NZ260293A - Substituted thiourea derivatives, preparation and pharmaceutical compositions thereof - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £60293 ♦ 9 CompU/ii Speeifiojtion Fit<»d: Class: (&) coi.c3.3a l.i b.; Maarnlifcw»»\ ColSZicftM:, CQl£A*alJ&G&&M&lii3Si, jblication Data: llWLM. .0. Journal No: )Mr.lfc>.

NO DRAWINGS 260293 Under tho provisions of Regulation 23 (1) the .............

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Specification ha1 batxi anio-cii'x-d to 19 9.?^ Initfods Class Cont: wsaaalj"?; ctfuwrcM; Q9TR3&3/^QpWPSl y cqTPc*n|ni; as,*^ S3^ ' DIVIDED OUT OF NEW ZEALAND No.: 243750 Date: 28 JULY 1992 NEW ZEALAND PATENTS ACT, 1953 COMPLETE SPECIFICATION COMPOUNDS AND MEDICAMENTS FOR INHIBITION OF HIV AND RELATED VIRUSES We, MEDIVIR AKTDEBOLAG, a corporation of Sweden, having a principal place of business at Lunastigen 7, S-14444 Huddinge, Sweden, hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- (followed by page 1A) N.2. PATENT OFFICE 21 MAR 1937 received X-8571A 260293 COMPOUNDS AND MEDICAMENTS FOR INHIBITION OF HIV AMP RELATED VIRUSES FiPlri af. the Invention The present invention relates to compounds and 1 0 pharmaceutical^ acceptable salts thereof and medicaments for treating infections by HIV and related viruses and/or the treatment of Acquired Immune Deficiency Syndrome (AIDS).

This invention also relates to pharmaceutical compositions containing the compounds and the use of the present compounds in 1 5 the preparation of medicaments alone or in combination with other agents, for the treatment and inhibition of AIDS and viral infection from HIV.

Background of the Invention A retrovirus designated Human Immunodeficiency Virus (HIV) is believed to be the causative agent of the complex disease termed Acquired Immune Deficiency Syndrome (AIDS) and is a member of the lentivirus family of 25 retroviruses (M. A. Gonda, F. Wong-Staal NR. C. Gallo, "Sequence Homology and Morphological Similarity of HTLV III and Visna Virus, A Pathogenic Lentivirus", Science. 227, 173, (1985); and P. Sonigo and N. Alizon, et al., "Nucleotide Sequence of the Visna Lentivirus: Relationship 30 to the AIDS Virus", Cell. 42, 369, (1985)). The HIV virus (also referred to as the AIDS virus) was previously known N.Z. PATENT OFPirc 21 mm Received 26 0 2 X-8571A -2- as or referred to as LAV, HTLV-III, or ARV, and is now designated by HIV-1. Other closely related variants of HIV-1 include HIV-2 and SIV (simian immunodeficiency virus), and mutants thereof.

The complex disease AIDS includes progressive destruction of the immune system and degeneration of the central and peripheral nervous system. The HIV virus appears to preferentially attack helper T-cells (T-lymphocytes or OKT4-bearing T-cells) and also other human 10 cells, e.g., certain cells within the brain. The helper T-cells are invaded by the virus and the T-cell becomes an HIV virus producer. The helper T-cells are quickly destroyed and their number in the human being is depleted to such an extent that the body's B-cells as well as other 1 5 T-cells normally stimulated by helper T-cells no longer function normally or produce sufficient lymphokines and antibodies to destroy the invading virus or other invading microbes.

While the HIV virus does not necessarily cause 2 0 death per se, it does cause the human's immune system to be so severely depressed that the human falls prey to various other diseases such as herpes, Pneumocistis carinii. toxoplasmosis, cytomegalovirus, Kaposi's sarcoma, and Epstein-Barr virus related lymphomas among others. These 2 5 secondary infections are separately treated using other medications as is conventional. Early during infection, humans with HIV virus seem to live on with little or no symptoms, but have persistent infections. Later in the disease, humans suffer mild immune system depression with 3 0 various symptoms such as weight loss, malaise, fever, and swollen lymph nodes. These syndromes have been called X-8571A. 260 293 persistent generalized lymphadenopathy syndrome (PGL) and AIDS related complex (ARC) and develop into AIDS.

In all cases, those infected with the AIDS virus are believed to be persistently infective to others.

Further, AIDS and AIDS related complex is after some time » fatal.

A description of the mechanism by which the virus infects its host is given in an article by R. Yarchoan, and S. Broder, "Development of Antiretroviral 1 0 Therapy for the Acquired Immunodeficiency Syndrome and Related Disorders", New England Journal of Medicine. 316, 557-564- (February 26, 1987).

Considerable efforts are being directed toward the control of HIV by means of inhibition of the reverse 1 5 transcriptase of HIV, required for replication of the virus. (V. Merluzzi et al., "Inhibition of the HIV-1 Replication by a Nonnucleoside Reverse Transcriptase Inhibitor", Science. 25, 1411 (1990)). For example, a currently used therapeutic compound, AZT, is an inhibitor 2 0 of the viral reverse transcriptase (U.S. Patent No. 4,724,232). Unfortunately, many of the known compounds suffer from toxicity problems, lack of bioavailability or are short lived in vivo, viral resistance, or combinations thereof. 2 5 Therefore it is an object of the invention to provide compounds and pharmaceutically acceptable salts thereof- to inhibit and/or treat HIV and AIDS.

Another object of the present invention is to provide therapeutic formulations that are of value in the 3 0 inhibition and/or treatment of infection by HIV and the X-8571A -4- 260293 treatment or inhibition of the acquired immune deficiency syndrome.

Other objects, features, and advantages will become apparent to those skilled in the art from the following description and claims.

The following compounds are described but not claimed 1n this specification.

S II \ /c\ /' N N (IB) R12V ^R13 \ R,r '(cH2)n'z wherein n is 0 to 4; 15 z is ^C=Y or Y is 0 or S; Rll is of the formula I" C—R14 Ris PATENT OFFICE 21 mm RECEIVED X-8571A --5 - 26 0 2 R14 is a stable saturated or unsaturated, substituted or unsubstituted, 3 to 8 membered organic monocyclic ring having 0 to 4 hetero atoms selected from S, 0, and N; or R14 is a stable, saturated or unsaturated, substituted or unsubstituted, 7 to 10 membered organic bicyclic ring having 0 to 5 hetero atoms selected from S, 0, and N; or R14 is a group of the formula (RlO)y-X- wherein y is 1 or 2; X is N, S, 0 and Rio is a stable saturated or unsaturated, substituted or unsubstituted, 3 to 8 membered organic monocyclic ring having 0 to 4 hetero atoms selected from S, O, and N; or Rio is a stable, saturated or unsaturated, substituted or unsubstituted, 7 to 10 membered organic bicyclic ring having 0 to 5 hetero atoms selected from S, O, and N; or Rio is hydrogen, Ci-Ce alkyl, C2-C6 alkenyl, or C2-C6 alkynyl; or R14 is hydrogen, halo, cyano, carboxy, amino, thio, hydroxy, C1-C4 alkoxy, C1-C6 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, or C2-C8 alkenoxy; R15 and Ri6 are independently C3-C8 cycloalkyl, hydrogen, C1-C6 alkyl, C2-C6 alkenyl, halo, amino, nitro, cyano, C1-C5 alkoxy, hydroxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, carbamoyl, or a halo substituted C1-C6 alkyl; R12 is hydrogen, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, amino, cyano, nitro, C1-C5 alkoxy, carboxy, hydroxymethyl, aminomethyl, carboxymethy 1, C1-C4 alkylthio, C1-C4 alkanoyloxy, halo-substituted (C1-C6)alkyl, or carbamoyl; R13 is a stable saturated or unsaturated, substituted or unsubstituted, 3 to 8 membered organic monocyclic ring having 0 to 4 hetero atoms selected from S, O, and N; or 1 5 X-6571A - 6 - 260293 R13 is a stable, saturated or unsaturated, substituted or unsubstituted, 7 to 10 membered organic bicyclic ring having 0 to 5 hetero atoms selected from s, O, and N; or R13 is Rn as defined; or salts thereof.

The following compounds are also described but not claimed in this specification. s II R "\ /C\ /R" N N ^ (ib) R1 ( '<CH2)ny 1 0 wherein n is 0 to 4; Z is \ wherein Y is S or 0; Rll is of the formula ,c=y or ;ch2 R 16 —c Ri4 R15 wherein R14 is cyclo(C3-C8)alkyl, cyclo (C3-C8) alkenyl; isothiazolyl, substituted isothiazolyl, tetrazolyl, 20 substituted tetrazolyl, triazolyl, substituted triazolyl, pyridyl, substituted pyridyl, imidazolyl, substituted imidazolyl, phenyl, substituted phenyl, naphthyl, P/vrc.-JT OFF! 1 7 NOV 1995 CE 1 5 # 20 • 25 260 2 9 X-8571A - 7 - substituted naphthyl, benzoxazoly1, substituted benzoxazolyl, benzimidazolyl, substituted benzimidazolyl,thiazolyl, substituted thiazolyl, oxazolyl, substituted oxazolyl, benzothiazolyl, substituted benzothiazolyl, pyrazinyl, substituted pyrazinyl, pyridazinyl, substituted pyridazinyl, thiadiazolyl, substituted thiadiazolyl, benzotriazolyl, substituted benzotriazolyl, pyrrolyl, substituted pyrrolyl, indolyl, substituted indolyl, benzothienyl, substituted benzothienyl, thienyl, substituted thienyl, benr,ofuryl, substituted benzofuryl, furyl, substituted furyl, quinolinyl, substituted quinolinyl, isoquinolinyl, substituted isoquinolinyl, pyrazolyl, and substituted pyrazolyl; or R14 is a group of the formula (RlO)y-X- wherein'y is 1 or 2; X is N, S, or 0, and RlO is cyclo(C3-C8)alkyl, cyclo (C3-C8) alkenyl; isothiazolyl, substituted isothiazolyl, tetrazolyl, substituted tetrazolyl, triazolyl, substituted triazolyl, pyridyl, substituted pyridyl, imidazolyl, substituted imidazolyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl» benzoxazolyl, substituted benzoxazolyl, benzimidazolyl, substituted benzimidazolyl,thiazolyl, substituted thiazolyl, oxazolyl, substituted oxazolyl, benzothiazolyl, substituted benzothiazolyl, pyrazinyl, substituted pyrazinyl, pyridazinyl, substituted pyridazinyl, thiadiazolyl, substituted thiadiazolyl, benzotriazolyl, substituted benzotriazolyl, pyrrolyl, substituted pyrrolyl, indolyl, substituted indolyl, benzothienyl, substituted X-8571A - 18j ^602 benzothienyl, thienyl, substituted thienyl, benzofuryl, substituted benzofuryl, furyl, substituted furyl, quinolinyl, substituted quinolinyl, isoquinolinyl, substituted isoquinolinyl, pyrazolyl, and substituted 5 pyrazolyl; or Rl4 is halo, cyano, carboxy, amino, thio, • hydroxy, C1-C4 alkoxy, C2-C8 alkonyl, C2-C8 alkynyl, or C2-Cs alkenoxy; Rl2 is hydrogen, hydroxy, C1-C6 alkyl, C2-C6 10 alkenyl, amino, cyano, nitro, C1-C5 alkoxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, halo substituted C1-C6 alkyl, or carbamoyl; and Rl3 is cyclo(C3-C8)alkyl, cyclo (C3-C8) alkenyl? 1 5 isothiazolyl, substituted isothiazolyl, tetrazolyl, substituted tetrazolyl, triazolyl, substituted triazolyl, pyridyl, substituted pyridyl, imidazolyl,. substituted imidazolyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, benzoxazolyl, substituted 20 benzoxazolyl, benzimidazolyl, substituted benzimidazolyl,thiazolyl, substituted thiazolyl, oxazolyl, substituted oxazolyl, benzothiazolyl, substituted benzothiazolyl, pyrazinyl, substituted pyrazinyl, pyridazinyl, substituted pyridazinyl, thiadiazolyl, 25 substituted thiadiazolyl, benzotriazolyl, substituted benzotriazolyl, pyrrolyl, substituted pyrrolyl, indolyl, substituted indolyl, benzothienyl, substituted benzothienyl, thienyl, substituted thienyl, benzofuryl, substituted benzofuryl, furyl, substituted furyl, 30 quinolinyl, substituted quinolinyl, isoquinolinyl, X-8571A " 9 260293 substituted isoquinolinyl, pyrazolyl, and substituted pyrazolyl; or R13 is Rn as defined; Rl5 and Ri6 are independently C3-C8 cycloalkyl, 5 hydrogen, C1-C6 alkyl, C2-C6 alkenyl, halo, amino, nitro, cyano, C1-C5 alkoxy, hydroxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, carbamoyl, or halo substituted (Ci~C6)alkyl; and salts thereof, with the proviso that R12 is not 10 hydrogen when R15 and Ri6 are both hydrogen, R14 is phenyl, Rl3 is phenyl, Z is >- . and n is 0. 1 0 Description of the Invenr.lnn The present invention provides compounds useful for the inhibition and/or treatment of HIV and AIDS, either as compounds, pharmaceutically acceptable salts, 15 pharmaceutical composition ingredients, whether or not in combination with other anti-virals, immunomodulators, antibiotics, or vaccines. Methods of treating or inhibiting AIDS, methods of inhibiting replication of Hrv in vivo and methods of treating or inhibiting HIV in humans are 20 also disclosed, but are not claimed.

The compounds used in the present invention are those of the formula (IA) below S PATENT ncci^r- RX (IA) 21 MAR 1997 ■N c—N- R4 R, I -^EC£weo in which Ri is a stable saturated or unsaturated, substituted or unsubstituted, 3 to 8 membered organic X-8571A - 10- - monocyclic ring having 0 to 4 hetero atoms selected from S, O, and N; or Ri is a stable, saturated or unsaturated, substituted or unsubstituted, 7 to 10 membered organic bicyclic ring having 0 to 5 hetero atoms selected from 3, O, and N; R2 is a group of the formula wherein R5 is Ri as defined above; or R5 is a group of the formula (RlO)y-X- wherein y is 1 or 2; X is N, S, 0 and Rio is Ri as defined; or Rio is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl; or R5 is hydrogen, halo, cyano, carboxy, amino, thio, hydroxy, C1-C4 alkoxy, C1-C6 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, or C2-C8 alkenoxy; R6, R7, R8« and Rg are independently C3-C8 cycloalkyl, hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, amino, nitro, cyano, C1-C5 alkoxy, hydroxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanpyloxy, carbamoyl, or a halo substituted C1-C6 alkyl; or two of which, along with the carbons to which they are attached, combine to form a stable, saturated or unsaturated, substituted or unsubstituted, 3 to 7 membered organic monocylic ring having 0 to 4 hetero atoms selected from S, O, or N; or R6 and R8, or R7 and R9, along with the carbon to which they X-&571A" 26 0 2 are attached, form a stable, saturated or unsaturated, substituted or unsubstituted, 3 to 7 membered organic monocylic ring having 0 to 4 hetero atoms selected from S, O, or N; R3 and R4 are independently hydrogen, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, amino, cyano, nitro, C1-C5 alkoxy, carboxy, hydroxymethyl, aminomethyl, carboxymr hyl, C1-C4 alkyl thio, C1-C4 alkanqyloxy, halo-substituted (C1-C6)alkyl, or carbamoyl; or salts thereof; The invention also encompasses compounds of the formula S j| R, N C N Rx (IA) I I R4 R-* in which Ri is a stable saturated or unsaturated, substituted or unsubstituted, 3 to 8 membered organic monocyclic ring having 0 to 4 hetero atoms selected from S, O, and N; or Ri is a stable, saturated or unsaturated, substituted or unsubstituted, 7 to 10 membered organic bicyclic ring having 0 to 5 hetero atoms selected from S, O, and N; R2 is a group of the formula X-8571A -12- 260293 r5 c c Rf, Rq wherein R5 is Ri as defined above; or R5 is a group of the 5 formula (RlO)y-X- wherein-y is 1 or 2; X is N, S, 0 and Rio is Ri as defined; or Rio is hydrogen, C1-C6 alkyl, C2-C6 alkenyl,or C2-C6 alkynyl; or R5 is hydrogen, Ci-Cg alkyl, halo, cyano, 10 carboxy, amino, thio, hydroxy, C1-C4 alkoxy, C2-C8 alkenyl, C2-C8 alkynyl, or C2 to C8 alkenoxy; R6 and R7 are independently C3-C8 cycloalkyl, hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, amino, nitro, cyano,. C1-C5 alkoxy, hydroxy, carboxy, 15 hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, carbamoyl, or a halo substituted C1-C6 alkyl; R8 and R9, along with the carbons to which they are attached, combine to form a stable, saturated or 20 unsaturated, substituted or unsubstituted, 3 to 7 membered organic monocylic ring having 0 to 4 hetero atoms selected from S,• 0, or N; R3 and R4 are independently hydrogen, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, amino, cyano, 25 nitro, C1-C5 alkoxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, halo-substituted (C1-C6)alkyl, or carbamoyl; or salts thereof.

X-8571A -13- 2 6 0 2 9 3 The invention also encompasses compounds of the formula S II R2 N C N R, (IA) R '4 wherein Ri is cyclo(C3-C8)alkyl, cyclo (C3-C8) alkenyl; isothiazolyl, substituted isothiazolyl, tetrazolyl, substituted tetrazolyl, triazolyl, substituted triazolyl, 10 pyridyl, substituted pyridyl, imidazolyl, substituted imidazolyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, benzoxazolyl, substituted benzoxazolyl, benzimidazolyl, substituted benzimidazolyl,thiazolyl, substituted thiazolyl, oxazolyl, 15 substituted oxazolyl, benzothiazolyl, substituted benzothiazolyl, pyrazinyl, substituted pyrazinyl, fj pyridazinyl, substituted pyridazinyl, thiadiazolyl, substituted thiadiazolyl, benzotriazolyl, substituted benzotriazolyl, pyrrolyl, substituted pyrrolyl, indolyl, 20 substituted indolyl, benzothienyl, substituted benzothienyl, thienyl, substituted thienyl, benzofuryl, substituted benzofuryl, furyl, substituted furyl, quinolinyl, substituted quinolinyl, isoquinolinyl, substituted isoquinolinyl, pyrazolyl, and substituted 2 5 pyrazolyl; R2 is a group of the formula X-8571A 2 6 0 2 P Rn Rq wherein R5 is pyridyl, substituted pyridyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, cyclohexenyl, benzyl, or R5 is a group of the formula (RlO)y-X- wherein y is 1 or 2; X is N, S, 0 and Rio is Ri as defined; or Rio is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;or R5 is hydrogen, Ci-Cg alkyl, halo, cyano, carboxy, amino, thio, hydroxy, C1-C4 alkoxy, C2-C8 alkenyl, C2-C8 alkynyl, or C2 to C8 alkenoxy; R6, R7, R8» and R9 are independently C3-C8 cycloalkyl, hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C5 alkynyl, halo, amino, nitro, cyano, C1-C5 alkoxy, hydroxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, carbamoyl, or a halo-substituted C1-C6 alkyl; or R6 and R8, or R7 and R9, along with the carbon to which they are attached, form a stable, saturated or unsaturated, substituted or unsubstituted, 3 to 7 membered organic monocylic ring having 0 to 4 hetero atoms selected from S, O, or N; R3 and R4 are independently hydrogen, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, amino, cyano, nitro, C1-C5 alkoxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, halo-substituted C1-C6 alkyl; or carbamoyl; or salts thereof, with the proviso that when X-8571A 2 6 0 z 9 3 Rl is pyridyl or pyridyl monosubstituted with halogen, hydroxy, C1-C6 alkyl, or C1-C6 alkoxy; and R3 and R4 are hydrogen; and R6» R7« R8» and R9 are hydrogen; R5 is not non-substituted phenyl.

When referring to the above as formula (I)', it is understood to encompass formulae (IA) and (IB). It should also be understood that when the term "HIV" is used, it includes HIV-1, components, mutant variations, subtypes, and serotypes thereof, and related viruses, components, mutant variations, subtypes, and serotypes thereof. When the term "inhibit" is used, its ordinary meaning is intended, which is to prohibit, hold in check, or discourage, and is not to be construed to be limited to a particular process, procedure, or mechanism of action.

The terms "stable, saturated or unsaturated, substituted or unsubstituted, 3 to 8 membered", or "3 to 7 membered organic monocyclic ring having 0 to 4 hetero atoms selected from S, 0, and N" include those wherein the nitrogen and sulfur hetero atoms are optionally oxidized, and the nitrogen hetero atom optionally quatemized. The substituted ring may have 1-8 substituents independently selected from aryl, substituted aryl, halo, C1-C6 alkyl, C1-C5 alkoxy, C2-C6 alkenyl, C2-C8 alkynyl, C2-C8 alkenoxy, amino, nitro, cyano, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, hydroxy, C1-C4 alkanoyloxy, carbamoyl, halo-substituted C1-C6 alkyl, a group of the formula -S02Rx wherein Rx is C1-C6 alkyl, aryl, substituted aryl, or amino; or a group of the formula 2 6 0 X-8571A -16- 4. V U O II -C-Rx wherein ^ is as defined above.

The term "stable; saturated or unsaturated, substituted or unsubstituted, 7 to 10 membered organic bicyclic rings having 0 to 5 hetero atoms selected from S, O, and N" includes those wherein the nitrogen and sulfur hetero atoms are optionally oxidized, and the nitrogen hetero atom(s) optionally quaternized. The bicyclic rings may be substituted 1 to 8 times, the substituents independently selected from those above listed for the monocyclic rings.

Examples of such monocyclic and bicyclic rings are cyclo(C3-C8)alkyl, cyclo(C3-C8)alkenyl; isothiazolyl, substituted isothiazolyl, tetrazolyl, substituted tetrazolyl, triazolyl, substituted triazolyl, pyridyl, substituted pyridyl, imidazolyl, substituted imidazolyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, benzoxazolyl, substituted benzoxazolyl, benzimidazolyl, substituted benzimidazolyl,thiazolyl, substituted thiazolyl, oxazolyl, substituted oxazolyl, benzothiazolyl, substituted benzothiazolyl, pyrazinyl, substituted pyrazinyl, pyridazinyl, substituted pyridazinyl, thiadiazolyl, substituted thiadiazolyl, benzotriizolyl, substituted benzotriazolyl, pyrrolyl, substituted pyrrolyl, indolyl, substituted indolyl, benzothienyl, substituted benzothienyl, thienyl, substituted thienyl, benzofuryl, substituted benzofuryl, furyl, substituted furyl, quinolinyl, substituted quinolinyl, isoquinolinyl. ® 25 X-8571A 26 0 A L substituted isoquinolinyl, pyrazolyl, and substituted pyrazolyl. other examples of such ring systems may be found in J. Fletcher, 0. Dermer, R. Fox, Nomenclature of Organic Compounds, pp. 20-63 (1974), and in the Examples herein.

The term "C1-C6 alkyl" includes such groups as methyl, ethyl, n-propyl, isopropyl, n-butyl, s-butyl, t-butyl, n-pentyl, n-hexyl, 3-methylpentyl, and the like.

The term "halo" and "halogen" refer to chloro, bromo, fluoro, and iodo.

"C1-C5 alkoxy" refers to those groups such as methoxy, ethoxy, propoxy, t-butoxy, and the like. "c2~c6 alkenyl" refers to those groups such as vinyl, l-propene-2-yl, l-butene-4-yl, l-pentene-5-yl, 1-butene-l-yl, and the like.

"C1-C4 alkylthio" refers to those groups such as methylthio, ethylthio, t-butylthio, and the like.

"C1-C4 alkanoyloxy" refers to those groups such as acetoxy, propionoxy, formyloxy, butyryloxy, and the like.

The term "C2-C8 alkenoxy" includes groups such as ethenyloxy, propenyloxy, iso-butoxy ethenyl, and the like.

The term "C2-C8 alkynyl" includes groups such as ethynyl, propynyl, pentynyl, butynyl, and the like.

The term halo-substituted C1-C6 alkyl includes alkyIs substituted 1, 2, or 3 times by a halogen, including groups such as trifluoromethyl, 2-dichloroethyl, 3,3-difluoropropyl, and the like.

The term "aryl" includes 3 to 8 membered stable saturated or -unsaturated organic monocyclic rings having 0 to 4 hetero atoms selected from S, o, and N; and 7 to 10 X-8571A 260203 membered organic stable, saturated or unsaturated, bicyclic rings having 0 to 5 hetero atoms selected from S, 0, N; both of which may be substituted by halo, C1-C6 alkyl, Ci-C5 alkoxy, C2-C6 alkenyl, amino, nitro, cyano, carboxy, 5 hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, hydroxy, C1-C4 alkanoyloxy, carbamoyl, or halo-substituted C1-C6 alkyl.

The following are preferred compounds. 1 0 N-(2-phenethy1)-N'-(2-thiazolyl)thiourea N-(2-phenethyl)-N*-[2-(4-methyl)thiazolyl]thiourea N- (2-phenethy1)-N'-[2-(4,5-dimethyl)thiazolyl]thiourea . N-(2-phenethyl)-N'-[2-(4-cyano)thiazolyl]thiourea N-(2-phenethyl)-N'-[2-(4-1 5 tri fluoromethyl)thiazolyl]thiourea N- (2-rphenethyl) -N' - (2-benzothiazolyl) thiourea N-'{2-phenethyl) -N' - [2-(6-fluoro)benzothiazolyl]thiourea N-(2-phenethyl)-N*-[2-(6-chloro)pyrazinyl]thiourea 20 N-(2-phenethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N-(2-phenethyl)-N*-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-(2-phenethyl)-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea 25 N- (2-phenethyl) -N' - (2-pyridyl) thiourea N-(2-phenethyl)-N*-[2-(6-bromo)pyridyl]thiourea N-(2-phenethyl)-N'-[2-(6-chloro)pyridyl]thiourea N-(2-phenethyl)-N'-[2-(6-methyl)pyridyl]thiourea N-(2-phenethyl)-N'-[2-(5-methyl)pyridylj thiourea 3 0 N-(2-phenethyl)-N'-[2-(6- tri fluoromethyl)pyridyl]thiourea N-(2-phenethyl)-N'-[2-(5-trifluoromethyl)pyridyl]thiourea N-(2-phenethy1)-N * -[2-(6-ethyl)pyridyl]thiourea 3 5 N-(2-phenethyl)-N'-[2-(5-ethy1)pyridyl]thiourea N- (2-phenethyl) -N' - [2- (6-bromo)pyrazinyl] thiourea N- (2-phenethyl) -IT -[ (3- (6-bromo)pyridazinyl) ] thiourea N-(2-phenethyl)-N*-[2-(6-cyano)pyridyl]thiourea N- (2-phenethyl)-N'-[2-(5 ^-cyano)pyridyl]thiourea 40 N- (2-phenethyl) -N* - [2 - (5-cyano) pyrazinyl] thiourea N-(2 -phenethy1)-N'-[2-(6-cyano)pyrazinyl]thiourea N-(2-phenethyl)-N*-[(3-(6-cyano)pyridazinyl)]thiourea 40 45 X-8571A -19- ^ ^ 0 2. B N-(2-phenethyl)-N'-(2-[1,3,4-thiadiazoyl])thiourea N-(2-phenethyl)-N'-(2-benzimidazolyl)thiourea N-(2-phenethyl)-N*-(2-imidazolyl thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- thiazolyl)thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- (4- methyl)thiazolyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- (4,5- dimethyl)thiazolyl]thiourea • N-(2-(2-methoxyphenyl)ethyl -N' - 2- benzothiazolyl)thiourea N-(2-(2-methoxyphenyl)ethyl -N'- 2- (6- fluoro)benzothiazolyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- (6- chloro)pyrazinyl]thiourea N- (2- (2-methoxyphenyl)ethyl -N' - 2- (4- (3- pyridyl)thiazolyl)]thiourea N-(2-(2-methoxyphenyl)ethyl -N" - 2- (4- (3- nitrophenyl)thiazolyl)]thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- pyridyl)thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- (6- bromo)pyridyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N" - 2- (6- chloro)pyridyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N'- 2- (6- methyl)pyridyl]thiourea N-(2-(2-methoxyphenyl)ethyl _N<- 2- (5- methyl)pyridyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- (6- trifluoromethyl)pyridyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- (5- trifluoromethyl)pyridyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N* - 2- (6- ethyl)pyridyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- (5- ethyl) pyridyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- (6- bromo)pyrazinyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N' - (3 -(6- bromo)pyridazinyl)]thiourea N-(2-(2-methoxyphenyl)ethyl -N" - 2- (6- cyano)pyridyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- (5- cyano)pyridyl]thiourea N-(2-(2-methoxyphenyl)ethyl -N' - 2- (5- cyano)pyrazinyl]thiourea 1 5 20 25 ® 30 35 40 45 X-8571A -20- 2 6 0 2 9 3 N-(2-(2-methoxyphenyl)ethyl)-N'-[2-(6-cyano)pyrazinyl]thiourea N- (.2- (2-methoxyphenyl) ethyl) -N• - [ (3- (6-cyano)pyridazinyl)]thiourea N-(2-{2-methoxyphenyl)ethyl)-N'-(2-[1/3,4-thiadiazoyl])thiourea N-(2-(2-methoxyphenyl)ethyl)-N'-(2-benzimidazolyl)thiourea N-(2-(2-methoxyphenyl)ethyl)-N'-(2-imidazolyl)thiourea N- (2-(3-methoxyphenyl)ethyl)-N*-(2-thiazolyl)thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(4-methyl)thiazolyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(4,5-dimethyl)thiazolyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-(2-benzothiazolyl)thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(6-fluoro)benzothiazolyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(6-chloro)pyrazinyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-(2-pyridyl)thiourea N-(2-(3-methoxyphenyl)ethyl)-N'- [2-(6-bromo)pyridyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N1 -[2-(6-chloro)pyridyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-n'-[2-(6- methyl)pyridyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(5-methy1)pyridyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(6-tri fluoromethyl)pyridyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(5-tri fluoromethyl)pyridyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(6-ethyl)pyridyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(5-ethyl)pyridyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N' -[2-(6-bromo)pyrazinyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[(3-(6-bromo) pyridazinyl) ] thiourea 20 25 ® 30 35 40 45 X-8571A -21- 2 6 0 2 9? N-(2-(3-methoxyphenyl)ethyl)-N' cyano)pyridyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N' cyano)pyridyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N' cyano)pyrazinyl]thiourea N- (2- (3 -methoxyphenyl) ethyl) -N • cyano)pyrazinyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N' cyano)pyridazinyl)]thiourea N- (2 - (3 -methoxyphenyl) ethyl) -N' thiadiazoyl])thiourea N- (2 - (3 -methoxypheny 1) ethyl) -N' benzimidazolyl)thiourea N- (2 - (3 -methoxyphenyl) ethyl) -N' N- (2- (4-methoxyphenyl) ethyl) -N' N- (2- (4-methoxyphenyl)ethyl)-N' methyl)thiazolyl]thiourea N- (2-(4-methoxyphenyl)ethyl)-N' dimethyl)thiazolyl]thiourea N- (2 - (4-methoxyphenyl) ethyl) -N' cyano)thiazolyl]thiourea N-'(2- (4-methoxyphenyl) ethyl) -N' trifluoromethyl)thiazolyl]thiourea N- (2 - (4 -methoxyphenyl) ethyl) -N' benzothiazolyl)thiourea N- (2 - (4-methoxyphenyl) ethyl) -N' fluoro)benzothiazolyl]thiourea N- (2 - (4 -methoxyphenyl) ethyl) -N' chloro)pyrazinyl]thiourea N- (2 - (4-methoxyphenyl) ethyl) -N' ethyl)thiazolyl]thiourea N- (2- (4-methoxyphenyl) ethyl) -N' pyridyl)thiazolyl)]thiourea N-(2-(4-methoxyphenyl)ethyl)-N' nitrophenyl)thiazolyl)]thiourea N- (2- (4-methoxyphenyl) ethyl) -N' N- (2 - (4 -me thoxypheny 1) ethyl) -N' bromo)pyridyl]thiourea N- (2 - (4-methoxyphenyl) ethyl) -N' bromo)pyridyl]thiourea N- (2 - (4 -methoxyphenyl) ethyl) -N' chloro)pyridyl]thiourea N- (2 - (4 -methoxyphenyl) ethyl) -N' chloro)pyridyl]thiourea 2- (6-2 — (5— 2- (5-2- (6-(3-(6-2-[1,3,4-2- 2-imidazolyl)thiourea 2-thiazolyl)thiourea 2 — (4— 2-(4,5- 2- (4- 2— (4— 2- 2- (6-2 — (6— 2- (4-2—(4—(3— 2- (4-(3- 2-pyridyl)thiourea 2- (6- 2- (5- 2- (6- 2-(5- 20 25 40 45 X-8571A -22- 260203 N- (2-{4-methoxyphenyl)ethyl -N' - 2- (6- methyl)pyridyl]thiourea N-(2-(4-methoxyphenyl)ethyl -N'- 2- (5- methyl)pyridyl]thiourea N-(2-(4-methoxyphenyl)ethyl -N' - 2- (6- tri fluoromethyl)pyridyl]thiourea N-(2-(4-methoxyphenyl)ethyl -N' - 2- (5- trifluoromethyl)pyridyl]thiourea • N-(2-(4-methoxyphenyl)ethyl -N' - 2- (6- ethyl)pyridyl]thiourea N-{2-(4-methoxyphenyl)ethyl -N'- 2- (5- ethyl)pyridyl]thiourea N- (2-(4-methoxyphenyl)ethyl -N' - 2- (5- chloro)pyrazinyl]thiourea N-(2-(4-methoxyphenyl)ethyl -N' - 2- (6- bromo)pyrazinyl]thiourea N- (2 - (4 -methoxyphenyl) ethyl -N' - 2- (5- bromo)pyrazinyl]thiourea N-{2-(4-methoxyphenyl)ethyl -N' - (3 -(6- bromo)pyridazinyl)]thiourea N-(2-(4-methoxyphenyl)ethyl -N'- (3 -(6- chloro)pyridazinyl)]thiourea N-(2-(4-methoxyphenyl)ethyl -N' - 2- (6- cyano)pyridyl]thiourea N- (2 - (4 -methoxyphenyl) ethyl -N' - 2- (5- cyano)pyridyl]thiourea N-(2-(4-methoxyphenyl)ethyl -N'- 2- (5- cyano)pyrazinyl]thiourea N-(2-(4-methoxypheny1)ethyl -N'- 2- (6- cyano)pyrazinyl]thiourea N-(2-(4-methoxypheny1)ethyl -N' - (3 -{6- cyano)pyridazinyl)]thiourea N- {2-(4-methoxyphenyl)ethyl _N»- 2- [1,3,4- thiadiazoyl])thiourea N-(2-(4-methoxyphenyl)ethyl -N' - 2- benzimidazolyl)thiourea N-(2-(4-methoxyphenyl)ethyl -N' - 2- imidazolyl) thiovurea N- (2- (2-ethoxyphenyl)ethyl) -N' - (2-thiazolyl) thiourea N- (2- (2-ethoxyphenyl)ethyl) -N' -[2-(4-methyl)thiazolyl]thiourea N-(2-(2-ethoxyphenyl)ethyl)-N' -[2-(4,5-dimethyl)thiazolyl]thiourea N- (2-(2-ethoxyphenyl)ethyl)-N' -(2-benzothiazolyl)thiourea N-(2-(2-ethoxyphenyl)ethyl)-N'-[2-(6-fluoro)benzothiazolyl]thiourea X-8571A 2® 0 2 9 N- (2 - (2-ethoxyphenyl) ethyl chloro)pyrazinyl]thiourea N- (2- (2-ethoxyphenyl) ethyl pyridyl) thiazolyl) ] thiourea 5 N-(2-(2-ethoxyphenyl)ethyl nitrophenyl)thiazolyl)]thiourea N-(2-(2-ethoxyphenyl)ethyl N- (2 - (2-ethoxyphenyl) ethyl bromo)pyridyl]thiourea N- (2- (2-ethoxyphenyl) ethyl chloro)pyridyl]thiourea N- (2 - (2-ethoxyphenyl) ethyl methyl)pyridyl]thiourea N- (2-(2-ethoxyphenyl)ethyl 1 5 methyl)pyridyl]thiourea N-(2-(2-ethoxyphenyl)ethyl trifluoromethyl)pyridyl]thiourea N- (2- (2-ethoxyphenyl) ethyl trifluoromethyl)pyridyl]thiourea N- (2- (2-ethoxyphenyl) ethyl ethyl)pyridyl]thiourea N- (2- (2-ethoxyphenyl) ethyl ethyl)pyridyl]thiourea N- (2- (2-ethoxyphenyl) ethyl 2 5 bromo)pyrazinyl]thiourea N-(2-(2-ethoxyphenyl)ethyl bromo)pyridazinyl)]thiourea N-(2-(2-ethoxyphenyl)ethyl cyano)pyridyl]thiourea 3 0 N- (2 - (2 -ethoxyphenyl) ethyl cyano)pyridyl]thiourea N- (2- (2-ethoxyphenyl) ethyl cyano)pyrazinyl]thiourea N- (2- (2-ethoxyphenyl) ethyl 3 5 cyano)pyrazinyl]thiourea N- (2- (2-ethoxyphenyl) ethyl cyano)pyridazinyl)]thiourea N- (2- (2-ethoxyphenyl) ethyl thiadiazoyl])thiourea 40 N- (2 - (2-ethoxyphenyl) ethyl benzimidazolyl)thiourea N- (2 - (2-ethoxyphenyl) ethyl N- (2- (2-methylphenyl) ethyl N- (2- (2-methylphenyl) ethyl 4 5 methyl)thiazolyl]thiourea -N' - -N' - -N' - -N' --N'- -N'- -N' - -N' - -N' - -N' - -N' - -N' - -N' - -N'- -N' - -N'- -N' - -N' - -N' - -N' - -N'- -N'--N' --N" - 2- (6-2- (4- (3-2- (4- (3- 2 -pyr ictyl) thiourea 2- (6- 2 — (6— 2 — (6— 2- (5- 2- (6- 2-(5- 2-(6- 2 — (5— 2- (6- (3-(6- 2- (6- ; i 2 — (5— 2 — (5 — 2- (6-(3- (6-2-[1,3,4-2- 2-imidazolyl)thiourea 2-thiazolyl)thiourea 2- (4- 20 25 ® 30 35 40 45 X-8571A -24- ^ 6 0 £ Q ^ N- (2- {2 -me thy lpheny 1) ethyl) -N" - 2- (4,5- dimethyl)thiazolyl]thiourea N-(2-(2-methylphenyl)ethyl) -N' - 2- benzothiazolyl)thiourea N-(2-(2-methylphenyl)ethyl) -N' - 2- (6- fluoro)benzothiazolyl]thiourea N-(2-(2-methylphenyl)ethyl) -N" - 2- (6- chloro)pyrazinyl]thiourea • N- (2-(2-methylpheny1)ethyl) -N' - 2- (4-(3- pyridyl)thiazolyl)]thiourea N-(2-(2-methylpheny1)ethyl) -N'- 2- (4— (3 — nitrophenyl)thiazolyl)]thiourea N-(2-(2-me thylpheny1)ethyl) -N' - 2- pyridyl)thiourea N-(2-(2-methylphenyl)ethyl) -N'- 2- (6- bromo)pyridyl]thiourea N-(2-(2-methylphenyl)ethyl) -N'- 2- (5- chloro)pyridyl]thiourea N-(2-(2-methylphenyl)ethyl) -N' - 2- (6- methyl) pyridyl ] thioxirea N- (2 - (2-methylphenyl) ethyl) -N' - 2- (5- methyl)pyridyl]thiourea N-.(2- (2-methylphenyl) ethyl) -N' - 2- (6- trif luoromethyl) pyridyl] thioxirea N- (2- (2-methylphenyl) ethyl) -N' - 2- (5- trif luoromethyl) pyridyl] thiourea , N- (2- (2-methylphenyl) ethyl) -N" - 2- (6- ethyl) pyridyl ] thioxirea N- (2- (2-methylphenyl) ethyl) -N' - 2- (5- ethyl) pyr idyl ] thioxirea N- (2- (2-methylphenyl) ethyl) -N' - 2- (6- bromo)pyrazinyl]thiourea N-(2-(2-methylphenyl)ethyl) -N'- (3 -(6- bromo)pyridazinyl) ] thioxirea N- (2- (2-methylphenyl) ethyl) -N" - 2- (6- cyano) pyr idyl ] thioxirea N-(2-(2-methylpheny1)ethyl) -N" - 2- (5- cyano) pyridyl ] thioxirea N- (2 - (2-methylphenyl) ethyl) -N'- 2- (5- cyano) pyrazinyl ] thiourea N- (2- (2-methylphenyl) ethyl) -N" - 2- (6- cyano)pyrazinyl]thiourea N- (2- (2-methylphenyl) ethyl) -N' - (3 - (6- cyano)pyridazinyl) ] thioxirea N- (2 - (2-methylphenyl) ethyl) -N' - 2- [1,3,4- thiadia'zoyl]) thioxirea 40 45 X-8571A 26 0 2 9 N- (2- (2-methylphenyl) ethyl) -N' - (2-benzimidazolyl) thiourea N- (.2- (2-methylphenyl) ethyl) -N' - (2-imidazolyl) thiourea N-(2-(3-methylphenyl)ethyl)-N'-(2-thiazolyl)thiourea N-(2-(3-methylphenyl) ethyl)-N'-[2-(4-methyl)thiazolyl]thiourea N-(2-(3-methylphenyl) ethyl) -N'-[2- (4,5-dimethyl)thiazolyl]thiourea N-(2-(3-methylpheny1)ethyl)-N'-[2-(4-cyano)thiazolyl]thiourea N-(2-(3-methylphenyl) ethyl) -N*-[2- (4-trifluoromethyl)thiazolyl]thiourea N-(2-(3-methylpheny1)ethyl)-N * -(2-benzothiazolyl)thiourea N-(2-(3-methylphenyl)ethyl)-N'-[2-(6-fluoro)benzothiazolyl]thiourea N-(2-(3-methylphenyl)ethyl)-N'-[2-(6-chloro)pyrazinyl]thiourea N-(2-(3-methylphenyl)ethyl)-N'-[2-(4-ethy1)thiazolyl]thiourea N-(2-(3-methylphenyl)ethyl)-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N- (2- (3-methylphenyl) ethyl) -N' - [2 - (4- (3-nitrophenyl)thiazolyl)]thiourea N-(2-(3-methylpheny1)ethyl)-N'-(2-pyridyl)thiourea N- (2- (3-methylphenyl) ethyl) -N' -12- (6-bromo)pyridyl]thiourea N-(2-(3-methylphenyl)ethyl)-N*-[2-(5-bromo)pyridyl]thiourea N-(2-(3-methylphenyl)ethyl)-N'-[2-(6-chl or o) pyridyl ] thioxirea N-12-(3-methylphenyl) ethyl) -N' -[2- (5-chloro)pyridyl]thiourea N- (2- (3-methylpheivl)ethyl) -N' -[2- (6-methy1)pyridyl]thiourea N- (2- (3-methylphenyl) ethyl) -N' - [2- (5-methyl)pyridyl]thiourea N- (2- (3-methylphenyl) ethyl) -N' -[2- (6-trif luoromethyl) pyridyl] thiourea N- (2- (3-methylphenyl) ethyl) -N' -12- (5-tri f luoromethyl) pyridyl ] thiourea N-(2-(3-methylphenyl)ethyl)-N'-[2-(6-ethyl)pyridyl]thiourea N- (2-(3-methylphenyl) ethyl) -N'-[2- (5-ethyl) pyridyl] thioxirea 20 25 35 40 260^3 X-8571A -26- N- (2-(3-methylphenyl)ethyl chloro)pyrazinyl]thiourea N-(2-(3-methylphenyl)ethyl bromo)pyrazinyl]thiourea N-{2-(3-methylphenyl)ethyl bromo)pyrazinyl]thiourea N-(2-(3-methylphenyl)ethyl bromo)pyridazinyl)]thiourea N-(2-(3-methylphenyl)ethyl chloro)pyridazinyl)]thiourea N-(2-(3-methylphenyl)ethyl cyano)pyridyl]thiourea N-(2-(3-methylphenyl)ethyl cyano)pyridyl]thiourea N-'(2- (3 -methylphenyl) ethyl cyano)pyrazinyl]thiourea N- (2-(3-methylphenyl)ethyl cyano)pyrazinyl]thiourea N- (2-(3-methylphenyl)ethyl cyano)pyr idaziny1)]thiourea N-(2-(3-methylphenyl)ethyl thiadiazoyl])thiourea N- (2-(3-methylphenyl)ethyl benzimidazolyl)thiourea N-(2-(3-methylphenyl)ethyl N-(2-(2-fluorophenyl)ethyl N-(2-(2-fluorophenyl)ethyl methyl)thiazolyl]thiourea N-{2-(2-fluorophenyl)ethyl dimethyl)thiazolyl]thiourea N-(2-(2-fluorophenyl)ethyl benzothiazolyl)thiourea N- (2-(2-fluorophenyl)ethyl fluoro)benzothiazolyl]thiourea N-(2-(2-fluorophenyl)ethyl chloro)pyrazinyl]thiourea N-.(2- (2-f luorophenyl) ethyl pyridyl) thiazolyl) ] thiourea N-(2-(2-fluorophenyl)ethyl nitrophenyl)thiazolyl}]thiourea N- (2-(2-fluorophenyl)ethyl N- (2-(2-fluorophenyl)ethyl bromo)pyridyl]thiourea N- (2-(2-fluorophenyl)ethyl chloro)pyridyl]thiourea -N'- 2- (5- -N'- 2- (6- -N' - 2- (5- -N' - (3- (6- -N' - (3-(6- -N' - 2- (6- -N' - 2- (5- _N<- 2- (5- -N' - 2- (6- -N'- (3- (6- -N'- 2-11.3,4- -N' - 2- i i i 53 55 2 i i i 2-imidazolyl)thiourea 2-thiazolyl)thiourea 2- (4- -N'- 2- (4,5— -N' - 2- -N'- 2- (6- -M' - 2- (6- -N' - 2- (4- (3- -N" - 2- (4- (3- i i S5 ^ i i 2-pyridyl)thiourea 2- (6- -N" - [2- (6- v 40 45 X-8571A 260293 N-- (2 - (2 - f luorophenyl) ethyl) -N' - 2- (6- methyl)pyridyl]thiourea N- C2-(2-fluorophenyl)ethyl) -N' - 2- (5- methyl)pyridyl]thiourea N-(2-(2-fluorophenyl)ethyl) -N' - 2- (6- trifluoromethyl)pyridyl]thiourea N-(2-(2-fluorophenyl)ethyl) -N' - 2- (5- trif luoromethyl) pyridyl] thioxirea • N-(2-(2-fluorophenyl)ethyl) -N' - 2- (6- ethyl)pyridyl]thiourea N-(2-(2-fluorophenyl)ethyl) -N' - 2- (5- ethyl)pyridyl]thiourea N-(2-(2-fluorophenyl)ethyl) -N' - 2- (6- bromo) pyr az iny 1 ] thiourea N-(2-(2-fluorophenyl)ethyl) -N' - (3 -(6- bromo)pyridazinyl)]thiourea N-(2-(2-fluorophenyl)ethyl) -N' - 2- (6- cyano) pyridyl ] thioxirea N-(2-(2-fluorophenyl)ethyl) -N' - 2- (5- cyano)pyridyl]thiourea N-(2-(2-fluorophenyl)ethyl) -N' - 2- (5- cyano)pyrazinyl]thiourea N-. (2 - (2 - f luorophenyl) ethyl) -N' - 2- (6- cyano) pyrazinyl ] thiourea N-(2-(2-fluorophenyl)ethyl) -N' - (3 -(6- cyano) pyridazinyl) ] thioxirea N-(2-(2-fluorophenyl)ethyl) -N' - 2- [1,3,4- thiadiazoyl])thiourea N-(2-(2-fluorophenyl)ethyl) -N' - 2- benzimidazolyl) thioxirea N-(2-(2-fluorophenyl)ethyl) -N* - 2- imidazolyl)thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2—(4,5— dimethyl) thiazolyl] thioxirea N-(2-(2,6-difluorophenyl)ethyl)-N'-(2-benzothiazolyl) thioxirea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(6-fluoro)benzothiazolyl]thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(6-chloro) pyrazinyl ] thioxirea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(4- (3-pyridyl) thiazolyl) ] thioxirea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(4- (3-nitrophenyl) thiazolyl) ] thioxirea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(6-chloro)pyridyl]thiourea X-8571A ^6 0 2 93 N- (2-(2,6-difluorophenyl)ethyl)-N'-[2-(6-methyl)pyridyl]thiourea N-(2-{2,6-difluorophenyl)ethyl)-N•-[2-(6-trifluoromethyl)pyridyl]thiourea N- (2-(2,6-difluorophenyl)ethyl)-N'-[2-(6-ethyl) pyridyl] thiourea N- (2- (2,6-difluorophenyl)ethyl)-N'-[2-(6-bromo)pyrazinyl]thiourea N- (2-(2,6-difluorophenyl)ethyl)-N'-[(3-(6-bromo) pyridazinyl.) ] thiourea N- (2-(2,6-difluorophenyl)ethyl)-N'-[2-(6-cyano)pyridyl]thiourea N- (2-(2,6-difluorophenyl)ethyl)-N'-[2- (5-cyano)pyrazinyl]thiourea.

N- (2-(2,6-difluorophenyl)ethyl)-N'-[2-(6-cyano)pyrazinyl]thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[(3 —(6-cyano)pyridazinyl)]thiourea N- (2-(2,6-difluorophenyl)ethyl)-N'-(2-[l,3,4-thiadiazoyl])thiourea N- (2-(2,6-difluorophenyl)ethyl)-N'-(2-benzimidazolyl) thiourea N- (2- (2,6-difluorophenyl) ethyl) -N' - (2-imidazoly1)thiourea N- (2-(2-fluoro-6-methoxyphenyl)ethyl)-N'-(2-thiazoly1)thiourea N- (2-(2-fluoro-6-methoxyphenyl)ethyl)-N1 -[2- (4-methyl)thiazolyl]thiourea N-(2-(2-fluoro-6-methoxyphenyl)ethyl)-N'-[2-(4,5-dimethyl)thiazolyl]thiourea N-'(2- (2-fluoro-6-methoxyphenyl) ethyl) -N' - (2-benzothiazolyl) thiourea...

