonitrile, ethyl acetate, dichloromethane, or N, N- dimethylformamide 2 (wherein the substituents R ₁ -R _5, And X are as hereinbefore described, is reacted with an appropriately substituted isothiocyanate 3, wherein substituents R ₉ -R ₁₂ and G are as previously described, to give the desired thiourea 1. Likewise, appropriately substituted isothiocyanates 4 (where the substituents R ₁ -R ₅ and X are as described above equals) the appropriately substituted anilines 5 (where the substituents R ₉ -R ₁₂ and G are described above in a suitable solvent as described above To give the desired thiourea 1.

Methods 31 and 34

Alternatively, the appropriately substituted thiourea 1 may be reacted with a 1 molar equivalent of 1,1'-thiocarbonyldiimidazole in a suitable solvent such as dichloromethane and tetrahydrofuran or a mixture thereof at room temperature or a mixture of dichloromethane and tetrahydrofuran or mixtures thereof In an appropriate solvent, in the presence of 1 molar equivalent of 1,1'-thiocarbonyl-di- (1,2,4) -triazole, anilines 2 and 5, wherein R ₁ -R ₅ , R ₉ -R ₁₂ and G are as hereinbefore defined.

Method 32, 33

In certain cases, subsequent chemical modification of the final thiourea 1 was required. This method, Methods 35-39, is summarized below.

Thiourea ₁ , wherein at least one of R ₁ -R ₅ is 1-hydroxyethoxy or carboxy-methoxy, R ₉ -R ₁₂ and G are as defined above, and X is a bond, At room temperature according to Scheme 36, from the corresponding alkyl esters by alkaline hydrolysis with aqueous sodium or potassium hydroxide in a suitable solvent such as methanol, tetrahydrofuran or mixtures thereof.

Thiourea ₁ , wherein at least one of R ₁ -R ₅ is 1-acyloxyethoxy or methanesulfonoxyethoxy, R ₉ -R ₁₂ and G are as defined above, and X is a bond, And acylation with a suitable acylating agent such as benzoic acid chloride or methanesulfonic acid chloride in the presence of a suitable tertiary amine base such as triethylamine or diisopropylethylamine in a suitable solvent such as dichloromethane at room temperature, Can be prepared from the corresponding 1-hydroxyethoxy derivatives.

Thiourea 1 in which at least one of R ₁ -R ₅ is 1-aminoethoxy, R ₉ -R ₁₂ and G are as defined above, and X is a bond, is reacted with tetrahydrofuran and Methanesulfonoxy-ethoxy derivatives by reaction with a suitable secondary amine such as dimethylamine in an appropriate solvent mixture such as water.

Thiourea 1 in which at least one of R ₁ -R ₅ is 1-aminoalkyl, R ₉ -R ₁₂ and G are as defined above and X is a bond is prepared according to Method 40 at room temperature with methanol, Can be prepared from the corresponding 1-arginylalkyl derivative by reaction with stannous chloride in the same suitable solvent.

The intermediate isothiocyanates 3 and 4 shown in Methods 31 and 34 above are essentially prepared by the methods described in Staab, HA, and Walther, G. Justus Liebigs Ann. Chem. (Wherein R ₁ -R ₅ , R (R ₆₎ , R ₇ , R ₈ , R ₉ , R ₉ and R 9 are as defined above, in a suitable solvent such as dichloromethane and tetrahydrofuran or mixtures thereof, _9- R < ₁₂ > and G are as hereinbefore defined and X is as defined above, with 1 molar equivalent of 1,1'-thiocarbonyldiimidazole.

Method 41

Intermediates 2 and 5 can be prepared according to the following protocol:

According to methods 1A-1G, the amine 2, wherein R ₁ -R ₅ are as defined above and X is as defined above, and amine 5, wherein R ₉ -R ₁₂ are as defined above, Is prepared by reducing the appropriately substituted nitrobenzene according to various procedures known to the skilled artisan and described in RJ Lindsay, Comprehensive Organic Chemistry (ed. Sutherland), Volume 2, Chapter 6.3.1, Aromatic Amines, 1979 . This process

a) iron powder and a strong acid such as hydrochloric acid (Method 1A) in an alcohol solvent such as methanol or ethanol in a pure solvent or at a temperature ranging from room temperature to the reflux temperature of the solvent;

b) iron powder and glacial acetic acid (Method B) in a pure solvent or in an alcohol solvent such as methanol or ethanol, at a temperature ranging from room temperature to the reflux temperature of the solvent;

c) an iron powder and aqueous ammonium chloride (Method C) in a pure solvent or an alcoholic solvent such as methanol or ethanol, at a temperature ranging from room temperature to the reflux temperature of the solvent;

d) tin and strong inorganic acids such as hydrochloric acid (Method D) in a pure solvent or an alcoholic solvent such as methanol or ethanol, at room temperature to the reflux temperature of the solvent;

e) when R ₁ -R ₅ and R ₉ -R ₁₂ are selected from Cl, Br, i, - (OSO ₂ ) -CF ₃ , or - (OSO ₂ ) -1- (4-methylphenyl) By catalytic reduction (Method E) using palladium on carbon and hydrogen under atmospheric pressure in an appropriate solvent such as ethanol or ethyl acetate;

f) when R ₁ -R ₅ and R ₉ -R ₁₂ are selected from Cl, Br, I, - (OSO ₂ ) -CF ₃ , or - (OSO ₂ ) -1- (4-methylphenyl) By catalytic reduction (method E) using palladium on cyclohexene and carbon in a suitable solvent such as ethanol, at room temperature to the reflux temperature of the solvent;

g) in an alcohol solvent at a temperature ranging from room temperature to the reflux temperature of the solvent, aqueous sodium hydrosulfite (Method 1G)

To reduce nitrobenzene to form aniline.

Alternatively, according to Method 3A-3C, an amine 2, wherein R ₁ -R ₅ are as defined above and X is as defined above, and aniline 5 wherein R ₉ -R ₁₂ are as defined above, According to various procedures known to those skilled in the art and described in Greene, Protective Groups in Organic Synthesis volume 2, Chapter 7, 1991, amides are prepared by cleaving aniline nitrogen-carbon bonds of carbamate derivatives of these anilines . This process includes the following:

a) exposing the appropriately substituted arylamino-tert-butyl-carbamate to a strong acid such as trifluoroacetic acid in a pure solvent or a suitable solvent such as dichloromethane at 0 < 0 > C to room temperature (Method 3A);

b) Arylamino- (2-trimethylsilylethyl) -carbamate, suitably substituted in aqueous acetonitrile or tetrahydrofuran or mixtures thereof, at room temperature to the reflux temperature of the solvent, is reacted with a base such as tetrabutylammonium fluoride or potassium fluoride Exposure to fluoride ion (Method 3B), or;

c) exposing the arylamino-trifluoroacetamide, suitably substituted in an alcoholic solvent such as methanol or ethanol, to a strong base such as sodium or potassium hydroxide or sodium or potassium carbonate at a temperature from room temperature to the reflux temperature of the solvent (Method 3C).

Alternatively, according to Method 11, R ₁ -R ₅ have the same meanings as defined above, X is as defined above R ₁ -R 2 amine is at least one substituent is defined as the plastic of the _five is basically described by reference: According to the procedure of V. Farina and GP Roth in Advances in Metal-Organic Chemistry, Vol. 5, 1-53, 1996, in a suitable solvent such as tetrahydrofuran or N-methylpyrrolidinone at room temperature to the reflux temperature of the solvent Palladium catalysts such as tris (dibenzylidineacetone) -bipalladium, and bromo or iodo-anilines suitably substituted with ligands such as triphenylarsine, for example 3-chloro-4-iodo-aniline And palladium catalyzed coupling of vinyltrialkyltin, for example tributylvinyltin.

Alternatively, according to Method 42, the amine 2 in which R ₁ -R ₅ is as defined above and X corresponds to a bond and at least one of R ₂ or R ₄ is defined as dialkylamino is basically described in JF Hartwig such as bis (dibenzylidineacetone) palladium, in a suitable solvent such as tetrahydrofuran or toluene at a temperature between room temperature and 100 < 0 > C, Palladium catalyst, and a ligand such as tri-o-tolylphosphine and at least two molar equivalents of a strong base such as lithium bis- (trimethylsilyl) amide in a sealed tube. Can be prepared by palladium catalyzed amination of 3- or 5-bromo- or iodo-anilines, for example 3-amino-5-bromobenzotrifluoride.

Alternatively, according to Method 43, the amine 2 in which R ₁ -R ₅ is as defined above and X is as previously defined and at least one of R ₂ or R ₄ is defined as alkyl is reacted with tetra (II) chloride-dichloromethane complex and a palladium catalyst such as 9-borabicyclo [3.3.1] hept-2-ene in a suitable solvent such as tetrahydrofuran and 1,1'-bis (diphenylphosphino) Bromo-or iodo-aniline, such as 3-amino-5-bromobenzotrifluoride, in the presence of a suitable base such as triethylamine, Lt; RTI ID = 0.0 > palladium < / RTI >

Acyl and carbamoylamine derivatives used as starting materials in methods 3A-3C can be prepared according to various procedures known to those skilled in the art and described in Greene, Protective Groups in Organic Synthesis volume 2. Chapter 7, 1991 Lt; / RTI > can be prepared by derivatisation of an amine corresponding to that described in 2A-2G. This process includes the following:

a) in an appropriate solvent such as acetone, tetrahydrofuran, dimethylformamide, dichloromethane and the like in the presence or in the absence of at least one equivalent of a tertiary amine such as triethylamine or N, N-diisopropylethylamine, Reacting an appropriately substituted amine with di-tert-butyl-dicarbonate (Method 2A) to yield the corresponding arylamino-tert-butyl-carbamate;

b) in the presence of a tertiary amine such as triethylamine or diisopropylethylamine in an appropriate solvent such as dimethylformamide at room temperature, an appropriately substituted aniline is reacted with 1- [2- (trimethylsilyl) ethoxycarbonyl -Oxy] benzotriazole (Method 2B) to yield the corresponding arylamino- (2-trimethylsilylethyl) -carbamate;

c) in a suitable solvent such as a pure solvent or a suitable solvent such as tetrahydrofuran, dimethylformamide, dichloromethane, pyridine and the like, in the presence of at least one molar equivalent of a tertiary amine base such as triethylamine or N, N-diisopropylethyl- Reacting the resulting aniline with a carboxylic acid chloride or acid anhydride (Method 2C) to produce the corresponding arylaminoamide;

d) in the absence of one or more molar equivalents of a tertiary amine, such as triethylamine or N, N-diisopropylethylamine, in a pure solvent or a suitable solvent such as tetrahydrofuran, 1,4-dioxane, (Method 2D) to produce the corresponding nitroarylaminoamide in the presence of a suitable base, e.g.

e) Synthesis of benzotriazol-1-yloxy-tris- (dimethylamino) -phosphonium hexafluorophosphate, 2- (lH-benzotriazol- l-yloxy) -1,1,3,3- In the presence of a coupling agent such as methyluronium hexafluorophosphate, dicyclohexylcarbodiimide and the like and a tertiary amine such as triethylamine or diisopropylethylamine in an appropriate solvent such as dichloromethane, dimethylformamide and the like, At room temperature, reacting an appropriately substituted aniline with a carboxylic acid (Method 2E) to produce the corresponding arylaminoamide;

in f) pyridine and a suitable solvent, such as dichloromethane, dimethylformamide, etc. in the presence of a suitable base such as, from 0 ℃ to room temperature range, arylamino -tert- butyl- appropriately protected aniline such as carbamate, etc. (where R ₁ Wherein at least one of the -R ₁₂ substituents is defined as -WY- (CH ₂ ) _n -Z and W, Y and Z are as defined above, with a carboxylic acid anhydride (Method 2F) to produce the corresponding carboxylic acid ester ;

g) in a suitable solvent such as acetone, tetrahydrofuran, dimethylformamide, dichloromethane and the like, in the absence of one or more molar equivalents of a tertiary amine such as triethylamine or N, N-diisopropylethylamine, In the reflux temperature range of the solvent, an appropriately substituted aniline (wherein at least one of R ₁ -R ₅ is defined as hydroxyl) is reacted with di-tert-butyl-dicarbonate (Method 2G) to yield the corresponding arylamino- tert-butyl-carbamate.

Nitrobenzene intermediates that are eventually converted to amines 2 and 5 by the process shown in Methods 1A-1G above can be prepared according to Methods 4A, 4C, 4E-4F.

In methods 4A, 4C and 4E-4H, it is converted eventually to amine 2, R ₂ and R ₄ are as hereinbefore defined and R ₁ , R ₃ and / or R ₅ is alkoxy, thioalkoxy, Sulfinyl, and dialkylamino can be prepared by reacting a nitrobenzene intermediate, such as 2-, 4-, and / or 6-fluoro-, chloro-, bromo-, iodo-, trifluoro- Or by nucleophilic substitution of (4-methylphenyl) sulfonyl-substituted nitrobenzene:

a) in a suitable solvent such as a pure solvent or a suitable solvent such as tetrahydrofuran, dioxane, acetonitrile, N, N-dimethylformamide or dimethylsulfoxide, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium hydride Halo-or sulfonate esters of nitrobenzene or benzonitrile with an appropriately substituted 2- or 4-halo- or sulfonate ester in the presence or absence of one or more equivalents of a base such as hydrochloric acid, Reaction of alcohol;

b) in a suitable solvent such as a pure solvent or tetrahydrofuran, dioxane, acetonitrile, N, N-dimethylformamide or dimethylsulfoxide at a temperature ranging from room temperature to the reflux temperature of the solvent, The reaction of preformed sodium, lithium or potassium phenoxide with a 2- or 4-halo- or sulfonate ester;

c) in a suitable solvent such as a pure solvent or tetrahydrofuran, dioxane, acetonitrile, N, N-dimethyl-formamide or dimethylsulfoxide at a temperature ranging from room temperature to the reflux temperature of the solvent, Reaction of the resulting 2- or 4-halo- or sulfonate ester with ammonia, primary or secondary amine (Method 4C, F);

d) in a suitable solvent such as tetrahydrofuran, at a temperature ranging from 0 < 0 > C to the reflux temperature of the solvent, with an appropriately substituted 2- or 4-halo- or sulfonate ester of nitrobenzene or benzonitrile, Reaction with potassium salt (Method 4G), or;

e) in a suitable solvent such as a pure solvent or tetrahydrofuran, dioxane, acetonitrile, N, N-dimethylformamide or dimethylsulfoxide at a temperature ranging from room temperature to the reflux temperature of the solvent, Following the reaction of the 2- or 4-halo- or sulfonate ester with sodium sulfide, the alkyl halide is added directly to the reaction mixture (Method 4E).

Alternatively, in the case of Processes 5C and 6, the nitrobenzene intermediate which is finally converted to the amine 2, wherein at least one of the R ₁ -R ₅ is defined as alkoxy, is reacted with the corresponding substituted hydride Roxy-nitrobenzene: < RTI ID = 0.0 >

a) in the presence of a base such as potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, potassium hydride or a base such as sodium hydride, in the presence of a base such as acetone, N, N-dimethylformamide, tetrahydrofuran Nitrobenzene is reacted with an alkyl halide or dialkyl sulfonate ester (Method 5C) in an appropriate solvent such as, for example, tetrahydrofuran or dimethyl sulfoxide, at a temperature ranging from room temperature to the reflux temperature of the solvent;

b) Hydroxy-nitrobenzene is reacted with an alkyl alcohols in an anhydrous aprotic solvent such as diethyl ether or tetrahydrofuran, at a temperature ranging from 0 < 0 > C to the reflux temperature of the solvent, basically according to the method described in Mitsunobu, O, Synthesis 1981, , Triphenylphosphine, and dialkyl azadicarboxylate, for example, diethyl azodicarboxylate (method 6).

Additionally, in the case of the methods 5A and 5E, the carbamoylamine derivative used as a starting material in the method 3A-3C, which is finally converted to amine 2 (wherein at least one of R ₁ -R ₅ is defined as alkoxy) In the presence of a suitable base such as potassium carbonate in an appropriate solvent such as acetone, toluene or N, N-dimethylformamide, at a temperature ranging from room temperature to the reflux temperature of the solvent, to the corresponding substituted hydroxyarylamino-tert-butyl- Halide, trifluoromethane-sulfonate, 4-methylbenzenesulfonate, dialkylsulfonate, ethylene carbonate, and the like.

Alternatively, in the case of the methods 7A-G, the nitrobenzene intermediate which is finally converted to the amine 2 (R ₁ and / or R ₃ is alkoxy and R ₂ and / or R ₄ is halogen and X corresponds to the bond) Can be prepared by standard halogenation reactions comprising:

a) reaction of 2- or 4-hydroxy-nitrobenzene with aqueous sodium hippuronite at room temperature (methods 7A and 7B);

b) in a suitable solvent such as chloroform, dichloromethane, glacial acetic acid, etc., in the presence or absence of silver trifluoroacetate, at room temperature, with 2-hydroxy-4-methoxy or 2,4-dimethoxynitrobenzene and bromine Reactions (Methods 7C and 7D), or;

c) the reaction of 2,4-dimethoxynitrobenzene with benzyltrimethylammonium dichloroiodate (Method 7E) in an appropriate solvent such as glacial acetic acid in the presence of anhydrous zinc chloride at room temperature;

d) reacting 2-hydroxy-4-methoxynitrobenzene with benzyltrimethyl-ammonium dichloroiodate in a suitable solvent mixture such as dichloromethane and methanol in the presence of sodium bicarbonate at room temperature (Method 7F);

e) Reaction of 2,4-dimethoxynitrobenzene with 3,5-dichloro-1-fluoropyridine triflate in a suitable solvent such as tetrachloroethane at room temperature to the reflux temperature of the solvent (Method 7G).

In the case of Method 8, the nitrobenzene intermediate, which is finally converted to amine 2, wherein R ₄ = -CF ₃ -, R ₁ -R ₃ and R ₅ -R ₈ are as defined above and X corresponds to a bond, In an appropriate solvent such as N, N-dimethylformamide, in the presence of a cuprous iodide and potassium fluoride in a sealed reaction vessel, at a temperature ranging from room temperature to the reflux temperature of the solvent, - Nitrobenzene with trimethyl (trifluoromethyl) silane.

In the case of methods 19A and 19B, finally the amine 2, wherein R ₄ = -HNCOCH ₂ NR ₇ R ₈ or -HNCOCH ₂ SR ₆ , and R ₁ -R ₃ and R ₅ -R ₈ are as defined above and X is The corresponding nitrobenzene intermediate is converted to the corresponding substituted 4- (N-chloroacetyl) -nitroaniline in a suitable solvent, such as tetrahydrofuran and / or water mixtures, at room temperature to the reflux temperature of the solvent With an appropriate secondary amine, such as dimethylamine, morpholine, or the like, in the presence of a suitable base such as sodium or potassium carbonate, in a suitable solvent such as tetrahydrofuran, 1,4-dioxane, Can be prepared by reacting the corresponding substituted 4- (N-chloroacetyl) -nitroaniline with the appropriate thiol in the reflux temperature range.

In the case of Method 25, the nitrobenzene intermediate finally converted to amine 2, wherein at least one of R ₁ -R ₅ is defined as triflate and X corresponds to a bond, is reacted with triethylamine or diisopropyl-ethylamine In the presence of a tertiary amine such as dichloromethane, in a suitable solvent such as dichloromethane, at a temperature ranging from 0 < 0 > C to room temperature, by reacting the corresponding phenol with trifluoromethane-sulfonic anhydride.

9 how, in the case of 9B and 10, a method is used as a starting material in 3A-3C, cover that is finally converted into amines 2 (where at least one substituent R ₁ -R ₅ is defined as an alkyl phenyl alcohol or alkylsulfinyl search) Molecular amine derivatives are prepared by reacting the appropriate 4-alkylthioacylarylamino or carbamoylarylamino derivatives with an appropriate oxidizing agent such as dimethyloxirane or sodium perodate in a suitable solvent mixture such as acetone and dichloromethane or water at room temperature ≪ / RTI >

In the case of Method 12, it is used as the starting material in Methods 3A-3C and finally reacted with amine 2 where R ₄ is defined as 1-hydroxyethyl, R ₁ -R ₃ and R ₅ are as defined above, Is converted to the corresponding 4-vinylcarbamoyl aniline with sodium borohydride in the presence of mercuric acetate in a suitable solvent such as tetrahydrofuran, 1,4-dioxane and water, at room temperature, Lt; / RTI >

In the case of Method 13, it is used as the starting material in Method 3A-3C and finally the amine 2, wherein R ₄ is defined as 2-hydroxyethyl, R ₁ -R ₃ and R ₅ are as defined above, The carbamoylamine derivative is converted to the corresponding 4-vinylcarbamoyl aniline in the presence of glacial acetic acid in an appropriate solvent such as tetrahydrofuran, 1,4-dioxane, and the like at 0 < 0 ≪ / RTI > with sodium borohydride.

In the case of Method 14, the starting materials used in Methods 3A-3C and finally the amine 2 where R ₄ is defined as _1- azidethyl, R ₁ -R ₃ and R ₅ are as defined above, Carbamoylamine derivatives which are converted to the corresponding compounds of formula (I), in the presence of a dialkyl azodicarboxylate, such as diethyl azodicarboxylate and triphenylphosphine, in a suitable solvent mixture, for example tetrahydrofuran and dichloro (1-hydroxyethyl) carbamoyl aniline with hydrazoic acid in the presence of a base, e.g.

In Method 15, it is used as the starting material in Methods 3A-3C and finally the amine 2 where R ₄ is defined as 3-dimethylaminoprop-1-enyl and R ₁ -R ₃ and R ₅ are as defined above And X is a bond) can be prepared by reacting bis (triphenylphosphine) palladium (II) chloride and cuprous (II) chloride in a suitable tertiary amine solvent such as triethylamine or diisopropylethylamine, Can be prepared by reacting the corresponding 4-iodocarbamoyl aniline with 1-dimethylamino-2-propyne in the presence of an iodide, at a temperature ranging from room temperature to the reflux temperature of the solvent.

In the case of Method 16, it is used as starting material in Methods 3A-3C and finally with amine 2 where R ₄ is defined as 3-dimethylaminoacryloyl, R ₁ -R ₃ and R ₅ are as defined above, and X is Bond), can be prepared by reacting the corresponding 4- (3-dimethylaminoprop-1-ynyl) carbamoyl aniline in a suitable solvent mixture, such as dichloromethane and methanol, at 0 ≪ RTI ID = 0.0 > acid. ≪ / RTI >

In the case of Processes 17 and 18, the starting materials used in Methods 3A-3C and finally the amine 2, wherein R ₄ is defined as 4-isoxazol-5-yl or 4- (1H-pyrazol-3-yl) Wherein R ₁ -R ₃ and R ₅ are as defined above and X is a bond, can be prepared by reacting the corresponding 4- ( 3-dimethylamino-acryloyl) carbamoyl aniline with hydroxylamine hydrochloride or hydrazine hydrate.

In Method 20, used as starting materials in Methods 3A-3C and finally in the presence of amine 2, where R ₄ = -HNCO ₂ Z, R ₁ -R ₃ and R ₅ and Z are as defined above and X corresponds to a bond, Is reacted with a corresponding 4-aminocarbamoyl aniline in a suitable solvent mixture such as tetrahydrofuran and dichloromethane at a temperature ranging from room temperature to the reflux temperature of the solvent to 1,1-carbonyl-di- (1 , 2,4) -triazole with an appropriately substituted alcohol.

In the case of Processes 26 and 30, it is used as the starting material in Processes 3A-3C and finally converted to the amine 2, wherein at least one of the substituents R ₁ -R ₅ is defined as dialkylamino and X is as defined above The carbamoylamine derivative can be reacted with a suitably substituted aldehyde and 10% palladium on carbon in the presence of sodium cyanoborohydride or hydrogen gas in a suitable solvent such as water, methanol, tetrahydrofuran mixture or toluene, at room temperature ≪ / RTI >

For methods 27 and 28, amine 2, wherein at least one of R ₁ -R ₅ is defined as hydroxy and X is as defined above, is reacted in a suitable solvent mixture such as a methanol-water mixture, at a temperature ranging from room temperature to the reflux temperature of the solvent , Can be prepared by reacting the corresponding ester, such as acetate, with an appropriate base such as sodium bicarbonate or sodium hydroxide.

For Method 29, the amine 2, wherein at least one of R ₁ -R ₅ is defined as 2-hydroxybenzamido and X is as defined above, in a suitable solvent such as tetrahydrofuran, diethyl ether, , The corresponding N- (4-aminophenyl) phthalimide with lithium borohydride.

An intermediate amine 2 in which R ₁ -R ₅ is as defined above and X is -CH ₂ - or - (CH ₂ ) ₂ can be prepared by the following procedure:

a) reduction of the appropriately substituted benzo-or phenylacetonitrile with a borane-dimethylsulfide complex (method 44) in an appropriate solvent such as ethylene glycol dimethyl ether, tetrahydrofuran or the like at a temperature ranging from room temperature to the reflux temperature of the solvent;

b) in an appropriate solvent such as ethylene glycol monomethyl ether, ethyl acetate, ethanol or the like in the presence of an acid such as 5% or 10% palladium on carbon and 4-methyl-benzenesulfonic acid, Reduction (Method 50);

c) reduction with lithium aluminum hydride in a suitable solvent such as tetrahydrofuran or diethyl ether at 0 < 0 > C to room temperature (Method 51).

Unsaturated nitro precursors which are used as starting materials in Method 51 and which are finally converted to the amine 2 (in which R ₁ -R ₅ is as defined above and X corresponds to - (CH ₂ ) ₂ -) are reacted in the presence of ammonium acetate, In a suitable solvent such as acetic acid, at a temperature ranging from room temperature to the reflux temperature of the solvent (Method 53), by reacting an appropriately substituted benzaldehyde with nitro-methane; The benzaldehyde used as starting material in Method 53 can be prepared by diisobutyl aluminum hydride reduction of an appropriately substituted benzonitrile (method 52). The substituted benzonitrile used as starting material in Method 52 can be prepared by reacting the corresponding aryl bromide with a copper cyanide in an appropriate solvent such as N, N-dimethylformamide, at a temperature ranging from room temperature to the reflux temperature of the solvent (Method 59).

When R ₁ -R ₅ is as defined above and X is an amine-2 corresponding to ether-O (CH ₂ ) ₂ NH ₂ or -S (CH ₂ ) ₂ NH ₂ , the requisite nitrile precursor may be reacted with a suitable May be prepared by reacting appropriately substituted phenol or thiophenol with bromoacetonitrile in an appropriate solvent such as acetone in the presence of a base at room temperature according to Method 49.

Alternatively, for amine 2 where R ₁ -R ₅ is as defined above and X corresponds to - (CH ₂ ) ₃ -, the nitrile precursor is prepared essentially as described in Wilk, B. Synthetic Comm. 23, 2481 (1993)] in an appropriate solvent such as diethyl ether or tetrahydrofuran, in the presence of a suitable azodicarboxylate such as diethyl azodicarboxylate, Can be prepared by reacting substituted phenoxyethanol with acetone cyanohydrin and triphenylphosphine (method 54).

Alternatively, the intermediate amine 2 in which R ₁ -R ₅ is as defined above and X corresponds to - (CH (CH ₃ )) - is reacted with a suitable acid catalyst such as 6N hydrochloric acid or an appropriate acid catalyst such as 5N sodium or potassium hydroxide (Method 46) in an appropriate solvent mixture such as water and methanol or water and ethanol using a base catalyst, at a temperature ranging from room temperature to the reflux temperature of the solvent, or by acid or base catalytic hydrolysis of the corresponding formamide.

The formamide precursor which is used as the starting material in Method 46 and which is finally converted to the amine 2 is treated with suitably substituted acetophenone using ammonium formate, formic acid and formamide at a temperature ranging from room temperature to the reflux temperature of the solvent according to Method 45 .

Alternatively, the amine 2 in which R ₁ -R ₅ is as defined above and X is - (CH (CH ₃ )) - is basically described in Itsuno, S., Sakurai, Y., Ito, K. Synthesis 1988, 995, in an appropriate solvent such as tetrahydrofuran or diethyl ether in the presence of sodium borohydride and zirconium tetrachloride at room temperature, by reduction of the appropriately substituted O-methyl oxime. The required O-methyl oxime can be prepared from the corresponding acetophenone by reaction with methoxylamine hydrochloride and pyridine, in an appropriate solvent such as ethanol or methanol, at a temperature ranging from room temperature to the reflux temperature of the solvent. (Method 47)

Amine 2 corresponding to R ₁ -R ₅ is as hereinbefore defined and X is -CH (J) - (J is as defined above) is reacted with an appropriately substituted Can be prepared by reduction of the ketone. Such essential ketones, which are not normally available, can be obtained by reaction of appropriately substituted benzaldehydes in an appropriate solvent such as diethyl ether or tetrahydrofuran at a temperature ranging from -78 ° C to 0 ° C with an appropriate organometallic agent such as phenyllithium, isopropylmagnesium bromide Or ethyl magnesium bromide (method 57). The resulting alcohol can be oxidized to the corresponding ketone using an appropriate oxidizing agent such as chromium trioxide at room temperature in an appropriate solvent such as aqueous sulfuric acid and acetone or pyridinium chlorochromate or pyridinium dichromate, (Method 58).

The intermediate aniline 5 can be prepared according to Method 3A described above. Treatment of phenylcarbamic acid tert-butyl ester 6 (where G is as previously described) with pure trifluoroacetic acid followed by neutralization with aqueous sodium hydroxide gives the desired aniline 5 at room temperature. The required carbamic acid ester 6 (R ₉ -R ₁₂ and G as previously described) is reacted in the presence of triethylamine, as shown in Method 2C, with a suitable base such as dichloromethane, dimethylsulfoxide or dimethylformamide or mixtures thereof Aminophenylcarbamic acid tert-butyl ester 7, wherein R ₉ -R ₁₂ are as defined above, in a solvent, in the presence of a base (e.g. The carboxylic acid chloride 8 is either commercially available or prepared from the corresponding carboxylic acid by reaction with oxalyl chloride in a suitable solvent such as dichloromethane at room temperature.

Method 2C, 3A

Alternatively, carbamic acid ester 6, wherein R ₉ -R ₁₂ and G are as previously described, is reacted with benzotriazol-1-yloxy-tris- (dimethylamino) phosphonium hexafluorophosphate In the presence of a suitable coupling agent such as 2- (1H-benzotriazol-1-yloxy) -1,1,3,3-tetramethyluronium hexafluorophosphate, dicyclohexylcarbodiimide and the like. In a suitable solvent such as dichloromethane, dimethylformamide and the like in the presence of a tertiary amine base such as an amine or diisopropylethylamine at room temperature, a substituted carboxylic acid 8a (wherein G is as hereinbefore described) and a suitably substituted 4- Aminophenylcarbamic acid tert-butyl ester 7 to give the corresponding arylaminoamide.

The carboxylic acid 8a is commercially available or prepared according to literature methods. For example, if G is a substituted thiadiazole, the acid is available from the corresponding carboxylic acid ester by reacting the appropriate base with sodium or potassium hydroxide at room temperature in a suitable solvent mixture of methanol or ethanol and water.

Likewise, when G is a (unsubstituted) substituted or unsubstituted thiazole, a substituted or unsubstituted oxazole, a substituted or unsubstituted isothiazole or a substituted or unsubstituted isoxazole, the corresponding carboxylic acid 8a is reacted at room temperature In a suitable solvent mixture such as methanol or ethanol and water by reacting the corresponding ethyl or methyl ester with an appropriate base such as sodium or potassium hydroxide. These esters are commercially available or can be prepared according to literature methods.

If a carboxylic acid ester precursor which is finally converted to the acid 8a is not commercially available, it can be prepared by methods known in the literature. For example, 5-substituted-1,2,3-thiadiazole-4-carboxylic acid esters are prepared essentially according to Caron, MJ Org. Chem. 51, 4075 (1986) and Taber, D. F., Ruckle, R.E.J. Amer. Chem. Soc. 108, 7686 (1986). Thus, according to Method 21, in a suitable solvent such as acetonitrile in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine, 4-methylbenzenesulfonyl azide or methanesulfonyl azide, -Ketocarboxylic acid ester is obtained, the corresponding diazo-beta-ketocarboxylic acid ester is obtained. This compound is reacted with 2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane-2, Treatment with 4-disulfide gives the desired 5-substituted-1,2,3-thiadiazole-4-carboxylic acid ester.

Alternatively, 4-substituted -1,2,3-thiadiazole-5-carboxylic acid esters can be prepared essentially according to Shafiee, A., Lalezari, I., Yazdani, S., Shahbazian. F. M., Partovi, T.J. Pharmaceutical Sci. 65, 304 (1976). Thus, according to methods 22 and 23, a beta-ketocarboxylic acid ester suitably substituted in a suitable alcohol solvent such as methanol or ethanol in the presence of a suitable base such as pyridine at room temperature to the reflux temperature of the solvent is treated with aqueous solution of semicarbazide hydrochloride To give the corresponding semicarbazone derivatives. Treatment of these compounds with pure thionyl chloride at 0 < 0 > C followed by treatment with an excess of aqueous sodium bicarbonate affords the corresponding 4-substituted-1,2,3-thiadiazole-5-carboxylic acid ester.

The 4-carboalkoxy thiazole is basically prepared according to the method of Schollkopf, U., Porsch, P., Lau, H. Liebigs Ann. Chem. 1444 (1979). Thus, according to methods 55 and 56, reacting ethylisocyanate with N, N-dimethylformamide dimethylacetal in a suitable alcohol solvent such as ethanol at room temperature gives the corresponding 3-dimethylamino-2-iso Ano-acrylic acid ethyl ester is obtained. A solution of this compound in a suitable solvent such as tetrahydrofuran is treated with gaseous hydrogen sulfide at room temperature in the presence of a suitable tertiary amine base such as triethylamine or diisopropylethylamine to give the corresponding 4-carboethoxy- Thiazole is obtained.

Additional suitably substituted thiazoles can be prepared essentially according to the procedures described in Bredenkamp, M. W., Holzafel, C. W., van Zyl, W. J. Synthetic Comm. 20, 2235 (1990). Suitable unsaturated oxazoles are essentially those described in Henneke, K. H., Schollkopf, U., Neudecker, T. Liebigs Ann. Chem. 1979 (1979)]. Substituted oxazoles are basically prepared according to the method of Galeotti, N., Montagne, C., Poncet, J., Jouin. P. Tetrahedron Lett. 33, 2807, 1 (992) and Shin, C., Okumura, K., Ito, A., Nakamura, Y. Chemistry Lett. 1305, (1994).

The following specific examples are set forth and are not to be construed as limiting the scope of the invention.