N- (2- (2-fluoro-6-methoxyphenyl) ethyl) -N1 - [2- (6-fluoro)benzothiazolyl]thiourea N- (2- (2-fluoro-6-methoxyphenyl)ethyl)-N'-[2-(6-chloro)pyrazinyl]thiourea N- (2-(2-fluoro-6-methoxyphenyl)ethyl)-N'-[2-(4-(3-pyridyl) thiazolyl) ] thioxirea N- (2- (2-fluoro-6-methoxyphenyl) ethyl) -N' - [2- (4- (3-nitrophenyl)thiazolyl)]thiourea N- (2- (2-fluoro-6-methoxyphenyl) ethyl) -N' - (2-pyridyl)thiourea ; N-(2-(2-fluoro-6-methoxyphenyl)ethyl)-N'-[2-(6-bromo)pyridyl]thiourea : N-(2-(2-fluoro-6-methoxyphenyl)ethyl)-N'-[2-(6-chloro)pyridyl]thiourea 40 45 2 6 0 ? g X-8571A -29- W N-(2-(2-fluoro-6-methoxyphenyl methy1)pyridyl]thiourea N-(2-(2-fluoro-6-methoxyphenyl methyl)pyridyl]thiourea N-(2-(2-fluoro-6-methoxyphenyl trifluoromethyl)pyridyl]thiourea N-(2-(2-fluoro-6-methoxyphenyl tri fluoromethyl)pyridyl]thiourea N-(2-(2-fluoro-6-methoxyphenyl ethyl)pyridyl]thiourea N- (2-(2-fluoro-6r-methoxyphenyl ethyl)pyridyl]thiourea N-(2-(2-fluoro-6-methoxyphenyl bromo)pyraz iny1]thiourea N-(2- (2-fluoro-6-methoxyphenyl bromo)pyridazinyl)]thiourea N-(2-(2-fluoro-6-methoxyphenyl cyano)pyridyl]thiourea N- (2- (2-fluoro-6-methoxyphenyl cyano) pyridyl ] thiourea N- (2- (2-f luoro-6-methoxyphenyl cyano)pyrazinyl]thiourea N- (2 - (2-f luoro-6-methoxyphenyl cyano) pyraz inyl ] thiourea N- (2- (2-fluoro-6-methoxyphenyl cyano) pyridaz inyl) ] thioxirea N- (2- (2-fluoro-6-methoxyphenyl thiadiazoyl])thiourea N-(2-(2-fluoro-6-methoxyphenyl benzimidazolyl)thiourea N-(2-(2-fluoro-6-methoxyphenyl imidazolyl)thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl) thiazolyl)thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl) methyl) thiazolyl ] thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl) dimethyl)thiazolyl]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl) benzothiazolyl)thiourea N-(2-(2-fluoro-6-ethoxypheny1)ethyl) fluoro)benzothiazolyl]thiourea N- (2-(2-fluoro-6-ethoxyphenyl)ethyl) chloro)pyrazinyl]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl) pyridyl)thiazolyl)j thiourea ethyl -N'- 2- (6- ethyl -N' - 2- (5- ethyl -N' - 2- (6- ethyl -N' - 2- (5- • ethyl -N' - 2- (6- ethyl -N' - 2- (5- ethyl -N' - 2- (6- ethyl -N' - (3 -(6- ethyl -N' - 2- (6- ethyl -N' - 2- (5- ethyl -N'- 2- (5- ethyl -N'- 2- (6- ethyl -W- (3 -(6- ethyl -N' - 2- [1,3,4- ethyl -N' - 2- ethyl -N'- 2- -N'-(2- -N'-[2-(4- -N'-[2-(4,5- -N'-(2- -N'-[2-(6- -N'-[2-(6- -N'-[2-(4-(3- X-8571A 26 0 y 5 t _ -N • — -N' -N'- -N" _N« -N' -N' -N'- -N -N • — • • N- (2-(2-fluoro-6-ethoxyphenyl)ethyl)-N nitrophenyl)thiazolyl)]thiourea N-(.2- (2-fluoro-6-ethoxyphenyl)ethyl) -N' -pyridyl)thiourea 5 N- (2-(2-fluoro-6-ethoxyphenyl)ethyl bromo)pyridyl]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl chloro)pyridyl]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl 1 0 methyl) pyridyl] thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl methyl)pyridyl]thiourea ; N-(2-(2-fluoro-6-ethoxyphenyl)ethyl tri fluoromethyl)pyridyl]thiourea N- (2- (2-f luoro-6-ethoxyphenyl) ethyl tri fluoromethyl)pyridyl]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl ethyl) pyridyl ] thioxirea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl 2 0 ethyl) pyridyl ] thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl bromo)pyraz inyl]thiourea N-'(2- (2-fluoro-6-ethoxyphenyl) ethyl bromo) pyridaz inyl) ] thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl cyano) pyridyl ] thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl cyano) pyridyl ] thioxirea r N-(2-(2-fluoro-6-ethoxyphenyl)ethyl 3 0 cyano) pyrazinyl ] thiourea N-{2-(2-fluoro-6-ethoa^phenyl)ethyl cyano)pyrazinyl]thiourea N-(2-(2-fluoro-6-ethoxypheny1)e thyl cyano)pyridazinyl) ] thiourea 3 5 N- (2- (2-fluoro-6-ethoxyphenyl) ethyl thiadiazoyl])thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl benzimidazolyl) thioxirea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl 40 imidazolyl)thiourea N- (2-(2,3,5,6-tetrafluorophenyl)ethyl)-N thiazolyl)thiourea N-(2-(2,3,5,6-tetrafluorophenyl)ethyl)-N methyl)thiazolyl]thiourea 4 5 N--(2- (2,3,5,6 -tetraf luorophenyl) ethyl) -N dimethyl) thiazolyl] thioxirea N' -N" -N' -N' -N' -N ( _ -N" -N1 [2—(4—(3— (2- [2-(6-[2-(6- i [2-(6-[2-(5-12-(6-[2-(5-[2-(6-[2-(5-[2-(6-[(3-(6-[2-(6-[2-(5-12 — (5— [2-(6-[ (3- {6-(2-[lf3,4-(2-(2-'.-(2-' - [2- (4-• -12- (4,5- 40 45 X-8571A 2 6 :' 0 Okifl 3 N- (2 - (2,3,5,6-tetrafluorophenyl cyano)thiazolyl]thiourea N-C2- (2,3,5,6-tetrafluorophenyl trifluoromethyl)thiazolyl]thiourea N-(2-(2,3,5,6-tetrafluorophenyl benzothiazolyl)thiourea N- (2- (2,3,5,6-tetrafluorophenyl f luoro) benzothiazolyl ] thiourea N-(2-(2,3,5,6-tetrafluorophenyl chloro) pyraziny 1 ] thiourea N- (2-(2,3,5,6-tetrafluorophenyl ethyl)thiazolyl]thiourea N-(2- (2,3,5,6-tetrafluorophenyl pyridyl) thiazolyl) ] thiourea N-(2-(2,3,5,6-tetrafluorophenyl nitrophenyl)thiazolyl)]thiourea N-(2- (2,3,5,6-tetrafluorophenyl pyridyl)thiourea N-(2-(2,3,5,6-tetrafluorophenyl bromo)pyridyl]thiourea N-(2-(2,3,5,6-tetrafluorophenyl bromo)pyridyl]thiourea N-(2-(2,3,5,6-tetrafluorophenyl chloro)pyridyl]thiourea N-(2 - (2,3,5,6-tetrafluorophenyl chloro)pyridylj thiourea N- (2-(2,3,5,6-tetrafluorophenyl methyl) pyridyl ] thioxirea N-(2-(2,3,5,6-tetrafluorophenyl methyl)pyridyl]thiourea N-(2 - (2,3,5,6-tetrafluorophenyl tri fluoromethyl)pyridyl]thiourea N-(2-(2,3,5,6-tetrafluorophenyl trifluoromethyl)pyridyl]thiourea N-(2-(2,3,5,6-tetrafluorophenyl ethyl)pyridyl]thiourea N-(2-(2,3,5,6-tetrafluorophenyl ethyl)pyridyl]thiourea N- (2-.(2,3,5, 6-tetrafluorophenyl chloro) pyrazinyl ] thiourea N-(2-(2,3,5,6-tetrafluorophenyl bromo) pyrazinyl ] thiourea N-(2-(2,3,5,6-tetrafluorophenyl bromo) pyrazinyl ] thiourea N- (2- (2,3,5,6 -^tetraf luorophenyl bromo) pyridazinyl) ] thioxirea ethyl -N* - 2- (4- ethyl -N* - 2- (4- ethyl -N' - 2- ethyl -N' - 2- (6-• ethyl -N* - 2- (6- ethyl -N' - 2- (4- ethyl -N' - 2- (4- (3- ethyl -N' - 2- (4- (3- ethyl -N" - 2- ethyl -N' - 2- (6- ethyl -N* - 2- (5- ethyl -N' - 2- (6- ethyl -N" - 2- (5- ethyl -N" - 2- (6- ethyl -N' - 2- (5- ethyl -N' - 2- (6- ethyl -N' - 2- (5- ethyl -N* - 2- (6- ethyl -N'- 2- (5- ethyl -N' - 2- (5- ethyl -N'- 2- (6- ethyl -N'- 2- (5- ethyl -N*- (3 -(6- 40 45 . / "V.: .. •-rv'yc ■ X-8571A 260293 N-(2-(2,3,5,6-tetrafluorophenyl)ethyl)-N* -1(3-(6-chloro)pyridazinyl)]thiourea N- (2-(2,3,5,6-tetrafluorophenyl)ethyl)-N•-(2-(6-cyano) pyridyl] thiourea N- (2- (2,3,5,6-tetrafluorophenyl)ethyl)-N'-[2-(5-cyano)pyridyl]thiourea N- (2-(2,3,5,6-tetrafluorophenyl)ethyl)-N' -[2-(5-cyano)pyraziny1]thiourea N- (2-(2,3,5,6-tetrafluorophenyl)ethyl)-N'-[2-(6-cy ano) pyraziny 1 ] thiourea N- (2- (2,3,5,6-tetraf luorophenyl) ethyl) -N' - [ (3- (6-cyano)pyridazinyl) ] thiourea N-(2-(2,3,5,6-tetraf luorophenyl) ethyl )-N'-(2-[l,3,4-thiadiazoyl]) thioxirea N- (2- (2,3,5,6-tetrafluorophenyl)ethyl)-N' -12-benzimidazolyl) thioxirea N-(2-(2,3,5,6-tetrafluorophenyl)ethyl)-N' -(2-imidazolyl) thioxirea N- (2- (2-chlorophenyl)ethyl) -N' - (2-thiazolyl) thiourea N-(2-(2-chlorophenyl)ethyl)-N*-[2-(4-methyl) thiazolyl] thioxirea N- (2- (2-chlorophenyl) ethyl) -N' - [2-(4,5- dimethyl) thiazolyl] thioxirea N- (2- (2-chlorophenyl) ethyl) -N' - (2-benzothiazolyl) thioxirea N-(2-(2-chlorophenyl)ethyl)-N'-[2-(6-fluoro)benzothiazolyl]thiourea N- (2- (2-chlorophenyl)ethyl)-N'-[2-(6-chloro) pyraz inyl] thioxirea N- (2-(2-chloropheny 1)ethyl)-N'-[2-(4-(3-pyridy1) thiazolyl) ] thioxirea N-(2-(2-chlorophenyl)ethyl)-N'-[2-(4-(3-nitrophenyl) thiazolyl) ] thioxirea N- (2 - (2-chlorophenyl) ethyl) -N' - (2-pyridyl) thiourea N- (2- (2-chlorophenyl)ethyl) -N' - [2- (6-bromo) pyr i^l ] thiourea N- (2- (2-chlorophenyl)ethyl)-N'-[2-(6-chloro)pyridyl]thiourea N- (2-(2-chlorophenyl)ethyl)-N'-[2-(6-methyl) pyridyl ] thioxirea N- (2- (2-chlorophenyl) ethyl) -N' - [2- (5-methyl)pyridyl]thiourea N- (2- (2-chlorophenyl) ethyl) -N' - [ 2 - (6-trif luoromethyl) pyridyl] thioxirea N-(2-(2-chlorophenyl)ethyl)-N'-12-(5-trif luoromethyl) pyrictyl] thioxirea Vji«' 1 0 40 45 X-8571A 2 6 0 c S N-.(2-(2-chlorophenyl)ethyl) -N'-[2- (6-ethyl)pyridyl]thiourea N-(2-(2-chlorophenyl)ethyl)-N'-[2-(5-ethy1)pyridyl]thiourea N-(2-(2-chlorophenyl)ethyl)-N•-[2-(6-bromo)pyrazinyl]thiourea N-(2-(2-chlorophenyl)ethyl)-N'- [ (3-(6-bromo)pyridazinyl)]thiourea N- (2-(2-chlorophenyl)ethyl)-N•-[2 -(6-cyano)pyridyl]thiourea N-(2-(2-chlorophenyl)ethyl)-N*-[2- (5-cyano)pyridyl]thiourea N- (2-(2-chlorophenyl)ethyl)-N'-[2-(5-cyano)pyrazinyl]thiourea N-(2-(2-chlorophenyl)ethyl)-N'-[2- (6-cyano)pyrazinyl]thiourea N- (2-(2-chlorophenyl)ethyl)-N'-[(3-(6-cyano)pyridazinyl)]thiourea N- (2-(2-chlorophenyl)ethyl)-N'-{2-[l,3,4-thiadiazoyl])thiourea N- (2-(2-chlorophenyl)ethyl)-N'-(2-benzimidazolyl)thiourea N-(2-(2-chlorophenyl)ethyl)-N'-(2-imidazolyl)thiourea N-(2-(3-chlorophenyl)ethyl)-N'-(2-thiazolyl)thiourea N- (2-(3-chlorophenyl)ethyl)-N'-[2-(4-methyl)thiazolyl]thiourea N- (2-(3-chlorophenyl)ethyl)-N*-[2-(4,5-dimethyl)thiazolyl]thiourea N-(2-(3-chloropheny1)ethyl)-N' - (2-benzothiazolyl)thiourea N-(2-(3-chlorophenyl)ethyl)-N'-[2 -(6-fluoro)benzothiazolyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-[2-(6-chloro)pyrazinyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-{2-(4-(3-pyridyl)thiazolyl)]thiourea N-(2-(3-chlorophenyl)ethyl)-IT -[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N- (2 - (3-chlorophenyl)ethyl)-N'-(2-pyridyl)thiourea N-(2-(3-chlorophenyl)ethyl)-N"-[2-(6-bromo)pyridyl]thiourea N- (2- (3-chlorophenyl)ethyl)-N«-[2 -(6-chloro)pyridyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-[2-(6-methyl)pyridyl]thiourea 1 0 1 5 40 45 260 Z* o X-8571A -34- N-(2-(3-chlorophenyl)ethyl)-N'-[2-(5-methyl)pyridyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N•-[2-(6-trifluoromethyl)pyridyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-[2-(5-trifluoromethyl)pyridyl]thiourea N- (2-(3-chlorophenyl)ethyl)-N'-[2-(6-ethyl)pyridyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N4-[2-(5-ethy1)pyridyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-[2-(6~ bromo)pyrazinyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-t(3-(6-bromo)pyridazinyl)]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-[2-(6-cyano)pyridyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N•-[2-(5-cyano)pyridyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-[2-(5-cyano)pyrazinyl]thiourea N- (2-(3-chlorophenyl)ethyl)-N'-[2-(6-cyano)pyrazinyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-f(3-(6-cyano)pyridazinyl)]thiourea N- (2- (3-chlorophenyl) ethyl) -N' - (2- [1., 3,4-thiadiazoyl])thiourea N- (2-(3-chlorophenyl)ethyl)-N•-(2-benzimidazolyl)thiourea N-(2-(3-chlorophenyl)ethyl)-N'-(2-imidazolyl)thiourea N- (2- (1-cycloMxenyl) ethyl) -N' - [2 - (4,5-dimethyl)thiazolyl]thiourea N-(2-(1-cyclohexenyl)ethyl)-N'-(2-benzothiazolyl)thiourea N-(2-(1-cyclohexenyl)ethyl)-N*-[2-(6-fluoro)benzothiazolyl]thiourea N-(2-(1-cyclohexenyl)ethyl)-N'-[2-(6-chloro)pyrazinyl]thiourea N-(2-(1-cyclohexenyl)ethyl)-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-(2-(1-cyclohexenyl)ethyl)-N'-[2- (4- (3-nitrophenyl)thiazolyl)]thiourea N-(2-(1-cyclohexenyl)ethyl)-N*-[2-(6-bromo)pyridyl]thiourea N-(2-(1-cyclohexenyl)ethyl)-N'-[2-(6-chloro)pyridyl]thiourea 1 5 40 45 X-8571A- 2 6 u l. $ N-(2-(l-cyclohexenyl)ethyl)-N'- [2- (6-methyl)pyridyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[2- (6-trifluoromethyl)pyridyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[2 - (6-ethy1)pyridyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[2 - (6-bromo)pyrazinyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[(3- (6-bromo)pyridazinyl)]thiourea N-(2-(l-cyclohexenyl)ethyl)~N'-[2-(6-cyano)pyridyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[2-(6-cyano)pyrazinyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-(2-[1,3,4-thiadiazoyl])thiourea N-.(2- (l-cyclohexenyl) ethyl) -N' - (2-benzimidazolyl)thiourea N-(2-(l-cyclohexenyl)ethyl) -N'-(2-imidazolyl)thiourea N- (2-(2-naphthyl)ethyl)-N'-(2-thiazolyl)thiourea N-(2-(2-naphthyl)ethyl)-N'-[2-(4-methyl)thiazolyl]thiourea N-{2-(2-naphthyl)ethyl)-N'-[2-(4,5-dimethyl)thiazolyl]thiourea N-(2-(2-naphthyl)ethyl)-N*-[2-(4-cyano)thiazolyl]thiourea N-(2-(2-naphthyl)ethyl) -N'-[2- (4-trifluoromethyl)thiazolyl]thiourea N-(2-(2-naphthyl)ethyl) -N'-(2-benzothiazolyl)thiourea N-(2-(2-naphthyl)ethyl)-N'-[2- (6-fluoro)benzothiazolylj thiourea N-(2-(2-naphthyl)ethyl)-N'-[2- (6-chloro)pyrazinyl]thiourea N-(2-(2-naphthyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N-(2-(2-naphthyl)ethyl)-N'-[2- (4- (3-pyridyl)thiazolyl)]thiourea N-(2-(2-naphthyl)ethyl)-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-'(2- (2-naphthyl) ethyl) -N' - (2-pyridyl) thiourea N-(2-(2-naphthyl)ethyl)-N'-[2-(6-bromo)pyridyl]thiourea N-(2-(2-naphthyl)ethyl)-N'-[2- (5-bromo)pyridyl]thiourea N-(2-(2-naphthyl)ethyl)-N'-[2-(6-chloro)pyridyl]thiourea ^6 0 2 y 5 X-8571A -36- N-(2-(2-naphthyl)ethyl)-K'-[2-(5-chloro)pyridyl]thiourea N- (2- (2-naphthyl)ethyl)-N' -- [2- (6-methyl)pyridyl]thiourea 5 N-(2-(2-naphthyl)ethyl)-N'-[2— <5 — methyl)pyridyl]thiourea N-(2-(2-naphthyl)ethyl)-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N-(2-(2-naphthyl)ethyl)-N'-[2- (5- 1 0 trifluoromethyl)pyridyl]thiourea N-(2-(2-naphthyl)ethyl)-N'-[2-(6-ethy1)pyridyl]thiourea N-(2-(2-naphthyl)ethyl)-N' — [2 —(5 — ethyl)pyridyl]thiourea N- (2- (2-naphthyl) ethyl) -N' - [2-(5- chloro)pyrazinyl]thiourea N-(2-(2-naphthyl)ethyl)-N'-[2-(6-bromo)pyrazinyl]thiourea N-(2-(2-naphthyl)ethyl)-N'-[2— {5— 2 0 bromo)pyrazinyl]thiourea N-(2-(2-naphthyl)ethyl)-N'-[(3-(6-bromo)pyridazinyl)]thiourea N-(2-(2-naphthyl)ethyl)-N'-t(3-(6-chloro)pyridazinyl)]thiourea 2 5 N-(2-(2-naphthyl)ethyl)-N'-[2-(6- cyano)pyridyl]thiourea N-(2-(2-naphthyl)ethyl)-N' — [2 —(5— cyano)pyridyl]thiourea N- (2-(2-naphthyl)ethyl)-N1-[2 —(5 — 3 0 cyano) pyraz inyl] thiourea N-(2-(2-naphthyl)ethyl)-N*-[2-(6-cyano)pyrazinyl]thiourea N-(2-(2-naphthyl)ethyl)-N'-[(3-(6-cyano)pyridaz inyl)]thiourea 3 5 N- (2- (2-naphthyl) ethyl) -N' - (2-[1,3, 4-thiadiazoyl])thiourea N-(2-(2-naphthyl)ethyl)-N' -(2-benzimidazolyl)thiourea N- (2- (2-naphthyl) ethyl) -N' - (2-imidazolyl) thiourea N- (2-(2,5-dimethoxypheny1)ethyl)-N'- (2- 4 0 thiazolyl)thiourea N- (2-(2,5-dimethoxyphenyl)ethyl)-N'-[2- (4-methyl)thiazolyl]thiourea N- (2- (2,5-dimethoxyphenyl)ethyl)-N'-[2- (4,5-dimethyl)thiazolyl]thiourea 4 5 N-(2-(2,5-dimethoxyphenyl)ethyl)-N'- (2- benzothiazolyl)thiourea 1 0 I > 40 45 X-8571A 260 293 N- (2- (2, 5-dimethoxyphenyl) ethyl) -N' - [2- (6-fluoro)benzothiazolyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2- (6-chloro)pyrazinyl]thiourea N- (2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-(2-(2, 5-dimethoxyphenyl)ethyl)-N'-[2- (4- (3-nitrophenyl)thiazolyl)]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-(2-pyridyl)thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(6-bromo)pyridyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(6-chloro)pyridyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(6-methy1)pyridyl]thiourea N- (2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(5-methyl)pyridyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(5-tri fluoromethyl)pyridyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N1-[2-(6-ethyl)pyridyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(5-ethyl)pyridyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(6-bromo)pyrazinyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[(3-(6-bromo)pyridazinyl)]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(6-cyano)pyridyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(5-cyano)pyridyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(5-cyano)pyrazinyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(6-cyano)pyrazinyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)—N' — [(3 —{6-cyano)pyridazinyl)]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-(2-[l,3,4-thiadiazoyl])thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-(2-benzimidazolyl)thiourea I ) 40 45 X-8571A 26 0 £ o 3 N- (2- (2,5-dimethoxyphenyl) ethyl) -N' - (2-imidazolyl)thiourea N-(2-(2-azidophenyl)ethyl)-N'-(2-thiazolyl)thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(4-methyl)thiazolyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(4,5-dimethyl)thiazolyl]thiourea N-(2-(2-azidophenyl)ethyl)-N1-[2-(4-cyano)thiazolyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-(2-benzothiazolyl)thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(6-fluoro)benzothiazolyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(6-chloro)pyrazinyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-(2-(2-azidophenyl)ethyl)-N'-(2-pyridyl)thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(6-bromo)pyridyl]thiourea N-(2-(2-azidophenyl)ethyl)-N1-[2-(5-bromo)pyridyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(6-chloro)pyridyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(6-methy1)pyridyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(5-methyl)pyridyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N—(2-(2-azidophenyl)ethyl)-N'-[2-(5-trifluoromethyl)pyridyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2—(6— ethyl)pyridyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(5-ethyl)pyridyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea X-8571A -39- 26 0 N- (2- (2-azidophenyl)ethyl) -N' - [2- (6-bromo)pyrazinyl]thiourea N—(.2- (2-azidophenyl) ethyl) -N' - [2- (5-bromo)pyrazinyl]thiourea N- (2-(2-azidophenyl)ethyl)-N'-[ (3- (6-bromo)pyridazinyl)]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2-(6-cyano)pyridyl]thiourea N-(2- (2-azidophenyl)ethyl)-N'-[2-(5-cyano)pyridyl]thiourea N- (2-(2-azidophenyl)ethyl)-N1-[2-(5-cyano)pyrazinyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[2- (6-cyano)pyraz inyl]thiourea N-(2-(2-azidophenyl)ethyl)-N'-[ (3- (6-cyano)pyridazinyl)]thiourea N-(2-(2-azidophenyl)ethyl)-N'-(2-[l,3,4-thiadiazoyl])thiourea N-(2-(2-azidophenyl)ethyl)-N'-(2-benzimidazolyl)thiourea N-(2-(2-azidophenyl)ethyl) -N'-(2-imidazolyl)thiourea N-(2 - (2,3,4-trifluorophenyl)ethyl)-N* -(2-thiazolyl)thiourea N-(2 - (2,3/4-trifluorophenyl)ethyl)-N'-[2 - (4-methyl)thiazolyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[2- (4,5-dimethyl)thiazolyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N' -[2 - (4-cyano)thiazolyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N1-[2-(4-trifluoromethyl)thiazolyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N' -(2-benzothiazolyl)thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[2- (6-fluoro)benzothiazolyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[2- (6-chloro)pyrazinyl]thiourea N-(2 -(2,3,4-trifluorophenyl)ethyl)-N'-[2- (4-ethyl)thiazolyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N' -[2- (4-(3-pyridyl)thiazolyl)]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N' -[2- (4- (3-nitrophenyl)thiazolyl)]thiourea 40 45 X-8571A 26 0 29 N-(2-(2,3,4-trifluorophenyl)ethyl)-N'- (2-pyridyl)thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(6-bromo)pyridyl]thiourea N- (2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(5-bromo)pyridyl]thiourea N- (2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(6-chloro)pyridyl]thiourea N- (2-(2,3,4-trifluorophenyl)ethyl)-N*-[2-(5-chloro)pyridyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(6-methyl)pyridylj thiourea N- (2 - (2,3,4-trifluorophenyl)ethyl)-N'-[2-(5-methyl)pyridyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N- (2 - (2,3,4-trifluorophenyl)ethyl)-N'-[2-fS-trif luoromethyl )pyridyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(6-ethyl)pyridyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(5-ethyl)pyridyl]thiourea N- (2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea N- (2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(6-bromo)pyrazinyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[(3-(6-bromo)pyridazinyl)]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea N- (2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(6-cyano)pyridyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(5-cyano)pyridyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[2-(5-cyano)pyrazinyl]thiourea N- (2- (2,3,4-trifluorophenyl)ethyl)-N'-[2-(6-cyano)pyrazinyl]thiourea N-(2-(2,3,4-trifluorophenyl)ethyl)-N'-[(3-(6-cyano)pyridazinyl)]thiourea N- (2 - (2,3,4-trifluorophenyl)ethyl)-N'-(2-[l,3,4-thiadiazoyl])thiourea N- (2-(2,3,4-trifluorophenyl)ethyl)-N*-(2-benzimidazolyl)thiourea ' 30 ) 40 45 X-8571A 260 29 N- (2- (2,3,4-trifluorophenyl)ethyl) -N' -'(2-imidazolyl)thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-(2-thiazolyl)thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(4-methyl)thiazolyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N' - [2 - (4,5-dimethyl)thiazolyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-(2-benzothiazolyl)thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(6-fluoro)benzothiazolyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N' — 12—(6— chloro)pyrazinyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N* — [2— (4—(3-pyridyl) thiazolyl) ] thiourea N-'(2- (2-fluoro-6-chlorophenyl) ethyl) -N' - [2- (4- (3-nitrophenyl)thiazolyl)]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N' - (2-pyridyl)thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(6-bromo)pyridyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(6-chloro)pyridyl]thiourea N- (2- (2-fluoro-6-chlorophenyl) ethyl) ---N' -[2-(6-methyl)pyridyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(5-methy1)pyridyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(5-tri fluoromethyl)pyridyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(6-ethyl)pyridyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N' -[2- (5-ethyl)pyridyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(6-bromo)pyrazinyl]thiourea N--(2- (2-fluoro-6-chlorophenyl) ethyl) -N' -[ (3- (6-bromo)pyridazinyl)]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(6-cyano)pyridyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N1 -[2-(5-cyano)pyridyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(5-cyano)pyrazinyl]thiourea 26 0 2 9 X-8571A N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(6-cyano)pyrazinyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[(3- (6-cyano)pyridazinyl)]thiourea 5 N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-(2-[l,3,4- thiadiazoyl])thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N*-(2-benzimidazolyl)thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-(2- 1 0 imidazolyl) thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-(2-thiazolyl)thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N' -[2-(4-methyl)thiazolyl]thiourea N-(2-(2, 6-dimethoxyphenyl)ethyl)-N'-[2-(4,5- dimethyl)thiazolyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-(2-benzothiazolyl)thiourea N-(2-(2, 6-dimethoxyphenyl)ethyl)-N'-[2-(6- 2 0 fluoro)benzothiazolyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(6-chloro)pyrazinyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-.{2- (2,6-dimethoxyphenyl)ethyl) -N' - [2- (4- (3- nitrophenyl)thiazolyl)]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-(2-pyridyl)thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(6-bromo)pyridyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethy1)-N'-[2-(6-chloro)pyridyl]thiourea N-(2-(2, 6-dimethoxyphenyl)ethyl)-N'-[2-(6-methy1)pyridyl]thiourea 3 5 N-(2-(2,6-dimethoxyphenyl)ethyl)-N*-[2-(5-methyl)pyridyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(6-tri fluoromethyl)pyridyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(5- 4 0 tri fluoromethyl)pyridyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(6-ethyl)pyridyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-M'-[2-(5-ethyl)pyridyl]thiourea 4 5 N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(6- bromo)pyrazinyl]thiourea «?o 260 29 X-8571A -43- N-(2-(2,6-dimethoxyphenyl)ethyl)-N'—[(3-(6— bromo)pyridazinyl)]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(6-cyano)pyridyl]thiourea 5 N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2- (5- cyano)pyridyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N1-[2-(5-cyano)pyrazinyl]thiourea N- (2-(2,6-dimethoxyphenyl)ethyl)-N'-[2- (6- 1 0 cyano)pyrazinyl]thiourea N- (2- (2,6-dimethoxyphenyl)ethyl)-N1-[(3-(6-cyano)pyridazinyl)]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-(2-11,3,4-thiadiazoyl])thiourea N- (2 - (2, 6 -dimethoxyphenyl) ethyl)-N1 -(2- benzimidazolyl)thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-(2-imidazolyl)thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-(2- 2 0 thiazolyl)thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N"-[2- (4-methyl)thiazolyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2 - (4,5-dimethyl)thiazolyl]thiourea 2 5 N- (2- (2,3, 6-trichlorophenyl) ethyl) -N' - [2- (4- cyano)thiazolyl]thiourea N-(2-(2,3,6-ti ichlorophenyl)ethyl)-N'-[2 - (4-trifluoromethyl)thiazolyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-(2- 3 0 benzothiazolyl)thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2- (6-fluoro)benzothiazolyl]thiourea N-'(2- (2,3, 6-trichlorophenyl) ethyl) -N' - [2- (6-chloro)pyrazinyl]thiourea 3 5 N- (2- (2,3, 6-trichlorophenyl) ethyl) -N' - [2- (4- ethyl)thiazolyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2- (4- (3-pyridyl)thiazolyl)]thiourea N- (2- (?.,3, 6-trichlorophenyl) ethyl) -N' - [2- (4- (3- 4 0 nitrophenyl)thiazolyl)]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-(2-pyridyl)thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-W-[2- (6-bromo)pyridyl]thiourea 4 5 N- (2- (2,3, 6-trichlorophenyl) ethyl) -N' - [2- (5- bromo)pyridyl]thiourea 1 0 40 45 X-8571A- 26 0 2 9 N-(2-(2,3,6-trichlorophenyl)ethyl)-N' -[2- (6-chloro)pyridyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2-(5-chloro)pyridylj thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2-(6-methyl)pyridyl]thiourea N- (2-(2,3,6-trichlorophenyl)ethyl)-N'-[2-(5-methy1)pyridyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2-(6-tri fluoromethyl)pyridyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2-(5-trifluoromethyl)pyridyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2- (6-ethyl)pyridyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2- (5-ethyl)pyridyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2-(6-bromo)pyrazinyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2- (5-bromo)pyrazinyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[(3 - (6-bromo)pyridazinyl)]thiourea N- (2-(2,3,6-trichlorophenyl)ethyl)-N'-r(3-(6-chloro)pyridazinyl)]thiourea N- (2-(2,3,6-trichlorophenyl)ethyl)-N'-[2-(6-cyano)pyridyl]thiourea N- (2-(2,3,6-trichlorophenyl)ethyl)-N'-[2-(5-cyano)pyridyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2-(5-cyano)pyrazinyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[2-(6-cyano)pyrazinyl]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-[(3-(6-cyano)pyridazinyl)]thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-(2-[1,3,4-thiadiazoyl])thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-(2-benzimidazolyl)thiourea N-(2-(2,3,6-trichlorophenyl)ethyl)-N'-(2-imidazolyl)thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-(2-thiazolyl)thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(4-methyl)thiazolyl]thiourea X-8571A -45- 26 0 2 N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(4f 5-dimethyl)thiazolyl]thiourea N- (.2- (2, 6-dichlorophenyl)ethyl) -N'-(2-benzothiazolyl)thiourea 5 N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(6- fluoro)benzothiazolyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(6-chloro)pyrazinyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(4-(3-1 0 pyridyl)thiazolyl)]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N' -(2-pyridyl)thiourea N- (2-(2,6-dichlorophenyl)ethyl)-N*-[2-(6- 1 5 bromo)pyridyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(6-chloro)pyridyl]thiourea N- (2-(2,6-dichlorophenyl)ethyl)-N'-[2-(6-methy1)pyridyl]thiourea 2 0 N- (2 - (2, 6-dichlorophenyl)ethyl) -N' - [2- (5- methy1)pyridyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N- (2-(2,6-dichlorophenyl)ethyl)-N'-[2-(5- 2 5 trifluoromethyl)pyridyl]thiourea N-.(2- (2, 6-dichlorophenyl)ethyl) -N' - [2- (6-ethy1)pyridyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(5-ethyl)pyridyl]thiourea 3 0 N- (2- (2, 6-dichlorophenyl) ethyl) -N' - [2- (6- bromo)pyrazinyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N1 -[(3 -(6-bromo)pyridazinyl)]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(6- 3 5 cyano)pyridyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(5-cyano)pyridyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(5-cyano)pyrazinyl]thiourea 4 0 N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(6- cyano)pyrazinyl]thiourea N- (2- (2,6-dichlorophenyl)ethyl)-N'-[(3-(6-cyano)pyridazinyl)]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-(2-[1,3,4-4 5 thiadiazoyl]) thiourea 2 9 X-8571A -46- 26 0 N-(2-(2,6-dichlorophenyl)ethyl)-N' -(2-benzimidazolyl)thiourea N- (2-(2,6-dichlorophenyl)ethyl)-N'-(2-imidazolyl)thiourea 5 N- (2-(2,3,5-trichlorophenyl)ethyl)-N'-(2- thiazolyl)thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(4-methyl)thiazolyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(4,5- 1 0 dimethyl)thiazolyl]thiourea N—(2 - (2,3,5-trichlorophenyl)ethyl)-N'-[2-(4-cyano)thiazolyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea 15 N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-(2- benzothiazolyl)thiourea N- (2 - (2,3,5-trichlorophenyl)ethyl)-N'-[2-(6-fluoro)benzothiazolyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(6- 2 0 chloro)pyraz inyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N- (2 - (2,3,5-trichlorophenyl)ethyl)-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea 2 5 N- (2- (2,3, 5-trichlorophenyl) ethyl) -N-' -[2- (4- (3- nitrophenyl)thiazolyl)]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-(2-pyridyl)thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N*-[2-(6- 3 0 bromo)pyridyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(5-bromo)pyridyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(6-chloro)pyridyl]thiourea 3 5 N-(2-(2,3,5-trichlorophenyl)ethyl)-N*-[2-(5- chloro)pyridyl]thiourea N- (2-(2,3,5-trichlorophenyl)ethyl)-N*-[2-(6-methy1)pyridylj thiourea N-(2- (2,3,5-trichlorophenyl)ethyl)-N'-[2-(5-40 methyl) pyr idyl j thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N*-[2-(5-tri fluoromethyl)pyridyl]thiourea 45 N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(6- ethyl)pyridyl]thiourea 1 0 1 5 3 5 40 45 X-8571A 2 6 0 N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2- (5-ethyl)pyridyl]thiourea N- (2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(6-bromo)pyrazinyl]thiourea N- (2- (2,3,5-trichlorophenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[(3-(6-bromo)pyridazinyl)]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[(3- (6-chloro)pyridazinyl)]thiourea N- (2- (2,3,5-trichlorophenyl)ethyl)-N'-[2-(6-cyano)pyridyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(5-cyano)pyridyl]thiourea N- (2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(5-cyano)pyrazinyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[2-(6-cyano)pyrazinyl]thiourea N-(2-(2,3,5-trichlorophenyl)ethyl)-N'-[(3-(5-cyano)pyridazinyl)]thiourea N- (2- (2,3,5-trichlorophenyl)ethyl)-N'-(2-[1,3,4-thiadiazoyl])thiourea N-(2-(2,3,5-trichloropheny1)ethyl)-N'-(2-benzimidazolyl)thiourea N- (2-(2,3,5-trichlorophenyl)ethyl)-N'-(2-imidazolyl)thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-(2-thiazolyl)thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2-(4-methy1)thiazolyl]thiourea N- (2- (3,5-dichlorophenyl)ethyl)-N'-[2-(4,5-dimethyl) thiazolyl] thioxirea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2-(4-cyano)thiazolyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N1-[2-(4-trifluoromethyl)thiazolyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-(2-benzothiazolyl)thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N1-[2-(6-fluoro)benzothiazolyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2-(6-chloro)pyrazinyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea X-8571A -48- 2 6 0 2 9 3 N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2- (4- (3-pyridyl)thiazolyl)]thiourea N-(2- (3,5-dichlorophenyl)ethyl)-N'-[2-(4- (3-nitrophenyl)thiazolyl)]thiourea 5 N-(2- (3,5-dichlorophenyl)ethyl)-N'-(2-pyridyl)thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2-(6-bromo)pyridyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2-(5-bromo)pyridyl]thiourea N- (2-(3,5-dichlorophenyl) ethyl) -N' - [2-(6- chloro)pyridyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2-(6- 1 5 methyl)pyridyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2-(5-methy1)pyridyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2-(6— trifluoromethyl)pyridyl]thiourea 2 0 N- (2- (3,5-dichlorophenyl) ethyl) -N' - [2 - (5- tri fluoromethyl)pyridyl]thiourea N- (2- (3,5-dichlorophenyl)ethy1)-N'-[2-(6-ethyl)pyridyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[2-(5- 2 5 ethyl)pyridyl]thiourea N- (2- (3,5-dichlorophenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N*-[2-(6-bromo)pyrazinyl]thiourea 3 0 N- (2 - (3,5-dichlorophenyl) ethyl) -N' - [2 - (5- bromo)pyrazinyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[(3- (6-bromo)pyridazinyl)]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[(3- (6- 3 5 chloro)pyridazinyl)]thiourea N-(2-(3,5-dichlorophenyl)ethyl)—N * -[2- (6 — cyano)pyridyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N■-[2-(5-cyano)pyridyl]thiourea 40 N- (2- (3,5-dichlorophenyl) ethyl) -N' - [2- (5- cyano)pyrazinyl]thiourea N-(2-{3,5-dichlorophenyl)ethyl)-N'-[2- (6 -cyano)pyrazinyl]thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-[(3- (6- 4 5 cyano)pyridazinyl)]thiourea 1 0 15 20 25 40 45 260293 X-8571A -49- N-(2-(3,5-dichlorophenyl)ethyl)-N'-(2-[1,3,4-thiadiazoyl])thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-(2-benzimidazolyl)thiourea N-(2-(3,5-dichlorophenyl)ethyl)-N'-(2-imidazolyl)thiourea N-(2-(3-fluorophenyl)ethyl) -N' -N-(2- (3-fluorophenyl)ethyl)-N'-methyl)thiazolyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-dimethyl)thiazolyl]thiourea N-' (2 - (3 - f luorophenyl) ethyl) -N' -benzothiazolyl)thiourea N-(2-(3-fluorophenyl)ethyl)-N'-fluoro)benzothiazolyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-chloro)pyrazinyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N1 -pyridyl)thiazolyl)]thiourea N-(2-(3-fluorophenyl)ethyl) -N' -nitrophenyl)thiazolyl)]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-N-(2-(3-fluorophenyl)ethyl)-N'-bromo)pyridyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-chloro)pyridyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-methyl)pyridyl]thiourea N-(2-{3-fluorophenyl)ethyl) -N' -methyl)pyridyl]thiourea N-(2-(3-fluorophenyl)ethyl) -N' -trifluoromethyl)pyridyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-trifluoromethyl)pyridyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-ethyl)pyridyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-ethyl)pyridyl]thiourea N- (2- (3-fluorophenyl)ethyl)-N'-bromo)pyrazinyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N•-bromo)pyridazinyl)]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-cyano)pyridyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N*-cyano)pyridyl]thiourea 2-thiazolyl)thiourea 2- (4- 2- (4,5- 2- 2- (6-2- (6-2- (4-(3-2— (4— (3 — 2-pyridyl)thiourea 2- (6- 2- (6t 2- (6-2- (5-2- (6-2- (5-2-(6-2- (5-2- (6-(3 —(6— 2-(6-2- (5- X-8571A -50- - O 26 0 2!9 N-(2-(3-fluorophenyl)ethyl)-N'-[2-(5-cyano)pyrazinyl]thiourea N- (2- (3-fluorophenyl)ethyl)-N'-[2-(6-cyano)pyrazinyl]thiourea 5 N-(2-(3-fluorophenyl)ethyl)-N* - [(3-(6- cyano)pyridazinyl)]thiourea N- (2-(3-fluorophenyl)ethyl)-N'-(2-[1,3,4-thiadiazoyl])thiourea N-(2-(3-fluorophenyl)ethyl)-N'-(2- 1 0 benzimidazolyl)thiourea N-(2-(3-fluorophenyl)ethyl)-N'-(2-imidazolyl)thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'- (2-thiazolyl)thiourea N- (2- (2, 4-dimetho^phenyl) ethyl)-N'-[2-(4- 1 5 methyl)thiazolyl]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[2-(4,5-dimethyl)thiazolyl]thiourea b- (2-(2,4-dimethoxyphenyl)ethyl)-N'-12-(4-cyano)thiazolyl]thiourea N- (2- (2, 4-dimethoxyphenyl) ethyl) -N' - 12- (4- trifluoromethyl)thiazolyl]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-(2-benzothiazolyl)thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N*-[2-(6- 2 5 fluoro)benzothiazolyl]thiourea N- (2-(2,4-dimethoxyphenyl)ethyl)-N*-[2-(6-chloro)pyrazinyl]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea 3 0 N~ (2, 4-dimethoxyphenyl)ethyl) -N' - [2- (4- (3- pyridyl)thiazolyl)]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N*-(2- 3 5 pyridyl)thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N1 -[2-(6-bromo)pyridyl]thiourea N- (2- (2,4-dimethoxyphenyl)ethyl)-N' -[2-(5-bromo)pyridy1]thiourea 40 N- (2- (2,4-dimethoxyphenyl)ethyl)-N'-[2- (6- chloro)pyridyl]thiourea N-(2-'2,4-dimechoxyphenyl)ethyl)-N•-[2 -(5-chloro)pyridyl]thiourea N- (2-(2,4-dimethoxyphenyl)ethyl)-N'-12-(6- 4 5 methyl)pyridyl]thiourea 260 r L X-8571A -51- N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-(2-(5-methyl)pyridyl]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[2-(6-trifluoromethyl)pyridyl]thiourea 5 N-(2-(2, 4-dimethoxyphenyl)ethyl)-N'-[2- (5- tri fluoromethyl)pyridyl]thiourea N- (2-(2,4-dimethoxyphenyl)ethyl)-N'-12-(6-ethyl)pyridyl]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[2- (5- 1 0 ethyl)pyridyl]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[2-(6-bromo)pyrazinyl]thiourea 15 N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[2- (5- bromo)pyrazinyl]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)—N'-[(3—(6— bromo)pyridazinyl)]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[(3-(6- 2 0 chloro)pyridazinyl)]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'- [2- (6-cyano)pyridyl]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[2-(5-cyano)pyridyl]thiourea 25 N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[2-(5- cyano)pyrazinyl]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[2-(6-cyano)pyrazinyl]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-[(3-(6- 3 0 cyano)pyridazinyl)]thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N' - (2 - [1,3, 4 -thiadiazoyl])thiourea N-(2-(2,4-dimethoxyphenyl)ethyl)-N'-(2-benzimidazolyl)thiourea 3 5 N- (2- (2/4-dimetho5QTphenyl)ethyl) -N' - (2- imidazolyl)thiourea N-[(4-methyl)-3-pentenyl]-N'-(2-thiazolyl)thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(4-methyl)thiazolyl]thiourea 40 N-t(4-methyl)-3-pentenyl]-N'-[2-(4,5- dimethyl)thiazolyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-12-{4-cyano)thiazolyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(4-45 trifluoromethyl)thiazolyl]thiourea 20 25 40 45 X-8571A -52- 2 6 0 2 9 N-[(4-methyl)-3-pentenyl]-N'-(2-benzothiazolyl)thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea N-t(4-methyl)-3-pentenyl]-N'-[2-(6-chloro)pyrazinyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(4-ethyl)thiazolyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(4- (3-pyridyl)thiazolyl)]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(4- (3-nitrophenyl)thiazolyl)]thiourea N- [(4-methyl)-3-pentenyl]-N'-(2-pyridyl)thiourea N-t(4-methyl)-3-pentenyl]-N'-[2-(6-bromo)pyridyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(5-bromo) pyridyl]thiourea N-[(4-methyl)-3-pentenyl]—N'-[2-(6-chloro)pyridyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(5-chloro)pyridyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(6-methyl)pyridyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(5-methyl)pyridyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(5-trifluoromethyl)pyridyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(6-ethyl)pyridyl]thiourea N- [(4-methyl)-3-pentenyl]-N•-[2-(5-ethyl)pyridyl]thiourea N-'[ (4-methyl) -3-pentenyl] -N' - [2- (5-chloro)pyrazinyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(6-bromo)pyrazinyl]thiourea N-[(4-methyl)-3-pentenyl]-N•-[2-(5-bromo)pyrazinyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[(3-(6-bromo)pyridazinyl)]thiourea N-[(4-methyl)-3-pentenyl]-N"-[(3-(6-chloro)pyridazinyl)]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(6-cyano)pyridyl]thiourea X-8571A 260 L. c 1 0 40 45 N- [ (4-methyl) -3-pentenyl] -N' - [2- (5-cyano)pyridyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[2-(5-cyano)pyrazinyl]thiourea N-[{4-methyl)-3-pentenyl]-N'-[2-(6-cyano)pyrazinyl]thiourea N-[(4-methyl)-3-pentenyl]-N'-[(3-(6-cyano)pyridazinyl)]thiourea N-[(4-methyl)-3-pentenyl]-N'-(2-[1,3,4-thiadiazoyl])thiourea N-[(4-methyl)-3-pentenyl]-N'-(2-benzimidazolyl)thiourea N-[(4-methyl)-3-pentenyl]-N'-(2-imidazolyl] thiourea N-(2-cis-phenylcyclopropyl -N' -[2- (4- methyl)thiazolyl]thiourea N-(2-cis-phenylcyclopropyl -N' -[2- (4,5- dimethyl)thiazolyl]thiourea N- (2-cis-phenylcyclopropyl -N' -(2- benzothiazolyl)thiourea N- (2-cis-phenylcyclopropyl -N1 -[2- (6- fluoro)benzothiazolyl]thiourea N-(2-cis-phenylcyclopropyl -N' (6- chloro)pyrazinyl]thiourea N- (2-cis-phenylcyclopropyl -N" -[2- (4-(3- pyridyl)thiazolyl)]thiourea N- (2-cis-phenylcyclopropyl -N' -[2- (4-(3- nitrophenyl)thiazolyl)]thiourea N- (2-cis-phenylcyclopropyl -N' -[2- (6- bromo)pyridyl]thiourea N-(2-cis-phenylcyclopropyl -N' -[2- (6- chloro)pyridyl]thiourea N-(2-cis-phenylcyclopropyl -N' (6- methyl)pyridyl]thiourea N- (2-cis-phenylcyclopropyl -N' -[2- (6- trifluoromethyl)pyridyl]thiourea N- (2-cis-phenylcyclopropyl -N' -[2- (6- ethyl)pyridyl]thiourea N-(2-cis-phenylcyclopropyl -N' -[2- (6- bromo)pyrazinyl]thiourea N-(2-cis-phenylcyclopropyl -N* (6- cyano)pyridylJ thiourea N- (2-cis-phenylcyclopropyl -N' -[2- (5- cyano)pyrazinyl]thiourea N-(2-cis-phenylcyclopropyl -N' (6- cyano)pyrazinyl]thiourea X-8571A -54- ■" v v L. 4 2 6 0 " N-(2-cis-phenylcyclopropyl)-N1-[(3 - (6-cyano)pyridazinyl)]thiourea N-(2-cis-phenylcyclopropyl)-N'-(2-[l,3,4-thiadiazoyl])thiourea 5 N-(2-cis-phenylcyclopropyl)-N'-(2- benzimidazolyl)thiourea K-(2-cis-phenylcyclopropyl)-N'-(2-imidazolyl)thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'- (2-thiazolyl)thiourea N- [ (2-methyl) -2- (2, 6-dichlorophenyl)ethyl] -N' - [2 - (4- methyl)thiazolyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2- (4,5-dimethyl)thiazolyl]thiourea N- [ (2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(4- 1 5 cyano)thiazolyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-(2-benzothiazolyl)thiourea 2 0 N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(6- fluoro)benzothiazolyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(6-chloro)pyrazinyl]thiourea N-1(2-methyl)-2- (2,6-dichlorophenyl)ethyl]-N'-[2-(4- 2 5 ethyl)thiazolyl]thiourea N-'[ (2-methyl) -2- (2, 6-dichlorophenyl) ethyl] -N' - [2- (4-(3-pyridyl)thiazolyl)]thiourea N-t(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea 3 0 N- [ (2-methyl) -2- (2, 6-dichlorophenyl) ethyl] -N* - (2- pyridyl)thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(6-bromo)pyridyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2- (5- 3 5 bromo)pyridyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(6-chloro)pyridyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea 40 N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(6- methyl) pyridyl ] thioxirea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(5-methy1)pyridyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2 - (6- 4 5 trifluoromethyl)pyridylj thiourea 15 20 25 40 2 6 0 2 S 3 X-8571A -55- N-[ (2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(5-trifluoromethyl)pyridyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N' -[2 - (6-ethy1)pyridyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N' -[2 - (5-ethyl)pyridyl]thiourea .