Example 1 (Method 1A)

4-Methoxy-3-trifluoromethyl-phenylamine

A suspension of 4-methoxy-3-trifluoromethyl-nitrobenzene (2.2 g) and iron powder (1.68 g) was dissolved in ethanol (35 mL) and water (15 mL) ) ≪ / RTI > (0.42 mL) and the mixture is heated to reflux for approximately 1 hour. The mixture is cooled, filtered and concentrated under reduced pressure. The resulting oil was dissolved in ethyl acetate and extracted three times with 5% aqueous hydrochloric acid. The combined acidic extracts are cooled in an ice bath and basified with solid potassium carbonate and extracted with ethyl acetate. This organic extract is washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure and then passed through a short silica gel column (ethyl acetate is used as eluent) to give the desired compound of the amber oil.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

2,6-Dichloro-benzene-1,4-diamine

3-Chloro-4-methylsulfanyl-phenylamine

2,6-dibromo-benzene-1,4-diamine

3-Chloro-4-trifluoromethyl-phenylamine

3-Chloro-4-ethylsulfanyl-phenylamine

4-Methoxy-3-trifluoromethyl-phenylamine

3,5-Dichloro-4-methoxy-2-methyl-phenylamine

5-Chloro-2-ethoxy-4-methoxy-phenylamine

5-Chloro-4-ethoxy-2-methoxy-phenylamine

5-Iodo-2,4-dimethoxy-phenylamine

3,5-Diiodo-2,4-dimethoxy-phenylamine

3,5-Dibromo-2,4-dimethoxy-phenylamine

5-Chloro-2-methoxy-4-methyl-phenylamine

2-Chloro-N (1), N (1) -dimethyl-benzene-

3-Chloro-4-piperidin-l-yl-phenylamine

3-Chloro-4-pyrrolidin-l-yl-phenylamine

N (1) -benzyl-2-chloro-benzene-1,4-diamine

Chloro-4- (4-methyl-piperazin-l-yl) -phenylamine

2-Chloro-N (1) -methyl-N (1) - (1 -methyl-piperidin-

2-Chloro-N (1) -methyl-N (1) - (1 -methyl-pyrrolidin-

2-Chloro-N (1) -methyl-N (1) -phenyl-benzene-

N (1) - (1-Benzyl-pyrrolidin-3-yl) -2-chloro- N (1)

2-Chloro-N (1) -cyclopentyl-N (1) -methyl-benzene-

2- [(4-Amino-2-chloro-phenyl) - (2-hydroxy-ethyl) -amino]

2-Chloro-N (1) -hexyl-N (1) -methyl-benzene-

2-Chloro-N (1) -isobutyl-N (1) -methyl-benzene-1,4-diamine

2 - [(4-Amino-2-chloro-phenyl) -methyl-amino]

2-Chloro-N (1) - (3-dimethylamino-propyl) -N (1) -methyl-

2-Chloro-N (1) - (2-dimethylamino-ethyl) -N (1) -methyl-

2-chloro-N (1) - (2-dimethylamino-ethyl) -benzene-1,4-diamine

N (1) - (1-Benzyl-piperidin-4-yl) -2-chloro-benzene-

2-Chloro-N (1) - (2-methoxy-ethyl) -N (1) -methyl-

2-Chloro-N (1) - (3-dimethylamino-propyl) -benzene-1,4-diamine

N (1) - (1-Benzyl-pyrrolidin-3-yl) -2-chloro-benzene-

3-Chloro-4- (l-methyl-piperidin-4-yloxy) -phenylamine

3-Chloro-4- (2-dimethylamino-ethoxy) -phenylamine

3-Chloro-4- (3-dimethylamino-propoxy) -phenylamine

3-Chloro-4- (l-methyl-pyrrolidin-3-yloxy) -phenylamine

3-Chloro-4-cyclohexyloxy-phenylamine

Example 2 (Method 1B)

4-Bromo-2,4-dimethoxy-phenylamine

A suspension of 4-bromo-2,4-dimethoxy-nitrobenzene (0.48 g) and iron powder (0.42 g) in acetic acid (10 mL) and ethanol (10 mL) is heated to 120 < 0 > C for approximately 5 hours. The mixture is cooled, filtered and concentrated under reduced pressure. Water is added and the mixture is cooled in an ice bath, then neutralized with solid potassium carbonate and extracted with dichloromethane. This organic extract was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure and then chromatographed on silica gel (20% ethyl acetate in hexanes used as eluent) to give the desired compound of amber oil .

Example 3 (Method 1C)

(4-Amino-2,6-dichloro-phenoxy) -acetic acid tert-butyl ester

A solution of iron powder (0.861 g) and ammonium chloride (86 mg) was added to a solution of (4-nitro-2,6-dichloro-phenoxy) -acetic acid tert- butyl ester (1 g) in ethanol (17 mL) and water (8.6 mL) ≪ / RTI > and the mixture is heated to reflux for approximately 1 hour. The mixture is filtered and concentrated under reduced pressure. The resulting oil is partitioned between water and ethyl acetate and the organic phase is washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the desired compound as a pale yellow solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

4-Chloro-benzene-l, 2-diamine

N- (4-Amino-2-chloro-phenyl) -acetamide

(4-amino-2,6-dichloro-phenoxy) -acetonitrile

(4-Amino-2,6-dichloro-phenoxy) -acetic acid tert-butyl ester

(2-Amino-4-chloro-5-methoxy-phenoxy) -acetonitrile

(4-Amino-2-chloro-5-methoxy-phenoxy) -acetic acid methyl ester

(4-Amino-2-chloro-5-methoxy-phenoxy) -acetic acid tert-butyl ester

(2-Amino-4-chloro-5-methoxy-phenoxy) -acetic acid tert-butyl ester

N (1) -Benzyl-4-chloro-5-methoxy-benzene-

N- (4-Amino-2-chloro-phenyl) -2-fluoro-benzamide

N- (4-Amino-5-chloro-2-hydroxy-phenyl) -acetamide

N- (4-Amino-5-chloro-2-hydroxy-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (4-amino-2-chloro-phenyl)

(4-Amino-2-chloro-phenyl) -carbamic acid ethyl ester

N- (4-Amino-5-chloro-2-methyl-phenyl) -acetamide

N- (4-Amino-5-chloro-2-methyl-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (4-amino-5-chloro-2-methyl- phenyl)

N- (4-amino-3-chloro-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (4-amino-3-chloro-phenyl)

N- (4-Amino-2-chloro-phenyl) -2-dimethylamino-acetamide

N- (4-Amino-2-chloro-phenyl) -2-piperidin-

N- (4-Amino-2-chloro-phenyl) -2-morpholin-4-yl-acetamide

N- (4-Amino-2-chloro-phenyl) -methanesulfonamide

N- (4-Amino-2-chloro-phenyl) -benzamide

N- (4-Amino-2-chloro-phenyl) -2-diethylamino-acetamide

N- (4-Amino-2-chloro-phenyl) -2- pyrrolidin-1-yl-acetamide

N- (4-Amino-2-chloro-phenyl) -2-azepan-1-yl-acetamide

2- (2-methyl-piperidin-l-yl) -acetamide <

2- (3-methyl-piperidin-l-yl) -acetamide <

3-Chloro-benzene-l, 2-diamine

4-Chloro-N, N-dimethyl-benzene-l, 2-diamine

Example 4 (Method 1D)

3,5-Dichloro-4-phenoxy-phenylamine

Dissolve concentrated hydrochloric acid (60 mL) in a slurry of 3,5-dichloro-4-phenoxy-nitrobenzene (6.1 g) and tin powder (12 g). Ethanol (60 mL) is added and the mixture is heated to reflux for approximately 1 hour. The mixture is cooled in an ice bath and basified by the addition of solid sodium hydroxide. The resulting suspension is filtered through a pad of diatomaceous earth and extracted three times with ethyl acetate. The combined organic extracts are washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield the desired product as a yellow solid. Recrystallization from ethyl acetate-hexane gave a pale yellow solid product.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

1-furan-2-yl-ethylamine

3-Chloro-4-isopropoxy-phenylamine

2-Butoxy-5-chloro-4-methoxy-phenylamine

3,5-Dichloro-2-methoxy-4-methyl-phenylamine

2-Benzyloxy-5-chloro-4-methoxy-phenylamine

4-Benzyloxy-5-chloro-2-methoxy-phenylamine

5-fluoro-2,4-dimethoxy-phenylamine

(4-amino-2,6-dichloro-phenoxy) -acetic acid ethyl ester

3,5-Dichloro-4-phenoxy-phenylamine

2- (4-Amino-2-chloro-5-methoxy-phenoxy) -acetamide

(4-Amino-2-chloro-5-methoxy-phenoxy) -acetonitrile

2- (2-Amino-4-chloro-5-methoxy-phenoxy) -ethanol

2- (4-Amino-2-chloro-5-methoxy-phenoxy) -ethanol

4- (4-Amino-2-chloro-5-methoxy-phenoxy) -butyronitrile

4-Amino-2-chloro-5-methoxy-phenol

2-Amino-4-chloro-5-methoxy-phenol

5-Chloro-4-methoxy-2-morpholin-4-yl-phenylamine

4-chloro-5-methoxy-N (1), N (1) -dimethyl-

5-Chloro-4-methoxy-2-piperidin-l-yl-phenylamine

5-Chloro-4-methoxy-2-pyrrolidin-l-yl-phenylamine

2-Chloro-N (1) -cyclohexyl-N (1) -methyl-benzene-

N (2) -benzyl-4-methoxy-benzene-l, 2-diamine

2- (4-Amino-2-chloro-phenoxy) -ethanol

2-Chloro-N (1) -cyclohexyl-N (1) -ethyl-benzene-1,4-diamine

4-Butoxy-3-chloro-phenylamine

(4-Amino-2-chloro-phenoxy) -acetonitrile

2-Chloro-N (1) -cyclohexyl-benzene-1,4-diamine

2-chloro-N (1), N (1) -dipropyl-benzene-1,4-diamine

3-Chloro-4- (2,2,2-trifluoro-ethoxy) -phenylamine

3-Chloro-4- (octahydro-quinolin-l-yl) -phenylamine

N (1) -allyl-2-chloro-N (1) -cyclohexyl-benzene-1,4-diamine

N- (4-Amino-2-methoxy-5-methyl-phenyl) -2-fluoro-

Furan-2-carboxylic acid (4-amino-2-methoxy-5-methyl- phenyl)

N- (4-amino-naphthalen-1-yl) -2-fluoro-benzamide

3-Chloro-N, N-dimethyl-benzene-l, 2-diamine

3-Chloro-4-propoxy-phenylamine

3-Iodo-4-methoxy-phenylamine

3-Chloro-2,4-dimethoxy-aniline

3-Bromo-4-methoxy-phenylamine

3-Chloro-4-ethoxy-phenylamine

Example 5 (Method 1E)

(4-amino-phenyl) -carbamic acid isobutyl ester

To a solution of N- (4-nitro-phenyl) -isobutylamide (2.0 g) in 100 mL ethylene glycol monomethyl ether (100 mL) was added 10% palladium on carbon (275 mg). The mixture is hydrogenated at 30 psi hydrogen in a Parr hydrogenation apparatus at room temperature for 2 hours. The catalyst is removed by filtration through diatomaceous earth and the filtrate is azeotropically mixed with heptane three times and evaporated to dryness under reduced pressure. Trituration of the residue with heptane gives the desired product of a white solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

2-methyl-3H-benzoimidazol-5-ylamine

N- (4-amino-phenyl) -formamide

1H-benzoimidazol-5-ylamine

(4-amino-phenyl) -carbamic acid isobutyl ester

N- (4-amino-phenyl) -isobutyramide

N- (5-amino-pyridin-2-yl) -2-methyl-benzamide

Furan-2-carboxylic acid (5-amino-pyridin-2-yl)

N- (5-Amino-pyridin-2-yl) -2-fluoro-benzamide

[6- (2,2,2-Trifluoro-acetylamino) -pyridin-3-yl] -carbamic acid tert-butyl ester

N- (5-amino-pyridin-2-yl) -2,2,2-trifluoro-acetamide

(4-Amino-benzyl) -carbamic acid tert-butyl ester

2- (3,5-Bis-trifluoromethyl-phenyl) -ethylamine

1-tert-butyl-1H-imidazol-2-ylamine

3- (3-Dimethylamino-propyl) -5-trifluoromethyl-phenylamine

Example 6 (Method 1F)

N- (4-amino-2-methylphenyl) -2-fluorobenzamide

(30 mL), ethanol (70 mL), water (30 mL) and 10% palladium on charcoal (3 g, ) Is heated at reflux for 30 minutes. The mixture is filtered through diatomaceous earth and concentrated under reduced pressure. The resulting oil is dissolved in 50 mL of ethyl acetate and cooled at 4 [deg.] C for 12 hours. Filtration yields the product of a tan solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

N- (4-Amino-2-methyl-phenyl) -acetamide

2-methyl-benzooxazol-6-ylamine

N- (4-amino-3-methoxy-phenyl) -acetamide

2-Acetylamino-5-amino-benzoic acid

N- (4-amino-phenyl) -acetamide

[4- (3-Amino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2-Amino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

N- (4-Amino-2-cyano-phenyl) -acetamide

N- (4-amino-2,5-dimethoxy-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (4-amino-2,5-dimethoxy-phenyl) -amide

N- (4-Amino-2-cyano-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (4-amino-2-methoxy-phenyl)

N- (4-Amino-2-methoxy-phenyl) -2-fluoro-benzamide

N- (4-Amino-2-methoxy-5-methyl-phenyl) -acetamide

N- (4-Amino-2-benzoyl-phenyl) -acetamide

N- (4-Amino-2-benzoyl-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (4-amino-2-benzoyl-phenyl)

N- (4-amino-3-methyl-phenyl) -acetamide

N- (4-Amino-3-methyl-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (4-amino-3-methyl-phenyl)

5-Amino-2 - [(2-fluorobenzoyl) amino] -N-phenylbenzamide

Furan-2-carboxylic acid (4-amino-2-phenylcarbamoyl-phenyl) amide

N- (4-Amino-naphthalen-1-yl) -acetamide

Furan-2-carboxylic acid (4-amino-naphthalen-l-yl) -amide

N- (4-Amino-2-trifluoromethyl-phenyl) -acetamide

Furan-2-carboxylic acid (4-amino-2-cyano-phenyl)

Furan-2-carboxylic acid (4-amino-2-trifluoromethyl-phenyl) -amide

N- (4-Amino-2-methyl-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (4-amino-2-methyl-phenyl)

5-Amino-2- (2-fluoro-benzoylamino) -benzoic acid

5-Amino-2 - [(furan-2-carbonyl) -amino] -benzoic acid

N- (4-Amino-2-cyano-phenyl) -2,2,2-trifluoro-acetamide

N- (4-Amino-3-methyl-phenyl) -2,6-difluoro-benzamide

N- (4-Amino-3-trifluoromethyl-phenyl) -acetamide

N- (4-Amino-3-trifluoromethyl-phenyl) -2-fluoro-benzamide

N- (4-Amino-2-trifluoromethyl-phenyl) -2,2,2-trifluoro-acetamide

N- (4-Amino-2-methoxy-phenyl) -2,2,2-trifluoro-acetamide

N- (4-Amino-2-trifluoromethyl-phenyl) -2-fluoro-N- (2- fluoro-benzoyl)

N- (4-Amino-2-trifluoromethyl-phenyl) -2-fluoro-benzamide

Implementation 7 (Method 1G)

N- (4-amino-2-chlorophenyl) -2-thiomorpholino-4-yl-acetamide

A solution of 3.0 g of N- (2-chloro-4-nitrophenyl) -2-thiomorpholino-4-yl-acetamide in ethanol (200 mL) ) Solution. The mixture is heated at reflux for 12 hours, cooled and then poured into water. The mixture is extracted with ethyl acetate. The ethyl acetate solution is washed twice with saturated aqueous sodium chloride, dried over anhydrous potassium carbonate, filtered through a pad of diatomaceous earth and then concentrated under reduced pressure to give an oil. Addition of toluene and cooling of the solution gives the desired product of a bright orange crystalline solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

N- (4-Amino-2-chloro-phenyl) -2-thiomorpholin-

N- (4-Amino-2-chloro-phenyl) -2-dipropylamino-acetamide

Example 8 (Method 2A)

(3-Chloro-4-iodo-phenyl) -carbamic acid tert-butyl ester

Di-tert-butyl-dicarbonate (8.6 g) was added to a solution of 3-chloro-4-iodo-aniline (10 g) in tetrahydrofuran (40 mL) containing diisopropylethylamine (6.9 mL) And the mixture is heated to reflux. After approximately 15 hours, an additional portion of diisopropylethylamine (6.9 mL) and di-tert-butyl-dicarbonate (21 g) are added and heated continuously for approximately 24 hours. The solution was cooled, concentrated under reduced pressure, then diluted with ethyl acetate and washed three times with 5% aqueous hydrochloric acid and once with saturated aqueous sodium chloride. The solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the desired crude product of the brown oil. Hexane is added to crystallize and the collected solid is recrystallized from hexane to give the desired product of a white solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

N '- (4-nitro-benzoyl) -hydrazinecarboxylic acid tert-butyl ester

(3-Chloro-4-iodo-phenyl) -carbamic acid tert-butyl ester

(4-Bromo-3-chloro-phenyl) -carbamic acid tert-butyl ester

(3-Chloro-4-vinyl-phenyl) -carbamic acid tert-butyl ester

(3-Chloro-4-methylsulfanyl-phenyl) -carbamic acid tert-butyl ester

(4-Amino-3-chloro-phenyl) -carbamic acid tert-butyl ester

(4-chloro-2-nitro-phenyl) -carbamic acid tert-butyl ester

(3-tert-Butoxycarbonylamino-5-chloro-phenyl) -carbamic acid tert-butyl ester

(4-nitro-benzyl) -carbamic acid tert-butyl ester

(3-Bromo-5-trifluoromethyl-phenyl) -carbamic acid tert-butyl ester

(2-Amino-3-chloro-5-trifluoromethyl-phenyl) -carbamic acid tert-butyl ester

Example 9 (Method 2B)

(3-Chloro-4-vinyl-phenyl) -carbamic acid-2-trimethylsilanyl-ethyl ester

To a solution of 3-chloro-4-vinyl-phenylamine (3.4 g) in N, N-dimethylformamide (44 mL) containing diisopropylethylamine (5.8 mL) was added 1- [2- (trimethylsilyl) Oxycarbonyl-oxy] benzotriazole (7.1 g) was added and the mixture was stirred at room temperature under an argon atmosphere for 3 days. The solution is diluted with water and extracted three times with diethyl ether. The combined organic extracts are washed successively with water, saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Chromatography of the resulting residue on silica gel (using 10% ethyl acetate in hexanes as eluent) gave the desired product of the yellow oil.

Example 10 (Method 2C)

[4- (2-Fluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

To a solution of mono-N- (t-butoxycarbonyl) -1,4-phenylenediamine (1.58 g) and triethylamine (1.50 mL) in 25 mL of dichloromethane was added o-fluorobenzoyl chloride (1.20 g) . A solid is formed immediately, which is filtered and washed with fresh solvent to give 1.90 g of a white solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

N- (3-Methoxy-4-nitro-phenyl) -acetamide

N- (4-amino-phenyl) -isobutylamide

2,2,2-Trifluoro-N- (2-methoxy-4-nitro-phenyl) -acetamide

[4- (2-methyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

Acetic acid 2- (4-tert-butoxycarbonylamino-phenylcarbamoyl) -phenyl ester

[4- (4-Fluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (3-Fluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2-Fluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2-Methoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (3-Methoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (4-Methoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2,2-Dimethyl-propionylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2-Bromo-acetylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2,2,2-Trifluoro-acetylamino) -phenyl] -carbamic acid tert-butyl ester

(4-Benzoylamino-phenyl) -carbamic acid tert-butyl ester

(4-methanesulfonylamino-phenyl) -carbamic acid tert-butyl ester

(4-phenylacetylamino-phenyl) -carbamic acid tert-butyl ester

{4 - [(Thiophene-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

[4- (3-nitro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (3-Acetylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (3-Methanesulfonylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

Ethyl [3 - [[4 - [[(1,1-dimethylethoxy) carbonyl] amino] phenyl] amino] carbonyl] phenyl] carbamate

[4- (2-Trifluoromethyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2,6-Difluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2-Chloro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2-Bromo-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2-nitro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

{4 - [(benzo [b] thiophene-2-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester

{4 - [(pyridine-4-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester

{4 - [(Naphthalene-2-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester

{4 - [(Naphthalene-1-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester

{4 - [(3-Bromo-thiophene-2-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester

{4 - [(biphenyl-2-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester

N- (4-tert-Butoxycarbonylamino-phenyl) -phthalamic acid

[4- (2,3-Difluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2,5-Difluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2,4-Difluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2-Acetylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2-Methanesulfonylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2,3,4-Trifluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (2,3,4,5,6-pentafluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

N- (4-tert-Butoxycarbonylamino-phenyl) -isophthalamic acid methyl ester

2-Methylsulfanyl-N- [4- (2,2,2-trifluoro-acetylamino) -phenyl] -benzamide

[4- (3-Benzyloxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (3-Butoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

{4 - [(5-Difluoromethyl-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(Thiophene-3-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4- [(5-methyl-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(5-Bromo-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

(4-hexanoylamino-phenyl) -carbamic acid tert-butyl ester

[4- (2-Thiophen-2-yl-acetylamino) -phenyl] -carbamic acid tert-butyl ester

{4 - [(Pyridine-3-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(4-Bromo-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(furan-3-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

(4-phenoxycarbonylamino-phenyl) -carbamic acid tert-butyl ester

{4 - [(Benzo [1.3] dioxol-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

[4- (3-Trifluoromethoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

N- (2,5-dimethoxy-4-nitro-phenyl) -2-fluoro-benzamide

{4 - [(furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

[4- (2-phenoxy-acetylamino) -phenyl] -carbamic acid tert-butyl ester

{4 - [(5-Nitro-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(5-Chloro-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(3-Methyl-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

[4- (2-Methoxy-acetylamino) -phenyl] -carbamic acid tert-butyl ester

{4 - [(4-Furan-3-yl- [1.2.3] thiadiazole-5-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4- [(5-tert-Butyl-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

N- [3-cyano-4- (2,2,2-trifluoro-acetylamino) -phenyl] -2-fluoro-benzamide

Furan-2-carboxylic acid [3-cyano-4- (2,2,2-trifluoro-acetylamino) -phenyl]

N- (4-Acetylamino-2-cyano-phenyl) -2,2,2-trifluoro-acetamide

2,2,2-Trifluoro-N- (4-nitro-2-trifluoromethyl-phenyl) -acetamide

N- (4-acetylamino-2-trifluoromethyl-phenyl) -2,2,2-trifluoro-acetamide

2-fluoro-N- [4- (2,2,2-trifluoro-acetylamino) -3-trifluoromethyl-phenyl]

Furan-2-carboxylic acid [4- (2,2,2-trifluoro-acetylamino) -3-trifluoromethylphenyl] amide

2-Fluoro-N- (2-methyl-benzooxazol-6-yl) -benzamide

4- (2-Fluoro-benzoylamino) -2-hydroxy-benzoic acid phenyl ester

{4 - [(isoxazole-5-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

N- (4-acetylamino-2-methoxy-phenyl) -2,2,2-trifluoro-acetamide

2-fluoro-N- [3-methoxy-4- (2,2,2-trifluoro-acetylamino) -phenyl]

Fluoro-N- (2-fluoro-benzoyl) -N- (4-nitro-2- trifluoromethyl- phenyl)

{4 - [(lH-pyrazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(lH-imidazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(5-methyl- [1,2,3] thiadiazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

4 - [(5-Furan-3-yl- [1,2,3] thiadiazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

2,2,2-Trifluoro-N- (5-nitro-pyridin-2-yl) -acetamide

{4 - [(1 -methyl-1 H-pyrazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

4- (2-Fluoro-benzoylamino) -2-hydroxy-benzoic acid methyl ester

N- (5-Chloro-2,4-dimethoxy-phenyl) -oxalamic acid

5-carboxylic acid (4-amino-phenyl) -amide

2-Fluoro-N- (4-nitro-benzyl) -benzamide

Furan-2-carboxylic acid 4-nitro-benzylamide

N- [3-chloro-5- (2,2,2-trifluoro-acetylamino) -phenyl] -2,2,2-trifluoro-acetamide

N- (3-Amido-5-chloro-phenyl) -2,2,2-trifluoro-acetamide

[4- (2-Fluoro-benzoylamino) -benzyl] -carbamic acid tert-butyl ester

[4- (2,6-Difluoro-benzoylamino) -benzyl] -carbamic acid tert-butyl ester

2,6-Difluoro-N- (4-nitro-benzyl) -benzamide

{4 - [(furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

N- (3-Amino-5-chloro-phenyl) -acetamide

[4- (3-Chloro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (4-Chloro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

[4- (4-Dimethylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

(4-Benzenesulfonylamino-phenyl) -carbamic acid tert-butyl ester

[4- (3-Trifluoromethyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

2,2,2-Trifluoro-N- (5-nitro-pyrimidin-2-yl) -acetamide

Example 11 (Method 2D)

2-Chloro-N- (2-chloro-4-nitrophenyl) acetamide

A solution of 2-chloro-4-nitroaniline (19.0 g) and chloroacetyl chloride (30 mL) in tetrahydrofuran (150 mL) is heated at reflux for 1 hour. The solution is cooled and concentrated under reduced pressure to yield a wet yellow solid. Ether (250 mL) is added and the yellow solid is collected.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

N- (4-nitro-3-trifluoromethyl-phenyl) -acetamide

(2-Chloro-4-nitro-phenyl) -carbamic acid ethyl ester

2-Acetylamino-5-nitro-benzoic acid

Furan-2-carboxylic acid (5-chloro-2-hydroxy-4-nitro-phenyl)

Furan-2-carboxylic acid (2-methyl-4-nitro-phenyl) -amide

Furan-2-carboxylic acid (2-methoxy-4-nitro-phenyl) -amide

N- (2-Chloro-4-nitro-phenyl) -benzamide

2-Methoxy-N- (4-nitro-phenyl) -acetamide

N- (4-nitro-phenyl) -acrylamide

N- (4-nitro-phenyl) -isobutylamide

[(4-acryloylamino) -phenyl] -carbamic acid tert-butyl ester

(4-nitro-phenyl) -carbamic acid isobutyl ester

[1,2,3] thiadiazole-4-carboxylic acid (5-nitro-pyridin-2-yl)

Furan-2-carboxylic acid (5-nitro-pyridin-2-yl)

2-Fluoro-N- (5-nitro-pyridin-2-yl) -benzamide

N- (2-Chloro-4-nitro-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (2,5-dimethoxy-4-nitro-phenyl) -amide

N- (2-cyano-4-nitro-phenyl) -2-fluoro-benzamide

2-Fluoro-N- (2-methoxy-4-nitro-phenyl) -benzamide

Methyl-N- (5-nitro-pyridin-2-yl) -benzamide

Furan-2-carboxylic acid (2-methoxy-5-methyl-4-nitro-phenyl)

2-Fluoro-N- (2-methoxy-5-methyl-4-nitro-phenyl)

N- (2-Benzoyl-4-nitro-phenyl) -acetamide

N- (2-Benzoyl-4-nitro-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (2-benzoyl-4-nitro-phenyl) -amide

N- (3-methyl-4-nitro-phenyl) -acetamide

2-Fluoro-N- (3-methyl-4-nitro-phenyl) -benzamide

Furan-2-carboxylic acid (3-methyl-4-nitro-phenyl) -amide

2-acetylamino-5-nitro-N-phenyl-benzamide

2 - [(2-fluorobenzoyl) amino] -5-nitro-N-phenylbenzamide

Furan-2-carboxylic acid (4-nitro-2-phenylcarbamoyl-phenyl) -amide

2-Fluoro-N- (4-nitro-naphthalen-l-yl) -benzamide

Furan-2-carboxylic acid (4-nitro-naphthalen-l-yl) -amide

N- (5-chloro-2-hydroxy-4-nitro-phenyl)

N- (5-chloro-2-hydroxy-4-nitro-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (2-chloro-4-nitro-phenyl) -amide

N- (4-nitro-2-trifluoromethyl-phenyl) -acetamide

Furan-2-carboxylic acid (2-cyano-4-nitro-phenyl)

2-Fluoro-N- (4-nitro-2-trifluoromethyl-phenyl) -benzamide

Furan-2-carboxylic acid (4-nitro-2-trifluoromethyl-phenyl) -amide

2-Fluoro-N- (2-methyl-4-nitro-phenyl) -benzamide

N- (5-Chloro-2-methyl-4-nitro-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (5-chloro-2-methyl-4-nitro-phenyl)

2- (2-Fluoro-benzoylamino) -5-nitro-benzoic acid

2 - [(furan-2-carbonyl) -amino] -5-nitro-benzoic acid

N- (3-chloro-4-nitro-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (3-chloro-4-nitro-phenyl) -amide

2,6-difluoro-N- (3-methyl-4-nitro-phenyl) -benzamide

2-Fluoro-N- (4-nitro-3-trifluoromethyl-phenyl) -benzamide

Furan-2-carboxylic acid (4-nitro-3-trifluoromethyl-phenyl) -amide

2-Chloro-N- (2-chloro-4-nitro-phenyl) -acetamide

N- (2-chloro-4-nitrophenyl) methanesulfonamide

Furan-2-carboxylic acid [3-methoxy-4- (2,2,2-trifluoro-acetylamino) -phenyl]

N- (2-Chloro-4-nitro-phenyl) -2,2,2-trifluoro-acetamide

Example 12

{4 - [(4-Phenyl- [1,2,3] thiadiazole-5-carbonyl) -amino] -phenyl} carbamic acid tert-butyl

To a solution of l- (N-tert-butoxycarbonyl) -1,4-phenylenediamine (0.8 g) and 4-phenyl [l, 2,3] thiadiazole-5-carboxylic acid (1 g) in dichloromethane 1.7 g) is treated with triethylamine (1.3 mL) and benzotriazole-1-yloxy-tris (dimethylamino) phosphonium hexa-fluorophosphate (1.6 g). After stirring at room temperature, the reaction is diluted with water and extracted with dichloromethane. The organic layer is washed with 0.5 N hydrochloric acid, saturated sodium bicarbonate and water, then dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain the desired product.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

{4 - [(lH-pyrrole-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(pyrazine-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4- [(5-methyl-thiophene-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(l-methyl-lH-pyrrole-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(Quinoline-8-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(Benzofuran-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(isoquinoline-1-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(Quinoline-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(pyridine-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(isoquinoline-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [([1,2,3] thiadiazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(1H- [1.2.3] thiazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

[4- (2-Methylsulfanyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

{4 - [(Quinoline-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(4-methyl- [1,2,3] thiadiazole-5-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(4-Phenyl- [1,2,3] thiadiazole-5-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

{4 - [(lH-indole-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

[1,2,3] thiadiazole-4-carboxylic acid 4-nitro-benzylamide

{4 - [([1,2,3] thiadiazole-4-carbonyl) -amino] -benzyl} -carbamic acid tert-butyl ester

Acetic acid 4- (4-tert-butoxycarbonylamino-phenylcarbamoyl) -phenyl ester

{4 - [(Quinoline-6-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester

Example 13 (Method 2F)

Acetic acid 2- (4-tert-Butoxycarbonylamino-2,6-dichloro-phenoxy) -ethyl ester

A solution of [3,5-Dichloro-4- (2-hydroxy-ethoxy) -phenyl] -carbamic acid tert-butyl ester (0.85 g) in pyridine (14 mL) was treated with acetic anhydride (1.24 mL) Is stirred at room temperature for 15 hours. The solvent is removed under reduced pressure and the residue is dissolved in ethyl acetate. This solution is washed twice with 5% aqueous hydrochloric acid and once with saturated aqueous sodium bicarbonate followed by saturated aqueous sodium chloride. The solution is dried over anhydrous magnesium sulfate and the solvent is removed under reduced pressure to give the desired product of a colorless oil.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

Phenylsulfanyl-acetonitrile

Acetic acid 2- (4-tert-Butoxycarbonylamino-2,6-dichloro-phenoxy) -ethyl ester

Example 14 (Method 2G)

(3,5-Dichloro-4-hydroxy-phenyl) -carbamic acid tert-butyl ester

Di-tert-butyl-dicarbonate (11.7 g) is added to a solution of 2,6-dichloro-4-aminophenol (9.5 g) in tetrahydrofuran (130 mL) and the mixture is heated to reflux for approximately 15 hours. The solution is cooled, concentrated under reduced pressure, diluted with ethyl acetate and washed three times with 5% aqueous hydrochloric acid and once with saturated aqueous sodium chloride. The solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the desired crude product. When this material is triturated with cold dichloromethane, a white solid product is obtained.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

(3-Amino-5-chloro-phenyl) -carbamic acid tert-butyl ester

Example 15 (Method 3A)

3,5-Dichloro-4-ethoxy-phenylamine

Trifluoroacetic acid (5 mL) is added to solid (3,5-dichloro-4-ethoxy-phenyl) carbamic acid tert-butyl ester (0.97 g) and the mixture is stirred at room temperature for approximately 45 minutes. Water is added and the mixture is cooled in an ice bath and then basified with solid potassium carbonate. The solution is extracted three times with ethyl acetate and the combined organic phases are washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. Concentration under reduced pressure and recrystallization from hexane gives the desired product of a pale yellow crystalline solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

5-Bromo-pyridin-3-ylamine

3-Chloro-4-methanesulfonyl-phenylamine

N- (4-Amino-phenyl) -2-methyl-benzamide

Acetic acid 2- (4-amino-phenylcarbamoyl) -phenyl ester

N- (4-amino-phenyl) -4-fluoro-benzamide

N- (4-Amino-phenyl) -3-fluoro-benzamide

N- (4-amino-phenyl) -2-fluoro-benzamide

N- (4-amino-phenyl) -2-methoxy-benzamide

N- (4-amino-phenyl) -3-methoxy-benzamide

N- (4-amino-phenyl) -4-methoxy-benzamide

N- (4-amino-phenyl) -2-phenyl-acetamide

N- (4-Amino-phenyl) -2,2-dimethyl-propionamide

N- (4-amino-phenyl) -2,2,2-trifluoro-acetamide

Thiophene-2-carboxylic acid (4-amino-phenyl) -amide

Pyrrole-2-carboxylic acid (4-amino-phenyl) -amide

N- (4-amino-phenyl) -3-nitro-benzamide

3-Acetylamino-N- (4-amino-phenyl) -benzamide

N- (4-amino-phenyl) -3-dimethylamino-benzamide

N- (4-amino-phenyl) -3-methanesulfonylamino-benzamide

N- (4-Amino-phenyl) -2-trifluoromethyl-benzamide

N- (4-amino-phenyl) -2,6-difluoro-benzamide

N- (4-amino-phenyl) -2-chloro-benzamide

N- (4-amino-phenyl) -2-bromo-benzamide

N- (4-amino-phenyl) -2-nitro-benzamide

Pyrazine-2-carboxylic acid (4-amino-phenyl) -amide

5-methyl-thiophene-2-carboxylic acid (4-amino-phenyl) -amine

Quinoline-8-carboxylic acid (4-amino-phenyl) -amide

Methyl-lH-pyrrole-2-carboxylic acid (4-amino-phenyl) -amide

Benzo [b] thiophene-2-carboxylic acid (4-amino-phenyl) -amide

Benzofuran-2-carboxylic acid (4-amino-phenyl) -amide

N- (4-amino-phenyl) -isonicotinamide

Naphthalene-2-carboxylic acid (4-amino-phenyl) -amide

Naphthalene-1-carboxylic acid (4-amino-phenyl) -amide

Isoquinoline-1-carboxylic acid (4-amino-phenyl) -amide

Quinoline-2-carboxylic acid (4-amino-phenyl) -amide

3,5-Dichloro-4-ethoxy-phenylamine

4-Butoxy-3,5-dichloro-phenylamine

Isoquinoline-4-carboxylic acid (4-amino-phenyl) -amide

[1,2,3] thiadiazole-4-carboxylic acid (4-amino-phenyl) -amide

1 H- [1,2,3] triazole-4-carboxylic acid (4-amino-phenyl)

3-Bromo-thiophene-2-carboxylic acid (4-amino-phenyl) -amide

4-Benzyloxy-3,5-dichloro-phenylamine

2- (4-Amino-2,6-dichloro-phenoxy) -acetamide

(4-amino-2,6-dichloro-phenoxy) -acetic acid methyl ester

[3- (4-Amino-phenylcarbamoyl) -phenyl] -carbamic acid ethyl ester

2-Amino-N- (4-amino-phenyl) -benzamide

Biphenyl-2-carboxylic acid (4-amino-phenyl) -amide

N- (4-amino-phenyl) -2,3-difluoro-benzamide

N- (4-Amino-phenyl) -2,5-difluoro-benzamide

N- (4-amino-phenyl) -2,4-difluoro-benzamide

2-Acetylamino-N- (4-amino-phenyl) -benzamide

N- (4-amino-phenyl) -2-methanesulfonylamino-benzamide

N- (4-amino-phenyl) -2,3,4-trifluoro-benzamide

N- (4-amino-phenyl) -2,3,4,5,6-pentafluoro-benzamide

N- (4-amino-phenyl) -2-methylsulfanyl-benzamide

Acetic acid 2- (4-amino-2,6-dichloro-phenoxy) -ethyl ester

N- (4-amino-phenyl) -isophthalamic acid methyl ester

N- (4-amino-phenyl) -3-benzyloxy-benzamide

N- (4-amino-phenyl) -3-butoxy-benzamide

[3- (4-Amino-phenylcarbamoyl) -phenoxy] -acetic acid ethyl ester

Pyridine-2-carboxylic acid (4-amino-phenyl) -amide

Quinoline-4-carboxylic acid (4-amino-phenyl) -amide

5-Methyl-furan-2-carboxylic acid (4-amino-phenyl) -amide

5-difluoromethyl-furan-2-carboxylic acid (4-amino-phenyl) -amide

Indole-2-carboxylic acid (4-amino-phenyl) -amide

Methyl [l, 2,3] thiadiazole-5-carboxylic acid (4-amino-phenyl) -amide

Thiophene-3-carboxylic acid (4-amino-phenyl) -amide

5-Chloro-furan-2-carboxylic acid (4-amino-phenyl) -amide

5-Nitro-furan-2-carboxylic acid (4-amino-phenyl) -amide

N- (4-amino-phenyl) -2-thiophen-2-yl-acetamide

3-Methyl-furan-2-carboxylic acid (4-amino-phenyl) -amide

5-Bromo-furan-2-carboxylic acid (4-amino-phenyl) -amide

4-Bromo-furan-2-carboxylic acid (4-amino-phenyl) -amide

N- (4-amino-phenyl) -nicotinamide

N- (4-aminophenyl) -3-furancarboxamide

4-phenyl- [l, 2,3] thiadiazole-5-carboxylic acid (4-amino- phenyl)

Acetic acid 3- (4-amino-phenylcarbamoyl) -phenyl ester

Benzo [l, 3] dioxole-4-carboxylic acid (4-amino-phenyl)

N- (4-amino-phenyl) -3- (2-dimethylamino-ethoxy) -benzamide

N- (4-amino-phenyl) -3-trifluoromethoxy-benzamide

N- (4-amino-phenyl) -3- (2-morpholin-4-yl-ethoxy)

(4-Amino-phenyl) -carbamic acid hexyl ester

Furan-2-carboxylic acid (4-amino-phenyl) -amide

(4-amino-phenyl) -carbamic acid phenyl ester

Hexanoic acid (4-amino-phenyl) -amide

N- (4-amino-phenyl) -acrylamide

N- (4-Amino-phenyl) -2-methoxy-acetamide

4-furan-3-yl [1,2,3] thiadiazole-5-carboxylic acid (4-amino- phenyl)

5-tert-Butyl-furan-2-carboxylic acid (4-amino-phenyl)

3-Chloro-4-methanesulfinyl-phenylamine

5-Methyl- [l, 2,3] thiadiazole-4-carboxylic acid (4-amino-phenyl)

2- (4-Amino-2-chloro-phenyl) -ethanol

(4-Amino-2-chloro-phenyl) -carbamic acid 2-piperidin-1-yl-ethyl ester

5-Chloro-N, N-dimethyl-benzene-1,3-diamine

3- (2-Methyl-butyl) -5-trifluoromethyl-phenylamine

3-isobutyl-5-trifluoromethyl-phenylamine

Furan-2-carboxylic acid (4-aminomethyl-phenyl) -amide

N- (4-Aminomethyl-phenyl) -2-fluoro-benzamide

[1,2,3] thiadiazole-4-carboxylic acid (4-aminomethyl-phenyl) -amide

N- (4-Aminomethyl-phenyl) -2,6-difluoro-benzamide

Oxazole-4-carboxylic acid (4-amino-phenyl) -amide

N- (4-amino-phenyl) -3-chloro-benzamide

N- (4-amino-phenyl) -4-chloro-benzamide

Acetic acid 4- (4-amino-phenylcarbamoyl) -phenyl ester

N- (4-amino-phenyl) -4-dimethylamino-benzamide

L- (4-Amino-phenyl) -3- (3,5-bis-trifluoromethyl-phenyl) -thiourea

N- (4-Amino-phenyl) -2-iodo-benzamide

N- (4-amino-phenyl) -3-trifluoromethyl-benzamide

Example 16 (Method 3B)

L- (4-Amino-2-chloro-phenyl) -ethanol

A 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (5.7 mL) was added to a solution of [3-chloro-4- (1-hydroxy-ethyl) -phenyl] carbamic acid 2-trimethylsilanyl- And the mixture is stirred at room temperature for approximately 3.5 hours. The solution is concentrated under reduced pressure, dissolved in a 1: 1 mixture of ethyl acetate and hexane, successively washed with water and then saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. Removal of the solvent under reduced pressure followed by chromatography on silica gel (40% ethyl acetate in hexanes was used as eluent) gave the product of the amber oil.

Example 17 (Method 3C)

N- (4-amino-3-cyanophenyl) -2-fluoro-benzamide

(5.0 g) was added to a solution of N- [3-cyano-4- (2,2,2-trifluoroacetyl-amino) -phenyl] -2-fluoro Benzamide (2.5 g) and the mixture is refluxed overnight. After the solvent is removed under reduced pressure, the residue is suspended in water and extracted with dichloromethane. The organic extracts are collected, washed with water followed by saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to yield the desired compound as a white solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

N- (4-amino-phenyl) -2-methanesulfinyl-benzamide

N- (4-Amino-3-cyano-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (4-amino-3-cyano-phenyl)

N- (4-amino-3-cyano-phenyl) -acetamide

Furan-2-carboxylic acid (4-amino-3-trifluoromethyl-phenyl) -amide

N- (4-amino-3-methoxy-phenyl) -acetamide

N- (4-Amino-3-methoxy-phenyl) -2-fluoro-benzamide

Furan-2-carboxylic acid (4-amino-3-methoxy-phenyl)

Example 17 (Method 4A)

2-Chloro-1-cyclohexyloxy-4-nitro-benzene

Cyclohexanol (2.9 g) in dimethyl sulfoxide (20 mL) is slowly added to a flask containing potassium hydride (0.90 g, prewashed with hexane 3 times) under an argon atmosphere and the solution is stirred at room temperature for about 1 hour. A solution of 3-chloro-4-fluoro-nitrobenzene (1 g) in dimethyl sulfoxide (10 mL) is added and the resulting dark red solution is heated to approximately 100 ° C for 3 hours. The reaction mixture is cooled, diluted with diethyl ether (300 mL) and then washed successively with saturated aqueous ammonium chloride, then with water, then with saturated aqueous sodium chloride. The organic layer is dried over anhydrous magnesium sulfate, the solvent is removed under reduced pressure and the resulting oil is chromatographed on silica gel (eluting with 5% ethyl acetate in hexanes) to give the desired product as an orange solid.

Example 18 (Method 4C)

(2-chloro-4-nitro-phenyl) -methyl- (1-methyl-pyrrolidin-

3-Chloro-4-fluoronitrobenzene (1.0 g) and N, N'-dimethyl-3-aminopyrrolidine (1.72 g) were collected and stirred for about 24 hours. The mixture is diluted with ethyl acetate, washed twice with water, once with saturated sodium chloride, and dried over anhydrous sodium sulfate. After removal of the solvent under reduced pressure, the residue is chromatographed on silica gel (using pure ethyl acetate followed by pure methanol as eluent) to give the desired product of a yellow oil.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

(2-Chloro-4-nitro-phenyl) -dipropyl-amine

L- (2-Chloro-4-nitro-phenyl) -piperidine

L- (2-Chloro-4-nitro-phenyl) -pyrrolidine

(2-Chloro-4-nitro-phenyl) -cyclohexyl-methyl-amine

Benzyl- (2-chloro-4-nitro-phenyl) -amine

(2-chloro-4-nitro-phenyl) -methyl- (1-methyl-piperidin-

(2-Chloro-4-nitro-phenyl) -cyclohexyl-ethyl-amine

(2-Chloro-4-nitro-phenyl) -cyclohexyl-amine

(2-chloro-4-nitro-phenyl) -methyl- (1-methyl-pyrrolidin-

(L-Benzyl-pyrrolidin-3-yl) - (2-chloro-4-nitro- phenyl)

(2-Chloro-4-nitro-phenyl) -cyclopentyl-methyl-amine

L- (2-Chloro-4-nitro-phenyl) -decahydro-quinoline

Allyl- (2-chloro-4-nitro-phenyl) -cyclohexyl-amine

2 - [(2-Chloro-4-nitro-phenyl) - (2- hydroxy- ethyl) -amino]

(2-Chloro-4-nitro-phenyl) -isobutyl-methyl-amine

(2-Chloro-4-nitro-phenyl) -hexyl-methyl-amine

2 - [(2-Chloro-4-nitro-phenyl) -methyl- amino] -ethanol

N- (2-chloro-4-nitro-phenyl) -N, N ', N'-trimethyl-

N- (2-chloro-4-nitro-phenyl) -N, N ', N'-trimethyl-

(L-Benzyl-piperidin-4-yl) - (2-chloro-4-nitro- phenyl)

N- (2-Chloro-4-nitro-phenyl) -N ', N'-dimethyl-

N- (2-chloro-4-nitro-phenyl) -N ', N'-dimethyl-

(2-chloro-4-nitro-phenyl) - (2-methoxy-ethyl)

(L-Benzyl-pyrrolidin-3-yl) - (2-chloro-4-nitro- phenyl)

4-Piperidin-1-yl-3-trifluoromethyl-benzonitrile

4-Dimethylamino-3-trifluoromethyl-benzonitrile

4- (4-Methyl-piperazin-1-yl) -3-trifluoromethyl-benzonitrile

Example 19 (Method 4E)

Butyl- (2-chloro-4-nitro-phenyl) thioether

A solution of 3-chloro-4-fluoro-nitrobenzene (5.0 g) and sodium sulfide (2.5 g) in N, N-dimethylformamide (30 mL) was stirred at room temperature for 1 hour and then 1-iodobutane 12.6 g). The solvent is removed under reduced pressure and the resulting residue is treated with ethyl acetate and hexane to precipitate inorganic salts. The solids are removed by filtration and the filtrate is reduced under reduced pressure. The residue produced using dichloromethane as an eluent is passed through a hydrous magnesium silicate to give the desired compound in the form of a yellow solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

1-Butylsulfanyl-2-chloro-4-nitro-benzene

2-Chloro-1-cyclohexylsulfanyl-4-nitro-benzene

2-Chloro-l-ethylsulfanyl-4-nitro-benzene

Example 20 (Method 4F)

(4-Chloro-5-methoxy-2-nitro-phenyl) -dimethyl-amine

Dimethylamine (4.0 mL of 40% aqueous solution) was added to a solution of trifluoro-methanesulfonic acid 4-chloro-5-methoxy-2-nitro-phenyl ester (1.0 g) in tetrahydrofuran (2.0 mL) Lt; / RTI > for about 15 hours. The solution is concentrated under reduced pressure and the residue is dissolved in ethyl acetate and washed with water. The aqueous layer is extracted once with ethyl acetate and the combined organic layers are washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. The solvent is removed by evaporation under reduced pressure and the residue is triturated with hexane to give the desired product as a colorless solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

(4-Chloro-2-nitro-phenyl) -dimethyl-amine

4- (4-Chloro-5-methoxy-2-nitro-phenyl) -morpholine

(4-Chloro-5-methoxy-2-nitro-phenyl) -dimethyl-amine

L- (4-Chloro-5-methoxy-2-nitro-phenyl) -piperidine

L- (4-Chloro-5-methoxy-2-nitro-phenyl) -pyrrolidine

Benzyl- (4-chloro-5-methoxy-2-nitro-phenyl) -amine

(2-Chloro-6-nitro-phenyl) -dimethyl-amine

Example 21 (Method 4G)

(2-Chloro-4-nitro-phenyl) -methyl-phenyl-amine

n-Butyl lithium (12.5 mL of 2.5 M solution in hexane) is added dropwise to a solution of N-methylaniline (3.0 g) in tetrahydrofuran (75 mL) at 0 ° C. The mixture is slowly warmed to room temperature and then canned again to a solution of 3-chloro-4-fluoronitrobenzene (4.9 g) in tetrahydrofuran (35 mL), re-cooled to 0 ° C and maintained at -78 ° C. After addition, the reaction mixture is warmed to room temperature over 1 hour, concentrated under reduced pressure, quenched with saturated aqueous ammonium chloride, and extracted three times with ethyl acetate. The combined organic layers are washed three times with 5% aqueous hydrochloric acid, once with water, once with saturated aqueous sodium bicarbonate, once with saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the residue is chromatographed on silica gel (eluting with 5% diethyl ether in hexanes) to give the desired product of a clear, colorless oil.

Example 22 (Method 4H)

2,6-dichloro-4-nitrophenol

3,4,5-Trichlorobenzene (14.86 g) is added to a solution of potassium phenoxide (8.66 g) in diethylene glycol (66 mL) and the mixture is heated to 160 DEG C for approximately 15 hours. The resulting dark brown solution is cooled to room temperature, poured onto 100 mL cold water, and extracted twice with diethyl ether. The combined organic extracts are washed with water, 10% aqueous sodium hydroxide and dried over anhydrous magnesium sulfate. After the solvent is removed under reduced pressure, the resulting oil is distilled using a Kugelrohr apparatus to obtain a yellow oil which solidifies upon standing. Recrystallization from ethanol-water gives the desired product of a pale yellow solid.

Example 23 (Method 5A)

(3,5-Dichloro-4-ethoxy-phenyl) -carbamic acid tert-butyl ester

Ethyl iodide (0.36 mL) was added to a solution of (3,5-dichloro-4-hydroxy-phenyl) -carbamic acid tert-butyl ester (1.0 g) and potassium carbonate (1.0 g) in acetone And the mixture is stirred at room temperature for approximately 15 hours. The solution is filtered, concentrated under reduced pressure, and partitioned between ethyl acetate and water. The separated aqueous layer was extracted twice more with ethyl acetate, and the combined organic extracts were washed successively with 10% aqueous sodium hydroxide, water, and dried over anhydrous sodium sulfate. Evaporation of the solvent under reduced pressure gives the desired product of a tan solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

(3,5-Dichloro-4-ethoxy-phenyl) -carbamic acid tert-butyl ester

(4-Butoxy-3,5-dichloro-phenyl) -carbamic acid tert-butyl ester

(4-Benzyloxy-3,5-dichloro-phenyl) -carbamic acid tert-butyl ester

(4-Carbamoylmethoxy-3,5-dichloro-phenyl) -carbamic acid tert-butyl ester

[3,5-Dichloro-4- (2-nitrilo-ethoxy) -phenyl] -carbamic acid tert-butyl ester

(4-tert-Butoxycarbonylamino-2,6-dichloro-phenoxy) -acetic acid methyl ester

3-Butoxy-benzoic acid methyl ester

3-tert-Butoxycarbonylmethoxy-benzoic acid methyl ester

3-Carbamoylmethoxy-benzoic acid methyl ester

[4- (3-Carbamoylmethoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

{4- [3- (2-Chloro-ethoxy) -benzoylamino] -phenyl} -carbamic acid tert-butyl ester

Example 24 (Method 5C)

(2,6-Dichloro-4-nitro-phenoxy) -acetic acid tert-butyl ester

Tert-Butyl-bromoacetate (10 mL) was added to a solution of 2,6-dichloro-4-nitrophenol (2.5 g) and potassium carbonate (3.3 g) in dimethylformamide (50 mL) Stir for 2 days. The solution is poured into 500 mL of water, extracted three times with hexane, and the combined organic extracts are washed with saturated aqueous ammonium chloride and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting oil is triturated with hexane to give the desired product of a white solid.

Using the above procedure and starting materials the following compounds were prepared:

3-Dimethylamino-l- (4-nitro-phenyl) -propenone

2-chloro-1-isopropoxy-4-nitro-benzene

1,3-dichloro-2-methoxy-4-methyl-5-nitro-

1-Chloro-4-ethoxy-2-methoxy-5-nitro-

1-Butoxy-4-chloro-5-methoxy-2-nitro-benzene

Chloro-2-methoxy-5-nitro-4- (phenylmethoxy) benzene (CA name)

Chloro-4-methoxy-5-nitro-2- (phenylmethoxy) benzene (CA name)

(2,6-Dichloro-4-nitro-phenoxy) -acetic acid tert-butyl ester

(2,6-Dichloro-4-nitro-phenoxy) -acetonitrile

1-Chloro-4-methoxy-2-methyl-5-nitro-

2- (4-Chloro-5-methoxy-2-nitro-phenoxy) -acetamide

2- (2-Chloro-5-methoxy-4-nitro-phenoxy) -acetamide

(4-Chloro-5-methoxy-2-nitro-phenoxy) -acetonitrile

(2-Chloro-5-methoxy-4-nitro-phenoxy) -acetonitrile

4- (2-Chloro-5-methoxy-4-nitro-phenoxy) -butyronitrile

2- (4-Chloro-5-methoxy-2-nitro-phenoxy)

2- (2-Chloro-5-methoxy-4-nitro-phenoxy)

(2-Chloro-5-methoxy-4-nitro-phenoxy) -acetic acid tert-butyl ester

(2-Chloro-5-methoxy-4-nitro-phenoxy) -acetic acid methyl ester

(4-Chloro-5-methoxy-2-nitro-phenoxy) -acetic acid methyl ester

(4-Chloro-5-methoxy-2-nitro-phenoxy) -acetic acid tert-butyl ester

(2-Chloro-4-nitro-phenoxy) -acetonitrile

1-Butoxy-2-chloro-4-nitro-benzene

2-Chloro-4-nitro-1- (2,2,2-trifluoro-ethoxy)

2-Chloro-4-nitro-1-propoxy-benzene

2-chloro-1-ethoxy-4-nitro-benzene

1,3-Diiodo-2,4-dimethoxy-5-nitro-benzene

1,3-dibromo-2,4-dimethoxy-5-nitro-benzene

3-Chloro-2,4-dimethoxy-nitrobenzene

Example 25 (Method 5E)

[3,5-Dichloro-4- (2-hydroxy-ethoxy) -phenyl] -carbamic acid tert-butyl ester

To a solution of (3,5-dichloro-4-hydroxy-phenyl) -carbamic acid tert-butyl ester (1.0 g) and potassium carbonate (0.55 g) in toluene (20 mL) was added ethylene carbonate (1.6 g) Is heated at reflux for 3 hours. To the cooled reaction mixture is added 2.5M aqueous sodium hydroxide (50 mL) and the separated organic layer is successively washed with water, saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. The solvent is removed by evaporation under reduced pressure and the resulting residue is chromatographed on silica gel (eluting with 30% ethyl acetate in hexanes) to give the desired product of the white foam.

Example 26 (Method 6)

3- (2-Chloro-4-nitro-phenoxy) -l-methyl-pyrrolidine

To a solution of 2-chloro-4-nitrophenol (2.0 g) in tetrahydrofuran (60 mL) were added 1-methyl-3-pyrrolidinol (2.3 g), triphenylphosphine (6.0 g) and diethyl azodicarboxyl (3.6 mL) is added and the mixture is stirred at room temperature under an argon atmosphere for 1.5 hours. The solution is concentrated under reduced pressure, diluted with ethyl acetate, washed successively with 10% aqueous sodium hydroxide, water, saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate. The solvent is removed by evaporation under reduced pressure and the residue is chromatographed on silica gel (using ethyl acetate followed by 10% methanol in dichloromethane). Recrystallization of the collected product fractions with hexane gives the desired product of a yellow solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

4- (2-Chloro-4-nitro-phenoxy) -l-methyl-piperidine

3- (2-Chloro-4-nitro-phenoxy) -l-methyl-pyrrolidine

[2- (2-Chloro-4-nitro-phenoxy) -ethyl] -dimethyl-amine

[3- (2-Chloro-4-nitro-phenoxy) -propyl] -dimethyl- amine

Example 27 (Method 7A)

2-chloro-3-methoxy-6-nitro-phenol and 2,4-dichloro-3-methoxy-

To a flask containing 3-methoxy-6-nitro-phenol (0.5 g) was added aqueous sodium hypochlorite (5.25% aqueous solution, 21 mL) and the mixture was stirred at room temperature for approximately 24 hours. The mixture was cooled in an ice bath, acidified with concentrated hydrochloric acid, and extracted twice with ethyl acetate. This organic extract was dried over anhydrous magnesium sulfate, the solvent was removed by evaporation under reduced pressure, and the residue was chromatographed on silica gel (using 15% acetone in hexane as eluent) to afford mono- and di-chlorination of the yellow solid The product is obtained.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

3-Chloro-2-hydroxy-4-methoxy-nitrobenzene

3,5-Dichloro-2-hydroxy-4-methoxy-nitrobenzene

Example 28 (Method 7B)

2,4-dichloro-3-methyl-6-nitro-phenol

To a solution of 3-methyl-4-nitro-phenol (5.0 g) in water (150 mL) was added aqueous sodium hypochlorite (5.25% aqueous solution, 230 mL) and the mixture was stirred at room temperature for approximately 15 hours. Additional aqueous sodium hypochlorite (5.25% aqueous solution, 230 mL) is added and the mixture is stirred at room temperature for 2.5 days. The mixture is cooled in an ice bath, acidified with concentrated hydrochloric acid and extracted twice with ethyl acetate. The organic extracts are dried over anhydrous magnesium sulfate, the solvent is removed by evaporation under reduced pressure, and the residue is chromatographed on silica gel (using ethyl acetate as eluent) to give the desired product of a yellow solid. Once recrystallized with chloroform, a pure sample is obtained by analysis.

Example 29 (Method 7C)

1-Bromo-2,4-dimethoxy-5-nitro-benzene

A solution of bromine (0.23 g) in chloroform (1 mL) was added dropwise to a solution of 2,4-dimethoxy-nitrobenzene (0.50 g) in chloroform (3 mL) and the mixture was stirred at room temperature for approximately 15 hours. Additional bromine (0.15 g) in chloroform (1 mL) is added and the reaction is stirred for an additional 4 h. The mixture is poured onto 5% aqueous sodium bisulfite and extracted with chloroform. The combined organic extracts are washed successively with 5% aqueous sodium bisulfite followed by saturated sodium chloride and dried over anhydrous sodium sulfate. Removal of the solvent under reduced pressure and recrystallization of the residue with toluene gives the desired product of a yellow solid.

Example 30 (Method 7D)

2,4-dibromo-3-methoxy-6-nitro-phenol

A solution of bromine (1.42 g) in glacial acetic acid (3 mL) was added dropwise to a solution of 5-methoxy-2-nitro-phenol (0.25 g) and silver trifluoroacetate (0.49 g) in glacial acetic acid (3 mL) Lt; / RTI > for about 24 hours. The solution is partitioned between ethyl acetate and water and the organic layer is washed three times with 5% aqueous sodium bisulfite, three times with saturated aqueous sodium bicarbonate, and once with saturated aqueous sodium chloride. The organic layer is dried over anhydrous magnesium sulfate and the solvent is dried under reduced pressure. The residue was chromatographed on silica gel (20% ethyl acetate in hexane as eluent) and recrystallized from chloroform to give the desired bromide product of an orange solid.

Example 31 (Method 7E)

1-Iodo-2,4-dimethoxy-5-nitro-benzene

Benzyltrimethylammonium dichloroiodate (1.90 g) and anhydrous zinc chloride (1.0 g) were added to a solution of 2,4-dimethoxy-nitrobenzene (1.0 g) in glacial acetic acid (30 mL) and the mixture was stirred do. Additional benzyltrimethylammonium dichloroiodate (0.4 g) is added after 5 h and after 24 h. Additional zinc chloride (0.5 g) and glacial acetic acid (15 mL) are added after 24 h. The mixture is stirred for 3 days at room temperature and filtered, then diluted with 5% aqueous sodium bisulfite and extracted three times with ethyl acetate. The combined organic layers are successively washed with 5% aqueous sodium bisulfite, saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the residue is triturated with hexane to give the desired product of a pale yellow solid.

Example 32 (Method 7F)

2,4-Diiodo-3-methoxy-6-nitro-phenol

Benzyltrimethylammonium dichloroiodate (1.08 g) and sodium bicarbonate (0.85 g) were added to a solution of 5-methoxy-2-nitro-phenol (0.25 g) in dichloromethane (15 mL) and methanol The mixture is stirred at room temperature for 24 hours. The solution is filtered, the filtrate is concentrated under reduced pressure, the residue is dissolved in ethyl acetate and successively washed with 5% aqueous sodium bicarbonate, 5% aqueous sodium bisulfite and saturated aqueous sodium chloride. After drying over anhydrous magnesium sulfate, the solvent is removed by evaporation under reduced pressure, and the residue is recrystallized from toluene to give the desired product in the form of a yellow needle.

Example 33 (Method 7G)

1-Fluoro-2,4-dimethoxy-5-nitro-benzene

3,5-Dichloro-1-fluoro-pyridinium triflate (85%, 5.07 g) was added to a solution of 2,4-dimethoxy-nitrobenzene (1.0 g) in tetrachloroethane (10 mL) Heat to 120 < 0 > C for 5 hours. Additional 3,5-dichloro-1-fluoro-pyridinium triflate (85%, 0.25 g) is added and heating is continued for 1 hour. The solution is cooled to room temperature and passed through a silica gel column (using hexane followed by 30% ethyl acetate in hexanes as eluent). The product containing fractions were pooled, evaporated under reduced pressure and the residue crystallized with hexane to give the desired product as a tan solid.

Example 34 (Method 8)

3-Chloro-4-trifluoromethyl-nitrobenzene

(2.26 g), trimethyl (trifluoromethyl) silane (5.68 g), copper (I) iodide (2.28 g) in N, N-dimethylformamide g) and potassium fluoride (0.56 g) in a sealed tube is heated to 80 < 0 > C for 40 hours. The solution is cooled, diluted with diethyl ether, filtered through diatomaceous earth, and the filtrate is successively washed with water, saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue chromatographed on silica gel (using 1% diethyl ether in hexanes followed by 10% ethyl acetate in hexanes as eluent) to give the desired product of a colorless oil.

Example 35 (Method 9)

(3-Chloro-4-methanesulfinyl-phenyl) -carbamic acid tert-butyl ester

To a solution of (3-chloro-4-thiomethyl-phenyl) -carbamic acid tert-butyl ester (0.89 g) in dichloromethane (15 mL) at 0 ° C was added a solution of dimethyldioxirane (~0.11 M in acetone, 34 mL) Is added and the mixture is stirred at 0 < 0 > C for 1 hour. The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane, washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Removal of the solvent under reduced pressure gives the desired product in the form of an orange foam.

Example 36 (Method 9B)

[4- (2-methylsulfinyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

To a solution of 2-methylsulfanyl-N- [4- (2,2,2-trifluoro-acetylamino) -phenyl] benzamide (234 mg) was added saturated sodium peridate solution (5 mL) Is stirred for 12 hours. The purple mixture is poured into water, extracted with ethyl acetate, dried over anhydrous potassium carbonate and evaporated to give 101 mg of a red solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared.

[4- (2-Methanesulfinyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

2-methanesulfinyl-N- [4- (2,2,2-trifluoro-acetylamino) -phenyl] -benzamide

Implementation 37 (Method 10)

(3-Chloro-4-methanesulfonyl-phenyl) -carbamic acid tert-butyl ester

A solution of dimethyldioxirane (~0.11 M in acetone, 80 mL) was added to a solution of (3-chloro-4-thiomethyl-phenyl) -carbamic acid tert- butyl ester (0.90 g) in dichloromethane (30 mL) Is added and the mixture is stirred at 0 < 0 > C for 1 hour. The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane, washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Removal of the solvent under reduced pressure gives the desired product of the orange foam.

Example 38 (Method 11)

3-Chloro-4-vinyl-phenylamine

Oxygen removal of 3-chloro-4-iodo-aniline (6.95 g), triphenylarsine (0.67 g) and tris (dibenzylideneacetone) palladium (0) (0.50 g) in tetrahydrofuran Was added tributylvinyltin (10 g) at 50 < 0 > C and the mixture was stirred under an argon atmosphere at 50 < 0 > C for approximately 15 hours. The reaction is cooled, filtered through diatomaceous earth, and the filtrate is evaporated to dryness under reduced pressure. The residue is dissolved in hexane and extracted three times with 5% aqueous hydrochloric acid. This aqueous acidic extract is basified with solid potassium carbonate and extracted three times with ethyl acetate. The combined organic extracts are washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and the solvent is removed under reduced pressure. Chromatographing the resulting residue on silica gel (using hexane followed by 10% ethyl acetate in hexanes as eluent) gave the desired product of the amber oil.

Example 39 (Method 12)

[3-Chloro-4- (1-hydroxy-ethyl) -phenyl] -carbamic acid 2-trimethylsilanyl-ethyl ester

(2.6 g) was added to a solution of mercury acetate (3.48 g) in water (7 mL) and tetrahydrofuran (5.25 mL) And the mixture is stirred for approximately 15 hours. 3N Aqueous sodium hydroxide (8.7 mL) and a 0.5 M solution of sodium borohydride in 3N aqueous sodium hydroxide (8.7 mL) are added and stirred continuously for 6 hours. The solution is saturated with sodium chloride and extracted with ethyl acetate. This organic extract is washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. Removal of the solvent under reduced pressure and chromatography of the residue on silica gel (using 20% ethyl acetate in hexanes as eluent) gave the desired product as a white solid.

Example 40 (Method 13)

[3-Chloro-4- (2-hydroxy-ethyl) -phenyl] -carbamic acid tert-butyl ester

To a stirred suspension of sodium borohydride (0.45 g) in tetrahydrofuran (13 mL) at 0 C is added glacial acetic acid (0.75 mL) and the mixture is stirred at 0 < 0 > C for 1 hour. The solution is warmed to room temperature and (3-chloro-4-vinyl-phenyl) -carbamic acid 2-trimethylsilanyl-ethyl ester (1.0 g) is added. The reaction is stirred at room temperature for approximately 15 hours and then heated to reflux for approximately 20 hours. The mixture was cooled and a solution of 5 N aqueous sodium hydroxide (0.80 mL) and 30% aqueous hydrogen peroxide (0.56 mL) was added. After stirring for an additional 15 hours the layers were separated and the aqueous layer was washed with diethyl ether After extraction, the organic extracts are dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the residue is chromatographed on silica gel (using 40% ethyl acetate in hexanes as eluent) to give the desired product of the amber oil.

Example 41 (Method 14)

[4- (1-Azido-ethyl) -3-chloro-phenyl] -carbamic acid 2-trimethylsilanyl-ethyl ester

To a solution of 3-chloro-4- (1-hydroxy-ethyl) -phenyl] -carbamic acid 2-trimethylsilanyl-ethyl ester (1.25 g) in tetrahydrofuran (20 mL) Phenyl-phosphine (2.6 g), hydrazoic acid (approximately 2.5 molar equivalents in dichloromethane, prepared by the method of Fieser and Fieser, Reagents for Organic Synthesis, Vol.1, pg.444; Wiley, New York) Add azodicarboxylate (1.72 g). After approximately 10 minutes, the solvent is removed under reduced pressure and the residue chromatographed on silica gel (using 5% ethyl acetate in hexanes as eluent) to give the desired product of a colorless oil.

Example 42 (Method 15)

[3-Chloro-4- (3-dimethylamino-prop-1-ynyl) -phenyl] -carbamic acid tert-butyl ester

To a degassed solution of (3-chloro-4-iodo-phenyl) -carbamic acid tert-butyl ester (10.0 g) in triethylamine (120 mL) (Triphenylphosphine) palladium (II) chloride (0.4 g), and cuprous iodide (0.054 g). The mixture is stirred at room temperature under an argon atmosphere for approximately 6 hours and then heated rapidly to 60 [deg.] C (10 minutes). The reaction mixture is cooled, filtered through diatomaceous earth, and then the solvent is removed by evaporation under reduced pressure. The residue was dissolved in ethyl acetate, washed three times with water, once with saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. The solvent was removed by evaporation under reduced pressure and the residue chromatographed on silica gel (eluting with 80% ethyl acetate in hexanes) to give a purified product of the amber oil which solidified on standing.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

[3-Chloro-4- (3-dimethylamino-prop-1-ynyl) -phenyl] -carbamic acid tert-butyl ester

[3- (4-Methoxy-phenyl) -prop-2-ynyl] -dimethyl-amine

4- (3-Dimethylamino-prop-1-ynyl) -benzonitrile

Dimethyl- [3- (4-nitro-phenyl) -prop-2-ynyl] -amine

Example 43 (Method 16)

[3-Chloro-4- (3-dimethylamino-acryloyl) -phenyl] -carbamic acid tert-butyl ester

To a cold solution of [3-chloro-4- (3-dimethylamino-prop-1 -inyl) -phenyl] carbamic acid tert-butyl ester (4.0 g) in dichloromethane (30 ml) was added a small amount of 3- Oxybenzoic acid (2.34 g). After stirring the reaction at 0 ° C for 20 minutes, the mixture is passed over 20 parts of basic alumina (Brockmann Grade I, 150 mesh) and the N-oxide is eluted with a 5% methanol solution in dichloromethane. All fractions containing the desired amine N-oxide are pooled and evaporated to dryness under reduced pressure. The residue is treated three times with a small amount of methanol (50 ml), evaporated to dryness under reduced pressure, and then the volume of the solution is adjusted to 250 mL by addition of methanol. The N-oxide methanol solution is heated to reflux for approximately 15 hours, then cooled, and the solvent is evaporated to dryness under reduced pressure. Purification of the residue by chromatography on silica gel (using 80% ethyl acetate in hexanes as eluent) gave the desired product as a pale yellow solid.