N- [ (2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N' -[2- (5-chloro)pyrazinyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2 - (6-bromo)pyrazinyl]thiourea N-'[ (2-methyl) -2- (2, 6-dichlorophenyl) ethyl] -N' - [2- (-5-bromo)pyrazinyl]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N' - [ (3- (6-bromo)pyridazinyl)]thiourea N- [ (2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[(3 —(6-chloro)pyridazinyl)]thiourea N-[ (2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2- (6-cyano)pyridyl]thiourea N- [ (2-methyl) -2- (2,6-dichlorophenyl)ethyl] -N' - [2 - (15-cyano)pyridyl]thiourea N- [ (2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[2-(5-cyano) pyraz inyl ] thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N' -[2- (6 -cyano)pyrazinyl]thiourea N-[ (2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-[ (3- (6-cyano)pyridazinyl)]thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N'-(2-[1,3,4-thiadiazoyl])thiourea N- [ (2-methyl) -2- (2,6-dichlorophenyl)ethyl] -N' - (2-benzimidazolyl)thiourea N-[(2-methyl)-2-(2,6-dichlorophenyl)ethyl]-N' - (2-imidazolyl)thiourea N-[ (2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl]-N'-(2-thiazolyl)thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl]-N*-[2-(4-methyl)thiazolyl]thiourea N- [ (2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl]-N * -[2-(4,5-dimethyl)thiazolyl]thiourea N- [ (2,2-dimethyl)-2-(2-fluoro-6-chloropheni1)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N- [ (2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl]-N'-(2-benzothiazolyl)thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea X-d57.lA 260 i 9 1 0 1 5 3 5 40 45 N' -N' -n1 -n' -N' -N' -n' -N' -n' -n1 -n' -n' -N' -n' -n' -n'-n'-N' -N'-n' -N' -N'-N' - N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(6-chloro)pyrazinyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(4-ethyl)thiazolyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(4-(3-pyridyl)thiazolyl)]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-pyridyl)thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(6-bromo)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(5-bromo)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(6-chloro)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(5-chloro)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2 —(6-methyl)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(5-methyl)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(6-trifluoromethyl)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(5-trifluoromethyl)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(6-ethyl)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(5-ethyl)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(5-chloro)pyrazinyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(6-bromo)pyrazinyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chloropheny1)ethyl 2-(5-bromo)pyrazinyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl (3-(6-bromo)pyridazinyl)]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl (3-.(6-chloro)pyridazinyl) ] thiourea N-[(2,2-dimethyl) - 2 - (2 - £luoro-6-chlorophenyl)ethyl 2-(6-cyano)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl 2-(5-cyano)pyridyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6~chlorophenyl)ethyl 2-(5-cyano)pyrazinyl]thiourea 260 9 v., w X-8571A -57- N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl]-N'-[2-(6-cyano)pyrazinyl]thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl]-N'-[(3-(6-cyano)pyridazinyl)]thiourea 5 N-t(2,2-dimethyl)-2-(2-fluoro~6-chlorophenyl)ethyl]- N'-(2-[1,3,4-thiadiazoyl])thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl]-N'-(2-benzimidazolyl)thiourea N-[(2,2-dimethyl)-2-(2-fluoro-6-chlorophenyl)ethyl]- N'-(2-imidazolyl) thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(4,5-dimethyl) thiazolyl] thiourea N- [2-(2-pyridyl)ethyl]-N'-(2-benzothiazolyl)thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(6- 1 5 fluoro)benzothiazolyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(6-chloro)pyrazinyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea 2 0 N- [ 2 - (2 -pyridyl) ethyl ]-N'-[2-(4-(3- nitrophenyl)thiazolyl)]thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(6-bromo)pyrazinyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(6-cyano)pyridyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(6- cyano)pyrazinyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-(2-[l,3,4-thiadiazoyl])thiourea N-[2-(2-pyridyl)ethyl]-N'-(2-benzimidazolyl)thiourea 3 0 N- [2- (2-pyridyl) ethyl] -N'- (2-imidazolyl) thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'- [2-(4,5-dimethyl) thiazolyl] thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N' -(2-benzothiazolyl)thiourea 3 5 N-[2-(2-(6-methoxy)pyridyl)ethyl]-N' - [2- (6- fluoro)benzothiazolyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N1 -[2-(6-chloro)pyrazinyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(4-(3- 4 0 pyridyl)thiazolyl)]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N' - [2-(6-bromo)pyridyl]thiourea 45 N- [2 - (2 - (6-methoxy)pyridyl)ethyl] -N' - [2 - (6- chloro)pyridyl]thiourea 1 0 25 #35 40 45 0 X-8571A -58- """ ** 260 0 N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(6-methy1)pyridyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-£2 —(6— trifluoromethyl)pyridyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(6-ethyl)pyridyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(5-ethy1)pyridyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N1-[2-(6-bromo)pyrazinyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[(3-(6-bromo) pyridazinyl)]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(6-cyano)pyridyl]thiourea N-[2-(2-{6-methoxy)pyridyl)ethyl]-N'-[2-(5-cyano)pyridyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N' -[2- (5-cyano)pyrazinyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-{6-cyano)pyrazinyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethy1]-N'-[(3-(6-cyano)pyridazinyl)]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'- (2-[1,3,4-thiadiazoyl])thiourea N- [2- (2- (6-methoxy)pyridyl) ethyl] -N' r- [2-benzimidazolyl)thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N' -(2-imidazolyl)thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2-(4,5-dimethyl)thiazolyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]—N'-(2 — benzothiazolyl)thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2-(6-chloro)pyrazinyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2-(4- (3-pyridyl)thiazolyl)]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N*-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'—[2—(6-bromo)pyridyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2- (6-chloro)pyridyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2- (6-methyl)pyridyl]thiourea 40 45 X-8571A 2^0293 N-[2-(2-(6-ethoxy)pyridyl)ethyl -N' -[2- (6- trifluoromethyl)pyridyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl -N' -[2- (6- ethyl)pyridyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl -N' -[2- (5- ethyl)pyridyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl -N' -[2- (6- bromo)pyrazinyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl -N' -[ (3 -(6- bromo)pyridazinyl)]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl; -N' - [2-- (6- cyano)pyridyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl] -N' -[2- (5- cyano)pyrazinyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl; -N' -[2- (6- cyano)pyrazinyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl -N' -[ (3 -(6- cyano)pyridazinyl)]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl -N' -(2- [1,3,4- thiadiazoyl])thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl -N' -(2- benzimidazolyl)thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl -N1 -(2- imidazolyl)thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' -[2- (4,5- dimethyl)thiazolyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' -(2- benzothiazolyl)thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' -[2- (6- fluoro)benzothiazolyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' -[2- (6- chloro)pyrazinyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl; -N' -[2- (4-(3- pyridyl)thiazolyl)]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' -[2- (4-(3- nitrophenyl)thiazolyl)j thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' (6- bromo)pyridyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' -[2- (6- chloro)pyridyl]thiourea N-'[2- (2- (6-fluoro)pyridyl)ethyl -N1 -[2- (6- methyl)pyridyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N1 -[2- (6- trifluoromethyl)pyridyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N -[2- (6- bromo)pyraz inyl]thiourea 35 40 X-8571A -60- 26 0 N- [2-(2-(6-fluoro)pyridyl bromo)pyridazinyl)]thiourea N~[2-(2-(6-fluoro)pyridyl cyano)pyridyl]thiourea N-[2-(2-(6-fluoro)pyridyl cyano)pyrazinyl]thiourea N- [2-(2-(6-fluoro)pyridyl cyano)pyrazinyl]thiourea N-[2-(2-(6-fluoro)pyridyl cyano)pyridazinyl)]thiourea N- [2-(2-(6-fluoro)pyridyl thiadiazoyl])thiourea N- [2-(2-(6-fluoro)pyridyl benzimidazolyl)thiourea N- [2-(2-(6-fluoro)pyridyl imidazolyl)thiourea N- [2-(2-(5-fluoro)pyridyl thiazolyl)thiourea N- [2-(2-(5-fluoro)pyridyl methyl)thiazolyl]thiourea N-[2-(2-(5-fluoro)pyridyl dimethyl)thiazolyl]thiourea N- [2-(2-(5-fluoro)pyridyl cyano)thiazolyl]thiourea N-[2-(2-(5-fluoro)pyridyl] trifluoromethyl)thiazolyl]thiourea N- [2-(2-(5-fluoro)pyridyl) benzothiazolyl)thiourea N- [2-(2-(5-fluoro)pyridyl fluoro)benzothiazolyl]thiourea N- [2-(2-(5-fluoro)pyridyl chloro)pyrazinyl]thiourea N- [2-(2-(5-fluoro)pyridyl ethyl)thiazolyl]thiourea N- [2-(2-(5-fluoro)pyridyl pyridyl)thiazolyl)]thiourea N- [2-(2-(5-fluoro)pyridyl nitrophenyl)thiazolyl)j thioure N-[2-(2-(5-fluoro)pyridyl pyridyl)thiourea N- [2- (2-(5-fluoro)pyridyl bromo)pyridyl]thiourea N-[2-(2-(5-fluoro)pyridyl bromo)pyridyl]thiourea N- [2-(2-(5-fluoro)pyridyl chloro)pyridyl]thiourea ethyl -N'~ (3- (6- ethyl -N'- 2- (6- ethyl -N' - 2- (5- ethyl -N'- 2- (6- ethyl -N' - (3-(6- ethyl! -N* - 2-11/3,4- ethyl! -N'- 2- ethyl -N' - 2- ethyl -N" - 2- ethyl -N' - 2- (4- ethyl -N' - 2- (4,5- ethyl -N' - 2 — (4 — ethyl -N' - 2- (4- rea ethyl -N' - 2- ethyl -N' - 2- (6- ethyl -N" - 2- (6- ethyl -N'- 2-(4- ethyl -N' - 2—(4—(3— ethyl -N' - 2— (4— (3 — , ethyl -N' - 2- ethyl -N' - 2 — (6— ethyl -N' - 2- (5- ethyl -N' - 2- (6- 1 0 1 5 l \ 40 45 X-8571A 260 2 9 3 N-[2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (5- chloro)pyridyl]thiourea N-[2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (6- methyl)pyridyl]thiourea N- [2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (5- methyl)pyridyl]thiourea N-[2-(2-(5-fluoro)pyridyl)ethyl -N* - 2- (6- trifluoromethyl)pyridyl]thiourea N-[2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (5- trifluoromethy3)pyridyl]thiourea N-[2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (6- ethyl)pyridyl]thiourea N- [2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (5- ethyl)pyridyl]thiourea N-[2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (5- chloro)pyrazinyl]thiourea N- [2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (6- bromo)pyraz inyl]thiourea N-[2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (5- bromo)pyrazinyl]thiourea N-[2-(2-(5-fluoro)pyridyl)ethyl -N' - (3 - (6- bromo)pyridazinyl)]thiourea N- [2- (2 - (5-fluoro)pyridyl.) ethyl -N' - (3 -(6- chloro)pyridazinyl)]thiourea N- [2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (6- cyano)pyridyl]thiourea N-[2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (5- cyano)pyridyl]thiourea N-[2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- (5- cyano)pyrazinyl]thiourea N- [2 - (2-(5-fluoro)pyridyl)ethyl -N' - 2- (6- cyano)pyrazinyl]thiourea N-'[2- (2- (5-fluoro)pyridyl) ethyl -N' - (3 -(6- cyano) pyridazinyl) ] thiourea N- [2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- [1,3,4- thiadiazoyl])thiourea N- [2-(2-(5-fluoro)pyridyl)ethyl -N'- 2- benzimidazolyl)thiourea N-[2-(2-(5-fluoro)pyridyl)ethyl -N' - 2- imidazolyl)thiourea N- [2-(2-(4-fluoro)pyridyl)ethyl -N'_ 2- thiazolyl)thiourea N- [2-(2-(4-fluoro)pyridyl)ethyl -N'- 2- (4- methyl)thiazolyl]thiourea N- [2-(2-(4-fluoro)pyridyl)ethyl -N' - 2- (4,5- dimethyl)thiazolyl]thiourea 40 45 X-8571A 260 2 9 3 N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-(2-benzothiazolyl)thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2- (6-chloro)pyrazinyl]thiourea N-£2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2- (4-(3-nitrophenyl)thiazolyl)]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-(2-pyridyl)thiourea N-12-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(6-bromo)pyridyl]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(6-chloro)pyridyl]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(5-chloro) pyridyl] thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N"-[2-(6-methyl)pyridyl]thiourea N- [2-(2-(4-fluoro)pyridyl)ethyl]-N"-[2-(5-methyl)pyridyl]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N- [2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(5-tri fluoromethyl)pyridyl]thiourea N- [2-(2-(4-fluoro)pyridyl)ethyl] -N' -[2-(6-ethyl)pyridyl]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N* — [2 —(5— ethyl)pyridyl]thiourea N-[2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(5-chloro)pyrazinyl]thiourea N-.[2- (2- (4-fluoro)pyridyl)ethyl] -N* - [2- (6-bromo)pyrazinyl]thiourea N-(2-(2-(4-fluoro)pyridyl)ethyl]-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-(2-(4-fluoro)pyridyl)ethyl]-N'-[(3-(6-bromo)pyridazinyl)]thiourea 35 40 X-8571A -63- 26 0 2 9 N- [2-(2-(4-fluoro)pyridyl ethyl -N' -[(3 -(6- chloro)pyridazinyl)]thiourea N- [2- (2-(4-fluoro)pyridyl ethyl -N' -[2- (6- cyano)pyridyl]thiourea N- [2-(2-(4-fluoro)pyridyl ethyl] -N' -[2- (5- cyano)pyridyl]thiourea N- [2-(2-(4-fluoro)pyridyl ethyl -N' -[2- (5- cyano)pyrazinyl]thiourea N- [2-(2-(4-fluoro)pyridyl ethyl -N' (6- cyano)pyrazinyl]thiourea N- [2-(2-(4-fluoro)pyridyl ethyl -N' - [ (3 -(6- cyano)pyridazinyl)]thiourea N- [2- (2- (4-fluoro)pyridyl ethyl! -N' -(2- tl,3,4- thiadiazoyl])thiourea N-[2-(2-(4-fluoro)pyridyl ethyl -N' -(2- benzimidazolyl)thiourea N-[2-(2-(4-fluoro)pyridyl ethyl! -N' -(2- imidazolyl)thiourea N- [2-(2-(3-fluoro)pyridyl ethyl -N' -(2- thiazolyl)thiourea N-[2-(2-(3-fluoro)pyridyl ethyl -N' (4- methyl)thiazolyl]thiourea N-[2-(2-(3-fluoro)pyridyl ethyl -N' (4,5- dimethyl)thiazolyl]thiourea N- [2- (2-(3-fluoro)pyridyl ethyl -N' ~(2- benzothiazolyl)thiourea N-[2-(2-(3-fluoro)pyridyl ethyl -N' -t2- (6- fluoro)benzothiazolyl]thiourea N-[2-(2-(3-fluoro)pyridyl ethyl -N' (6- chloro)pyrazinyl]thiourea N-[2-(2-(3-fluoro)pyridyl ethyl -N' (4- (3- pyridyl)thiazolyl)]thiourea N-[2-(2-(3-fluoro)pyridyl ethyl -N' -[2- (4 — (3 — nitrophenyl)thiazolyl)]thiourea N- [2- (2-(3-fluoro)pyridyl ethyl -N' -(2- pyridyl)thiourea N-[2-(2-(3-fluoro)pyridyl ethyl -N' -[2- (6- bromo)pyridyl]thiourea N-[2-(2-(3-fluoro)pyridyl ethyl -N' -[2- -(6- chloro)pyridyl]thiourea N- [2 - (2-(3-fluoro)pyridyl ethyl -N' -[2- ■(6- methyl)pyridyl]thiourea N-[2-(2-(3-fluoro)pyridyl ethyl -N' -[2- ■(5- methyl)pyridyl]thiourea N-[2-(2-(3-fluoro)pyridyl ethy] -N -(6- trifluoromethyl)pyridyl]thiourea 1 0 20 25 40 45 2 6 0 2 y i X-8571A -64- U v U N- [2-(2- (3-fluoro)pyridyl)ethyl -N' ■ -[2- (5- trifluoromethyl)pyridyl]thiourea N- [2 - (2-(3-fluoro)pyridyl)ethyl -N' -[2- (6- ethyl)pyridyl]thiourea N-12- (2-(3-fluoro)pyridyl)ethyl! -N' -[2- (5- ethyl)pyridyl]thiourea N- [ 2- (2- (3-fluoro)pyridyl)ethyl _N. -[2- (6- bromo)pyrazinyl]thiourea N- [2-(2-(3-fluoro)pyridyl)ethyl -N' -[(3 -(6- bromo)pyridazinyl)]thiourea N-[2-(2-(3-fluoro)pyridyl)ethyl -N' -[2- (6- cyano)pyridyl]thiourea N- [2- (2-(3-fluoro)pyridyl)ethyl -N* -t2- (5- cyano)pyridyl]thiourea N- [2- (2-(3-fluoro)pyridyl)ethyl -N' -[2- (5- cyano)pyrazinyl]thiourea N- [2- (2-(3-fluoro)pyridyl)ethyl -N' -[2- (6- cyano)pyrazinyl]thiourea N- [2- (2-(3-fluoro)pyridyl)ethyl -N* -[(3 -(6- cyano)pyridazinyl)]thiourea N- [2- (2- (3-fluoro)pyridyl)ethyl -N' -(2- [1,3,4- thiadiazoyl])thiourea N- [2-(2-(3-fluoro)pyridyl)ethyl -N' -(2- benzimidazolyl)thiourea N- [2- (2-(3-fluoroJpyridyl)ethyl -N' -(2- imidazolyl)thiourea N- [ 2- (2-(6-chloro)pyridyl)ethyl; -N' -(2- thiazolyl)thiourea N-[2-(2-(6-chloroJpyridyl)ethyl; _N< -[2- (4- methyl)thiazolyl]thiourea N- [2-(2-(6-chloro)pyridyl)ethyl -N' (4,5- dimethyl)thiazolyl]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -(2- benzothiazolyl)thiourea N-[2- (2-r (6-chloroJpyridyl) ethyl -N' -[2- (6- fluoro)benzothiazolyl]thiourea N- [2-(2-(6-chloro)pyridyl)ethyl -N' - [2- (6- ch3 nro)pyrazinyl]thiourea N-[2-(2-(6-chloroJpyridyl)ethyl -N' -[2- - (4— (3 — pyridyl)thiazolyl)]thiourea N-[2- (2-(6-chloro)pyridyl)ethyl -N' -[2- - (4- (3- nitrophenyl)thiazolyl)]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -(2- pyridyl)thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -[2- -(6- bromo)pyridyl]thiourea X-8571A 260 r\ s' **0 40 45 N-[2-(2-(6-chloro)pyridyl)ethyl -N' -[2- (6- chloro)pyridyl]thiourea N-[2-(2- (6-chloro)pyridyl)ethyl -N' -[2- (6- methyl)pyridyl]thiourea N- [2 - (2-(6-chloro)pyridyl)ethyl -N' -[2- (5- methyl)pyridyl]thiourea N- [2 - (2-(6-chloro)pyridyl)ethyl -N' - [2- (6- tri fluoromethyl)pyridyl]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' - [2- (5- tri fluoromethyl)pyridyl]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -[2- (6- ethyl)pyridyl]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -[2- (5- ethyl)pyridyl]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -[2- (6- bromo)pyrazinyl]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -[(3 -(6- bromo)pyridazinyl)]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -[2- (6- cyano)pyridyl]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' - [2- (5- cyano)pyridyl]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' - [2- (5- cyano)pyrazinyl]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -[2- (6- cyano)pyrazinyl]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -[(3 -(6- cyano)pyridazinyl)]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -(2- [1,3,4- thiadiazoyl])thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -(2- benzimidazolyl)thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' -(2- imidazolyl)thiourea N-[2-(2^(5-chloro)pyridyl)ethyl -N' -(2- thiazolyl)thiourea N-[2-(2-(5-chloro)pyridyl)ethyl -N' (4- methyl)thiazolyl]thiourea N- [2- (2-(5-chloro) pyrictyl) ethyl -N' (4,5- dimethyl)thiazolyl]thiourea N-'[2- (2-(5-chloro)pyridyl) ethyl -N' -[2- • (4- cyano)thiazolyl]thiourea N-[2-(2-(5-chloro)pyridyl)ethyl -N -(4- trifluoromethyl)thiazolyl]thiourea N-[2-(2-(5-chloro)pyridyl)ethyl -N -(2- benzothiazolyl)thiourea 15 25 35 40 45 2 6 0 2 .9 3 X-8571A -66- N- [2-(2-(5-chloro)pyridyl fluoro)benzothiazolyl]thiourea N-[2-(2-(5-chloro)pyridyl chloro)pyrazinyl1 thiourea N-'[2- (2- (5-chloro) pyridyl ethyl)thiazolyl]thiourea N- [2-(2- (5-chloro)pyridyl pyridyl)thiazolyl)]thiourea N-[2-(2-(5-chloro)pyridyl nitrophenyl)thiazolyl)j thiourea N-[2-(2-(5-chloro)pyridyl pyridyl)thiourea N-[2-(2-(5-chloro)pyridyl bromo)pyridyl]thiourea N-[2-(2-(5-chloro)pyridyl bromo)pyridyl]thiourea N-[2-(2-(5-chloro)pyridyl chloro)pyridyl]thiourea N-[2-(2-(5-chloro)pyridyl chloro)pyridyl]thiourea N-[2-(2-(5-chloro)pyridyl methyl)pyridyl]thiourea N-[2-(2-(5-chloro)pyridyl methyl)pyridyl]thiourea N- [2 - (2- (5-chloro)pyridyl tri fluoromethyl)pyridyl]thiour N-[2-(2-(5-chloro)pyridyl trifluoromethyl)pyridyl]thiour N-[2-(2-(5-chloro)pyridyl ethyl)pyridyl]thiourea N- [2-(2-(5-chloro)pyridyl ethyl)pyridyl]thiourea N-[2-(2-(5-chloro)pyridyl chloro)pyrazinyi]thiourea N- [2-(2-(5-chloro)pyridyl bromo)pyrazinyl]thiourea N- [2 - (2 - (5-chloro)pyrictyl bromo)pyrazinyl]thiourea N-[2-(2-(5-chloro)pyridyl bromo)pyridazinyl)]thiourea N-[2-(2-(5-chloro)pyridyl chloro)pyridazinyl)]thiourea N-[2-(2-(5-chloro)pyridy] cyano)pyridyl]thiourea N- [2-(2-(5-chloro)pyridyl cyano)pyridyl]thiourea ethyl]-N'-[2-(6-]-N'-[2-(6-]-N'-[2-(4-]-N'-[2-(4-(3--N'-[2-{4-(3--N'-(2--N'-[2-(6--N'-[2-(5--N'-[2-(6--N'-[2-(5--N'-[2-(6--N1-[2-(5--N'-[2-(6--N'-[2-(5--N'-[2-(6--N' -[2-(5--N'-[2-(5--N1 -[2-(6--N'-[2-(5--N' -t (3 —(6— -N(-[(3-(6--N,-[2-(6-ethyl]-N'-[2-(5- ethyl ethyl ethyl ethyl ethyl ethyl ethyl ethyl ethyl ethyl ethyl ethyl a ethyl a ethyl ethyl ethyl ethyl ethyl ethyl ethyl ethyl X-8571A -67- 260 2 93 N-[2-(2-(5-chloro)pyridyl)ethyl]-N'-[2-(5-cyano)pyrazinyl]thiourea N- [2- (2- (5-chloro)pyridyl)ethyl]-N'-[2- (6-cyano)pyrazinyl]thiourea 5 N-[2-(2-(5-chloro)pyridyl)ethyl]-N'-[(3-(6- cyano)pyridazinyl)]thiourea N-[2-(2-(5-chloro)pyridyl)ethyl]-N'-(2-[1,3,4-thiadiazoyl])thiourea N-[2- (2- (5-chloro)pyridyl)ethyl]-N•-(2-10 benzimidazolyl) thiourea N-[2-(2- (5-chloro)pyridyl)ethyl]-N'-(2-inddazolyl)thiourea N-[2- (2- (4-chloro)pyridyl)ethyl]-N'-(2-thiazolyl)thiourea 15 N- [2- (2- (4-chloro)pyridyl) ethyl] -N" - [2- (4- methy1)thiazolyl]thiourea N- [2- (2 - (4-chloro)pyridyl)ethyl] -N* - [2 - (4, 5-dimethyl)thiazolyl]thiourea N-[2-(2-(4-chloro)pyridyl)ethyl]-N'-[2- (4-2 0 cyano)thiazolyl]thiourea N-[2-(2-(4-chloro)pyridyl)ethyl]-N'-[2-(4-tri fluoromethyl)thiazolyl]thiourea N-[2- (2- (4-chloro)pyridyl)ethyl]-N'-(2-benzothiazolyl)thiourea 2 5 N- [2- (2-(4-chloro)pyridyl)ethyl]-N'-[2-(6- fluoro)benzothiazolyl]thiourea N- [2- (2- (4-chloro)pyridyl)ethyl] -N' - [2- (*>-chloro)pyrazinyl]thiourea N- [2- (2- (4-chloro)pyridyl)ethyl]-N'-[2-(4- 3 0 ethyl)thiazolyl]thiourea N-[2-(2-(4-chloro)pyridyl)ethyl]-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-[2-(2-(4-chloro)pyridyl)ethyl]-N*- [2- (4- (3-nitrophenyl)thiazolyl)]thiourea 3 5 N- [2-(2-(4-chloro)pyridyl)ethyl]-N'-(2- pyridyl)thiourea N-[2-(2-(4-chloro)pyridyl)ethyl]-N'-[2-(6-bromo)pyridyl]thiourea N-[2-(2-{4-chloro)pyridyl)ethyl]-N'-[2-(5- 4 0 bromo)pyridyl]thiourea N- [2- (2- (4-chloro)pyri-3yl) ethyl] -N" - [2- (6-chloro)pyridyl]thiourea N-[2-(2-(4-chloro)pyridyl)ethyl]-N1 -[2-(5-chloro)pyridyl]thiourea 4 5 N-[2-(2-(4-chloro)pyridyl)ethyl]-N'-[2-(6- methyl)pyridyl]thiourea 35 40 26 0 0 () X-8571A -68- ^ U ^ u y N-[2-(2-(4-chloro)pyridyl)ethyl -N'- 2- (5- methyl)pyridyl]thiourea N-[2-(2-(4-chloro)pyridyl)ethyl -N'- 2- (6- trifluoromethyl)pyridyl]thiourea N-[2 - (2-(4-chloro)pyridyl)ethyl -N'- 2- (5- trifluoromethyl)pyridyl]thiourea N-[2-(2-(4-chloro)pyridyl)ethyl -N'- 2- (6- ethyl)pyridyl]thiourea N- [2- (2- (4-chloro)pyridyl)ethyl! -N'- 2- (5- ethyl)pyridyl]thiourea N-[2- (2- (4-chloro)pyridyl)ethyl -N'- 2- (5- chloro)pyrazinyl]thiourea N-[2-(2-(4-chloro)pyridyl)ethyl! -N' - 2- (6- bromo)pyrazinylJ thiourea N-[2-(2-(4-chloro)pyridyl)ethyi: -N' - 2- (5- bromo)pyrazinyl]thiourea N-[2-(2-(4-chloro) pyridyl)ethyl -N' - (3 -(6- bromo)pyridazinyl)]thiourea N- [2- (2- (4-chloro)pyridyl)ethyl -N' - (3 -(6- chloro)pyridazinyl)]thiourea N-[2-(2-(4-chloro)pyridyl)ethyl -N' - 2- (6- cyano)pyridyl]thiourea N-[2 - (2 - (4-chloro)pyridyl)ethyl -N' - 2- (5- cyano)pyridyl]thiourea N-[2- (2-(4-chloro)pyridyl)ethyl -N' - 2- (5- cyano)pyrazinyl]thiourea N-[2-(2-(4-chloro)pyridyl)ethyl: -N' - 2- 16- cyano)pyrazinyl]thiourea N-[2-(2-(4-chloro)pyridyl)ethyl: -N' - (3 -(6- cyano)pyridazinyl)]thiourea N- [2- (2- (4-chloro)pyridbyl) ethyl -N' - 2- [1,3,4- thiadiazoyl])thiourea N-[2-(2-(4-chloro)pyridyl)ethyl -N' - 2- benzimidazolyl)thiourea N- [2- (2-» (4-chloro)pyridyl) ethyl -N' - 2- imidazolyl)thiourea N- [2 - (2- (3-chloro)pyridyl)ethyl -N' - 2- thiazolyl)thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- (4- methyl)thiazolyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- (4,5- dimethyl)thiazolyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- (4- cyano)thiazolyl]thiourea N-[2- (2-(3-chloro)pyridyl)ethyl -N' - 2- (4- trifluoromethyl) thiazolyl] thiourea 1 5 3 5 40 45 X-8571A 260 2 9 N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- benzothiazolyl)thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- (6- fluoro)benzothiazolyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- <6- chloro)pyrazinyl]thiourea N-12-(2-(3-chloro)pyridyl)ethyl -N' - 2- (4- ethyl)thiazolyl]thiourea N- [2-(2-(3-chloro)pyridyl)ethyl -N' - 2- (4- (3- pyridyl)thiazolyl)]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- (4- (3- nitrophenyl)thiazolyl)j thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N'- 2- pyridyl)thiourea N-[2-(2-{3-chloro)pyridyl)ethyl; -N' - 2- (6- bromo)pyridyl]thiourea N- [2-(2-(3-chloro)pyridyl)ethyl -N'- 2- (5- bromo)pyridyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- (6- chloro)pyridyl]thiourea N-[2-{2-(3-chloro)pyridyl)ethyl -N' - 2- (5- chloro)pyridyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N'- 2- (6- methyl)pyridyl]thiourea N- [2-(2-(3-chloro)pyridyl)ethyl -N'- 2- (5- methyl)pyridyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N'- 2- (6- trifluoromethyl)pyridyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N'- 2- (5- tri fluoromethyl)pyridyl]thiourea N- [2 - (2 - (3-chloro )pyritlyl) ethyl -N' - 2- (6- ethyl)pyridyl]thiourea N-[2-{2-(3-chloro)pyridyl)ethyl -N' - 2- (5- ethyl)pyridyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- (5- chloro)pyrazinyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- (6- bromo)pyrazinyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- (5- bromo)pyrazinyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - (3 -(6- bromo)pyridazinyl)]thiourea N- [ 2-(2-(3-chloro)pyridyl)ethyl -N' - (3 -(6- chloro)pyridazinyl)]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl -N' - 2- (6- cyano)pyridyl]thiourea X-8571A £60 2 9 N-[2-(2-(3-chloro)pyridyl)ethyl]-N'-[2-(5-cyano)pyridyl]thiourea N- [2- (2- (3-chloro.Vrvridyl) ethyl] -N' - [2- (5-cyano)pyrazinyl]thiourea 5 N-[2-(2-(3-chloro)pyridyl)ethyl]-N'-[2-(6- cyano)pyrazinyl]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl]-N'-[(3-(6 cyano)pyridazinyl)]thiourea N-[2-(2-(3-chloro)pyridyl)ethyl]-N'-(2-[1, 1 0 thiadiazoyl])thiourea N-[2-(2-(3-chloro)pyridyl)ethyl]-N'-(2-benzimidazolyl)thiourea N-.[2- (2- (3-chloro)pyridyl)ethyl]-N'-(2-imidazoly1)thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl thiazolyl)thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl methyl)thiazolyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl 2 0 dimethyl)thiazolyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl cyano)thiazolyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl trifluoromethyl)thiazolyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl benzothiazolyl)thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl fluoro)benzothiazolyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl 3 0 chloro) pyraz inyl] thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl ethyl)thiazolyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl (3-pyridyl)thiazolyl)]thiourea 3 5 N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl (3-nitrophenyl)thiazolyl)]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl pyridyl)thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl 4 0 bromo)pyridyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl bromo)pyridyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl chloro)pyridyl]thiourea 45 N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl chloro)pyridyl]thiourea 3,4- -N' - -N'- -N1 - -N' - -N'- -N'- -N'- -N'- -N'- -N'- -N' -N' -N' -N' -N' -N' (2- [2-(4-E 2 —(4,5-[2-(4-[2-(4-(2- E 2 - (6— E2-(6- ■ [2-(4- ■ [2-(4--12— (4 — -(2- - [2— (6 — - [2-(5- - [2-(6- - [2- (5- 20 25 35 40 45 Z6 X-8571A -71- N-[2~(2-(5-methoxy-6-fluoro)pyridyl)ethyl -N' - 2- (6- methyl)pyridyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl -N' - 2- (5- methyl)pyridyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl -N' - 2- (6- tri fluoromethyl)pyridyl]thiourea N-[2-(2-(5-methoxy-6-fluoro) pyridyl)ethyl; -N' - 2- (5- tri fluoromethyl)pyridyl]thiourea N-[2- (2-(5-methoxy-6-fluoro)pyridyl)ethyl -N' - 2- (6- ethyl)pyridyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl -N' - 2- (5- ethyl)pyridyl]thiourea N- [2- (2- (5-methoxy-6-f luoro)pyridyl) ethyl -N' - 2- (5- chloro)pyrazinyl]thiourea N-[2- (2-(5-methoxy-6-fluoro)pyridyl)ethyl -N' - 2- (6- bromo)pyrazinyl]thiourea N-[2- (2-(5-methoxy-6-fluoro)pyridyl)ethyl -N' - 2- (5- bromo)pyrazinyl]thiourea N-[2-(2-(5-methoxy-6-fluoro)pyridyl)ethyl -N1 - (3 -<6- bromo)pyridazinyl)]thiourea N-[2 - (2-(5-methoxy-6-fluoro)pyridyl)ethyl -N' - (3 -(6- chloro)pyridazinyl)]thiourea N-[2- (2-(5-methoxy-6-fluoro)pyridyl)ethyl -N'- 2- (6- cyano)pyridyl]thiourea N-[2- (2-(5-methoxy-6-fluoro)pyridyl)ethyl; -N' - 2- (5- cyano)pyridyl]thiourea N-[2 - (2-(5-methoxy-6-fluoro)pyridyl)ethyl -N'- 2- (5- cyano)pyrazinyl]thiourea N-[2 - (2-(5-methoxy-6-fluoro)pyridyl)ethyl -N' - 2- (6- cyano)pyrazinyl]thiourea N- [2 - (2 - (5-methoxy-6-fluoro)pyridyl)ethyl -N' - (3 -(6- cyano)pyridazinyl)]thiourea N-[2- {2- (5-methoxy-6-fluoro)pyridy1)ethyl; -N' - 2- [1,3,4-thiadiazoyl])thiourea N-[2 - (2- (5-methoxy-6-fluoro)pyridyl)ethyl -N'- 2- benz imida-iu lyl) thiourea N-[2- (2-(5-methoxy-6-fluoro)pyridyl)ethyl -N' - 2- imidazolyl)thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl -N'- 2- thiazolyl)thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl -N' - 2- (4,5- dimethyl)thiazolyl]thiourea N-'[2- (2- (3-methoxy-6-fluoro)pyridyl) ethyl -N' - 2- benzothiazolyl)thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl -N'- 2- (6- fluoro)benzothiazolyl]thiourea 40 45 X-8 57.1A 260 2Q N- [2- (2- (3-methoxy-6-fluoro)pyridyl)ethyl] -N' - [2- (6-chloro)pyrazinyl]thipurea N- [2- (2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-[2-(2 • (3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-'[2- (2- (3-methoxy-6-fluoro)pyridyl) ethyl] —N' - [2- (6— bromo)pyridyl]thiourea N- [2- (2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(6-chloro)pyridyl]thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(6-methy1)pyridyl]thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(5-methy1)pyridyl]thiourea N- [2- (2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-fS-trif luoromethyl )pyridyl]thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(6-ethy1)pyridyl]thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(5-ethy1)pyridyl]thiourea N- [2- (2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(6-bromo)pyrazinyl]thiourea N- [2- {2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[(3-(6-bromo)pyridazinyl)]thiourea N-[2-{2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(6-cyano)pyridyl]thiourea N—[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-12-(5 — cyano)pyridyl]thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(5-cyano)pyrazinyl]thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(6-cyano)pyrazinyl]thiourea N- [2- (2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[(3-(6-cyano)pyridazinyl)]thiourea N- [2 - (2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-(2-[1,3,4-thiadiazoyl])thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N"-(2-benzimidazolyl)thiourea N- [2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-(2-imidazolyl)thiourea N- [2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl]-N'-(2-thiazolyl)thiourea N- [2- (2-(6-methoxy-3-fluoro)pyridyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea 40 26 0 2 X-8571A -73- N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' -[2- (4,5- dimethyl)thiazolyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl; -N' -[2- (4- cyano)thiazolyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' -[2- (4- trifluoromethyl)thiazolyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' -(2- benzothiazolyl)thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' -[2- (6- fluoro)benzothiazolyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl; -N* (6- chloro)pyrazinyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl; -N' -[2- (4- ethyl)thiazolyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' -[2- (4- (3-pyridyl)thiazolyl)]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' -[2- (4- (3-nitrophenyl)thiazolyl)]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N* -(2- pyridyl)thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' (6- bromo)pyridyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl; -N' (5- bromo)pyridyl]thiourea N- [2 - (2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' (6- chloro)pyridyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' (5- chloro)pyridyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' (6- methyl)pyridyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' (5- methyl)pyridyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' (6- trifluoromethyl)pyridyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' (5- trifluoromethyl)pyridyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' (6- ethyl)pyridyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' -[2- (5- ethyl)pyridyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' -[2- (5- chloro)pyrazinyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' -[2- (6- bromo)pyraz inyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl -N' -[2- -(5- bromo)pyrazinyl]thiourea 40 45 X-8571A 2 6 0 2 9 N-[2- (2- (6-methoxy-3-fluoro)pyridyl)ethyl] -N1 -[ (3- (6-bromo)pyridazinyl)]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl]-N'-[(3- (6-chloro)pyridazinyl)]thiourea N-[2-(2- (6-methoxy-3-fluoro)pyridyl)ethyl]-N'-[2-(6-cyano) pyridyl ] thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl]-N'-[2-(5-cyano)pyridyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl]-N'-[2- (5-cyano)pyrazinyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl]-N'-[2-(6-cyano)pyrazinyl]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl]-N'-1 (3-(6-cyano)pyridazinyl)]thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl]-N' - (2-[1, 3,4-thiadiazoyl])thiourea N-[2-(2-(6-methoxy-3-fluoro)pyridyl)ethyl]-N' - (2-benzimidazolyl)thiourea N-[2-(2-(6-metho3^-3-fluoro)pyridyl)ethyl]-N'-(2-imidazolyl)thiourea N-12-{2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N' - (2-thiazolyl)thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N' -[2- (4,5-dimethyl)thiazolyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N' -(2-benzothiazolyl)thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N1 -[2-(6-cluoro)benzothiazolyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(6-chloro)pyrazinyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-(2-pyridyl)thiourea N-[2-(2-(5-ethoxy-6-fluoro) pyridyl)ethyl]-N'-[2-(6-bromo)pyridyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'- [2- (6-chloro)pyridyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2- (6-methy1)feyridyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2- (5-methyl)pyridyl]thiourea 1 0 25 ® 30 35 40 45 26 0 2 9 X-8571A -75- N-[2-(2-{5-ethoxy-6-fluoro)pyridyl)ethyl]-N'- 12-(6-trifluoromethyl)pyridyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(5-trifluoromethyl)pyridyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'- [2-(6-ethyl)pyridyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'- [2- (5-ethy1)pyridyl]thiourea N-[2 - (2- (5-ethoxy-6-fluoro)pyridyl)ethyl]-N*-f2 —(6— bromo)pyrazinyl]thiourea N- [2- (2- (5-ethoxy-6-fluoro)pyridyl) ethyl] -N' - [ (3- (61-bromo)pyridazinyl)]thiourea N-[2-(2-{5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(6-cyano)pyridyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N' -[2-(5-cy ano)pyridyl]thiourea N- [2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N' — [2 —(5— cyano)pyrazinyl]thiourea N- [2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(6-cyano)pyrazinyl]thiourea N- [2-(2-(5-ethoxy-6-fluoro) pyridyl)ethyl]-N'-[(3-(6-cyano)pyridazinyl)]thiourea N- [2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-(2-[1,3,4-thiadiazoyl])thiourea N- [2 - (2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N' - (2-benzimidazolyl)thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'- (2-imidazolyl)thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-N"-(2-thiazolyl)thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-N1-[2-(4-methyl)thiazolyl]thiourea N- [2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl]~N' - [2- (4,5-dimethyl)thiazolyl]thiourea N- [2- (2- (3-ethoxy-6-fluoro)pyridyl)ethyl]-N'-(2-benzothiazolyl)thiourea N- [2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea N- [2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-N"-[2-(6-chloro)pyrazinyl]thiourea N- [2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(4-(3 pyridyl)thiazolyl)]thiourea N- [2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(4-(3 nitrophenyl)thiazolyl)]thiourea N- [2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-N'-(2-pyridyl)thiourea 25 40 45 X-8571A -76- 2 8 0 19 3 N-[2-(2-(3-ethoxy 6 -fluoro)pyridyl)ethyl -N' -[2- (6- bromo)pyridyl3 thiourea N-[2-(2 - (3-ethoxy-6-fluoro)pyridyl)ethyl! -N' -[2- (6- chloro)pyridy1]thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N' (6- methyl)pyridyl]thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N' (5- methyl)pyridyl]thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N1 -[2- (6- trifluoromethyl)pyridyl]thiourea N- [2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N' (5- trifluoromethyl)pyridyl]thiourea N- [2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N' (6- ethyl)pyridyl]thiourea N-'[2- (2- (3-ethoxy-6-fluoro)pyridyl) ethyl -N* (5- ethyl)pyridyl]thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl _N< -[2- (6- bromo)pyrazinyl]thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N' -1 (3 -(6- bromo)pyridazinyl)]thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N' -[2- (6- cyano)pyridyl]thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N' -[2- (5- cyano)pyridyl]thiourea N- [2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N' -[2- (5- cyano)pyrazinyl]thiourea N- [2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N* - [2- (6- cyano)pyrazinyl]thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N' -[ (3 -(6- cyano)pyridazinyl)]thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl! -N* -(2- [1,3,4-thiadiazoyl])thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N* -(2- benzimidazolyl)thiourea N- [2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl -N' -(2- imidazolyl)thiourea N-.[2- (2 - (6-ethoxy-3-fluoro)pyridyl) ethyl -N' -(2- thiazolyl)thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- (4- methyl)thiazolyl]thiourea N- [2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- -(4,5- dimethyl)thiazolyl]thiourea N- [2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- ■ (4- cyano)thiazolyl]thiourea N- [2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- -(4- trifluoromethyl)thiazolyl]thiourea 25 35 40 45 2 6 0 k. & 3 X-8571A -77- N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -(2- benzothiazolyl)thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' - [2- (6- fluoro)benzothiazolyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' - [2- (6- chloro)pyrazinyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- (4- ethyl)thiazolyl]thiourea N- [2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- (4- (3- pyridyl)thiazolyl)]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' (4-(3 - nitrophenyl)thiazolyl)]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -(2- pyridyl)thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- (6- bromo)pyridyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -C2- (5- biomo)pyridyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- (6- chloro)pyridyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- (5- chloro)pyridyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- (6- methyl)pyridyl]thiourea N-[2-{2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' (5- methyl)pyridyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' (6- trifluoromethyl)pyridyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' (5- trifluoromethyl)pyridyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- (6- ethyl)pyridyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- (5- ethyl)pyridyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- (5- chloro)pyrazinyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- <6- bromo)pyrazinyl]thiourea N-[2 - (2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' (5- bromo)pyrazinyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -1 (3 -(6- bromo)pyridazinyl)]thiourea N- [2 - (2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[(3 -(6- chloro)pyridazinyl)]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl -N' -[2- -(6- cyano)pyridyl]thiourea X-8571A 2 6 0^^3 N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl]-N' - [2- (5-cyano)pyridyl]thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl]-N'-[2- (5-cyano)pyrazinyl]thiourea 5 N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl]-N*-[2- (6- cyano)pyrazinyl]thiourea N-'[2- (2- (6-ethoxy-3-fluoro)pyridyl) ethyl] -N' - [ (3- (6-cyano)pyridazinyl)]thiourea N-[2-<2-(6-ethoxy-3-fluoro)pyridyl)ethyl]-N' - (2-10 [1,3,4-thiadiazoyl])thiourea N- [2- (2- (6-etho3Qr-3-fluoro)pyridyl) ethyl] -N' - (2-benzimidazolyl)thiourea N-[2-(2-(6-ethoxy-3-fluoro)pyridyl)ethyl]-N"-(2-imidazolyl)thiourea 15 N- [2- (5, 6-fluoro)pyridyl) ethyl] -N' - (2- thiazolyl)thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N'-[2-(4,5- 2 0 dimethyl)thiazolyl]thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N*-[2-{4-trifluoromethyl)thiazolyl]thiourea 25 N-[2-(5, 6-fluoro)pyridyl)ethyl]-N'- (2- benzothiazolyl)thiourea N- [2-(5,6-fluoro)pyridyl)ethyl]-N'-[2-(6-fluoro)benzothiazolylj thiourea N-[2-(5,6-fluoroJpyridyl)ethyl]-N'-[2-(6- 3 0 chloro) pyrazinyl] thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N1- [2-(4-ethyl)thiazolyl]thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea 3 5 N- [2- (5,6-fluoro)pyridyl) ethyl] -N' - [2- (4- (3- nitrophenyl)thiazolyl)]thiourea N-[2-(5,6-fluoroJpyridyl)ethyl]-N'-(2-pyridyl)thiourea N- [2-(5,6-fluoro)pyridyl)ethyl]-N'-[2-(6-bromo)pyridyl]thiourea 40 N- [2- (5,6-fluoro)pyridyl)ethyl] -N' - [2- (5- bromo)pyridyl]thiourea N- [2- (5,6-fluoroJpyridyl)ethyl]-N'-[2-(6-chloro)pyridyl]thiourea N- [2-(5,6-fluoroJpyridyl)ethyl]-N1 -[2-(5- 4 5 chloro)pyridyl]thiourea 1 0 40 45 X-8571A 2 6 0 t j N- [2- (5,6-fluoro)pyridyl)ethyl]-N'-[2-(6-methy1)pyridyl]thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N'-[2-(5-methylJpyridyl]thiourea N- [2- (5,6-fluoro)pyridyl)ethyl]-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N-[2 - (5,6-fluoro)pyridyl)ethyl]-N'-[2-(5-trifluoromethyl)pyridyl]thiourea N-[2- (5,6-fluoro)pyridyl)ethyl]-N'-[2-(6-ethy1)pyridyl]thiourea N-[2 - (5,6-fluoro)pyridyl)ethyl]-N'-[2-{5-ethyl)pyridyl]thiourea N-[2 - (5,6-fluoro)pyridyl)ethyl]-N'-[2-(5-chloro)pyrazinyl]thiourea N-[2 - (5,6-fluoro)pyridyl)ethyl]-N'-[2-(6-bromo)pyrazinyl]thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N'-[2-(5-bromo)pyrazinyl]thiourea N- [2 - (5,6-fluoro)pyridyl)ethyl]-N'-[(3-(6-bromo)pyridazinyl)]thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N'-[(3-(6-chloro)pyridazinyl)]thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N'-[2-(6-cyano)pyridyl]thiourea N-[2-(5,6-fluoroJpyridyl)ethyl]-N'-[2-(5-cyano)pyridyl]thiourea N-[2 - (5,6-fluoro)pyridyl)ethyl]-N'-[2-(5-cyano)pyrazinyl]thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N'-[2-(6-cyano)pyrazinyl]thiourea N-[2- (5,6-fluoroJpyridyl)ethyl]-N'-[(3-(6-cyano) pyridazinyl) ] thiourea N-[2-(5,6-fluoro)pyridyl)ethyl]-N'-(2-[l,3,4-thiadiazoyl])thiourea N-[2- (5,6-fluoro)pyridyl)ethyl]-N*-(2-benzimidazolyl)thiourea N-[2- (5,6-fluoro)pyridyl)ethyl]-N'-(2-imidazolyl)thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl]-N*-(2-thiazolyl)thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl]-N"-[2- (4-methyl)thiazolyl]thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl]-N"-[2-(4,5-dimethyl)thiazolyl]thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea X-8571A -80- N- [2-(2-{5,6-difluoroJpyridyl)ethyl trifluoromethyl)thiazolyl]thiourea N- [2- (2-(5,6-difluoro)pyridyl)ethyl] benzothiazolyl)thiourea 5 N-[2- (2-(5,6-difluoro)pyridyl)ethyl fluoro)benzothiazolyl]thiourea N- [2- (2-(5,6-difluoro)pyridyl)ethyl chloro)pyrazinyl]thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl 1 0 ethyl)thiazolyl]thiourea N- [2 - (2-(5,6-difluoro)pyridyl)ethyl pyridyl)thiazolyl)]thiourea N- [2-(2-(5,6-difluoro)pyridyl)ethyl nitrophenyl)thiazolyl)]thiourea N- [2- (2- (5,6-dif luoro) pyr idyl) ethyl pyridyl)thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl bromo)pyridyl]thiourea N- [2-(2-(5,6-difluoro)pyridyl)ethyl 2 0 bromo)pyridyl]thiourea N--[2- (2- (5,6-difluoro)pyridyl) ethyl; chloro)pyridyl]thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl chloro)pyridyl]thiourea N- [2- (2-(5,6-difluoro)pyridyl)ethyl methyl)pyridyl]thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl methyl)pyridyl]thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl 3 0 trifluoromethyl)pyridyl] thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl trif luoromethyl jpyridyl] thiourea N-[2- (2-(5,6-difluoro)pyridyl)ethyl ethyl)pyridyl]thiourea 3 5 N-[2-(2-(5,6-difluoro)pyridyl)ethyl ethyl)pyridyl]thiourea N-[2- (2-(5,6-difluoro)pyridyl)ethyl chloro)pyrazinyl]thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl 4 0 bromo)pyrazinyl]thiourea N-[2- (2-(5,6-difluoro)pyridyl)ethyl bromo)pyraz inylj thiourea N-.[2- (2- (5,6-dif luoro) pyridyl) ethyl bromo)pyridazinyl)]thiourea 4 5 N- [2- (2- (5,6-difluoro)pyridyl) ethyl chloro)pyridazinyl)]thiourea 2 6 0 c N' - [2- (4-N'-(2-•N' - [ 2 - (6 -•N' - [2 - (6-■N' - [2- (4-•N' - [2- (4- (3-•N'-[2-(4-(3--N'- (2-■N' - [2- (6--N1 - [ 2 - (5 --N*-[2-(6--N'-[2-(5-:N'-[2-(6--N'-[2-(5--N' — [ 2 — (6 — -N' — 12 — (5 — -N' — [2 —(6 — -N'-[2-(5--N*-[2-(5--N'-[2-(6-—N" — 12 — (5 — -N'-[(3-(6--N'-[(3-(6- 40 45 260293 X-8571A -81- N-12-(2-(5,6-difluoroJpyridyl)ethyl]-N*-[2-(6-cyano)pyridyl]thiourea N-[2-(2-(5,6-difluoroJpyridyl)ethyl]-N'-[2-(5-cyano)pyridyl]thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl]-N'-[2-(5-cyano) pyrazinyl ] thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl]-N'-[2-(6-cyano)pyrazinylj thiourea N- [2- (2-(5,6-difluoro)pyridyl)ethyl]-N'-[(3-(6-cyano)pyridazinyl)]thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl]-N'-(2-[l,3,4-* thiadiazoyl])thiourea N-[2-(2-(5,6-difluoro)pyridyl)ethyl]-N'-(2-benzimidazolyl)thiourea N- [2-(2-(5,6-difluoroJpyridyl)ethyl]-N'-(2-imidazoly1)thiourea N-[2-{2-(3,6-difluoroJpyridyl)ethyl]-N'-(2-thiazolyl)thiourea N-[2-(2-(3,6-difluoro)pyridyl)ethyl]-N*-[2-(4-methyl)thiazolyl]thiourea N- [2- (2- (3,6-difluoro)pyridyl)ethyl]-N'-[2-(4,5-dimethy1)thiazolyl]thiourea N- [2- (2-(3,6-difluoro)pyridyl)ethyl]-N'-(2-benzothiazolyl)thiourea N-[2-(2-{3,6-difluoro)pyridyl)ethyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea N- [2- (2-(3,6-difluoro)pyridyl)ethyl]-N*-[2-(6-chloro)pyrazinyl]thiourea N- [2-(2-(3,6-difluoro)pyridyl)ethyl]-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-[2-(2-(3,6-difluoroJpyridyl)ethyl]-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-[2- (2-(3,6-difluoroJpyridyl)ethyl]-N'-(2-pyridyl J thiourea N-[2- (2-(3,6-difluoroJpyridyl)ethyl]-N'-[2-(6-bromo)pyridyl]thiourea N-[2-(2-(3,6-difluoroJpyridyl)ethyl]-N'-[2-(6-chloro J pyridyl]thiourea N-12- (2-(3,6-difluoroJpyridyl)ethyl]-N*-[2-(6-methy1J pyridyl]thiourea N- [2- (2-(3,6-difluoro J pyridyl)ethyl]-N'-[2-(5-methylJ pyridyl]thiourea N-12- (2-(3,6-difluoroJpyridyl)ethyl]-N'-[2-(6-tri fluoromethyl)pyridyl]thiourea N-[2 - (2-(3,6-difluoro)pyridyl)ethyl]-N'-[2-(5-tri fluoromethyl)pyridyl]thiourea 1 5 20 25 ® 30 35 40 45 X-8571A -82- 260 293 N-[2-(2-(3,6-difluoro)pyridyl)ethyl -N* - 2- (6- ethyl)pyridylJ thiourea N-[2-(2-(3,6-difluoro)pyridyl)ethyl -N' - 2- (5- ethyl)pyridyl]thiourea N-[2-(2-(3,6-difluoro)pyridyl)ethyl; -N' - 2- (6- bromo)pyrazinyl]thiourea N-[2-(2-(3,6-difluoro)pyridyl)ethyl -N' - (3 -(6- bromo)pyridazinyl)]thiourea N-[2-(2-(3,6-difluoro)pyridyl)ethyl -N' - 2- (6- cyano)pyridyl]thiourea N-[2 - (2 - (3,6-difluoro)pyridyl)ethyl -N' - 2- (5- cyano)pyridyl]thiourea N-'[2- (2- (3,6-difluoro Jpyridyl) ethyl -N' - 2- (5- cyano)pyrazinylj thiourea N-[2-(2-(3,6-difluoro)pyridyl)ethyl -N' - 2- (6- cyano)pyrazinyl]thiourea N-[2-(2-(3,6-difluoro)pyridyl)ethyl; -N' - (3 -{6- cyano)pyridazinyl)]thiourea N- [2-(2 - (3,6-difluoro)pyridyl)ethyl -N' - 2- [1,3,4- thiadiazoyl])thiourea N-[2-(2- (3,6-difluoro)pyridyl)ethyl -N' - 2- benzimidazolyl)thiourea N-[2- (2-(3,6-difluoroJpyridyl)ethyl; -N'- 2- imidazolyl)thiourea N-[2-(2-{5,6-dichloroJpyridyl)ethyl -N' - 2- thiazolyl)thiourea N-[2-(2-(5,6-dichloro)pyridyl)ethyl -N'- 2- (4- methyl)thiazolyl]thiourea N-[2-(2-(5,6-dichloro)pyridyl)ethyl -N' - 2- (4,5- dimethyl)thiazolyl]thiourea N- [2- (2- (5,6-<2ichloro) pyridyl) ethyl -N' - 2- (4- cyano)thiazolyl]thiourea N-[2-(2-(5,6-dichloro)pyridyl)ethyl -N' - 2- (4- trifluoromethyl)thiazolyl]thiourea N-.[2- (2- (5, 6-dichloroJpyridyl) ethyl -N'- 2- benzothiazolyl)thiourea N- [2- (2-(5,6-dichloroJpyridyl)ethyl -N' - 2- (6- fluoro)benzothiazolyl]thiourea N- [2- (2 - (5,6-dichloroJpyridyl)ethyl -N'- 2- (6- chloro)pyrazinyl]thiourea N-[2-(2-(5,6-dichloroJpyridyl)ethyl -N' - 2- (4- ethylJ thiazolylj thiourea N-[2-(2-(5,6-dichloroJpyridyl)ethyl -N' - 2- (4- (3- pyridyl)thiazolyl)]thiourea N-[2-(2-(5,6-dichloroJpyridyl)ethyl -N' - 2- • (4- (3- nitrophenyl)thiazolylJ]thiourea 20 35 40 2 6 0 2 9 3 X-8571A -83- N-[2-(2-(5,6-dichloroJpyridyl? ethyl]■ pyridyl)thiourea N-[2-(2-(5,6-dichloro)pyridyl)ethyl]■ bromo)pyridyl]thiourea N- [ 2 - (2 - (5,6 -dichloro) pyricjy 1J ethyl ] ■ bromo)pyridyl]thiourea N- [2 - (2- (5,6-dichloro)pyri<$y 1) ethyl]■ chloro) pyi. idyl ] thiourea N-[2-(2-(5,6-dichloro)pyridyl)ethyl] chloroJpyridyl]thiourea N-I2-(2- (5,6-dichloroJpyridyl)ethyl] methyl)pyridyl]thiourea N-[2-(2-(5,6-dichloro)pyridyl)ethyl] methyl)pyridyl]thiourea N-[2-(2-(5,6-dichloro)pyridyl)ethyl] trifluoromethylJ pyridyl]thiourea N-[2-(2-(5,6-dichloroJpyridyl)ethyl] tri fluoromethylJ pyridyl]thiourea N-[2-(2-(5,6-dichloroJpyridyl)ethyl] ethylJ pyridyl]thiourea N- [2 - (2- (5,6-dichloroJpyridyl)ethyl] ethyl)pyridyl]thiourea N-[2-(2-(5,6-dichloroJpyridyl)ethyl] chloro)pyrazinyl]thiourea N- [2-(2-(5,6-dichloro)pyridyl)ethyl] bromo)pyrazinyl]thiourea N-[2-(2-(5,6-dichloro)pyridyl)ethyl] bromo)pyrazinylj thiourea N-[2-(2-(5,6-dichloro)pyridyl)ethyl] bromo)pyridazinyl)]thiourea N- [2-(2-(5,6-dichloro)pyridyl)ethyl] chloro)pyridazinyl)]thiourea N- [2-(2-(5,6-dichloro)pyridyl)ethyl] cyano)pyridyl]thiourea N- [2-(2-{5,6-dichloro)pyridyl)ethyl] cyano)pyridyl]thiourea N- [2 - (2-(5,6-dichloro)pyridylJethyl] cyano)pyrazinyl]thiourea N-[2-(2-(5,6-dichloro)pyridyl)ethyl] cyano)pyrazinyl]thiourea N- [2-{2-(5,6-dichioro)pyridyl)ethyl] cyano)pyridazinyl)]thiourea N-[2-(2-{5,6-dichloro)pyridyl)ethyl] thiadiazoyl])thiourea N- [2-(2-(5,6-dichloroJpyridyl)ethyl] benzimidazolyl)thiourea -N' ■ -N* ■ -N' • -N' ■ -N' ■ -N' -N' ■ -N' -N' -N' -N' -N' -N' -N.