Example 44 (Method 17)

(3-Chloro-4-isoxazol-5-yl-phenyl) -carbamic acid tert-butyl ester

A solution of [3-chloro-4- (3-dimethylamino-acryloyl) -phenyl] -carbamic acid tert-butyl ester (270 mg) in dioxane (3 ml) was treated with hydroxylamine hydrochloride And the mixture is stirred at room temperature for 10 days. The mixture is diluted with ethyl acetate and washed successively with water, 5% aqueous sodium bicarbonate, saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent is removed by evaporation under reduced pressure and the resulting residue is chromatographed on silica gel (eluting with 33% ethyl acetate in hexanes) to give the desired product as a colorless solid.

Example 45 (Method 18)

[3-Chloro-4- (lH-pyrazol-3-yl) -phenyl] -carbamic acid tert-butyl ester

A solution of [3-chloro-4- (3-dimethylamino-acryloyl) -phenyl] -carbamic acid tert-butyl ester (250 mg) in ethanol (1.25 ml) was treated with hydrazine hydrate (0.25 ml) Is stirred at room temperature for 3 hours. The mixture is diluted with 30 mL of diethyl ether, washed three times with water, once with saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. The solvent is removed by evaporation under reduced pressure and the resulting residue is chromatographed on silica gel (eluting with 67% ethyl acetate in hexanes) to give the desired product in the form of an oil.

Example 46 (Method 19A)

N- (2-chloro-4-nitrophenyl) -2-thiomorpholino-4-yl-acetamide

To a solution of N- (chloroacetyl) -2-chloro-4-nitroaniline (3.80 g) in tetrahydrofuran (50 mL) was added thiomorpholine (10 mL) and the solution was allowed to stand for 1 hour. The reaction mixture was poured into water, and a pale yellow solid was collected and then recrystallized from hot 2-propanol to obtain a pale yellow crystal solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

(4- {2- [Bis- (2-hydroxy-ethyl) -amino] -acetylamino} -phenyl} -carbamic acid tert-butyl ester

[4- (2-Dimethylamino-acetylamino) -phenyl] -carbamic acid tert-butyl ester

{4- [3- (2-Dimethylamino-ethoxy) -benzoylamino] -phenyl} -carbamic acid tert-butyl ester

{4- [3- (2-Morpholin-4-yl-ethoxy) -benzoylamino] -phenyl} -carbamic acid tert-butyl ester

N- (2-Chloro-4-nitro-phenyl) -2-dimethylamino-acetamide

N- (2-Chloro-4-nitro-phenyl) -2-piperidin-1-yl-acetamide

N- (2-Chloro-4-nitro-phenyl) -2-morpholin-4-yl-acetamide

N- (2-chloro-4-nitro-phenyl) -2-dipropylamino-acetamide

N- (2-Chloro-4-nitro-phenyl) -2-thiomorpholin-4-yl-acetamide

N- (2-Chloro-4-nitro-phenyl) -2-diethylamino-acetamide

N- (2-Chloro-4-nitro-phenyl) -2-pyrrolidin- 1-yl-acetamide

2-Azepan-1-yl-N- (2-chloro-4-nitro-phenyl) -acetamide

N- (2-Chloro-4-nitro-phenyl) -2- (2- methyl- piperidin- l-yl) -acetamide

N- (2-Chloro-4-nitro-phenyl) -2- (3- methyl- piperidin- l-yl) -acetamide

N- (2-Chloro-4-nitro-phenyl) -2- (4-methyl- piperidin- 1- yl) -acetamide

Example 47 (Method 19B)

N- (2-chloro-4-nitrophenyl) -2- (2-dimethylaminoethylsulfanyl) acetamide

To a solution of N- (chloroacetyl) -2-chloro-4-nitroaniline (3.01 g) in N, N-dimethylformamide (100 mL) was added powdered sodium carbonate (6.0 g) and 2-dimethylaminoethanethiol Chloride (6.0 g) is added. The mixture is stirred at 25 < 0 > C for 1 hour, poured into water and then extracted with ethyl acetate. The ethyl acetate solution is dried over anhydrous potassium carbonate and concentrated under reduced pressure to give an oil. The oil was crystallized from toluene-hexane (3: 1) to give a pale yellow crystalline solid.

Implementation 48 (Method 20)

(4-tert-Butoxycarbonylamino-2-chloro-phenyl) -carbamic acid 2-

Piperidin-1-yl-ethyl ester

To a suspension of 1,1-carbonyl-di- (1,2,4) -triazole (4.0 g) in dichloromethane (40 mL) was added a solution of (4-amino- Carbamic acid tert-butyl ester (5.0 g) was added dropwise over 20 minutes. When the reaction product is stirred at room temperature for 30 minutes, a precipitate is formed at this point. Piperidine ethanol (6.6 mL) is added to this mixture and tetra-hydofuran (20 mL) is added to keep it homogeneous. After heating at reflux overnight, the reaction is cooled and poured into water, and the organic layer is separated and washed with saturated aqueous sodium chloride. The solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield crude which was purified by chromatography on silica gel (using 5% methanol in dichloromethane as eluent) to give the desired product in the form of a white foam .

Example 49

5-phenyl- [1,2,3] thiadiazole-4-carboxylic acid methyl ester

A solution of ethyl benzoylacetate (1.1 g) in acetonitrile (10 mL) is treated with 4-methylbenzenesulfonyl azide (1.3 g) and triethylamine (1.6 g). After stirring at room temperature overnight, the reaction is concentrated under reduced pressure and the resulting crude product is dissolved in ethyl acetate and washed with 1N sodium hydroxide. The organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a yellow oil. This oil is taken up in dichloromethane, filtered through a functional magnesium silicate pad and eluted with dichloromethane to give a partially purified diazo ketone of a colorless oil. The diazo ketone sample (1.2 g) was dissolved in toluene (25 mL) and 2,4-bis -Disulfide < / RTI > (2.8 g) and the reaction is then heated to reflux. After 3 hours, the reaction was cooled to room temperature, loaded onto a silica gel pad and then eluted with dichloromethane. After removal of the solvent under reduced pressure, the resulting oil was purified by chromatography on silica gel (using 30% diethyl ether in petroleum ether as eluent) and recrystallization from hexanes to give the desired product in the form of a pale yellow needle.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

5-phenyl- [l, 2,3] thiadiazole-4-carboxylic acid ethyl ester

5-phenyl- [1,2,3] thiadiazole-4-carboxylic acid methyl ester

Example 50

Ethyl benzoyl acetate < RTI ID = 0.0 >

Ethylbenzoyl acetate (5.0 g) is dissolved in methanol (10 mL) and added rapidly to a hot solution of water (130 mL) semicarbazide hydrochloride (29 g). To this was added pyridine (4.1 g) and heated at reflux for 5 min, then the reaction mixture was cooled to -20 < 0 > C overnight. The resulting solid semicarbazone is collected by filtration and washed with water followed by diethyl ether to yield the desired product of white crystals.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

Ethyl (Z) -3 - [(aminocarbonyl) hydrazono] -4,4,4-trifluorobutanoate

3 - [(Z) -2- (aminocarbonyl) hydrazono] -3-phenylpropanoic acid ethyl ester

3 - [(E) -2- (aminocarbonyl) hydrazono] -3- (3-furyl) propanoic acid ethyl ester

Example 51

5-phenyl- [l, 2,3] thiadiazole-5-carboxylic acid ethyl ester

A solution of ethyl benzoylacetate semicarbazone (2.5 g) in neat thionyl chloride (5 mL) was stirred at 0 < 0 > C for 1 hour. Dichloromethane (25 mL) is added and excess thionyl chloride is slowly destroyed with saturated aqueous sodium bicarbonate. The precipitate formed upon cooling is removed by filtration and the filtrate is extracted with dichloromethane. The combined organic extracts are dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Chromatography on silica gel (using 50% hexane in dichloromethane as eluent) gives the desired product of a colorless oil.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

Methyl- [l, 2,3] thiadiazole-5-carboxylic acid methyl ester

4-phenyl- [l, 2,3] thiadiazole-5-carboxylic acid ethyl ester

Furan-3-yl- [1,2,3] thiadiazole-5-carboxylic acid ethyl ester

Example 52

Methyl- [l, 2,3] thiadiazole-5-carboxylic acid

4-Methyl- [l, 2,3] thiadiazole-5-carboxylic acid methyl ester (1.7 g) is dissolved in methanol (15 mL) and treated with 1 N sodium hydroxide (16 mL). After stirring at room temperature for 1 hour, the reaction was treated with concentrated hydrochloric acid (1.5 mL) and then concentrated under reduced pressure. The resulting cloudy water layer is extracted twice with diethyl ether, and the combined organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain the desired compound of white powder.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

3-Ethoxycarbonylmethoxy-benzoic acid

5-furan-3-yl- [1,2,3] thiadiazole-4-carboxylic acid

Thiazole-4-carboxylic acid

Methyl- [l, 2,3] thiadiazole-5-carboxylic acid

5-Methyl- [l, 2,3] thiadiazole-4-carboxylic acid

Example 53 (Method 25)

Trifluoro-methanesulfonic acid 4-chloro-5-methoxy-2-nitro-phenyl ester

To a solution of 4-chloro-5-methoxy-2-nitro-phenol (6.5 g) in dichloromethane (150 mL) at 0 C under argon atmosphere was added triethylamine (10 g) followed by dichloromethane (30 mL) Is added a solution of tri-fluoro-methanesulfonic anhydride (13.5 g). The solution is stirred at 0 < 0 > C for 10 min, then diluted with dichloromethane and then washed successively with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. After drying over anhydrous sodium sulfate, the solvent is removed by evaporation under reduced pressure, the residue is dissolved in 20% dichloromethane solution in hexane and a short column of dihydrate magnesium silicate is passed through (20% dichloromethane in hexane is used as eluent) . The fractions containing the product are collected and the solvent is removed by evaporation under reduced pressure to obtain the desired product of the yellow oil.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

Trifluoro-methanesulfonic acid 4-chloro-5-methoxy-2-nitro-phenyl ester

Trifluoro-methanesulfonic acid 4-chloro-2-nitro-phenyl ester

Trifluoro-methanesulfonic acid 2-chloro-6-nitro-phenyl ester

Example 54 (Method 26)

[4- (3-Dimethylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

(505 mg), sodium cyanoborohydride (250 mg), acetic acid (3 drops) and 1: 2 tetrahydrofuran-2-carboxylic acid tert- A solution of 40% aqueous formaldehyde (4 mL) in methanol (15 mL) is stirred for 15 minutes, poured into saturated aqueous sodium bicarbonate and then extracted with ethyl acetate. The ethyl acetate solution was dried over anhydrous potassium carbonate and concentrated under reduced pressure to obtain a solid which was recrystallized from acetonitrile to give a pale pink crystalline solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

[4- (3-Dimethylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester

(3-Bromo-5-trifluoromethyl-phenyl) -dimethyl-amine

N- (3-chloro-5-dimethylamino-phenyl) -acetamide

Example 55 (Method 27)

N- (4-aminophenyl) -2-hydroxybenzamide

To a solution of 2- (4-aminophenylcarbamoyl) phenylacetate (580 mg) in methanol (10 mL) is added saturated sodium bicarbonate (2 mL) and water (3 mL). The mixture is heated at 80 < 0 > C for 30 minutes, poured into semi-saturated aqueous sodium chloride and then extracted with ethyl acetate. The ethyl acetate solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give an oil which is triturated with diethyl ether to give the desired product as a white solid.

Example 56 (Method 28)

[4- (3- (Hydroxybenzoylamino) phenyl} carbamic acid tert-butyl ester

To a solution of 3- (4-aminophenylcarbamoyl) phenylacetate (4.34 g) in methanol (75 mL) was added 0.1 N aqueous sodium hydroxide (25 mL) and tetrahydrofuran (25 mL). The solution is heated at 40 < 0 > C for 30 minutes, cooled, poured into 1 M hydrochloric acid and extracted with ethyl acetate. The ethyl acetate solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a white solid which is further purified by trituration with diethyl ether.

Example 57 (Method 29)

N- (4-aminophenyl) -2-hydroxymethylbenzamide

Lithium borohydride (1.0 g) was added to a solution of N- (4-aminophenyl) phthalimide (332 mg) in tetrahydrofuran (4 mL) and the mixture was stirred at 25 ° C for 1 hour. The mixture is poured into water and extracted with ethyl acetate. The ethyl acetate solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a white foam which is triturated with diethyl ether to give the desired product of a white powder.

Example 58 (Method 30)

(3-Chloro-5-dimethylamino-phenyl) -carbamic acid tert-butyl ester

To the solution of (3-amino-5-chloro-phenyl) -carbamic acid tert-butyl ester (0.32 g) in toluene (10 mL) was added aqueous formaldehyde (37%, 1.5 mL) followed by 10% palladium on carbon 0.50 g) is added and the mixture is stirred under a hydrogen atmosphere for approximately 15 hours. The solution is filtered through diatomaceous earth and the filtrate is concentrated under reduced pressure. Chromatographing the residue on silica gel (using 50% dichloromethane in hexane as eluent) gave the desired product as a white solid.

Example 59 (Method 35)

N- (4- {3- [3,5-Dichloro-4- (2-hydroxy-ethoxy) -phenyl] -thioureido}

Phenyl) acetamide

To a stirred solution of 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy} ethyl ester in a 1: 1 mixture of tetrahydrofuran and methanol (0.16 g) in 1 N aqueous sodium hydroxide (1 mL) is added and the mixture is stirred at room temperature for approximately 2 hours. The solution is poured into 2 M aqueous hydrochloric acid (3 mL), extracted with ethyl acetate, and the extract is dried over anhydrous sodium sulfate. The solvent is removed by evaporation under reduced pressure and the residue is triturated with diethyl ether to give the desired product of a white solid.

Example 60 (Method 36)

{4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy}

To a solution of {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy} -acetic acid ethyl ester (0.29 g) in a 1: 1 mixture of tetrahydrofuran and methanol g) is added 1N aqueous sodium hydroxide (2 mL) and the mixture is stirred at room temperature for approximately 2 hours. The solution is poured into 2 M aqueous hydrochloric acid (5 mL), extracted with ethyl acetate, and the extract is dried over anhydrous sodium sulfate. The solvent is removed by evaporation under reduced pressure and the residue is triturated with diethyl ether to give the desired product of a white solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

{4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy}

2- {3- [4-Acetylamino-phenyl) -thioureido] -4-chloro-5-methoxy-phenoxy}

2-chloro-5-methoxy-phenoxy} -acetic acid < / RTI >

Example 61 (Method 37)

Benzoic acid 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy} -

Ethyl ester

To a solution of N- (4- {3- [3,5-Dichloro-4- (2-hydroxy-ethoxy) -phenyl] thioureido} -phenyl) -methanone in pyridine (2 mL) and tetrahydrofuran ) Acetic acid (0.20 g) was added benzoyl chloride (0.08 g) and the mixture was stirred at 0 < 0 > C for 1.5 h. The mixture is diluted with ethyl acetate, washed twice with 2% aqueous hydrochloric acid, once with saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, the residue was chromatographed on silica gel (using 5% methanol in dichloromethane as eluent). The fractions containing the product were collected and evaporated under reduced pressure, and the residue was recrystallized from acetone-hexane A desired product of the white powder is obtained.

Example 62 (Method 38)

Methanesulfonic acid 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy} -ethyl ester

To a solution of N- (4- {3- [3,5-Dichloro-4- (2-hydroxy-ethoxy) -phenyl] thioureido} -phenyl) -methanone in pyridine (2 mL) and tetrahydrofuran ) Acetamide (0.20 g) in methanesulfonyl chloride (0.11 g) was added and the solution was stirred at 0 ° C for 45 minutes. The reaction mixture is diluted with ethyl acetate, washed twice with 2% aqueous hydrochloric acid, once with saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. The solvent is removed by evaporation under reduced pressure, and the resulting residue is recrystallized from acetone-hexane to obtain the desired product of white powder.

Example 63 (Method 39)

(4- {3- [3,5-Dichloro-4- (2-dimethylamino-ethoxy) -phenyl] -thioureido} -phenyl) -

Acetamide

To a solution of methanesulfonic acid 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichlorophenoxy} -ethyl ester (0.33 g) in tetrahydrofuran (6 mL) Aqueous dimethyl-amine (8.8 M, 0.5 mL) is added and the mixture is stirred at room temperature for 5 days. The reaction mixture is diluted with ethyl acetate, washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the residue is chromatographed on silica gel (using pure methanol as eluent). The fraction containing the collected product is evaporated under reduced pressure and the residue is recrystallized from acetonitrile to obtain the desired product of the white powder.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

- (4- {3- [3,5-Dichloro-4- (2-dimethylamino-ethoxy) -phenyl] -thioureido} -phenyl) acetamide

Benzoic acid 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy} ethyl ester

Example 64 (Method 40)

Carboxylic acid (4- {3- [4- (1-amino-ethyl) -3-chloro-phenyl] -thioureido}

Phenyl) amide

To a solution of furan-2-carboxylic acid (4- {3- [4- (1-azido-ethyl) -3-chloro-phenyl] -tetrahydroisoquinoline (0.25 g) in methanol (2.5 mL) -Ureido} -phenyl) -amide (0.22 g) is added and the solution is stirred at room temperature for approximately 15 hours. The solution is diluted with ethyl acetate, washed successively with saturated aqueous sodium bicarbonate followed by saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. After evaporation of the solvent under reduced pressure, the residue is chromatographed on silica gel (using 8% methanol in dichloromethane containing 1% triethylamine as eluent) to give the desired product as a yellow solid.

Example 65 (Method 41)

[1,2,3] thiadiazole-4-carboxylic acid (4-isothiocyanato-phenyl) -amide

To an ice cold solution of 1,1'-thiocarbonyldiimidazole (7.28 g) in tetrahydrofuran (50 mL) was added [1,2,3] -thiadiazole-4-carboxylic acid (4-amino-phenyl) amide (9.0 g). After approximately 1 hour the solvent is evaporated off and the residue is dissolved in ethyl acetate. Diethyl ether is added to precipitate the crude product, which is collected by filtration, dissolved in dichloromethane, and passed through a hydrous magnesium silicate plug. After removal of the solvent, the residue is recrystallized from ethyl acetate-hexane to give the desired product of a weak yellow solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

2-fluoro-N- (4-isothiocyanato-phenyl) -benzamide

Furan-2-carboxylic acid (4-isothiocyanato-phenyl) -amide

[1,2,3] thiadiazole-4-carboxylic acid (4-isothiocyanato-phenyl) -amide

Thiazole-4-carboxylic acid (4-isothiocyanato-phenyl) -amide

Example 66 (Method 42)

N, N-dimethyl-5-trifluoromethyl-benzene-1,3-diamine

To a solution of 3-amino-5-bromo-benzotrifluoride (1.0 g) in degassed (argon) tetrahydrofuran (2 mL) was added bis- (tri- o- tolylphosphino) palladium (2 M, 4.2 mL) and a solution of lithium bis (trimethylsilyl) amide in tetrahydrofuran (1 M, 10.4 mL) in tetrahydrofuran were added. The reaction mixture is heated to 100 < 0 > C for about 2.5 hours in a sealed vessel to terminate the reaction. The mixture is cooled to room temperature, water is added, cooled and then diluted with ethyl acetate. The product is extracted three times with 5% aqueous hydrochloric acid, and the acidic extract is collected and then basified with cooling with addition of 5N aqueous sodium hydroxide. This basic solution is extracted with ethyl acetate and the combined organic extracts are washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure. Chromatographing the resulting residue on silica gel (using 20-30% ethyl acetate in hexanes as eluent) gives the desired product of a light pale solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

3- (4-Methyl-piperazin-l-yl) -5-trifluoromethyl-phenylamine

3-Morpholin-4-yl-5-trifluoromethyl-phenylamine

3-Piperidin-l-yl-5-trifluoromethyl-phenylamine

3-pyrrolidin-l-yl-5-trifluoromethyl-phenylamine

N, N-dimethyl-5-trifluoromethyl-benzene-1,3-diamine

N-isobutyl-N-methyl-5-trifluoromethyl-benzene-1,3-diamine

N-butyl-N-methyl-5-trifluoromethyl-benzene-1,3-diamine

Example 67 (Method 43)

(3-isobutyl-5-trifluoromethyl-phenyl) -carbamic acid tert-butyl ester

Bubbled isobutylene in a sealed tube containing tetrahydrofuran (5 mL) capped with a rubber membrane and cooled in a dry ice-acetone bath for about 5 minutes. A solution of 9-borabicyclo [3.3.1] nonane in tetrahydrofuran (0.5 M, 11 mL) was added and the vessel was sealed with a Teflon cap, then warmed slowly to room temperature and maintained at room temperature for approximately 2.5 hours. The mixture is re-cooled in a dry ice-acetone bath, the Teflon cap is replaced with a rubber membrane, and excess isobutylene is removed by bubbling the mixture through argon. A solution of (3-bromo-5-trifluoromethyl-phenyl) -carbamic acid tert-butyl ester (1.7 g) in tetrahydrofuran (12 mL) Phosphino) -ferrocene] palladium (II) chloride-dichloromethane complex (0.12 g) and 3 N aqueous sodium hydroxide are added. The vessel is resealed with a Teflon cap and then heated to 65 ° C for approximately 15 hours. The mixture is cooled to room temperature, diluted with hexane, washed with water, saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. Chromatograph the resulting oil on silica gel (using 5% ethyl acetate in hexanes as eluent) to give the desired product of a white powder.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

[3- (2-Methyl-butyl) -5-trifluoromethyl-phenyl] -carbamic acid tert-butyl ester

(3-isobutyl-5-trifluoromethyl-phenyl) -carbamic acid tert-butyl ester

Example 68 (Method 44)

2- (3,5-Dichloro-phenylsulfanyl) -ethylamine

0.61 mL of 10 M borane dimethyl sulfide complex is added to a solution of (3,5-dichlorophenylthio) acetonitrile (1.2 g) in 3.0 mL of ethylene glycol dimethyl ether and the mixture is heated at reflux for 0.5 hour. Cool the reaction in an ice bath and add 2.0 mL of water and 2.0 mL of concentrated hydrochloric acid. This mixture is heated to reflux for 0.5 h. The clear solution is cooled, basified with 5N sodium hydroxide and extracted with ether. The ether extract is dried over potassium carbonate, filtered and concentrated to give 1.0 g of a colorless oil.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

2- (3-Bromo-phenylsulfanyl) -ethylamine

2- (4-Bromo-phenoxy) -ethylamine

2- (4-Iodo-phenoxy) -ethylamine

2- (3,4-Dichloro-phenoxy) -ethylamine

2- (3-Chloro-phenylsulfanyl) -ethylamine

2- (3,4-Dichloro-phenylsulfanyl) -ethylamine

3- (4-Bromo-phenyl) -propylamine

2- (2-Fluoro-phenoxy) -ethylamine

2- (2-Chloro-phenoxy) -ethylamine

2- (3-Bromo-phenoxy) -ethylamine

2- (3-Fluoro-phenoxy) -ethylamine

2- (3-Iodo-phenoxy) -ethylamine

2- (3,5-Dichloro-phenylsulfanyl) -ethylamine

2-phenylsulfanyl-ethylamine

L- (2-Chloro-phenyl) -ethylamine

Example 69 (Method 45)

N- (1-naphthalen-2-yl-ethyl) -formamide

A mixture of 2-acetylnaphthylene (3.0 g), ammonium formate (11.0 g), formic acid (3.3 mL) and formamide (3.5 mL) was heated at 190 占 폚 for 3 hours. The mixture is cooled, poured into water and then extracted with ether. The ether extract was dried over anhydrous potassium carbonate, filtered and concentrated to give a yellow oil, which upon crystallization with toluene-hexane gave 1.97 g of a white solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

N- [1- (4-Fluoro-phenyl) -2-methyl-propyl] -formamide

N- (1-naphthalen-2-yl-ethyl) -formamide

Example 70 (Method 46)

1- (2-naphthyl) ethylamine

A mixture of N- (1-naphthalen-2-yl-ethyl) -formamide (1.12 g), ethanol (10 mL) and 5N sodium hydroxide (10 mL) is heated at reflux for 1 hour. The solution is cooled, poured into water and extracted with ether. The ether solution is dried over anhydrous potassium carbonate, filtered and concentrated to give the product (0.95 g) as a pale yellow oil.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

1- (3-Trifluoromethyl-phenyl) -ethylamine

L- (4-Fluoro-phenyl) -2-methyl-propylamine

[3- (1-Amino-ethyl) -phenyl] -dimethyl-amine

3- (1-Amino-ethyl) -benzonitrile

Example 71 (Method 47)

1- (3-Trifluoromethyl-phenyl) -ethanone O-Methyl-oxime

Methoxylamine hydrochloride (2.33 g) is added to a solution of 3 '- (trifluoromethyl) -acetophenone (1.5 g) in ethanol (20 mL) and pyridine (2 mL). The solution is heated at reflux for 45 minutes. The reaction mixture is cooled, concentrated under reduced pressure, and partitioned between water and ethyl acetate. The aqueous layer is extracted with ethyl acetate. The combined organic layers are washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the desired product (1.61 g) as a colorless solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

3,5-Bis-trifluoromethyl-benzaldehyde oxime

L- (4-Fluoro-phenyl) -propan-l-one O-Methyl-oxime

1- (2-Chloro-phenyl) -ethanone O-Methyl-oxime

1- (3-Bromo-phenyl) -ethanone O-methyl-oxime

1- (3-Chloro-phenyl) -ethanone O-methyl-oxime

1-o-tolyl-ethanone O-methyl-oxime

1- (4-Fluoro-phenyl) -pentan-l-one O-Methyl-oxime

1- (4-Fluoro-phenyl) -2-phenyl-ethanone O-Methyl-oxime

1-o-tolyl-ethanone O-methyl-oxime

1-m-Tolyl-ethanone O-methyl-oxime

1- (2-Fluoro-phenyl) -ethanone O-Methyl-oxime

3- (1-Methoxyimino-ethyl) -benzonitrile

4- (1-Methoxyimino-ethyl) -benzonitrile

1- (4-Methoxy-phenyl) -ethanone O-Methyl-oxime

1- (2-Methoxy-phenyl) -ethanone O-Methyl-oxime

1- (4-Dimethylamino-phenyl) -ethanone O-Methyl-oxime

1- (2-Trifluoromethyl-phenyl) -ethanone O-Methyl-oxime

1- (3-Methoxy-phenyl) -ethanone O-Methyl-oxime

1- (3-Trifluoromethyl-phenyl) -ethanone O-Methyl-oxime

1- (4-Trifluoromethyl-phenyl) -ethanone O-Methyl-oxime

1-furan-2-yl-ethanone O-methyl-oxime

1-pyridin-4-yl-ethanone O-methyl-oxime

1- (l-Methyl-lH-pyrrol-2-yl) -ethanone O-

1-Thiophen-3-yl-ethanone O-methyl-oxime

(4-Fluoro-phenyl) -phenyl-methanone O-Methyl-oxime

1- (4-Methoxyphenyl) ethanone O-Methyl-oxime

1- (3-Chloro-4-methoxy-phenyl) -ethanone O-Methyl-oxime

4- (1-Methoxyimino-ethyl) -benzenesulfonamide

4- (1-Methoxyimino-ethyl) -N, N-dimethyl-benzenesulfonamide

1- [4- (Piperidine-l-sulfonyl) -phenyl] -ethanone O-Methyl-oxime

4- (1-methoxyimino-ethyl) -N, N-dipropyl-benzenesulfonamide

2-Fluoro-N- [4- (1-methoxyimino-ethyl) -phenyl] -benzamide

1- (3,5-Bis-trifluoromethyl-phenyl) -ethanone O-Methyl-oxime

1- [4- (1H-imidazol-1-yl) phenyl] -1-ethanone, O-

1- [4- (trifluoromethyl) phenyl] -1-ethanone, O-methyl oxime

1- [1,1'-biphenyl] -4-yl-1-ethanone, O-methyloxime

1- (4-methylphenyl) -1-ethanone, O-methyl oxime

1- [4-fluoro-3- (trifluoromethyl) phenyl] ethanone O-methyl oxime

1- [3,5-bis (trifluoromethyl) phenyl] ethanone O-Benzyl oxime

1- [4-chloro-3- (trifluoromethyl) phenyl] ethanone O-methyl oxime

1- [3-fluoro-5- (trifluoromethyl) phenyl] ethanone O-methyl oxime

1- [2-fluoro-4- (trifluoromethyl) phenyl] ethanone O-methyl oxime

1- [2-fluoro-5- (trifluoromethyl) phenyl] ethanone O-methyl oxime

1- (2, 4-dichlorophenyl) ethanone O-methyloxime

1- (2,4-dimethylphenyl) ethanone O-methyloxime

1- [2,4-bis (trifluoromethyl) phenyl] ethanone O-methyl oxime

1- (3-bromophenyl) ethanone O-methyl oxime

1- (3-methylphenyl) ethanone O-methyl oxime

1- [4- (4-morpholinyl) phenyl] ethanone O-Methyl oxime

1- (2-Chloro-4-fluorophenyl) ethanone O-Methyl oxime

1- (4-Bromo-2-fluorophenyl) ethanone O-Methyl oxime

1- (3,4-difluorophenyl) ethanone O-methyl oxime

1- [3- (trifluoromethyl) phenyl] ethanone O-methyl oxime

1- [2- (trifluoromethyl) phenyl] ethanone O-methyl oxime

1- (2,4-difluorophenyl) ethanone O-Methyl oxime

1- [3-fluoro-4- (trifluoromethyl) phenyl] ethanone O-Methyl oxime

1- (3,4-Dichlorophenyl) ethanone O-Methyl oxime

1- [4-fluoro-2- (trifluoromethyl) phenyl] ethanone O-methyl oxime

1- (3-Chloro-4-fluorophenyl) ethanone O-Methyl oxime

1- (4-Chloro-3-fluorophenyl) ethanone O-Methyl oxime

1- (2,5-difluorophenyl) ethanone O-Methyl oxime

1- (2-bromo-4-fluorophenyl) ethanone O-Methyl oxime

1- (3,4-dibromophenyl) ethanone O-methyloxime

1- (2-bromophenyl) ethanone O-Methyl oxime

Example 72 (Method 48)

L- (2-Trifluoromethyl-phenyl) -ethylamine

Sodium borohydride (1.17 g) is slowly added to a flask containing zirconium tetrachloride (1.8 g) in tetrahydrofuran (27 mL). A solution of 1- (2-trifluoromethylphenyl) -ethanone O-methyl-oxime (1.34 g) in tetrahydrofuran (7,7 mL) is added and the resulting solution is stirred at 25 ° C for 12 hours. The reaction mixture is cooled to 0 < 0 > C and water (16 mL) is slowly added. Excess ammonium hydroxide is added and the solution is extracted twice with ethyl acetate. The organic portion is washed twice with 1N hydrochloric acid. The aqueous (acid) layer is basified with sodium hydroxide and extracted twice with ethyl acetate. The organic layer is washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Removal of the solvent under reduced pressure gave the desired product (0.20 g) of a yellow oil.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

1- (3-Methoxy-phenyl) -ethylamine

1- (4-Fluoro-phenyl) -propylamine

1-naphthalen-2-yl-ethylamine

4- (1-Amino-ethyl) -benzonitrile

L- (4-Trifluoromethyl-phenyl) -ethylamine

1- (4-Methoxy-phenyl) -ethylamine

1-prop-2-ynyl-pyrrolidine

L- (2-Methoxy-phenyl) -ethylamine

1-m-Tolyl-ethylamine

L- (2-Bromo-phenyl) -ethylamine

1-o-tolyl-ethylamine

C- (4-Fluoro-phenyl) -C-phenyl-methylamine

1- (4-Fluoro-phenyl) -pentylamine

L- (4-Fluoro-phenyl) -2-phenyl-ethylamine

L- (2-Trifluoromethyl-phenyl) -ethylamine

L- (3-Bromo-phenyl) -ethylamine

L- (3-Chloro-phenyl) -ethylamine

[4- (1-Amino-ethyl) -phenyl] -dimethyl-amine

L- (l-Methyl-lH-pyrrol-2-yl) -ethylamine

1-Thiophen-3-yl-ethylamine

1- [3,5-bis (trifluoromethyl) phenyl] propylamine

1- [3,5-bis (trifluoromethyl) phenyl] -1-butane amine or 1- [3,5-bis (trifluoromethyl) phenyl]

1- [3,5-bis (trifluoromethyl) phenyl] -1-pentanamine

1- (4-methylphenyl) ethanamine

1- [3- (trifluoromethyl) phenyl] ethylamine

1- [4-Trifluoromethyl) phenyl] ethylamine

1- (3-methylphenyl) ethanamine

1- (3,4-dichlorophenyl) ethanamine

L- (2-Bromo-phenyl) -ethylamine

L- (2-Trifluoromethyl-phenyl) -ethylamine

L- (3-Bromo-phenyl) -ethylamine

L- (3-Chloro-4-methoxy-phenyl) -ethylamine

4- (1-amino-ethyl) -N, N-dimethyl-benzenesulfonamide

1- [4- (Piperidine-1-sulfonyl) -phenyl] -ethylamine

1-quinolin-6-yl-ethylamine

L- (3,5-Bis-trifluoromethyl-phenyl) -ethylamine

4 - [(1S) -1-aminoethyl] benzonitrile

(S) -alpha-methyl-3,5-bis (trifluoromethyl) -benzene methanamine (S)

1-Biphenyl-4-yl-ethylamine

L- (4-Fluoro-phenyl) -ethylamine

1- [4-fluoro-3- (trifluoromethyl) phenyl] ethanamine

1- [4-chloro-3- (trifluoromethyl) phenyl] ethanamine

N- {4 - [(1 R) -1-aminoethyl] phenyl} -1,2,3-thiadiazole-4-carboxamide

N- {4 - [(1S) -1-aminoethyl] phenyl} -1,2,3-thiadiazole-4-carboxamide

1- [3-fluoro-5- (trifluoromethyl) phenyl] ethylamine

1- [2-fluoro-4- (trifluoromethyl) phenyl] ethylamine

1- [2-fluoro-5- (trifluoromethyl) phenyl] ethylamine

1- (2,4-dichlorophenyl) ethylamine

1- (2,4-dimethylphenyl) ethylamine

1- [2,4-bis (trifluoromethyl) phenyl] ethylamine

1- (2-Chloro-4-fluorophenyl) ethylamine

1- (3,4-difluorophenyl) ethylamine

1- (4-Bromo-2-fluorophenyl) ethylamine

1- (3-fluorophenyl) ethylamine

1- (2,4-difluorophenyl) ethylamine

1- [3-fluoro-4- (trifluoromethyl) phenyl] ethylamine

1- [4-fluoro-2- (trifluoromethyl) phenyl] ethylamine

1- (3-Chloro-4-fluorophenyl) ethylamine

1- (4-Chloro-3-fluorophenyl) ethylamine

1- (3,4-dibromophenyl) ethylamine

1- (2-Bromo-4-fluorophenyl) ethanamine To a solution of l- (2-bromo-4-fluorophenyl) ethylamine

Example 73 (Method 49)

(2-fluoro-5-trifluoromethyl-phenoxy) -acetonitrile

A solution of 2-fluoro-5-trifluoromethylphenol (25 g) in tentacetate acetone (0.55 L) is treated with solid potassium carbonate (7.7 g) followed by rapid addition of pure bromoacetonitrile (10 mL). The heterogeneous mixture is vigorously stirred for approximately 20 hours under water and extracted with diethyl ether. The combined ether extracts are washed with saturated sodium chloride and dried over anhydrous potassium carbonate. Filtration and concentration under reduced pressure gave a pale orange solid which was chromatographed on silica gel eluting with dichloromethane to give the desired product (28.3 g) as a white solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

(3-bromo-phenylsulfanyl) -acetonitrile

(3-chloro-phenylsulfanyl) -acetonitrile

(4-Iodo-phenoxy) -acetonitrile < / RTI >

(3-Trifluoromethyl-phenylsulfanyl) -acetonitrile < / RTI >

(3,5-Dichloro-phenylsulfanyl) -acetonitrile

(3,4-Dichloro-phenylsulfanyl) -acetonitrile

(3,4-Dichloro-phenoxy) -acetonitrile

(2-Fluoro-phenoxy) -acetonitrile < / RTI >

(3-Fluoro-phenoxy) -acetonitrile < / RTI >

(2-Chloro-phenoxy) -acetonitrile

(3-Bromo-phenoxy) -acetonitrile < / RTI >

(2-fluoro-5-trifluoromethyl-phenoxy) -acetonitrile

(3-Iodo-phenoxy) -acetonitrile

(4-Bromo-phenoxy) -acetonitrile < / RTI >

Example 74 (Method 50)

3-fluoro-5-trifluoromethylphenethylamine tosylate

To a solution of 2.5 g of 3-fluoro-5-trifluoromethylphenylacetonitrile and 2.34 g (12.3 mmol) of p-toluenesulfonic acid in 75 ml of ethylene glycol monomethyl ether was added 200 mg of 10% palladium on carbon catalyst at 40 psi at room temperature ≪ / RTI > for 3 hours. The catalyst is filtered and the solvent is evaporated to half its volume. Upon standing, the desired p-toluenesulfonic acid salt of 3-fluoro-5-trifluoromethylphenethylamine is crystallized. Filtration gave 4.26 g (91%) of white crystals.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

2- (3,5-Difluoro-phenyl) -ethylamine

2- (4-Trifluoromethyl-phenyl) -ethylamine

2- (3,4-Difluoro-phenyl) -ethylamine

2- (2-Fluoro-phenyl) -ethylamine

2- (3-Fluoro-5-trifluoromethyl-phenyl) -ethylamine

2- (2-Fluoro-3-trifluoromethyl-phenyl) -ethylamine

2- (2,4-Bis-trifluoromethyl-phenyl) -ethylamine

2- (4-Fluoro-3-trifluoromethyl-phenyl) -ethylamine

Example 75 (Method 51)

(4-Aminomethyl-2-trifluoromethyl-phenyl) -dimethyl-amine

A solution of 4-dimethylamino-3-trifluoromethylbenzonitrile (0.35 g) in tetrahydrofuran (2 mL) was slowly added to a suspension of lithium aluminum hydride (0.1 g) in tetrahydrofuran (2 mL) at 0 ° C And stirred under an argon atmosphere for 2 hours. Water (0.1 mL) is slowly added at 0 ° C followed by 5% sodium hydroxide (0.1 mL) and water (0.3 mL). The resulting gray solid is filtered off and washed with tetrahydrofuran. The filtrate was collected and concentrated under reduced pressure, and the resulting oil was chromatographed on silica gel (using 15% methanol in methylene chloride as eluent) to give the desired product (0.164 g) as a pale orange oil.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

4-Piperidin-1-yl-3-trifluoromethyl-benzylamine

(4-Aminomethyl-2-trifluoromethyl-phenyl) -dimethyl-amine

4- (4-Methyl-piperazin-1-yl) -3-trifluoromethyl-benzylamine

(3-Aminomethyl-5-trifluoromethyl-phenyl) -dimethyl-amine

[3- (2-Amino-ethyl) -5-trifluoromethyl-phenyl] -dimethyl-amine

[4- (2-Amino-ethyl) -2-methyl-phenyl] -dimethyl-amine

Example 76 (Method 52)

3-Dimethylamino-5-trifluoromethyl-benzaldehyde

Diisobutyl aluminum hydride (10 mL of a 1 M solution of methylene chloride) was added dropwise to a solution of 3-dimethylamino-5-trifluoromethylbenzonitrile (1.06 g) in methylene chloride (25 mL) at 0 ° C and the mixture was stirred for 2 hours Lt; / RTI > A saturated aqueous solution of sodium potassium tartrate (8 mL) is slowly added at 0 ° C and the solution is stirred for 1.5 hours. The reaction mixture is extracted with ethyl acetate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the desired product (0.97 g) as a yellow solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

3-Dimethylamino-5-trifluoromethyl-benzaldehyde

4-Dimethylamino-3-methyl-benzaldehyde

Example 77 (Method 53)

Dimethyl- [3- (2-nitro-vinyl) -5-trifluoromethyl-phenyl] -amine

Nitromethane (0.473 g) is added to a solution of 3-dimethylamino-5-trifluoromethylbenzaldehyde (0.885 g) and ammonium acetate (0.339 g) in acetic acid (3.4 mL) and the solution is heated at 110 C for 6 h . The reaction mixture is cooled to 0 < 0 > C, filtered and washed with 1: 1 water-acetic acid to form a solid. Recrystallization of this solid with ethanol gave the desired product (0.39 g) as a red solid.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

Dimethyl- [3- (2-nitro-vinyl) -5-trifluoromethyl-phenyl] -amine

Dimethyl- [2-methyl-4- (2-nitro-vinyl) -phenyl] -amine

Example 78 (Method 54)

3- (4-Bromo-phenyl) -propionitrile

Diethyl azodicarboxylate (5.2 g) is added dropwise to a solution of 4-bromo-phenethyl alcohol (2.01 g) and triphenylphosphine (7.9 g) in diethyl ether (16 mL) at 0 ° C. The reaction mixture is stirred for 10 minutes and a solution of acetone cyanohydrin (2.6 g) in diethyl ether (10 mL) is added. The clear orange solution is stirred at 0 < 0 > C for 5 min followed by 25 < 0 > C for 12 h. The reaction mixture is filtered and washed with diethyl ether. The filtrate is concentrated under reduced pressure and chromatographed on silica gel (10% ethyl acetate-hexane as eluent) to give the desired product (2.04 g) as a pale yellow oil.

Example 79 (Method 55)

3-Dimethylamino-2-isocyano-acrylic acid ethyl ester

N, N-dimethyl-formamide dimethyl acetal (6.5 g) was added dropwise over 10 minutes to a solution of ethyl isocyanoacetate (5.0 g) in ethanol (100 mL) while stirring. The reaction is stirred for 24 h and the ethanol is evaporated. The oil produced using 50% ethyl acetate-hexane as an eluent is passed through magnesium silicate. The solvent was removed and the resulting oil was crystallized from ethyl acetate-hexane to give 3.0 g of a light yellow needle.

Example 80 (Method 56)

4-Carboethoxytriazole

A solution of 3-dimethylamino-2-isocyano-acrylic acid ethyl ester (1.0 g) and triethylamine (3.0 g) in tetrahydrofuran (30 mL) is treated with gaseous hydrogen sulfide until all starting material is consumed . The mixture is concentrated to an oil and purified by column chromatography using silica and 25% ethyl acetate-hexane as eluent. The purified material (0.61 g) is isolated in oil form.

Example 81 (Method 34)

- {[(5-chloro-2,4-dimethoxy-phenyl) -ureido] -phenyl} -2-fluoro-benzamide

A suspension of N- (4-amino-phenyl) -2-fluoro-benzamide (0.43 g) in acetonitrile (4 mL) is treated with 5-chloro-2,4-dimethoxyphenyl isocyanate (0.40 g) . The mixture becomes a solution and it is allowed to stand for 12 hours. A white solid forms and is collected by filtration (0.79 g). [M + H] < / RTI > 444.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

Example M + H Compound Name

81 445 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) ureido] phenyl} -2-

Oro-benzamide

82 441 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) ureido] phenyl} -2-

Benzamide

83 435 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (5-chloro-2,4-

Phenyl) ureido] phenyl} -amide

84 443 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-chloro-3-

Phenyl) ureido] phenyl} -amide < / RTI >

85 453 N- {4- [3- (4-Chloro-3-trifluoromethyl-phenyl) ureido] phenyl} -2-

Fluoro-benzamide

86 409 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl) urea

Iso] phenyl} -amide

87 486 N- {4- [3- (3,5-Bis-trifluoromethyl-phenyl) ureido] phenyl} -2-

≪ RTI ID = 0.0 >

88 458 furan-2-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-phenyl) urea

Iso] phenyl} -amide

89 476 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,5-bis-trifluoro-

Yl-phenyl) ureido] phenyl} -amide

90 423 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,4-dichloro-benzyl) urea

Isopropyl] -amide < / RTI >

Example 91 (Method 31)

[1,2,3] -thiadiazole-4-carboxylic acid {4- [3 (3,5-bis-trifluoromethylphenyl)

Thioureido] -phenyl} amide

To a solution of [1,2,3] -thiadiazole-4-carboxylic acid (4-amino-phenyl) amide (2.0 g) in acetonitrile (50 mL) 3,5-Bis-trifluoromethyl-benzene (2.5 g) is rapidly added dropwise and the reaction is stirred at room temperature. After 90 minutes, the solvent is removed under reduced pressure and the resulting brown solid is recrystallized from ethyl acetate / hexane to yield the pure product. [M + H] < / RTI > 492.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

Example M + H Compound Name

92 506 [3-Chloro-5- (3- {4 - ([1,2,3] thiadiazole-

Thioureido) phenyl] carbamic acid tert-butyl ester

93 409 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (4-morpholin-

Thiourea

94 370 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (4-methylsulfanyl-

Thiourea

95 338 1- (5-Chloro-2,4-dimethoxy-phenyl) -3-p-tolyl-thiourea

96 414 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) thioureido] phenylsulfanyl}

Acetic acid

97 384 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- [4- (2-hydroxy-

Phenyl] -thiourea

98 340 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (4-hydroxy-phenyl) -thiourea

99 395 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -N-

Methyl acetamide

100 381 N- {3- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Acetamide

101 411 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) thioureido] phenyl} carbamic acid

Ethyl ester

102 319 1- (2,4-Dimethoxy-phenyl) -3- (4-methoxy-phenyl) -thiourea

103 346 N- {4- [3- (2,4-Dimethoxy-phenyl) -thioureido] -phenyl} -acetamide

104 316 N- {4- [3- (4-Methoxy-phenyl) -thioureido] -phenyl} -acetamide

105 316 N- {4- [3- (2-Methoxy-phenyl) -thioureido] -phenyl} -acetamide

106 351 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl}

mid

107 351 N- {4- [3- (5-Chloro-2-methoxy-phenyl) -thioureido] -phenyl}

mid

108 371 N- {4- [3- (3,5-Dichloro-4-hydroxy-phenyl) -thioureido] -phenyl} -

Acetamide

109 385 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -

Acetamide

110 381 N- {4- [3- (4-Chloro-2,5-dimethoxy-phenyl) -thioureido] -phenyl} -

Acetamide

111 389 N- {4- [3- (2-Chloro-5-trifluoromethyl-phenyl) -thioureido] -

Phenyl} -acetamide

112 389 N- {4- [3- (4-Chloro-3-trifluoromethyl-phenyl) -thioureido]

Phenyl} -acetamide

113 422 benzoic acid 4- [3- (4-acetylamino-phenyl) thioureido] -3-hydroxy-

Phenyl ester

114 457 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Methylbenzamide

115 501 Acetic acid 2- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) thioureido]

Phenylcarbamoyl} phenyl ester

116 461 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -4-

Fluoro-benzamide

117 461 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-

Fluoro-benzamide

118 461 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

119 473 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Methoxy-benzamide

120 473 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-

Methoxy-benzamide

121 473 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -4-

Methoxy-benzamide

122 443 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Benzamide

123 417 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Methane-sulfonamide

124 331 N- {4- [3- (3-Nitro-phenyl) -thioureido] -phenyl} -acetamide

125 339 1- (3-Chloro-4-methoxy-phenyl) -3- (3-nitro-phenyl) -thiourea

126 337 N- {4- [3- (5-Chloro-2-hydroxy-phenyl) -thioureido] -phenyl} -

Acetamide

127 439 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Carbamic acid tert-butyl ester

128 351 N- {4- [3- (3-Chloro-4-hydroxy-5-methyl-phenyl) -thioureido]

Phenyl} -acetamide

129 385 N- {4- [3- (3,5-Dichloro-4-hydroxy-2-methyl-phenyl) -thioureido]

Phenyl} -acetamide

130 318 N- {4- [3- (2,4-Dihydroxy-phenyl) -thioureido] -phenyl} -acetamide

131 414 N- {4- [3- (2,4-Dimethoxy-5-trifluoromethyl-phenyl) -thioureido]

Phenyl} -acetamide

132 332 N- {4- [3- (2-Hydroxy-4-methoxy-phenyl) -thioureido] -phenyl} -

Acetamide

133 465 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -4-

Fluoro-benzamide

134 500 3-Acetylamino-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thiourea

Iso] -phenyl} -benzamide < / RTI >

135 488 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-

Nitro-benzamide

136 486 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-

Dimethylamino-benzamide

137 536 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-

Methanesulfonyl-amino-benzamide

138 511 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Trifluoromethyl-benzamide < RTI ID = 0.0 >

139 459 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Hydroxy-benzamide

140 479 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

2,6-difluoro-benzamide

141 477 2-Chloro-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -benzamide

142 522 2-Bromo-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -benzamide

143 488 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Nitro-benzamide

144 445 pyrazine-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Iso] -phenyl} -amide

145 463 5-Methyl-thiophene-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -phenyl} -amide < / RTI >

146 494 Quinoline-8-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thiourea

Iso] -phenyl} -amide

147 446 1 -Methyl-1 H-pyrrole-2-carboxylic acid {4- [3- (5- chloro-2,4-

Thioureido] -phenyl} -amide < / RTI >

148 369 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (2-nitro- phenyl) -thiourea

149 369 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (4-nitro- phenyl) -thiourea

150 425 N- {4- [3- (5-Bromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Acetamide

151 376 N- {4- [3- (3,4,5-trimethoxy-phenyl) -thioureido] -phenyl} -

Acetamide

152 399 N- {4- [3- (3,5-Dichloro-2-methoxy-4-methyl-phenyl) -thioureido]

Phenyl} -acetamide

153 499 Benzo [b] thiophene-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -phenyl} -amide < / RTI >

154 483 benzofuran-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Yl] -phenyl} -amide < / RTI >

155 444 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Isonicotinamide

156 493 Naphthalene-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy- phenyl)

Thioureido] -phenyl} -amide < / RTI >

157 493 naphthalene-1-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -amide < / RTI >

158 494 isoquinoline-1-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -amide < / RTI >

159 494 Quinoline-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -amide < / RTI >

160 444 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Nicotinamide

161 478 5-Nitro-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -phenyl} - amide carbamic acid phenyl ester

162 459 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

163 467 5-Chloro-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -phenyl} -amide < / RTI >

164 439 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Carbamic acid isobutyl ester

165 397 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Carbamic acid methyl ester

166 433 Furan-3-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -amide < / RTI >

167 447 3-Methyl-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -phenyl} -amide < / RTI >

168 512 5-Bromo-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -phenyl} -amide < / RTI >

169 512 4-Bromo-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -phenyl} -amide < / RTI >

170 433 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -amide < / RTI >

171 467 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Carbamic acid hexyl ester

172 494 isoquinoline-4-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -amide < / RTI >

173 451 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (5-chloro-2,4-

Phenyl) -thioureido] -phenyl} -amide

174 434 1H- [1,2,3] triazole-4-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Phenyl) -thioureido] -phenyl} -amide

175 528 3-Bromo-thiophene-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -phenyl} -amide < / RTI >

176 399 N- {4- [3- (3,5-Dichloro-4-ethoxy-phenyl) -thioureido] -phenyl} -

Acetamide

177 427 N- {4- [3- (4-Butoxy-3,5-dichloro-phenyl) -thioureido] -phenyl} -

Acetamide

178 461 N- {4- [3- (4-Benzyloxy-3,5-dichloro-phenyl) -thioureido] -phenyl} -

Acetamide

179 381 N- {4- [3- (3-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Acetamide

180 530 (3- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenylcarbamoyl} -phenyl) -carbamic acid ethyl ester

181 458 2-Amino-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -benzamide

182 519 biphenyl-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -amide < / RTI >

183 469 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- [4- (1,3- dioxo-

Isoindol-2-yl) -phenyl] -thiourea

184 487 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Phthalamic acid

185 473 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Hydroxy-methyl-benzamide

186 479 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

2,3-difluoro-benzamide

187 479 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

2,5-difluoro-benzamide

188 479 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

2,4-difluoro-benzamide

189 500 2-Acetylamino-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -benzamide < / RTI >

190 441 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (6-oxo-5,6-

Phenanthridin-2-yl) -thiourea

191 536 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Methanesulfonylamino-benzamide

192 497 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

2,3,4-Trifluoro-benzamide

193 533 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

2,3,4,5,6-pentafluoro-benzamide

194 489 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Methyl-sulfanyl-benzamide

195 431 5-Methyl-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -phenyl} -amide < / RTI >

196 467 5-Difluoromethyl-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Phenyl) -thioureido] -phenyl} -amide

197 472 N- {4- [3- (5-Iodo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Acetamide

198 364 N- {4- [3- (5-Fluoro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Acetamide

199 365 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido] -phenyl}

Acetamide

200 459 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl-

Yl-phenyl) -thioureido] -phenyl} -amide

201 455 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro-

Phenyl) -thioureido] -phenyl} -amide

202 392 N- {4- [3- (3-Chloro-4-diethylamino-phenyl) -thioureido] -phenyl} -

Acetamide

203 432 N- (4- {3- [3-Chloro-4- (cyanohexyl-methyl-amino) -phenyl] -

Thioureido} -phenyl) -acetamide < / RTI >

204 506 1 -Hydroxy-naphthalene-2-carboxylic acid {4- [3- (4-acetylamino-phenyl)

Thioureido] -2-chloro-phenyl} -amide

205 406 N- {4- [3- (3-Chloro-4-morpholin-4-yl-phenyl) -thioureido] -phenyl} -

Acetamide

206 443 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (3-chloro-

Phenyl) -thiourea

207 372 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (5-chloro-

Thiourea

208 501 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Isophthalamic acid methyl ester

209 487 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Isophthalamic acid

210 549 3-Benzyloxy-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -benzamide < / RTI >

211 434 N- (4- {3- [5-Chloro-2-methoxy-4- (4-nitrilo-butoxy) -phenyl]

Thioureido} -phenyl) -acetamide < / RTI >

212 406 N- (4- {3- [5-Chloro-2-methoxy-4- (2-nitrilo-ethoxy) -phenyl] -

Thioureido} phenyl) acetamide

213 406 N- (4- {3- [5-Chloro-4-methoxy-2- (2-nitrilo-ethoxy) -phenyl] -

Thioureido} phenyl) acetamide

214 411 N- (4- {3- [5-Chloro-2- (2-hydroxy-ethoxy) -4- methoxy-

Thioureido} phenyl) acetamide

215 411 N- (4- {3- [5-Chloro-4- (2-hydroxy-ethoxy) -2- methoxy-

Thioureido} phenyl) -acetamide

216 481 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-5-methoxy-

Phenoxy} -acetic acid tert-butyl ester

217 439 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-5-methoxy-

Phenoxy} acetic acid methyl ester

218 481 {2- [3- (4-Acetylamino-phenyl) -thioureido] -4-chloro-5-methoxy-

Phenoxy} acetic acid tert-butyl ester

219 515 3-Butoxy-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -benzamide

220 505 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Methane-sulfinyl-benzamide

221 545 (3- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenylcarbamoyl} -phenoxy) acetic acid ethyl ester

222 517 (3- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenylcarbamoyl} -phenoxy) -acetic < / RTI > acid

223 367 N- {4- [3- (5-Chloro-4-hydroxy-2-methoxy-phenyl) -thioureido]

Phenyl} -acetamide

224 444 Pyridine-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -amide < / RTI >

225 494 Quinoline-4-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -amide < / RTI >

226 436 N- {4- [3- (5-Chloro-4-methoxy-2-morpholin-

Thioureido] -phenyl} -acetamide < / RTI >

227 394 N- {4- [3- (5-Chloro-2-dimethylamino-4-methoxy-phenyl)

Thioureido] -phenyl} -acetamide < / RTI >

228 420 N- {4- [3- (5-Chloro-4-methoxy-2-pyrrolidin-

Thioureido] -phenyl} -acetamide < / RTI >

229 434 N- {4- [3- (5-Chloro-4-methoxy-2-piperidin-

Thioureido] -phenyl} -acetamide < / RTI >

230 405 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-methyl-

Thioureido] -phenyl} -amide < / RTI >

231 415 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

232 427 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -phenyl} -3-methoxy-

Benzamide

233 387 furan-2-carboxylic acid {4- [3- (3-chloro-4-methyl- phenyl) -thioureido]

Phenyl} -amide

234 411 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -phenyl}

Benzamide

235 433 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -phenyl}

Difluoro-benzamide

236 398 Pyridine-2-carboxylic acid {4- [3- (3-chloro-4-methyl- phenyl) -thioureido]

Phenyl} -amide

237 502 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3-chloro-4- (cyclohexyl-

Methyl-amino) -phenyl] -thioureido} -phenyl) -amide

238 512 N- (4- {3- [3-Chloro-4- (cyclohexyl-methyl-amino) -phenyl] -

Thioureido} -phenyl) -2-fluoro-benzamide

239 404 N- {4- [3- (3-Chloro-4-piperidin-l-yl-phenyl) -thioureido] -phenyl} -

Acetamide

240 364 N- {4- [3- (3-Chloro-4-dimethylamino-phenyl) -thioureido] -phenyl} -

Acetamide

241 426 N- {4- [3- (4-Benzylamino-3-chloro-phenyl) -thioureido] -phenyl} -

Acetamide

242 390 N- {4- [3- (3-Chloro-4-pyrrolidin- 1 -yl-phenyl) -thioureido] -phenyl} -

Acetamide

243 419 N- (4- {3- [3-Chloro-4- (4-methyl-piperazin- 1- yl) -phenyl] -

Thioureido} -phenyl) -acetamide < / RTI >

244 469 N- {4- [3- (4-Chloro-3-trifluoromethyl-phenyl) -thioureido]

Phenyl} -2-fluoro-benzamide

245 422 N- {4- [3- (2-Benzylamino-4-methoxy-phenyl) -thioureido] -phenyl} -

Acetamide

246 484 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (cyclohexyl- methyl-

Phenyl] thioureido} phenyl) -amide

247 508 N- (4- {3- [3-Chloro-4- (cyclohexyl-methyl-amino) -phenyl] -

Thioureido} -phenyl) -2-methyl-benzamide

248 530 N- (4- {3- [3-Chloro-4- (cyclohexyl-methyl-amino) -phenyl] -

Thioureido} -phenyl) -2,6-difluoro-benzamide

249 495 Pyridine-2-carboxylic acid (4- {3- [3-chloro-4- (cyclohexyl-

Amino) -phenyl] -thioureido} -phenyl) -amide

250 524 N- (4- {3- [3-Chloro-4- (cyclohexyl-methyl-amino) -phenyl] -

Thioureido} -phenyl) -3-methoxy-benzamide

251 376 N- (4- {3- [3-Chloro-4- (2-nitrilo-ethoxy) -phenyl] -thioureido}

Phenyl) -acetamide

252 393 N- {4- [3- (4-sec-Butoxy-3-chloro-phenyl) -thioureido] -phenyl} -

Acetamide

253 501 Acetic acid 3- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl-carbamoyl} -phenyl ester

254 459 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-

Hydroxy-benzamide

255 487 Benzo [1, 3] dioxole-4-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -phenyl} -amide < / RTI >

256 527 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-

Trifluoromethoxy-benzamide < RTI ID = 0.0 >

257 530 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-

(2-dimethylamino-ethoxy) -benzamide

258 572 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-

(2-morpholin-4-yl-ethoxy) -benzamide

259 406 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-cyano-

Phenyl} -acetamide

260 521 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2,5-

Dimethoxy-phenyl} -2-fluoro-benzamide < / RTI >

261 441 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2,5-

Dimethoxy-phenyl} -acetamide < / RTI >

262 527 2- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenoxy} -

5-Chlorobenzenesulfonic acid

263 562 2- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenoxy} -

4,5-Dichlorobenzenesulfonic acid

264 527 4-Phenyl [l, 2,3] thiadiazole-5-carboxylic acid {4- [3- (5-

Dimethoxyphenyl) -thioureido] -phenyl} -amide < / RTI >

265 381 N- (4- {3- [3-Chloro-4- (2-hydroxy-ethoxy) -phenyl] -thioureido}

Phenyl) acetamide

266 393 N- {4- [3- (4-Butoxy-3-chloro-phenyl) -thioureido] -phenyl} -

Acetamide

267 446 N- (4- {3- [3-Chloro-4- (cyclohexyl-ethyl-amino) -phenyl] -

Thioureido} -phenyl) acetamide < / RTI >

268 365 N- {4- [3- (3-Chloro-4-ethoxy-phenyl) -thioureido] -phenyl} -

Acetamide

269 427 N- {4- [3- (4-Benzyloxy-3-chloro-phenyl) -thioureido] -phenyl} -

Acetamide

270 317 {4- [(3-Methyl-furan-2-carbonyl) amino] phenyl} -carbamic acid tert- butyl

ester

271 456 N- {4- [3- (2-Benzylamino-5-chloro-4-methoxy-phenyl) -thioureido]

Phenyl} -acetamide

272 420 N- {4- [3- (3-Chloro-4-dipropylamino-phenyl) -thioureido] -phenyl} -

Acetamide

273 458 N- (4- {3- [4- (Allyl-cyclohexyl-amino) -3-chloro-phenyl] -

Thioureido} -phenyl) acetamide < / RTI >

274 411 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy-

Phenyl} -acetamide

275 415 N- {2-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} acetamide

276 493 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -2,5-dimethoxy-phenyl} -amide

277 486 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-cyano-

Phenyl} -2-fluoro-benzamide

278 495 N- {2-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -2-fluoro-benzamide

279 465 5-Methyl- [l, 2,3] thiadiazole-4-carboxylic acid {4- [3- (5-

Dimethoxy-phenyl) -thioureido] -phenyl} -amide

280 517 5-Furan-3-yl- [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (5-

Dimethoxy-phenyl) thioureido] -phenyl} amide

281 527 5-Phenyl- [l, 2,3] thiadiazole-4-carboxylic acid {4- [3- (5-

Dimethoxy-phenyl) thioureido] -phenyl} amide

282 458 N- (4- {3- [3-Chloro-4- (octahydro-quinolin- 1 -yl) -phenyl] -

Thioureido} phenyl) acetamide

283 458 N- [5 - [[[(5-chloro-2,4-dimethoxyphenyl) amino] thioxomethyl]

2-pyridinyl] -2-methylbenzamide

284 434 furan-2-carboxylic acid {5- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -pyridin-2-yl} -amide

285 425 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy-

5-methylphenyl} -acetamide

286 505 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy-

5-methylphenyl} -2-fluoro-benzamide

287 477 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -2-methoxy-5-methyl-phenyl} -amide

288 517 4-Furan-3-yl- [1,2,3] thiadiazole-5-carboxylic acid {4- [3- (5-

Dimethoxy-phenyl) -thioureido] -phenyl} -amide

289 462 N- {5- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -pyridin-

Yl} -2-fluoro-benzamide

290 384 N- {4- [3- (4-Methoxy-3-trifluoromethyl-phenyl) -thioureido]

Phenyl} -acetamide

291 394 N- {4- [3- (3-Chloro-4 - [(2-hydroxy- ethyl) -methyl-

Thioureido) -phenyl] -acetamide < / RTI >

292 485 N- {2-Benzoyl-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -acetamide

293 565 N- {2-Benzoyl-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -2-fluoro-benzamide

294 537 furan-2-carboxylic acid {2-benzoyl-4- [3- (5-chloro-2,4-dimethoxy- phenyl)

Thioureido] -phenyl} -amide < / RTI >

295 475 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -2-fluoro-benzamide

296 447 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -3-methyl-phenyl} -amide

297 395 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -acetamide

298 435 N- [4- (3- {3-Chloro-4 - [(3-dimethylamino-propyl)

Phenyl} -thioureido) -phenyl] -acetamide < / RTI >

299 418 N- {4- [3- (3-Chloro-4-cyclohexylamino-phenyl) -thioureido]

Phenyl} -acetamide

300 421 N- [4- (3- {3-Chloro-4 - [(2- dimethylamino-ethyl) -methyl-

Thioureido) -phenyl] -acetamide < / RTI >

301 580 5 - [[[(5-chloro-2,4-dimethoxyphenyl) amino] thioxomethyl]

[(2-fluorobenzoyl) amino] -N-phenyl-benzamide

302 552 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -2-phenylcarbamoyl-phenyl} -amide

303 491 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy-

Phenyl} -2-fluoro-benzamide

304 463 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -2-methoxy-phenyl} -amide

305 449 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-

Trifluoromethyl-phenyl} -acetamide < / RTI >

306 458 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -2-cyano-phenyl} -amide

307 467 furan-2-carboxylic acid {2-chloro-4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -phenyl} -amide < / RTI >

308 501 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -2-trifluoromethyl-phenyl} -amide

309 395 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -acetamide

310 475 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -2-fluoro-benzamide

311 447 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -2-methyl-phenyl} -amide

312 378 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -

Acetamide

313 408 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -

Carbamic acid ethyl ester

314 382 N- {5- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -pyridin-

Yl} -acetamide

315 509 N- (4- {3- [4- (l-Benzyl-piperidin-4-ylamino) -3-chloro-

Thioureido} -phenyl) -acetamide < / RTI >

316 407 N- (4- {3- [3-Chloro-4- (2-dimethylamino-ethylamino) -phenyl] -

Thioureido} -phenyl) -acetamide < / RTI >

317 408 N- [4- (3- {3-Chloro-4 - [(2- methoxy-ethyl) -methyl-

Thioureido) phenyl] -acetamide

318 421 N- (4- {3- [3-Chloro-4- (3-dimethylamino-propylamino) -phenyl] -

Thioureido} -phenyl) -acetamide < / RTI >

319 495 N- (4- {3- [4- (l-Benzyl-pyrrolidin-3- ylamino) -3-chloro-

Thioureido} -phenyl) -acetamide < / RTI >

320 483 Furan-2-carboxylic acid {5-chloro-4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -2-hydroxy-phenyl} -amide

321 431 N- {5-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

2-hydroxy-phenyl} -acetamide

322 511 (5H, 11H-benzo [e] pyrrolo [1,2-a] [1,4] diazepin-

Yl-phenyl) -methanone < / RTI >

323 451 [1,2,3] Thiadiazole-5-carboxylic acid {4- [3- (5-chloro-2,4-

Phenyl) thioureido] -phenyl} -amide

324 483 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] naphthalen-l-yl} -amide

325 511 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -naphthalene-

Yl} -2-fluoro-benzamide < / RTI >

326 429 N- {5-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

2-methyl-phenyl} -acetamide

327 509 N- {5-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

2-methylphenyl} -2-fluoro-benzamide

328 481 furan-2-carboxylic acid {5-chloro-4- [3- (5-chloro-2,4-dimethoxy-

Thioureido] -2-methyl-phenyl} -amide

329 431 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -naphthalene-

1-yl} -acetamide < / RTI >

330 416 furan-2-carboxylic acid {4- [3- (3-chloro-4-dimethylamino-

Thioureido] -phenyl} -amide < / RTI >

331 561 furan-2-carboxylic acid [4- (3- {4 - [(1-benzyl- pyrrolidin-

3-chloro-phenyl} -thioureido) -phenyl] -amide

332 513 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl-pyrrolidin-

Phenyl} thioureido) -phenyl] -2-fluoro-benzamide

333 463 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido] -phenyl}

2,6-difluoro-benzamide

334 420 N- (4- {3- [3-Chloro-4- (l-methyl-pyrrolidin-3- yloxy) -phenyl] -

Thioureido} phenyl) -acetamide

335 434 N- (4- {3- [3-Chloro-4- (1 -methyl-piperidin-4- yloxy) -phenyl] -

Thioureido} phenyl) -acetamide

336 422 N- (4- {3- [3-Chloro-4- (3-dimethylamino-propoxy) -phenyl] -

Thioureido} phenyl) -acetamide

337 425 2-Acetylamino-5- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] benzoic acid

338 505 5- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2- (2-

Benzoylamino) -benzoic acid

339 477 5- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2 - [(furan-

Carbonyl) amino) -benzoic acid

340 545 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl- piperidin-

Phenyl} thioureido) -phenyl] -2,6-difluoro-benzamide

341 503 [1,2,3] thiadiazole-4-carboxylic acid [4- (3- {3-chloro-4- [methyl-

Pyrrolidin-3-yl) -amino] -phenyl} -thioureido) -phenyl] -amide

342 443 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido] -phenyl} -2-

Methyl-benzamide

343 408 N- (4- {3- [3-Chloro-4- (2-dimethylamino-ethoxy) -phenyl] -

Thioureido} -phenyl) -acetamide < / RTI >

344 499 Furan-2-carboxylic acid [4- (3- {3-chloro-4- [methyl- (1 -methyl-piperidin-

Amino] -phenyl} -thioureido) -phenyl] -amide

345 419 N- {4- [3- (3-Chloro-4-cyclohexyloxy-phenyl) -thioureido] -

Phenyl} -acetamide

346 440 N- {4- [3- (3-Chloro-4-dimethylamino-phenyl) -thioureido] -phenyl} -2-

Methyl-benzamide

347 493 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -2,6-difluoro-benzamide

348 462 N- {4- [3- (3-Chloro-4-dimethylamino-phenyl) -thioureido] -phenyl} -

2,6-difluoro-benzamide

349 531 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl-pyrrolidin-

Phenyl} -thioureido) -phenyl] -2,6-difluoro-benzamide

350 427 Pyridine-2-carboxylic acid {4- [3- (3-chloro-4-dimethylamino-

Thioureido] -phenyl} -amide < / RTI >

351 430 Pyridine-2-carboxylic acid {4- [3- (3-chloro-4-methylsulfanyl- phenyl)

Thioureido] -phenyl} -amide < / RTI >

352 428 Pyridine-2-carboxylic acid {4- [3- (5-chloro-2-methoxy-

Thioureido] -phenyl} -amide < / RTI >

353 417 furan-2-carboxylic acid {4- [3- (5-chloro-2-methoxy-

Thioureido] -phenyl} -amide < / RTI >

354 496 Pyridine-2-carboxylic acid {4- [3- (3-chloro-4- [methyl-

Yl) -amino] -phenyl} -thioureido) -phenyl] -amide

355 495 N- {3-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -2-fluoro-benzamide