-N' -N' -N' -N' -N' -N' -N' -N" -N' -<2- - [2-(6- - [2-(5- - [2-(6--12- (5--12-(6- - [2-(5--12-(6--[2- (5--[2- (6--[2- (5--[2- (5--[2- (6--[2- (5- - [ (3-(6--[ <3-(6--[2- (6--12- (5--[2-(5--[2-(6--[(3- (6--(2-[l,3,4--(2- 1 0 20 25 ® 30 3 5 40 45 X-8571A -84- ^ ^ Q 2 Q 3 N-[2-(2-(5,6-dichloro)pyridyl)ethyl -N1 - 2- imidazolyl)thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl -N' - 2- thiazolyl)thiourea N-[2- (2-(3,6-dichloro)pyridyl)ethyl -N' - 2- (4- methyl)thiazolyl)thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl -N' - 2- (4,5- dimethyl)thiazolyl]thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl -N' - 2- (4- cyano)thiazolyl]thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl! -N' - 2- (4- trif luoromethyl) thiazolyl] thic *a N- [2 - (2 - (3,6-dichloro)pyi /l)ethyl -N" - 2- benzothiazolyl)thiourea N-[2-(2-(3,6-dichloroJpyridyl)ethyl -N' - 2- (6- fluoro)benzothiazolyl]thiourea N-[2- (2- (3,6-dichloro)pyridyl)ethyl -N' - 2- (6- chloro)pyraz inyl]thiourea N- [2-(2-(3,6-dichloro)pyridyl)ethyl -N' - 2- (4- ethyl)thiazolyl]thiourea N- [2 - (2- (3,6-dichloro)pyridyl)ethyl] -N' - 2- (4-(3- pyridyl)thiazolyl)]thiourea N-- [2 - (2- (3,6-dichloro)pyridyl)ethyl! -N" - 2- (4- (3- nitrophenyl)thiazolyl)]thiourea N-[2- (2-(3,6-dichloro)pyridyl)ethyl -N' - 2- pyridyl)thiourea N-[2 - (2 - (3,6-dichloro)pyridyl)ethyl -N>- 2- (6- bromo)pyridyl]thiourea N-[2- (2- (3, 6-dichloro)pyridyl)ethyl -N' - 2- (5- bromo)pyridyl]thiourea N-[2 - (2-*3,6-dichloro)pyridyl)ethyl -N' - 2- (6- chloro)pyridyl]thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl -N' - 2- (5- chloro)pyridyl]thiourea N- [2- (2- (3,6-dichloro)pyrictyl) ethyl -N' - 2- (6- methyl)pyridyl]thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl -N' - 2- (5- methyl)pyridyl]thiourea N-[2- (2- (3,6-dichloro)pyridyl)ethyl -N' - 2- (6- trifluoromethyl)pyridyl]thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl -N'- 2- (5- trifluoromethyl)pyridyl]thiourea N- [2- (2- (3,6-dichloro)pyridyl)ethyl -N'- 2- (6- ethyl)pyridyl]thiourea N-[2-(2-(3,6-dichloro)pyridyl)etbyl -N'- 2- (5- ethyl)pyridyl]thiourea X-8571A 26 0 2 0 7 < ' cj N- [2- (2 - (3,6-dichloro)pyridyl)ethyl chloro)pyrazinyl]thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl bromo)pyrazinylj thiourea 5 N-[2-(2-(3,6-dichloro)pyridyl)ethyl bromo)pyraz inyl]thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl bromo)pyridazinyl)]thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl 10 chloro) pyridazinyl)] thiourea N- [2- (2- (3, 6-dichloro) pyridyl") ethyl cyano)pyridyl]thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl cyano)pyridyl]thiourea 15 N- [2- (2- (3, 6-dichloro Jpyridyl) ethyl cyano)pyrazinyl]thiourea N-[2-(2-(3,6-dichloro)pyri dyl)ethyl cyano)pyrazinyl]thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl 2 0 cyano)pyridazinyl)]thiourea N-[2-(2-(3,6-dichloroJpyridyl)ethyl thiadiazoyl])thiourea N-[2-(2-(3,6-dichloro)pyridyl)ethyl benzimidazolyl)thiourea 25 N-[2 - (2 - (3, 6-dichloro Jpyridyl) ethyl imidazolyl)thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N' thiazolyl)thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N' 3 0 methyl)thiazolyl]thiourea N-[2-{cis-2-pyridyl)cyclopropyl]-N' dimethyl)thiazolyl]thiourea N-[2 - (cis-2-pyridyl)cyclopropyl]-N1 benzothiazolyl)thiourea 3 5 N-'t2- (cis-2-pyridyl)cyclopropyl] -N' fluoro)benzothiazolyl]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N' chloro)pyrazinyl]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N' 4 0 pyridyl)thiazolyl)]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N' nitrophenyl)thiazolyl)]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N' bromo)pyridyl]thiourea 45 N-[2-(cis-2-pyridyl)cyclopropyl]-N' chloro)pyridyl]thiourea -N' — 12—(5 — -N' -[2- (6- -N' - [2- (5- -N' - [ (3-(6- -N' -[ (3-(6- -N' — 12 — (6 — -N' -[2- (5- -N' — [ 2 — (5 — -N' -[2- (6- -N' -[(3-(6- -N' -(2-11,3,4- -N' - (2- tN' - (2- (2- •[2- (4- ■12- (4,5- •(2- •12- (6- (6- ■ (4- (3- -[2- •(4- (3- -[2- •(6- -[2- -(6- X-8571A 2 6 0 r\ N-[2-(cis-2-pyridyl)cyclopropyl]-N'-[2- (6-methyl)pyridyl]chiourea N-[2-(cia-2-pyridyl)cyclopropyl]-N'-[2-(6-trifluoromethylJpyridyl]thiourea 5 N-[2-(cis-2-pyridyl)cyclopropyl]-N'-[2-(6- ethyl)pyridyl]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N'-[2- (6-bromo)pyraz inyl]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N'-[(3- (6-1 0 bromo)pyridazinyl)]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N'—[2-(6— cyano)pyridyl]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N'-[2- (5-cyano)pyridyl]thiourea 1 5 N-[2-(cis-2-pyridyl)cyclopropyl]-N*-[2-(5- cyano)pyraz inyl]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N'-[2-(6-cyano)pyrazinyl]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N'-[(3-(6- 2 0 cyano)pyridazinyl)]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N'-(2-[1,3,4-thiadiazoyl])thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N1- (2-benzimidazolyl)thiourea 25 N-[2-(cis-2-pyridyl)cyclopropyl]-N'-(2- imidazolyl)thiourea N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N'-(2-thiazolyl)thiourea N-[2-(cis-2-(6-fluoroJpyridyl)cyclopropyl]-N'-[2-(4- 3 0 methyl)thiazoJyl]thiourea N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N'-[2-(4,5-dimethyl)thiazolyl]thiourea N-[2-(cis-2-(6-fluoroJpyridyl)cyclopropyl]-N'-(2-benzothiazolyl)thiourea 3 5 N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N'-[2-(6- fluoro)benzothiazolyl]thiourea N-[2-(cis-2-(6-fluoroJpyridyl)cyclopropyl]-N'-[2-(6-chloro)pyraz inyl]thiourea N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N1-[2-(4-40 (3 -pyridyl) thiazolyl) ] thiourea N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N'-[2-(4-(3-nitrbphenyl)thiazolyl)]thiourea N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N'-[2 - (6-bromo)pyridyl]thiourea 45 N-[2-(cis-2-(6-fluoroJpyridyl)cyclopropyl]-N'-[2-(6- chloro)pyridyl]thiourea 35 40 X-8571A -87- 260 29 N- [2- (cis-2- (6-fluoro)pyridyl) cyclopropyl -N' -[2- (6- methyl)pyridyl]thiourea N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl -N' -[2- (6- trifluoromethyl)pyridyl]thiourea N-'[2- (cis-2- (6-fluoroJpyridyl) cyclopropyl -N' -[2- (5- tri fluoromethyl)pyridyl]thiourea N-[2- (cis-2-(6-fluoroJpyridyl)cyclopropyl -N' -[2- (6- ethyl)pyridyl]thiourea (5- N-[2- (cis-2-(6-fluoro)pyridyl)cyclopropyl -N' -[2- ethyl)pyridyl]thiourea -[2- (6- N-[2 - (cis-2-(6-fluoro)pyridyl)cyclopropyl -N' bromo)pyrazinyl]thiourea N-[2- (cis-2-(6-fluoroJpyridyl)cyclopropyl -N1 -[(3 -(6- bromo)pyridazinyl)]thiourea N-[2- (cis-2-(6-fluoro)pyridyl)cyclopropyl] -N' -[2- (6- cyano)pyridyl]thiourea N-[2- (cis-2-(6-fluoro)pyridyl)cyclopropyl] -N' -[2- (5- cyano)pyridyl]thiourea N-[2 - (cis-2-(6-fluoro)pyridyl)cyclopropyl -N' -[2- (5- cyano)pyrazinyl]thiourea N-[2-(cis-2-(6-fluoroJpyridyl)cyclopropyl -N' (6- cyano)pyrazinyl]thiourea N-[2-(cis-2-(6-fluoroJpyridyl)cyclopropyl -N' -[ (3 -(6- cyano J pyridazinyl)]thiourea N- [2- (cis-2-(6-fluoroJpyridyl)cyclopropyl -N' -(2- [1,3,4-thiadiazoyl]J thiourea N—[2- (cis-2-(6-fluoroJpyridyl)cyclopropyl -N' -(2- benzimidazolyl)thiourea N-[2-(cis-2-(6-fluoroJpyridyl)cyclopropyl -N1 -(2- imidazolyl)thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -(2- thiazolyl)thiourea N-[2-(cis-2-(6-chloroJpyridyl)cyclopropyl -N' -[2- (4- methyl)thiazolyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (4,5- dimethyl)thiazolyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (4- cyano)thiazolyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N" -[2- ■ (4- trifluoromethyl)thiazolyl)thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -(2- benzothiazolyl)thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- -(6- fluoro)benzothiazolyl]thiourea N- [2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- -(6- chloro)pyrazinyl]thiourea 40 45 X-8571A 260 29 N- [2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' - -[2- (4- ethyl)thiazolyl]thiourea N- [2-(cis-2-(6-chloro)pyridyl)cyclopropyl! -N' - [2- (4- (3-pyridyl)thiazolyl)]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (4- (3-nitrophenyl)thiazolyl)]thiourea N-[2-(cis-2-(6-chloroJpyridyl)cyclopropyl -N' -(2- pyridyl)thiourea N- [2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (6- bromo)pyridyl]thiourea N-[2-(cis-2-(6-chloroJpyridyl)cyclopropyl! -N' -[2- (5- bromo)pyridyl]thiourea N- [2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (6- chloro)pyridyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (5- chloro)pyridyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (6- methyl)pyridyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (5- methyl)pyridyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' - [2- (6- trifluoromethyl) pyridyl ] thiourea N- [2- (cis-2- (6-chloro ).pyridyl) cyclopropyl -N' -[2- (5- trifluoromethyl) pyridyl ] thiourea N-[2-(cis-2-(6-chloroJpyridyl)cyclopropyl -N' -[2- (6- ethyl)pyridyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (5- ethyl)pyridyl]thiourea N- [2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (5- chloro)pyrazinyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' - [2- (6- bromo)pyrazinyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (5- bromo)pyrazinyl]thiourea N- [2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[ (3 -(6- bromo)pyridazinyl)]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -t (3 -(6- chloro)pyridazinyl)]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- (6- cyano)pyridyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N' -[2- •(5- cyano)pyridyl]thiourea N-[2-(cis-2-(6-chloroJpyridyl)cyclopropyl -N' -t2- - (5- cyano)pyrazinyl]thiourea N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl -N -[2- -(6- cyano)pyrazinyl]thiourea X-8571A 260 2 9 3 N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl]-cyano)pyridazinyl)]thiourea N- [2- (cis-2 - (6-chloroJpyridyl) cyclopropyl] -: [1,3,4-thiadiazoyl])thiourea 5 N-[2-(cis-2-(6-chloro)pyridyl)cyclopropyl]- benzimidazolyl)thiourea N-[2-(cis-2- (6-chloro)pyridyl)cyclopropyl] imidazolyl)thiourea N-[2-(cis-2-(6-methoxyJpyridyl)cyclopropyl 10 thiazolyl) thiourea N-[2-(cis-2-(6-methoxy)pyridyl)cyclopropyl methyl)thiazolyl]thiourea N-[2-(cis-2-(6-methoxyJpyridyl)cyclopropyl (4,5-dimethyl)thiazolyl]thiourea 1 5 N-[2-(cis-2-(6-methoxy Jpyridyl)cyclopropyl benzothiazolyl)thiourea N-[2-(cis-2-(6-methoxyJpyridyl)cyclopropyl fluoro)benzothiazolyl]thiourea N—[2-(cis-2-(6-methoxy Jpyridyl)cyclopropyl 2 0 chloro) pyrazinyl] thiourea N-[2-(cis-2-(6-methoxyJpyridyl)cyclopropyl (3-pyridyl)thiazolyl)]thiourea N-[2-(cis-2-(6-methoxy)pyridyl)cyclopropyl (3-nitrophenyl)thiazolyl)]thiourea 2 5 N-[2-(cis-2-(6-methoxy Jpyridyl)cyclopropyl pyridyl)thiourea N- [2 - (cis-2- (6-ir -jthoxy) pyr idyl) cyclopropyl bromo)pyridyl]thiourea N-[2-(cis-2-(6-methoxyJpyridyl)cyclopropyl 3 0 chloro J pyridyl]thiourea N-[2- (cis-2-(6-methoxyJpyridyl)cyclopropyl methyl)pyridyl]thiourea N-[2 - (cis-2-(6-methoxyJpyridyl)cyclopropyl methyl)pyridyl]thiourea 3 5 N-[2-(cis-2-(6-methoxy)pyridyl)cyclopropyl trifluoromethyl)pyridyl]thiourea N-[2-(cis-2-(6-methoxyJpyridyl)cyclopropyl tri fluoromethylJ pyridyl]thiourea N- [2-(cis-2-(6-methoxyJpyridyl)cyclopropyl 4 0 ethyl)pyridyl]thiourea N-.[2- (cis-2- (6-methoxy)pyridyl)cyclopropyl ethyl)pyridyl]thiourea N- [2-(cis-2-(6-methoxy Jpyridyl)cyclopropyl bromo)pyrazinyl]thiourea 4 5 N-[2-(cis-2-(6-methoxyJpyridyl)cyclopropyl bromo)pyridazinylJ]thiourea N'-[(3-(6-N'-(2-N'-(2-N'-(2--N"-(2--N'-[2-(4--N'-[2--N'-(2--N'-[2-(6--N'-[2-(6--N'-[2-(4--N'-[2-(4--N'-(2--N'-[2- (6--N' -[2-(6--N'-[2-(6--N*-[2-(5--N*-[2-(6--N'-[2-(5--N'-[2-(6--N'-[2-(5--N'-[2-(6--N' - [ (3 - (6- 1 5 40 45 X-8571A 260 2 9 N-[2-(cis-2-(6-methoxy)pyridyl) cyclopropyl]-N' -[2-(6-cyano)pyridyl]thiourea N- [?.- (cis-£- (6-methoxy)pyridyl) cyclopropyl] -N' - [2- (5-cyano)pyri dyl]thiourea N-[2- (cis-2- (6-methoxy) pyr idyl) cyclopropyl] -N' - [2- (5-cyano) pyrazinyl] thiourea N- [2- (cis-2- (6-methoxy)pyridyl) cyclopropyl] -N' - [2-(6-cyano) pyrazinyl ] thiourea N-[2-(cis-2-(6-methoxy)pyridyl)cyclopropyl]-N' - [ (3- (6 -cyano)pyridazinyl)]thiourea N-[2-(cis-2-(6-methoxy)pyridyl) cyclopropyl]-N' - (2-[1,3,4-thiadiazoyl])thiourea N-[2-(cis-2-(6-methoxyJpyridyl)cyclopropyl]-N' - (2-benzimidazolyl)thiourea N-[2-(cis-2- (6-methoxy)pyridyl)cyclopropyl]-N' - (2-imidazolyl)thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl]-N' -(2-thiazolyl)thiourea N- [2- (cis-2- (6-ethoxyJpyridyl) cyclopropyl] -N' - [2- (4-methy1)thiazolyl]thiourea N-[2 - (cis-2- (6-ethoxyJpyridyl) cyclopropyl] -n' -[2- (4,5-dimethyl )thiazolyl]thiourea N- [2-(cis-2-(6-ethoxy)pyridyl) cyclopropyl]-N1 -(2-benzothiazolyl)thiourea N-[2-(cis-2-(6-ethoxy)pyridyl) cyclopropyl]-N' -[2-(6-fluoro)benzothiazolyl]thiourea N- [2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl]-N' -[2- (6-chloro)pyrazinyl]thiourea N-[2-(cis-2-(6-ethoxyJpyridyl) cyclopropyl]-N' -[2- (4-(3-pyridylJ thiazolylJ]thiourea N-[2-(cis-2-(6-ethoxyJpyridyl) cyclopropyl]-n' -[2- (4-(3-nitrophenyl)thiazolylJ]thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl]-N' - (2-pyridyl)thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl]-N' -[2-(6-bromo)pyridyl]thiourea N- [2-(cis-2- (6-ethoxyJpyridyl)cyclopropyl]-N' -[2-(6-chloroJpyridyl]thiourea N-[2-(cis-2-(6-ethoxy)pyridyl) cyclopropyl]-N' -[2-(6-methy1)pyridyl]thiourea N-[2-(cis-2-(6-ethoxyJpyridyl)cyclopropyl]-N' -[2-(5-methy1J pyridyl]thiourea N- [2-(cis-2-(6-ethoxyJpyridyl)cyclopropyl]—N'-[2 —(6-trifluoromethyl)pyridyl]thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl]-N" -[2- (5-trifluoromethyl)pyridyl]thiourea X-8571A 260293 N-[2-(cis-2-(6-ethoxy)pyridyl) cyclopropyl ethyl)pyridyl]thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl ethyl)pyridyl]thiourea 5 N-12-(cis-2-(6-ethoxy)pyridyl)cyclopropyl bromo)pyrazinyl]thiourea N-[2-(cis-2-(6-ethoxyJpyridyl)cyclopropyl bromo)pyridazinyl)]thiourea N-[2-(cis-2-(6-ethoxyJpyridyl)cyclopropyl 10 cyano) pyridyl] thiourea N-[2-(cis-2-(6-ethoxy)pyridyl) cyclopropyl cyano)pyridyl]thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl cyano)pyrazinyl]thiourea 15 N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl cyano)pyraz inyl]thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl cyano)pyridazinyl)]thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl 2 0 [1,3,4-thiadiazoyl])thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl benzimidazolyl)thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl imidazolyl)thiourea 2 5 N- [2- (2 - [1,3-pyrimidyl]) ethyl] -N' - (2-. thiazolyl)thiourea N-[2-(2-[1,3-pyrimidyl])ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea N-[2-(2-[1,3-pyrimidyl])ethyl]-N'-[2-(4,5- 3 0 dimethyl)thiazolyl]thiourea N-[2-(2-[1,3-pyrimidyl])ethyl)-N'-[2- (4-cyano)thiazolyl]thiourea N-[2-(2-[1,3-pyrimidyl])ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea 3 5 N- [2- (2-[1,3-pyrimidyl]) ethyl] -N' - (2- benzothiazolyl)thiourea N-[2-(2-[1,3-j 3yl])ethyl]-N'-[2-(6- f luoro) benzothiazolyj thiourea N-[2-(2-[1,3-pyrimidyl])ethyl]-N'-[2-(6- 4 0 chloro) pyrazinyl] thiourea N-[2-(2-[1,3-pyrimidyl])ethyl]-N1 -[2- (4-ethyl)thiazolyl]thiourea N-[2-(2-[1,3-pyrimidyl])ethyl]-N' -[2- (4- (3-pyridyl)thiazolyl)]thiourea 4 5 N- [2- (2- [1,3-pyrimidyl]) ethyl] -N' - [2- (4- (3- nitrophenyl)thiazolyl)]thiourea -N'-[2-(6- -N'-[2-(5--N1 -[2-(6--N'-[(3-(6--N'-[2-(6--N'-[2-(5--N'-[2-(5--N'-[2-(6--N'-((3-(6--N'-(2--N'-(2--N'-(2- 40 X-8571A -92- 260 2 9 3 N-[2-(2-[1,3-pyrimidyl )ethyl -N' -(2-pyridyl)thiourea N- [2-(2-[1,3-pyrimidyl! )ethyl -N' -[2- (6- bromo)pyridyl]thiourea N- [2-(2-[1,3-pyrimidyl )ethyl -N' (5- bromo)pyridyl]thiourea N- [2-(2-[1,3-pyrimidy1! )ethyl -N' -[2- (6- chloroJpyridyl]thiourea N-[2-(2-[1,3-pyrimidyl )ethyl -N' -[2- (5- chloro)pyridyl]thiourea N- [2- (2-[1,3-pyrimidyl )ethyl -N' - [2- (6- methyl)pyridyl]thiourea • N-[2-(2-[1,3-pyrimidyl )ethyl -N' -[2- (5- methyl)pyridyl]thiourea N- [2-(2-[1,3-pyrimidy1 )ethyl -N' -[2- (6- trifluoromethyl)pyridyl]thiourea N- [2- (2-[1,3-pyrimidyl )ethyl -N' -f2- (5- trifluoromethyl)pyridyl]thio urea N- [2-(2-[1,3-pyrimidy1 )ethyl -N' (6- ethyl)pyridyl]thiourea N-12-(2-[1,3-pyrimidy1! )ethyl -N' -[2- (5- ethyl)pyridyl]thiourea N-.[2- (2- [1,3-pyrimidy1 )ethyl -N" -[2- (5- chloro). pyrazinyl] thiourea N- [2- (2-[1,3-pyrimidyl )ethyl! -N' - [2~ (6- bromo)pyrazinylj thiourea N- [2-(2-[1,3-pyrimidyl )ethyl -N' -C2- (5- bromo)pyrazinyl]thiourea N- [2- (2- [1,3-pyrimi(^l )ethyl -N' -[(3 -(6- bromo)pyridazinyl)]thiourea N- [2-(2-[1,3-pyrimidyl )ethyl -N' -[(3 -(6- chloro)pyridazinyl)]thiourea N-[2-(2-[1,3-pyrimidyl )ethyl -N -[2- (6- cyano)pyridyl]thiourea N-[2-(2-[1,3-pyrimidyl )ethyl -N' -[2- (5- cyano)pyridyl]thiourea N-[2-(2-[1,3-pyrimidyl )ethyl -N -[2- (5- cyano)pyrazinyl]thiourea N-[2-(2-[1,3-pyrimidyl )ethyl -N -[2- (6- cyano)pyrazinyl]thiourea N-[2-(2-[1,3-pyrimidyl )ethyl -N -[(3 -(6- cyano)pyridazinyl)]thiourea N- [2-(2-[1,3-pyrimidyl )ethyl -N -(2- [1,3,4- thiadiazoyl])thiourea N-[2-(2-[1,3-pyrimidyl )ethyl -N -(2- ber.zimidazolyl) thiourea 1 0 1 5 40 45 X-8571A 260 2 p^ N-[2~ (2- [1,3-pyrimidyl] )ethyl] -N' - (2-imidazoly1)thiourea N- [2-(2-pyrazinyl]ethyl]-N'-(2-thia zoly1)thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(4,5-dimethyl)thiazolyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-(2-benzothiazolyl)thiourea N-[2-(2-pyrazinyl]ethylj-N'-[2-(6-fluoro)benzothiazolyl]thiourea N- [2-(2-pyrazinyl]ethyl]-N'-[2-(6-chloro)pyrazinyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-[2-(2-pyrazinyl]ethyl]-N'—[2—(4—(3— nitrophenyl)thiazolyl)]thiourea N- [2-(2-pyrazinyl]ethyl]-N'-(2-pyridyl)thiourea N- [2-(2-pyrazinyl]ethyl]-N'- [2 - (6-bromo)pyridyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(5-bromo)pyridyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N' — [2—(6 — chloro)pyridyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(5-chloro)pyridyl]thiourea N- [2-(2-pyrazinyl]ethyl]-N'-[2-(6-methyl)pyridyl]thiourea N- [2-(2-pyrazinyl]ethyl]-N'-[2-(5-methyl)pyridyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(6-tri fluoromethyl)pyridyl]thiourea N- [2-(2-pyrazinyl]ethyl]-N*-[2-(5-tri fluoromethyl)pyridyl]thiourea N- [2-(2-pyrazinyl]ethyl]-N'-[2-(6-ethyl)pyridyl]thiourea N- [2-(2-pyrazinyl]ethyl]-N'-[2-(5-ethy1)pyridyl]thiourea N- [2-(2-pyrazinyl]ethyl]-N'-[2-(5-chloro)pyrazinyl]thiourea 1 0 1 5 40 45 X-8571A 260 2 9 N-[2-(2-pyrazinyl]ethyl]-N'-[2-(6-bromo)pyrazinyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(5-bromo)pyrazinyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N' — [(3 -( bromo)pyridazinyl)]thiourea N-[2-{2-pyrazinyl]ethyl]-N'-[(3-(6-chloro)pyridazinyl)]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(6-cyano)pyridyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(5-cyano)pyridyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(5-cyano)pyrazinyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[2-(6-cyano)pyrazinyl]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-[(3- (6-cyano)pyridazinyl)]thiourea N-[2-(2-pyrazinyl]ethyl]-N'-(2-[l,3,4-thiadiazoyl])thiourea N-[2-(2-pyrazinyl]ethyl]-N'-(2-benzimidazolyl)thiourea N-[2-(2-pyrazinyl]ethyl]-N'-(2-imidazolyl)thiourea N-[2-(3-pyridazinyl)ethyl]-N1-(2-thiazolyl)thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(4,5-dimethyl)thiazolylJ thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-(2-benzothiazolyl)thiourea N-(2-(3-pyridazinyl)ethyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea N-[2-(3-pyridazinyl)ethylJ-N'-[2-(6-chloro)pyrazinyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N1 -[2-(4-(3-pyridyl)thiazolyl)]thiourea N-[2-(3-pyridazinyl)ethyl]-N"-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-(2-pyridyl)thiourea N-i2-(3-pyridazinyl)ethyl]-N'-[2-(6-bromo)pyridyl]thiourea 1 0 1 5 3 5 40 45 X-8571A 26 0 2 9 3 N-[2-(3-pyridazinyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea N- [2-(3-pyridazinyl)ethyl]-N' — [2 —(6— chloro)pyridyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(6-methy1)pyridyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(5-methy1)pyridyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(5-tri fluoromethyl)pyridyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(6-ethyl)pyridyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(5-ethy1)pyridyl]thiourea N- [2-(3-pyridazinyl)ethyl]-N'-[2-(5-chloro)pyrazinyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(6-bromo)pyrazinyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(5-bromo)pyrazinyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N' - [(3 —(6 —• bromo)pyridazinyl)]thiourea N- [2-(3-pyridazinyl)ethyl]-N'-[(3- (6-chloro)pyridazinyl)]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(6-cyano)pyridyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(5-cyano)pyridyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(5-cyano)pyrazinyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[2-(6-cyano)pyrazinyl]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-[(3-(6-cyano)pyridazinyl)]thiourea N-[2-(3-pyridazinyl)ethyl]-N'-{2-[l,3,4-thiadiazoyl])thiourea N-[2-(3-pyridazinyl)ethyl]-N'-(2-benzimidazolyl)thiourea N- [2- (3-pyridaz.inyl)ethyl] -N* - (2-imidazolyl) thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl]-N'-(2-thiazolyl)thiourea X-8571A 260 £ 0 * N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl methyl)thiazolyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl dimethyl)thiazolyl]thiourea 5 N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl cyano)thiazolyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl trifluoromethyl)thiazolyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl 10 benzothiazolyl) thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl fluoro)benzothiazolyl]thiourea N-[2-(2,6-difluoro-3-methos^phenyl)ethyl chloro)pyrazinyl]thiourea 15 N- [2-(2,6-difluoro-3-methoxyphenyl)ethyl ethyl)thiazolyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl pyridyl)thiazolyl)]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl 2 0 nitrophenyl)thiazolyl)]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl pyridyl)thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl bromo)pyridyl]thiourea 2 5 N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl chloro)pyridyl]thiourea N- [2-(2,6-difluoro-3-methoxyphenyl)ethyl chloro)pyridyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl 3 0 methyl)pyridyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl methyl)pyridyl]thiourea N- [2 - (2,6-difluoro-3-methoxyphenyl)ethyl trifluoromethyl)pyridyl]thiourea 3 5 N- [2-(2,6-difluoro-3-methoxyphenyl)ethyl trifluoromethyl)pyridyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl ethyl)pyridyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl 4 0 ethyl) pyridyl] thiourea N-[2-(2, 6-difluoro-3-methoxyphenyl)ethyl chloro)pyrazinyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl bromo)pyrazinyl]thiourea 4 5 N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl bromo)pyra z iny1]thiourea -N'-[2--N' - [2--N'-[2--N' - [2--N'-(2--N'-[2--N'-[2--N'-[2--N'-[2--N ' - [ 2 --N'-(2--N'-[2--N'-[2--N'-[2--N1-[2--N'-[2--N'-[2--N'-[2--N1 -[2--N'-[2--N'-[2--N'-[2--N'-[2- (4-(4,5-(4-(4- (6-(6-(4- (4-(3-(4-(3- (6-(6-(5-(6-(5-(6-(5-(6-(5-(5-(6-(5- X-8571A -97- 26 0 2 9 N- [2- (2, 6-dif luoro-3-methoxyphenyl) ethyl] -N1 - [2- (3- (6-bromo]pyridazinyl)]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl]-N'-[2-(3-[6-chloro]pyridazinyl)]thiouiea 5 N-[2-(2, 6-difluoro-3-methoxyphenyl)ethyl]-N'-[2- (6- cyano)pyridyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl]-N'-[2-(5-cyano)pyridyl]thiourea N- [2 - (2,6-difluoro-3-methoxyphenyl)ethyl]-N'-[2-(5- 1 0 cyano)pyrazinyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl]-N'- [2- (6-cyano)pyrazinyl]thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl]-N'-[2-(3-[6-cyano]pyridazinyl)]thiourea 1 5 N-'(2- (2, 6-dif luoro-3-methoxyphenyl) ethyl] -N1 - (2- [1,3,4-thiadiazoyl])thiourea N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl]-N'-(2-benzimidazolyl)thiourea N- [.?- (2, 6-difluoro-3-methoxyphenyl) ethyl] -N' - (2- 2 0 imidazolyl)thiourea N- [2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-(2-thiazolyl)thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N*-[2-(4-methyl)thiazolyl]thiourea 2 5 N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-[2-(4,5- dimethyl)thiazolyl]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-[2-(4- 3 0 tri fluoromethyl)thiazolyl]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-(2-benzothiazolyl)thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea 3 5 N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-[2-(6— chloro)pyrazinyl)thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-[2-(4-(3- 4 0 pyridyl)thiazolyl)]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-(2-pyridyl)thiourea 45 N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl]-N'-[2-<6- bromo)pyridyl]thiourea X-8571A 2 6 o 2 9 N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl bromo)pyridyl]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl chloro)pyridyl]thiourea 5 N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl chloro)pyridyl]thiourea N-[2- (2,6-difluoro-3-ethoxyphenyl)ethyl methyl)pyridyl]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl 1 0 methyl)pyridyl]thiourea N-[2-(2,6-^ifluoro-3-ethoxyphenyl)ethyl trifluoromethyl)pyridyl]thiourea N-[2-(2, 6-difluoro-3-ethoxyphenyl)ethyl trifluoromethyl)pyridyl]thiourea 15 N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl ethyl)pyridyl]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl ethyl)pyridyl]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl 20 chloro) pyrazinyl] thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl bromo)pyrazinyl]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl bromo)pyrazinyl]thiourea 25 N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl bromo]pyridazinyl)]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl chloro]pyridazinyl)]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl 3 0 cyano)pyridyl]thiourea N-[2-(2, 6-difluoro-3-ethoxyphenyl)ethyl cyano)pyridyl]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl cyano)pyrazinyl]thiourea 3 5 N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl cyano)pyrazinyl]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl cyano]pyridazinyl)]thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl 4 0 thiadiazoy}])thiourea N- [2- (2, 6-dif luoro-3-etho^phenyl) ethyl benzimidazolyl)thiourea N-[2-(2,6-difluoro-3-ethoxyphenyl)ethyl imidazolyl)thiourea 45 N-'[2- (2, 6-difluoro-4-methoxyphenyl) ethyl] -N" - (2- thiazolyl)thiourea -N'-[2-(5--N'-[2-(6--N'-[2-(5--N'-[2- (6--N'-[2-(5--N'-[2-(6--N'-[2-(5--N'-[2-(6--N'-[2-(5--N1 -[2-(5--N'-[2-(6--N'-[2-(5--N'-[2-(3-[6--N'-[2-(3 —[6 — -N' — 12 — C 6 — -N'-[2-(5--N'-[2-(5--N1 -[2-(6--N'-[2-{3 — 16 — -N'-(2-[l,3,4--N'-(2--N'-(2- 1 0 1 5 40 2 6 0 2 8 3 X-8571A -99- N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N'- t2- (4- methyl)thiazolyl]thiourea N-[2-(2, 6-difluoro-4-methoxyphenyl)ethyl -N'- [2- (4,5- dimethyl)thiazolyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N' - t2- (4- cyano)thiazolyl]thiourea N-[2- (2,6-difluoro-4-methoxyphenyl)ethyl -N' - [2- (4- tri f luoromethyj.) thiazolyl] thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N'- (2- benzothiazolyl)thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N'- [2- (6- fluoro)benzothiazolyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N' - [2- (6- chloro)pyrazinyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl! -N'- [2- (4- ethyl)thiazolyl]thiourea N-[2- (2,6-difluoro-4-methoxyphenyl)ethyl -N'- [2- (4- (3- pyridyl)thiazolyl)]thiourea N- [2- (2,5-difluoro-4-methoxyphenyl)ethyl! -N' - 12- (4- (3- nitrophenyl)thiazolyl)]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N'- (2- pyr idyl)thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N' - 12- (6- bromo)pyridyl]thiourea N- [2 - (2,6-difluoro-4-methoxyphenyl)ethyl -N' - [2- (5- bromo)pyridyl]thiourea N- [2-(2, 6-difluoro-4-methoxyphenyl)ethyl -N' - [2- (6- chloro)pyridyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N' - [2- (5- chloro)pyridyl]thiourea N- [2- (2,6-difluoro-4-methoxyphenyl)ethyl -N' - [2- (6- methyl)pyridyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N' - 12- (5- methyl)pyridyl]thiourea N- [2-(2,6-difluoro-4-methoxyphenyl)ethyl -N'- [2- (6- trifluoromethylJpyridyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N' - [2- (5- trifluoromethyl)pyridyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N' - •[2- (6- ethyl)pyridyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N'- [2- (5- ethyl)pyridyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N' - •C2- (5- chloro)pyrazinyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl -N' - ■12- -(6- bror-* pyrazinyl]thiourea 1 0 1 5 3 5 40 45 X-8571A 2 6 o 2 9 3 N- [2-(2,6-difluoro-4-methoxyphenyl)ethyl]-N'-[2-(5-bromo)pyrazinyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl]-N'-[2-(3-16-bromo] pyridazinyl )]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl]-N'-[2-(3-[6-chloro]pyridazinyl)]thiourea N- [2-(2,6-difluoro-4-methoxyphenyl)ethyl]-N'-[2-(6-cyano)pyridyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl)-N'-[2-(5-cyano)pyridyl]thiourea N-[2- (2, 6-difluoro-4-methoxyphenyl) ethyl] -N' - P- (5--cyano1 .jyrazinyl] thiourea N- [2-(2,6-difluoro-4-methoxyphenyl)ethyl]-N'- [2-(6-cyano)pyrazinyl]thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl]-N'-[2-(3-[6-cyano]pyridazinyl)]thiourea N- [2 - (2,6-difluoro-4-methoxyphenyl)ethyl]-N'-(2-[1,3,4-thiadiazoyl])thiourea N- [2-(2,6-difluoro-4-methoxyphenyl)ethyl]-N'- (2-benzimidazolyl)thiourea N-[2-(2,6-difluoro-4-methoxyphenyl)ethyl]-N'-(2-imidazoly1)thiourea N-[2-(2,6-difluoro-4-ethoxyphenyl)ethyl]-N'-(2-thiazolyl)thiourea N-[2-(2,6-difluoro-4-ethoxyphenyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea N- [2-(2,6-difluoro-4-ethoxyphenyl)ethyl]-N'-[2-(4,5-dimethyl)thiazolyl]thiourea N- [2-(2,6-difluoro-4-ethoxyphenyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea N- [2- (2, 6-difluoro-4-ethoxyphenyl) e^.hyl] -N' - [2- (4-trifluoromethyl)thiazolyl]thiourea N-[2-(2,6-difluoro-4-ethoxyphenyl)ethyl]-N'-(2-benzothiazolyl)thiourea N- [2-(2,6-difluoro-4-ethoxyphenyl)ethyl]-N'-[2-(6-fluoro)benzothiazolyl]thiourea N-.[2- (2, 6-dif luoro-4-ethoxyphenyl) ethyl] -N' - [2- (6-chloro)pyrazinyl]thiourea N-[2-(2,6-difluorc-4-ethoxyphenyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea N- [2-(2,6-difluoro-4-ethoxyphenyl)ethyl]-N'-[2-(4-(3-pyridyl)thiazolyl)]thiourea N-[2-(2,6-difluoro-4-ethoxyphenyl)ethyl]-N'-[2-(4-(3-nitrophenyl)thiazolyl)]thiourea N- [2-(2,6-difluoro-4-ethoxyphenyl)ethyl]-N'-(2-pyridyl)thiourea 15 20 30 40 X-8571A -101- 2 6 0 2 9 .1 N-[2-(2,6-difluoro-4-ethoxyphenyl)ethyl] bromo)pyridyl]thiourea N-[2- (2,6-difluoro-4-ethoxyphenyl)ethyl] bromo)pyridyl]thiourea N-[2- (2,6-difluoro-4-ethoxyphenyl)ethyl] chloro)pyridyl]thiourea N-[2-(2,6-difluoro-4-ethoxyphenyl)ethyl] chloro)pyridyl]thiourea N-[2-(2,6-difluoro-4-ethoxyphenyl)ethyl] methyl)pyridyl]thiourea N-[2- (2,6-difluoro-4-ethoxyphenyl)ethyl] methyl)pyridyl]thiourea N- [2-(2,6-difluoro-4-ethoxyphenyl)ethyl] trifluoromethyl)pyridyl]thiourea N-[2-(2,6-difluoro-4-ethoxyphenyl)ethyl] trifluoromethyl)pyridyl]thiourea N- [2- (2,6-difluoro-4-ethoxyphenyl)ethyl] ethyl)pyridyl]thiourea N-[2-(2,6-difluoro-4-ethoxyphenyl)ethyl] ethyl)pyridyl]thiourea N- [2- (2,6-difluoro-4-ethoxyphenyl)ethyl] chloro)pyrazinyl]thiourea N- [2- (2,6-difluoro-4-ethoxyphenyl)ethyl] bromo)pyrazinyl]thiourea N- [2-(2,6-difluoro-4-ethoxyphenyl)ethyl] bromo)pyrazinyl]thiourea N- [2- (2,6-difluoro-4-ethoxyphenyl)ethyl] bromo1pyridazinyl)]thiourea N- [2- (2, 6-difluoro-4-etho3Qrphenyl) ethyl ] chloro]pyridazinyl)]thiourea N- [2-(2,6-difluoro-4-ethoxyphenyl)ethyl 1 cyano)pyridyl]thiourea N- [2 - (2,6-difluoro-4-ethoxyphenyl)ethyl] cyano)pyridyl]thiourea N- [2- (2,6-difluoro-4-ethoxyphenyl)ethyl] cyano)pyraz inyl]thiourea N-[2-(2,6-difluoro-4-ethoxyphenyl)ethyl] cyano)pyrazinyl]thiourea N- [2- (2,6-difluoro-4-ethoxyphenyl)ethyl] cyano]pyridazinyl)J thiourea N- [2-(2,6-dif3"oro-4-ethoxyphenyl)ethyl] thiadiazoy1])thiourea N- [2-(2,6-difluoro-4-ethoxyphenyl)ethyl] benzimidazolyl)thiourea N- [2-(2,6-difluoro-4-ethoxyphenyl)ethyl] imidazolyl)thiourea -N' ■ -N'- -N' ■ -N' • -N' • -N' • -N' • -N'- -N' • -N' -N' • -N' -N' -N' -N' -N' -N' -N' -N' -N' -N' -N' -N' [2-(6-12 —(5— [2-(6-[2-(5-[2-(6-[2-(5- • [2-(6-[2-(5-[2-(6-[2-(5-[2-(5-[2-(6-[2-(5- • [2-(3-[6- ■ [2-(3-|6- • [2-(6- - [2— (5 — ■ [2- (5- - [2-(6- • [2-(3-[6- - (2-[1,3,4--(2- -(2- 40 45 X-8571A 26 0 c9 N-[2-(2-(3-ethoxy)pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea N-[2-(2-(3-methoxy)pyridyl)ethyl]-N'-[2-(5-bromo) pyridyl ] thiourea N-(2-phenethyl)-N'-[2-(3-ethyl)pyridyl]thiourea N-[2-(2,6-difluorophenyl)ethyl]-N' - [3- (6-methoxy)pyridazinyl]thiourea N-[2-(2,6-difluoro-3-N-methylcarboxamidephenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea N-[2-(2-fluoro-6-chlorophenyl)ethyl]-N'-(2-thiazolyl)thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(5-nitro)pyridyl]thiourea N- [2- (3-bromo-b-methoxyphenyl)ethyl]-N' - (2-thiazolyl)thiourea (±)N-[2-[(2,6-difluorophenyl)-2-(methyl)]ethyl]-N'-(2-thiazolyl)thiourea N-[2-(3-ethoxyphenyl)ethyl]-N'-(2-thiazolyl)thiourea N-[2-(3-bromo-6-ethoxyphenyl)ethyl]-N' - (2-thiazolyl)thiourea N-[2-(cis-(2-fluoro)phenyl)cyclopropyl]-N'-(2-thiazolyl)thiourea N-[2-(3-(2-fluoroJpyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea (±)N-[cis-2-(3-chlorophenylJcyclopropyl]-N'-[2-(5-chloro)pyridyl]thiourea (±)N- [cis-2-(3-fluorophenyl)cyclopropyl]-N'-[2-(5-chloro)pyridyl]thiourea N-[2-(2-vinyl)phenethy1]-N'-[2-(5-bromo)pyridyl]thiourea N-[2-(3-vinyl)phenethyl]-N'-[2-(5-bromo)pyridyl]thiourea N-[2-(3-methoxycarbony1)phenethyl]-N'-[2-(5-bromo)pyridyl]thiourea N-[2-(5,6-dimethylbenzotriazolyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea N-[2-(l-cyclohexenyl)ethyl]-N'-[2-(5,6-dichloro-4-azabenzimidazolyl)]thiourea N-[2-(2,3-difluoro-6-methoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea (±)N-[cis-2-(4-methylphenyl)cyclopropyl]-N'-[2-(5-chloro)pyridyl]thiourea (±)N-[cis-2-(2-fluorophenyl)cyclopropyl]-N'-[2-(5-chloro)pyridyl]thiourea (±)N-[cis-2-(3-cyanophenyl)cyclopropyl]-N'-[2-(5-chloro)pyridyl]thiourea 40 45 X-8571A 260 29 3 (±)N- tcis-2- (2,6-difluoro-3-cyanophenyl) cyclopropyl] -N' - [ 2 - (5 - chloro) pyridyl ] thiourea (±)-cis-N-(3,4-benzo-cis-bicyclo-[3.1.0]-hexen-6-yl)-N'- [2 - (5-chloro)pyridyl] thiourea N- [2- (3-ethynylpheny 1) ethyl] -N' • [2- (5-bromo)pyridyl]thiourea N- [2-(2,5-diethoxyphenyl)ethyl]-N'-[2- (5-bromo)pyridyl]thiourea N- [2- (2-methoxypheny 1) ethyl]-N'-[4-(6-aminopyrimidinyl)]thiourea N- [ 2 - (2 -methoxyphenyl) ethyl ] -N' - (4 -pyrimidiny1)thiourea (±)N-[2-(cis-2-pyridyl)]-N'-[2-(3-pyridazinyl)]thiourea (±)N-[2-(cis-2-pyridyl)]-N'-[2-(3-(6-methyl)pyridazinyl)]thiourea (±)N- [2- (cis-2-pyridyl) ] -N* - (2-pyrazinyl) ] thiourea (±)N-[2-(cis-2-pyridyl)]-N'-[2-(5-methyl)pyrazinyl)]thiourea (±)N-[2-(cis-2-(3-fluoro)pyridyl)]-N*-[2- (3-pyridazinyl)]thiourea (±)N-[2-(cis-2-(3-fluoro)pyridyl)]-N*-[2- (3- (6-methy1)pyridaz inyl)]thiourea (±)N-[2-(cis-2-(3-fluoro)pyridyl)]-N'-(2-pyrazinyl)]thiourea (±)N-[2-(cis-2-(3-fluoro)pyridyl)]-N'-[2- (5-methyl)pyrazinyl)]thiourea N- (2-cis-phenylcryclopropyl) -N' - [2- (3-pyridazinyl)]thiourea N-(2-cis-phenylcyclopropyl)-N'-[2-(3-(6-methyl)pyridazinyl)]thiourea N- (2-cis-phenylcyclopropyl) -N' - (2-pyrazinyl) ] thiourea N-(2-cis-phenylcyclopropyl)-N'-[2-(5-methyl)pyrazinyl)]thiourea N-[2-(cis-2-fluorophenyl)cyclopropyl)]-N' - [2- (3-pyridazinyl)]thiourea N-12-(cis-2-fluorophenyl)cyclopropyl)]-N'- [2-(3 -(6-methyl)pyridazinyl)]thiourea N-[2-(cis-2-fluorophenyl)cyclopropyl)]-N'- (2-pyrazinyl)]thiourea N-[2-(cis-2-fluorophenyl)cyclopropyl)]-N' - [2-(5-methyl)pyrazinyl)]thiourea N-[2-(cis-2,6-difluorophenyl) cyclopropyl)]-N'-[2-(3-pyridazinyl)]thiourea N-[2-(cis-2,6-difluorophenyl)cyclopropyl)]-N'-[2-(3-(6-methyl)pyridazinyl) ] thiourea X-8571A -104- 26 0 2. o i W vJ N-[2-(cis-2,6-difluorophenyl)cyclopropyl)]-N*-(2-pyrazinyl)]thiourea N-[2-(cis-2,6-difluorophenyl)cyclopropyl)]-N'-[2- (5-methyl)pyrazinyl)]thiourea 5 N- [2- (cis-3-methoxyphenyl) cyclopropyl) ] -N' - [2- (3- pyridasinyl)]thiourea N-\2-(cis-3-methoxyphenyl) cyclopropyl)]-N'-[2-(3-(6-methyl)pyridazinyl)]thiourea N-[2- (cis-3-methoxyphenyl)cyclopropyl) ] -N' - (2-1 0 pyrazinyl)]thiourea N- [2-(cis-3-methoxyphenyl)cyclopropyl)]-N'-[2-(5-methyl)pyrazinyl)]thiourea \A/H3 Hv.A.yC(CH3' s K v / n" n r„X0 rf 0 r? \J \J vVO cs/~\ 6 d vvQ S /==\ I 5 X-8571A -105- 260 2 93 The following are more preferred compounds.

N-(2-phenethyl)-N'-[2-(5-bromo)pyridyl]thiourea 5 N-(2-phenethyl)-N'-[2-(5-chloro)pyridyl]thiourea N-(2-phenethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea N-(2-phenethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-phenethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea N-(2-(2-methoxyphenyl)ethyl)-N'-[2-(5-10 chloro) pyraz inyl] thiourea N- (2- (2-methoxyphenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-(2-methoxyphenyl)ethyl)-N'-[(3-(6-chlorc *pyridazinyl)]thiourea 15 N- (2- (3-methoxyphenyl)ethyl) -N1 - [2- (5- chioro)pyrazinyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[(3-(6-2 0 chloro)pyridazinyl)]thiourea N-(2-(2-ethoxyphenyl)ethyl)-N'-[2-(4-cyano)thiazolyl]thiourea N-(2- (2-ethoxyphenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea 2 5 N- (2- (2-ethoxyphenyl) ethyl) -N' - [2- (4- ethyl)thiazolyl]thiourea N- (2- (2-ethoxyphenyl)ethyl) -N' - [2- (5-chloro)pyrazinyl]thiourea N-(2- (2-ethoxyphenyl)ethyl)-N'-[2-(5- 3 0 bromo)pyrazinyl]thiourea N-(2- (2-ethoxyphenyl)ethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea N- (2- (2-methylphenyU ethyl) -N' - [2- (4-cyano) thiazolyl ] thiourea 3 5 N- (2- (2-methylphenyl) ethyl) -N' - [2- (4- trifluoromethyl)thiazolyl]thiourea N-(2- (2-methylphenyl)ethyl)-N'-[2 -(4-ethyl)thiazolyl]thiourea N- (2- (2-methylphenyl)ethyl)-N' — [2-(5 — 4 0 bromo)pyridyl]thiourea N-(2- (2-methylphenyl)ethyl)-N'-[2-(6-chloroJpyridyl]thiourea N- (2- (2-methylphenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea 4 5 N-(2-(2-methylphenyl)ethyl)-N' -[2-(5- bromo)pyrazinyl]thiourea 1 0 1 5 40 45 X-8571A 26 0 2 9 N-(2-(2-methylphenyl)ethyl)-N'-[(3- (6-chloro)pyridazinyl)]thiourea N- (2-(2-fluorophenyl)ethyl)-N'-[2-(4-cyano)thiazolyl,chiourea.

N- (2-(2-fluorophenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N- (2-(2-fluorophenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N- (2-(2-fluorophenyl)ethyl)-N'-[2-(5-bromo)pyridyl]thiourea N- (2-(2-fluorophenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea N- (2-(2-fluorophenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea N- (2- (2-fluorophenyl)ethyl)—N' — [2—(5 — bromo)pyrazinyl]thiourea N- (2-(2-fluorophenyl)ethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea N- (2 - (2,6-difluorophenyl)ethyl)-N1-(2-thiazolyl)thiourea N- (2-(2,6-difluorophenyl)ethyl)-N'-[2-(4-methyl)thiazolyl]thiourea N- (2- (2, 6-dif luorophenyl) ethyl) -N' - (2-pyr idyj.) thiourea N- (2-(2,6-difluorophenyl)ethyl)-N'-[2-(6-bromo)pyridyl]thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(5-methyl)pyridyl]thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(5-trifluoromethylJpyridyl]thiourea N- (2-(2,6-difluorophenyl)ethyl)-N'-[2-(5-ethyl)pyridyl]thiourea N- (2-(2,6-difluorophenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(5-cyano)pyridyl]thiourea N-(2-(2-fluoro-6-methoxyphenyl)ethyl)-N1-[2-(4-cyano)thiazolyl]thiourea N-(2-(2-fluoro-6-methoxyphenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N-(2-(2-fluoro-6-methoxyphenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N-(2-(2-fluoro-6-methoxyphenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea N- (2-(2-fluoro-6-methoxyphenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea 40 45 X-8571A 26 0 2 9 3 N-(2-(2-fluoro-6-methoxyphenyl)ethyl)-N' -[(3— (6-chloro)pyridazinyl)]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl)-N'-[2-(4-cyano)thiazolyl]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl)thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl)-N'-[2-(5-bromo)pyridyl]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)euhyl)-N' - [2-(5-chloro)pyrazinyl]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl)-N"-[2-(5-bromo)pyrazinyl]thiourea N-(2-(2-fluoro-6-ethoxyphenyl)ethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea N-(2-(2-chlorophenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N-'(2- (2-chlorophenyl) ethyl) -N' - [2- (5-chloro)pyrazinyl]thiourea N-(2-(2-chlorophenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-(2-chlorophenyl)ethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea N- (2-(3-chlorophenyl)ethyl)-N•-[2 -(4-trifluoromethyl)thiazolyl]thiourea N- (2-(3-chlorophenyl)ethyl)-N'-[2 -(5-chloro) p:*raziny 1 ] thiourea N- (2- (3-chlorophenyl) ethyl) -N*-[2-(5-bromo)pyrazinyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea N-(2-(l-cyclohexenyl)ethyl)-N*-(2-thiazolyl)thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[2-(4-methyl)thiazolyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N*-(2-pyridyl)thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[2- (5-methyl)pyridyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[2-(5-trifluoromethyl)pyridyl]thiourea N-.(2- (l-cyclohexenyl) ethyl) -N' - [2- (5-ethyl)pyridyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea 1 0 40 45 X-8571A 26 0 29 3 N-(2-(l-cyclohexenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N' -[2 - (5-cyano)pyridyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[2-(5-cyano)pyrazinyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[(3-(6-cyano)pyridazinyl)]thiourea N-(2 - (2,5-dimethoxyphenyl)ethyl)-N'-[2- (4-cyano)thiazolyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2- (4-trifluoromethyl)thiazolyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(5-bromo)pyridyl]thiourea N-(2-(2,5-dimethoxyphenyl)ethyl)-N"-[(3-(6-chloro)pyridazinyl)]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N' - [2-(4-cyano) thifizolyl] thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N* - [2-(5-bromo)pyridyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N' - [2-(5-chloro)pyridyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N' -[2-(5-bromo)pyrazinyl]thiourea N-(2-(2-fluoro-6-chlorophenyl)ethyl)-N' - [ (3-(6-chloro)pyridazinyl)]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(4-cyano)thiazolyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N' - [2- (4-trifluoromethyl)thiazolyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-(2- (4-ethyl)thiazolyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2- (5-bromo)pyridyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(5-chloroJpyridyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea 40 45 X-8571A 260^9 3 N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-(2,6-dimethoxyphenyl)ethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(4-cyano)thiazoly?]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N- (2-(2,6-dichlorophenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(5-bromo)pyridyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(5-ohloro)pyridyl]thiourea N-(2-(2,6-dichlorophenyl}ethyl)-N•-[2-(5-chloro)pyrazinyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-(2,6-dichlorophenyl)ethyl)-N'-[ (3- (6-chloro)pyridazinyl)]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-[2- (4-cyano)thiazolyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-[2- (4-ethyl)thiazolyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N*-[2-(5-bromo)pyridyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea N-(2-(3-fluoropheayl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-[2- (5-bromo)pyraz inyl]thiourea N-(2-(3-fluorophenyl)ethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea N-(2-cis-phenylcyclopropyl)-N'-(2-thiazolyl)thiourea N-(2-cis-phenylcyclopropyl)-N'-[2-(4-cyano)thiazolyl]thiourea N-(2-cis-phenylcyclopropyl)-n*-[2-(4- trifluoromethyl)thiazolyl]thiourea N-(2-cis-phenylcyclopropyl)-N'-[2-(5-methylJpyridyl]thiourea N-(2-cis-phenylcyclopropyl)-n'-[2-(4-ethyl)thiazolyl]thiourea N-(2-cis-phenylcyclopropyl)-N'-(P-pyridyl)thiourea X-8571A 2^0293 N-(2-cis-phenylcyclopropyl)-N'-[2-(5-trifluoromethyl)pyridyl]thiourea N-(2-cis-phenylcyclopropyl)-N'-[2-(5-ethy1)pyridyl]thiourea 5 N-(2-cis-phenylcyclopropyl)-N'-[2-(5— chloro)pyrazinyl]thiourea N-(2-cis-phenylcyclopropyl)-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-cis-phenylcyclopropyl)-N'-[(3 -(6 — 1 0 bromo)pyridazinyl)]thiourea N-(2-cis-phenylcyclopropyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea N-(2-cis-phenylcyclopropyl)-N*-[2-(5-cyano)pyridyl]thiourea 15 N-[2-(2-pyridyl)ethyl]-N'-(2-thiazolyl)thiourea N-[2-(2-pyridyl)ethyl]-N'-[2 —(4-methyl)thiazolyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea 20 N- [2- (2-pyridyl) ethyl] -N' - [2 - (4- trifluoromethyl)thiazolyl]thiourea N-[2-(2-pyridyl)ethyl]-N*- 12-(4-ethyl)thiazolyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-(2-pyridyl)thiourea 25 N-[2-(2-pyridyl)ethyl]-N'-[2-(6-bromoJpyridyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(6-chloro)pyridyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(6-methyl)pyridyl]thiourea 3 0 N- [2- (2-pyridyl) ethyl] -1J' - [2- (5- methyl)pyridyl]thiourea N-12-(2-pyridyl)ethyl]-N'-[2-(6-trifluoromethyl)pyridyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(6-ethylJpyridyl]thiourea 3 5 N- [2-(2-pyric£rl) ethyl] -N' - [2-(5- chloro)pyrazinyl]thiourea N-[2-(2-pyridyl)ethyl]-N1 -[2-(5-bromo)pyrazinyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-[(3-(6- 4 0 bromo)pyridazinyl)]thiourea N- [2-(2-pyridyl)ethyl]-N'-[(3-(6-chloro)pyridazinyl)]thiourea N—[2-(2-pyridyl)ethyl]-N'-[2-(5-cyanoJpyridyl]thiourea N- [2-(2-pyridyl)ethyl]-N'-[2-(5-4 5 cyano)pyraz inyl]thiourea 260 P 3 X-8571A -111- N- [2- (2-pyridyl) ethyl ]-~N' - [ (3- (6-cyano)pyridazinyl)]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-(2-thiazolyl)thiourea 5 N-[2-(2-(6-methoxy)pyridyl)ethyl] -N'-[2-(4- methy1)thiazolyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'- £2-(4 — 1 0 trifluoromethyl)thiazolyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl] -N'-[2-(4-ethyl)thiazolyl]thiourea N-[2-(2-(6-methoxyJpyridyl)ethyl]-N'-(2-pyridyl)thiourea 1 5 N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(5- methy1)pyridyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(5-trifluoromethyl)pyridylj thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl] -N' -[2-(5- 2 0 chloro) pyrazinyl] thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(5-bromo)pyrazinyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl] -N'-[(3-(6-chloro)pyridazinyl)]thiourea 2 5 N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-(2- thiazolyl)thiourea N-[2-(2-(6-ethoxyJpyridyl)ethyl]-N'-[2-(4-methyl)thiazolyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2-(4- 3 0 cyano)thiazolyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea 3 5 N- [2- (2- (6-ethoxyJpyridyl)ethyl] -N' - (2- pyridyl)thiourea N-[2-(2-(6-ethoxy Jpyridyl)ethyl]-N'-[2-(5-methy1)pyridyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2-(5- 4 0 trif luoromethyl) pyridyl ] thiourea N- [2- (2- (6-ethoxy)pyridyl)ethyl] -N' - [2- (5-chloro)pyrazinyl]thiourea N-[2-(2-(6-ethoxy)pyridyl)ethyl] -N"-[2-(5-bromo)pyrazinyl]thiourea 45 N- [2- (2- (6-ethoxy)pyridyl)ethyl] -N' - [ (3- (6- chloro)pyridazinyl)]thiourea 1 0 1 5 20 25 40 45 x~6571A 2 6 0 y p 7 -112- ' } N-[2- (2-(6-ethoxy)pyridyl)ethyl -N'- 2- (5- cyano)pyridyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N'- 2- thiazolyl)thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' - 2- (4- it-ethyl) thiazolyl] thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' - 2- (4- cyano)thiazolyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' - 2- (4- trifluoromethyl)thiazolyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N * - 2- (4- ethyl)thiazolyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N* - 2- pyridyl)thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' - 2- (5- methyl)pyridyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N* - 2- (5- trifluoromethyl)pyridyl]thiourea N-[2-(2-(6-fluoroJpyridyl)ethyl -N" - 2- (6- ethyl)pyridyl]thiourea N- [2- (2-(6-fluoro)pyridyl)ethyl -N' - 2- (5- ethyl)pyridyl]thiourea N- [2-(2-(6-fluoro)pyridyl)ethyl -N* - 2- (5- chloro)pyrazinyl]thiourea N-[2-(2-(6-fluoroJpyridyl)ethyl -N' - 2- (5- bromo)pyrazinyl]thiourea N- [2- (2-(6-fluoro)pyridyl)ethyl -N' - (3 -(6- chloro)pyridazinyl)]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl -N' - 2- (5- cyano)pyridyl]thiourea N- [2 - (2-(3-fluoro)pyridyl)ethyl -N' - 2- (4- cyano)thiazolyl]thiourea N-[2-(2-(3-fluoro)pyridyl)ethyl -N' - 2- (4- trifluoromethyl)thiazolyl]thiourea N-.[2- (2- (3-fluoroJpyridyl) ethyl -N« - 2- (4- ethyl)thiazolyl]thiourea N- [2-(2-(3-fluoro)pyridyl)ethyl -N' - 2- (5- chloro)pyrazinyl]thiourea N-[2-(2-(3-fluoro)pyridyl)ethyl -N' - 2- (5- bromo)pyrazinyl]thiourea N- [2-(2 - (3-fluoro)pyridyl)ethyl -N' - (3 -(6- chloro)pyridazinyl)]thiourea N-[2-(2-(6-chloro)pyridyl)ethyl -N' - 2- (4- cyano)thiazolyl]thiourea N-[2-(2-(6-chloroJpyridyl)ethyl -N' - 2- (4- trifluoromethyl)thiazolyl]thiourea X-8571A -113- 260283 N- [2-(2- (6-chloro)pyridyl)ethyl]-N'-[2-(4-ethyl)thiazolyl]thiourea N- [2-(2-(6-chloro)pyridyl)ethyl]-N'-[2-(5-chloro)pyrazinyl]thiourea 5 N- [2-(2-(6-chloroJpyridyl)ethyl]-N' - 12- (5- bromo)pyrazinyl]thiourea N-[2-(2-(6-chloroJpyridyl)ethyl]-N* - [(3-(6-chloro)pyridazinyl)]thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(4- 1 0 methyl)thiazolyl]thiourea N- [ 2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea N- [2- (2- (3-methoxy-6-fluoro)pyridyl)ethyl]-N' - [2- (4-trifluoromethyl)thiazolyl]thiourea N- [2- (2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(4- ethyl)thiazolyl]thiourea N- [2- (2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-(2-pyridyl)thiourea N- [2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl3-N'-[2-(5- 2 0 chloro)pyrazinyl]thiourea N- [2- (2- (3-methoxy-n-f luoro) pyr idyl) etrhyl] -N' - [2- (5-bromo)pyrazinyl]thiourea N- [2- (2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[(3-(6-chloro)pyridazinyl)]thiourea N- [2- (2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(4- cyano) thiazolyl] -hiouroa N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2- (4-trifluoromethyl)thiazolyl]thiourea N- [2- (2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-(2-(4- 3 0 ethyl)thiazolyl]thiourea N- [2- (2- (5-etho3^-6-fluoro)pyridyl) ethyl] -N" - [2- (5-chloro)pyrazinyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N*-[2-(5-br omo) pyr az irry 1 ] thiourea 3 5 N- [2- (2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[(3-(6- chloro)pyridazinyl)]thiourea N- [2- (2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-N1 -[2-(4-cyano)thiazolyl]thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl)-N'-[2- (4- 4 0 trifluoromethyl)thiazolyl]thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-N'- [2- (4-ethy1)thiazolyl]thiourea N- [2- (2- (3-etho^-6-fluoro)pyri(tyl) ethyl] -N* - [2- (5-chloro)pyrazinyl]thiourea 45 N- [2- (2- (3-ethoxy-6-fluoro)pyridyl) ethyl] -N' - [2- (5- bromo)pyrazinyl]thiourea X-8571A -114- 260 N-[2- (2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-tt'-[(3-(6-chloro)pyridazinyl)]thiourea N- [2-(2-(3,6-difluoro)pyridyl)ethyl]-N'-[2-(4-cyano)thiazolyl]thiourea 5 N- [2-(2-(3,6-difluoro)pyridyl)ethyl]-N'-[2-(4- trifluoromethyl)thiazolyl]thiourea N- [2- (2-(3,6-difluoro)pyridyl)ethyl]-N'-[2-(4-ethyl)thiazolylj thiourea N-[2- (2-(3,6-difluoro)pyridyl)ethyl]-N'-[2-(5-1 0 chloro)pyrazinyl]thiourea N-[2-{2-(3,6-difluoro)pyridyl)ethyl]-N'-[2-(5-bromo)pyrazinyl]thiourea N-12-(2- (3,6-difluoroJpyridyl)ethyl]-N'-[(3- (6-chloro)pyridazinyl)]thiourea 1 5 N- [2-{cis-2-pyridyl)cyclopropyl]-N*-[2-(4- cyano)thiazolyl]thiourea N- [2-(cis-2-pyridyl)cyclopropyl]-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea N- [2- (cis-2-pyridyl)cyclopropyl]-N'-[2-(4- 2 0 ethyl)thiazolyl]thiourea N- [2-(cis-2-pyridyl)cyclopropyl]-N'-(2-pyridyl)thiourea N- [2-(cis-2-pyridyl)cyclopropyl]-N'-[2-(5-methy1)pyridyl]thiourea 25 N-[2-(cis-2-pyridyl)cyclopropyl]-N'-[2-(5- trifluoromethyl)pyridyl]thiourea N- [2- (cis-2-pyridyl)cyclopropyl]-N'-[2-(5-ethy1)pyridyl]thiourea N- [2- (cis-2-pyridyl)cyclopropyl]-N' -[2-(5- 3 0 chloro)pyrazinyl]thiourea N- [2 - (cis-2-pyridyl)cyclopropyl]-N'-[2-(5 -bromo)pyrazinyl]thiourea N- [2-(cis-2-pyridyl)cyclopropyl]-N'-[(3-(5-chloro)pyridazinyl)]thiourea 35 N- [2-(cis-2-(6-fluoroJpyridyl)cyclopropyl]-N'-12—(4 — cyano)thiazolyl]thiourea N- [2- (cis-2- (6-fluoro)pyridyl)cyclopropyl]-r.' - [2- (4-tri fluoromethyl) thiazolyl] thioxirea N- [2-(cis-2-(6-fluoroJpyridyl)cyclopropyl]-N'-[2-(4- 4 0 ethyl) thiazolyl ] thiourea N- [2- (cis-2-(6-fluoroJpyridyl)cyclopropyl]-N'-(2-pyridyl)thiourea N- [2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N'-[2-(5-methyl)pyridyl]thiourea 45 N- [2- (cis-2-(6-fluoro)pyridyl)cyclopropyl]-N'-[2-(5- chloro)pyrazinyl]thiourea X-8571A -115- 260293 N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N'-[2-(5-bromo)pyrazinyl]thiourea N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N' - [ (3- (6-chloro)pyridazinyl)]thiourea 5 N-[2-(cis-2-(6-methoxyJpyridyl)cyclopropyl]-N' - [2- (4- cyano)thiazolyl]thiourea N-[2-(cis-2-(6-methoxy)pyridyl)cyclopropyl]-N'-[2- (4-trifluoromethyl)thiazolyl]thiourea N-[2-(cis-2-(6-methoxy)pyridyl)cyclopropyl]-N1- [2- (4- 1 0 ethyl)thiazolyl]thiourea N-[2- (cis-2-(6-methoxy)pyridyl)cyclopropyl]-N'-[2- (5-chloro)pyrazinyl]thiourea N-[2-(cis-2-(6-methoxy)pyridyl)cyclopropyl]-N'- [2- (5-bromo)pyrazinyl]thiourea 15 N-[2-(cis-2-(6-methoxy)pyridyl)cyclopropyl]-N'-[(3-(6- chloro)pyridazinyl)]thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl]-N'-[2- (4-cyano)thiazolyl]thiourea F-[2- (cis-2-(6-ethojy)pyridyl)cyclopropyl]-N'-[2-(4- 2 0 trifluoromethyl)thiazolyl]thiourea N-[2- (cis-2-(6-ethoxy)pyridyl)cyclopropyl]-N'-[2-(4-ethyl)thiazolyl]thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl]-N'-[2- (5-chloro)pyrazinyl]thiourea 25 N-[2- (cis-2-(6-ethoxy)pyridyl)cyclopropyl]-N'-[2- (5- bromo)pyrazinyl]thiourea N-[2-(cis-2-(6-ethoxy)pyridyl)cyclopropyl]-N'-[ (3- (6-chloro)pyridazinyl)]thiourea The following are most preferred compounds.

N-(2-(2-methoxyphenyl)ethyl)-N'-[2-(4-cyano)thiazolyl]thiourea 3 5 N-(2-(2-methoxyphenyl)ethyl)-N'-[2-(4- trifluoromethyl)thiazolyl]thiourea N-(2-(2-methoxyphenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N-(2-(2-methoxyphenyl)ethyl)-N'-[2 - (5- 4 0 bromo)pyridyl]thiourea N-(2-(2-methoxyphenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N1 -[2- (4-cyano)thiazolyl]thiourea 26 0 2 9 3 X-8571A -116- v/ v/ N- (2- (3-methoxyphenyl) ethyl) -N' -[2-(4-tri fluoromethyl)thiazolyl]thiourea N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea 5 N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(5- bromo)pyridyl]thiourea N- (2- (3-methoxyphenyl) ethyl) -N' - [ 2- (5-chloroJpyridyl]thiourea N-(2-(2-ethoxyphenyl)ethyl)-N'-[2-(5- 1 0 bromo)pyridyl]thiourea N-(2-(2-ethoxyphenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(4-cyano)thiazolyl]thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2 - (4- trifluoromethyl)thiazolyl]thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(5- 2 0 bromo) pyr idyl] thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea N-(2-(2,6-difluorophenyl)ethyl)-N* — [(3 —(6- chloro)pyridazinyl)]thiourea N-(2-(2-fluoro-6-methoxyphenyl)ethyl)-N' - [2- (5-bromo)pyridyl]thiourea N-(2-(2-fluoro-6-methoxypheny1)ethyl)-N" - [2- (5- 3 0 chloro) pyridyl] thiourea N-(2-(2-chlorophenyl)ethyl)-N'-[2 -(4-cyano)thiazolyl]thiourea N-(2-(2-chlorophenyl)ethyl)-N'-[2- (4-ethyl)thiazolyl]thiourea k3 5 N-(2-(2-chlorophenyl)ethyl)-N'-[2-(5- bromo)pyridyl]thiourea N-(2-(2-chlorophenyl)ethyl) -N'-[2-(5-chloro)pyridyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-[2-(4- 4 0 cyano)thiazolyl]thiourea N-(2-(3-chlorophenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea N- (2- (3-chlorophenyl)ethyl) -N' -[2- (5-bromo)pyridyl]thiourea 45 N-(2-(3-chlorophenyl)ethyl)-N'-[2-(5- chloroJpyridyl]thiourea X-8571A -117- 2 6 0 2 9 3 N-(2-(l-cyclohexenyl)ethyl)-N'-[2- (4-cyano)thiazolyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'- [2-(4-trifluoromethyl)thiazolylj thiourea 5 N-(2-(l-cyclohexenyl)ethyl)-N'-[2-(4- ethyl)thiazolyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[2-(5-bromo)pyridyl]thiourea N-(2-(l-cyclohexenyl)ethyl)-N'-[2-(5-10 chloro Jpyridyl] thiourea N- (2- (l-cyclohexenyl) ethyl) -N* - [ (3- (6-chloro)pyridazinyl)]thiourea N-(2-(2,5-dimethoxypheny1)ethy1)-N'-[2-(5-chloro)pyrazinyl]thiourea 1 5 N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2- (5- bromo)pyraziny1]thiourea N-(2-cis-phenylcyclopropyl)-N'-[2-(5-bromo)pyridyl]thiourea N-(2-cis-phenylcyclopropyl)-N*-[2-(5- 2 0 chloro )pyridyl] thiourea N-[2-(2-pyridyl)ethyl 3-N" '2-(5-bromo)pyridyl]thiourea N-[2-(2-pyridyl)ethylI -i2- (5-chloro)pyridyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(5- 2 5 trifluoromethylJpyridyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-[2-(5-ethylJpyridyl]thiourea N-[2-(2-pyridyl)ethyl]-N'-12-(5-methyl)pyridyl]thiourea N- [2-(2- (6-methoxyJpyridyl)ethyl]-N'-[2-(5- 3 0 bromo)pyridyl]thiourea N-[2-(2-(6-methoxy)pyridyl)ethyl]-N' - [2- (5-chloro)pyridyl]thiourea N-[2-(2-(6-ethoxy)Tyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea 35 N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2- (5- chloro)pyridyl]thiourea N- [2- (2- (6-fluoro) pyrictyl) ethyl j -W - [2- (5-bromo)pyridyl]thiourea N-[2-(2-(6-fluoro)pyridyl)ethyl]-N'-[2- (5-40 chloroJpyridyl]thiourea N-[2-(2-(3-fluoro)pyridyl)ethyl)-N'-t2- (5-bromoJpyridyl]thir N-[2-(2 (3- ^Jpyridyl)ethyl]-N'-[2-(5- chloro)pyridylH' *ea 45 N-[2-(2-(6 v. lioro) pyridyl) ethyl]-N'- [2-(5- bromo) p~ridyl ] t tiiourea X-8571A -118- 260 N- [2- (2- (6-chloro)pyridyl) ethyl] -N' - [2- (5-chloro)pyridyl]thiourea N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea 5 N-[2-(2-(3-methoxy-6-fluoroJpyridyl)ethyl]-N'-[2- (5- chloro)pyridyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl] -N'-[2-(5-bromo)pyridyl]thiourea N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(5-10 chloro) pyridyl] thiourea N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2 —(5-* bromo)pyridyl]thiourea N-'[2- (2- (3-ethoxy-6-fluoro)pyridyl) ethyl] -N' - [2- (5-chloro)pyridyl]thiourea 15 N- [2- (2- (3 , 6-dif luoro Jpyridyl) ethyl] -N' - [2- (5- bromo)pyridyl]thiourea N-[2-(2-(3,6-difluoro)pyridyl)ethyl]-N'-[2- (5-chloroJpyridyl]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N1-[2-(5- 2 0 bromo)pyridyl]thiourea N-[2-(cis-2-pyridyl)cyclopropyl]-N'-[2-(5-chloroJpyridyl]thiourea N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N'-[2-(5-bromo) pyridyl]thiourea 25 N-[2-(cis-2-(6-fluoroJpyridyl)cyclopropyl]-N'-[2-(5- chloroJpyridyl]thiourea N-[2-(cis-2-(6-methoxy)pyridyl)cyclopropyl]-N'- [2- (5-bromo)pyridyl]thiourea N-[2-(cis-2-(6-methoxyJpyridyl)cyclopropyl]-N'-[2- (5- 3 0 chloro)pyridyl]thiourea N-[2-(cis-2-(6-ethoxyJpyridyl)cyclopropyl]-N'-[2-(5-bromo J pyridyl]thiourea N-[2-(cis-2-(6-ethoxyJpyridyl)cyclopropyl]-N'-[2-(5-chloro J pyridyl]thiourea 3 5 N~[2-(2,6-difluoro-3-methoxyphenyl)ethyl]-N*-[2-(5- bromo)pyridyl]thiourea Especially preferred is N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromo J pyridyl]thiourea, and its hydrochloride 40 salt.

As mentioned above, the invention includes pharmaceutically acceptable salts of the compounds defined by the above formula (I). Although generally neutral, a X-8571A 260 2 particular compound of this invention can possess a sufficiently acidic, a sufficiently basic, or both, functional groups, and accordingly react with any of a number of nontoxic inorganic bases, and nontoxic inorganic 5 and organic acids, to form a pharmaceutically acceptable salt. Acids commonly employed to form acid addition salts are inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid and the like, and organic acids such as p-toluene sulfonic, 1 0 methanesulfonic acid, oxalic acid, p-bromophenylsulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid, acetic acid, and the like. Examples of such pharmaceutically acceptable salts thus are the sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, 15 monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caproate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, 20 butyne-1,4-dioate, hexyne-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, sulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, g-hydroxybutyrate, 25 glycollate, tartrate, methanesulfonate, propanesulfonate, naphthalene-l-sulfonate, naphthalene-2-sulfonate, mandelate and the like. Preferred pharmaceutically acceptable acid addition salts are those formed with mineral acids such as hydrochloric acid and hydrobromic acid, and those formed 3 0 with organic acids such as maleic acid and methanesulfonic acid.

X-8571A -120- 2 () 0 2 9 Base addition salts include those derived from inorganic bases, such as ammonium or alkali or alkaline earth metal hydroxides, carbonates, bicarbonates, and the like. Such bases useful in preparing the salts of this 5 invention thus include sodium hydroxide, potassium hydroxide, ammonium hydroxide, potassium bicarbonate, calcium hydroxide, calcium carbonate, and the like.

The pharmaceutically acceptable salts of the invention are typically formed by reacting a compound as 10 defined with an equimolar or excess amount of acid or base. The reactants are generally combined in a mutual solvent such as diethyl ether or benzene, for acid addition salts, or water or alcohols for base addition salts, and the salts normally precipitate out of solution within about one hour 15 to about ten days and can be isolated by filtration or other conventional methods. The salts of the compounds of the invention will convert to the compound per se after administration and are thus prodrugs. All prodrugs are administered in an amount sufficient to generate an 2 0 effective amount of the compound to contact the virus and interact with it (e.g. inhibit replication thereof).

The compounds of the present invention also include racemates, racemic mixtures, and individual enantiomers or diastereomers. All asymmetric forms, 25 individual isomers and combinations thereof are within the scope of the present invention.

As noted, the optically active diastereomers of the compounds of Formula 1 are considered part of this invention and such optically active isomers may be prepared 3 0 from their respective optically active precursors by the procedures described herein, or by resolving the racemic • 5 1 5 X-8571A -121- O ~ 26 0 P 93 mixtures. The resolution can be carried out in the presence of a resolving agent, by chromatography, by repeated crystallization or by some combination of these techniques which are known to those skilled in the art. Further details regarding resolutions can be found in Jacques, et al., Enantiomers. Raceroates. and Resolutions.

John Wiley & Sons 1981.

The compounds of the present invention, or their precursors, are prepared using procedures known to those of ordinary skill in art. More particularly, the compounds of Formula (1) are prepared according to the procedures shown below in Schemes I, II, and III, and as described following the Schemes.

SCHEME I Rg R7 I I Re C C N=c=s + R-1NHR1 Re R9 (1) Rg R7 S I I II Rc C C N C N Ri III I Rg Rg H Rj (3) X-8571A -122- 26 0 ? P In Scheme I, a derivative of isothiocyanate (1) is reacted with an amino group (2) in approximately 1:1 molar ratio, in an inert organic solvent such as N,N-dimethyl formamide and stirred at an appropriate temperature of between about 0-150°C for a period of time between about 1 and 72 hours. The time and temperature used depends upon the reactivity of the individual reagents. The product (3) may be isolated by conventional techniques.

Scheme II . j. j, R5—c—c—NR4H + Re Rg (1) |c ^7 ! R c C N C N R II I I ' &8 R9 R4 H (3) Scheme II is run under the same general reaction 15 conditions as Scheme I.

X-8571A 260 r\ L, o Scheme III R8 Scheme III is a process analogous to that described in J. Org. Chem. ,Vol. 49, 4123 (1984) herein incorporated by reference.

The compounds employed as initial star .ng materials in the synthesis of the compounds of this invention are well known and, to the extent not commercially available, are readily synthesized by standard procedures commonly employed by those or ordinary skill in the art.

Other teaching for preparing the compounds of the invention may be found in Organic Synthesis. 15., 69 (1965); Synthesis, 289 (1974); Journal of the American Chem. Society# 21. 1236 (1957); and Organic Synthesis. 20., 69, (1940), and Synthesis. May 1983, p. 391, incorporated herein by reference.

Tests with the above compounds of Formula 1 have indicated activity as inhibitors of HIV. while not being bound by theory, it is believed that the compounds act as R9 (1) c nr4h + r c r' + r3hnr r6 r -n- ro Rg Ra -NRI R} X-8571A -124- 26 reverse transcriptase inhibitors, and thereby act to inhibit replication of the virus.

The following is a description of the test systems used in analyzing compounds in effectiveness against HIV.

Testa A. b. C. and P (xtt) MT4 cells in a medium of RPMI 1640, 5% FCS, penicillin/streptomycin are adjusted to 2x10^ cells/ml and seeded into microplates (96 wells/plate) 100 ml cell suspension/well giving 2xl04 cells/well. The compound to be tested is made into a 10 mg/ml mixture in DMSO and stored at -20°C. The compound in DMSO is diluted with medium containing 10% DMSO in a 10-fold dilution series to give 1 mg/ml, 10 mg/ml, and 100 mg/ml solutions. Further dilutions to 400, 40, 4 and 0.4 mg/ml are made in medium containing microplates. Fifty ml of the 400, 40, and 4 mg/ml are transferred to the cell-containing microplates with a multi-channel pipette (final concentration: 100, 10, and 1 mg/ml). Finally, 50 ml of virus suspension is added to each well (with a repetitive "Eppendorf" multipipett). Each plate has at least six wells with the following: [Test A: HIV virus; Test B: HIV(II) virus; Test C: SIV virus; Test D: No virus]; with no drug (virus control) and six we-ils without virus (medium control) . The plate is put into a plastic bag and incubated for six days in C02 atmosphere. To each well in the plate is added 50 ml of XTT ((2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide), (1 mg/ml 0.01-0.02 mM N-metyl-phenazonium methosulfate). After six hours of incubation in C02 atmosphere the plates are covered with adhesive plate sealers and gently mixed on a X-8571A 260 29 3 vortex. Optical densities are determined at a wavelength of 450 nm and a reference wavelength of 650 nm. The percent reduction of cytotoxocity caused by the virus infection is calculated as follows: OD450 compound - OD450 inf cells x 100 OD450 uninf cells - OD450 inf cells Tast-.H E. F. d. H (HIV-IRT, HIV-2RT, SIVRT, no virus) MT-4/H9-cells are adjusted to 2x10^ cels/ml medium (RPMI 1640, 5% FCS, penicillin/streptomycin) and seeded into microplates (96 wells/plate) 100 ml cell suspension/well giving 2 x 10^ cells/well. The compound to 15 be tested is made 10 mg/ml in DMSO = stock solution (stored at -20°C). The compound dissolved in DMSO is diluted 25 times in medium to give 400 mg/ml. Further dilutions to 40 mg/ml and 4 mg/ml are made in microplates. 50 ml of the dilutions 400 mg/ml, 40 mg/ml and 20 4mg/ml are transferred to the "cell-containing" microplate with a multichannel pipette. (Final concentration: 100, 10 and 1 mg/ml).

Finally 50 ml of virus suspension is added to each well (with a repetitive "Eppendorf multipett"). [Test 25 E-HIV-1; Test F-HIV-2; Test G-SIV; Test H-no virus].

Each plate has at least four wells with virus but no drug (virus control) and two wells without virus (medium control). The plate is put into a plastic bag to avoid evaporation and incubated for six days in CO2-3 0 atmosphere. 10 ml supernatant from each well is transferred with a multichannel pipette into a new X-8571A 26 o p microplate to which 40 ml VDB, (50 mM Tris-HCl pH = 7.6, 35 mM KCl, 4 mM DTT, 1 mM EDTA, 1.3% Triton X-100), have been added tp each well. The addition of 50 ml RT-reaction mix, (10 ml culture supernatant, 40 ml VDB and 50 ml reaction 5 mixture giving a final concentration of: 100 mM Tris-HCl PH = 7.6, 100 mM KCl, 4 mM MgCl2, 4 mM DTT, 275 mg/ml BSA/ml, 5 mg (rA)n(dT) 12-18/ml 0.3 mM 3H dTTP (specific activity 18.000 cpm/pmcl)) gives a final volume of 100 ml/well. After 60 minutes of incubation the whole assay 1 0 volume is transferred by use of a cell harvester to a filter mat prewetted with 5% TCA. The filter is washed in 5% TCA and rinsed once in ethanol. After drying the filter mat at 60°C for 30 min. each filter (96/mat) is punched out and put into counting vials 2 ml of scintillation fluid is 1 5 added and the samples are counted (1 min) or the whole filter mat is put into a plastic bag, 10 ml of scintillation fluid is added and the filter mat is counted in a Beckman Betaplate counter. Percent reduction of RT activity is determined by comparing RT activity for virus 20 control with the RT activity measured for each dilution of the compound.

Test I (HIVRT (rAdt)) The compounds were tested for direct inhibitory 25 activity on HIV-RT in a volume of 100 ml recombinant HIV-RT (diluted in virus disruption buffer to give 200.000 cpm). 100 rrtM Tris-HCl pH 7.6, 100 mM KCl, 4 mM MgCl2, 4 mM DTT, 275 mg/ml BSA, 0.5 mg (rA)n(dT) 12-18 and 0.3 mM 3H-=dTTP (specific activity 18.000 cpm/mol). After 60 3 0 minutess of incubation 40 ml in duplicate were spotted on paper discs and washed in 5% TCA. After rinsing the paper X-8571A 2 6 02 p3 discs in ethanol they were dried and counted in scintillation fluid.

The following Tables illustrate activities of compounds in the above-described tests. The numbers represent % inhibition.

X-8571A 260:93 Table ftl /"A/Vh h~0 100 ^icr/ml Wff 1 IW/ffll 0,1 wg/ml A 99 41 13 A _ 100 100 2 A 48 100 80 4 A 70 62 8 A 58 100 78 4 A 64 98 77 0 D 45 33 18 31 B 50 28 48 0 B 84 0 B 0 0 0 19 C 6 0 0 C 9 75 0 0 C 22 40 8 0 C 65 17 2 1 E 99 99 99 E 99 99 99 1 F 95 57 75 43 F 86 76 79 43 X-8571A -129- 260 29 3 Table A2 O^A \ / v N N—Rx H H £1 Test 100 tof/ml wcr/ml 1 i^q/ml 0.1 Uff/ml -is1 A hACF, 66 24 100 - H A 4 16 75 62 A 31 31 84 84 D 68 75 46 0 C 43 11 9 I 73 73 63 I — 75 75 68 E 97 96 97 98 F 96 98 95 56 H B IP 38 V ) 21 H>S1 N C(CH3)3 0 9 0 0 N I - 8 8 X-8571A 2 6 0 2 9 Table A2 (continued) El Teat 100 iw/ml IP Uff/lTll 1 LKT/ml 0.1 ua/ml svCH3 -*x n ch3 A 99 85 71 - II A 100 88 6 7 N D 0 0 _ M I _ 38 39 34 H c 0 1 0 — II E 94 91 23 1 tl F 93 61 92 1 II B 85 100 100 13 "^1 N\x 0 0 63 - ft A 0 0 51 84 II D 93 70 53 0 N c 0 2 11 H I 94 93 72 H I 95 95 73 tl E 98 98 98 99 M F 96 94 91 67 M B 0 0 90 74 2 6 0 ? 0 2 9 * X-8571A -131- Table K2 (continued) El Test 100 lia/ml Wtf/ml 1 ua/ml .0.1 wg/ml -<y 0 s>och3 0 0 0 - 11 I _ 13 l i -«1 A "U ci 18 0 0 - I — 1 l l A ^ Br 0 0 - I - 1 l l X-8571A 260 2g Table h2 (continued) El Test 100 ucr/ml u<a/ml 1 Utf/ml 0.1 Uff/ml -^1 A "X! 51 32 - A 14 65 46 S«.^Ci4H29 ^^\l 33 0 0 - I — 1 1 1 -o * 0 0 - I __ 16 16 1 ——^ Cl A 0 67 17 - I - 29 4 X-8571A 2 6 0 c 9 3 Table A2 (continued) Ri TEST 100 |la/ml lia/ml 1 u<a/ml 0.1 ucr/ml -Q~ A - 41 0 n A 0 32 -Q c.l A 0 52 0 - I — 50 31 -^y-so2mi2 A - 22 0 3 —^^-C02nBu A 0 0 0 -O A 6 2 0 - N—^ "O N=/ A 22 23 0 - N I - 6 12 X-8571A 26 Q p o Table A2 (continued) Ri TEST 100 LKT/Irl iwr/ml 1 n?/ml .0,1 hlfl/ml -T> A N=< CH, 100 64 42 - II I 9 •9 II B 100 27 0 _ n C 0 0 0 _ -ry a N=/ 100 100 4 - M I — 36 27 1 M C 100 2 _ -<N1 A 0 0 - ~iN> A N-N 45 27 11 - II I 14 14 12 tt c 8 _ M D 0 33 33 X-8571A 2 6 0 2 9 3 Table A2 (continued) El test 100 ucr/ml wa/ml 1 Lttr/ml 0.1 pa/ml s^ch3 a (1 \-N 38 3 1 i 18 21 1 s ch2ch3 a —<\ Y 17 7 0 - M i _ 11 53 12 H i 17 9 12 "^1 1 n - 14 14 12 rt a 100 100 100 _ N c 0 17 0 II b 96 57 100 -O ' n=< ci 100 100 94 - N a 38 49 37 ...

M b 26 16 1 8 — It b 100 60 55 - * « 260£33 X-8571A -136- V Table A2 (continued) Ri TEST 100 |io/ml Ufl/ml 1 ua/ml 0.1 ua/ml -0 A N - 0 0 0 I A _ 0 0 0 —A ij" 0 0 0 - 1 I 38 8 l -rQ - \=N 0 71 0 — c^C°> A - 7 3 ■ 1 X _ 12 7 X-8571A 26 0 £ fi3 Table A2 (mnt-.lnued) ri TEST 100 ua/ml wa/ml 1 IKT/ml 0.1 Jlcr/ml /■V ~~\A J A 100 100 63 - u D 23 27 32 _ M C 8 l 0 W I 40 36 39 N A 41 99 53 0 tl E 95 96 77 1 II F 96 84 87 1 H b 50 100 99 17 /S^ ?' ch3 50 28 8 - If I - 24 12 12 X-8571A 2 6 0 ? a 7 ■ ■■ • »• >' %J Table a2 (continued) El test 100 ua/ml Ufl/ml 1 wq/ml 0,1 Mg/ml -CO* CI 100 19 4 II e 97 8 li _ (1 f 93 72 6 l H b 36 100 22 18 II i 1 6 9 II c 17 2 0 M g 87 1 1 .och2ch3 -ic ■ 33 0 1 i - 8 1 X-8571A 260293 Table A2 (continued) El TEST 100 ^lo/ml iw/ml 1 ivg/ml 0.1 Utt/ml -<x vC1 y. 68 63 0 - H A 49 67 0 _ rt E 96 51 l N F 98 79 l — II I 18 18 12 H B 27 67 9 24 II C 21 0 0 — II G 90 12 1 -cc X'" 100 100 100 - II A 100 100 100 n A 100 100 100 _ u D 0 28 n C 19 2 N I 39 38 33 N E 95 16 51 1 n F 97 62 77 4 M B 93 12 40 4 n A 72 21 3 - X-8571A -140- ^ n f) 9 26 Table A3 ^ A N R* TEST 100 ug/ml ua/ml 1 ug/ml 0.1 Wff/nil CO A - 0 0 0 tl A _ 0 0 0 1 A 0 0 0 / \ A —N NMe \ / 0 0 0 — / \ —N 0 \_J A - 9 13 0 X-8571A 26 0 ■" ( Table A4 Rs\/\ A/0 ^ N N N H H £5 TEST 100 iw/ml lid/ml 1 flcr/ml 0. lp.cr/ml MeO—^ ■ A MeO 0 54 4 - A 0 58 44 _ A 73 79 - A 71 93 22 _ CI A 0" F 100 100 100 - M A 16 52 98 II I - . 92 77 43 X-8571A 26 0 i g Table A4 (continued) R5 TEST 100 U<a/ml LLcf/ml 1 jicr/ml 0.1 Uo/m] Q- * OC,H* 100 100 96 - H B 100 91 100 tt C 0 0 H I - 33 12 % 26 n - , ^ X-8571A -143- ^ _ t, Table A5 s \ A /r» N N Ell El 3 TEST 1M in 1 iL_l Ph, Ph H A _ 0 0 0 Ph, Ph Ph A 0 0 0 Ph Ph A _ 0 0 0 Ph AC A 0 0 0 CH2Ph H A _ 28 8 CH2Ph .

CH3 A 100 24 0 n H H 100 34 0 H II E 94 7 13 — N n F 98 1 1 1 N M B 100 63 0 34 It n C 100 26 0 CH2Ph nBu A 100 0 _ CH2Ph nBu A 100 31 N M n 100 52 0 N N E 98 9 11 _ II N F 98 1 1 _ U n B 100 82 1 M M C 100 22 3 «_ CH2Ph Ac A 26 6 N n B 100 0 16 _ N N C 100 6 7 - X-8571A -144- / . 0 Table A5 (continued) fill El 3 TEST 10Q 1 £L-1 ciirPh-pOx- Ac A 18 3 CHjPh Ph A 100 16 2 II H C 100 12 0 — II h D 3 0 0 _ II II A 99 12 0 — H H E 98 63 41 H H F 95 1 33 42 It II B 80 48 37 24 CH2Ph CH2Ph A 100 46 0 II M H 100 29 4 II II E 98 9 1 _ II M F 98 59 1 1 II H B 58 100 0 II II C 100 2 H It G 93 1 1 CH2Ph-p-OH H A _ 0 0 0 CH2Ph-p-OH Ph A 34 4 1 CHjPh-p-OH Ph A 99 19 44 ■ il B 100 12 0 ■ H C 100 28 6 - X-8571A 760293 A feature of this invention also disclosed is a method of administering to a human in need thereof the compounds of the invention or their pharmaceutically acceptable salts to treat or inhibit HIV/AIDS, to inhibit the replication of the HIV/AIDS virus in infected human cells and to inhibit AIDS from developing in humans infected with the HIV/AIDS virus or carrying antibodies to the HIV/AIDS virus.

The present invention also discloses the compounds of the invention and their salts for use in the treatment of the condition referred to above, as well as claiming the use of such compounds in the preparation of pharmaceutical formulations and medicaments for the treatment of such conditions.

In general for the treatment as described above, a suitable effective dose of the compound or its pharmaceutically acceptable salt will be in the range of 0.5 to 250 mg per kilogram bodyweight of recipient per day. Administration may be by any suitable route including oral, rectal, nasal, topical (including buccal and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous and intradermal) administration. It will be appreciated that the preferred route may vary with, for example, the condition, age, and weight of the recipient.

The administered ingredients may be used as a therapy in conjunction with other therapeutic agents, (other anti-virals, anti-bacterials, compounds useful for preventing resulting secondary or contemporaneous afflictions associated with HIV/AIDS) such as AZT, ddl, ddC, 9-[[2-hydroxy-l-(hydroxymethyl)ethoxy]methyl]guanine, f N rVUfcNT OFFICE 21 MAR 1997 . received X-8571A 260 9-(2-hydroxyethoxymethyl)guanine(acyclovir), 2-amino-9-(2-hydroxyethoxymethyl)purine, suramin, ribavarin, antimoniotungstate (HPA-23), interferon, e.g., a interferon, interleukin II, and phosphonoformate (Foscarnet) or in conjunction with other immune modulators including bone marrow or lymphocyte transplants or other medications such as levamisol or thymosin which would increase lymphocyte numbers and/or function as is appropriate.

For example, in an evaluation of the combination of AZT and a compound of the formula a synergistic effect was observed. The combination was evaluated against HIV-1 in CEM cells using the technique of Prichard and Shipman (Antiviral Research, 14, 181-206 (1990)). The peak of synergy was observed at 0.5 |ig/ml of the compound of the formula above and 0.005 |ig/ml of AZT. ingredients to be administered alone, it is preferable to present them as part of a pharmaceutical formulation. The formulations of the present invention comprise at least one administered ingredient, as above-defined together with one or more acceptable carriers thereof and optionally other therapeutic ingredients. The carrier(s) must be "acceptable" in the sense of being compatible with the h h While it is possible for the administered X-8571A- 26 Q ~ q ? other ingredients of the formulation and not deleterious to the recipient thereof.

The formulations include those suitable for oral, rectal, nasal, topical (including buccal and 5 sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous and intradermal) administration. The formulations may conveniently be presented in unit dosage form, e.g., tablets and sustained release capsules, and may be prepared by any methods well known in the art of 10 pharmacy.

Such methods include the step of bringing into association the to be administered ingredients with the carrier which constitutes one or more accessory ingredients. In general, the formulations are prepared by 15 uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then if necessary shaping the product.

Formulations of the present invention suitable 20 for oral administration may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water 25 liquid emulsion or a water-in-oil liquid emulsion and as a bolus, etc.

With regard to compositions for oral administration (e.g. tablets and capsules), the term "suitable vehicle" means common excipients such as binding 30 agents, for example, syrup, acacia, gelatin, sorbitol, tragacanth, polyvinylpyrrolidine (Povidone), X-8571A methylcellulose, ethylcellulose, sodium carboxy-methylcellulose, hydroxypropylmethylcellulose, sucrose and starch; fillers and carriers, for example corn starch, gelatin, lactose, sucrose, microcrystalline cellulose, kaolin, mannitol, dicalcium phosphate, sodium chloride and alginic acid; disintegrators such as microcrystalline cellulose, corn starch, sodium starch glycolate, alginic acid; and lubricants such as magnesium stearate and other metallic stearates, stearic acid, silicone fluid, talc, waxes, oils and colloidal silica. Flavoring agents such as peppermint, oil of wintergreen, cherry flavoring or the like can also be used. It may be desirable to add a coloring agent to make the dosage form more aesthetically pleasing in appearance or to help identify the product. The tablets may also be coated by methods well known in the art.

A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface-active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active ingredient therein.

Formulations suitable for topical administration include lozenges comprising the ingredients in a flavored basis, usually sucrose and acacia or tragacanth; pastilles X-8571A 26 0 2 9 comprising the active ingredient in an inert basis such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the ingredient to be administered in a suitable liquid carrier.

Formulations suitable for topical administration to the skin may be presented as ointments, creams, gels and pastes comprising the ingredient to be administered and a pharmaceutically acceptable carrier. An exemplary topical delivery system is a transdermal patch containing the ingredient to be administered.

Formulations for rectal administration may be presented as a suppository with a suitable base comprising, for example, cocoa butter or a salicylate.

Formulations suitable for nasal administration wherein the carrier is a solid include a coarse powder having a particle size, for example, in the range 20 to 500 microns which is administered in the manner in which snuff is taken, i.e., by rapid inhalation through the nasal passage from a container of the powder held close up to the nose. Suitable formulaf' ^ns wherein the carrier is a liquid, for administration, as for example, a nasal spray or as nasal drops, include aqueous or oily solutions of the active ingredient.

Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams, or spray formulations containing in addition to the active ingredient such carriers as are known in the art to be appropriate.

Formulations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions which may contain anti-oxidants, X-8571A -150- ^ Q 0 P 0 buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents. The formulations may be presented in unit-dose or multi-dose containers, for example, sealed ampules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, or example water for injections, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from 3terile powders, granules, and tablets of the kind previously described.

Preferred unit dosage formulations are those containing a daily dose or unit, daily sub-dose, as herein above recited, or an appropriate fraction thereof, of the administered ingredient.

The antiviral compounds of Formula I can be used as surface disinfectants. Solutions containing as little as 0.1 percent by weight of the antiviral compound maybe effective for disinfecting purposes. Preferably, such solutions also can contain a detergent or other cleansing agent. The solutions maybe useful for disinfecting objects such as glassware, dental and surgical instruments, and surfaces such as walls, floors, and tables in areas where maintenance of sterile conditions is important, for example., hospitals, food-preparation areas, and the like.

In practicing the method for treating or inhibiting HIV and/or AIDS, the antiviral can be administered in a single daily dose or in multiple doses per day. The treatment regime may require administration over extended periods of time, e.g., for several days or X-8571A 26 0 £ for Beveral months or years. The amount administered per dose or the total amount administered will depend on such factors as the nature and severity of the infection, the age and general health of the patient, the tolerance of both the patient and the microorganism or microorganisms involved in the infection to the antiviral compound.

The following formulation examples represent specific pharmaceutical formulations employing compounds comprehended by the present method. The formulations may employ as active compounds any of the compounds of Formula I or a pharmaceutically acceptable salt thereof. The examples are illustrative only and are not intended to limit the scope of the invention in any way.

Formularion 1 Hard gelatin capsules are prepared using the following ingredients: Quantity <mg/capsule) Compound 1250 Starch dried 200 Magnesium stearate 10 The above ingredients are mixed and filled into hard gelatin capsules in 460 mg quantities.

X-8571A -152- 2 6 n ~ n *' & Formulation 2 A tablet formula is prepared using the ingredients below: Quantity (ma/tablet) Compound 250 Cellulose, microcrystalline 400 Silicon dioxide, fumed 10 Stearic acid 5 Magnesium stearate 10 The components are blended and compressed to form tablets each weighing 675 mg.

Formulation 3 An aerosol solution is prepared containing the 15 following components: Weight Compound 0.25 Ethanol 29.75 Propellant 22 70.00 70 (Chlorodifluoromethane) The active compound is mixed with ethanol and the mixture added to a portion of the propellant 22, cooled to -30°C and transferred to a filling device. The required amount is then placed in a stainless steel container and 25 diluted with the remainder of the propellant. The valve units are then fitted to the container.

X-8571A -153- Q r* - 0 '1 '■ Q 7 - ^ y o Formulation 4 Tablets each containing 60 mg of active ingredient are made up as follows: Compound 60 mg Starch 45 mg Microcrystalline cellulose 35 mg Polyvinylpyrrolidone (as 10% solution in water) 4 mg Sodium carboxymethyl starch 4.5 mg Magnesium stearate 0.5 mg Talc 1 mg The active ingredient, starch and cellulose are passed through a No. 45 mesh u.s. sieve and mixed 15 thoroughly. The solution of polyvinylpyrrolidone is mixed with the resultant powders which are then passed through a No. 14 mesh u.s. sieve. The granules so produced are dried at 40°-60°C and passed through a No. 18 mesh u.s. sieve. The sodium carboxymethyl starch, magnesium stearate and 20 talc, previously passed through a No. 60 mesh u.s. sieve, are then added to the granules which, after mixing, are compressed on a tablet machine to yield tablets each weighing 150 mg.

Formulation 5 Capsules each containing 80 mg of medicament are made as follows: Compound 80 mg Starch 59 mg Microcrystalline cellulose 59 mg Silicone fluid 2 mg X-8571A -154- ^ r 26 n The active ingredient, cellulose, starch and magnesium stearate are blended, passed through a No. 45 mesh U.S. sieve, and filled into hard gelatin capsules in 200 mg quantities.

Formulation 6 Suppositories each containing 225 mg of medicament are made as follows: Compound 225 mg Saturated fatty acid glycerides 2 mg The active ingredient is passed through a No. 60 mesh U.S. sieve and suspended in the saturated fatty acid 15 glycerides previously melted using the minimum heat necessary. The mixture is then poured into a suppository mold of nominal 2 g capacity and allowed to cool.

Formulation 7 As intravenous formulation is prepared as follows: Compound 100 mg Isotonic saline 1000 ml The solution of the above ingredients is 25 administered intravenously at a rate of 1 ml/minute to a mammal in need of treatment.

It should be understood that in addition to the ingredients particularly mentioned above the formulations of this invention may include other agents conventional in 30 the art having regard to the type of formulation in question. 26 0 X-8571A -155- tOy 9 The following examples further illustrate the compounds of the present invention and methods for the synthesis. The examples are not intended to be limiting to the scope of the invention in any respect and should not be so construed.

Examnles and Procedures The following are experimentals illustrating methods for preparing the compounds of the invention.

Example 1 N-(2-Phenethy1)-N'-T2-(1.3.4-thiadiazolyl)1 thiourea S ♦ H2N—^ J N=C«=S H2N—^ N" A s- r"Cl A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 2-amino-l,3,4-thiadiazole (2.02 g, 20 mmol) in .N,W-dimethylformamide (50 mL) was heated to 100°C. After 68 h, the reaction was cooled to room 20 temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, and water. The organic layer was filtered and the solid obtained (2.24 g) triturated with ethyl acetate to provide 1.9 g (36%) of the title 25 product : — w 0 X-8571A -156- W W 26 0 mp 210-211.5 C; IR (KBr, cm"1) 3320, 2924, 2869, 2685, 1645, 1543, 1453, 1384, 1344, 1278, 762, 749, 700, 650; NMR (300 MHz, DMSO-d6) 6 12.35 (br s, 1H), 8.92 (s, 1H), 8.78 (br s, 1H), 7.38-7.18 (m, 5H), 3.84-3.72 (m, 2H), 2.92 (t, J=6 Hz, 2H); MS (FD) m/e 264 (M+); UV (EtOH) 277nm, 253nm, 205nm.

Anal. Calcd for C11H12N4S2: Theory: C, 49.98; H, 4.57; N, 21.19.

Found: C, 50.07; H, 4.66; N, 21.48.

Example 2 N- (2-Phener.hvl) -N' - f 4 . 5-dimethyl-(2-thiazolvl) 1 thiourea 2-Amino-4,5-dimethylthiazole hydrochloride (3.3 g, 20 mmol) was slurried with methylene chloride and shaken 20 with saturated sodium bicarbonate solution. The layers were separated and the aqueous washed with methylene chloride (2x). The combined organics were dried over magnesium sulfate, filtered and concentrated. To the resulting solid was added 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 25 mL) and iff^-dimethylformamide (50 mL). The resulting solution was heated to 100°C. After 95.25 h, the reaction w 0 ^ n X-8571A -157- ^ C. was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, and water (2x). The organic layer was filtered and the solid obtained 5 (3.9 g) recrystallized from ethyl acetate to provide 3.3 g (57%) of the title product: mp 186-7°C; IR (KBr, cm"1) 3166, 3022, 1523, 1502, 1289, 1215, 737, 695; !h NMR (300 MHz, DMSO-d6> 6 11.42 (br s, 1H), 9.83 (br s, 1H), 7.36-7.16 (m, 5H), 3.86-3.73 (m, 2H), 2.91 (t, J=7 Hz, 2H), 2.19 (s, 3H), 2.08 (s, 3H); MS (FD) m/e 291 (M+); UV (EtOH) 298nm (£=17987), 257nm (e=9939), 204nm (6=20802). 15 Anal. Calcd for C14H17N3S2: Theory: C, 57.70; H, 5.80; N, 14.42.

Found: C, 57,41; H, 5.85; N, 14.39.

Example 3 N- F2-(4-Methvl)-1-phenethvl1-N'-(2-thiazolvl) thiourea A solution of 2-(4-methylphenethyl) isothiocyanate (820 mg, 4.6 mmol) and 2-aminothiazole (565 mg, 5.65 mmol) in N,J7-dimethylformamide (15 mL) was heated X-8571A -158- 26 n - f > .0 to 100°C. After 20.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), saturated sodium bicarbonate solution, and brine. The organic layer 5 was dried over magnesium sulfate, filtered and concentrated. The solid obtained (1.1 g) was purified by flash chromatography on silica gel (1% ethyl acetate in methylene chloride) to provide 570 mg (45%) of the titled compound. A sample was recrystallized from ethyl acetate: 10 mp 132-3°C; IR (KBr, cm"1) 3168, 2990, 1560, 1513, 1166, 808, 705; % NMR (300 MHz, DMSO-d6) 5 11.62 (br s, 1H), 9.69 (br s, 1H), 7.36 (d, J=4 H", 1H), 7.20-7.06 (m, 5H), 3.83-3.73 (m, 2H), 2.87 (t, J=7 hi, 2H), 2.30 (s, 3H); MS (FD) m/e 277 (M+); UV (EtOH) 288nm (£=18773), 257nm (6=11948), 212nm (e=14509).

Anal. Calcd for C13H15N3S2: Theory: C, 56.29; H, 5.45; N, 15.15. 20 Found: C, 56.55; H, 5.52; N, 15.04.

Example 4 N- (2-phenethv 1) -Kf' - (2-pvridvl) thiourea N N—^ ^ H H N X-8571A -159- 26 <— A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 2-aminopyridine (1.90 g, 20 mmol) in 2S7,JV-dimethylformamide (50 mL) was heated to 100°C. After 5 4 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic solution was washed with water (3x). The organic layer was dried over sodium sulfate, filtered and concentrated. The resulting white solid was recrystallized from ethyl acetate to provide 1.86 10 g (36%) of the titled product: mp 153-154°C; IR (KBr, cm"1) 3232, 1536, 1477, 1319, 775; !h NMR (300 MHz, CDCI3) 8 11.72 (br s, 1H) , 8.59 (br s, 1H) , 7.97 (d, J=4.2 Hz, 1H) , 7.64 (dt, J=1.7,8.2 Hz, 1H) , 15 7.37-7.26 (m, 5H) , 6.92 (dd, J=7.2,5.1 Hz, 1H) , 6.74 (d, J=8.2 Hz, 1H), 4.06 (m, J=6.8 Hz, 2H), 3.04 (t, J=6.9 Hz, 2H) ; MS (FD) m/e 257 (M+); UV (EtOH) 293nm (£=12040), 266nm (£=12961), 247nm (e=11912) 20 202nm (£^12963).

Anal. Calcd for C14H15N3S: Theory: C, 65.35; H, 5.87; N, 16.33.

Found: C, 65.46; H, 5.82; N, 16.24 X-8571A -160- 26 n " Example 5 N-(2-phenethy1)-N'-(4-pvridvl) thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 4-aminopyridine (1.92 g, 20 mmol) in iV/W-dimethylformamide (50 mL) was heated to 100°C. After 4.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic solution was washed with water (2x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The oil obtained was purified by flash chromatography on silica gel (5% methanol in ethyl acetate to 10% methanol in ethyl acetate). This material was recrystallized from ethyl acetate yielding 1.85g (36%) of the title product: mp 154.5°C; IR (KBr, cm"1) 3142, 1579, 1518, 1328, 1276, 750; *H NMR .(300 MHz, CDCI3) 6 8.42 (dd, J=l,5 Hz, 2H), 7.94 (br s, 1H), 7.39-7.23 (m, 5H), 6.81 (d, J=5 Hz, 2H), 6.38 (br s, 1H), 3.99 (m, J=6 Hz, 2H), 3.02 (t, J=6 Hz, 2H): MS (FD) m/e 258 (M+l); UV (EtOH) 281nm (e=16486), 255nm (6=21182), 208nm (6=25744). Anal. Calcd for C14H15N3S: Theory: C, 65.34; H, 5.87; N, 16.33.

Found: C, 65.43; H, 5.97; N, 16.17.

X-8571A -161- ' ^ ~ o C 260 Example 6 N-(2-phenethy 1)-N'- f2 - (6-fluoro)-benzothiazolyl1 thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0mL) and 2-amino-6-fluoro-benzothiazole (3.36 g, 20 mmol) in dimethylsulfoxide (10 mL) was heated to 10 150°C. After 5 h, the reaction was cooled to room temperature and filtered. The filtrate was poured into ethyl acetate, washed with water (5x) and brine (2x). The organic layer was concentrated and recrystallized from ethyl acetate to provide 729.5 mg (11%) of the titled 15 product: mp 212-213°C; IR (KBr, cm"1) 3175, 3025, 1561, 1534, 1461, 1249, 1215; l-H NMR (300 MHz, CDCI3) 8 11.81 (br s, 1H) , 9.83 (br s, 1H), 7.77 (dd, J=8.7, 2.4 Hz, 1H), 7.52 (br s, 1H) , 7.31-20 7.15 (m, 6H), 3.79 (m, 2H), 2.90 (t, J=6.6 Hz, 2H); MS (FD) m/e 331 (M+); UV (EtOH) 310nm, 289nm, 245nm, 208nm, 201nm.

X-8571A -162- 26 Anal. Calcd for C16H14N3S2F: Theory: C, 57.98; H, 4.26; N, 12.68.

Found: C, 57.74; H, 4.39; N, 12.53.

Example 7 N- (2-phenefchvH -w - f2- (4-phenvl-5-tetradecvl) -thiazolvll thiourea (CH2)13CH3 A N N 4 H H > J (CH2)13CH3 A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3 mL) and 2-amino-4-phenyl-5-tetradecylthiazole (7.45 g, 20 mmol) in N,iV-dimethylformamide (50 mL) was heated to 100°C. After 24 h, the reaction was cooled to room temperature and poured into ethyl acetate. The 15 organic solution was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The material was recrystallized from ethyl acetate (once) and hexanes (once) to provide 20 4.93 g (46%) of the title product: mp 108.5-109°C; X-8571A -163- - v P 260 IR (KBr, cm"1) 3166, 3022, 2915, 1850, 1574, 1523, 1502, 1215, 695; iH NMR (300 MHz, CDCI3) 8 10.87 (br s, 1H), 9.28 (br s, 1H), 7.55-7.16 (m, 10H), 4.00-3.95 (m, 2H), 2.99 (t, J=7 5 Hz, 2H), 2.79 (t, J=9Hz, 2H) , 1.65-1.00 (m, 24H) , 0.86 (t, J=6 Hz, 3H); MS (FD) m/e 535 (M+); UV (EtOH) 299nm (6=19199), 261nm (E=17809), 203nm (6=31542). Anal. Calcd for C32H45N3S2: Theory: C, 71.73; H, 8.46; N, 7.84.

Found: C, 71.93; H, 8.75; N, 7.92.

Example 8 N-r 2-(3.4-dimethoxv)-nhenethvl 1 -N'-(2-thiazolvl) thiourea A solution of 2-(3,4-dimethoxyphenethyl) isothio-cyanate (0.52 g, 2.33 mmol) and 2-aminothiazole 20 (233 mg, 2.33 mmol) in N,N-dimethylformamide (10 mL) was heated to 100°C. After 24 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic, solution was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and X-8571A brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The oil was recrystallized from toluene to provide 129mg (17%) of the title product: mp 139°C; IR (KBr, cm"1) 3168, 3112, 3013, 1572, 1550, 1516, 1461, 1263, 1237, 1183; iH NMR (300 MHz, DMSO-d6) 5 11.55 (br s, 1H), 9.80-9.62 (br s, 1H), 7.35 (m, 1H), 7.15 (br s, 1H), 6.90-6.75 (m, 3H), 3.80-3.70 (m, 2H), 3.72 (s, 6H), 2.84 (t, J=6 Hz, 2H); MS (FD) m/e 323 (M+); UV (EtOH) 287nm (e=21678), 258nm (e=11828), 228nm (e=11401), 205nm (e=36669).

Anal. Calcd for C14H17N3O2S2: Theory: C, 51.99; H, 5.30; N, 12.99.

Found: C, 51.96; H, 5.51; N, 13.02.

X-8571A -165- U (/ n O «V 26 (9 Rvamnle 9 N-(2-phenethvl)-N'-f2-(4-(4-bromophenvl))thiazolvl1 thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3 mL) and 2-amino-4-(4-bromophenyl)thiazole (5.15 g, 20 mmol) in N,W-dimethylformamide (50 mL) was heated to 100°C. After 65 h, the reaction was cooled to 10 room temperature and poured into ethyl acetate. The organic solution was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer contained as solid which was filtered. The filtrate was dried over sodium sulfate, 15 filtered and concentrated and added to the filtered solid.

The combined material was recrystallized from ethyl acetate to provide 12.04 g (24%) of the title product: mp 215.5-216.5°C; IR (KBr, cm"1) 3166, 3022, 1574, 1523, 1502, 737, 695; X-8571A -166- ^ 0 2 Q !h NMR (300 MHz, DMSO-d6) 8 11-70 (br s, 1H), 9.40 (br s, 1H), 7.74-7.54 (m, 5H), 7.36-7.18 (m, 5H), 3.90-3.81 (m, 2H), 2.96 (t, J=6 Hz, 2H); MS (FD) m/e 419 (M+l); UV (EtOH) 287nm (e=28740), 268nm (e=24574), 246nm (e=18009), 203nm (6=35813).

Anal. Calcd for CisHi6N3S2Br: Theory: C, 51.68; H, 3.86; N, 10.04.

Found: C, 51.39; H, 3.77; N, 9.77.

Example 10 N- T2 - (4-Chloro)-nhenethvl1-N'-(2-fchiazolvl) thiourea cl 7 o A solution of 2-(4-chloro)-phenethy1 isothiocyanate (657 mg, 3.3 mmol) and 2-aminothiazole (335 mg, 3.3 mmol) in .N,iV-dimethylformamide (10 mL) was heated to 100°C. After 20.5 h, the reaction was cooled to room 20 temperature and poured into ethyl acetate. The organic solution was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, and water (3x). The organic layer was dried over sodium sulfate, filtered and X-8571A -167- 26 0 concentrated. The material was recrystallized from ethyl acetate (2x) to provide 136 mg (14%) of title product: mp 154-155°C; IR (KBr, cm"1) 3090, 2991, 1561, 1515, 1490, 1176; !h NMR .(300 MHz, DMSO-d6) 5 11.58 (br s, 1H), 9.78-9.60 (br s, 1H), 7.40-7.28 (m, 5H), 7.12 (br s, 1H), 3.81-3.72 (m, 2H), 2.92 (t, J=6 Hz, 2H); MS (FD) m/e 297 (M+); UV (EtOH) 289nm (e=19572), 257nm (£=12071), 220nm (£=15393), 202nm (£=22079).

Anal. Calcd for C12H12N3S2CI: Theory: C, 48.40; H, 4.06; N, 14.11.

Found: C, 48.17; H, 4.02; N,13.83.

Example 11 N-(2-Phenefchvl)-N'-T2-(4.5-dihvdro)thiazolvl1 thiourea h ,NCS O + h2n ^ n- •H ■h H (§r hAh H N- ■h •H H A solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol, 1.5 mL) and 2-amino-4,5-dihydrothiazole (1.02 g, 10 mmol) in dimethylsulfoxide (10 mL) was heated to 100°C. After 2.5 h, the reaction was cooled to room X-8571A 26 0 temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x). water (4x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was recrystallized from ethyl acetate to provide 1.48 g (56%) of title product as a white crystalline solid. A sample was recrystallized a second time from ethyl acetate: mp 132-134°C; IR (KBr, cm"1) 3161, 3027, 2945, 2862, 1630, 1574, 1552, 1221, 1033; !h NMR (300 MHZ, CDCI3) 5 11.11 (br s, 1H), 8.36 (s, 1H), 7.32-7.14 (m, 5H), 4.05-3.97 (m, 2H), 3.90-3.83 (m, 2H) , 3.30-3.22 (m, 2H), 2.94 (t, J=7.1 Hz, 2H); MS (EI) m/e 265 (M+); UV (EtOH) 269nm (e=18349), 206nm (e=18745).

Anal. Calcd for C12H15N3S2: Theory: C, 54.31; H, 5.70; N, 15.83.

Found: C, 54.36; H, 5.66; N, 15.78.

Example 12 N-(2-Phenethvl)-N'-f 2 -f 4-methvlthiazolvl)1 thiourea X-8571A 2 6 0 9 a •* A solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol, 1.5 mL), 2-amino-4-methylthiazole hydrochloride (1.51 g, 10 mmol) and JV,JV-diisopropylethylamine (1.29 g, 10 mmol, 1.74 mL) in dimethylsulfoxide (10 mL) was heated to 5 100°C. After 21 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (3x), and brine. The organic layer was dried over sodium sulfate, filtered and 10 concentrated. The solid obtained was purified by flash chromatography on silica gel (1% ethyl acetate in c?: chloromethane) , followed by recrystallization from ethyl acetate to provide 1.05 g (38%) of the title product as a very light green crystalline solid: mp 190-192°C; IR (KBr, cm-1) 3456, 3169, 3084, 3024, 1565, 1533, 1506, 1214; !h NMR (300 MHZ, CDCI3) 8 10.92 (s, 1H) , 10.08 (s, 1H) , 7.33-7.20 (m, 5H), 6.31 (s, 1H), 4.04-3.98 (m, 2H), 3.01 20 (t, J=6.9 Hz, 2H), 2.17 (s, 3H); MS (EI)' m/e 277 (M+); UV (EtOH) 293nm (e=18119), 258nm (e=10137), 204nm (e=18979). Anal. Calcd. for C13H15N3S2: Theory: C, 56.29; H, 5.45; N, 15.15. 25 Found: C, 56.53; H, 5.53; N, 15.18.

X-8571A 2®0.?9 Example 13 N-(2-Phenethvl)-N1 - f 2 - (4 -(efchvlglvoxvlate)thiazolvl)1 thiourea g, 20 mmol, 3.0 mL) and ethyl 2-amino-4-thiazoleglyoxylate (4.0 g, 20 mmol) in dimethylsulfoxide (20 mL) was heated to 110°C. After 68 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, water (5x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (10% ethyl acetate in dichloromethane) and treated with decolorizing carbon to provide 2.37 g (33%) of the title product as a light yellow solid. -A sample was recrystallized from ethyl acetate: mp 168-169°C; IR (KBr, cm"1) 3174, 3029, 1724, 1685, 1558, 1530, 1215, 1133, 1054; X-8571A 2 6 0 2 P J iH NMR (300 MHZ, CDCI3) 8 10.67 (s, 1H), 8.21 (s, 1H), 7.34-7.17 (m, 5H), 4.39 (q, J=7.1 Hz, 2H), 3.96-3.85 (m, 2H), 3.09-2.93 (m, 2H), 1.40 (t, J=7.lHz, 3H); MS (FD) m/e 363 (M+); UV (EtOH) 284nm (e=18549), 255nm (e=17141), 204nm (e=23447) .

Anal. Calcd for C16H17N3O3S2: Theory: C, 52.87; H, 4.71; N, 11.56.

Found: C, 53.08; H, 4.80; N, 11.55.

Example 14 N-(2-Phenethy1)-N'-f 2-(5.6-dimethvlbenzothiazolvl)1 thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 2-amino-5,6-dimethylbenzothiazole (3.57 g, 20 mmol) in w,iV-dimethyl-formamide (50 mL) was heated to 100°C. After 24 h, the reaction was cooled to 20 room temperature and poured into ethyl acetate, with formation of a precipitate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (2x) and brine. The organic layer was filtered and the solid obtained (3.0 g) triturated with 20% 25 ethanol in ethyl acetate to provide 2.91 g (43%) of the title product as a pale yellow solid: mp 226-'228°C; X-8571A 26 0 2 IR (KBr, cm-1) 3178, 3047, 1557, 1530, 1462, 1254, 1220; !h NMR (300 MHZ, DMSO-dff) 8 11.69 (S, 1H) , 10.30 (s, 1H) , 7.55 (s, 1H), 7.35-7.16 (m, 6H), 3.80-3.73 (m, 2H), 2.90 (t, J=7.0 Hz, 2H), 2.25 (s, 3H), 2.23 (s, 3H); MS (EI) m/e 341 (M+); UV (EtOH) 307nm, 253nm, 204nm.

Anal. Calcd for C18H19N3S2: Theory: C, 63.31; H, 5.61; N, 12.31.

Found: C, 63.15; H, 5.63; N, 12.14.

Example 15 N-(2-Phenethvl)-N'-T2-(S-methoxybenggthiazglyl)1 thiourea ,och3 A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 2-amino-6-methoxybenzothiazole (3.60 g, 20 mmol) in iy,iV-dimethylformamide (50 mL) was heated to 100°C. After 16 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer was filtered to provide 550 mg of the title product. The filtrate was concentrated and the X-8571A -173- O t> C o u resulting solid recrystallized from ethyl acetate to provide, another 830 mg of the title product. Total yield: 1.38 g (20%) of the title product as a fluffy white solid: mp 217-218°C; IR (KBr, cm"1) 3182, 3050, 1556, 1534, 1473, 1437, 1221, 1055; ^•H NMR (300 MHZ, CDCI3) 5 10.99 (s, 1H) , 9.29 (s, 1H) , 7.46-6.99 (m, 8H), 4.12-4.06 (m, 2H), 3.86 (s, 3H), 3.08 (t, J=6.8 Hz, 2H); MS (FD) m/e 343 (M+); UV (EtOH) 312nm (6=22725), 251nm (£=11152), 204nm (£=26183) Anal, calcd for C17H17N3OS2: Theory: C, 59.45; H, 4.99; N, 12.23.

Found: C, 59.21; H, 4.97; N, 12.19. 2-Amino-4-cvanothiazole M nM EEPQ TFA ®3CN ,CO2H N—OH Ethyl 1,2-dihydro-2-ethoxy-1- quinolinecarboxylate (6.68 g, 27.0 mmol) was added to a solution of ethyl [2-(tritylamino)thiazol-4-yl]-(Z)-hydroxyiminoacetate (11.46 g, 26.7 mmol) in W,W-dimethyl-formamide (100 mL) and stirred for 6 h at room temperature.

The reaction was poured into ethyl acetate, washed with In hydrochloric acid (2x), water (3x) and brine, dried over sodium sulfate, filtered and concentrated. The resulting white foam (9.9 g) was dissolved in dichloromethane (300 X-8571A 26 G q , - & o mL) , treated with triethylsilane (12.44 g, 107 mmol, 17 mL) and trifluoroacetic acid (25 mL) and stirred for 2.5 h at room temperature. The reaction was concentrated in vacuo. dissolved in ethyl acetate, washed with saturated sodium 5 bicarbonate solution and brine, dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (1:1 ethyl acetate and hexanes) to provide 2.75 g (82%) of the title product as a white solid: mp 154-156°C; IR (KBr, cm"1) 3416, 3291, 3118, 2234, 1638, 1547, 1315, 1108; iH NMR (300 MHZ, CDCI3) 8 7.23 (s, 1H), 5.19 (br S, 2H); MS (FD) m/e 125 (M+); UV (EtOH) 278nm (e=4359), 235nm (e=4047), 210nm (e=16728). Anal. Calcd for C4H3N3S: Theory: C, 38.39; H, 2.42; N, 33.57.

Found: C, 38.65; H, 2.46; N, 33.24.

Example 17 N-(3-Phenvlprqpv1)-N'-(2-thiazolvl) thiourea """0 X-8571A -175- 26 0 w A solution of 3-phenylpropy1 isothiocyanate (500 mg, 2.82 mmol) and 2-aminothiazole (300 mg, 3.0 mmol) in iV,JV-dimethylformamide (10 mL) was heated to 100°C. After 20 h, the reaction was cooled to room temperature and 5 poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, water (3x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (1% ethyl acetate in 10 dichloromethane) and then recrystallized from ethyl acetate to provide 129 mg of the title product. A second crop was recrystallized from 1:1 ethyl acetate/hexanes to provide another 110 mg of the title product. Total yield of the title product: 239 mg (30%) as an off-white solid. A 15 sample was recrystallized again from ethyl acetate: mp 126.5-127.5°C; IR (KBr, cm"1) 3166, 3022, 1574, 1523, 1502, 1215, 1166; !h NMR (300 MHZ, CDCI3) 8 10.88 (s, 1H), 10.42 (s, 1H) , 7.37-7.15 (m, 6H), 6.82 (d, J=3.6 Hz, 1H), 3.82-3.71 (m, 20 2H), 2.74 (t. J=7.7 Hz, 2H), 2.12-2.01 (m, 2H); MS (FD) m/e 277 (M+); UV (EtOH) 288nm (e=19598), 256nm (e=11329), 206nm (e=19259).

Anal. Calcd for C13H15N3S2: Theory: C, 56.29; H, 5.45; N, 15.15.

Found: C, 56.29; H, 5.38; N, 15.00.

X-8571A -176- 2 6 0 C> > & o Example 18 N-(2-Phenethvl)-N'-T2-(6-ethoxvbenzothiazolvl)1 thiourea g, 20 mmol, 3.0 mL) and 2-amino-6-ethoxy-benzothiazole (3.88 g, 20 mmol) in i^N-dimethylformamide (50 mL) was heated to 100°C. After 20 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic'layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was recrystallized from ethyl acetate to provide. 649 mg (9%) of the title product as a tan solid: mp 204-205°C; IR (KBr, cm"1) 3166, 3022, 1574, 1523, 1502, 1435, 1215; iH NMR (300 MHZ, CDCI3) 8 11.01 (s, 1H), 9.77 (s, 1H), 7.43-6.95 (m, 8H), 4.08-4.01 (m, 4H), 3.06 (t, J=6.6 Hz, 2H), 1.43 (t, J=6.8 Hz, 3H); MS (FD) m/e 357 (M+); X-8571A -177- V/ U y 26 0 UV (EtOH) 312nm (e=23035), 251nm (e=11355), 204nm (e=26891).

Anal. Calcd for C18H19N3OS2: Theory: C, 60.48; H, 5.36; N, 11.75.

Found: C, 60.21; H, 5.10; N, 11.52.