356 467 furan-2-carboxylic acid {3-chloro-4- [3- (5- chloro-2,4-dimethoxy- phenyl)

Thioureido] -phenyl} -amide < / RTI >

357 515 N- {4- [3- (3-Chloro-4-cyclohexylsulfanyl-phenyl) -thioureido] -

Phenyl} -2-fluoro-benzamide

358 449 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-

Trifluoromethylphenyl} -acetamide < / RTI >

359 529 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-

Trifluoromethylphenyl} -2-fluoro-benzamide < / RTI >

360 421 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-

Dimethylamino-acetamide

361 473 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-

Acetylamino) phenyl] -thioureido} -phenyl) -amide

362 501 N- (4- {3- [3-Chloro-4- (2-dimethylamino-acetylamino) -phenyl] -

Thioureido} -phenyl) -2-fluoro-benzamide

363 461 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-

Piperidin-1-yl-acetamide

364 541 N- (4- {3- [3-Chloro-4- (2-piperidin- 1- yl-acetylamino) -phenyl] -

Thioureido} -phenyl) -2-fluoro-benzamide

365 513 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-

Acetylamino) phenyl] -thioureido} -phenyl) -amide

366 463 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-

Morpholin-4-yl-acetamide

367 543 N- (4- {3- [3-Chloro-4- (2-morpholin-4- yl- acetylamino) -phenyl] -

Thioureido} -phenyl) -2-fluoro-benzamide

368 515 furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-morpholin-

Acetylamino) phenyl] -thioureido} -phenyl) -amide

369 414 N- {4- [3- (3-Chloro-4-methanesulfonylamino-phenyl) -thioureido]

Phenyl} -acetamide

370 494 N- {4- [3- (3-Chloro-4-methanesulfonylamino-phenyl) -thioureido]

Phenyl} -2-fluoro-benzamide

371 466 furan-2-carboxylic acid {4- [3- (3-chloro-4-methanesulfonylamino-phenyl)

Thioureido] -phenyl} -amide < / RTI >

372 481 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-

(2-dimethylamino-ethylsulfanyl) -acetamide

373 561 N- [4- (3- {3-Chloro-4- [2- (2-dimethylamino-ethylsulfanyl)

Acetylamino] -phenyl} -thioureido) -phenyl] -2-fluoro-benzamide

374 585 N- [4- (3- {4 - [(1-Benzyl-pyrrolidin-3- yl) -methyl-

Phenyl} -thioureido) -phenyl] -2-methyl-benzamide

375 523 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl- piperidin-

Phenyl} -thioureido) -phenyl] -2-methyl-benzamide

376 510 Pyridine-2-carboxylic acid [4- (3- {3-chloro-4- [methyl- (1 -methyl-piperidin-

Yl) -amino] phenyl} -thioureido) -phenyl] -amide

377 347 N- {4- [3- (3-Chloro-4-vinyl-phenyl) -thioureido] phenyl} -acetamide]

378 441 furan-2-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl- phenyl)

Thioureido] -phenyl} -amide < / RTI >

379 452 Pyridine-2-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl- phenyl)

Thioureido] -phenyl} -amide < / RTI >

380 487 N- {4- [3- (4-Chloro-3-trifluoromethyl-phenyl) -thioureido]

Phenyl} -2,6-difluoro-benzamide

381 486 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-

Phenyl} -2-fluoro-benzamide

382 458 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -3-cyano-phenyl} -amide

383 406 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-

Phenyl} -acetamide

384 395 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -2-methyl-isothioureido]

Phenyl} -acetamide

385 396 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -2-methyl-isothioureido]

Phenyl} -acetamide

386 461 N- {4- [3- (3-Chloro-4-ethylsulfanyl-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

387 489 N- {4- [3- (4-Butylsulfanyl-3-chloro-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

388 411 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-methoxy-

Phenyl} -acetamide

389 491 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-methoxy-

Phenyl} -2-fluoro-benzamide

390 463 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -3-methoxy-phenyl} -amide

391 531 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3-chloro-4- (2-piperidin-

Yl-acetyl-amino) -phenyl] -thioureido} -phenyl) -amide

392 481 N- {4- [3- (3-Chloro-4-methanesulfinyl-phenyl) -thioureido] -phenyl}

Difluoro-benzamide

393 497 N- {4- [3- (3-Chloro-4-methanesulfonyl-phenyl) -thioureido] -phenyl}

Difluoro-benzamide

394 459 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido]

Phenyl} -2-fluoro-benzamide

395 429 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -2-methyl-

Fluoro-benzamide

396 533 furan-2-carboxylic acid [4- (3- {3-chloro-4- [2- (2-

Ethylsulfanyl) acetylamino] -phenyl} -thioureido) -phenyl] -amide

397 458 N- {4- [3- (4-Acetylamino-3-chloro-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

398 460 [2-Chloro-4- (3- {4- [(furan-2-carbonyl) -amino] -phenyl}

Thioureido) -phenyl] -carbamic acid ethyl ester

399 488 (2-Chloro-4- {3- [4- (2-fluoro-benzoylamino) -phenyl] -

Thioureido} -phenyl) carbamic acid ethyl ester

400 440 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -

Benzamide

401 520 N- {4 - [({[4- (Benzoylamino) -3-chloro-phenyl] -amino} -thioxomethyl)

Amino] -phenyl} -2-fluoro-benzamide

402 529 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-

Trifluoromethyl-phenyl} -2-fluoro-benzamide < / RTI >

403 492 Furan-2-carboxylic acid {4- [3- (4-benzoylamino-3-chloro-phenyl)

Thioureido] -phenyl} -amide < / RTI >

404 416 N- {4- [3- (4-Amino-3-chloro-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

405 479 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-

Thiomorpholin-4-yl-acetamide

406 531 furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-thiomorpholin-

Acetylamino) phenyl] -thioureido} -phenyl) -amide

407 559 N- (4- {3- [3-Chloro-4- (2-thiomorpholin-4- yl- acetylamino) -phenyl] -

Thioureido} -phenyl) -2-fluoro-benzamide

408 461 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido]

Phenyl} -2-fluoro-benzamide

409 430 furan-2-carboxylic acid {4- [3- (4-acetylamino-3-chloro-phenyl)

Thioureido] phenyl} -amide

410 477 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-

Dipropylamino-acetamide

411 529 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-

Acetylamino) phenyl] -thioureido} -phenyl) -amide

412 449 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-

Diethylamino-acetamide

413 501 furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-

Acetylamino) -phenyl] -thioureido} -phenyl) -amide < / RTI >

414 529 N- (4- {3- [3-Chloro-4- (2-diethylamino-acetylamino) -phenyl] -

Thioureido} -phenyl) -2-fluoro-benzamide

415 447 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-

Pyrrolidin-1-yl-acetamide

416 499 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-pyrrolidin-

Acetylamino) phenyl] -thioureido} -phenyl) -amide

417 527 N- (4- {3- [3-Chloro-4- (2-pyrrolidin- 1 -yl- acetylamino) -phenyl] -

Thioureido} -phenyl) -2-fluoro-benzamide

418 475 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido] -3-

Methoxy-phenyl} -2-fluoro-benzamide

419 445 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -3-methoxy-

2-Fluoro-benzamide

420 477 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido] -3-methoxy-

Phenyl} -2-fluoro-benzamide

421 388 furan-2-carboxylic acid {4- [3- (4-amino-3-chloro-phenyl) -thioureido]

Phenyl} -amide

422 527 furan-2-carboxylic acid (4- {3- [4- (2-azepan-1-yl- acetylamino)

Phenyl] -thioureido} -phenyl) -amide

423 555 N- (4- {3- [4- (2-Azepan-1-yl-acetylamino)

Thioureido} -phenyl) -2-fluoro-benzamide

424 527 furan-2-carboxylic acid [4- (3- {3-chloro-4- [2-

Acetyl-amino] -phenyl} -thioureido) -phenyl] -amide

425 555 N- [4- (3- {3-Chloro-4- [2- (2-methyl- piperidin- 1- yl) -acetylamino]

Phenyl} -thioureido) -phenyl] -2-fluoro-benzamide

426 339 furan-2-carboxylic acid [4- (3-pyridin-2-yl-thioureido) -phenyl]

427 339 Furan-2-carboxylic acid [4- (3-pyridin-4-yl-thioureido) -phenyl]

428 367 2-Fluoro-N- [4- (3-pyridin-3-yl-thioureido) -phenyl] -benzamide

429 339 furan-2-carboxylic acid [4- (3-pyridin-3-yl-thioureido) -phenyl]

430 353 Furan-2-carboxylic acid {4- [3- (3-amino-phenyl) -thioureido] -phenyl}

431 406 furan-2-carboxylic acid {4- [3- (3-trifluoromethyl-phenyl) -thioureido]

Phenyl} -amide

432 380 2-Fluoro-N- [4- (3-m-tolyl-thioureido) -phenyl] -benzamide

433 434 2-Fluoro-N- {4- [3- (3-trifluoromethyl-phenyl) -thioureido] -

Phenyl} benzamide

434 381 N- {4- [3- (3-Amino-phenyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

435 388 furan-2-carboxylic acid {4- [3- (3-amino-5-chloro-phenyl) -thioureido]

Phenyl} -amide

436 352 Furan-2-carboxylic acid [4- (3-m-tolyl-thioureido) -phenyl] -amide

437 416 N- {4- [3- (2-Amino-5-chloro-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

438 571 (2-Chloro-4- {3- [4- (2-fluoro-benzoylamino) -phenyl] -

Thioureido} -phenyl) -carbamic acid 2-piperidin-1-yl-ethyl ester

439 543 [2-Chloro-4- (3- {4- [(furan-2-carbonyl) -amino] -phenyl}

Thioureido) -phenyl] -carbamic acid 2-piperidin-1-yl-ethyl ester

440 388 furan-2-carboxylic acid {4- [3- (2-amino-5-chloro-phenyl) -thioureido]

Phenyl} -amide

441 363 furan-2-carboxylic acid {4- [3- (3-cyano-phenyl) -thioureido] -phenyl} -

amides

442 416 N- {4- [3- (3-Amino-5-chloro-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

443 367 2-Fluoro-N- [4- (3-pyridin-2-yl-thioureido) -phenyl] -benzamide

444 367 2-Fluoro-N- [4- (3-pyridin-4-yl-thioureido) -phenyl] -benzamide

445 374 furan-2-carboxylic acid {4- [3- (6-chloro-pyridin-3- yl) -thioureido]

Phenyl} -amide

446 388 furan-2-carboxylic acid {4- [3- (2-amino-3-chloro-phenyl) -thioureido]

Phenyl} -amide

447 396 Furan-2-carboxylic acid {4- [3- (3-hydrazinocarbonyl-phenyl)] - thioureido]

Phenyl} -amide

448 410 2-Fluoro-N- (4- {3- [3- (1 -hydroxy-ethyl) -phenyl] -thioureido}

Phenyl) -benzamide

449 414 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-hydrazinocarbonyl- phenyl)

Thioureido] -phenyl} -amide < / RTI >

450 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3- isopropyl- phenyl)

Thioureido] -phenyl} -amide < / RTI >

451 380 Furan-2-carboxylic acid {4- [3- (3-isopropyl-phenyl) -thioureido] -phenyl} -

amides

452 409 2-Fluoro-N- {4- [3- (3-isopropyl-phenyl) -thioureido] -phenyl} -

Benzamide

453 381 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-cyano- phenyl)

Thioureido] -phenyl} -amide < / RTI >

454 410 N- {4- [3- (3-Dimethylamino-phenyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

455 381 furan-2-carboxylic acid {4- [3- (3-dimethylamino-phenyl) -thioureido]

Phenyl} -amide

456 370 [1,2,3] Thiadiazole-4-carboxylic acid [4- (3-m-tolyl-thioureido) -phenyl] -

amides

457 424 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-trifluoromethyl- phenyl)

Thioureido] -phenyl} -amide < / RTI >

458 479 N- {3-Chloro-4- [3- (5-chloro-2-methoxy-4-methyl- phenyl) -thioureido]

Phenyl} -2-fluoro-benzamide

459 449 N- {3-Chloro-4- [3- (3-chloro-4-methyl-phenyl) -thioureido] -phenyl}

2-Fluoro-benzamide

460 481 N- {3-Chloro-4- [3- (3-chloro-4-methylsulfanyl- phenyl) -thioureido]

Phenyl} -2-fluoro-benzamide

461 391 N- {4- [3- (3-Cyano-phenyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

462 395 Furan-2-carboxylic acid {4- [3- (3-acetylamino-phenyl) -thioureido]

Phenyl} -amide

463 424 2-Fluoro-N- {4- [3- (3-hydrazinocarbonyl-phenyl) -thioureido] -

Phenyl} -benzamide

464 400 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (1 -hydroxy-

Thioureido} -phenyl) -amide < / RTI >

465 434 N- {4- [3- (2-Amino-3-chloro-phenyl) -thioureido] -phenyl}

Difluoro-benzamide

466 406 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-amino-

Thioureido] -phenyl} -amide < / RTI >

467 398 furan-2-carboxylic acid {4- [3- (3,5-dimethoxy-phenyl) -thioureido] -phenyl} -

amides

468 416 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-dimethoxy- phenyl)

Thioureido] -phenyl} -amide < / RTI >

469 454 5- (3- {4 - [(Furan-2-carbonyl) -amino} -phenyl} -thioureido)

Isophthalic acid dimethyl ester

470 434 isoxazole-5-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -amide < / RTI >

471 392 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (6-chloro-pyridin-

Thioureido] -phenyl} -amide < / RTI >

472 382 Furan-2-carboxylic acid (4- {3- [3- (1 -hydroxy-ethyl) -phenyl] -thioureido}

Phenyl) -amide

473 368 Furan-2-carboxylic acid {4- [3- (3-methoxy-phenyl) -thioureido] -phenyl} -

amides

474 354 Furan-2-carboxylic acid {4- [3- (3-hydroxy-phenyl) -thioureido] -phenyl} -

amides

475 382 2-Fluoro-N- {4- [3- (3-hydroxy-phenyl) -thioureido] -phenyl} -

Benzamide

476 396 2-Fluoro-N- {4- [3- (3-hydroxymethyl-phenyl) -thioureido] -phenyl} -

Benzamide

477 423 N- {4- [3- (3-Acetylamino-phenyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

478 413 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-acetylamino- phenyl)

Thioureido] -phenyl} -amide < / RTI >

479 400 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-dimethylamino-

Thioureido] -phenyl} -amide < / RTI >

480 340 furan-2-carboxylic acid [4- (3-pyrimidin-4-yl-thioureido) -phenyl]

481 378 furan-2-carboxylic acid {4- [3- (lH-indazol-5-yl) -thioureido] -phenyl}

amides

482 395 Furan-2-carboxylic acid [4- (3-benzothiazol-5-yl-thioureido) -phenyl] -

amides

483 406 2-Fluoro-N- {4- [3- (lH-indazol-5-yl) -thioureido] -phenyl} -

Benzamide

484 424 N- [4- (3-Benzothiazol-5-yl-thioureido) -phenyl] -2-fluoro-

Benzamide

485 473 5- (3- {4 - ([1,2,3] thiadiazole-4-carbonyl) -amino]

Thioureido) -isophthalic acid dimethyl ester

486 442 furan-2-carboxylic acid (4- {3- [4- (1-azido-ethyl)

Thioureido} -phenyl) -amide < / RTI >

487 396 2-Fluoro-N- {4- [3- (3-methoxy-phenyl) -thioureido] -phenyl} -

Benzamide

488 368 Furan-2-carboxylic acid {4- [3- (3-hydroxymethyl-phenyl) -thioureido]

Phenyl} -amide

489 416 furan-2-carboxylic acid {4- [3- (5-chloro-2-dimethylamino-

Thioureido] -phenyl} -amide < / RTI >

490 444 N- {4- [3- (5-Chloro-2-dimethylamino-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

491 506 [3-Chloro-5- (3- {4 - [([1,2,3] thiadiazole-4-carbonyl) -amino]

Thioureido) -phenyl] -carbamic acid tert-butyl ester

492 470 N- (4- {3- [4- (1-Azido-ethyl) -3-chloro-phenyl] -thioureido} -phenyl) -

2-Fluoro-benzamide

493 337 Furan-2-carboxylic acid [4- (1H-thiazolo [5,4- b] pyridin- 2- ylideneamino)

Phenyl] -amide

494 378 furan-2-carboxylic acid {4- [3- (lH-benzoimidazol-5-yl) -thioureido]

Phenyl} -amide

495 392 Furan-2-carboxylic acid {4- [3- (2-methyl-lH-benzoimidazol-

Thioureido] -phenyl} -amide < / RTI >

496 406 N- {4- [3- (lH-Benzoimidazol-5-yl) -thioureido] -phenyl} -2-fluoro-

Benzamide

497 420 2-Fluoro-N- {4- [3- (2-methyl-lH-benzoimidazol-

Thioureido] -phenyl} -benzamide < / RTI >

498 452 [1,2,3] Thiadiazole-4-carboxylic acid {5- [3- (5-chloro-2,4-dimethoxy-

Phenyl) -thioureido] -pyridin-2-yl} -amide

499 445 Pyridine-2-carboxylic acid {5- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -pyridin-2-yl} -amide

500 434 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (5-chloro-2-dimethylamino-

Phenyl) -thioureido] -phenyl} -amide

501 484 [1,2,3] Thiadiazole-4-carboxylic acid (4- {3- [4- (2- amino-pyrimidin-

Yl) -3-chloro-phenyl] -thioureido} -phenyl) -amide

502 494 N- (4- {3- [4- (2-Amino-pyrimidin-4-yl) -3-chloro-

Thioureido} -phenyl) -2-fluoro-benzamide

503 434 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-2-

Phenyl) -thioureido] -phenyl} -amide

504 462 N- {4- [3- (3-Chloro-2-dimethylamino-phenyl) -thioureido] -phenyl} -

2,6-difluoro-benzamide

505 416 furan-2-carboxylic acid {4- [3- (3-chloro-2-dimethylamino-

Thioureido] -phenyl} -amide < / RTI >

506 445 Pyridine-2-carboxylic acid {6- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -pyridin-3-yl} -amide

507 462 N- {6- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -pyridin-

Yl} -2-fluoro-benzamide

508 482 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-iodo-phenyl)

Thioureido] -phenyl} -amide < / RTI >

509 413 [l, 2,3] Thiadiazole-4-carboxylic acid {4- [3- (3- tert-

Thioureido] -amide

510 387 Furan-2-carboxylic acid {4- [3- (3-chloro-benzyl) -thioureido] -phenyl} -

amides

511 415 N- {4- [3- (3-Chloro-benzyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

512 434 furan-2-carboxylic acid {6- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -pyridin-3-yl} -amide

513 435 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-bromo-phenyl)

Thioureido] -phenyl} -amide < / RTI >

514 452 [1,2,3] Thiadiazole-4-carboxylic acid {6- [3- (5-chloro-2,4-

Phenyl) -thioureido] -pyridin-3-yl} -amide

515 426 [1,2,3] Thiadiazole-4-carboxylic acid {5- [3- (3,5-dichloro- phenyl)

Thioureido] -pyridin-2-yl} -amide

516 474 furan-2-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-phenyl)

Thioureido] -phenyl} -amide < / RTI >

517 502 N- {4- [3- (3,5-Bis-trifluoromethyl-phenyl) -thioureido] -phenyl} -

2-Fluoro-benzamide

518 450 N- {4- [3- (4-Amino-3,5-dichloro-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

519 539 N- {4- [3- (4-Amino-3,5-dibromo-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

520 392 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (5-chloro-pyridin-

Thioureido] -phenyl} -amide < / RTI >

521 529 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-amino-3,5-dibromo-

Phenyl) -thioureido] -phenyl} -amide

522 434 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-5-dimethylamino-

Phenyl) -thioureido] -phenyl} -amide

523 444 N- {4- [3- (3-Chloro-5-dimethylamino-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

524 416 furan-2-carboxylic acid {4- [3- (3-chloro-5-dimethylamino-

Thioureido] -phenyl} -amide < / RTI >

525 436 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (5-bromo-pyridin-

Thioureido] -phenyl} -amide < / RTI >

526 379 furan-2-carboxylic acid {4- [3- (lH-benzotriazol-5-yl) -thioureido]

Phenyl} -amide

527 425 N- {4- [3- (1H-Benzotriazol-5-yl) -thioureido] -phenyl} -2,6-

Difluoro-benzamide

528 388 N- [4 - ({[2- (3-Chloro-phenyl) -hydrazino] -thioxomethyl}

Phenyl] -furan-2-carboxamide

529 416 N- [4 - ({[2- (3-Chloro-phenyl) -hydrazino] -thioxomethyl}

Phenyl] -2-fluoro-benzamide

530 456 Furan-2-carboxylic acid {4- [3- (2-amino-3-chloro-5-trifluoromethyl-

Phenyl) -thioureido] -phenyl} -amide

531 513 N- {4- [3- (3-Bromo-5-trifluoromethyl-phenyl) -thioureido] -

Phenyl} -2-fluoro-benzamide

532 503 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-bromo-5-trifluoro

Methyl-phenyl) -thioureido] -phenyl} -amide

533 374 {4- [(furan-2-carbonyl) -amino] -phenyl} -thiocarbamic acid O- (3-chloro-

Phenyl) ester

534 474 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-amino-

Trifluoromethyl-phenyl) -thioureido] -phenyl} -amide < / RTI >

535 508 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-piperidin-

Trifluoromethyl-phenyl) -thioureido] -phenyl} -amide < / RTI >

536 380 N- [4- (3-Benzyl-thioureido) -phenyl] -2-fluoro-benzamide

537 439 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,4-dichloro-benzyl) -

Thioureido] -phenyl} -amide < / RTI >

538 449 N- {4- [3- (3,4-Dichloro-benzyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

539 370 [1,2,3] thiadiazole-4-carboxylic acid [4- (3-benzyl-thioureido) -phenyl] -

amides

540 424 N- [4- (3-Benzo [1,3] dioxol-5-ylmethyl-thioureido) -phenyl] -2-

Fluoro-benzamide

541 414 [1,2,3] Thiadiazole-4-carboxylic acid [4- (3-benzo [1,3] dioxol-

Thioureido) -phenyl] -amide < / RTI >

542 506 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-

Benzyl) -thioureido] -phenyl} -amide

543 516 N- {4- [3- (3,5-Bis-trifluoromethyl-benzyl) -thioureido] -phenyl} -

2-Fluoro-benzamide

544 352 Furan-2-carboxylic acid [4- (3-benzyl-thioureido) -phenyl] -amide

545 421 furan-2-carboxylic acid {4- [3- (3,4-dichloro-benzyl) -thioureido] -phenyl} -

amides

546 396 Furan-2-carboxylic acid [4- (3-benzo [1,3] dioxol-5-ylmethyl-thioureido)

Phenyl] -amide

547 488 furan-2-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-benzyl) -

Thioureido] -phenyl} -amide < / RTI >

548 503 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-bromo-3- trifluoro

Methyl-phenyl) -thioureido] -phenyl} -amide

549 529 N- {4- [3- (3-Bromo-4-trifluoromethoxy-phenyl) -thioureido] -

Phenyl} -2-fluoro-benzamide

550 519 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-bromo-4-trifluoro

Methoxy-phenyl) -thioureido] -phenyl} -amide

551 473 furan-2-carboxylic acid {4- [3- (3-chloro-4-trifluoromethylsulfanyl- phenyl)

Ureido] -phenyl} -amide

552 412 2-Fluoro-N- (4- {3- [2- (3-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

553 412 2-Fluoro-N- (4- {3- [2- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

554 402 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-fluoro-

Thioureido} -phenyl) -amide < / RTI >

555 402 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-fluoro-

Thioureido} -phenyl) -amide < / RTI >

556 495 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (2-methyl-

Trifluoromethyl-phenyl] -thioureido} -phenyl) -amide < / RTI >

557 481 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-isobutyl-5-trifluoro

Methyl-phenyl) -thioureido] -phenyl} -amide

558 523 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (4- methyl- piperazin-

5-trifluoromethyl-phenyl] -thioureido} -phenyl) -amide

559 510 [1,2,3] thiadiazole-4-carboxylic acid {4- {3- (3-morpholin-

Trifluoromethyl-phenyl) -thioureido] -phenyl} -amide < / RTI >

560 494 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-pyrrolidin-

Trifluoromethyl-phenyl) -thioureido] -phenyl} -amide < / RTI >

561 384 furan-2-carboxylic acid (4- {3- [2- (4-fluoro-phenyl)

Thioureido} -phenyl) amide

562 419 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-chloro-phenyl)

Thioureido} -phenyl) -amide < / RTI >

563 429 N- (4- {3- [2- (3-Chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

564 401 furan-2-carboxylic acid (4- {3- [2- (3-chloro-phenyl) -ethyl] -thioureido}

Phenyl) -amide

565 402 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [1- (4-fluoro-

Thioureido} -phenyl) -amide < / RTI >

566 504 2-Fluoro-N- {4- [3- (3-pyrrolidin-1-yl-5-trifluoromethyl- phenyl)

Thioureido] -phenyl} -benzamide < / RTI >

567 477 N- {4- [3- (3-Dimethylamino-5-trifluoromethyl-phenyl) -

Thioureido] -phenyl} -2-fluoro-benzamide

568 520 2-Fluoro-N- {4- [3- (3-morpholin-4-yl-5-trifluoromethyl-

Thioureido] -phenyl] -benzamide < / RTI >

569 533 2-Fluoro-N- (4- {3- (4-methyl-piperazin- 1 -yl) -5- trifluoromethyl-

Phenyl] -thioureido} -phenyl) -benzamide < / RTI >

570 518 2-Fluoro-N- {4- [3- (3-piperidin-l-yl-5-trifluoromethyl- phenyl)

Thioureido] -phenyl} -benzamide < / RTI >

571 468 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-dimethylamino-

Trifluoromethyl-phenyl) -thioureido] -phenyl} -amide < / RTI >

572 405 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-benzyl) -

Thioureido] -phenyl} -amide < / RTI >

573 384 furan-2-carboxylic acid (4- {3- [2- (3-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -amide

574 366 Furan-2-carboxylic acid [4- (3-phenethyl-thioureido) -phenyl] -amide

575 384 [1,2,3] thiadiazole-4-carboxylic acid [4- (3-phenethyl-thioureido) -phenyl] -

amides

576 394 2-Fluoro-N- [4- (3-phenethyl-thioureido) -phenyl] -benzamide

577 505 2-Fluoro-N- (4- {3- [3- (2-methyl-butyl) -5- trifluoromethyl-

Thioureido} -phenyl) -benzamide < / RTI >

578 491 2-Fluoro-N- {4- [3- (3-isobutyl-5-trifluoromethyl-phenyl)

Thioureido] -phenyl} -benzamide < / RTI >

579 388 furan-2-carboxylic acid {4- [3- (3,5-difluoro-benzyl) -thioureido]

Phenyl} -amide

580 416 N- {4- [3- (3,5-Difluoro-benzyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

581 406 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-difluoro-benzyl) -

Thioureido] -phenyl} -amide < / RTI >

582 421 furan-2-carboxylic acid {4- [3- (3,5-dichloro-benzyl) -thioureido] -phenyl}

amides

583 449 N- {4- [3- (3,5-Dichloro-benzyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

584 439 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro-

Thioureido] -phenyl} -amide < / RTI >

585 438 Furan-2-carboxylic acid {4- [3- (3-fluoro-5-trifluoromethyl-

Thioureido] -phenyl} -amide < / RTI >

586 466 2-Fluoro-N- {4- [3- (3-fluoro-5-trifluoromethyl-benzyl) -

Thioureido] -phenyl} -benzamide < / RTI >

587 456 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-fluoro-

Trifluoromethyl-benzyl) -thioureido] -phenyl} -amide < / RTI >

588 384 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (1-phenyl- ethyl) -thioureido]

Phenyl} -amide

589 394 2-Fluoro-N- {4- [3- (1-phenyl-ethyl) -thioureido] -phenyl} -

Benzamide

590 366 Furan-2-carboxylic acid {4- [3- (1-phenyl-ethyl) -thioureido] -phenyl}

591 412 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

592 384 Furan-2-carboxylic acid (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -amide

593 413 N- {4- [3- (1-tert-Butyl-1H-imidazol-2-yl) -thioureido] -phenyl} -2-

Fluorobenzamide

594 510 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (isobutyl-

5-trifluoromethyl-phenyl] -thioureido} -phenyl) -amide

595 510 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (3-hydroxy-pyrrolidin-

Yl) -5-trifluoromethyl-phenyl] -thioureido} -phenyl) -amide

596 520 2-Fluoro-N- (4- {3- [3- (isobutyl-methyl-amino) -5-trifluoro

Methyl-phenyl] -thioureido} -phenyl) -benzamide < / RTI >

597 510 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (butyl- methyl-

Trifluoromethyl-phenyl] -thioureido} -phenyl) -amide < / RTI >

598 520 N- (4- {3- [3- (Butyl-methyl-amino) -5-trifluoromethyl-phenyl]

Thioureido} -phenyl) -2-fluoro-benzamide

599 520 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,5-

Methylphenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >

600 442 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-fluoro-3-

Methylphenyl) -thioureido] -phenyl} -amide

601 522 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-piperidin-

Trifluoromethyl-benzyl) -thioureido] -phenyl} -amide < / RTI >

602 482 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-dimethylamino-

Trifluoromethyl-benzyl) -thioureido] -phenyl} -amide < / RTI >

603 381 Furan-2-carboxylic acid (4- {3- [2- (4-amino- phenyl) -ethyl] -thioureido}

Phenyl) -amide

604 445 Furan-2-carboxylic acid (4- {3- [2- (4-bromo-phenyl) -ethyl] -thioureido}

Phenyl) -amide

605 380 Furan-2-carboxylic acid {4- [3- (2-p-tolyl-ethyl) -thioureido] -phenyl} -

amides

606 463 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (4-bromo- phenyl)

Thioureido} -phenyl) -amide < / RTI >

607 396 Furan-2-carboxylic acid (4- {3- [2- (3-methoxy-phenyl) -ethyl] -thioureido}

Phenyl) -amide

608 403 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (1-tert- butyl-

Yl) -thioureido] -phenyl} -amide

609 384 furan-2-carboxylic acid {4- [3- (l-tert-butyl- lH-imidazol-

Thioureido] -phenyl} -amide < / RTI >

610 492 N- {4- [3- (4-Dimethylamino-3-trifluoromethyl-benzyl) -

Thioureido] -phenyl} -2-fluoro-benzamide

611 427 furan-2-carboxylic acid (4- {3- [2- (3,4-dimethoxy-phenyl)

Thioureido} -phenyl) -amide < / RTI >

612 380 Furan-2-carboxylic acid {4- [3- (3-phenyl-propyl) -thioureido] -phenyl} -

amides

613 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-phenyl-

Thioureido] -phenyl} -amide < / RTI >

614 502 furan-2-carboxylic acid (4- {3- [2- (3,5-bis-trifluoromethyl-phenyl)

Ethyl] -thioureido} -phenyl) -amide

615 550 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-iodo-3- trifluoro

Methyl-phenyl) -thioureido] -phenyl} -amide

616 532 2-Fluoro-N- {4- [3- (4-piperidin-l-yl-3- trifluoromethyl-

Thioureido] -phenyl} -benzamide < / RTI >

617 537 [l, 2,3] Thiadiazole-4-carboxylic acid (4- {3- [4- (4-methyl-piperazin-

3-trifluoromethyl-benzyl] -thioureido} -phenyl) -amide

618 482 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-dimethylamino-

Trifluoromethyl-benzyl) -thioureido] -phenyl} -amide < / RTI >

619 488 furan-2-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-phenyl)

Thioureido-methyl] -phenyl} -amide < / RTI >

620 421 furan-2-carboxylic acid {4- [3- (3,5-dichloro-phenyl) -thioureidomethyl] -

Phenyl} -amide

621 421 furan-2-carboxylic acid {4- [3- (3,4-dichloro-phenyl) -thioureidomethyl] -

Phenyl} -amide

622 455 furan-2-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl- phenyl)

Thioureido-methyl] -phenyl} -amide < / RTI >

623 466 2-Fluoro-N- {4- [3- (4-fluoro-3-trifluoromethyl-benzyl) -

Thioureido] -phenyl} -benzamide < / RTI >

624 456 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-fluoro-

Trifluoromethyl-benzyl) -thioureido] -phenyl} -amide < / RTI >

625 410 2-Fluoro-N- {4- [3- (2-phenoxy-ethyl) -thioureido] -phenyl} -

Benzamide

626 382 furan-2-carboxylic acid {4- [3- (2-phenoxy-ethyl) -thioureido] -phenyl} -

amides

627 400 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-phenoxy- ethyl)

Thioureido] -phenyl} -amide < / RTI >

628 409 2-Fluoro-N- {4- [3- (3-phenyl-propyl) -thioureido] -phenyl} -

Benzamide

629 425 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (5-trifluoromethyl-

3-yl) -thioureido] -phenyl} -amide

630 439 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)

Thioureido-methyl] -phenyl} -amide < / RTI >

631 473 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-chloro-3-trifluoro

Methyl-phenyl) -thioureidomethyl] -phenyl} -amide

632 381 2-Fluoro-N- [4- (3-pyridin-3-ylmethyl-thioureido) -phenyl] -

Benzamide

633 353 Furan-2-carboxylic acid [4- (3-pyridin-3-ylmethyl-thioureido) -phenyl] -

amides

634 371 [l, 2,3] Thiadiazole-4-carboxylic acid [4- (3-pyridin-

Thioureido) phenyl] -amide

635 439 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl)

Thioureidomethyl] -phenyl} -amide < / RTI >

636 492 N- {4- [3- (3-Dimethylamino-5-trifluoromethyl-benzyl) -

Thioureido] -phenyl} -2-fluoro-benzamide

637 415 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-methoxy- phenyl)

Thioureido} -phenyl) -amide < / RTI >

638 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-p-

Thioureido] -phenyl} -amide < / RTI >

639 445 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,4- dimethoxy- phenyl)

Ethyl] -thioureido} -phenyl) -amide

640 506 [l, 2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-bis-

Phenyl) -thioureidomethyl] -phenyl} -amide

641 516 N- {4- [3- (3,5-Bis-trifluoromethyl-phenyl) -thioureidomethyl] -

Phenyl} -2-fluoro-benzamide

642 449 N- {4- [3- (3,5-Dichloro-phenyl) -thioureidomethyl] -phenyl} -2-

Fluoro-benzamide

644 448 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-acetylamino-

Phenyl) -thioureido] -phenyl} -amide

645 453 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,4-

Ethyl] -thioureido} -phenyl) -amide

646 413 [l, 2,3] Thiadiazole-4-carboxylic acid {4- [3- (l-

Thioureido] -phenyl} -amide < / RTI >

647 463 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [1- (4-bromo- phenyl)

Thioureido} -phenyl) -amide < / RTI >

648 413 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-phenyl-

Thioureido] -phenyl} -amide < / RTI >

649 397 [1,2,3] Thiadiazole-4-carboxylic acid [4- (3-indan-1-yl-thioureido)

Phenyl] -amide

650 400 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-methoxy-benzyl) -

Thioureido] -phenyl} -amide < / RTI >

651 415 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-methoxy- phenyl)

Thioureido} -phenyl) -amide < / RTI >

652 415 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-methoxy- phenyl)

Thioureido} -phenyl) -amide < / RTI >

653 506 N- (4- {3- [2- (3-Dimethylamino-5-trifluoromethyl-phenyl) -ethyl] -

Thioureido} -phenyl) -2-fluoro-benzamide

654 510 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (3- dimethylamino-

5-trifluoromethyl-phenyl] -thioureido} -phenyl) -amide

655 417 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (2-phenylsulfanyl- ethyl)

Thioureido] -phenyl} -amide < / RTI >

656 427 2-Fluoro-N- {4- (2-phenylsulfanyl-ethyl) -thioureido] -phenyl} -

Benzamide

657 399 furan-2-carboxylic acid {4- [3- (2-phenylsulfanyl-ethyl) -thioureido] -phenyl} -

amides

658 381 2-Fluoro-N- [4- (3-pyridin-4-ylmethyl-thioureido) -phenyl] -

Benzamide

659 353 Furan-2-carboxylic acid [4- (3-pyridin-4-ylmethyl-thioureido) -phenyl] -

amides

660 371 [l, 2,3] Thiadiazole-4-carboxylic acid [4- (3-pyridin-

Thioureido) phenyl] -amide

661 506 2-Fluoro-N- {4- [3- (3-iodo-benzyl) -thioureido] -phenyl} -

Benzamide

662 478 furan-2-carboxylic acid {4- [3- (3-iodo-benzyl) -thioureido] -phenyl} -

amides

663 496 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-iodo-benzyl) -

Thioureido] phenyl} -amide

664 479 N- (4- {3- [2- (3,5-Dichloro-phenoxy) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

665 451 Furan-2-carboxylic acid (4- {3- [2- (3,5-dichloro-phenoxy)

Thioureido} -phenyl) -amide < / RTI >

666 445 N- (4- {3- [2- (3-Chloro-phenoxy) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

667 417 Furan-2-carboxylic acid (4- {3- [2- (3-chloro-phenoxy) -ethyl] -thioureido}

Phenyl) -amide

668 435 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-chloro-phenoxy)

Thioureido} -phenyl) -amide < / RTI >

669 466 2-Fluoro-N- {4- [3- (2-fluoro-5-trifluoromethyl-benzyl) -

Thioureido] -phenyl} -benzamide < / RTI >

670 438 furan-2-carboxylic acid {4- [3- (2-fluoro-5-trifluoromethyl-benzyl) -

Thioureido] -phenyl} -amide < / RTI >

671 456 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (2-fluoro-5-trifluoro

Methyl-benzyl) -thioureido] -phenyl} -amide

672 416 N- {4- [3- (3,4-Difluoro-benzyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

673 452 N- (4- {3- [2- (4-Dimethylamino-3-methyl-phenyl) -ethyl] -thioureido}

Phenyl) -2-fluoro-benzamide

674 496 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-dimethylamino-

Trifluoromethylphenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >

675 388 furan-2-carboxylic acid {4- [3- (3,4-difluoro-benzyl) -thioureido]

Phenyl} -amide

676 406 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,4-difluoro-benzyl) -

Thioureido] -phenyl} -amide < / RTI >

677 433 N- {4- [3- (3-Chloro-4-fluoro-benzyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

678 495 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-bromo- phenylsulfanyl)

Ethyl] -thioureido} -phenyl) -amide

679 477 furan-2-carboxylic acid (4- {3- [2- (3-bromo-phenylsulfanyl)

Thioureido} -phenyl) -amide < / RTI >

680 505 N- (4- {3- [2- (3-Bromo-phenylsulfanyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

681 493 [l, 2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (3-bromo-4-

Ethyl] -thioureido} -phenyl) -amide

682 493 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (5-bromo-2-methoxy-

Ethyl] -thioureido} -phenyl) -amide

683 419 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-

Thioureido} -phenyl) -amide < / RTI >

684 402 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2- fluoro-

Thioureido} -phenyl) -amide < / RTI >

685 419 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-chloro-phenyl)

Thioureido} -phenyl) -amide < / RTI >

686 475 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,3-diphenyl-

Thioureido] -phenyl} -amide < / RTI >

687 547 2-Fluoro-N- (4- {3- [4- (4-methyl-piperazin- 1- yl) -3-trifluoro

Methyl-benzyl] -thioureido} -phenyl) -benzamide < / RTI >

688 469 [1,2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (3,5- dichloro-phenoxy)

Ethyl] -thioureido} -phenyl) -amide

689 423 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-fluoro-

Thioureido] -phenyl} -amide < / RTI >

690 427 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4- tert- butyl-

Thioureido] -phenyl} -amide < / RTI >

691 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,5-dimethyl-

Thioureido] -phenyl} -amide < / RTI >

692 442 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-

Phenyl) -ethyl] -thioureido} -phenyl) -amide

693 479 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-bromo- phenoxy)

Thioureido} -phenyl) -amide < / RTI >

694 526 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-iodo-phenoxy)

Thioureido} -phenyl) -amide < / RTI >

695 489 N- (4- {3- [2- (4-Bromo-phenoxy) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

696 536 2-Fluoro-N- (4- {3- [2- (4-iodo-phenoxy) -ethyl] -thioureido}

Phenyl) -benzamide

697 461 Furan-2-carboxylic acid (4- {3- [2- (4-bromo-phenoxy) -ethyl] -thioureido}

Phenyl) -amide

698 508 Furan-2-carboxylic acid (4- {3- [2- (4-iodo-phenoxy) -ethyl] -thioureido}

Phenyl) -amide

699 408 Oxazole-4-carboxylic acid {4- [3- (3,4-dichloro-phenyl) -thioureido]

Phenyl} -amide

700 424 Thiazole-4-carboxylic acid {4- [3- (3,5-dichloro-phenyl) -thioureido]

Phenyl} -amide

701 491 Thiazole-4-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-phenyl)

Thioureido] -phenyl} -amide < / RTI >

702 408 Oxazole-4-carboxylic acid {4- [3- (3,5-dichloro-phenyl) -thioureido]

Phenyl} -amide

703 469 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,4- dichloro-phenoxy) -

Ethyl] -thioureido} -phenyl) -amide

704 424 Thiazole-4-carboxylic acid {4- [3- (3,4-dichloro-phenyl) -thioureido]

Phenyl} -amide

705 458 Thiazole-4-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl- phenyl)

Thioureido] -phenyl} -amide < / RTI >

706 400 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-phenylamino-ethyl)

Thioureido] -phenyl} -amide < / RTI >

707 453 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2,4-

Ethyl] -thioureido} -phenyl) -amide

708 452 [1,2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (3- trifluoromethyl-

Phenyl) -ethyl] -thioureido} -phenyl) -amide

709 453 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2,6-dichloro- phenyl)

Ethyl] -thioureido} -phenyl) -amide

710 485 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,4-

Phenylsulfanyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >

711 503 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-fluoro-

Trifluoromethyl-phenylsulfanyl) -ethyl] -thioureido} -phenyl) -amide

712 668 N- (4- {3- [3-Chloro-5- (3- {4 - [(1,2,3] thiadiazole-

Amino] -phenyl} -thioureido) -phenyl] -thioureido} -phenyl) - [l, 2,3]

Thiadiazole-4-carboxamide

713 413 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-ethyl-

Thioureido} -phenyl) -amide < / RTI >

714 442 OXAZOLE-4-CARBOXYLIC ACID {4- [3- (4-Chloro-3-trifluoromethyl-phenyl)

Thioureido] -phenyl} -amide < / RTI >

715 475 < / RTI > Oxazole-4-carboxylic acid {4- [3- (3,5-bis- trifluoromethyl- phenyl)

Thioureido] -phenyl} -amide < / RTI >

716 420 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,4- difluoro-

Ethyl] -thioureido} -phenyl) -amide

717 452 [l, 2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (4-trifluoromethyl-

Phenyl) -ethyl] -thioureido} -phenyl) -amide

718 435 Furan-2-carboxylic acid (4- {3- [2- (3,4-dichloro-phenyl)

Thioureido} -phenyl) -amide < / RTI >

719 463 N- (4- {3- [2- (3,4-Dichloro-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

720 420 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,5- difluoro-

Ethyl] -thioureido} -phenyl) -amide

721 412 2-Fluoro-N- (4- {3- [2- (2-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

722 429 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-nitro- phenyl)

Thioureido} -phenyl) -amide < / RTI >

723 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (1-methyl-

Thioureido] -phenyl} -amide < / RTI >

724 437 N- {4- [3- (4-tert-Butyl-benzyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

725 409 N- {4- [3- (3,5-Dimethyl-benzyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

726 400 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-hydroxy-

Thioureido] -phenyl} -amide < / RTI >

727 409 2-Fluoro-N- {4- [3- (1 -methyl-1-phenyl- ethyl) -thioureido] -phenyl} -

Benzamide

728 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (1-methyl-

Thioureido] -phenyl} -amide < / RTI >

729 405 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (2-chloro-benzyl) -

Thioureido] -phenyl} -amide < / RTI >

730 388 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (2-fluoro-

Thioureido] -phenyl} -amide < / RTI >

731 438 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-trifluoromethyl-benzyl) -

Thioureido] -phenyl} -amide < / RTI >

732 388 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-fluoro-

Thioureido] -phenyl} -amide < / RTI >

733 435 [l, 2,3] Thiadiazole-4-carboxylic acid (4- [3- [2- (2-chloro-phenoxy)

Thioureido} -phenyl) -amide < / RTI >

734 479 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-bromo- phenoxy)

Thioureido} -phenyl) -amide < / RTI >

735 418 [1,2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (2-fluoro-phenoxy)

Ethyl] -thioureido} -phenyl) -amide

736 418 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-fluoro-phenoxy)

Ethyl] -thioureido} -phenyl) -amide

737 486 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-fluoro-

Trifluoromethyl-phenoxy) -ethyl] -thioureido} -phenyl) -amide < / RTI >

738 384 furan-2-carboxylic acid (4- {3- [2- (2-fluoro-phenyl)

Thioureido} -phenyl) -amide < / RTI >

739 435 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-bromo-phenyl)

Thioureido] -phenyl} -amide < / RTI >

740 374 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-fluoro-

Thioureido] -phenyl} -amide < / RTI >

741 388 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-fluoro-

Thioureido] -phenyl} -amide < / RTI >

742 405 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-chloro-benzyl) -

Thioureido] -phenyl} -amide < / RTI >

743 449 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-bromo-benzyl)

Thioureido] -phenyl} -amide < / RTI >

744 332 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -

Acetamide

745 438 Thiazole-4-carboxylic acid {4- [3- (3,4-dichloro-benzyl) -thioureido]

Phenyl} -amide

746 455 Thiazole-4-carboxylic acid {4- [3- (2-fluoro-5-trifluoromethyl-benzyl) -

Thioureido] -phenyl} -amide < / RTI >

747 426 Thiazole-4-carboxylic acid {4- [3- (4-tert-butyl-benzyl) -thioureido]

Phenyl} -amide

748 374 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (2-fluoro-phenyl)

Thioureido] -phenyl} -amide < / RTI >

749 374 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-fluoro- phenyl)

Thioureido] -phenyl} -amide < / RTI >

750 526 [l, 2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (3-iodo-phenoxy)

Thioureido} -phenyl) -amide < / RTI >

751 409 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl)

Acetamide

752 425 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -2-

Methoxy-benzamide

753 425 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -3-

Methoxy-benzamide

754 425 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -4-

Methoxy-benzamide

755 429 2-Chloro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

756 429 4-Chloro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

757 453 Acetic acid 4- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenylcarbamoyl) -phenyl ester

758 394 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -

Benzamide

759 395 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -

Isonicotinamide

760 410 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -4-

Hydroxy-benzamide

761 429 3-Chloro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

762 470 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-fluoro-

Trifluoromethyl-phenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >

763 520 [l, 2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (2,4-

Methyl-phenyl) -ethyl] -thioureido} -phenyl) -amide

764 470 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4- fluoro-3- trifluoro

Methyl-phenyl) -ethyl] -thioureido} -phenyl) -amide

765 438 4-Dimethylamino-N- (4- {3- [1- (4-fluoro- phenyl)

Thioureido} -phenyl) -benzamide < / RTI >

766 470 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-fluoro-

Trifluoromethyl-phenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >

767 470 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-fluoro-

Trifluoromethyl-phenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >

768 510 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-

Thioureido} -phenyl) -amide < / RTI >

769 470 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-

Trifluoromethyl-phenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >

770 463 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-bromo- phenyl)

Thioureido} -phenyl) -amide < / RTI >

771 427 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -propyl] -thioureido}

Phenyl) -benzamide

772 475 2-Fluoro-N- (4- {3 - [(4-fluoro-phenyl) -phenyl- methyl] -thioureido}

Phenyl) -benzamide

773 455 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -pentyl] -thioureido}

Phenyl) -benzamide

774 489 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -2-

Thioureido} -phenyl) -benzamide < / RTI >

775 409 2-Fluoro-N- {4- [3- (1-o-tolyl-ethyl) -thioureido] -phenyl} -

Benzamide

776 409 2-Fluoro-N- {4- [3- (1-m-tolyl-ethyl) -thioureido] -phenyl} -

Benzamide

777 425 2-Fluoro-N- (4- {3- [1- (4-methoxy-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

778 412 2-Fluoro-N- (4- {3- [1- (2-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

779 429 N- (4- {3- [l- (3-Chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

780 473 N- (4- {3- [1- (3-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

781 429 N- (4- {3- [l- (4-Chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

782 409 2-Fluoro-N- {4- [3- (1-p-tolyl-ethyl) -thioureido] -phenyl} -

Benzamide

783 473 N- (4- {3- [1- (2-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

784 429 N- (4- {3- [l- (2-Chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

785 462 2-Fluoro-N- (4- {3- [1- (2-trifluoromethyl-phenyl)

Thioureido} -phenyl) -benzamide < / RTI >

786 462 2-Fluoro-N- (4- {3- [1- (3-trifluoromethyl-phenyl) -ethyl] -

Thioureido} -phenyl) -benzamide < / RTI >

787 462 2-Fluoro-N- (4- {3- [l- (4-trifluoromethyl-phenyl) -ethyl] -

Thioureido} -phenyl) -benzamide < / RTI >

788 425 2-Fluoro-N- (4- {3- [1- (2-methoxy-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

789 425 2-Fluoro-N- (4- {3- [1- (3-methoxy- phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

790 441 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -2-methyl-

Thioureido} -phenyl) -benzamide < / RTI >

791 419 N- (4- {3- [1- (3-Cyano-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

792 419 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

793 438 N- (4- {3- [1- (4-Dimethylamino-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

794 438 N- (4- {3- [1- (3-Dimethylamino-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

795 473 2-Bromo-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

796 446 Quinoline-2-carboxylic acid- (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -phenyl) -amide < / RTI >

797 410 2-Fluoro-N- {4- [3- (2-hydroxy-1-phenyl- ethyl) -thioureido]

Phenyl} -benzamide

798 332 2-Fluoro-N- [4- (3-isopropyl-thioureido) -phenyl] -benzamide

799 445 2-Fluoro-N- {4- [3- (1 -naphthalen-2-yl-ethyl) -thioureido] -phenyl} -

Benzamide

800 412 3-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

801 412 4-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

802 384 2-Fluoro-N- {4- [3- (1-furan-2-yl-ethyl) -thioureido] -phenyl}

Benzamide

803 395 2-Fluoro-N- {4- [3- (1-pyridin-4- yl- ethyl) -thioureido] -phenyl} -

Benzamide

804 397 2-Fluoro-N- (4- {3- [l- (1 -methyl-lH-pyrrol-

Thioureido} -phenyl) -benzamide < / RTI >

805 401 2-Fluoro-N- {4- [3- (1 -thiophen-3-yl-ethyl) -thioureido] -phenyl} -

Benzamide

806 445 N- {4- [3- (3-Chloro-4-ethoxy-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

807 459 N- {4- [3- (3-Chloro-4-propoxy-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

808 459 N- {4- [3- (3-Chloro-4-isopropoxy-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

809 473 N- {4- [3- (4-Butoxy-3-chloro-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

810 522 2-Fluoro-N- {4- [3- (3-iodo-4-methoxy-phenyl) -thioureido]

Phenyl} -benzamide

811 475 N- {4- [3- (3-Bromo-4-methoxy-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

812 520 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -2-

Iodo-benzamide

813 346 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -

Propionamide

814 286 N- [4- (3-Phenyl-thioureido) -phenyl] -acetamide

Example 815 (Method 32)

[1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2,5-dichloro-phenyl) -thioureido]

Phenyl} -amide

To the solution of 2,5-dichloroaniline (0.16 g) in tetrahydrofuran (20 mL) is added newly prepared 1,1'-thiocarbonyldiimidazole (0.20 g) and the mixture is stirred at room temperature for about 30 minutes. [1,2,3] thiadiazole-4-carboxylic acid (4-amino-phenyl) amide (0.22 g) is added to the reaction flask and the mixture is stirred for approximately 6 hours. The solvent is removed by evaporation under reduced pressure and warm acetonitrile (3 mL) is added. After 15 hours the mixture is filtered and the collected precipitate is washed with acetonitrile followed by diethyl ether and air dried to give the desired product of a white powder.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

Example M + H Compound Name

816 321 N- {4- [3- (3-Chloro-phenyl) -thioureido] -phenyl} -acetamide

817 413 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -

Benzamide

818 443 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -2-

Methoxy-benzamide

819 443 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -3-

Methoxy-benzamide

820 443 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -4-

Methoxy-benzamide

821 431 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -4-

Methoxy-benzamide

822 431 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -3-

Fluoro-benzamide

823 431 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -4-

Fluoro-benzamide

824 437 furan-2-carboxylic acid {4- [3- (3,5-dichloro-4-methoxy- phenyl)

Thioureido] -phenyl} -amide < / RTI >

825 511 {4- [3- (5-Bromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Carbamic acid hexyl ester

826 481 hexanoic acid {4- [3- (5-bromo-2,4-dimethoxy-phenyl) -thioureido]

Phenyl} -amide

827 505 N- {4- [3- (5-Bromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

828 477 furan-2-carboxylic acid {4- [3- (5-bromo-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -amide < / RTI >

829 501 N- {4- [3- (5-Bromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-

Methoxy-benzamide

830 517 N- {4- [3- (5-Bromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -4-

Methoxy-benzamide

831 395 N- {4- [3- (5-Chloro-2-ethoxy-4-methoxy-phenyl) -thioureido]

Phenyl} -acetamide

832 395 N- {4- [3- (5-Chloro-4-ethoxy-2-methoxy-phenyl) -thioureido]

Phenyl} -acetamide

833 423 N- {4- [3- (2-Butoxy-5-chloro-4-methoxy-phenyl) -thioureido]

Phenyl} -acetamide

834 423 N- {4- [3- (4-Butoxy-5-chloro-2-methoxy-phenyl) -thioureido]

Phenyl} -acetamide

835 457 N- {4- [3- (2-Benzyloxy-5-chloro-4-methoxy-phenyl) -thioureido]

Phenyl} -acetamide

836 457 N- {4- [3- (4-Benzyloxy-5-chloro-2-methoxy-phenyl) -thioureido]

Phenyl} -acetamide

837 421 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-methoxy- phenyl)

Thioureido] -phenyl} -amide < / RTI >

838 424 2- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-5-methoxy-

Phenoxy} -acetamide

839 367 N- {4- [3- (5-Chloro-2-hydroxy-4-methoxy-phenyl) -thioureido]

Phenyl} -acetamide

840 367 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido] -phenyl} -

Acetamide

841 447 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl- piperidin-

Phenyl} -thioureido) -phenyl] -acetamide < / RTI >

842 426 N- (4- {3- [3-Chloro-4- (methyl-phenyl-amino) -phenyl] -thioureido}

Phenyl) -acetamide

843 509 N- [4- (3- {4 - [(1-Benzyl-pyrrolidin-3- yl) -methyl-

Phenyl} -thioureido) -phenyl] -acetamide < / RTI >

844 418 N- (4- {3- [3-Chloro-4- (cyclopentyl-phenyl-amino) -phenyl] -

Thioureido} -phenyl) -acetamide < / RTI >

845 433 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl-pyrrolidin-

Phenyl} -thioureido) -phenyl] -acetamide < / RTI >

846 419 furan-2-carboxylic acid {4- [3- (3-chloro-4-methylsulfanyl- phenyl)

Thioureido] phenyl} -amide

847 447 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido] -phenyl} -2-

Fluorobenzamide

848 465 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido] -phenyl} -2,6-

Difluorobenzamide

849 445 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido] -phenyl}

2-fluorobenzamide

850 441 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido] -phenyl} -

2-methyl-benzamide

851 434 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-chloro-

Phenyl) -thioureido] -phenyl} -amide

852 444 N- {4- [3- (3-Chloro-4-dimethylamino-phenyl) -thioureido] -phenyl} -2-

Fluorobenzamide

853 517 [1,2,3] Thiadiazole-4-carboxylic acid [4- (3- {3-chloro-4- [methyl-

Piperidin-4-yl) -amino] -phenyl} -thioureido) -phenyl] -amide

854 579 [1,2,3] thiadiazole-4-carboxylic acid [4- (3- {4 - [(1 -benzyl- pyrrolidin-

Methyl-amino] -3-chloro-phenyl} -thioureido) -phenyl] -amide

855 527 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl- piperidin-

Phenyl} -thioureido) -phenyl] -2-fluoro-benzamide

856 435 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (5-chloro-2-methoxy-

Methylphenyl) -thioureido] -phenyl} -amide

857 589 N- [4- (3- {4 - [(1-Benzyl-pyrrolidin-3- yl) -methyl-

Phenyl} -thioureido) -phenyl] -2-fluoro-benzamide

858 501 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -3-trifluoromethyl-phenyl} -amide

859 366 2-Fluoro-N- [4- (3-phenyl-thioureido) -phenyl] -benzamide

860 338 Furan-2-carboxylic acid [4- (3-phenyl-thioureido) -phenyl] -amide

861 356 [1,2,3] thiadiazole-4-carboxylic acid [4- (3-phenyl-thioureido) -phenyl] -

amides

862 365 N- (4- {3- [3-Chloro-4- (l-hydroxy-ethyl) -phenyl] -thioureido}

Phenyl) -acetamide

863 435 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3-chloro-4- (1-

Ethyl) -phenyl} -thioureido) -phenyl] -amide

864 365 N- (4- {3- [3-Chloro-4- (2-hydroxy-ethyl) -phenyl] -thioureido}

Phenyl) -acetamide

865 445 N- (4- {3- [3-Chloro-4- (l-hydroxy-ethyl) -phenyl] -thioureido}

Phenyl) -2-fluoro-benzamide

866 417 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (1-

Thioureido} -phenyl) -amide < / RTI >

867 371 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-amino-

Thioureido] -phenyl} -amide < / RTI >

868 501 furan-2-carboxylic acid {4- [3- (3-bromo-4-trifluoromethoxy-phenyl)

Thioureido] phenyl} -amide

869 423 N- {4- [3- (3-tert-Butyl-phenyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

870 440 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-chloro-3,5-

Phenyl) -thioureido] -phenyl} -amide

974485 N- {4- [3- (1-Benzofuran-2-yl-ethyl) -thioureido] -phenyl} -2-

Trifluoromethyl-benzamide < RTI ID = 0.0 >

975 412 N- (4-Fluoro-phenyl) -4- {3- [l- (4-fluoro- phenyl)

Thioureido} -benzamide

976 446 isoquinoline-1-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -phenyl) -amide < / RTI >

977 468 isoquinoline-1-carboxylic acid {4- [3- (1-benzofuran-2-yl-ethyl)

Thioureido] -phenyl} -amide < / RTI >

978 506 isoquinoline-1-carboxylic acid (4- {3- [l- (4-bromo-phenyl)

Thioureido} -phenyl) -amide < / RTI >

979 453 isoquinoline-1-carboxylic acid (4- {3- [1- (4-cyano-phenyl)

Thioureido} -phenyl) -amide < / RTI >

980 435 Benzofuran-2-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -phenyl) -amide < / RTI >

981 457 Benzofuran-2-carboxylic acid {4- [3- (1-benzofuran-2-yl-ethyl) -thioureido]

Phenyl} -amide

982 495 Benzofuran-2-carboxylic acid (4- {3- [l- (4-bromo-phenyl)

Thioureido} -phenyl) -amide < / RTI >

983 442 Benzofuran-2-carboxylic acid (4- {3- [1- (4-cyano-phenyl)

Thioureido} -phenyl) -amide < / RTI >

984 446 isoquinoline-3-carboxylic acid (4- {3- [l- (4-fluoro- phenyl)

Thioureido} -phenyl) -amide < / RTI >

985 468 isoquinoline-3-carboxylic acid {4- [3- (1-benzofuran-2-yl-ethyl)

Thioureido] -phenyl} -amide < / RTI >

986 453 isoquinoline-3-carboxylic acid (4- {3- [1- (4-cyano-phenyl)

Thioureido} -phenyl) -amide < / RTI >

987 506 Isoquinoline-3-carboxylic acid (4- {3- [l- (4-bromo-phenyl)

Thioureido} -phenyl) -amide < / RTI >

988 446 Quinoline-3-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -phenyl) -amide < / RTI >

989 446 Quinoline-4-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -phenyl) -amide < / RTI >

6-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -

Thioureido} -phenyl) -amide < / RTI >

8-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -

Thioureido} -phenyl-amide

992 462 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -2-

Trifluoromethyl-benzamide < RTI ID = 0.0 >

993 419 2-Cyano-N- (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

994 473 N- {4- [3- (3-Chloro-4-isobutoxy-phenyl) -thioureido] -phenyl} -

Fluoro-benzamide

995 414 2-Fluoro-N- {4- [3- (3-fluoro-4-methoxy-phenyl) -thioureido]

Phenyl} -benzamide

996 475 N- (4- {3- [3-Chloro-4- (2-methoxy-ethoxy) -phenyl] thioureido}

Phenyl) -2-fluoro-benzamide

997 398 2-Fluoro-N- {4- [3- (3-fluoro-4-methyl-phenyl) -thioureido]

Phenyl} -benzamide

998 464 2-Fluoro-N- {4- [3- (4-methoxy-3-trifluoromethyl-phenyl)

Thioureido] -phenyl} -benzamide < / RTI >

999 449 N- {4- [3- (2-Amino-5-trifluoromethyl-phenyl) -thioureido] -

Phenyl} -2-fluoro-benzamide

1000 459 N- (4- {3- [1- (3-Chloro-4-methoxy-phenyl) -ethyl] -thioureido}

Phenyl) -2-fluoro-benzamide

1001 417 N- {4- [3- (5-Chloro-2-hydroxy-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

1002 435 N- {4- [3- (1-Benzofuran-2-yl-ethyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

1003 448 2-Fluoro-N- {4- [3- (4-methyl-3-trifluoromethyl- phenyl)

Thioureido] -phenyl} -benzamide < / RTI >

1004 473 (S) -N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

1005 473 N- (4- {3 - [(1 R) -1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

1006 494 2-Fluoro-N- (4- {3- [2-methoxy-4- (2,2,2- trifluoro-ethoxy)

Phenyl] -thioureido} -phenyl) -benzamide < / RTI >

1007 399 N- {4- [3- (2-Amino-5-fluoro-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

1008 502 N- (4- {3- [1- (4-Dimethylsulfamoyl-phenyl) -ethyl] -thioureido} -phenyl) -

2-Fluoro-benzamide

1009 542 2-Fluoro-N- [4- (3- {1- [4- (piperidine-1 -sulfonyl) -phenyl] -ethyl}

Thioureido) -phenyl] -benzamide < / RTI >

1010 562 N- (4- {3- [2,4-Bis- (2,2,2-trifluoro-ethoxy) -phenyl] -

Thioureido} -phenyl) -2-fluoro-benzamide

1011 409 2-Fluoro-N- {4- [3 - ((1S) -1-p-tolyl-ethyl) -thioureido] -phenyl}

Benzamide

1012 409 2-Fluoro-N- {4- [3 - ((1 R) -1-p-tolyl-ethyl) -thioureido] -phenyl}

Benzamide

1013 394 2-Fluoro-N- {4- [3 - ((1S) -1-phenyl- ethyl) -thioureido] -phenyl} -

Benzamide

(4-chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

1015 429 N- (4- {3 - [(1S) -1- (4-Chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-

Fluoro-benzamide

1016 394 2-Fluoro-N- {4- [3 - ((1 R) -1-phenyl- ethyl) -thioureido] -phenyl} -

Benzamide

1017 432 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -phenyl) -2-

Methoxy-benzamide

1018 447 N- {4- [3- (1-Benzofuran-2-yl-ethyl) -thioureido] -phenyl} -2-methoxy-

Benzamide

1019 485 N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-

Methoxy-benzamide

1020 419 3-Cyano-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

1021 462 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -4-

Trifluoromethyl-benzamide < RTI ID = 0.0 >

1022 419 4-Cyano-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -benzamide

1023 469 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

2,3,5,6-tetramethylphenyl) -benzamide

1024 480 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -2,5-dimethoxy-

Phenyl) -2-fluoro-benzamide

1025 473 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

2,5-dimethoxy-phenyl) -benzamide < / RTI >

1026 530 N- {3,5-Dichloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl)

Thioureido] -phenyl} -2-fluoro-benzamide

1027 447 N- (3-Chloro-4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -2-fluoro-benzamide

1028 447 2,3,4,5-Tetrafluoro-N- (4- {3- [1- (4-fluoro-phenyl)

Thioureido} -3-methyl-phenyl) -benzamide

1029 462 2,4,5-Trifluoro-N- (4- {3- [1- (4-fluoro-phenyl)

Thioureido} -3-methyl-phenyl) -benzamide

1030 427 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

3-methyl-phenyl) -benzamide < / RTI >

1031 457 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}

Methoxy-5-methyl-phenyl) -benzamide < / RTI >

1032 443 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

3-methoxy-phenyl) -benzamide < / RTI >

1033 570 N- (2,6-dibromo-4- {3- [l- (4-fluoro-phenyl)

Thioureido} -phenyl) -2-fluoro-benzamide

1034 480 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

2-trifluoromethyl-phenyl) -benzamide < / RTI >

1035 541 N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2-

Trifluoromethyl-phenyl) -2-fluoro-benzamide < / RTI >

1036 487 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -2-

Trifluoromethyl-phenyl) -2-fluoro-benzamide < / RTI >

1037 503 N- {4- [3- (1-Benzofuran-2-yl-ethyl) -thioureido] -2-

Trifluoromethyl-phenyl} -2-fluoro-benzamide < / RTI >

1038 447 N- (2-Chloro-4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -2-fluoro-benzamide

1039 454 N- (2-Chloro-4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido}

Phenyl) -2-fluoro-benzamide

1040 437 N- (2-Cyano-4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -2-fluoro-benzamide

1041 498 N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2-cyano-

Phenyl) -2-fluoro-benzamide

1042 445 N- (2-Cyano-4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido}

Phenyl) -2-fluoro-benzamide

1043 460 N- {4- [3- (1-Benzofuran-2-yl-ethyl) -thioureido] -2-cyano-

2-Fluoro-benzamide

1044 517 N- (2-Benzoyl-4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -2-fluoro-benzamide

1045 427 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}

2-methyl-phenyl) -benzamide < / RTI >

1046 487 N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2-methyl-

2-Fluoro-benzamide

1047 434 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -2- methyl-

2-Fluoro-benzamide

2-yl-ethyl) -thioureido] -2-methyl-phenyl} -2- (4-methoxy-

Fluoro-benzamide

1049 456 N- (2-Dimethylamino-4- {3- [l- (4-fluoro-phenyl)

Thioureido} -phenyl) -2-fluoro-benzamide

1050 526 N- (2-Benzyloxy-4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido} -2-

Fluoro-benzamide

1051 519 N- (2-Benzyloxy-4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -2-fluoro-benzamide

1052 603 N- [4- {3- [l- (4-Bromo-phenyl) -ethyl] -thioureido} -2- (2-

4-yl-ethoxy) phenyl] -2-fluoro-benzamide

1053 603 N- [4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2- (2-

4-yl-ethoxy) phenyl] -2-fluoro-benzamide

1054 542 2-Fluoro-N- [4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

2- (2-morpholin-4-yl-ethoxy) phenyl] -benzamide

1055 485 N- (2-Butoxy-4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -2-fluoro-benzamide

1056 492 N- (2-Butoxy-4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido} -phenyl) -

2-Fluoro-benzamide

1057 589 N- [4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2-

Amino-ethoxy) phenyl] -2-fluoro-benzamide

4- {3- [1- (4-fluoro-phenyl) -ethyl] -

Thioureido} -phenyl) -2-fluoro-benzamide

1059 589 N- [4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2-

Amino-ethoxy) phenyl] -2-fluoro-benzamide

1060 457 N- (2-Ethoxy-4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}

Phenyl) -2-fluoro-benzamide

1061 464 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -2-ethoxy-

Phenyl) -2-fluoro-benzamide

1062 468 2-Fluoro-N- [4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

2- (2-Nitrilo-ethoxy) -phenyl] -benzamide

1063 475 N- [4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -2- (2-

Ethoxy) -phenyl] -2-fluoro-benzamide

1064 443 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}

2-methoxy-phenyl) -benzamide < / RTI >

1065 489 2-Fluoro-N- (5- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}

Biphenyl-2-yl) -benzamide

1066 514 isoquinoline-1-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -2-trifluoromethyl-phenyl) -amide

1067 503 Benzofuran-2-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -2-trifluoromethyl-phenyl) -amide

1068 514 isoquinoline-3-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -2-trifluoromethyl-phenyl) -amide

1069 471 Preparation of isoquinoline-1-carboxylic acid (2-cyano-4- {3- [1- (4-

Ethyl] -thioureido} -phenyl) -amide

1070 460 Benzofuran-2-carboxylic acid (2- cyano-4- {3- [l- (4-fluoro-

Thioureido} -phenyl) -amide < / RTI >

1071 471 isoquinoline-3-carboxylic acid (2-cyano-4- {3- [1- (4-fluoro-

Ethyl] -thioureido} -phenyl) -amide

1072 460 Isoquinoline-1-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -2-methyl-phenyl) -amide

1073 449 Benzofuran-2-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -2-methyl-phenyl) -amide

1074 460 Isoquinoline-3-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -2-methyl-phenyl) -amide

1075 396 Pyrazine-2-carboxylic acid (4- {3- [1- (4-fluoro-phenyl)

Thioureido} -phenyl) -amide < / RTI >

1076 401 Thiophene-2-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)

Thioureido} -phenyl) -amide < / RTI >

1077 401 Thiophene-3-carboxylic acid (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thiourea

Yl} -phenyl) -amide

1078 500 2-Isopropyl-thiazole-4-carboxylic acid {4- [3- (4-chloro-3-

Methyl-phenyl) -thioureido] -phenyl} -amide

1079 466 2-Isopropyl-thiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl)

Thioureido] -phenyl} -amide < / RTI >

1080 466 2-Isopropyl-thiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)

Thioureido] -phenyl} -amide < / RTI >

1081 534 2-Isopropyl-thiazole-4-carboxylic acid {4- [3- (3,5-bis-trifluoro

Methyl-phenyl) -thioureido] -phenyl} -amide

1082 480 2-Butyl-thiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)

Iso] -phenyl} -amide

1083 514 2-Butyl-thiazole-4-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl-

Phenyl) -thioureido] -phenyl} -amide

1084 480 2-Butyl-thiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl)

Iso] -phenyl} -amide

1085 548 2-Butyl-thiazole-4-carboxylic acid {4- [3- (3,5-bis- trifluoromethyl-

Phenyl) -thioureido] -phenyl} -amide

1086 438 2-Methyl-thiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl)

Iso] -phenyl} -amide

1087 438 2-Methyl-thiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)

Iso] -phenyl} -amide

1088 505 2-Methyl-thiazole-4-carboxylic acid {4- [3- (3,5-bis- trifluoromethyl-

Phenyl) -thioureido] -phenyl} -amide

1089 534 2-Phenyl-thiazole-4-carboxylic acid {4- [3- (4-chloro-3- trifluoromethyl-

Phenyl) -thioureido] -phenyl} -amide

1090 500 2-Phenyl-thiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl)

Iso] -phenyl} -amide

1091 500 2-Phenyl-thiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)

Iso] -phenyl} -amide

1092 568 2-Phenylthiazole-4-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-

Phenyl) -thioureido] -phenyl} -amide

1093 401 2-Fluoro-N- {4- [3- (1 -thiazol-2-yl-ethyl) -thioureido] -phenyl} -

Benzamide

1094 588 2-Fluoro-N- [4- (3- {1- [1- (toluene-4-sulfonyl) -lH- indol-

Ethyl} -thioureido) -phenyl] -benzamide < / RTI >

1095 446 2-Fluoro-N- {4- [3- (l-quinolin-2-yl-ethyl) -thioureido] -phenyl} -

Benzamide

1096 446 2-Fluoro-N- {4- [3- (l-quinolin-4-yl-ethyl) -thioureido] -phenyl}

Benzamide

1097 446 2-Fluoro-N- {4- [3- (1-isoquinolin-3-yl-ethyl) -thioureido]

Phenyl} -benzamide

1098 446 2-Fluoro-N- {4- [3- (1-isoquinolin-1-yl-ethyl) -thioureido]

Phenyl} -benzamide

1099 446 2-Fluoro-N- {4- [3- (l-quinolin-6-yl-ethyl) -thioureido] -phenyl} -

Benzamide

1100 446 2-Fluoro-N- {4- [3- (l-quinolin-3-yl-ethyl) -thioureido] -phenyl}

Benzamide

1101 413 2-Methoxy-N- {4- [3- (1 -thiophen-3-yl-ethyl) -thioureido] -phenyl}

Benzamide

Example 871 (Method 33)

[1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro-phenyl) -thioureido]

Phenyl} -amide

To a solution of 3,5-dichloroaniline (0.16 g) in tetrahydrofuran (20 mL) was added 1,1'-thiocarbonyl-di- (1,2,4) -thiazole (0.20 g) And the mixture is stirred at room temperature for approximately 30 minutes. [1,2,3] -thiadiazole-4-carboxylic acid (4-amino-phenyl) amide (0.22 g) is added to the reaction flask and the mixture is stirred for approximately 6 hours. The solvent is removed by evaporation under reduced pressure and warm acetonitrile (3 mL) is added. After 15 h the mixture is filtered and the collected precipitate is washed with acetonitrile followed by diethyl ether and air dried to give the desired product of a white powder. [M + H] < / RTI > 424.