Example 19 N- (2-Phenethv!) -N' - f2- (4-?:eT-f:-hiitvlthia2olvl) 1 thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 2-amino-4-tert-butylthiazole (3.13 g, 20 mmol) in N,N-dimethylformamide (50 mL) was heated to 100°C. After 64 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (2x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was recrystallized from ethyl acetate to provide 2.98 g (47%) of the title product as an off-white crystalline solid: mp 173.5-175°C; X-8571A -178- V (J 26n IR (KBr, cm"1) 3173, 2960, 1576, 1514, 1465, 1348, 1204, 1098; XH NMR (300 MHZ, CDCI3) 8 11.14 (s, 1H), 10.26 (s, 1H), 7.31-7.18 (m, 5H), 6.33 (s, 1H), 4.05-3.99 (m, 2H), 3.04 (t, J=7.1 Hz, 2H), 1.14 (S, 9H) ; MS (FD) m/e 319 (M+); UV (EtOH) 292nm (e=20804), 257nm (e=10502), 203nm (e=19085).

Anal. Calcd for CI6H21N3S2: Theory: C, 60.15; H, 6.63; N, 13.15.

Found: C, 59.95; H, 6.66; N, 13.15.

Rvamplp 20 N-(2-Phenethy1)-N'-T2-M-triflnoromethvlthiazolvl)^ r.Uiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 2-amino-4-trifluoromethylthiazole (3.84 g, 22.8 mmol) in W,N-dimethyl-formamide (50 mL) was heated to 100°C. After 20 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, water (3x) and 0 2 0 X-8571A -179- ^ ^ 26 brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was recrystallized from 1:1 ethyl acetate/hexanes to provide 846 mg (13%) of the title product as a white solid: 5 mp 162-163°C; IR (KBr, cm"1) 3166, 3033, 1562, 1516, 1469, 1242, 1126; XH NMR (300 MHZ, CDCI3) 8 10.49 (s, 1H) , 10.31 (S, 1H), 7.33-7.19 (m, 6H), 4.01-3.95 (m, 2H), 3.02 (t, J=6.9 Hz, 2H) ; MS (FD) m/e 331 (M+); UV (EtOH) 286nm (e=14352), 258nm (e=14149), 205nm (e=24571) .

Anal. Calcd for C13H12F3N3S2: Theory: C, 47.12; H, 3.65; N, 12.68. 15 Found: C, 47.34; H, 3.85; N, 12.72.

Example 21 N- (2-Phenethvl)-N'.N'-dimethyl thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 2-amino-5-chlorothiazole (2.69 g, X-8571A -180- ~ .... (j 260 - mmol) in J^W-dimethylformamide (50 mL) was heated to 100°C. After 20 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid and brine (3x). The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (1% ethyl acetate in dichloromethane) and then recrystallized twice from ethyl acetate to provide 606 mg (14%) of the title product as an off-white crystalline solid: mp 104.5-105.5°C; IR (K3r, cm-1) 3284, 1536, 1452, 1347, 901; !h NMR (300 MHZ, CDCI3) 8 7.33-7.19 (m, 5H), 5.37 (br s, 1H), 3.93-3.87 (m, 2H), 3.16 (s, 6H), 2.93 (t, J=6.8 Hz, 2H) ; MS (FD) m/e 208 (M+); UV (EtOH) 242nm (£=12899), 210nm (6=21286)..

Anal. Calcd for C11H16N2S: Theory: C, 63.42; H, 7.74; N, 13.45.

Found: C, 63.39; H, 7.80; N, 13.67.

X-8571A -181- lJ 1 ' ^ 0 Example 22 N- (2-Phf»nvathvl) -N' - \2- (4-cvanothiazolvl) thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 2-amino-4-cyanothiazole (2.50 g, 20 mmol) in JV,N-dimethylformamide (50 mL) was heated to 100°C. After 20 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution, water (3x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (1% ethyl acetate in dichloromethane) and then recrystallized from 1:1 ethyl acetate/hexanes to provide 132 mg of the title product (2%) as a white solid: mp 169-170°C; IR (KBr, cm"1) 3166, 3022, 1574, 1523, 1502, 1215, 1166; iH NMR (300 MHZ, CDCI3) 5 10.88 (s, 1H), 10.09 (s, 1H) , 7.50 's, 1H), 7.39-7.23 (m, 5H), 4.00-3.93 (m, 2H), 3.02 (t, J=6.9 Hz, 2H); MS (FD). m/e 288 (M+) ; UV (EtOH) 288nm (e=11104), 258nm (e=17433), 208nm (6=31355).

O c ^ X-8571A -182- ^ ^ U Anal. Calcd for C13H12N4S2: Theory: C, 54.14? H, 4.19; N, 19.43.

Found: C, 54.04; H, 4.23; N, 19.73.

Example 23 N- (2-Phenethy 1) -N' -2- f 4- (4-pivridv.1) - thiazolvl 1 thiourea 2-Amino-4-(4-pyridyl)thiazole hydrobromide1'2 was sluirried with methylene chloride and shaken with saturated sodium bicarbonate solution. The layers were separated and the aqueous washed with methylene chloride and ethyl acetate. The combined organic layers were concentrated. To the solid (1.0 g, 5.6 mmol) was added 2-phenethyl isothiocyanate (0.91 g, 5.6 mmol, 0.83mL) in N,N-dimethylformamide (12.5 mL). The resulting suspension was heated to 100°C. After 20.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with water (4x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The resulting solid was recrystallized from X-8571A 260 29 3 ethyl acetate (3x) to provide 133 mg (7%) of the title product: mp 196.5°C; IR (KBr, cm"1) 3250, 2939, 1723, 1604, 1506, 1223, 670, 664; NMR (300 MHz, DMSO-d6) 6 11.72 (S, 1H) , 9.21 (br S, 1H) , 8.54 (d, J=6 Hz, 2H), 7.82 (s, 1H), 7.63 (d, J=6 Hz, 2H), 7.30-7.15 (m, 5H), 3.84-3.77 (m, 2H), 2.89 (t( J=7 Hz, 2H); MS (FD) m/e 340 (M+); HRMS (FAB) m/e (M+) calcd 341.0895, obs 341.0909; UV (EtOH) 294nm (C=23935), 231nm (e=16356), 203nm (e=25793). (1) Nielsen, A.T. and Piatt, E.N. Heterocyclic Chem.. 1969, vol 6 p 896. (2) Brown, Cowden, Grigg, Kavulak Aust. J. Chem. 1980, 33, 2291. 26 Q - £ X-8571A -184- Example 24 N- (2 -phenethy 1 )-N'-f2-M-(4 -blohenvl) - thiazolvl 1 thiourea A solution of 2-phenethyl isothiocyanate (0.82 g, 5 mmol, 0.75 mL) and 2-amino-4-(4-biphenyl)thiazole (1.26 g, 5 mmol) in N,//-dimethylformamide (12.5 mL) was heated to 100°C. After 19.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The 10 organic solution was washed with IN hydrochloric acid. The mixture was filtered and the filtrate was separated and the organic phase washed with saturated sodium bicarbonate solution, water (4x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The 15 material was purified by flash chromatography on silica gel (1% ethyl acetate in dichloromethane to 2% ethyl acetate in dichloromethane) to provide 372 mg of the title product (18%). .The yellow solid was recrystallized from ethyl acetate: mp 208.5-209°C; 26 0 ? X-8571A IR (KBr, cm"1) 3437, 3172, 3029, 1570, 1553, 1511, 1211, 1060, 738; *H NMR (300 MHz, DMSO-dg) d 11.72 (s, 1H) , 9.54 (bx S, 1H) , 7.86-7.80 (m, 2H), 7.78-7.68 (m, 4H), 7.58 (s, 1H), 7,52-7.44 (m, 2H), 7.41-7.35 (m, 1H), 7.34-7.29 (m, 4H), 7.27-7.20 (m, 1H), 3.92-3.84 (m, 2H), 2.98 (t, J=3 Hz, 2H); MS (FD) m/e 415 (M+); UV (EtOH) 293nm, 212nm.

Anal. Calcd for C24H21N3S2: Theory: C, 69.36; H, 5.09; N, 10.11.

Found: C, 69.08; H, 5.10; N, 9.99.

Example 25 N-(2-Phenethy1)-N'-2-f 4-Cl - (1-ethvoxvcarbonlvl)-(3-t-butoxvcarbonvlmethoxv)Imlno)-thiazolvl1 thiourea N €Wl H H !!—C °~i C02-C(CH3)3 -Yvn N O—j C05-C(CH,), X-8:>71A 2-Amino-4-(1-(1-ethoxycarbonyl)-(3-t-butoxy-carbonylmethoxy ) imino) thiazole (2.64 g, 8 irtmol) and 2-phenethyl isothiocyanate (1.31 g, 8 mmol, 1.2 mL) in N,N-dimethylformamice (20 mL) were heated to 100°C. After 24 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The resulting solid was triturated with ethyl acetate to provide 801 mg (20%) of the title product: mp 188.5°C; IR (KBr, cm*1) 3293, 2975, 1749, 1594, 1543, 1453, 1382, 1231, 1154, 1054, 748, 698; iH NMR (300 MHz, DMSO-d6) d 11.85 (s, 1H) , 8.46 (br S,1H), 7.29-7.17 (m, 5H), 4.59 (s, 2H), 4.31-4.24 (q, J=7.1 Hz, 2H), 3.70-3.64 (m, 2H), 2.82 (t, J=7.1 Hz,. 2H), 1.36 (s, 9H), 1.23 (t, J= 7.1 Hz, 3H); MS (FD) m/e 492 (M+); UV (EtOH) 292nm, 257nm (e=16356), 203nm.

Anal. Calcd for C22H28N4O5S2: Theory: C, 53.64; H, 5.73; N, 11.37.

Found: C, 53.67; H, 5.83; N, 11.34.

Example 26 N-(2-Phenethyl)-N'-2-f4-C-butvl-5-methvlthiazglvll thiourea H H X-8571A -187 2-Amino-4-t-butyl-5-methylthiazole (1.87 g, 11 mmol) and 2-phenethyl isothiocyanate (1.80 g, 11 mmol, 1.64 mL) in itf,N-dimethylformamide (25 mL) were heated to 100°C. 5 After 18.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The 10 resulting solid was triturated with ether to provide 1.02 g (28%) of the title product: mp 153-153.5°C; IR (KBr, cm"1) 3171, 2966, 1474, 1534, 1510, 1455, 1346, 1221, 1186, 755, 704; lH NMR (300 MHz, DMSO-d6) 8 11.28 (BR S, 1H) , 9.90 (BR S, 1H), 7.28-7.14 (M, 5H), 3.78-3.34 (M, 2H), 2.84 (T, J=7 Hz, 2H), 2.27 (s, 3H), 1.16 (s, 9H) ; MS (FD) m/e 333 (M+); UV (EtOH) 297nm (6=19835), 257nm (6=9954), 202nm (e=21059). 20 Anal. Calcd for c17h23n3s2: Theory: C, 61.22; H, 6.95; N, 12.60.

Found: C, 61.42; H, 6.92; N, 12.55.

Example 27 N-(2-Fhenethvl)-N'-r5-methvl-T2-(1.3.4-thiadiazolvl)11 thiourea A solution of 2-amino-5-methyl 1,3,4-thiadiazole (2.30 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol', 3.0 mL) in JV,W-dimethylformamide (50 mL) was 30 heated to 100°C for 18 h. The reaction was cooled to room temperature and the solvent was removed in vacuo. The 26 0 a 6 's n X-8571A -188- resultant solid was crystallized from ethyl acetate to provide 1.86 g (33%) of the title product as a white solid: IR (KBr, cm"1) 3323, 3031, 1640, 1540, 1444, 1385, 781, 697, 652; iH NMR (300 MHZ, DMSO-d6) 8 12.4 (br S, 1H) , 8.75 (br S, 1H), 7.4-7.2 (m, 5H), 3.85-3.75 (m, 2H), 2.9 (t, J=7 Hz, 2H), 2.54 (S, 3H); MS (FD) m/e 278 (M+); UV (EtOH) 280nm (e=10188), 253nm (6=11849), 205nm (6=19724).

J Example 28 N-(2-Phenethv1)-N'-(2-pvrimidinvl) thiourea A solution of 2-aminopyrimidine (1.90 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 15 mL) in N,W-dimethylformamide (50 mL) was heated to 120°C for 40 h. The reaction was cooled to room temperature and the solvent was removed in vacuo. The resultant solid was recrystallized twice from ethyl acetate to provide 0.90 g (17%) of the title product as white needles: IR (KBr, cm"1) 3325, 1588, 1524, 1434, 1415, 1333, 1228, 1154, 797; l-H NMR (300 MHz, DMSO-dg) 8 11.25 (br s, 1H), 10.65 (br s, 1H), 8.6 (d, J=5 HZ, 2H) 7.4-7.2 (m, 6H), 3.85-3.75 (m, 2H) , 2.9 (t, J=7 Hs:, 2H) ; MS (FD) m/e 258 (M+); UV (EtOH) 286nm (6=17644), 267nm (6=15834), 244nm (6=12312), 205nm (e=21839) .

Anal. Calcd for C13H14N4S: Theory: C, 60.44; H, 5.46; N, 21.69. 30 Found: C, 60.15; H, 5.48; N, 21.89. • 2dn o „ X-8571A -189- & Example 29 N-(2-Phenethvl)-N'-T2-(4-(4-chloronhenvl)thiazolvl)1 thiourea A solution of 2-phenethyl isothiocyanate (0.77 5 g, 4.75 mmol) and 2-amino-4-(4-chlorophenyl)thiazole (1.0 g, 4.75 mmol) in AT/N-dimethylformamide (10 mL) was heated o to 120 C 20 h* The solvent was removed in vacuo. The resultant solid waa recrystallized from ethyl acetate to provide 0.30 g (17%) of the title product as a yellow 10 solid: IR (KBr, cm"1) 3176, 3029, 1579, 1515, 1231, 737, 698; !h NMR (300 MHz, DMSO-d6) 5 11.70 (br s, 1H), 9.40 (br s, 1H), 7.74-7.54 (m, 5H), 7.36-7.18 (m, 5H) , 3.9-3.8 (m, 2H), 2.96 (t, J=6 Hz, 2H); MS (FD) m/e 373 (M+) ; UV (EtOH) 273nm (e=35089), 247nm (e=21894) , 202nm (e=22213).

Anal. Calcd for C18H16N3S2CI: Theory: C, 57.82; H, 4.31; N, 11.24.

Found: C, 57.55; H, 4.24; N, 11.26.

Example 3Q N-(2-Phenethvl)-N'-f2-(6-chloro)benzothiazolyl1 thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol) and 2-amino-6-chlorobenzothiazole (3.69 g, 20 25 mmol) in N,N-dimethylformamide (50 mL) was heated to 120°C for 24 h. The solvent was removed in vacuo. The resultant solid was recrystallized from ethyl acetate to provide 3.68 g (53%) of the title product as a white solid: IR (KBr, cm"1) 3165, 3021, 1574, 1522, 1501, 1289, 1215; 30 1h NMR (300 MHz, CDCI3) 5 12.0 (br s, 1H), 9.8 (br s, 1H), 8.1-7.2 (m, 8H), 3.85 (m, 2H), 2.95 (t, J=7 Hz, 2H); X-8571A 26 0 o g MS (FD) m/e 347 (M+); UV (EtOH) 304nm, 292nm, 248nmf 220nm, 205nm.

Example 31 N-(2-Phenethvl)-N'-rs-ethvl-f2-(1.3.4-thiadiazolvl>11 thiourea A solution of 2-amino-5-ethyl-l,3,4-thiadiazole (2.58 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) in W,.W-dimethylformamide (50 mL) was 10 heated to 120°C for 8 h. The reaction was cooled to room temperature and the solvent was removed in vacuo. The resultant solid was crystallized from ethyl acetate to provide 2.45 g (33%) of the title product as a white solid: IR (KBr, cm"1) 3317, 1645, 1536, 1448, 1384, 783, 693, 651; 15 !h NMR (300 MHz, DMSO-d6) 5 12.4 (br s, 1H), 8.75 (br s, 1H), 7.4-7.2 (m, 5H), 3.85-3.75 (m, 2H), 3.0-2.8 (m, 4H), 1.25 (t, J=7 Hz, 3H); MS (FD) m/e 292 (M+); UV (EtOH) 281nm (e=13028), 253nm (8=13615), 206nm (£=23674).

Example 32 N- (2-Phenethv1)-N'-f4-chlorophenvll thiourea A solution of 4-chloroaniline (2.55 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) in 25 W,W-dimethylformamide (50 mL) was heated to 120°C for 18 h.

The reaction was cooled to room temperature and the solvent was removed in vacuo. The resultant solid was crystallized from ethyl acetato to provide 1.50 g (26%) of the title product, as a yellow solid: X-8571A 26 Q - p IR (KBr, cm"1) 3166, 3021, 1523, 1501, 1289, 1079, 802, 737, 695; l-H NMR (300 MHz, DMSO-d6) 5 9.6 (br s, 1H) , 7.9 (br s, 1H) , 7.5-7.2- (m, 9H), 3.8-3.65 (m, 2H), 3.0-2.8 (t, J=7 Hz, 2H); MS (FD) m/e 290 (M+); UV (EtOH) 270nm (6=14107), 247nm (8=18128), 206nm (8=27795). Anal. Calcd for C15H15N2SCI: Theory: C, 61.95; H, 5.20; N, 9.63.

Found: C, 62.19; H, 5.46; N, 9.87.

Example 33 N- (2-Phenethvl)-N'-f3-chlorophenvll thiourea A solution of 3-chloroaniline (2.55 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) in N, W-dimethylformamide (50 mL) was heated to 120°C for 20 h. The reaction was cooled to room temperature and the solvent was removed in vacuo. The resultant yellow oil was purified by HPLC on silica gel to provide 0.95 g (16%) of the title product as a white solid: IR (KBr, cm-1) 3310, 1591, 1542, 1495; XH NMR (300 MHz, DMSO-d6) 8 9.85 (br s, 1H), 7.9 (br s, 1H), 7.65-7.2 (m, 9H), 3.8-3.65 (m, 2H), 3.0-2.8 (t, J=7 Hz, 2H); MS (FD) m/e 290 (M+); UV (EtOH) 250nm (8=17296), 209nm (8=29630).

Anal. Calcd for C15H15N2SCI: Theory: C, 61.95; H, 5.20; N, 9.63.

Found: C, 61.65; H, 5.44; N, 9.84.

X-8571A -192- 2 S H ft O C, Example 34 N- (n-Pronvl) - w- f2-thiaznv3 1 thiourea A solution of 2-aminothiazole (2.0 g, 20 mmol) and n-propyl isothiocyanate (2.0 g, 20 mmol) in N,N~ 5 dimethylformamide (50 mL) was heated to 120°C for 20 h.

The reaction was cooled to room temperature and the solvent was removed in vacuo. The resultant yellow oil was recrystallized twice from ethyl acetate to provide 0.42 g (10%) of the title product as a white solid: IR (KBr, cm"1) 3179, 1556, 1514, 1471, 680; % NMR (300 MHz, DMSO-d6) 6 11.55 (br s, 1H), 9.7 (br s, 1H), 7.4 (d, J=5 Hz, 1H), 7.1 (d, J=5 Hz, 1H), 3.5 (m, 2H), 1.6 (m, 2H), 0.95 (t, J=7 Hz, 3H); MS (FD) m/e 201 (M+); UV (EtOH) 288nm (£=19469), 256nm (6=10151), 202nm (£=11550).

Anal. Calcd for C7H11N3S2: Theory: C, 41.77; H, 5.51; N, 20.87.

Found: C, 42.02; H, 5.61; N, 20.93.

Example 35 N-(2-Phenethvl)-N'-f2-(4.5.6.7-tetrahvdrobenzothiazolvl)1 thiourea A solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol) and 2-amino-4,5,6,7-tetrahydrobenzothiazole 25 (1.54 g, 10 mmol) in JV,W-dimethylformamide (25 mL) was heated to 120°C for 48 h. The solvent was removed in vacuo. The resultant solid was recrystallized from ethyl acetate to provide 0.32 g (11%) of the title product as a white solid: IR (KBr, cm-1) 3165, 3021, 2923, 1601, 1529, 1501, 1261, 1225; 0 26 n X-8571A -193- C" ^ ^-H NMR (300 MHz, DMSO-d6> 5 11.5 (br s, 1H), 10.0 (br s, 1H) , 7.4-7.2 (m, 5H), 3.85 (m, 2H), 2.95 (t, J=7 Hz, 2H) , 2.6-2.4 (m, 4H), 1.75 (m, 4H); MS (FD) m/e 317 (M+); UV (EtOH) 299nm (e=11440), 258nm (e=6011), 207nm (£=10579).

Example 36 N-(2-nhenethvl)-N'-f2-benzothiazolyl1 thiourea A solution of 2-phenethyl isothiocyanate (3.26 10 g, 20 mmol, 3.0 mL) and 2-aminobenzothiazole (3.0 g, 20 mmol) in toluene (50 mL) was heated to reflux. After 5 h, the reaction was cooled to room temperature and poured into ethyl acetate, washed with water, IN aqueous HC1, water, saturated sodium bicarbonate, and brine. The organic layer 15 was concentrated and the residue recrystallized from ethyl acetate to provide 1.8 g (29%) of the title product: mp 203-207°C; IR (KBr, cm"1) 3181, 3045, 1697, 1557, 1523, 1451, 1440, 1244, 749; lH NMR (300 MHz, CDCl3/DMSO-d6) 8 11.7 (br s, 1H) , 10.6 (br s, 1H), 7.8-7.2 (m, 9H), 3.95 (in, 2H), 3.05 (t, J=7 Hz, 2H) ; MS (FD) m/e 313 (M+); UV (EtOH) 300nm (6=24241), 207 nm (6=28964). 25 Anal. Calcd for C16H15N3S2: Theory: C, 61.31; H, 4.82; N, 13.41.

Found: C, 61.03; H, 4.67; N, 13.19.

X-8571A d 6 n '? Q w v ^ tU & Example 37 N-(2-Phenethvl)-N'-f2-(4-methvl)benzothiazolyl1 thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 2-amino-4-methylbenzothiazole (3.3 5 g, 20 mmol) in toluene (50 mL) was heated to reflux. After 5 h, the reaction was cooled to room temperature and poured into ethyl acetate, washed with water, IN aqueous HC1, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from 10 ethyl acetate to provide 1.68 g (26%) of the title product: mp 185-188°C; IR (KBr, cm"1) 3170, 3024, 1571, 1525, 1219, 767, 742, 698; lH NMR (300 MHZ, CDCl3/DMSO-d6) 8 11.4 (br s, 1H), 10.9 (br s, 1H), 7.6-7.1 (m, 8H), 4.05 (m, 2H), 3.05 (t, J=7 Hz, 15 2H), 2.37 (s, 3H); MS (FD) m/e 327 (M+) ; UV (EtOH) 303nm (6=27416), 204 nm (e=30294) .

Anal. Calcd for C17H17N3S2: Theory: C, 62.35; H, 5.23; N, 12.83. 20 Found: C, 62.56; H, 5.37; N, 12.77.

Example 38 N-(2-Phenethvl)-N'-T2-M-methoxv)benzothiazolyl1 thiourea A solution of 2-phenethyl isothiocyanate (3.26 25 g, 20 mmol, 3.0 mL) and 2-amino-4-methoxybenzothiazole (3.2 g, 20 mmol) in itf/W-diraethylformamide (20 mL) was heated at O 115 C for 24 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and 30 brine. The organic layer was concentrated and the residue 2 6 0 2 '*» '? X-8571A -195- recrystallized from ethyl acetate to provide 0.97 g (14%) of the titles product: mp 205-207°C; IR (KBr, cm"1) 3165, 3021, 1574, 1522, 1215, 736, 695, 655; 5 % NMR (300 MHz, DMSO-<?6) 8 12.4 (br s, 1H), 9.9 (br s, 1H), 7.6-7.0 (m, 8H), 3.9 (s, 3H), 3.85 (m, 2H), 2.95 (t, J=7 Hz, 2H); MS (FD) m/e 343 (M+) ; UV (EtOH) 293nm (e=20046), 248 nm (6=15731), 210 nm 10 (e=38172).

Example 39 N-l2-Phenethvl)-N'-T2-(4-chloro)benzothiazolyl1 thiourea A solution of 2-phenethyl isothiocyanate (3.26 15 g, 20 mmol, 3.0 mL) and 2-amino-4-chlorobenzothiazole (3.7 g, 20 mmol) in W/N-dimethylformamide (20 mL) was heated at 115°C for 24 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and 20 brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 2.56 g (37%) of the title product: mp 216-217°C; IR (KBr, cnT1) 3166, 2940, 1568, 1527, 766, 733, 673; 25 !h NMR (300 MHz, DMSO-d6) 8 12.2 (br s, 1H), 9.3 (br s, 1H), 7.6-7.0 (m, 8H), 3.85 (m, 2H), 2.95 (t, J=7 Hz, 2H); MS (FD) m/e 347 (M+); UV (EtOH) 301nm (6=20231), 249 nm (e=17615), 211 nm (6=31440) .

X-8571'A Z 6 Z 2 9 Example 4Q N-(2-Phenethvl) -N' - T 3 - (1. 2 .4-triazolvl) 1 thiourea A solution of 3-amino-l,2,4-triazole (1.70 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) in N,N-dimethylformamide (20 mL) was heated to 115°C for 24 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HC1, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 0.99 g (20%) of the title product: mp 160-162°C; IR (KBr-, cm""1) 3160, 3061, 2872, 1581, 1535, 1467, 1167, 977, 743, 681; iH NMR (300 MHz, DMSO-d6) 8 3-3.9 (br s, 1H) , 10.85 (br s, 1H), 10.0 (br s, 1H), 7.4-7.2 (m, 6H), 3.85 (m, 2H), 2.95 (t, J=7 Hz, 2H); MS (FD) m/e 247 (M+); UV (EtOH) 261mti (e=21785), 229 nm (e=11918), 206 nm (6=17437).

Anal. Calcd for C11H13N5S: Theory: C, 53.42 H, 5.30; N, 28.32.

Found: C, 53.69; H, 5.50; N, 28.07.

N- (2-Phenethvl) -N' -f3-cruinolinvl1 thiourea A solution of 3-aminoquinoline (2.90 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) in JV,iV-diniethylformamide (20 mL) was heated to 90°C for 72 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, X-8571A saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate- to provide 3.62 g (59%) of the title product: mp 162-164°C; IR (KBr, cm"1) 3143, 1537, 1493, 1350, 1283, 1239, 749, 705; XH NMR (300 MHZ, DMSO-d6) 8 9.9 (br s, 1H) , 8.87 (d, J=4 Hz), 1H), 8.35 (br s, 1H), 8.0 (d, J=8 Hz, 1H), 7.9 (d, J=8 Hz, 1H), 7.7-7.2 (m, 8H), 3.8 (m, 2H), 2.95 (t, J=7 Hz, 2H) ; MS (FD) m/e 308 (M+); UV (EtOH) 331nm (£=5945), 257nm (6=27215), 247nm (6=28319), 212 nm (6=37613).

Example 42 N-(2-Phenethvl)-N' — T2 —(4-methvl)pvrimidinel thiourea A solution of 2-aminopyrimidine (1.90 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) in J/,iV-diniethylformamide (20 mL) was heated to 115°C for 24 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 1.21 g (22%) of the title product: mp 174-176°C; IR (KBr, cm"1) 3184, 3034, 1561, 1409, 1344, 1291, 1165, 1030, 836, 792; 1h NMR (300 MHz, DMSO-d6) 8 11.3 (br s, 1H), 10.45 (br s, 1H), 8.4 (d, J=5 Hz, 2H) 7.4-7.2 (m, 5H), 7.0 (d, J=5 Hz, 1H), 3.85-3.75 (m, 2H), 2.9 (t, J=7 Hz, 2H), 2.3 (s, 3H); X-8571A -198- ^ 6 0 c MS (FD) m/e 272 (M+); UV (EtOH) 274nm (e=25263), 248nm (8=15528), 203nm (8=17107). Anal. Calcd for C14H16N4S: Theory: C, 61.74; H, 5.92; N, 20.57.

Found: C, 61.44; H, 6.11; N, 20.38.

Example 43 N- (2-phenethvl)-M'-T2-f4-(4-fluorophenyl))thiazolvl1 thiourea A solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol), triethylamine (1.01 g, 10 mmol), and 2-amino-4-(4—fluorophenyl)thiazole hydroiodide (3.2 g, 10 mmol) in N,N- dime thyl formamide (20 mL) was heated to 100°C for 24 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HC1, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 1.06 g (30%) of the title product: mp 224-228°C; IR (KBr, cm"1) 3178, 3030, 1553, 840, 737, 670; l-H NMR (300 MHz, DMSO-d6) 8 11.70 (br s, 1H), 9.50 (br s, 1H), 7.8-7.2 (m, 10H), 3.90-3.81 (m, 2H), 2.95 (t, J=6 Hz, 2H) ; MS (FD) rn/e 357 (M+); UV (EtOH) 282nm (6=15755), 264nm (e=17277), 239nm (8=13046), 209nm (e=18271).

Anal. Calcd for C18H16N3S2F: Theory: C, 60.42; H, 4.48; N, 11.74.

Found: C, 60.79; H, 4.48; N, 11.63.

X-8571A -199- 260 n Example 44 N-(2-phenethvl)-N'-r2-(4-thiagnlvlacetic acidl thiourea methyl eater A solution of 2-phenethyl isothiocyanate (0.82 5 g, 5 mmol) and 2-aminothiazoleacetic acid methyl ester (0.85 g, 5 mmol) in N,JV-dimethylformamide (20 mL) was heated to 100°C for 72 h, the reaction was cooled to room temperature and poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, 10 and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 0.52 g (31%) of the title product: mp 125-127°C; IR (KBr, cm"3-) 3168, 3085, 1740, 1557, 1524, ; 1h NMR (300 MHz, DMSO-c?6) 5 11.6 (br s, 1H), 9.4 (br s, 1H), 7.4-7.2 (m, 5H), 6.85 (s, 1H), 3.8 (m, 2H), 3.65 (s, 2H), 3.6 (s, 3H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 335 (M+); UV (EtOH) 291nm (e=19133), 258nm (6=10917), 202nm (6=21433). 20 Anal. Calcd for C15H17N3S2O2: Theory: C, 53.71; H, 5.11; N, 12.53.

Found: C, 53.96; H, 5.16; N, 12.79.

Example 45 N- (2-phenethyl)-N'- r2-thiazolvH thiourea A solution of 2-phenethyl isothiocyanate (7.5 g, 45.9 mmol) and 2-aminothiazole (4.6 g, 45.9 mmol) in N,N-dimethylformamide (100 mL) was heated at 115°C for 12 h. The reaction was cooled to room temperature, poured into 30 ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer X-8571A 2 6 C /"' p was concentrated and the residue recrystallized twice from ethyl acetate to provide 5.7 g (47%) of the title product: IR (KBr', cm"1) 3187, 3033, 2978, 1569, 1515, 1470, 1454, 1216, 1170, 1063; iH NMR (300 MHz, DMSO-d6) 8 H-6 (br s, 1H), 9.7 (br s, 1H), 7.4-7.2 (m, 6H), 7.1 (d, J=3 Hz, 1H), 3.8 (m, 2H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 263 (M+); UV (EtOH) 288run (e=19656), 257 nm (e=11658), 203 nm 10 (8=20054).

Anal. Calcd for C12H13N3S2: Theory: C, 54.72 H, 4.97; N, 15.95.

Found: C, 54.63; H, 5.02; N, 15.85.

Example 46 N-(2-r1-cvclohexenvl1 ethyl)-N'-f2-thiazolvll thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (3.3 g, 20 mmol) and 2-aminothiazole (2.0 g, 20 mmol) in tf,.N-dimethylformamide (20 mL) was heated at 100°C 20 for 24 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 2.66 g (50%) 25 of the title product: mp 147-148°C; IR (KBr, cm"1) 3170, 3118, 2989, 1566, 1513, 1180, 706; !h NMR (300 MHz, DMSO-d6) 6 11.6 (br s, 1H), 9.7 (br s, 1H), 7.38 (d, J=3 Hz, 1H), 7.1 (d, J=3 Hz, 1H), 5.45 (br s, 30 1H), 3.65 (m, 2H), 2.25 (t, J=7 Hz, 2H), 1.9 (m, 4H), 1.5 (m, 4H); X-8571A -201- ^ 6 Q ° Q Q 7 MS (FD) m/e 267 (M+); UV (EtOH) 288nm (6=19663), 256 nm (e=10534), 201 nm (£=14819) .

Anal. Calcd for C12H13N3S2: Theory: C, 53.89 H, 6.41; N, 15.71.

Found: C, 54.15; H, 6.52; N, 15.84.

Example 47 N-(2-phenethvl1-N1-f2-(4-thiazolvlacatic acidl thiourea 10 ethvl eater A solution of 2-phenethyl isothiocyanate (3.62 g, 20 mmol) and 2-aminothiazoleacetic acid ethyl ester (3.72 g, 20 mmol) in W, w-dimethylformamide (20 mL) was heated to 100°C for 24 h, the reaction was cooled to room 15 temperature and poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue was pvrified by HPLC on silica gel to provide 1.7 g (24%) of the title product: mp 80-83°C; IR (KBr, cm"1) 3184, 3109, 1730, 1580, 704, ; !h NMR (300 MHz, DMSO-d6) 8 11.6 (br s, 1H), 9.4 (br s, 1H), 7.4-7.2 (m, 5H), 6.85 (s, 1H), 4.1 (q, J=7 Hz, 2H), 3.8 (m, 2H), 3.65 (s, 2H), 2.9 (t, J=7 Hz, 2H), 1.2 (t, J=7 25 Hz, 3H); MS (FD) m/e 349 (M+) ; UV (EtOH) 291nm (£=15025), 250nm (6=10893), 203nm (£=24071). Anal. Calcd for C16H19N3S2O2: Theory: C, 54.99; H, 5.48; N, 12.02. 30 Found: C, 55.24; H, 5.62; N, 11.96.

X-8571A Example 48 N-(2-phenethvl)-N'-T2-(4-thiazolvlacetic acldl thiourea A solution of N-(2-phenethyl)-N'-[2-(4-thiazolylacetic acid] thiourea ethyl ester (0.7 g, 2.0 ituftol) and IN NaOH (2.5 mL, 2.5 mmol) in 50 mL of 1/1 acetonitrile-water was stirred at room temperature for 24 h. The reaction was poured into ethyl acetate and washed with saturated sodium bicarbonate. The aqueous layer was acidified to pH 2 with IN HCl and extracted with ethyl acetate. The organic extracts were washed with brine and concentrated. The residue was crystallized from ethyl acetate to provide 0.29 g (45%) of the title product: mp 188-190°C; IR (KBr, cm-1) 3200-2800 (br), 1659, 1586, 1377, 671, ; iH NMR (300 MHz, DMSO-d6) 5 12.0 (br s, 2H), 9.6 (br s, 1H), 7.4-7.2 (m, 5H), 6.85 (s, 1H), 3.8 (m, 2H), 3.65 (s, 2H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 322 (M+); UV (EtOH) 291nm (£=19464), 257nm (£=10601), 202nm (8=20396) Anal. Calcd for C14H15N3S2O2: Theory: C, 52.32; H, 4.70; N, 13.07.

Found: C, 52.58; H, 4.88; N, 13.34.

Example 49 Mr(beazvl)-N'-f2-thiazolYll thiourea A solution of benzyl isothiocyanate (1.5 g, 10 mmol) and 2-aminothiazole (1.0 g, 10 mmol) in N,tf-dimethyl formamide (25 mL) was heated at 100°C for 12 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, • 26 0 X-8571A -203- saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized twice from ethyl acetate to provide 1.15 g (46%) of the title product: mp 165-167°C; IR (KBr, cm"1) 3171, 3038, 1560, 1509, 1451, 1183, 972, 691; iH NMR (300 MHz, DMSO-dg) 5 11.7 (br s, 1H), 9.9 (br s, 1H), 7.4-7.2 (m, 6H), 7.C (d, J=3 Hz, 1H), 4.8 (m, 2H); MS (FD) m/e 249 (M+); UV (EtOH) 289nm (E=19103), 257 nm (£=12196), 204 nm (£=21328).

Anal. Calcd for C11H11N3S2: Theory: C, 52.99 H, 4.47; N, 16.85.

Found: C, 53.09; H, 4.50; N, 16.77.

Example 5Q N- (2-Phenethvl)-N'-(2-pvrazinvl) thiourea A solution of 2-aminopyrazine (1.90 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mnol, 3.0 mL) in 20 N,Jtf-dimethyl formamide (50 mL) was heated to 100°C for 17 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized twice from 25 ethyl acetate to provide 0.95 g (18%) of the title product: mp 142-143°C; IR (KBr, cm"1) 3181, 3049, 1606, 1533, 1472, 1314, 1221, 862, 725; iH NMR (300 MHz, DMSO-d6) 6 11.02 (br s, 1H), 10.95 (br s, 30 1H), 8.5 (s, 1H), 8.18 (d, J=2 Hz, 1H), 8.05 (d, J=2 Hz, 26 0 ? X-8571A -204- 1H), 7.4-7.2 (m, 5H), 3.85-3.75 (m, 2H), 2.9 (t, J=7 Hz, 2H) ; MS (FD) m/e 258 (M+); UV (EtOH) 318nm (8=10579), 263nm (e=17922), 202nm (e=15887) . Anal. Calcd for C13H14N4S: Theory: C, 60.44; H, 5.46; N, 21.69.

Found: C, 60.45; H, 5.63; N, 22.02.

Example 51 N- (2-Phenfjf.hyJL) -N' •• (3-pyrazolyl.) thiourea A solution of 3-aminopyrazole (1.66 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) in N,N-dimethylformamide (50 mL) ivas heated to 100°C for 18.5 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized twice from ethyl acetate to provide 2.38 g (48%) of the title product: mp 142-144°C; IR (KBr, cm"1) 3397, 3207, 3078, 1576, 1537, 1255, 1182, 751; !h NMR (300 MHz, DMSO-d6) 6 12.4 (br S, 1H), 10.35 (br S, 1H), 9.85 (br s, 1H), 7.6 (s, 1H), 7.4-7.2 (m, 5H), 5.83 (s, 1H), 3.75 (m, 2H), 2.85 (t, J=7 Hz, 2H)? MS (FD) m/e 246 (M+) ; UV (EtOH) 264nm (6=21473), 204nm (6=17842).

Anal. Calcd fo-^ C12H14N4S: Theory: C, 58.51; H, 5.73; N, 22.74.

Found: C, 58.80; H, 5.83; N, 23.00.

X-8571A -205- 2 6 0 2 0 w Example 52 Preparation of N-(2-Phenethvl)-N'-(phenyl) thiourea A solution of aniline (1.86 g, 20 mmol) and 2-5 phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) in N,N-dimethylformamide (50 mL) was heated to 100°C for 18 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer 10 was concentrated and the residue recrystallized from ethyl ether/hexanes to provide 2.88 g (56%) of the title product: mp 102-104°C; IR (KBr, cm"1) 3375, 1592, 1542, 1493, 1250, 1000, 695; !h NMR (300 MHz, CDCI3) 8 7.85 (br S, 1H), 7.5-7.0 (m, 10H), 6.0 (br s, 1H), 3.9 (m, 2H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 256 (M+); UV (EtOH) 248nm (e=15081) , 206nm (e=25573).

Anal. Calcd for C15H16N2S: Theory: C, 70.28; H, 6.29; N, 10.93. 20 Found: C, 70.14; H, 6.37; N, 10.97.

Example 53 N- (ethvl) -N' - (2-thiazolvl) thiourea A solution of ethyl isothiocyanate (1.74 g, 20 25 mmol) and 2-aminothiazole (2.0 g, 20 mmol) in W,N-dimethyl-formamide (50 mL) was heated at 100°C for 23 h. The reaction was cooled to room temperature, poured into ethyl acetate', washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer 30 was concentrated and the residue recrystallized twice from ethyl acetate to provide 0.48 g (13%) of the title product: X-8571A 260 ?Q mp 135-13 6°C; IR (KBr, cm-l) 3165, 3021, 1574, 1501, 1435, 1366, 1215, 1179, 695; iH NMR (300 MHz, DMSO-C?6) 8 10.4 (br S, 2H) , 7.4 (d, J=3 5 Hz, 1H), 6.8 (d, J=3 Hz, 1H) , 3.7 (m, 2H) , 1.4 (t, J=7 Hz, 3H) ; MS (FD) m/e 187 (M+) ; UV (EtOH) 287nm (£=19544), 256 nm (£=10213), 202 nm (£=11588).

Anal. Calcd for C6H9N3S2: Theory: C, 38.48 H, 4.84; N, 22.44.

Found: C, 38.71; H, 4.92; N, 22.66.

Example 54 N-(2-Phenethvl2-chlorophenyl) thiourea A solution of 2-chloroaniline (2.55 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) in N,W-dimethylformamide (50 mL) was heated to 100°C for 17 h. The reaction was cooled to room temperature, poured into 20 ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue was purified by HPLC on silica gel to provide 1.18 g (20%) of the title product as a white solid: IR (KBr, cm"3-) 3378, 3167, 1540, 1499, 1470, 1250, 1060, 758, 685; iH NMR (300 MHz, DMSO-d6) 8 7.55 (br s, 1H) , 7.5-7.2 (m, 9H), 5.9 (br s, 1H), 3.9 (m, 2H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 290 (M+); UV (EtOH) 245nm (£=16042), 209nm (£=29276).

X-8571A ^ 6 0 9 0 *.v Anal. Calcd for C15H15N2SCI: Theory: C, 61.95; H, 5.20; N, 9.63. Found: C, 61.69; H, 5.28; N, 9.84.

Example 55 N-(hengv1 1-w- f2-(5-chloro) thiazolvl 1 thiourea A solution of benzyl isothiocyanate (3.0 g, 20 mmol) and 2-amino-5-chlorothiazole (2.69 g, 20 mmol) in W,W-dimethylformamide (25 mL) was heated at 100°C for 20 h. 10 The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by HPLC on silica gel to provide 0.86 g (15%) of the title product: 15 mp 162-164°C; IR (KBr, cm"1) 3154, 3003, 2958, 1588, 1515, 1421, 1231, 1192, 726; iH NMR (300 MHz, DMSO-d6) 5 8.8 (br s, 1H), 7.45 (s 1H), 7.4-7.2 (m, 5H), 4.7 (m, 2H); MS (EI) m/e 283 (M+); UV (EtOH) 295nm (e=6457), 259 nm (e=5741) , 208 nm (e=11042).

Example 56 N~(3-Phenvlpromv1)-N'-T2-(5-chloro)thiazolvl! thiourea 25 A solution of 3-phenylpropyl isothiocyanate (3.54 g, 20 mmol) and 2-amino-5-chlorothiazole (2.69 g, 20 mmol) in N, tf-dimethylformamide (50 mL) was heated to 100°C. After 18 h, the reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous 30 HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by X-8571A 26 0 ■? o v HPLC on silica gel to provide 0.29 g (5%) of the title product: mp 121-13 0°C; IR (KBr, cm"1) 3160, 3100, 2949, 1565, 1517, 1493, 698; 5 XH NMR (300 MHZ, DMS0-d6) 5 10.8 (s, 1H), 8.5 (br s, 1H), 7.4 (s, 1H), 7.3 (m, 5H), 3.5 (m, 2H), 2.6 (t, J=7.7 Hz, 2H), 1.8 (m, 2H); MS (FD) m/e 311 (M+); UV (EtOH) 295nm (6=14069), 259nm (6=12092), 205nm (8=27316). 10 Anal. Calcd for C13H14N3S2CI: Theory: C, 50.07; H, 4.52; N, 13.47.

Found: C, 50.17; H, 4.51; N, 13.42.

Example 57 N-(2-Phenethvl)-N'-(5-tetrazovl) thiourea A solution of 5-aminotetrazole monohydrate (2.06 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) in N,N-dimethylformamide (50 mL) was heated to 100°C for 21 h. The reaction was cooled to room 20 temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized twice from ethyl acetate to provide 0.59 g (12%) of impure title product: mp 161-177°C; IR (KBr, cm"1) 3451, 3235, 3148, 1547, 1511, 1169, 697; !h NMR (300 MHz, DMSO-d6) 5 10.8 (s, 1H), 10.4 (m, 1H), 8.6 (br s, 1H), 7.2-7.0 (m, 5H), 3.8 (m, 2H), 2.8 (t, J=7 Hz, 2H) ; MS (FD) m/e 248 (M+); UV (EtOH) 258nm (6=13630), 234nm (6=15631), 204nm (6=15594).

X-8571A 26 0 £ Example 58 N- (2-t)hene thv 1) -N'-f2-M-methvl-5-acetvl)thiazolvll thiourea A solution of 2-phenethyl isothiocyanate (1.14 g, 7 mmol) and 2-amino-4-methyl-5-acetylthiazole (1.09 g, 7 mmol) in J7,W-dime thyl formamide (50 mL) was heated at 100°C for 23 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized twice from ethyl acetate to provide 0.21 g (9%) of the title product: IR (KBr, cm"1) 3314, 3060, 1694, 1610, 1555, 1507, 1372, 1233, 980, 667; !h NMR (300 MHz, DMSO-d6) 5 12.5 (br s, 1H), 8.8 (br s, 1H), 7.4-7.2 (m, 5H), 3.8 (m, 2H), 2.9 (t, J=7 Hz, 2H) 2.4 (s, 3H), 2.3 (s, 3H); MS (FD) m/e 319 (M+); UV (EtOH) 319nm (6=16944), 230 nm (e=13216), 201 nm (£=18476) .

Example 59 N-(2-Phenethvl)-N'-T2-(6-chloro)pvrazinvll thiourea A solution of 2-amino-6-chloropyrazine (2.59 g, 20 mmol) and 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) in J\r,W-dimethylformamide (50 mL) was heated to 100°C for 35 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue X-8571A 26 Q ? purified by HPLC on silica gel to provide 0.23 g (4%) of the title product: mp 194-195°C; IR (KBr, cm"1) 3171, 2932, 1575, 1517, 1465, 1359, 1270, 1169, 707; iH NMR (300 MHZ, DMSO-d6) 5 11.2 (s, 1H) , 10.2 (br s, 1H) , 8.5 (s, 1H), 8.3 (s, 1H), 7.4-7.2 (m, 5H) , 3.85-3.75 (m, 2H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 292 (M+); UV (EtOH) 328nm (£=12858), 265nm (£=17945), 201nm (£=17746).

Example 60 N-(2-phenbutvl)-N'-f2-thiazolvl1 thiourea A solution of 2-phenbutyl isothiocyanate (3.8 g, 20 mmol) and 2-aminothiazole (2.0 g, 20 mmol) in N,N-dimethyl-formamide (50 mL) was heated at 100°C for 26 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl ether to provide 2.3 g (39%) of the title product: mp 105-107°C IR (KBr, cm"1) 3171, 2932, 1575, 1517, 1465, 1359, 1169, 1064, 707; % NMR (300 MHz ™*0-d6) 5 11.5 (br s, 1H), 9.7 (br s, 1H), 7.4-7.1 (m, /H), 3.6 (m, 2H), 2.6 (m, 2H), 1.6 (m, 4H) ; MS (FD) m/e 291 (M+); UV (EtOH) 288nm (£=19013), 256 nm (£=10681), 203 nm (e=18908) .

X-8571A 26 0 2 Anal. Calcd for C14H17N3S2: Theory: C, 57.70; H, 5.88; N, 14.42.

Found: C, 57.60; H, 6.08; N, 14.56.

Example 61 N- (2-PhenPi-hvl) -N'- f2 - (4- (3-nitro) phenyl) thiazolvll thiourea A solution of 2-phenethy1 isothiocyanate (0.74 g, 4.5 mmol) and 2-amino-4-[(3-nitro)phenyl]-thiazole (1.0 g, 4.5 mmol) in W, JV-dimethylformamide (50 mL) was heated to 100°C for 120 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by HPLC on silica gel to provide 0.07 g (4%) of the title product: mp 192-19 6°C; IR (KBr, cm"1) 3165, 3023, 1571, 1517, 1352, 1217, 1166; % NMR (300 MHz, DMSO-d6) 5 11.7 (br s, 1H), 9.0 (br s, 1H), 8.6 (s, 1H), 8.2 (m, 2H), 7.75 (s, 1H), 7.6 (t, J=6 Hz, 1H) , 7.4-7.2 (m, 5H), 3.8 (m, 2H), 2.95 (t, J=6 Hz, 2H) ; MS (FD) m/e 384 (M+) ; UV (EtOH) 286nm (£=21349), 264nm (£=22766), 237nm (£=18307), 202nm (£=28514).

Anal. Calcd for C18H16N4S2O2: Theory: C, 56.23; H, 4.19; N, 14.57.

Found: C, 56.12; H, 4.24; N, 14.47.

X-8571A 26 0 Example 62 N-(n-Pronvl)-N'-r2-(5-chlorothiazovl) 1 thiourea A solution of 2-amino-5-chlorothiazole (2.69 g, 20 mmol) and n-propyl isothiocyanate (2.0 g, 20 mmol) in dime thyl formamide (50 mL) was heated to 100°C for 19 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by HPLC on silica gel to provide 0.17 g (4%) of the title product: mp 128-133°C; IR (KBr, cm"1) 3170, 2958, 1560, 1487, 1187, 691; !h NMR (300 MHz, DMSO-d&) 5 11.5 (br s, 1H) , 8.4 (br s, 1H), 7.4 (s 1H), 3.4 (m, 2H), 1.6 (m, 2H), 0.95 (t, J=7 Hz, 3H) ; MS (FD) m/e 235 (M+); UV (EtOH) 294nm (£=12928), 259nm (£=10257), 204nm (£=16979). Anal. Calcd for C7H10N3S2CI: Theory: C, 35.66; H, 4.28; N, 19.82.

Found: C, 35.85; H, 4.19; N, 19.78.

Example 63 N-(2-Phenethvl)-N'-f2-14-(2'.2'-dinhenvl-2'-cvano)ethvl\thiazovl1 thiouroa A solution of 2-amino(4-(2',2'-diphenyl-2'-cyano)ethyl)thiazole (0.91 g, 3 mmol) and 2-phenethyl isothiocyanate (0.49 g, 3 mmol) in N,N-dimethylformamide (50 mL) was heated to 100°C for 91 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated X-8571A 2 6 0 9 and the residue purified by HPLC on silica gel to provide 0.28 g (20%) of the title product: IR (KBr, cm"1) 3179, 3024, 2238, 1562, 1250, 698; ^ NMR (300 MHz, DMSO-d6) 5 11.5 (s, 1H) , 10.4 (br s, 1H) , 7.5-7.2 (m, 15H), 6.6 (s, 1H), 3.85 (s, 2H), 3.8 (m, 2H), 2.8 (t, J=7 Hz, 2H); MS (FD) m/e 468 (M+); UV (EtOH) 292nm (£=12023), 259nm (e=5862), 202 nm (e=25516). Anal. Calcd for C27H24N4S2: Theory: C, 69.20; H, 5.16; N, 11.95.

Found: C, 69.05; H, 5.33; N, 11.76.

Example 64 N- (2- ri-frvclohexenvll ethvl) -N1 - f2-benzothiazolvll thiourea 15 A solution of 2-(l-cyclohexenyl)ethyl isothio cyanate (3.3 g, 20 mmol) and 2-aminobenzothiazole (3.0 g, 20 mmol) in A7,W-dimeth.yl formamide (50 mL) was heated at 100°C for 17.5 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, 20 IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 2.57 g (40%) of the title product: mp 185-186°C; IR (KBr, cm"1) 3179, 3044, 2921, 2830, 1556, 1523, 1441, 1196; !h NMR (300 MHz, DMSO-d6) d 11.8 (br s, 1H), 10.2 (br s, 1H), 8.0-7.2 (m, 4H), 5.45 (s, 1H), 3.65 (m, 2H), 2.3 (t, J=7 Hz, 2H), 1.9 (m, 4H), 1.5 (m, 4H); MS (FD) m/e 317 (M+); UV (EtOH) 287nm (6=20679), 201 nm (£=25939).

X-8571A -214- V U p 0 260 Anal. Calcd for c16h19n3s2: Theory: C, 60.53; H, 6.03; N, 13.24.

Found: C, 60.29; H, 5.94; N, 13.49.

Example 65 N- (2 -phenethvl) -N' - \ 2 - (4-ethvl) thiazolvl 1 thiourea A solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol) and 2-amino-4-ethylthiazole (1.28 g, 10 mmol) in w,N-dimethylformamide (50 mL) was heated at 100°c for 23 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic- layer was concentrated and the residue recrystallized from ethyl acetate to provide 0.84 g (29%) of the title product: mp 145-146°C; IR (KBr, cm"1) 3199, 3049, 2962, 1591, 1275, 685; 3-H NMR (300 MHz, DMSO-c?6) 5 11.5 (br s, 1H) , 9.8 (br s, 1H), 7.4-7.2 (m, 5H), 6.6 (s, 1H) , 3.8 (m, 2H), 2.9 (t, J=7 Hz, 2H), 2.45 (q, J=7 Hz, 2H), 1.1 (t, J=7 Hz, 3H); MS (FD) m/e 291 (M+); UV (EtOH) 292nm (6=19382), 257 nm (£=10362), 202 nm (6=20282).

Anal. Calcd for C14H17N3S2: Theory: C, 57.70; H, 5.88; N, 14.42.

Found: C, 57.47; H, 5.91; N, 14.51.

Example 66 1-r(2-Lenzothiazolvl)thiocarbamovll imidazole A solution of 1,1'-thiocarbonyldiimidazole (8.9 g, 50 mmol) and 2-aminobenzothiazole (7.5 g, 50 mmol) in X-8571A 2 6 0 p o acetonitrile (125 mL) was stirred at room temperature for 20 h. The resulting precipitate was collected by filtration to provide 5.75 g (44%) of the title product: IR (KBr, cm"1) 3199, 3049, 2962, 1628, 1461, 738; 5 1h NMR (300 MHz, DMSO-d6) 8 8.85 (s, 1H), 8.1 (br s, 1H), 7.9-7.0 (m, 6H); MS (FD) m/e 261 (M+) ; UV (EtOH) 366nm (e=13072), 305 nm (£=11556), 213 nm (e=35893) .

Anal. Calcd for C11H8N4S2: Theory: C, 50.75; H, 3.10; N, 21.52.

Found: C, 50.50; H, 3.02; N, 21.49.

Example 67 N- 12- (2-chloronhpnvl) ethvll -N' - r2-hpn7.nthi agnlvll thiourea A solution of 1-[(2-benzothiazolyl)-thiocarbamoyl] imidazole (2.1 g, 8 mmol) and 2 — (2— chlorophenyl)-ethylamine (1.25 g, 8 mmol) in N,N-dimethylformamide (30 mL) was stirred at 100°C for 1.5 h, 20 the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 1.6 g (57%) of the title product: IR (KBr, cm-1) 3181, 3050, 1587, 1527, 1231, 753; !h NMR (300 MHz, DMSO-d6) 8 11.9 (br s, 1H), 10.0 (br s, 1H), 7.8-7.2 (m, 8H) , 3.95 (m, 2H), 3.1 (t, J=7 Hz, 2H); MS (FD) m/e 347 (M+); UV (EtOH) 301nm (e=23050), 202 nm (£=30924).

X-8571A 26 o : 0 Example 68 N-f2-(3-chlorophenyl)ethyl 1-N'-f2-benzothiazolyl1 thiourea A solution of 1-[(2-benzothiazolyl)-thiocarbamoyl] imidazole (1.04 g, 4 mmol) and 2-(3-5 chlorophenyl)ethylamine (0.63 g, 4 mmol) in N,N- dimethylformamide (15 mL) was stirred at 100°C for 1 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate*to provide 0.88 g (63%) of the title product: 10 IR (KBr, cm"1) 3180, 2997, 1569, 1527, 1209, 755; !h NMR (300 MHz, DMSO-d6) 5 11.9 (br s, 1H), 10.1 (br s, 1H), 7.8-7.2 (m, 8H), 3.9 (m, 2H), 3.0 (t, J=7 Hz, 2H); MS (FD) m/e 347 (M+) ; UV (EtOH) 301nm (£=25367), 202 nm (£=31735). 15 Anal. Calcd for C16H14N3S2CI: Theory: C, 55.24; H, 4.06; N, 12.08.

Found: C, 55.05; H, 4.05; N, 12.03.

Example 69 N- T?- (4-chlorophenvl)ethvl1-N'-f 2-benzothiazolvl1 thiourea A solution of 1-[(2-benzothiazolyl)-thiocarbamoyl] imidazole (1.04 g, 4 mmol) and 2-(4-chloropheny 1)ethylamine (0.63 g, 4 mmol) in N,N-dimethylformamide (15 mL) was stirred at 100°C for 1 h, the 25 reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 0.89 g (64%) of the title product: IR (KBr, cm-1) 3180, 2997, 1569, 1527, 1257, 755; iH NMR (300 MHz, DMSO-d6) 6 12.0 (br s, 1H), 10.0 (br s, 1H) , 7.S-7.2 (m, 8H), 3.85 (m, 2H), 2.95 (t, J=7 Hz, 2H); MS (FD) m/e 347 (M+); X-8571A -217- % 6 Qyny 1 o UV (EtOH) 301nro (8=25731), 218nm (e=29376), 202 nm (8=28033).

Anal. Calcd for C16H14N3S2CI: Theory: C, 55.24; H, 4.06; N, 12.08. 5 Found: C, 55.27; H, 4.02; N, 12.10.

Example 7Q.