Using the above procedure and the appropriate starting materials the following compounds were prepared:

Example M + H Compound name

872 465 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -3-

Fluoro-benzamide

873 467 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -2-

Methoxy-benzamide

874 465 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -2-

Fluoro-benzamide

875 477 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -3-

Methoxy-benzamide

876 399 N- {4- [3- (3,5-Dichloro-2-methoxy-4-methyl-phenyl) -thioureido]

Phenyl} -acetamide

877 365 N- {4- [3- (3-Chloro-4-methoxy-5-methyl-phenyl) -thioureido] -phenyl} -

Acetamide

878 331 N- {4- [3- (2-Nitro-phenyl) -thioureido] -phenyl} -acetamide

879 331 N- {4- [3- (4-Nitro-phenyl) -thioureido] -phenyl} -acetamide

880 477 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -4-

Methoxy-benzamide

881 351 N- {4- [3- (2-Chloro-5-methoxy-phenyl) -thioureido] -phenyl}

mid

882 428 2- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-

Glacial} -acetamide

883 443 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-

} -Acetic acid

884 457 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-

Yl} -acetic acid ethyl ester

885 447 N- {4- [3- (3,5-Dichloro-4-phenoxy-phenyl) -thioureido] -phenyl}

Cetamide

886 410 N- (4- {3- [3,5-Dichloro-4- (2-nitrilo-ethoxy) -phenyl] -thiourea

Yl} -phenyl) -acetamide < / RTI >

887 485 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-

Yl} acetic acid tert-butyl ester

888 469 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro-

Yl-phenyl) -thioureido] -phenyl} -amide

889 335 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -phenyl} -acetamide

890 335 N- {4- [3- (5-Chloro-2-methyl-phenyl) -thioureido] -phenyl}

De

891 703 N- {4- [3- (4- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-

Phenyldisulfanyl} -3-chloro-phenyl) -thioureido] -phenyl} -acetamide

892 369 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -acetic acid

Tamide

893 598 N- {4- [3- (3,5-Diiodo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Acetamide

894 504 N- {4- [3- (3,5-Dibromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -

Acetamide

895 317 N- {4- [3- (6-Methoxy-pyridin-3-yl) -thioureido] -phenyl} -acetamide

896 347 N- {4- [3- (2,6-Dimethoxy-pyridin-3-yl) -thioureido] -phenyl}

mid

897 457 Acetic acid 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-

Chloro-phenoxy} -ethyl ester

898 365 4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-benzoic acid

899 346 N- {4- [3- (3-Chloro-4-cyano-phenyl) -thioureido] -phenyl} -acetamide

900 512 N- (4- {3- [5-Chloro-2- (4-chloro-phenoxy) -4-pyrrol-

Ureido} -phenyl) -acetamide < / RTI >

901 355 N- {4- [3- (3,4-Dichloro-phenyl) -thioureido] -phenyl} -acetamide

902 339 N- {4- [3- (3-Chloro-4-fluoro-phenyl) -thioureido] -phenyl}

mid

903 447 N- {4- [3- (3-Chloro-4-iodo-phenyl) -thioureido] -phenyl}

De

904 400 N- {4- [3- (4-Bromo-3-chloro-phenyl) -thioureido] -phenyl}

De

905 424 N- [4- (3- {4- [Bis- (2-hydroxy-ethyl) -amino] -3-chloro-phenyl}

≪ RTI ID = 0.0 > oureido) -phenyl] -acetamide &

906 434 N- (4- {3- [3-Chloro-4- (hexyl-methyl-amino) -phenyl] -thioureido}

Yl) -acetamide

907 406 N- (4- {3- [3-Chloro-4- (isobutyl-methyl-amino) -phenyl] -thiourea

Yl} -phenyl) -acetamide < / RTI >

908 389 N- {4- [3- (3-Chloro-4-trifluoromethyl-phenyl) -thioureido] -phe

Yl} -acetamide

909 441 furan-2-carboxylic acid {4- [3- (3-chloro-4-trifluoromethyl- phenyl)

Ureido] -phenyl} -amide

910 459 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-trifluoromethyl-

Yl-phenyl) -thioureido] -phenyl} -amide

911 469 N- {4- [3- (3-Chloro-4-trifluoromethyl-phenyl) -thioureido] -phe

Yl} -2-fluoro-benzamide < / RTI >

912 435 N- {4- [3- (3,4-Dichloro-phenyl) -thioureido] -phenyl} -2-fluoro-

Zeamide

913 407 furan-2-carboxylic acid {4- [3- (3,4-dichloro-phenyl) -thioureido] -phenyl}

-amides

914 425 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)

Yl] -phenyl} -amide < / RTI >

915 480 N- {4- [3- (4-Bromo-3-chloro-phenyl) -thioureido] -phenyl} -2-

Benzamide

916 527 N- {4- [3- (3-Chloro-4-iodo-phenyl) -thioureido] -phenyl} -2-fluoro

Benzamide

917 452 Furan-2-carboxylic acid {4- [3- (4-bromo-3-chloro-phenyl) -thioureido]

Phenyl} -amide

918 499 furan-2-carboxylic acid {4- [3- (3-chloro-4-iodo-phenyl) -thioureido]

Phenyl} -amide

919 391 Furan-2-carboxylic acid {4- [3- (3-chloro-4-fluoro-phenyl) -thiourea

Iso] -phenyl} -amide

920 470 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-bromo-3-

Thioureido] -phenyl} -amide < / RTI >

921 517 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-

Thioureido] -phenyl} -amide < / RTI >

922 419 N- {4- [3- (3-Chloro-4-fluoro-phenyl) -thioureido] -phenyl} -2-

Oro-benzamide

923 409 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-fluoro-

Thioureido] -phenyl} -amide < / RTI >

924 388 N- {4- [3- (3-Chloro-4-isoxazol-5-yl-phenyl) -thioureido] -phenyl} -

Acetamide

925 387 N- (4- {3- [3-Chloro-4- (lH-pyrazol-3-yl) -phenyl] -thioureido}

Yl) -acetamide

926 355 N- {4- [3- (2,3-Dichloro-phenyl) -thioureido] -phenyl} -acetamide

927 435 N- {4- [3- (2,3-Dichloro-phenyl) -thioureido] -phenyl} -2-fluoro-

Zeamide

928 407 furan-2-carboxylic acid {4- [3- (2,3-dichloro-phenyl) -thioureido] -phenyl} -

amides

929 425 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2,3-dichloro- phenyl)

Yl] -phenyl} -amide < / RTI >

930 355 N- {4- [3- (2,5-Dichloro-phenyl) -thioureido] -phenyl} -acetamide

931 435 N- {4- [3- (2,5-Dichloro-phenyl) -thioureido] -phenyl} -2-fluoro-

Zeamide

932 407 furan-2-carboxylic acid {4- [3- (2,5-dichloro-phenyl) -thioureido] -phenyl} -

amides

933 355 N- {4- [3- (3,5-Dichloro-phenyl) -thioureido] -phenyl} -acetamide

934 435 N- {4- [3- (3,5-Dichloro-phenyl) -thioureido] -phenyl} -2-fluoro-

Zeamide

935 407 furan-2-carboxylic acid {4- [3- (3,5-dichloro-phenyl) -thioureido] -phenyl} -

amides

936 390 N- {4- [3- (3,4,5-Trichloro-phenyl) -thioureido] -phenyl} -acetamide

937 470 2-Fluoro-N- {4- [3- (3,4,5-trichloro-phenyl) -thioureido]

Phenyl} -benzamide

938 442 furan-2-carboxylic acid {4- [3- (3,4,5-trichloro-phenyl) -thioureido]

Phenyl} -amide

939 460 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,4,5-trichloro-phenyl)

Oureido] -phenyl} -amide < / RTI >

940 458 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-isoxazol-

Phenyl) -thioureido] -phenyl} -amide

941 457 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3-chloro-4- (lH-

Yl) -phenyl] -thioureido} -phenyl) -amide

942 391 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-chloro-phenyl)

Iso] -phenyl} -amide

943 373 Furan-2-carboxylic acid {4- [3- (3-chloro-phenyl) -thioureido] -phenyl}

mid

944 401 N- {4- [3- (3-Chloro-phenyl) -thioureido] -phenyl} -2-fluoro-

mid

945 373 Furan-2-carboxylic acid {4- [3- (4-chloro-phenyl) -thioureido] -phenyl}

mid

946 401 N- {4- [3- (4-Chloro-phenyl) -thioureido] -phenyl} -2-fluoro-

mid

947 391 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-chloro-phenyl)

Iso] -phenyl} -amide

948 401 N- {4- [3- (2-Chloro-phenyl) -thioureido] -phenyl} -2-fluoro-

mid

949 396 3- (3- {4- [(furan-2-carbonyl) -amino] -phenyl} -thioureido) -benzoic acid

Methyl ester

950 424 3- {3- [4- (2-Fluoro-benzoylamino) -phenyl] -thioureido} -benzoic acid

Methyl ester

951 414 3- (3- {4 - [([[1,2,3] thiadiazole-4-carbonyl) -amino] -phenyl} -thiourea

Iso) -benzoic acid methyl ester

952 409 N- [4 - [[[[3- (aminocarbonyl) phenyl] amino] thioxomethyl]

2-Fluoro-benzamide

953 373 Furan-2-carboxylic acid {4- [3- (2-chloro-phenyl) -thioureido] -phenyl}

mid

954 381 furan-2-carboxylic acid {4- [3- (3-carbamoyl-phenyl) -thioureido] -phenyl} -

amides

955 399 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-carbamoyl-phenyl) -thiourea

Iso] -phenyl} -amide

956 391 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-chloro-phenyl)

Iso] -phenyl} -amide

957 356 Furan-2-carboxylic acid {4- [3- (3-fluoro-phenyl) -thioureido] -phenyl} -

amides

958 383 Furan-2-carboxylic acid {4- [3- (3-nitro-phenyl) -thioureido] -phenyl}

mid

959 411 2-Fluoro-N- {4- [3- (3-nitro-phenyl) -thioureido] -phenyl}

mid

960 422 Furan-2-carboxylic acid {4- [3- (3-trifluoromethoxy-phenyl) -thiourea

Iso] -phenyl} -amide

961 450 2-Fluoro-N- {4- [3- (3-trifluoromethoxy-phenyl) -thioureido] -

Phenyl} -benzamide

962 384 2-Fluoro-N- {4- [3- (3-fluoro-phenyl) -thioureido] -phenyl}

amides

963 410 3- {3- [4- (2-Fluoro-benzoylamino) -phenyl] -thioureido} -benzoic acid

964 382 3- (3- {4- [(furan-2-carbonyl) -amino] -phenyl} -thioureido) -benzoic acid

965 408 N- {4- [3- (3-Acetyl-phenyl) -thioureido] -phenyl} -2-fluoro-

mid

966 502 N- {4- [3- (3-Butylsulfamoyl-phenyl) -thioureido] -phenyl} -2-fluoro-

Benzamide

967 380 Furan-2-carboxylic acid {4- [3- (3-acetyl-phenyl) -thioureido] -phenyl}

mid

968 447 furan-2-carboxylic acid (4- {3- [3- (2-hydroxy-ethanesulfonyl) -phenyl] -thio

Yl-phenyl) -amide < / RTI >

969 475 2-Fluoro-N- (4- {3- [3- (2-hydroxy-ethanesulfonyl) -phenyl] -thiourea

Iso} -phenyl) -benzamide < / RTI >

970 474 furan-2-carboxylic acid {4- [3- (3-butylsulfamoyl-phenyl) -thioureido] -phe

Yl} -amide

Example 971 (method 57)

1- (4-Fluoro-phenyl) -2-methyl-propan-

To a solution of 4-fluorobenzaldehyde (2.0 g) in diethyl ether (40 mL) at 0 ° C is added isopropyl magnesium bromide (2.0 M, 9.6 mL) with stirring. After 1.5 h, the reaction is quenched with aqueous ammonium chloride and extracted with diethyl ether. The diethyl ether extract is washed with saturated sodium chloride, dried over anhydrous magnesium sulfate, filtered and evaporated to give an oil. Purify the oil by silica gel chromatography eluting with 10% dichloromethane-hexane to give the product (1.76 g) of a yellow oil.

Example 972 (Method 58)

1- (4-Fluoro-phenyl) -2-methyl-propan-1-

To a solution of 1- (4-fluoro-phenyl) -2-methyl-propan-1-ol (1.6 g) in acetone (10 mL) at 0 ° C was added Jones ture (20 mL) with stirring. After 10 minutes isopropyl alcohol is added to destroy excess Jones tense. Diethyl ether is added followed by anhydrous magnesium and the mixture is filtered and evaporated to give the product (1.2 g) of a yellow oil.

Example 973 (Method 59)

3-Dimethylamino-5-trifluoromethyl-benzonitrile

To a solution of 3-dimethylamino-5-trifluoromethylbromobenzene (7.3 g) in N, N-dimethylformamide (20 mL) was added primary copper cyanide (2.7 g) and the reaction was refluxed for 12 h Lt; / RTI > Dilute the reaction with water (40 mL) and add dichloromethane. The dichloromethane fraction is washed with concentrated ammonium hydroxide followed by water. The solution was dried over anhydrous magnesium sulfate, filtered and concentrated to give a yellow solid which was recrystallized from hexane to give a yellow solid (4.7 g).

The compounds were tested for their activity as a Huff's virus inhibitor.

Human cytomegalovirus

Yield analysis. A monolayer culture of human foreskin fibroblasts is infected with HCMV wild type in the presence of inhibitory compounds (various concentrations), typically at an infection duplication of 0.2. On the third day after infection, the virus was collected from the cultured human phallic fibroblast 12-well plate and the concentration was measured to evaluate the total virus (i.e., virus yield) produced in the culture solution (performed in the absence of inhibitor). Plaque is quantified at 2 weeks after infection. The presence of an inhibitor of HCMV is confirmed by a decrease in the viral yield titer in the presence of the compound as compared to the titer under the absence of the compound. In this assay, the relative anti-HCMV activity of the inhibitor is typically measured by calculating the IC ₅₀ or IC ₉₀ value, the amount required to reduce the virus yield to 50% or 90%, respectively. Table I describes IC ₅₀ data for compounds tested against HCMV.

Microtiter plate analysis . To the 96-well culture medium of human foreskin fibroblasts in the presence of the inhibitor compound was added the HCMV recombinant mutant virus (the genome of which is the prokaryotic beta-glucuronidase gene (Jefferson, RA, SMBurgess, and D. Hirsh. 1986. Beta-glucuronidase from Escherichia coli as a gene fusion marker, Proc Natl Acad Sci USA 83: 8447-8451) and its expression is controlled by a viral promoter. An example of such a virus is RV145 (Jones, TR, VP Muzithras, and Y. Gluzman, 1991. Replacement mutagenesis of the human cytomegalovirus genome: US10 and US11 gene products are nonessential.J Virol. 65: 5860-5872). Since it is under the control of a viral promoter, beta-glucuronidase expression is an indirect indicator of the growth and replication of HCMV in this assay. Infected cell lysates were prepared at 96 hours post infection (using 50 mM sodium phosphate [pH 7.0] containing 0.1% Triton X-100 and 0.1% sarkosyl) and analyzed by colorimetry or spectrophotometry on a microphotometer Beta-glucuronidase activity is assessed using a substrate for an enzyme that produces a product whose fluorescence can be measured. Examples of such substrates are p-nitrophenyl-beta-D-glucuronide and methylumbelliferyl glucuronide, respectively. The presence of the antiviral compound is known by the reduced expression of the beta-glucuronidase gene present in the HCMV genome compared to the absence of the inhibitor. Thus, the generation of chromophore or fluorophore in this assay is correspondingly reduced. The IC _{50 values} of the inhibitor compounds are assessed using data from these assays performed with varying amounts of inhibitor compounds.

HSV antiviral (ELISA) analysis

100 ㎕ tissue culture DMEM (Dulbecco's modified Eagle media) per 3.5 x 10 Ting ⁴ play a 96-well tissue culture medium Vero cells (ATCC # CCL-81) on the plate of cells, and each well 2% state bovine serum (FBS) . Cells were either not treated or treated with the test compound (multiple concentrations) or the reference standard drug control 30 minutes before incubation (5% CO ₂ ) at 37 ° C and 30 minutes before infection with HSV-1 . After incubation at 37 ° C (5% CO ₂ ) for approximately 24 hours post infection, cells are fixed for ELISA analysis. The primary antibody is a rat anti-HSV glycoprotein D monoclonal primary antibody and the secondary antibody is a goat anti-mouse IgG linked to beta -galactosidase. After adding methylumbelliferyl-beta-D-galactoside (Sigma # M1633) substrate onto a microfluorescent analyzer (365 nm in the excited state and 450 nm in the emissive state), 4-methylumbelliferone fluorescence The cleavage product is quantitated to evaluate the activity of β-galactosidase to measure the degree of viral replication. The antiviral activity (IC ₅₀ ) of the test compound is measured by comparing the fluorescence obtained in the presence of the compound with the fluorescence obtained in the absence of the compound. The data are shown in Table 1.

VZV antiviral (ELISA) analysis

For stock VZV generated to be used for analysis, VZV strain Ellen (ATCC # VR-1367) using the infecting road (0.1) overlapping a lower human foreskin fibroblasts (HFF), incubated overnight in 5% CO ₂ and 37 ℃ do. After overnight incubation, a mixture of uninfected cells and VZV-infected HFF infected cells was harvested and resuspended in 96-well plates (3.5 x 10 ⁴ cells in 100 μl DMEM supplemented with 2% FBS) containing the test compound or reference standard drug control, (In 100 [mu] L DMEM supplemented with 2% FBS per well). The cells are incubated for 3 days at 5% CO ₂ and 37 ° C and then fixed for ELISA analysis. The primary antibody is a rat anti-VZV glycoprotein II monoclonal antibody (Applied Biosystems, Inc. # 13-145-100) and the secondary antibody is a goat anti-mouse IgG linked to beta -galactosidase. After adding methylumbelliferyl-beta-D-galactoside (Sigma # M1633) substrate onto a microfluorescent analyzer (365 nm in the excited state and 450 nm in the emissive state), 4-methylumbelliferone fluorescence The cleavage product is quantitated to evaluate the activity of β-galactosidase to measure the degree of viral replication. The antiviral activity (IC ₅₀ ) of the test compound is measured by comparing the fluorescence obtained in the presence of the compound with the fluorescence obtained in the absence of the compound. The data are shown in Table I.

Table I lists the IC ₅₀ data of the compounds tested against the Houghs virus.

Thus, in accordance with the present invention, the compounds of the present invention can be administered to patients suffering from VZV in an amount effective to inhibit the virus. The compounds of the present invention are useful for attenuating or eliminating VZV infection symptoms in mammals, including humans.

The compounds of the present invention may be administered to a patient without or in association with conventional pharmaceutical carriers.

Applicable solid carriers may include one or more substances which may act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, lubricants, compression aids, binders or tablet-disintegrating or encapsulating materials. In powders, the carrier is a finely divided solid present in admixture with the finely divided active component. In tablets, the active ingredient is mixed with the carrier having the necessary compressibility in suitable proportions and compressed to the desired shape and size. The powders and tablets preferably contain up to 99% of the active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugar, lactose, dextrin, starch, gelatin, cellulose, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidine, .

Liquid carriers can be used to prepare solutions, suspensions, emulsions, syrups and elixirs. The active ingredient of the present invention may be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of the two, or a pharmaceutically acceptable oil or fat. The liquid carrier may contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavors, suspensions, thickeners, pigments, viscosity modifiers, stabilizers or osmo-regulators. Suitable examples of liquid carriers for oral and parenteral administration include water (especially those containing such additives, such as cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (monohydric and polyhydric alcohols, e.g., For example, glycols, and derivatives thereof, and oils (e.g., fractionated coconut oil and arachis oil). For parenteral administration, the carrier may also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid carriers are used in sterile liquid compositions for parenteral administration.

Liquid pharmaceutical compositions that are sterile solutions or suspensions may be used, for example, for intramuscular, intraperitoneal, or subcutaneous injection. The sterile solution may also be administered intravenously. Oral administration can be in the form of a liquid or solid composition.

Preferably, the pharmaceutical composition is in unit dosage form, for example a tablet or capsule. In this form, the composition is subdivided into unit doses containing the appropriate amount of active ingredient; The unit dosage form can be a package composition, for example, packet powder, vial, ampoule, pre-filled syringe or liquid containing fresh shade. The unit dosage form may be, for example, a capsule or tablet itself, or it may be a suitable number of such compositions in packaged form.

Effective dosages for treatment used in the treatment of CMV infection are subjectively determined by the primary care physician. The relevant variables include the patient's health status, age and weight. A novel method of the invention for treating CMV infection comprises administering to a subject, including a human, an effective amount of at least one compound of formula I or a non-toxic pharmaceutically acceptable salt thereof. The compounds may be administered orally, rectally, parenterally or topically to the skin and mucous membranes. The usual daily dosage will depend on the particular compound, the method of treatment and the condition of the patient. The usual daily dosage is 0.01-1000 mg / Kg, preferably 0.5-500 mg / Kg for oral administration, 0.1-100 mg / Kg for parenteral administration, preferably 0.5-50 mg / Kg.

Claims (20)

A compound of formula (I); Or a pharmaceutically acceptable salt thereof: Formula I In this formula, R ₁ -R ₅ is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, 10 carbon atoms, cycloalkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, _{halogen, -CN, -NO 2, -CO 2} R 6, -COR 6, -OR 6, -SR 6 _{, -SOR 6, -SO 2 R 6} , -CONR 7 R 8, -NR 6 n (R 7 R 8), -N (R 7 R 8) or _{WY- (CH 2) n -Z (} R 1 - And at least one of R < ₅ > is not hydrogen; R ₂ and R ₃ or R ₃ and R ₄ together form a 3- to 7-membered heterocycloalkyl or a 3- to 7-membered heteroaryl; R ₆ and R ₇ are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl; R ₈ is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, 3 to 10 membered heterocycloalkyl, aryl or heteroaryl , R ₇ and R _{8 taken} together may form a 3- to 7-membered heterocycloalkyl; R ₉ -R ₁₂ are independently hydrogen, alkyl of 1 to 4 carbon atoms, perhaloalkyl of 1 to 4 carbon atoms, halogen, alkoxy of 1 to 4 carbon atoms, or cyano, or R ₉ and R ₁₀ or R ₁₁ and R _{12 taken} together may form an aryl of 5 to 7 carbon atoms; Provided that at least one of R < _9-12 > is not hydrogen; W is O, NR < ₆ > or absent; Y is - (CO) - or - (CO ₂ ), or is absent; Z is alkyl of 1 to 4 carbon _{atoms, -CN, -CO 2 R 6,} COR 6, -CONR 7 R 8, -OCOR 6, -NR 6 COR 7, -OCONR 6, -OR 6, -SR 6 , -SOR ₆ , -SO ₂ R ₆ , SR ₆ N (R ₇ R ₈ ), -N (R ₇ R ₈ ) or phenyl; G is monocyclic heteroaryl; X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J; J is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl; n is an integer of 1 to 6; The compound of claim 1, wherein R ₁ -R ₅ are independently hydrogen, alkyl of 1 to 6 carbon atoms, halogen, perhaloalkyl of 1 to 6 carbon atoms, OR ₆ or N (R ₇ R ₈ ) . The compound according to claim ₁ , wherein R ₁ , R ₂ and R ₃ are hydrogen and R ₄ and R ₅ are independently halogen or CF ₃ . The compound according to claim ₁ , wherein R ₁ , R ₂ and R ₄ are hydrogen and R ₃ and R ₅ are independently halogen or CF ₃ . 2. The compound according to claim 1, wherein G is thiazolyl, thiadiazolyl, oxazolyl or furyl. 2. The compound of claim 1, wherein G is furyl. The compound according to claim 1, wherein R ₉ -R ₁₂ are independently hydrogen, halogen, methyl, methoxy and cyano. 2. The compound according to claim 1, wherein X is a bond. 2. The compound of claim 1, wherein X is straight chain alkyl. 2. The compound of claim 1, wherein X is alkyl of 1 to 4 carbon atoms. The method according to claim 1, 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2,5-dimethoxy-phenyl} 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -3-trifluoromethyl-phenyl} 2-carboxylic acid {3-chloro-4- [3- (5-chloro-2,4-dimethoxy- phenyl) -thioureido] -phenyl} 2-carboxylic acid {5-chloro-4- [3- (5-chloro-2,4-dimethoxy- phenyl) -thioureido] -2- 2-carboxylic acid {5-chloro-4- [3- (5-chloro-2,4- dimethoxy- phenyl) -thioureido] -2-hydroxy- phenyl} 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -3- cyano- phenyl} 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -3-methyl- phenyl} 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy- 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -3-methoxy-phenyl} 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2-trifluoromethyl- phenyl} 2-carboxylic acid {2-chloro-4- [3- (5-chloro-2,4-dimethoxy- phenyl) -thioureido] -phenyl} 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2- cyano- phenyl} Thioureido] -2 - [(furan-2-carbonyl) -amino] -benzoic acid, 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2-phenylcarbamoyl- 2-carboxylic acid {2-benzoyl-4- [3- (5-chloro-2,4-dimethoxy- phenyl) -thioureido] -phenyl} 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy- phenyl) -thioureido] -2-methyl- phenyl} 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -naphthalen- 1- yl} -amide, and 2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy-phenyl} -amide and their pharmacological salt. A compound of formula (I): or a pharmaceutically acceptable salt thereof; And a pharmaceutically acceptable carrier or diluent. Formula I In this formula, R ₁ -R ₅ is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, 10 carbon atoms, cycloalkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, _{halogen, -CN, -NO 2, -CO 2} R 6, -COR 6, -OR 6, -SR 6 _{, -SOR 6, -SO 2 R 6} , -CONR 7 R 8, -NR 6 n (R 7 R 8), -N (R 7 R 8) or _{WY- (CH 2) n -Z (} R 1 - And at least one of R < ₅ > is not hydrogen; R ₂ and R ₃ or R ₃ and R ₄ together form a 3- to 7-membered heterocycloalkyl or a 3- to 7-membered heteroaryl; R ₆ and R ₇ are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl; Monocyclic R ₈ is selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, 3 to 10 membered heterocycloalkyl, Lt; / RTI > R ₇ and R _{8 taken} together may form a 3- to 7-membered heterocycloalkyl; R ₉ -R ₁₂ are independently hydrogen, alkyl of 1 to 4 carbon atoms, perhaloalkyl of 1 to 4 carbon atoms, halogen, alkoxy of 1 to 4 carbon atoms, or cyano, or R ₉ and R ₁₀ or R ₁₁ and R _{12 taken} together may form an aryl of 5 to 7 carbon atoms; Provided that at least one of R < _9-12 > is not hydrogen; W is O, NR < ₆ > or absent; Y is - (CO) - or - (CO ₂ ), or is absent; Z is alkyl of 1 to 4 carbon _{atoms, -CN, -CO 2 R 6,} COR 6, -CONR 7 R 8, -OCOR 6, -NR 6 COR 7, -OCONR 6, -OR 6, -SR 6 , -SOR ₆ , -SO ₂ R ₆ , SR ₆ N (R ₇ R ₈ ), -N (R ₇ R ₈ ) or phenyl; G is monocyclic heteroaryl; X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J; J is alkyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl; n is an integer of 1 to 6; A method of inhibiting the replication of a Huff's virus, comprising contacting a compound of formula (I), or a pharmaceutically acceptable salt thereof, with a Huff's virus: Formula I In this formula, R ₁ -R ₅ is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, 10 carbon atoms, cycloalkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, _{halogen, -CN, -NO 2, -CO 2} R 6, -COR 6, -OR 6, -SR 6 _{, -SOR 6, -SO 2 R 6} , -CONR 7 R 8, -NR 6 n (R 7 R 8), -N (R 7 R 8) or _{WY- (CH 2) n -Z (} R 1 - And at least one of R < ₅ > is not hydrogen; R ₂ and R ₃ or R ₃ and R ₄ together form a 3- to 7-membered heterocycloalkyl or a 3- to 7-membered heteroaryl; R ₆ and R ₇ are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl; R ₈ is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, 3 to 10 membered heterocycloalkyl, aryl or heteroaryl , R ₇ and R _{8 taken} together may form a 3- to 7-membered heterocycloalkyl; R ₉ -R ₁₂ are independently hydrogen, alkyl of 1 to 4 carbon atoms, perhaloalkyl of 1 to 4 carbon atoms, halogen, alkoxy of 1 to 4 carbon atoms, or cyano, or R ₉ and R ₁₀ or R ₁₁ and R _{12 taken} together may form an aryl of 5 to 7 carbon atoms; Provided that at least one of R < _9-12 > is not hydrogen; W is O, NR < ₆ > or absent; Y is - (CO) - or - (CO ₂ ), or is absent; Z is alkyl of 1 to 4 carbon _{atoms, -CN, -CO 2 R 6,} COR 6, -CONR 7 R 8, -OCOR 6, -NR 6 COR 7, -OCONR 6, -OR 6, -SR 6 , -SOR ₆ , -SO ₂ R ₆ , SR ₆ N (R ₇ R ₈ ), -N (R ₇ R ₈ ) or phenyl; G is monocyclic heteroaryl; X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J; J is alkyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl; n is an integer of 1 to 6; 14. The method of claim 13, wherein the Huff's virus is human cytomegalovirus. 14. The method of claim 13, wherein the Huff's virus is Huffs simplex virus. 14. The method according to claim 13, wherein the Huff's virus is Varicella zoster virus. Comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein: Formula I In this formula, R ₁ -R ₅ is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, 10 carbon atoms, cycloalkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, _{halogen, -CN, -NO 2, -CO 2} R 6, -COR 6, -OR 6, -SR 6 _{, -SOR 6, -SO 2 R 6} , -CONR 7 R 8, -NR 6 n (R 7 R 8), -N (R 7 R 8) or _{WY- (CH 2) n -Z (} R 1 - And at least one of R < ₅ > is not hydrogen; R ₂ and R ₃ or R ₃ and R ₄ together form a 3- to 7-membered heterocycloalkyl or a 3- to 7-membered heteroaryl; R ₆ and R ₇ are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl; R ₈ is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, 3 to 10 membered heterocycloalkyl, aryl or heteroaryl , R ₇ and R _{8 taken} together may form a 3- to 7-membered heterocycloalkyl; R ₉ -R ₁₂ are independently hydrogen, alkyl of 1 to 4 carbon atoms, perhaloalkyl of 1 to 4 carbon atoms, halogen, alkoxy of 1 to 4 carbon atoms, or cyano, or R ₉ and R ₁₀ or R ₁₁ and R _{12 taken} together may form an aryl of 5 to 7 carbon atoms; Provided that at least one of R < _9-12 > is not hydrogen; W is O, NR < ₆ > or absent; Y is - (CO) - or - (CO ₂ ), or is absent; Z is alkyl of 1 to 4 carbon _{atoms, -CN, -CO 2 R 6,} COR 6, -CONR 7 R 8, -OCOR 6, -NR 6 COR 7, -OCONR 6, -OR 6, -SR 6 , -SOR ₆ , -SO ₂ R ₆ , SR ₆ N (R ₇ R ₈ ), -N (R ₇ R ₈ ) or phenyl; G is monocyclic heteroaryl; X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J; J is alkyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl; n is an integer of 1 to 6; 18. The method of claim 17, wherein the Huffs virus is human cytomegalovirus. 18. The method of claim 17, wherein the Huff's virus is Huffs simplex virus. 18. The method according to claim 17, wherein the Huff's virus is Varicella zoster virus.