N- f 2 - (2-methoxvpherrvl) athvl 1 -N' - r2-benzothiazolvn thiourea A solution of 1-[(2-benzothiazolyl)-10 thiocarbamoyl] imidazole (1.04 g, 4 mmol) and 2-(2-methoxyphenyl)ethylamine (0.62 g, 4 mmol) in N,N-dimethylformamide (15 mL) was stirred at 100°C for 1 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl 15 acetate to provide 0.9 g (66%) of the title product: IR (KBr, cm"1) 3180, 1672, 1539, 1437, 1202, 1137, 783; l-H NMR (300 MHz, DMSO-d6) 8 12.0 (br s, 1H), 10.0 (br s, 1H), 7.9-7.0 (m, 8H), 3.85 (m, 2H), 3.75 (s, 3H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 343 (M+) ; UV (EtOH) 301nm (e=25894), 218nm (£=28357), 202 nm (£=32552).

Anal. Calcd for C17H17N3OS2: Theory: C, 59.45; H, 4.99; N, 12.23. 25 Found: C, 59.70; H, 5.01; N, 11.99.

Example 71 N-r 2 - (3-methoxyphenyl)ethvll-N'-T2-benzothiazolyl1 thiourea A solution of l-[(2-benzothiazolyl)-30 thiocarbamoyl] imidazole (1.04 g, 4 mmol) and 2-(3- X-8571A -218- W 0 260 methoxyphenyl)ethyl-amine (0.62 g, 4 mmol) in N,N-dimethylformamide (15 mL) was stirred at 100°C for 1 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 0.77 g (56%) of the title product: IR (KBr, cm"1) 3180, 1670, 1543, 1479, 1205, 1136, 718; ^•H NMR (300 MHz, DMSO-d6) 5 11.9 (br s, 1H), 10.05 (br s, 1H), 7.9-6.8 (m, 8H), 3.87 (m, 2H), 3.75 (s, 3H), 2.95 (t, J=7 Hz, 2H); MS (FD) rn/e 343 (M+); UV (EtOH) 301nm (e=24893), 216nm (6=28250), 203 nm (6=33504).

Anal. Calcd for C17H17N3OS2: Theory: C, 59.45; H, 4.99; N, 12.23.

Found: C, 59.36; H, 5.02; N, 12.00.

Example 72 N-\2-(4-methoxyphenyl)ethyl!-N'-r2-benzothiazolvl! thiourea A solution of 1-[(2-benzothiazolyl)-thiocarbamoyl] imidazole (1.04 g, 4 mmol) and 2- (4— methoxyphenyl)ethylamine (0.62 g, 4 mmol) in N,N~ dimethylformamide (15 mL) was stirred at 100°C for 1 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 0.85 g (62%) of the title product: IR (KBr, cm-1) 3162, 1610, 1572, 1255, 1208, 1106, 761; !h NMR (300 MHz, DMSO-d6) 8 11.9 (br s, 1H), 10.05 (br s, 1H), 7.9-6.8 (m, 8H), 3.85 (m, 2H), 3.75 (s, 3H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 343 (M+); X-8571A -219- C, 0 (/ • 0 ^ u 26 0 UV (EtOH) 301nm (£=22113), 218nm (£-23878), 201 nm (£=28098) .

Anal. Calcd for C17H17N3OS2: Theory: C, 59.45; H, 4.99; N, 12.23. 5 Pound: C, 59.33; H, 5.06; N, 12.04.

Example 73 1-f12-r4,5-dlmethvllthiazolvl) thiocarbamc/11 imidazole A solution of l,l'-thiocarbonyldiimidazole (1.8 g, 10 mmol), 2-amino-4,5-dimethylthiazole hydrochloride (1.65 g, 10 mmol) and triethylamine (1.01 g, 10 mmol) in acetonitrile (40 mL) was stirred at room temperature for 7 h. The solvent was removed in vacuo to afford crude of the 15 title product as a yellow solid used in the next step without purification.

Example 74 N-r 2-(2-Chlorophenyl)ethvl 1 -N'-f 2-(4.5-dimethvl)thiazolvl1 thiourea A solution of 1-[(2-[4.5-dimethyl]thiazolyl) thio-carbamoyl] imidazole (10 mmol) and 2-(2-chlorophenyl)-ethylamine (1.55 g, 10 mmol) in tf,JV-dimethylformamide (30 mL) was stirred at 90°C for 1 h. The reaction was cooled 25 to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 2.1 g (65%) of the title product: IR (KBr, cm-1) 3171, 3013, 1583, 1549, 1510, 1216, 759; X-8571A 26 o ^ n ' 1 !h NMR (300 MHz, DMSO-d6) 5 11.45 (br s, 1H), 9.75 (br s, 1H), 7.5-7.2 (m, 4H), 3.85 (m, 2H), 3.05 (t, J=7 Hz, 2H), 2.2 (s, 3H), 2.05 (s, 3H); MS (FD) m/e 325 (M+); UV (EtOH) 297nm (e=9209), 257nm (e=5133), 201 nm (e=14635) .

Example 75 N-T2-(3-chloronhanvl'ethvll-N'- f 2- (4 .5-rilmethvl) thiaznl vl1 thiourea A solution of 1-[(2-[4,5-dimethyl]thiazolyl) thio-carbamoyl] imidazole (10 mmol) and 2-(3-chlorophenyl)-ethylamine: (1.55 g, 10 mmol) in N,W-dimethylformamide (30 mL) was- stirred at 90°c for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate'to provide 2.2 g (67%) of the title product: IR (KBr, cm-1) 3182, 3018, 1584, 1549, 1511, 1215, 788; NMR (300 MHz, DMSO-d6> 6 11.45 (br s, 1H), 9.8 (br S, 1H), 7.4-7.2 (m, 4H), 3.85 (m, 2H), 2.9 (t, J=7 Hz, 2H), 2.2 (s, 3H), 2.05 (s, 3H); MS (FD) m/e 325 (M+); UV (EtOH) 297nm (8=6543), 257nm (8=3650).

Anal. Calcd for C14H16N3S2CI: Theory: C, 51.60; H, 4.95; N, 12.89. iound: C, 51.73; H, 4.99; N, 13.16.

X-8571A -221- v' L. 26 o P Example 76 N-T2-(2-methoxyphenyl)ethvll-N'-T2-(4.5-dimethyl)thiazolvl) thiourea A solution of 1-[(2-[4,5-dimethyl]thiazolyl) 5 thio-carbamoyl] imidazole (47) (10 mmol) and 2-(2-methoxyphenyl)ethylamine (1.51 g, 10 mmol) in N,N-dimethylformamide (30 mL) was stirred at 90°C for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, 10 saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 1.9 g (65%) of the title product: mp 178-180°C; IR (KBr, cxiT1) 3175, 2998, 1598, 1495, 1213, 760, 707; 15 1h NMR (300 MHz, DMSO-c?6) d 11.4 (br s, 1h), 9.75 (br s, 1H), 7.25-6.8 (m, 4H), 3.8 (s, 3H), 3.78 (m, 2H), 2.87 (t, J=7 Hz, 2H), 2.2 (s, 3H), 2.05 (s, 3H); MS (FD). m/e 321 (M+) ; UV (EtOH) 297nm (e=18573), 258nm (£=10587), 202 nm 20 (£=28862).

Anal. Calca for C15H19N3OS2: Theory: C, 56.04; H, 5.96; N, 13.09.

Found: C, 56.29; H, 6.19; N, 13.27.

Example 77 n-t 2-(3-methoxyphenyl)ethvl1-n'-r2-(4.5-dimethvl)thiazolvl1 thiourea A solution of 1-[(2-[4,5-dimethyl]thiazolyl) thiocarbamoyl] imidazole (10 mmol) and 2-(3-30 methoxyphenyl)ethylamine (1.51 g, 10 mmol) in N,N- dimethylformamide (30 mL) was stirred at 90°C for 1 h. The X-8571A 260 2 9 3 reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl 5 acetate to provide 2.2 g (69%) of the title product: mp 146-148°C; IR (KBr, cm-1) 3179, 3035, 1587, 1551, 1214, 701, 682; iH NMR (300 MHz, DMSO-de) 8 11.45 (br s, 1H), 9.8 (br s, 1H), 7.25-6.8 (m, 4H), 3.8 (m, 2H), 3.75 (s, 3H), 2.85 (t, 10 J=7 Hz, 2H), 2.2 (s, 3H), 2.05 (s, 3H); MS (FD) m/e 321 (M+); UV (EtOH) 297nm (£=16992), 258nm (£=9639), 202 nm (£=27993). Anal. Calcd for C15H19N3OS2: Theory: C, 56.04; H, 5.96; N, 13.09. 15 Found: C, 56.01; H, 5.96; N, 13.30.

Example 78 N-f2 -(4-methoxyphenyl)ethvl1-N'-f2-(4.5-dimethvl)thiazolvl1 thiourea A solution of l-[(2-[4,5-dimethyl]thiazolyl) thiocarbamoyl] imidazole (10 mmol) and 2-(4-methoxyphenyl)ethylamine (1.51 g, 10 mmol) in N,N-dime thyl formamide (30 mL) was stirred at 90°C for 1 h. The reaction was cooled to room temperature, poured into ethyl 25 acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 2.2 g (69%) of the title product: mp 178-180°C; IR (KBr, cm"1) 3174, 3024, 1590, 1552, 1214, 688; X-8571A iH NMR (300 MHz, DMSO-d6) 8 11.45 (br s, 1H), 9.8 (br s, 1H), 7.2 (d, J=8 Hz, 2H), 6.85 (d, J-8 Hz, 2H) , 3.78 (m, 2H), 3.75 (s, 3H), 2.85 (t, J=7 Hz, 2H), 2.2 (s, 3H), 2.05 (s, 3H); MS (FD) m/e 321 (M+); UV (EtOH) 297nm (6=8102), 258nm (e=4813), 223 nm (e=6614).

Example 79 N- (2-nhPnPf.hvl ) -N' - (5- n-methvll iaothlazolvl) thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 5-amino-3-methylisothiazole (3.0 g, 20 mmol) in N,J7-dimethylformamide (30 mL) was heated at 100°c 24 h, the reaction was cooled to room temperature and poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 5.5 g (100%) of the title product: mp 213-216°C; IR (KBr, cm-1) 3188, 2744, 1593, 1525, 1495, 1423, 1313, 1248, 829, 777, 752, 705, 670, 522; iH NMR (300 MHz, DMSO-dg) 8 9.3 (br S, 1H), 7.4-7.2 (m, 5H), 6.85 (br s, 1H), 3.7(m, 2H), 2.9 (t, J=7 Hz, 2H), 2.45 (s, 3H); MS (FD) m/e 278 (M+); UV (EtOH) 286nm (e=12263), 247 nm (e=14257), 206 nm (£=27381).

X-8571A ^ 6 0 2 o Example BQ l-Ff2-r6-fluorolbenzothiazolyl)thiocarbamovll imidazole A solution of 1,1'-thiocarbonyldiimidazole (17.8 g, 100 mmol) and 2-amino-6-fluorobenzothiazole (16.8 g, 100 5 mmol) in acetonitrile (700 mL) was stirred at room temperature for 20 h, then at 40°C for 6 h. The resulting precipitate was collected by filtration to provide 19.5 g (70%) of the title product: IR (KBr, cm"1) 3200, 3050, 2558, 1595, 1560, 1461, 1331, 10 121., 1088, 1040, 948, 740, 648, 627; !h NMR (300 MHz, DMSO-dg) 6 12.0 (br S, 1H), 8.85 (s, 1H) , 8.1 (br s, 1H), 7.9-7.0 (m, 4H); MS (FD) rn/e 279 (M+H); UV (EtOH) 364nm (e=7372), 306 nm (£=13593), 213 nm 15 (e=31325).

Anal. Calcd for C11H7N4S2F: Theory: C, 47.47; H, 2.54; N, 20.13.

Found: C, 47.72; H, 2.66; N, 20.09.

Example 81 N- T2 - (2-rhloronhenvl)ethvl1-N'-(2-f 6-fluoro1benzothiazolyl) thiourea A solution of 1-[(2-[6-fluoro]benzothiazolyl)-thio-carbamoyl] imidazole (2.1 g, 8 mmol) and 2-(2-chloro-25 phenyl)ethylamine (1.25 g, 8 mmol) in W,N-dimethylformamide (30 mL) was stirred at 100°C for 1.5 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 1.6 g (57%) of the title product: 30 mp 188-189°C; X-8571A -225- 26 Q IR (KBr, cm-1) 3166, 3014, 1560, 1538, 1460, 1217, 1198, 853; !h NMR (300 JHz, DMSO-dQ) d 11.6 (br s, 1H), 9.8 (br s, 1H), 7.9-7.2 (m, 7H), 3.9 (m, 2H), 3.1 (t, J=7 Hz, 2H); 5 MS (FD) m/e 365 (M+); UV (EtOH) 301nm (e=22535), 216nm (£=27344), 201 nm (£=28624) .

Anal. Calcd for C16H13N3S2CIF: Theory: C, 52.53; H, 3.58; N, 11.49. 10 Found: C, 52.79; H, 3.72; N, 11.76.

Example 82 N-\2- {3-Chlorophenyl)ethvJ1-K'-(2-\6-fluoro1benzothiazolyl) thiourea A solution of 1-[(2-[6-fluoro]benzothiazolyl)- thiocarbamoyl] imidazole (2.1 g, 8 mmol; and 2-(3-chlorophenyl)ethylamine (1.25 g, 8 mmol) in W/tf-dimethyl-formamide (30 mL) *vas stirred at 100°c for 1.5 h, the reaction was cooled to room temperature and the solvent 20 removed in vacuo. The residue was crystallized from ethyl acetate to provide 1.6 g (57%) of the title product: : mp 193-194°C; IR (KBr, cm"1) 3171, 3015, 1557, 1526, 1460, 1229, 1201, 866; iH NMR (300 MHz, DMSO-d6) 11.9 (br s, 1H) , 9.9 (br S, 1H), 7.9-7.2 (m, 7H), 3.85 (m, 2H), 3.0 (t, J=7 Hz, 2H); MS (FD) m/e 365 (M+); UV (EtOH) 301nm (£=24232), 217nm (£=30020), 201 nm (£=31875) .

X-8571A -226- 2 6 Q Anal. Calcd for c16h13n3s2cif: Theory: C, 52.53; H, 3.58; N, 11.49.

Found: C, 52.50; H, 3.67; N, 11.38.

Example 83 N-[2-(4-chloronhenvl)ethvll-N'-(2-f 6-fluorolbenzothiazolyl) thiourea A solution of 1-[(2-[6-fluoro]benzothiazolyl)-thio-carbamoyl] imidazole (2.1 g, 8 mmol) and 2-(4-chloro-phenyl)ethylamine (1.25 g, 8 mmol) in N,N-dimethylformamide (30 mL) was stirred at 100°C for 1.5 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 1.6 g (57%) of the title product: : mp 217-218°C; IR (KBr, cm"1) 3168, 3033, 1559, 1532, 1491, 1462, 1230, 1143, 809; !h NMR (300 MHz, DMSO-d6) d 11.85 (br s, 1H) , 9.8 (br s, 1H), 7.9-7.2 (m, 7H), 3.85 (m, 2H), 2.95 (t, J=7 Hz, 2H); MS (FD) m/e 365 (M+); UV (EcOH) 301nm (£=24527), 220nm (£=31031).

Anal. Calcd for C16H13N3S2CIF: Theory: C, 52.53; H, 3.58; N, 11.49.

Found: C, 52.80; H, 3.70; N, 11.34.

Example 84 N-F2-(2-methoxyphenyl)ethvll-N'-(2-T6- fluorolbenzothiazolyl) thiourea A solution of 1-[(2-[6-fluoro]benzothiazolyl)-thiocarbamoyl] imidazole (2.1 g, 8 mmol) and 2-(2-methoxyphenyl )ethylamine (1.25 g, 8 mmol) in N,W-dimethylformamide y & n X-8571A -227- ** V [j (30 mL) was stirred at 100°C for 1.5 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 1.6 g (57%) of the title product: : mp 20'8-209°C; IR (KBr, cm"1) 3168, 3034, 1561, 1536, 1462, 1242, 1198, 852; XH NMR (300 MHz, DMSO-d6) d 11.85 {br s, 1H), 9.8 (br s', 1H), 7.9-7.0 (m, 7H), 3.85 (m, 2H), 3.8 (s, 3H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 361 (M+); UV (EtOH) 300nm (e=24273), 218nm (6=28369), 201 nm (£=340:J6) .

Anal. Calcd for C17H16N3OS2CF: Theory: C, 56.49; H, 4.46; N, 11.63.

Found: C, 56.56; H, 4.59; N, 11.66.

Example 85 N- f 2 - (3 -metho WDhenv] ) e thv 11-N■-(2-f 6- fluoro1benzothiazolyl) thiourea A solution of 1-[(2-[6-fluoro]benzothiazolyl)-thiocarbamoyl] imidazole (2.1 g, 8 mmol) and 2-(3-methoxy-phenyl)ethylamine (1.25 g, 8 mmol) in N,W-dimethylformamide (30 mL) was stirred at 100°C for 1.5 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 1.6 g (57%) of the title product: mp 190-192°C; IR (KBr, cm"1) 3050, 1536, 1460, 1302,1221, 1060, 674; X-8571A 260 ^-H NMR (300 MHz, DMSO-d6) d 11.9 (br s, 1H), 9.9 (br s, 1H), 7.9-7.0 (m, 7H), 3.85 (m, 2H), 3.75 (s, 3H), 2.95 (t, J=7 Hz, 2H); MS (FD) m/e 361 (M+); UV (EtOH) 301nm (£=24608), 218nm (6=28535), 201 nm (6=37337).

Anal. Calcd for C17H16N3OS2CF: Theory: C, 56.49; H, 4.46; N, 11.63.

Found: C, 56.21; H, 4.54; N, 11.40.

Example 86 N- r 2- (4-methoxyphenyl)ethyl1-N'-(2-f 6- fluoro1benzothiazolyl) thiourea A solution of l-[(2-[6-fluoro]benzothiazolyl)-th.io-carbamoyl] imidazole (54) (2.1 g, 8 mmol) and 2- (4-metho3Qr-phenyl)ethylamine (1.25 g, 8 mmol) in N,N-dimethylformamide (30 mL) was stirred at 100°C for 1.5 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 1.6 g (57%) of the title product: : mp 203 -204 .5°C; IR (KBr, cm'1) 3001, 1561, 1539, 1458, 1251, 860, 818; !h NMR (300 MHz, DMSO-d6) d 11.85 (br a, 1H), 9.85 (br s, 1H), 7.9-6.9 (m, 7H), 3.85 (m, 2H), 3.75 (s, 3H), 2.9 (t, J=7 Hz,. 2H); MS (FD) m/e 361 (M+); UV (EtOH) 301nm (£=23562), 222 nm (£=28328).

Anal. Calcd for C17H16N3OS2CF: Theory: C, 56.49; H, 4.46; N, 11.63.

Found: C, 56.70; H, 4.42; N, 11.79.

X-8571A -229- U (j 0 I".- 1 26 0 Example 87 l-f (2- f5-chloro1 thiazolvl) thiocarbamoyl 1 imidazole A solution of 1,1'-thiocarbonyldiimidazole (25 g, 140 mmol) and 2-amino-5-chlorothiazole (18.8 g, 140 mmol) in acetonitrile (300 mL) was stirred at room temperature for 23 h. The resulting precipitate was collected by filtration to provide 21.2 g (62%) of the title product: iH NMR (300 MHz, DMSO-d6) 8 9.5 (s, 1H), 8.2 (s, 1H), 7.6 (s, 1H), 7.5 (s, 1H) ; MS (FD) m/e 176 (M+-C3H3N2)• Example 88 N-f 2 -(2-chlorophenyl)ethvl1-N'-f 2-(5-chloro)thiazolvl1 thiourea A solution of l-[(2-[5-chloro]thiazolyl)thiocarbamoyl] imidazole (0.68 g, 2.8 mmol) and 2-(2-chlorophenyl ) ethylamine (0.43 g, 2.8 mmol) in N,N-dimethylformamide (15 mL) was stirred at 100°C for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 0.68 g (73%) of the title product: mp 172-174°C; IR (KBr, cm-1) 3318, 2873, 1606, 'S26, 1513, 1436, 1351, 1237, 747; !h NMR (300 MHz, DMSO-d6) 8 10.7 (br s, 1H), 8.5 (br s, 1H), 7.4 (s, 1H), 7.4-7.2 (m, 4H), 3.8 (m, 2H), 2.9 (t, J=7 Hz, 2H); X-8571A 26 Q p q - • MS (FD) m/e 331 (M+); UV (EtOH) 295nm (6=11804), 259 nm (e=10397), 202 nm (6=27067) .

Anal, "alcd for C12H11N3S2CI2: Theory: C, 43.38; H, 3.34; N, 12.65.

Found: C, 43.61; H 3.57; N, 12.57.

Example 89 N-T2-(3-chlorophenyl)ethvll-N'-r2-(5-chloro)thiazolvll thiourea A solution of 1-[(2-[5-chloro]thiazolyl)thiocarbamoyl] imidazole (1.22 g, 5 mmol) and 2-(3-chlorophenyl ) ethylamine (0.78 g, 5 mmol) in N,W-dimethylformamide (20 mL) was stirred at 100°C for 1 h. The reaction was 15 cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl ether to provide 0.9 g (54%) of the title product: mp 154-155°C; IR (KBr', cm"1) 3178, 3044, 1557, 1520, 1458, 1346, 1196, 784, 755; l-H NMR (300 MHz, DMSO-d6) 8 H-6 (br s, 1H), 8.4 (br s, 1H), 7.4 (s, 1H), 7.4-7.2 (m, 4H) , 3.7 (m, 2H), 2.8 (t, J=7 25 Hz, 2H) ; MS (FD) m/e 331 (M+); UV (EtOH) 296nm (6=14281), 259 nm (6=12090), 205 nm (6=29809) .

X-8571A' Ryamole 90 N-f2-(4-chlorophenyl)ethv!1-N'-T2-(5-chloro)thiazolvl1 thiourea A solution of 1-[ (2-[5-chloro]thiazolyl)thiocarbamoyl] imidazole (1.22 g, 5 mmol) and 2-(4-chloro-phenyl)ethylamine (0.78 g, 5 mmol) in w,N-dimethylformamide (20 mL) was stirred at 100°C for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide' 1.1 g (66%) of the title product: mp 178-180°C; IR (KBr, cm-1) 2180, ".927, 1610, 1536, 1492, 1325, 1256, 1181, 1088, 1014, 811, 747, 643, 508; XH NMR (300 MHz. DMSO-d6) 8 11.6 (br s, 1H) , 8.4 (br s, 1H), 7.4 (s, 1H), 7.32 (d, J=8 Hz, 2H), 7.22 (d, J=8 Hz, 2H), 3.7 (m, 2H), 2.8 (t, J=7 Hz, 2H); MS (FD) m/e 331 (M+); UV (EtOH) 295nm (8=13675), 259 nm (8=12330), 202 nm (£=27524).

Anal. Calcd for C12H11N3S2CI2: Theory: C, 43.38; H, 3.34; N, 12.65.

Found: C, 43.61; H, 3.46; N, 12.85.

X-8571A -232- U xj Z6 Example 91 N-(2-(1-methvl)-2-Pvrrolvlethvl)-N'-(2-thiazolvl)thiourea An isothiocyanate of 2-(2-aminoethyl)-1-methyIpyrrole was prepared according uo Ann 657, 104-107 (1962). ^-H-NMR (CDC13) 8 2.95 (t, 2H) , 3.55 (s, 1H) , 3.65 (t, 2H), 5.9-5.95 (m, 1H), 6.05 (t, 1H), 6.55 (t, 1H). This isothiocyanate was dissolved in DMF (4 ml). To this solution was added 200 mg (2 mmol) of 2-aminothiazole and the solution was heated at 100°C for about 16 h. EtOAc was added and the organic phase was washed with sat. NH4CI-solution and brine. After drying (Na2SC>4) , the product was purified on a silica gel column, using EtOAc/Hexane 1:1, as eluent. This gave almost pure titled product. Recrystallization from toluene/hexanes gave 150 mg of the titled product.

Mp: 183-184°c (dec). !h-NMR (DMSO-dg) 8 2.86 (t, 2h), 3.55 (s, 3h), 3.75 (q, 2h), 5.85-5.90 (m, 2h), 6.62 (s, 1h), 7.09 (d, 1h), 7.36 (d, 1h), 9.74 (broad s, 1h), 11.65 (broad s, 1h). 13C-NMR (DMSO-dg) 8 25.03, 33.31, A'j.92, 106.24, 106.31, 112.03, 121.55, 129.33, 136./I, 161.68, 178.25.

Example 92 N- (2-(1-Pinerazinvlethvl))-N'-(2-thiazolvl)thiourea 1.78 g Thiocarbonyldiimidazole (10 mmol) was added to a solution of 1.29 g 1-(2-aminoethyl)piperazine (10 mmol) in 5 ml methylene chloride at 0°C. The reaction mixture was warmed to room temperature, and stirred for 30 minutes. The methylene chloride was evaporated, and 40 ml dimethylformamide together with 10.01 g 2-aminothiazole were added. The mixture was stirred 17 h at 100°C. The X-8571A -233- ** V (j c 26 product was purified by chromatography on a silica gel column eluted with mixtures of methanol and chloroform. Crystallization of the salt with oxalic acid gave further purification. !h-NMR (oxalate in D2O): 2.8-3.7 ppm (m), 6.75 ppm (d), 7.1 ppm (d).

Example 93 N-12-12-rhlnro)phenethvl)-N'-(2-th iazolvl)thiourea Thiocarbonyldiimidazolide (980 mg, 5.5 mmole) was dissolved in 20 ml methylene chloride. To the solution was added dropwise 2-chlorophenethylamine (0.69 ml, 5 mmole) in 20 ml methylene chloride at 0°C. After reaction for 30 min at 0°C, it was warmed up to room temperature, and then concentrated to small volume in vacuo. To the residue was added 20 ml DMF and 2-aminothiazole (700 mg, 7 mmole). It was kept at 100°C for 3 hours.- After cooling to room temperature, it was poured into 1 N HCl solution (100 ml) and extracted with ethyl acetate (2 x 100 ml); the organic phase was washed with brine and dried over magnesium sulfate. The solution was concentrated in vacuo and separated by silica gel column chromatography. Yield = 440 mg (30%). iH-NMR (cdci3) 8 7.38-7.17 (m, 5H, ClPh, thiazol) 6.81 (d, J = 3.7 Hz, 1H, thiazole), 4,02 (q, J = 7hz, 2H, CH2NH), 3.17 (t, J = 7.1 Hz, CH2). 13C-NMR (cdci3) 8177.5 (C=S), 161 (thiazol), 137.5 (thiazol), 136.0 (ClPh), 134.1 (ClPh), 131.1 (ClPh), 129.5 (ClPh), 128.0 (ClPh) and 126.7 (ClPh) 111.1 (thiazol), 44.8 (CH2) and 32.3 (CH2).

X-8571A -234- 260 Example 94 M-(2-(2-methnxv)phenethvl!-N'-(2-thiazolvl)thiourea To a solution of 1.8 g (10 mmol) 1,1'-thiocarbonyldiimidazole in CH2CI2 (30 ml) at 0°C was added 1.46 ml (10 mmol) of 2-methoxyphenethylamine. The solution was then stirred for 1 hour. After the addition of hexane, the reaction mixture was filtered and evaporated. The residue was dissolved in DMF (8 ml) and 1.0 g (10 mmol) 2-aminothiazole (Merck) was added. The reaction mixture was 10 heated at 100°C for about 16 h. Thereafter, EtOAc and diluted HCl-solution were added. The organic phase was separated and washed with diluted HCl-solution, sat. nh4ci- rolution and water (x 2), respectively. After drying over Na2SC>4, the product was purified on a silica gel column, 15 using hexanes/EtOAc (2:1) as eluent, to give 0.77 g crude product. Recrystallization from toluene gave 0.54 g of still crude titled product. A final purification was achieved fcy the use of a AI2O3 column eluted with chci3 (containing 0.5% EtOH) as the eluent. This gave 85 mg of 20 the titled product.

Mp: 126.0-127.5°C.

^■H-NMR (cdci3) 8 3.03 (t, 2H) , 3.82 (s, 3H) , 3.96 (q, 2H) , 6.79-6.93 (m, 3H), 7.20-7.26 (m, 3H), 10.?5 (broads, 1H), 10.73 (broad s, 1H).

ISc-nmr (CDCI3) 8 29.59, 45.69, 55.19, 110.22, 110.97, 120.40, 126.75, 127.96, 130.78, 137.72, 157.62, 161.58, 177.34.

Example 95 N- (2 - (4-fluoro)nhenethvl)-N'-(2-thiazolvl)thiourea 30 In a manner analogous to Example 94, using 4- fluorophenethylamine, the titled product resulted.

X-8571A -235- n i i 4. 26 Analyses: Calculated: C 51.22, H 4.30, N 14.93. Found: C 51.0, H 4.35, N 14.8.

Mp: 124.5-126.0°C.

Ih-NMR (CDCI3) 8 3.0 (t, 3H), 4.0 (q, 3H), 6.86 (d, 1H), 7.0-7.3 (m, 5H).

^C-NMR (CDCI3) 8 34.05, 46.82, 111.35, 115.38 (d, 2C), 130.39 (d, 2C), 134.20 (d, 1C), 137.46, 161.74 (d, 1C), 161.83, 177.52.

Example 96 N- (2-(4-nitro1phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 93, using 4-nitrophenethylamine, the titled product resulted. iH-NMR (CDCI3) 8 8.17 (d, J = 8.6 Hz, 2H, C>2NPh) , 7.45 (d, J = 8.6 Hz, 2H, C^NPh), 7.21 (d, J = 3.7 Hz, 1H, thiazole), 6.84 (d, J = 3.7 Hz, 1H, thiazole), 4.01 (q, J = 5.7 Hz, 2H, CH2NH) , 3.15 (t, J = 7.2 HZ, 2H, CH2) •• 13C-NMR (CDClj + CD3OD) 8 179 (C=S), 161 (thiazole), 146.4 (02NPh) , 136.9 (thiazole), 129 (C>2NPh), 123.4 (02NPh) , 111.1 (thiazole), 45.3 (CH2), 34.3 (CH2).

Example 97 N- (2- (A-amino)phenethvl > -N ■ - ( 2-thiazolvl) thiourea The titled product was prepared by reduction of the product from Example 96 with iron and hydrochloric acid using the literature procedure (Vogel, Textbook of Practical Organic Chemistry. 4th ed., p.657, Longman 1978). ^H-NMR (CDCI3) 8 7.23 (d, J = 3.8 Hz, 1H, thiazole), 7.07 (d, J =8.3 Hz, 2H, H2NPh), 6.79 (d, J = 3.7 Hz, 1H, thiazole), 6.65 (d, J = 8.3 Hz, 2H, H2NPh), 3.91 (q, 2H, CH2NH), 2.91 (t, J = 7.1 Hz, 2H, CH2). 26 0 X-8571A -23 6- C D / J O 13C-NMR (CDCI3 + CD3OD) 8 177 (OS), 161 (thiazole), 144 (H2NPI1), 137.3 (thiazole), 129.5 (H2NPh), 128.6 (H2NPI1), 115.4 (H2NPh), 110.9 (thiazole), 46.7 (CH2), 33.6 (CH2).

Example 98 N- (2-(4-methoxy)phenethyl)-N'-(2-thiazolyl)thiourfta In a manner analogous to Example 93, using 4-methoxyphenethylamine, the titled product resulted.

^H-NMR (CDCI3) 8 7.22-7.18 (t, 3H, MeOPh and thiazole), 6.85 (d, J = 8.5 Hz, 2 H, MeOPh), 6.81 (d, J = 3.7 Hz, 1 H, thiazole), 3.94 (q, J = 7.1 Hz, 2 H, CH2NH), 3.79 (s, 3H, MeO), 2.96 (t, J = 7.1 Hz, 2H, CH2). 13C-NMR (CDCI3) 8 177.3 (C=s), 161.6 (thiazole) 158.2 (MeOPh), 137.4 (th»«uo. • >>, 130.4 (MeOPh), 129.7 (MeOPh), 15 113.8 (MeOPh), 111.I azole), 55.1 (MeO), 47.0 (CH2), 33.8 (CH2).

Examnle 99 N- (2-(4-hydroxy)phenethvl)-N'-(2-thiazolvl)thiourea 20 The titled product was prepared by treatment of the product of Example 98 with iodotrimethyl silane in dichloroethane according to literature procedure (H. Sakurai, Synthesis, p. 740, 1979) (Example 97). iH-NMR (cdci3) 8 7.22 (d, J = 3.6 Hz, 1H, thiazole), 7.14 (d, J = 8.4 Hz, 2H, HOPh), 6.81-6.77 (t, 2H, thiazole, HOPh), 3.94 (q, 2H, CH2NH2), 2.94 (t, J a 7.2 Hz, 2H, CH2). 13C-NMR (cdci3) 8 177.4 (OS), 161.4 (thiazole), 154.1 (HOPh), 13".« (thiazole), 130.5 (HOPh), 129.9 (HOPh), 115.3 (HOPh) : (thiazole), 47.1 (CH2), 33.7 (CH2).

X-8571A -237- O £ , 2 o (j 2 I Example 1QQ N-12-(4-hromn)phenethvl)-N'-(2-thiazolvl)thiaurea In a manner analogous to Example 93, using 4-bromophenethylamine, the titled product resulted. 1-H-NMR (cdci3 + cd3od) 8 7.43 (d, J = 6.4 Hz, 2 H, BrPh) , 7.22 (d, J = 3.6 Hz, 1 H, thiazole), 7.15 (d, J = 6.3 Hz, 2 H, BrPh), 6.83 (d, J = 3.7 Hz, 1 H, thiazole), 3.95 (t, J = 7.1 Hz, 2H, ch2nh), 2.94 (t, J = 7 Hz, 2H, CH2)• 13C-NMR (cdci3 + CD3OD) 8 177.5 (C=S), 161.5 (thiazole), 137.4 (thiazole), 131.5 (BrPh), ''30.5 (BrPh), 120.3 (BrPh), 111.1 (thiazole), 46.2 (CH2), 34.0 (CH2).

Example 1Q1 N-(2-(1-pjperidinvl)ethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 93, using 1-piperidinylethylamine, the titled product resulted. l-H-NMR (cdci3) 8 7.32 (d, J = 3.7 Hz, 1 H, thiazole), 6.84 (d, J = 3.7 Hz, 1H, thiazole), 3.80 (t, 2H, CH2NH), ?.62 (t, J = 6.4 Hz, 2H, CH2), 2.48 (m, 2H, pip), 1.62 (m, 2H, pip), 1.46 (m, 1H, pip). 13C-NMR (cdci3 + cd3od): 177.3 (C=S), 161 (thiazole), 137.3 (thiazole), 111.1 (thiazole), 56.1 (CH2), 54.1 (pip), 42.2 (CH2), 25.6 (pip), 24.0 (pip).

Example 1Q2 N-(2-mQrpholinoethyl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 91, using morpholinoethylamine, the title product resulted.

X-8571A -238- 26 0 a ^•H-NMR (250 MHz, CDCI3) 8 7.38 (d, 1H, CH=CH) , 6.86 (d, 1H, CH=CH), 3.82 (q, 2H, CH2-NH), 3.86-3.71 (m, 4H, CH2-0-CH2), 2.67 (t, 2H,CH2~N (ring)), 2.62-2.52 (m, 4H, CH2-N-CH2). !3c-NMR (250 MHz, CDCI3) 8 178, 163, 138, 112, 67, 57, 53, 42.

Mp: 150.5 - 151.5°C.

Example 103 1-(2-Aminothiazole)-1■-imidazole thiocarbonvl 8.90 g Thiocarbonyldiimidazole (50 mmole) and 5.0 g 2-aminothiazole (50 mmole) was added to 50 ml acetonitrile. The mixture was heated to 40°C, and stirred for 2 hours at this temperature. The mixture was cooled to 15 0°C, and the solid was filtrated off, and washed with 300 ml cold acetonitrile. The yield of pure product after drying was 9.7 g (46 mmole).

Elemental anal: Found; C=39.3, H=2.8, N=26.2; Calc: C=40.0, H=2.87, N=26.6. iH-NMR (250 MHz, DMSO) 8 8.68 (s, 1H, N=CH-N), 7.97 (s, 1H, N-CH=CH-N), 7.76 (d, 1H, S-CH=CH-N), 7.33 (d, 1H, S-CH=CH-N) , 7.08 (S, 1H, N-CH=CH-N).

Example 1Q4 N- (2- Phenethvl) -N' - f 2 - (6-hydroxy) pvridvl 1 thiourea A stirred solution of phenethyl isothiocyanate (1.63 g, 10 mmol, 1.5 mL) and 2-amino-6-hydroxypyridine (1.10 g, 10 mmol) in 27-methylpyrrolidinone (20 mL) was heated to 100°C. After 87.25 h, the reaction was cooled to 30 room temperature and poured into ethyl acetate. The organic X-8571A 26 Q « n phase was washed with water (4x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (10% ethyl 5 acetate/dichloromethane to 15% ethyl acetate), followed by trituration with ethyl acetate to provide 1.15 g of the titled product (42%) aa an off-white solid: mp 196-197°C; IR (KBr, cm"1) 2937, 1668, 1595, 1475, 1428, 1365, 1219, 10 1158, 1023; ^■H NMR (300 MHZ, DMSO-d<j) 811.49 (br S, 1H) , 10.82 (s, 1H) , .33 (s, 1H), 7.52 (t, J=7.9 Hz, 1H) , 7.25-7.14 (m, 5H), 6.53 (d, J=7.9 Hz, 1H), 6.19 (d, J=8.0 Hz, 1H), 3.80-3.73 (m, 2H), 2.92 (t, J=7.7 Hz, 2H); MS (FD) m/e 273 (M+) ; UV (EtOH) 305nm (e= 20692) , 262nm (e= 13737), 247nm (e= 18743), 203nm (e= 19201).

Anal. Calcd for C14H15N3OS: C, 61.52; H, 5.53; N, 15.37. Found: C, 61.73; H, 5.72; N, 15.57.

Example 105 N- (2-(2-naphthyl)ethyl?-N'-(2-thiazolvl)thiourea 2-Naphthalenethylamine (256 mg, 1.5 mmole) and the product from Example 103 (400 mg, 1.9 mmole) was 25 suspended in DMF (5 ml). The reaction mixture was heated to 110°C and it became a clear solution in a few minutes. After 1 hour, the reaction mixture was cooled to room temperature, and 20 ml methylene chloride was added. The organic solution was washed successively with 0.5 N HCl 30 solution (70 ml), brine (50 ml) and water (50 ml). The organic solution was dried over magnesium sulfate, and then X-8571A -240- 0 V/ dried in vacuo. The product was purified by silica gel column chromatography (chloroform/eyelohexane = 1/1 v/v) . Yield = 324 mg (69%).

^H-NMR (CDCI3) 6 7.82-7.39 (m, 7H, naph), 6.98 (d, J = 3.6 Hz, 1H, thiazol), 6.73 (d, J = 3.1 Hz, 1H, thiazol), 4.07 (q, J = 7 Hz, 2H, CH2NH), 3.28 (t, J = 7 Hz, 2H, CH2) • 13C-NMR (CDCI3+CD3OD) 6 177 (C=S), 161 (thiazol), 137 (thiazol), 134.5 (naph), 133.6 (naph), 131.7 (naph), 128.5 (naph), 127.2 (naph), 126.8 (naph), 125.9 (naph), 125.5 10 (naph), 125.2 (naph), 123.6 (naph), 110.9 (thiazol), 45.8 (CH2), 31.7 (CH).

Example 1Q6 N- (1- (4-pentenyl) -N' - {2-thiazolvl) thiourea 15 A mixture o? 4-pentenol (3.04 g, 35.3 mmole), pyridine (2.79 g, 35.3 mmole) and 25 ml diethyl ether was cooled to -60°C. Trifluoromethanesulfonic anhydride (10 g, 35.4 mmol) was added dropwise at -60°C (5 min). The reaction was heated slowly (30 min) to room temperature, 20 and the salt formed was filtered off.

The filtrate was added dropwise to a mixture of 10 ml diethyl ether and 30 ml liquid ammonia kept at ca -30°C. The ammonia was evaporated while the remaining solution was allowed to reach room temperature. The ether 25 solution was extracted with 10 ml 10 M aqueous sodium hydroxide. Distillation at atmosphere pressure gave 4-pentenylamine (2.35 g, 27.6 mmole). 0.85 g (10 mmole) of this amine was condensed with 2.1 g of the product of Example 103 using the method 30 as described in Example 105. Crystallization from a mixture of n-hexane and toluene gave pure product. (0 X-8571A -241- ^ O? ^-H-NMR (cdci3) 8 1.85 ppm (m), 2.20 ppm (m), 3.7 ppm (m), 5.0-5.15 ppm (m) , 5.75-5.95 ppm (m), 6.85 ppm (d), 7.30 ppm (d) . 13C-NMR {CDCI3) 8 177, 162, 137, 137, 116, 111, 45, 31, 28 5 ppm.

Example 107 N-(2-(3-tri fluoromethyl}phenethvl)-N'-(2-thiazolyl)thiourea In a manner analogous to Example 106, using 1-10 trifluoromethyl-3-ethanolbenzene, the titled product resulted. iH-NMR (cdci3) 8 3.0 (t, PhCH2, 2H), 4.0 (q, CH2N, 2H), 6.8 (d, thiazole, 1H), 7.2 (d, thiazole, 1H), 7.4-7.6 (mult, o, m and p, 4H).

N- (cis-3-Hexenvl) )-N'- (2-thiagolvl) thiourea In a manner analogous to Example 106, using 3-cis-hexenol, the titled product resulted. iH-NMR (cdci3) 8 7.30 (d, J = 3.9 Hz, 1 H, thiazol), 6.83 (d, J = 3.8 Hz, 1H, thiazole), 5.56 and 5.40 (m, 2H, H-C=C-H), 3.75 (q, 2H, CH2NH), 2.47 (q, 2H, CH2), 2.09 (p, 2H, CH2), 0.95 (t, J = 5.4 Hz, 3H, CH3). 13C-NMR (cdci3) 8 177 (C=S), 161 (thiazole), 137.5 (thiazole), 134.8 (C=C), 124.6 (C=C), 111.0 (thiazole), 45.4 (CH2NH), 26.3 (CH2), 20.6 (CH2), 14.1 (ch3).

X-8571A -242- t O (i ? 26 o Example 1Q9 N-(2-(1-naphthvl)ethyl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 106, using (1-naphthyl)-2-ethanol, the titled product resulted. l-H-NMR (cdci3 + cd3od) 8 8.24-7.40 (m, 7H, naph), 7.16 (d, J =3.7 Hz, 1H, thiazole), 6.80 (d, J = 3.7 Hz, 1H, thiazole), 4.10 (t, J = 7.5 Hz, 2H, CH2NH), 3.49 (t, J = 7.5 Hz, 2H, CH2).

Example 110 N-(2-(2-fluoro)-Phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 106, using 1-fluoro-2-ethanolbenzene, the titled product resulted.

^-H-NMR (CDCI3) 5 7.28-7.03 (m, 5H, thiazole, FPh) , 6.81 (d, J = 3.8 Hz, 1H, thiazole), 3.99 (q, J = 7.1 Hz, 2H, CH2NH), 3.08 (t, J = 7 Hz, 2H, CH2)• 13C-NMR {CDCI3) 8 178 (C=S), 161 (thiazole), 137.4 (thiazole), 131 (d, C-F coupling, FPh), 128 (d, C-F coupling, FPh), 124 (FPh), 115.4 (FPh), 115 (FPh), 111 (thiazole), 45.3 (CH2), 28.1 (CH2).

Examnle 111 N-(2-(2-trifluoromethvl)phenethvl)-M'-(2-thiazolvl)thiourea In a manner analogous for Example 106, using 1-trifluoromethyl-2-ethanolbenzene, the title product resulted. iH-NMR (cdci3) 8 7.66 (d, 1H, TFMPh), 7.51 (m, 2H, TFMPh), 7.34 (m, 1H, TFMPh), 7.26 (d, J = 3.6 Hz, 1H, thiazole), 6.84 (d, J = 3.8 Hz, 1H, thiazole), 3.99 (q, J = 6.3 Hz, 2H, ch2nh), 3.23 (t, J = 7.6 Hz, 2H, CH2). 26 0 ? X-8571A -243- XJ £ 13C-NMR (CDCI3) 8 177.7 (C=S), 161.5 (thiazole), 137.6 (thiazole), 136.9 (TFMPh), 131.8 (TFMPh), 131.6 (TFMPh), 129 (q, C-F coupling, CF3), 126.6 (TFMPh), 125.9 (d, TFMPh), 111.1 (thiazole), 46.3 (CH2), 31.4 (CH2).

Example 112 N-N- (3-oentvnvl)-N'-(2-thiazolvl)thiourea The starting material, 3-pentynylamine, was synthesized from 3-pentyn-l-ol. 3-Pent;ynvlanine Trifluoromethanesulfonic anhydride (4.0 ml; 23.8 mmol) was added to a solution of 3-pentyn-l-ol (2.0 g; 23.8 mmol) and pyridine (1.92 ml; 23.8 mmol) in diethyl ether (50 ml) at -45°C. The mixture was stirred for 15 min at the same temperature and filtered cold into diethyl ether (-10 ml) saturated with NH3 at -45°C with stirring. The precipitate was washed with cold diethyl ether. The reaction mixture was stirred at RT for 3 h and evaporated to give yellow crystals (2.0 g, 36 %) as a salt of 3-pentynylamine and trifluoromethane sulfonic acid.

^H-NMR (250 MHz, D20) 8 3.12 (t, 2H, CH2-NH+3), 2.55 (m, 2H, CH2-CSC) , 178 (t, 3H,CH3-CSC). 13C-NMR (250 MHz, D20) 5 126, 83, 77, 41, 20, 5.

The titled product was then prepared in a manner analogous to Example 106. iH-NMR (250 MHz, CDCI3) 87.33 (d, 1H, CH=CH) , 6.87 (d, 1H, CH=CH) , 3.86 (q, 2H, CH2-NH), 2.56 (tt, 2H, CH2-CsC), 1.81 (t, 3H,CH3-CSC). 13C-NMR (250 MHz, CDCI3) 8178, 162, 138, 111, 45, 19, 4. Mp: 118.5-119.5°C.

X-8571A -244- 260 * i Example 113 3- (2-Phenethvl) -2-thioxo-l .2.3 .4-tetrahvdrocruinazoline 2-Nitrobenzaldehyde (10.0 g, 66 mmol) arid 2-phenylethylamine (8.3 ml, 66 mmol) was dissolved in 5 acetonitrile (200 ml). pH was adjusted to 6.0 with acetic acid.

Sodium cyanoborohydride (4.15 g, 66 mol) was added in small portions. The solution was stirred 40 min. The solution was diluted with water (400 ml) and extracted 10 with ether.

Acid-base partitioning [aq. HCl, nh4oh (aq.)] and evaporation gave an oil. The oil was suspended in water (200 ml) and iron dust (10 g, 180 mmol) was added. The mixture was heated to reflux and HCl (conc. aq.) (10 15 ml) was slowly added. Reflux was continued for 40 minutes.

The solution was cooled, basified with sodium hydroxide 40 % (aq.) to pH 14. The solution was stirred with toluene (700 ml) and filtered through a pad of celite.

Acid-base partitioning [(HCl (a.q.) nh4oh (a.q.)] and evaporation afforded an oil. The oil was dissolved in acetonitrile (20 ml) and N,N-thiocarbonyldi-imidazole (0.7 g, 6.6 mmol) was added. The solution was stirred for 78 hours at ambient temperature, heated to 75°C for 40 minutes and evaporated. The residue was purified by 25 flash-chromatography on silica gel by elution with ethyl acetate-cyclohexane (1:3). The product crystallized spontaneously from the pure fractions foirming long needles. ^H-NMR (cdci3) 8 3.0 (t, PhCH2, 2H), 4.1 (t, PhCH2£H2N, 2H), 4.4 (s, PhCH2N, 2H), 6.7-7.5 (mult., CsH5, CgH4, 9H), 30 8.7 (Broad singlet NH, 1H).

X-8571A -245- ^ ® 0 2 9 3 Example 114 N- (2-Phenethvl) -N' -T2-(3-methvl)-ovridvll thiourea A stirred solution of 2-phenethyl isothiocyanate (1.63 g* 10 mmol, 1.5 mL) and 2-amino~3-methylpyridine (1.08 g, 10 mmol) in J\Hmethylpyrrolidinone (20 mL) was heated to 100°C. After 16.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with water (4x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (2% ethyl acetate/dichloromethane) to provide 1.77 g of the titled product (65%). This material was recrystallized from ethyl acetate/hexanes to provide 878 mg of the titled product as a pale yellow crystalline solid: mp 82-84°C; IR (KBr, cm"1) 3430, 2945, 1594, 1555, 1454, 1268, 1243, 1161; 1H NMR (300 MHZ, DMSO-dff) 811.62 (br s, IK), 8.66 (s, 1H) , 7.90 (d-, J=4.1 Hz, 1H), 7.59 (d, J=7.2 Hz, 1H) , 7.28-7.15 (m, 5H), 6.96 (dd, J=7.4, 5.0 Hz, 1H), 3.84-3.78 (m, 2H) , 2.89 (t, J=7.0 Hz, 2H), 2.23 (s, 3H); MS (FD) m/e 271 (M+) ; UV (EtOH) 293nm (e=17290), 265nm (e= 14634), 244nm (e= 16338), 202nm (e= 19784).

Anal. Calcd for C15H17N3S: C, 66.39; H, 6.31; N, 15.48. Found: C, 66.66; H, 6.32; N, 15.73.

Example 115 N- (2 - (2-thienvl)ethvl)-N'-(2-thiazolvl)thiourea 6.4 g 2-(2-thienyl)ethanol (50 mmoles) was dissolved in 50 ml diethyl ether together with 3.95 g pyridine (50 mmoles).

X-8571A 260 > The mixture was cooled to -30°C, and 5.7 g methanesulfonylchloride (50 mmoles) was added dropwise under stirring. The reaction mixture was then heated and kept at reflux temperature for 30 minutes. The mixture was then cooled to room temperature and filtered. The filtrate was transferred to an autoclave together with 100 ml of a solution of ammonia in methanol (saturated at 0°C). The autoclave was sealed and heated to 150°C for 17 hours. The solvent, was removed by evaporation in vacuo, and 100 ml 5 M sodium hydroxide in water was added. The mixture was extracted twice with 100 ml methylene chloride to give a solution of 2-(2-thienyl)ethylamine together with some secondary amine.

The pure primary amine was obtained by fractional crystallization from methanol of the salts with oxalic acid, followed by addition of aqueous sodium hydroxide and extraction with methylene chloride. 500 mg of the pure 2-(2-thienyl)ethylamine (3.93 mmole) was added to a solution of 800 mg thiocarbonyl-diimidazole (4.5 mmole) in 5 ml methylene chloride at 0°C. The mixture was stirred at 0°C for 15 minutes, and then 1 hour at 20°C. The solvent was removed in vacuo, and 5 ml dimethylformamide and 500 mg 2-aminothiazole was added.

This mixture was allowed to react 17 hours at 110°C. After evaporation of solvent in vacuo 100 ml ethyl acetate was added, and the mixture was heated to 50°C. The warm mixture was washed twice with 20 ml 1 M HCl, and once with 20 ml H2O. Evaporation of solvent to a small volume gave crystals of the desired product. Recrystallization twice from ethyl acetate gave 340 mg of very pure product.

X-8571A -247- ^ ® U s 13c-NMR (CDCI3 + DMSO-dg) 5 178, 162, 141, 137, 127, 125, 124, 111, 46, 29 PPM.

Ih-NMR (CDCI3 + DMSO-dg) 8 3.3 ppm (t) , 3.9 ppm (m) , 6.85 ppm (d), 6.90 ppm (m), 7.20 ppm (d), 7.25 ppm (d).

Example 116 N- (2- (2-f lurvro-fi-chlfiro) nhenethvl) -N' - (2-thiazolvl) thiourea 2-Chloro-6-fluorophenylacetonitrile (2.5 g, 14.7 mmol) was dissolved in 30 ml diethyl ether. Lithium aluminium hydride (1.5 g) was added in small portions over a period of 10 minutes. The mixture was then heated to reflux for 15 minutes. After cooling to room temperature, 1.5 ml water, 1.5 ml aqueous sodium hydroxide, and 4 ml water was added slowly. The ether solution containing the product 2-chloro-6-fluorophenethylamine was decanted off and the solvent was removed in vacuo.

The amine formed was condensed with the product of Example 103 using the method as described in Examples 104 and 105 to give 270 mg of the titled product after recrystallization from ethanol. 1h-NMR (DMSO-d6) 8 3.1 ppm (t), 3.85 ppm (m), 7.1 ppm (d), 7.15-7.30 ppm (m), 7.40 ppm (d).

Example 117 N- (2- (3-Methoxv) -Phenethvl)-N' - (2-thia7:olvl) thiourea In a manner analogous to Example 105, the product of Example 103 was condensed with 3-methoxyphenethylamine to give the titled product.

X-8571A -248- 26 0 293 -1-H-NMR (DMSO-dg) S 2.9 (t, Ph, CH2 , 2H) , 3.75 (s, OCH3, 3H), 3,9 (q, CH2N, 2H), 6.8 (mult, o and p, 4H), 7.1 (d, thiazole, 1H), 7.2 (t, m, 1H), 7.4 (d, thiazole, 1H). | 5 Example 118 N- (2-phanethv1)-N' — T 2 — f5-methvl)t vridvll thiourea A stirred solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol, 1.5 mL) and 2-amino-5-methylpyridine (1.08 g, 10 mmol) in Jtf-methylpyrrolidinone (20 mL) was 10 heated to 125°C. After 16.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with water (4x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash 15 chromatography on silica gel (2% ethyl acetate/dichloromethane) to provide 2.01 g of the titled product (74%). This material was recrystallized from ethyl acetate/hexanes to provide 1.72 g of titled product as a white crystalline solid: mp 153-154°C; IR (KBr,cm"1) 3235, 2939, 1613, 1559, 1534, 1493, 1300, 1188; ^•H NMR (300 MHZ, DMSO-d^) 5 11.56 (br S, 1H) , 10.42 (s, 1H) , 7.84 (d, J=1.3 Hz, 1H), 7.52 (dd, J=8.5, 2.1 Hz, 1H), 7.31-7.16 (m, 5H), 6.99 (d, J=8.5 Hz, 1H), 3.82-3.75 (m, 2H), 25 2.87 (t, J=7.0 Hz, 2H), 2.16 (s, 3H) ; MS (FD) m/e 271 (M+) ; UV (EtOH) 2981TO (8=14080), 268nm (£=21638), 248nm (£= 15905), 201nm (£=18504).

Anal. Calcd for C15H17N3S: C, 66.39; H, 6.31; N, 15.48. 30 Found: C, 66.33; H, 6.26; N, 15.33.

X-8571A 260 p Example 119 N-Methyl-N-(2-phenethyl)-N'-(2-thiazolyl)thiourea In a manner analogous to Example 105, the product of Example 103 was condensed with N-methyl-phenethylamine, to give the titled product. ^-NMR(DMSO-d6) 82.9 (t,PhCH2,2H) , 3.2 (s,NCH3,3H) 4.0 (t, CH2N,2H), 6.8 (d,thiazole,1H), 7.2(m, thiazole,1H), 7.3(mult.,CgH5,5H) Example 12Q N-(2-Indanvl)-N1 -(2'-thiazolvl)thiourea In a manner analogous to Example 105, the product of Example 103 was condensed with 2-indanylamine, to give the titled product. iH-NMR (DMSO-d6) 8 2.4 (q, CH2, 2H), 3.3 (q, CH2, 2H), 4.8 (q, CHN, 1H),.7.0 (d, thiazole, 1H), 7.1-7.3 (mult., C6H4, 4H), 7.4 (d, thiazole, 1H).

Example 121 N-(2- (2-Azido)-phenethvl)-N'-(2-thiazolvl)thiourea 2-Aminophenethylalcohol (Aldrich) (0.8 g, 5.8 mmol) was dissolved in 15 ml H2O at 0°C. Trifluoroacetic acid (1.2 ml) was added. Sodium nitrite (0.41 g, 0.6 mmol) dissolved in cold water (2.0 ml) was added. The solution was stirred at 0°C for 10 minutes.

Lithium azide (0.59 g, 12 mmol) in water (2.0 ml) was added slowly. The solution was brought up to ambient temperature. The solution was extracted with diethyl ether (3 x 50 ml), the organic phase was washed with 1 N HCl (aq.) (2 x 20 ml), dried with Na2SC>4, filtered and evaporated.

X-8571A -250- 26q The residue was dissolved in dichloromethane (20 ml) under a nitrogen atmosphere. The solution was cooled to -10°C and ethyldiisopropylamine (1.1 ml, 6.4 mmol) was added. 5 Trifluoromethanesulfonic anhydride (0.87 ml, .17 mmol) was added dropwise. The solution was stirred at 0° for 20 minutes and then added to a solution of NH3 (g) in methanol (50 ml sat. at 0°C) under vigouros stirring. The solution was stirred for 40 minutes at 10 ambient temperature. The solution was diluted with water (100 ml) and extracted with dichloromethane (2 x 50 ml). Acid-base partitioning [NH4OH (aq)-HCl (aq)[ and evaporation gave 2-azidophenethylamine.

In a manner analogous to Examples 104 and 15 105, the product of Example 103 was condensed with 2-azidophenethylamine, to give the titled product. l-H-NMR (DMSO-d6) S 2.9 (t, PhCH2, 2H) , 3.8 (q, CH2N, 2H), 7.0-7.4 (m, Ph-o, m, p, thiazole, 6H).

Example 122 N-(2 -(3-Fluoro)Phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 105, the product of Example 103 was condensed with 3-fluorophenethylamine to give the titled product. l-H-NMR (DMSO-d6) 8 2.9 (t, PhCH2, 2H) , 3.8 (q, CH2N, 2H), 7.0-7.4 (m, Ph-o,m,p, thiazole, 6H).

X-8571A Examole 123 M- (2- (Tteny.enesulf onamida-4-ethvl) ) -N '-(?.-thiazolvl)thiourea In a manner analogous to Example 105, the product of Example 103 was condensed with 4—(2-aminoethyDbenzenesulfonamide to give the titled product.

^-NMRtDMSO-dg) 8 3.0(t), 3.8 (m), 7.1(d), 7.35(m), 7.45(d), 7.80(d). 13C-NMR (DMSO-d6) 8 178, 162, 143, 142, 137, 129, 126, 112, 45, 34.

Examnle 124 N-(2-(3.4-Dimethoxv)phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 105, the product of Example 103 was condensed with 3,4-dimethoxyphenethylamine to give the titled product. iH-NMR (DMSO-jjg-CDCl3) 8 2.95 (t) , 3.70 (t) , 3,85 (s) , 3.90 (s), 6.80 (s), 6.90 (d), 7.40 (d).

Example 125 N- (Phenvlpronan-1 -ol-2-vl) -N' - (2-thiazolvl) r.hinurea In a manner analogous to Example 105, the product of Example 103 was condensed with norephedrine to give the titled product. iH-NMR (DMSO-d6) 8 0.95 (d), 4.25 (m) , 4.95 (d), 7.1-7.5 (m) .

X-8571A -252- 26 0 2 Example 126 N- (2-12-Pvrirlvl) ethyl) -N' - (2-thiazolvl) thiourea In a manner analogous to Example 105, the prcduct of Example 103 was condensed with 2-(2-5 aminoethyl)pyridine to give the titled product.

^•H-NMR (DMSO-d6) 6 3.1 (t), 4.0 (m), 7.1 (d) , 7.2-7.4 (m), 7.7 (m), 8.5 (d) , 9.8 (s), 11.7 (s) .

Example 127 N-(2-(2.5-Dimethoxv)phenethvl)-N'-(2-thiazolvl)thiourea In a maimer analogous to Example 105, the product of Example 103 was condensed with 2,6-dimethoxyphenethylamine to give the titled product. 1h-NMR (CDC13) 8 3.00 (t), 3.73 (s), 3.77 (s), 3.97 (m), 6.70-6.85 (m), 7.24 (d), 10.80 (s). 13C-NMR (CDCI3) 8 177, 162, 153, 152, 138, 128, 117, 112, 111, 111, 56, 56, 46, 30.

N-(1-(2-PhenylIpropanvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 105, the product of Example 103 was condensed with l-amino-2-phenylpropane to give the titled product. l-H-NMR ,(DMSO-d6) 8 1.20 <d) , 3.13 (q) , 3.70 (t) , 7.09 (d), 7.20-7.50 (m).

Broad peaks 8 8.14, 9.33, 9.75 and 10.57. 0 0 5 X-B571A -253- _ _ 0 2 6 0 2 9 J Example 129 N- 12- (3-Tndol) ethyl) -N' - (2-thiazolvl) thiourea In a manner analogous to Example 105, the product of Example 103 was condensed with tryptamine to give the titled product. iH-NMR (CDCI3 + CD3OD) 8 7.68-7.06 (m, 6H, indole, thiazole), 6.84 (d, J = 3.7 Hz, 1H, thiazole), 4.02 (t, J = 7 Hz, 2H, CH2NH), 3.16 (t, J 8 6.9 Hz, 2H, CH2). 13C-NMR (CDCI3 + CD3OD) 8 177 (thiazole), 161 (thiazole), 137 (thiazole), 136 (indole), 127 (indole), 123 (indole), 121 (indole), 118 (indole), 117 (indole), 111 (thiazole,, 110 (indole), 109 (indole), 46 (CH2), 26 (CH2).

Example 13Q N-(2-(2-hvdroxvethoxv)ethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 105, the product of Example 103 was condensed with 2—(2— aminoethoxy) ethanol to give the titled product. iH-NMR (CDC13) 8 7.34 (d, J = 3.4 Hz, 1H, thiazole), 6.84 (d, J = 3.4 Hz, 1H, thiazole), 3.96 (t, J = 4.9 Hz, 2H, CII2NH), 3.76 (m, 4H, CH2), 3.66 (t, J = 4.3 Hz, 2H, CH2) . 13C-NMR (CDCI3) 8 177.4 (C=S), 161.8 (thiazole), 137.5 (thiazole), 111.2 (thiazole), 72.1, 68.4, 61.5, 44.9.

Example 131 N- (2- (5-Nitropyrid-2-vl)aminoethvl)-N'-(2- thiazplyl)thiourea In a manner analogous to Example 105, the product of Example 103 was condensed with 2-(2- X-8571A 2 aminoethylami.no) -5-nitropyridine to give the titled product.

^H-NMR (CDCI3 + CD3OD) 8 8.95 (d, 1H, pyr), 8.12 (dd, 1H, pyr), 7.26 (d, J = 3.8 Hz, 1H, thiazole), 6.86 (d, J = 3.8 Hz, 1H, thiazole), 6.52 (d, 1H, pyr), 3.99 (t, 2H, CH2NH), 3.78 (t, 2H, CH2).

Example 132 M- (2-(l-Methvlpyrrolid-2-vl)ethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 105, the product of Example 103 was condensed with 2-(2-aminoethyl)-1-methylpyrrolidine to give the titled product. !h-NMR (CDCI3) 8 7.32 (d, J = 4 Hz, 1h, thiazole), 6.83 (d, J = 3.6 Hz, 1H, thiazole), 3.78 (q, 2H, CH2NH), 3.08 (m, 1H, NCH(CH2)2), 2.34 (s, 3H, N-CH3), 2.16 (m, 2H, NCH2), 2.01 (m, 2H, CH2), 1.7 (m, 4H, pyr). 13C-NMR (CDCI3) 8 177 (C=S), 161 (thiazole), 137.5 (thiazole), 111.1 (thiazole), 64.1 (pyr), 57.1 (pyr), 43.1 (CH2), 40.6 (CH2), 32.1 (pyr), 30.3 (pyr), 22.2 (pyr).

Example 133 N-<2-(2»4-Dichloro)phenetiw 1) -N1 -(l-thiazplvl)thiourea In a manner analogous to Lxample 105, the product of Example 103 was condensed with 2,4-dichloro-phenethylamine to give the titled product.

Ih-NMR (CDCI3 + CD3OD) 8 7.40 (d, 1h, thiazole), 7.41 (s, 1H, DClPh), 7.24 (m, 2H, DClPh), 6.87 (d, 1H, thiazole), 3.95 (t, 2H, CH2NH), 3.14 (t, 2H, CH2).

X-8571A -255- 26 o 2 Example 134 N- (1.1 - (7.-p-hvdroxvphenvl)methoxvcarbonvlethvl) -N' - (2- thiazolvl thiourea In a manner analogous to Example 105, the 5 product of Example 103 was condensed with tyrosine methylester to give the titled product.

^H-NMR (CDCI3) 5 7.25 (d, J = 3.3 Hz, 1H, thiazole), 7.02 (d, J = 8.2 Hz, 2H, Tyr), 6.82 (d, J = 3.4 Hz, 1H, ' thiazole), 6.74 (d, J = 8.2 Hz, 2H, Tyr), 5.29 (t, 1H, 10 CH), 3.73 (s, 3Ht CH3), 3.19 (d, 2H, CH2). 13C-NMR- (CDCI3) 8 177.4 (C=S), 171.5 (C02Me), 161.2 (thiazole), 155.4 (Tyr), 136.9 (thiazole), 130.0 (Tyr), 126.2 (Tyr), 115.0 (Tyr), 111.1 (thiazole), 59.0 (CH) , 51.9 (CH3), 36.4 (CH2).

Example 135 1- (2-Thiazolvl) -4- (p-hvdroxvbenzvl) -2-t.hiohvdant:oin The titled product was obtained as a by product during the preparation of the product described 20 in Example 134.

■^■H-NMR (CDCI3 + CD30D) 8 7.78 (d, 1H, thiazole), 7.50 (d, 1H, thiazole), 7.07 (d, 2H, Tyr), 6.78 (d, 2H, Tyr), 4.50 (t, 1H, CH), 3.15 (m, 2H, CH2). '25 Example 136 N-(2-trans-ohenvlcvcloproPvl)-N'-2-(thiazolvl)thiourea In a manner analogous to Example 105 the product of Example 103 was condensed with trans-2-phenylcyclopropylamine to give the titled product.

X-8571A -256- 26 0 ^-NMR (CDCI3 + CD3OD) 8 7.32 (d, J = 3.8 Hz, 1H, thiazole), 7.23 (m, 5H, Ph), 3.38 (m, 1H, CHNH), 2.27 (m, 1H, CH), 1.91 (m, 2H, CH2). 13C-NMR (CDCI3 + CD3OD) 8 179.2 (C=S), 161.7 (thiazole), 5 139.8 (Ph), 137.3 (thiazole), 128.2 (Ph), 126.5 (Ph), 126.0 (Ph), 111.2 (thiazole), 36.1 (CH), 35.1 (CH), 16.1 (CH2).

Example 137 N- (4-Methvl- 3 -npnt.snvl ) -N' - (2-thiazolvl) thiourea The starting material, 4-methyl-3-pentenyl-amine, was prepared from 5-bromo-2-methyl-2-pentene. 4-Methyl-3-pentenylamine LiN3 (1 g, 20 mmol) was added to a solution of -bromo-2-methyl-2-pentene (1.63 g, 10 mmol) in 5 ml DMF. The solution was stirred at room temperature for two days. The reaction mixture was poured into a mixture of hexanes and sat. NH4Cl-solution. The organic phase was washed with sat. NH4Cl-solution, brine and water.

After drying, the solvent was removed and the crude azide was reacted with LiAlH4 (380 mg, 10 mmol) in ether at 0°C. After 2 h the reaction was quenched by the addition of 380 fil h20, 380 (il 15 % NaOH-solution and r25 1.14 ml h20, respectively. After filtration the solvent was evaporated and the residue was distilled in vacuo to give 0.42 g of the title amine.

B.p. 50°C/40 mm. iH-NMR (CDCI3) 8 1.5 (broad s, 2H), 1.60 (d, 3H), 1.70 30 (d, 3H), 2.68 (q, 2H), 5.05-5.15 (m, 1H). 293 X-8571A -257- 26 13C-NMR (CDCI3) 8 17.70, 18.39, 25.66, 32.22, 42.03, 121.64, 133.50.

In a manner analogous to Example 105, the 5 product of Example 103 was condensed with 4-methyl-3-pentenylamine to give the titled product. Mp: 87.5-88.5°C.

Analyses: Calculated: C 49.76, H 6.26, N 17.41. Found: C 49.35, H 6.20, N 17.15.

^-H-NMR (CDCI3) 8 1.65 (s, 3H), 1.75 (s, 3H) , 2.40 (q, 2H), 3.73 (q, 2H), 5.1-5.25 (m, 1H), 6.83 (d, 1H), 7.29 (d, 1H) . 13C-NMR (CDCI3) 8 17.93, 25.88, 27.31, 45.54, 111.22, 120.40, 135.10, 137.51, 161.94, 177.21.

Example 138 N-(Trans-3-hexenvl)-N'-(2-thiazolvl)thiourea The starting material, trans-3-hexenvlamine. was prepared from trans-3-hexen-l-ol. > Trans-3-hexenYlarcine To a stirred solution of trans-3-hexen-1-ol (5.0 g, 0.050 mol), Et3N (7.65 ml, 0.055 mol) and CH2CI2 (70 ml) at -30°C was added 4.33 ml (0.055 mol) 25 methanesulfonyl chloride. The solution was stirred at about -20°C for 2 h. After addition of CH2CI2, the organic phase was washed with sat. NaHC03 solution, sat. NH4Cl-solution and water, dried (Na2SC>4) and concentrated in vacuo. This gave a crude mesylate which 30 was dissolved in DMF (30 ml) and LiN3 (5 g, 100 mmol) X-8571A -258- 26 C~) £ was added. The reaction mixture was stirred overnight and poured into a mixture of ether and brine. The ether phase was washed with brine (x 2) and dried (Na2S04>.

The ether solution was concentrated to about 100 ml arid cooled to 0°C, whereafter 1.9 g (50 mmol) of LiAlH4 was added. After 1 h the reaction was quenched with 1.9 ml H2O, 1.9 ml 15 % NaOH-solution and 5.7 ml H2O, respectively. After filtration, the solvent was evaporated and the residue was distilled in vacuo to 10 give 2.35 g of the titled amine.

B.p. 34°C/20 mm iH-NMR (CDCI3) 8 0.92-1.05 (m, 3H) , 1.75 (broad s, 2H), 1.95-2.20 (m, 4H), 2.68-2.75 (m, 2H), 5.27-5.63 (m, 2H) . 13C-NMR (CDCI3) 8 13.80, 25.55, 36.62, 41.56, 126.10, 134.48.

In a manner analogous to Example 105, the product of Example 103 was condensed with trans-3-hexenylamine to give the titled product. '20 Mp: 116. 0-117. 0°C.

Analyses: Calculated: C 49.76, H 6.26, N 17.41. Found: C 49.6, H 6.3, N 17.4. l-H-NMR (CDCI3) 8 0.98 (t, 3H) , 2.0-2.1 (m, 2H) , 2.41 (q, 2H), 3.76 (q, 2H), 5.4-5.7 (m, 2H) , 6.83 (d, 1H), 7.29 '25 (d, 1H), 10.8 (broad s, 1H), 11.35 (broad s, 1H). 13C-NMR. (cdci3) 8 13.72, 25.65, 45.42, 111.25, 124.97, 135.56, 137.50, 161.95, 177.14.

X-8571A -259- 260 293 Example 139 N- T2 - (Cvclo-2-penten-l-vl) ethvll -N' - (2- thiazolvl)thiourea The starting material 2-(cyclo-2-penten-l-5 yl)ethylamine was prepared from 2-cyclopenten-l-yl acetic acid. 2-(Cyclo-2-penten-l-y1)ethylamine 2-Cyclopenten-l-ylacetic acid (5 ml, 0.042 10 mol) was dissolved in ether (100 ml). LiAlH4 (2.4 g, 0.063 mol) was added in portions. After the addition, the reaction mixture was stirred for 2 h at room temperature. The reaction mixture was quenched with 2.4 g H2O, 2.4 g 15 % NaOH-solution and 7.2 ml H20, respectively. Filtration and evaporation of the solvent gave 4.45 g of crude 2-(cyclo-2-penten-l-yl)ethanol.

This alcohol was transformed to the title amine by a procedure analogous to Example 138. iH-NMR {CDCI3) 8 1.4-1.8 (m, 4H), 2.0-2.15 (m, 1H), 2.2- 2.4 (m, 3H), 2.6-2.8 (m, 3H), 5.6-5.8 (m, 2H). 13C-NMR (CDC13) 8 29.68, 31.78, 40.00, 40.64, 42.97, 130.29, 134.61.

In a manner analogous to Example 105, the 25 product of Example 103 was condensed with 2-(cyclop-pent en-l-y 1) ethylamine to give the titled product. Mp: 139.0-140.0°C.

Analyses: Calculated: C 52.14, H 5.97, N 16.58. Found: C 52.20, H 6.05, N 16.35.

X-8571A 26 0 ? •1-H-NMR (CDCI3) 6 1.42-1.58 (m, 1H), 1.62-1.92 (m, 2H) , 2.06-2.45 (m, 3H), 2.72-2.86 (m, 1H), 3.71-3.84 (m, 2H) , 5.70-5.80 (m, 2H), 6.85 (d, 1H), 7.32 (d, 1H), 10.9 (broad s, 1H), 10.95 (broad s, 1H). 13C-NMR (CDCI3) 8 29.71, 32.01, 34.77, 43.23, 44.31, 111.15," 131.19, 134.13, 137. 66, 161.99, 177.28.

Example 140 N- (2-(trans-3-pentenvl))-N'-(2-thiazolvl)thiourea 10 The starting material trans-3-penten-l-ol was prepared by reduction of 3-pentyn-l-ol with lithium aluminium hydride in refluxing tetrahydrofuran and the titled product was then prepared in a manner analogous to Examples 106 and 112.

^H-NMR (250 MHz > CDCI3) 8 7.28 (d, 1H, CH=CH) , 6.83 (d, 1H, CH=CH), 5.66-5.38 (m, 2H, trans-CH=CH), 3.67 (q, 2H, CH2-NH), 2.37 (q, 2H, CH2-CH=CH), 1.72 (dd, 3H, CH=CH-CH3) . 13C-NMR (250 MHZ, CDCI3) 8 177, 162, 138, 129, 127, 111, 20 46, 32, 18.

Mp: 129-129.5°C.

Anal. Calcd. for C9H]_3N3S2: C, 47.5; H, 5.7; N, 18.5. Found: C, 47.9; H, 5.8; N, 17.8.

Example 141 N- (2- (cis-3-pentenvl)) -N' - f2-th3.flsolYl) thiourea The starting material cis-3-penten-l-ol was prepared by reduction of 3-pentyn-l-ol with hydrogen in acetone at about 5 psi for 20 minutes using palladium on 30 calcium carbonate as a catalyst (Lindlar catalyst), and X-8571A the titled product was then prepared in a manner analogous to Examples 106 and 112. l-H-NMB (250 MHz, CDCI3) 87.30 (d, 1H, CH=CH), 6.83 (d, 1H, CH=CH), 5.73-5.34 (m, 2H, cis-CH=CH) , 3.76 (q, 2H, CH2-NH), 2.48 (q, 2H, CH=CH-CH2), 1.66 (d, 3H,CH=CH-CH3) . 13C-NMR (250 MHz, CDCI3) 8 177, 162, 138, 127, 126, 111, 45, 26.

Mp: 76 .5°C.

Example 142 N- (2-(2-Methvl)-phenethvl)-N'-(2-thiazolvl)thiourea The starting material 1-methylphenethanol was prepared by reduction of o-tolylacetic acid with lithium aluminium hydride in refluxing tetrahydrofuran and the titled product was then prepared analogous to Examples 106 and 112.

Mp: 143-144°C.

Example 143 N-(2-(3,4,5 -trimethoxv)phenethvl)-N'-(2- thiazolvl)thiourea The starting material 2-(3,4,5-trimethoxy)-phenethylamine was prepared by reduction of 3,4,5-trimethoxyphenylacetonitrile with cobalt chloride and sodium borohydride, according to the general method described by L.S. Heinzman in J. Am. Chem. Soc. 104. p. 5801 (1982). 3,4,5-Trimethoxybenzonitrile (965 mg, 5 mmole) and cobalt chloride (2,37 g, 10 mmole) were dissolved in methanol (70 ml). To the solution was added sodium X-8571A -262- 26 0 9 borohydride (1.89 g, 50 mmole). After 3 hours, the reaction mixture was filtered through celite, and concentrated to small volume. It was then taken up in chloroform and extracted with IN HCl (100 ml). The 5 organic phase was discarded. The aqueous solution was basified with aqueous ammonia, and extracted with chloroform. The organic phase was dried over magnesium sulfate, and dried in vacuo to yield 2-(3,4,5-trimethoxy)phenethylamine (427 mg). l-H-NMR (CDC13) 8 6.58 (s, 2H, TMPh) , 3.85 (m, 8H, 2 x MeO, CH2), 3.82 (s, 3H, OMe), 3.80 (m, 2H, CH2) .

The titled product was then prepared analogous to Example 105. !h-NMR (CDCI3) 8 7.26 (d, 1h, thiazole), 6.85 (d, 1h, thiazole), 6.64 (s, 2H, TMPh), 4.84 (d, J = 5.7 Hz, 2H, CH2NH),' 3.86 (m, 11H, CH2, MeO). 13C-NMR (CDCI3) 8 177 (C=S), 161 (thiazole), 153 (TMPh), 138 (TMPh), 137 (thiazole), 132 (TMPh), 111 (thiazole), 20 104.8 (TMPh), 61 (MeO), 56.1 (MeO), 53 (CH2), 50 (CH2).

Example 144 N-(2-(2.4-Difluoro)phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 143, using 25 2,4-difluorophenylacetonitrile, the titled product resulted. ih-nmr (CDCI3) 8 7.26 (m, 1h, DFPh), 7.20 (d, 1h, thiazole), 6.80 (d, 1H, thiazole), 6.75 (m, 2H, DFPh), 3.85 (q, 2H, CH2NH), 3.04 (t, 2H, CH2).

X-8571A -263- U V C 26 Example 145 N-. 2-(2.fi -Di fluoro)phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 143, using 2,6-difluorophenylacetonitrile, the titled product resulted. l-H-NMR (CDCI3) 8 7.23 (d, J = 3.8 Hz, 1H, thiazole), 7.26-7.12 (m, 1H, DFPh), 6.86 (m, 2H, DFPh), 6.81 (d, J = 3.6 Hz, 1H, thiazole), 3.96 (q, 2H, CH2NH), 3.11 (t, J = 7 Hz, CH2).

I3c-NMR (CDCI3) 8 177 (C=S), 164 and 159 (dd, C-F coupling, DFPh), 162 (thiazole), 137 (thiazole), 128 (m, C-F coupling, DFPh), 111 (thiazole), 110.8 (d, C-F coupling, DFPh), 44.5 (CH2), 21.6 (CH2).

Example 146 N-(2-(3.4-Methvlenedioxv)phpnethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 143, using 3,4-methylenedioxyphenylacetonitrile, the titled product resulted. iH-NMR (CDC13) 8 7.24 (d, 1H, thiazole), 6.80 (m, 3H, Ph, thiazole), 6.74 (s, 1H, Ph), 5.93 (s, 2H, 0CH2O), 3.94 (q, 2H, CH2NH), 2.93 (t, 2H, CH2). 13C-NMR (CDCI3) 8 177.3 (C=S), 161.6 (thiazole), 148 (Ph), 146 (Ph), 137.4 (thiazole), 132.1 (Ph), 111.1 (thiazole), 109.2 (Ph), 108.2 (Ph), 100.7 (0CH20), 47.0 (CH2), 34.4 (CH2). t X-8571A 2 6 0 2 9 3 Example 147 N-12-(4-Trifluoromethyl)phenethvl)-N'-f 2- thiazolvl)thiourea In a manner analogous to Example 143, using 5 4-trifluoromethylphenylacetonitrile, the titled product resulted. l-H-NMR (CDCI3 + CD3OD) 5 7.57 (d, J = 8.3 Hz, 2H, TFMPh), 7.40 (d, J = 8.3 Hz, 2H, TFMPh), 7.19 (d, J = 3.7 Hz, 1H, thiazole), 6.83 (d, J = 3.7 Hz, 1H, 10 thiazole), 3.95 (t, J = 7.2 Hz, 2H, CH2NH), 3.08 (t, 2H, CH2) .

Example 148 (RS)-N-(2-Mefchvl-2-12.6-difluoro)phenethvl)-N'-(2- thiazolyl)thiourea 2,6-Difluorobenzyl cyanide (1.24 ml, 10 mmole) was reacted with sodium hydride (360 mg, 12 mmole) in THF (5 ml) for 2 hour. Then iodomethane was added to the reaction mixture. After 30 min, the 20 reaction mixture was worked up and the product was isolated by silica gel column chromatography. Yield 985 mg (59 %) .

^H-NMR (CDCI3) 8 (Mixture of two stereoisomers) 7.28 (m, 1H, DFPh), 6.98 (m, 2H, DFPh), 4.26 (m, 1H, CH), 1.69 25 and 1.66 (2 x s, 3H, CH3).

In a manner analogous to Example 143, using 2-methyl-2-(2,6-difluoro)phenethylamine, the titled product resulted.

X-8571A -265- 26 o ?. 9 7 ^H-NMR (CDCI3) 8 R and S stereomixture), 7.12 (m, 2H, DFPh, thiazole), 6.85 (t, 2H, DFPh), 6.77, 6.76, 6.75, 6.74 (2d, J = 3.6 Hz, 1H, thiazole), 4.11 (m, 1H, CH), 4.05-3.65 (m, 2Hf CH2), 1.45, 1.42, (2s, 3H, CH3).

Example 149 N-(2-17-Bromo)-phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 143, using 2-bromophenylacetonitrile, the titled product resulted. iH-NMR (DMSO-dg) 8 2.9 (t, PhCH2, 2H) , 3.05 (t, PhCH2, 2H), 3.8 (q, CH2N, 2H), 7.1 (d, thiazole, 1H), 7.15-7.6 (mult, o, m, p, thiazole, 5H).

Example 150 H-(2-(l-Phenyl-l-cyclopropane)ethyl)-N'-<2-thiasQlvl)thiourea In a manner analogous to Example 116, using 1-phenyl-l-cyclopropanecarbonitrile, the titled product resulted.

Ih-NMR (CDCI3) 8 1.0 (d), 3.8(d), 6.9 (d), 7.2 -7.4 (m), 7.9, 9.5 (nh).

Example 151 N-(2-(2.6-Dimethoxv)phenethvl)-N'-(2-thiazolvl)thiourea The starting material 2,6-dimethoxy-phenethylamine was prepared from 2,6-dimethoxy-benzaldehyde. Reaction with nitromethane according to the procedure described in Vogel, Textbook of Practical Organic Chemistry, p. 176 (Longman 1978, 4th Ed.) yielded 2,6-dimethoxy-fi-nitrostyrene. This comound (1.1 X-8571A -266- g g ^ g, 5.3 mmole) was dissolved in diethyl ether/tetrahydrofuran (2:1, 200 ml) and lithium aluminium hydride (0.5 g, 13 mmol) was added in small portions. The mixture was refluxed for 120 minutes and then treated with 0.6 ml H2O, 0.6 ml 15 % NaOH (aq) and 1.8 ml H2O. The mixture was filtered and purified by acid-base partitioning (NH4OH (aq) HCl dil. (aq)) and evaporated. The crude product 2,6-dimethoxyphenethylamine was pure enough to be used directly in the following reaction where it was condensed with the product of Example 103, in a manner analogous to Example 105, to give the titled product. ^-H-NMR (DMSO-dg) 8 2.9 (t, PhCH2, 2H) , 3,7 (q, CH2N, 2H), 3.8 (s, OCH3, 6H), 6.7 (d, o, 2H), 7.1 (d, thiazole, 1H), 7.2 (t, p, 1H), 7.3 (d, thiazole, 1H)).

Example 152 N-(2-(3.5-Dimethoxv)phenethvl)-N'-(thiazolvl)thiourea In a manner analogous to Example 151 the product of Example 103 was condensed with 3,5-dimethoxyphenethylamine, obtained from 3,5-dimethoxybenzaldehyde, to result in the titled product. 3-H-NMR (DMSO-dg) 8 2.8 (t, PhCH2, 2H) , 3.65 (a, uCh3 , 6H), 3.7 (q, CH2N, 2H) , 6.3 (t, p, 1H) , 6.4 (t. o, 2H), 7.1 (d, thiazole, 1H), 7.3 (d, thiazole, 1H).

Example 153 N-(2-(3.5-Dichloro)phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 151, the product of Example 103 was condensed with 3,5- X-8571A dichlorophenethylamine, obtained from 3,5-dichlorobenzaldehyde.

^H-NMR (DMSO-dg) 8 2.9 (t, PhCH2, 2H) , 3.8 (q, CH2N, 2H), 7.1 (d, thiazole, 1H), 7.3 (mult, o and p, 3H), 7.4 (d, thiazole, 1H).

Example 154 N- (2-(2.5-Dichloro-6-hvdroxv)phenethvl)-N' - (2-thiazolvl)thiourea In a manner analogous to Example 151, the product of Example 103 was condensed with 2,5-dichloro-6-hydroxyphenethylamine, obtained from 2,5-dichloro-6-hydroxybenzaldehyde.

^•H-NMR (CDC13) 8 3.0 (t, PhCH2, 2H) , 3.9 (q, CH2N, 2H) , 6.9 (d, o, 1H) ,• 7.1 (d, thiazole, 1H) , 7.2 (d, p, 1H), 7.3 (d, thiazole, 1H).

Example 155 N-(2.3.6-Tri chloro)phenethvl) -N'-(2-thiazolvl)thiourea In a manner analogous to Example 151, the product of Example 103, was condensed with 2,3,6-trichlorophenethylamine, obtained from 2,3,6-trichlorobenzaldehyde. iH-NMR (DMSO-dg) 8 3.3 (t, PhCH2, 2H) , 3.4 (q, CH2N, 2H), 7.1 (d, thiazole, 1H), 7.4 (d, thiazole, 1H), 7.5-7.5 (mult., m and p, 2H).

X-8571A Example 156 N-(2-(2.3.4-Trifluoro)phenethvl)-N'-(2-thiazolvl) thiourea In a manner analogous to Example 151, the product of Example 103 was condensed with 2,3,4-trifluorophenethylamine, obtained from 2,3,4-trifluorobenzaldehyde, to result in the titled product. 1H-NMR (CDCI3) 8 3.0 (t, PhCH2, 2H), 4.0 (q, CH2N, 2H), 6.8 (d, thiazole, 2H), 6.85-7.0 (mult., m and o, 2H), 7.2 (d, thiazole, 1H).

Example 157 N-(2-(2.3.5-Trichloro)phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 151, the product of Example 103 was condensed with 2,3,5-trichlorophenethylamine, obtained from 2,3,5-trichlorobenzaldehyde. iH-NMR (DMSO-dg) 8 3.05 (t, PhCH2, 2H) , 3.9 (q, CH2N, 2H), 7.1 (d, thiazol^ 1H), 7.4 (d, thiazole, 1H), 7.5 (d, o, 1H) , 7.7 (d, p, 1H) .

Example 158 N-(2-(2.4-Dimethoxv)phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 151, the product of Example 103 was condensed with 2,4-dimetho:xy-phenethylamine, obtained from 2,4-dimethoxybenzaldehyde. • 5 X-8571A -269- 26 0 2 •^-H-NMR (CDCI3 + CD3OD) 6 7.23 (d, J = 3.6 Hz, 1H, thiazole), 7.10 (d, J = 7.8 Hz, 1H, DMPh), 6.81 (d, 3.6 Hz, 1H, thiazole), 6.44 (s, 1H, DMPh), 6.42 (d, 1H, DMPh), 3.87 (t, 2H, CH2NH), 3.80 (s, 3H, OMe), 3.79 (s, 3H, OMe), 2.94 (t, 2H, CH2)• 13C-NMR (CDCI3 + CD3OD) 6 177.3 (C=S), 161.6 (thiazole), 159.7 (DMPh), 158.4 (DMPh), 137.5 (thiazole), 130.9 (DMPh) / 119.1 (DMPh), 110.9 (thiazole), 103.8 (DMPh), 99.3 (DMPh), 55.3 (OMe), 55.1 (OMe), 45.5 (CH2), 28.7 (CH2).

Example 159 N-(2-(2.3-Dimethoxv)Phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 151, the product of Example 103 was condensed with 2,3-dimethoxy-phenethylamine, obtained from 2,3-dimethoxybenzaldehyde. ^H-NMR (CDCI3) 8 7.23 (d, J = 3.7 Hz, 1H, thiazole), 7.02-6.83 (m, 3H, DMPh), 6.79 (d, J = 3.6 Hz, 1H, thiazole), 3.99 (q, J = 8.9 Hz, 2H, CH2NH), 3.87 (s, 3H, OMe), 3.86 (s, 3H, OMe), 3.05 (t, 2H, CH2). 13C-NMR (CDCI3) 8 177.3 (C=S), 161.6 (thiazole), 152.6 (DMPh), 147.3 (DMPh), 137.3 (thiazole), 132 (DMPh), 123.7 (DMPh), 122.2 (DMPh), 110.9 (thiazole), 110.8 (DMPh), 60.6 (OMe), 55.5 (OMe), 45.8 (CH2), 28.9 (CH2)• Example 16Q N- (2- (2.3.5. 6-Tet-.raf luoro) phenethvl) -N' - (2- thiasolvl)thiourea In a manner analogous to Example 151, the product of Example 103, was condensed with 2,3,5,6- X-8571A -270- 0 ft ri A 0 2 9 3 tetrafluorophenethylamine, obtained from 2,3,5,6-tetrafluorobenzaldehyde. iH-NMR (CDC13 + CD3OD) 8 7.24 (d, J = 3 Hz, 1H, tiiiazole), 6.98 (m, H-F coupling, 1H, TFPh), 6.83 (d, J 5 = 3 Hz, 1H, thiazole), 3.99 (t, J = 6.8 Hz, 2H, CH2NH), 3.18 (t, J = 6.9 Hz, 2H, CH2)• 13C-NMR(CDC13) 8 178.2(C=S), 161.5(thiazole), 147.6(m,TFPh), 143.6(m,TFPh), 137.3(thiazole), 117.6(t,TFPh), 111.1(thiazole), 104.3 It,TFPh), 10 53.3(CH2), 43.7(CH2).

Bxamnle 161 N- (2-12-Mefhoxv-5-bromo)phenethvl) -N' - (2-thiazolvl)thiourea 15 In a manner analogous to Example 151, the product of Example 103 was condensed with 2-methoxy-5-bromophenethylamine, obtained from 2-methoxy-5-bromobenzaldehyde. l-H-NMR (CDCI3) 8 7.34 (m, 3H, MBPh and thiazole), 6.81 (d, J = 3.6 Hz, 1H, thiazole), 6.72 (d, J = 8.4 Hz, 1H, MBPh), 3.95 (q, 2H, CH2NH), 3.79 (s, 3H, OMe), 2.98 (t, J = 6.8 Hz, 2H, CH2)• Examnle 162 '25 N- (2 - (2-Ethoxv)Phenethvl)-N'- (2-t-hiazolvl) thiourea In a manner analogous to Example 151, the product of Example 103, was condensed with 2-ethoxyphenethylamine, obtained from 2-ethoxy-benzaldehyde.

X-8571A iH-NMR (250MHz, CDCI3) 8 7.37-7.16 (m, 2H, arom.), 7.22 (d, 1H, CH=CH), 6.91-6.78 (m, 2H, arom), 6.78 (d, 1H, CH=CH), 4.07-3.93 (2xq, 2x2H, CH2-NH, CH2-0), 3.04 (t, 2H, Ph-CH2), 1.42 (t, 3H, OCH2CH3). 13C-NMR (250 MHz, CDCI3) 8 178, 162, 157, 138, 131, 128, 127, 120, 111. Ill, 63, 46, 30, 15.

Mp: 140°C.

Anal. Calcd. for Ci4Hi7N30S2: C, 54.6; H, 5.5; N, 13.7. Found: C, 54.4; H, 5.6; N, 13.3: Example 163 N-(2-(2.3-Dichloro)phenethvl)-N'-(2-thiazolvl)thiourea In a manner analogous to Example 151, the product of Example 103 was condensed with 2,3-dichloro-phenethylamine, obtained from 2,3-dichlorobenzaldehyde. iH-NMR (250 MHZ, DMSO) 8 7.55 (d, 1H, CH=CH), 7.42-7.32 (m, JH, arom), 7.12 (d, 1H, CH=CH), 3.86 (q, 2H, CH2-NH), 3.12 (t, 2H, Ph-CH2). 13C-NMR (250 MHz, DMSO) 8 178, 162, 138, 130, 129, 128, 112, 44, 33.

Example 164 N-T2-(4-chlorophenyl)ethvl1-M'-r2-(4 . 5-dimethvl)hhiazolvll A solution of 1-[(2-[4,5-dimcthyl]thiazolyl) thiocarbamoyl] imidazole (10 mmol) and 2- (4-chlorophenyl)ethylamine (1.55 10 mmol) in N,N-dimethylformamide (30 mL) was stirred at 90°C for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer X-8571A -272- 2 6 0 2 9 ,? was concentrated and the residue recrystallized fro.1 ethyl acetate, to provide 2.44 g (75%) of the titled product.

IR (KBr, cm"1) 3170, 3024, 1550, 1510, 1260, 1212, 708; l-H NMR (300 MHz, DMSO-d6) 8 11.45 (br s, 1H) , 9.8 (br s, 1H), 7.35 (d, J=8 Hz, 2H), 7.3 (d, J=8 Hz, 2H), 3.8 (m, 2H), 2.85 (t, J=7 Hz, 2H) , 2.2 (s, 3H), 2.05 (s, 3H); MS (FD) m/e 326 (M+); UV (EtOH) 297nm (e=17467), 257nm (e=10021), 219nm (e=16075, 201nm (e=22380)).

Anal. Calcd for C14H16N3S2CI: Theory: C, 51.60; H, 4.95; N, 12.89.

Found: C, 51.70; H, 5.07; N, 13.08.

Example 165 1-r (2 -naothon. 21 fchiagnlvl) thiocarbamoyl 1 imidazole A solution of 1,11-thiocarbonyldiimidazole (1.8 g, 20 mmol) and 2-aminonaptho[1,2]thiazole (2.0 g, 20 mmol) in acetonitrile (150 mL) was stirred at 65°C for 24 h. The resulting precipitate was collected by filtration to 20 provide 1.69 g (46%) of the titled product.

IR (KBr, cm"1) 3148, 2670, 1465, 706; !h NMR (300MHZ, DMSO-d6) 8 9.2 (n, 1H) 8.85 (s, 1H), 8.65 (d, J=8 HZ, 1H) , )8.2 (br S, 1H) , 8.0-7.3 (m, 5H) ; MS (FD). m/e 309 (M+-H); UV (EtOH) 383nm (e=8297), 244 nm (e=15160), 226 nm (6=17126) .

Anal. Calcd for C15H10N4S2: Theory: C, 58.04; H, 3.25; N, 18.05.

Found: C, 58.13; H, 3.21; N, 18.03.

X-8571A -273- U (J 0 26 Q p I Example 166 N-r 2-phenv1efchv11-M'-r 2-naptho f1.21thiazolvl1 thiourea A solution of l-[(2-naptho[1,2]thiazolyl)-thiocarbamoyl] imidazole (1.6 g, 5 mmol) and 2-5 phenylethylamine (0.62 g, 5.2 mmol) in N,N- dimethylformamide (20 mL) was stirred at 90°C for 1 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 1.5 g (82%) of the titled product: 10 IR (KBr, cm"1) 3171, 3027, 1581, 1521, 1213, 695; iH NMR (300 MHz, DMSO-d6) 6 11.7 (br s, 1H), 9.9 (br s, 1H), 8.25 (d, J=8 Hz, 1H), 8.0 (d, J=8 Hz, 2H), 7.8 (d, J=8 Hz, 1H), 7.6-7.2 (m, 7H), 3.95 (m, 2H), 3.05 (t, J=7 Hz, 2H) ; MS (FD) - m/e 364- (M+) ; UV (EtOH) 340nm (8=23922), 325nm (8=19262), 313nm (e=20808), 245nm (8=39665), 209 nm (e=36141).

Anal. Calcd for C20H17N3S2: Theory: C, 66.09; H, 4.71; N, 11.56. 20 Found: C, 65.86; H, 4.84; N, 11.48.

Example 167 l~n2-f 4-methyl! thiazolvl) thiocarbamoyl 1 imidazole A solution of 1,1'-thiocarbonyldiimidazole 25 (13.37 g, 75 mmol) and 2-amino-4-methylthiazole (8.55 g, 75 mmol) in acetonitrile (150 mL) was stirred at room temperature for 24 h. The resulting precipitate was collected by filtration to provide 14.22 g (85%) of the titled product: IR (KBr1, cm"1) 3179, 2558, 1455, 1217, 737; X-8571A 260 2 9 !h NMR (300 MHz, DMSO-dg) 8 8-55 (s, 1H) 7.9 (s, 1H), 7.05 (s, 1H), ), 6.9 (S, 1H), 2.3 (S, 3H); MS (FD) m/e 224 (M+-H); UV (EtOH) 359nm (6=10749), 291 nm (6=8720), 202 nm (6=20498).

Anal. Calcd for C8H8N4S2: Theory: C, 42.84; H, 3.59; N, 24.98.

Found: C, 42.90; H, 3.54; N, 24.89.

Example 168 N-(2-r1-cvclohexenvl1ethvl)-N'-\2 -(4-methvl)thiazolvl1 A solution of 1-[(2-[4-methyl]thiazolyl) thiocarbamoyl] imidazole (2.24 g, 10 mmol) and 2-(l-cyclohexenyl)ethylamine (1.25 g, 10 mmol) in N,N-dimethylformamide (25 mL) was stirred at 90°C for 4 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 2.4 g (86%) of the titled product: IR (KBr-, cm-1) 3177, 2918, 1565, 1505, 1202, 717; iH NMR (300 MHz, DMSO-d6) 6 11.55 (br s, 1H) , 9.85 (br s, 1H), 6.65 (s, 1H), 5.45 (s, 1H), 3.65 (m, 2H), 2.25 (m, 5H) , 1.9 (m, 4H), 1.55 (m, 4H); MS (FD) m/e 281 (M+); UV (EtOH) 291nm (6=19178), 257nm (6=9837), 201 nm (6=16247). Anal. Calcd for C13H19N3S2: Theory: C, 55.48; H, 6.80; N, 14.93.

Found: C, 55.40; H, 6.82; N, 14.77. • s X-8571A -275- w U ? 260 93 N-r 2-(2-ehlorophenvl)ethvl1-N'-T 2-(4-methvl)thiazolvl1 thiourea A solution of 1-[(2-[4-methyl]thiazolyl) thiocarbamoyl] imidazole (2.24 g, 10 mmol) and 2-(2-chlorophenyl)ethylamine (1.56 g, 10 mmol) in N,N-dimethylformamide (25 mL) was stirred at 90°C for 1.5 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate' to provide 2.4 g (77%) of the titled product: IR (KBr, cm"1) 3163, 3012, 1584, 1214, 754, 706; !h NMR (300 MHz, DMSO-d6> 8 11.6 (br s, 1H), 9.8 (br s, 1H), 7.5-7.2 (m, 4H), 6.65 (s, 1H) , 3.85 (m, 2H) , 3.05 (t, J=7 Hz, 2H), 2.2 (s, 3H); MS (FD) m/e 311 (M+); UV (EtOH) 292nm (e=18641), 257nm (e=10471), 202 nm (6=24729) .

Anal. Calcd for C13H14N3S2CI: Theory: C, 50.07; H, 4.52; N, 13.47.

Found: C, 49.99; H, 4.56; N, 13.45.

Example 17Q N-f2-(3-chlorophenyl)ethvll-N'-\2-(4-methvl)thiazolvl1 thiourea A solution of 1-[(2-[4-methyl]thiazolyl) thiocarbamoyl] imidazole (2.24 g, 10 mmol) and 2-(3-chlorophenyl)ethylamine (1.56 g, 10 mmol) in N,N-dimethylformamide (25 mL) was stirred at 90°C for 1.5 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 2.67 g (86%) of the titled product: X-8571A -276- * 6 £• * 9 IR (KBr, cm"1) 3171, 3016, 1581, 1214, 761, 713; XH NMR (300 MHz, DMSO-c?6) 8 11.6 (br s, 1H) , 9.85 (br s, 1H), 7.4-7.2 (m, 4H), 6.65 (s, 1H), 3.85 (m, 2H), 2.95 (t, J=7 Hz, 2H), 2.2 (S, 3H); MS (FD) m/e 311 (M+); UV (EtOH) 293nm (£=18976), 257nm (6=10523), 202 nm (6=27048).

Anal. Calcd for C13H14N3S2CI: Theory: C, 50.07; H, 4.52; N, 13.47. 10 Found: C, 49.94; H, 4.48; N, 13.37.

Example 171 N-f 2-(4-chlorophenyl)ethvl1-N'-T 2-(4-methvl)thiazolvl1 thiourea A solution of 1-f(2-[4-methyl]thiazolyl) thiocarbamoyl] imidazole (2.24 g, 10 mmol) and 2 —{4— chlorophenyl)ethylamine (1.56 g, 10 mmol) in N,N-dimethylformamide (25 mL) was stirred at 90°C for 1.5 h, the reaction was cooled to room temperature and the solvent 20 removed in vacuo. The residue was crystallized from ethyl acetate to provide 2.52 g (81%) of the titled product: IR (KBr, cm"1) 3170, 3022, 1562, 1215, 744, 709; iH NMR (300 MHz, DMSO-d6) 8 11.6 (br s, 1H), 9.85 (br s, 1H), 7.38 (d, J=8 Hz,, 2H), 7.30 (d, J=8 Hz,, 2H), 6.65 (s, 25 1H), 3.8 (m, 2H), 2.9 (t, J=7 Hz, 2H), 2.18 (s, 3H); MS (FD) m/e 311 (M+); UV (EtOH) 292nm (6=16470), 257nm (e=9506), 219nm (6=13695), 201 nm (e=20563) .

X-8571A -277- 2 6 0 2 9 3 Anal. Calcd for C13H14N3S2CI: Theory: C, 50.07; H, 4.52; N, 13.47.

Found: C, 49.94; H, 4.55; N, 13.58.

Example 172 N- r2 - (2-methoxyphenyl) ethvl 1 -N' - T 2- (4-methvl) thiazolvl 1 thiourea A solution of 1-[(2-[4-methyl]thiazolyl) thiocarbamoyl] imidazole(2.24 g, 10 mmol) and 2-(2-10 methoxyphenyl)ethylamine (1.51 g, 10 mmol) in N,N- dimethylformamide (25 mL) was stirred at 90°C for 2 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 2.2 g (73%) of the titled product: 15 IR (KBr, cr !) "3173, 3024, 1568, 1246, 1206, 750, 694; !h NMR (300 MHz, DMSO-d6) 5 11.55 (br s, 1H), 9.85 (br s, 1H), 7.2-6.8 (m, 4H), 6.65 (s, 1H), 3.75 (m, 5H), 2.9 (t, J=7 Hz, 2H), 2.18 (S, 3H); MS (FD) m/e 307 (M+); UV (EtOH) 291nm (8=18637), 259nm (e=10786), 202 nm (e=25565).

Anal. Calcd for C14H17N3OS2: Theory: C, 54.70; H, 5.57; N, 13.67.

Found: C, 54.68; H, 5.50; N, 13.46.

Example 173 N-f 2-(3-methoxyphenyl)ethvll-N'-[2-(4-methvl)thlazolvll thiourea A solution of 1-[ (2-[4-methyl]thiazolyl) 30 thiocarbamoyl] imidazole(2.24 g, 10 mmol) and 2-(3-methoxyphenyl)ethylamine (1.51 g, 10 mmol) in N,N- X-8571A 260 dimethylformamide (25 mL) was stirred at 90°C for 3.5 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 2.73 g (89%) of the titled product: IR (KBr, cm"1) 3170, 3029, 1586, 1213, 749, 691; !h NMR (300 MHz, DMSO-d6) 8 11.55 (br s, 1H), 9.9 (br s, 1H), 7.2-6.8 (m, 4H), 6.65 (s, 1H), 3.8 (m, 2H), 3.72 (s, 3H), 2.85 (t, J=7 Hz, 2H), 2.18 (s, 3H); MS (FD) m/e 307 (M+); UV (EtOH) 292nm (8=16935), 258nm (e=9604), 202 nm (E=27197). Anal. Calcd for C14H17N3OS2: Theory: C, 54.70; H, 5.57; N, 13.67.

Found: C, 54.97; H, 5.58; N, 13.60.

Example 174 N-r 2-(4-methoxypheny1)ethvl1-N'-f 2-(4-methvl)thiazolvl1 thiourea A solution of 1-[(2-[4-methyl]thiazolyl) thiocarbamoyl] imidazole (2.24 g, 10 mmol) and 2-(4-methoxyphenyl)ethylamine (1.51 g, 10 mmol) in N,N-dime thyl formamide (25 mL) was stirred at 90°C for 3 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 2.35 g (76%) of the titled product: IR (KBr, cm"1) 3171, 3009, 1565, 1511, 1218, 720, 514; 3-H NMR (300 MHz, DMSO-d6) 8 11.55 (br s, 1H), 9.9 (br s, 1H), 7.2 (d, J=8 Hz, 2H), 6.9 (d, J=8 Hz, 2H), 6.65 (s, 1H), 3.8 (m, 2H), 3.75 (s, 3H), 2.85 (t, J=7 Hz, 2H), 2.18 (s, 3H); MS (FD) m/e 307 (M+); X-8571A 2 6 0 p o 7 UV (EtOH) 292nm (e=18700), 258nm (8=11165), 223nm (e=14043), 201 nm (8=25520).

Anal. Calcd for C14H17N3OS2: Theory: C, 54.70; H, 5.57; N, 13.67. 5 Found: C, 54.62; H, 5.55; N, 13.69.

Example 175 N-f 2 -lA-methvlohenv1)ethvl1-M■-f 2-(4-methvl)thiazolvl1 thiourea A solution of 2-(4-methylphenyl)ethyl isothiocyanate (1.0 g, 5.64 mmol) and 2-amino-4-methylthiazole (0.644 g, 5.64 mmol) in N,N-dime thyl formamide (20 mL) was heated to 90°C for 24 h. The solvent was removed in vacuo. The resultant solid was 15 recrystallized from ethyl acetate to provide 0.67 g (41%) of the titled product as a white solid: IR (KBr, cm"1) 3170, 3020, 1562, 1507, 1203, 986; 1H NMR (300 MHZ, DMSO-d6) 8 11.55 (br s, 1H), 9.9 (br s, 1H), 7.18 (d, J=8 Hz, 2H), 7.18 (d, J=8 Hz, 2H), 6.65 (s, 20 1H), 3.8 (m, 2H), 2.85 (t, J=7 Hz, 2H), 2.26 (s, 3H), 2.18 (S, 3H)? MS (FD) m/e 291 (M+); UV (EtOH) 292nm (8=18863), 257nm (8=10889), 202 nm (8=21164).

Anal. Calcd for C14H17N3S2: Theory: C, 57.70; H, 5.88; N, 14.42.

Found: C, 57.83; H, 5.90; N, 14.36.

X-8571A 260 2 9 Example 176 N- f 2- (2-methoxyphenyl)ethvl1-N'-f 2-(5-chloro)thiazolvl1 thiourea A solution of 1-[(2-[5-chloro]thiazolyl)-thiocarbamoyl] imidazole (1.22 g, 5.0 mmol) and 2-(2-methoxyphenyl)ethylamine (0.77 g, 5.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90°C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 0.86 g (53%) of the titled product: mp 152-156°C; IR (KBr, cm-1) 3313, 2835, 1608, 1527, 1514, 1441, 1352, 1244, 1040; !h NMR (300 MHz, DMSO-c?6) 5 11.55 (br s, 1H), 8.4 (br s, 1H), 7.4 (s, 1H), 7.2-6.8 (m, 4H), 3.74 (s, 3H) , 3.68 (m, 2H), 2.8 (t, J=7 Hz, 2H); MS (FD) m/e 327 (M+); UV (EtOH) 295nm (£=14366), 261 nm (£=12558), 203 nm (£=31267) .

Example 177 N- f 2 - (3-methoxyphenyl) ethyl 1 -N' - T2 - (5-chloro) thiazjlyll thiourea A solution of 1-[ (2-[5-chloro]thiazolyl)-thiocarbamoyl] imidazole (1.22 g, 5.0 mmol) and 2-(3-methoxyphenyl)ethylamine (0.77 g, 5.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90°C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, X-8571A 26 0 p saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 0.86 g (53%) of the titled product: mp 106-107°C; IR (KBr, cm*"!) 3334, 2826, 1611, 1517, 1332, 1259, 1156, 1051, 777; !h NMR (300 MHz, DMSO-d6) 8 11.6 (br s, 1H), 8.4 (br s, 1H), 7.4 (s, 1H), 7.18 (m, lH), 6.77 (m, 3H), 3.7 (m, 5H), 2.8 (t, J=7 Hz, 2H) ; MS (FD) m/e 327 (M+) ; UV (EtOH) 295nm (e=13695), 260 nm (£=11987), 203 nm (£=32295).

Anal. Calcd for C13H14N3OS2CI: Theory: C, 47.63; H, 4.30; N, 12.81.

Found: C, 47.75; H, 4.41; N, 12.65.

Example 178 N-T2-(4-methoxypheny1)ethvl1-N'-T2-(5-chloro)thiazolvl1 thiourea A solution of 1-[(2-[5-chloro]thiazolyl)-thiocarbamoyl] imidazole (1.22 g, 5.0 mmol) and 2-(4-methoxyphenyl)ethylamine (0.77 g, 5.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90°C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate' to provide 1.2 g (74%) of the titled product: mp 156-158°C; IR (KBr, cm-1) 3315, 2934, 1601, 1511, 1320, 1243, 1180, 1034, 745; X-8571A 263 !h NMR (300 MHz, DMSO-d6) 8 11.6 (br s, 1H), 8.4 (br s, 1H), 7.4 (s, 1H), 7.1 (d, J=8 Hz, 2H), 6.8 (d, J=8 Hz, 2H), 3.67 (s, 3H) , 3.63 (m, 2H), 2.7 (t, J=7 Hz, 2H); MS (FD) m/e 327 (M+); UV (EtOH) 295mr, (8=13569), 260 nm (8=12490), 223 nm (e=18432), 202 nm (8=28264).

Anal. Calcd for C13H14N3OS2CI: Theory: C, 47.63; H, 4.30; N, 12.81.

Found: C, 47.59? H, 4.34; N, 12.53.

Example 179 N-r 2-(1-cvclohexenvl)ethvl 1 -N'-f 2-(5-chloro)thiazolvlT thiourea A solution of 1-[(2-[5-chloro]thiazolyl)-thiocarbamoyl] imidazole (1.22 g, 5.0 mmol) and 2-(1-cyclohexenyl)ethylamine (0.645 g, 5.0 mmol) in N,N-dimethylformamide (20 mL) was etirred at 90°C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from methylene chloride to provide 0.83 g (55%) of the titled product: mp 145-147 °C; IR (KBr, cm"1) 3167, 2929, 1564, 1488, 1230, 1183, 1098, 1030, 685; !h NMR (300 MHz, DMSO-d6) 8 11.6 (br s, 1H) , 8.4 (br s, 1H), 7.4 (s, 1H), 5.4 (s, 1H), 3.5 (m, 2H), 2.15 (t, J=7 Hz, 2H), 1.9 (m, 4H), 1.5 (m, 4H); MS (FD) m/e 301 (M+); X-8571A 2 6 0 2 9 3 UV (EtOH) 295nm (e=14231), 259 nm (6=11275), 204 nm (6=20953).

Anal. Calcd for C12H16N3S2CI: Theory: C, 47.75? H, 5.34? N, 13.92. 5 Found: C, 47.90? H, 5.47? N, 14.21.

Example 180 5-Benzvl-3-nhpnvl-2-thiohvdantnin A solution of DL-phenylalanine (1.65 g, 10 10 mmol), methyl N-phenyldithiocarbamate (1.85 g, 10 mmol), and triethylamine (1.4 mL, 10 mmol) in ethanol (30 mL) was heated at reflux for 5 h, the mixture was cooled to room temperature and the solvent removed in vacuo. The residue was dissolved in ethyl acetate, washed with IN aqueous HCl 15 and water. The organic layer was concentrated and the residue recrystallized form ethanol to provide 2.48 g (88%) of the titled product: mp 187-189°C? MS (FD) m/e 282 (M+).

Example 181 1-f(2-f5-bromo1 thiazolvl)thiocarbamoyl1 imidazole A solution of 1,1'-thiocarbonyldiimidazole (9.9 g, 50 mmol) and 2-amino-5-bromothiazole (8.95 g, 50 mmol) 25 in acetonitrile (200 mL) was stirred at 50°C for 24 h. The resulting precipitate was collected by filtration to provide 5.38 g (37%) of the titled product: iH NMR (300 MHz, DMSO-d6) 6 9.3 (s, 1H) , 8.25 (s, 1H) , 7.63 (s, 1H), 7.43 (s, 1H) ; MS (FD) m/e 288, 290 (M+).

X-8571A Exanrole 182 N-[2-(2-chloroohenvl1ethvl1-N■-f 2-(5-bromo)thiazolvl1 thiourea A solution of 1-[ (2-[5-bromo]thiazolyl)-thiocarbamoyl] imidazole (0.72 g, 2.5 mmol) and 2 —(2 — chlorophenyl)ethylamine (0.40 g, 2.5 mmol) in N,N-dimethylformamide (15 mL) was stirred at 100 °c for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by chromatography on silica gel to provide 0.06 g (5%) of the titled product: IR (KBr, cm"1) 3318, 2926, 1562, 1512, 1257, 1177, 1052, 749, 687; l-E NMR (300 MHZ, DMSO-d6) 8 11.6 (br s, 1H) , 8.4 (br S, 1H), 7.4-7.0 (m, 5H), 3.8 (m, 2H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 375, 377 (M+); UV (EtOH) 291nm (6=15522), 258 nm (6=11594), 202 nm (6=28572).

Example 183 N-r 2-(3-chloronhenv1)ethvl1-N'-f 2-(5-bromo)thiazolvl 1 thiourea A solution of 1-[ (2-[5-bromo]thiazolyl)-thiocarbamoyl] imidazole (0.72 g, 2.5 mmol) and 2-(3-chlorophenyl)ethylamine (0.40 g, 2.5 mmol) in N,N-dimethylformamide (15 mL) was stirred at 100°C fc±.- 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by chromatography X-8571A 2 6 0 2 9 on silica gel to provide 0.36 g (38%) of the titled product: mp 141-145 °C; IR (KBr, cm"1) 3168, 3019, 1568, 1514, 1331, 1251, 1189, 5 787, 686; XH NMR (300 MHz, DMSO-d6> 8 11.6 (br s, 1H), 8.4 (br s, 1H), 7.44 (s, 1H), 7.4-7.2 (m, 4H), 3.7 (m, 2H), 2.8 (t, J=7 Hz, 2H); MS (FD) m/e 377, 379 (M+); UV (EtOH) 296nm (6=10140), 259 nm (6=8392), 201 nm (6=23984).

Example 184 N-T 2-(4-chlorophenyl)ethvll-N'-f2-(5-bromo)thiazolvll thiourea A solution of 1-[(2-[5-bromo]thiazolyl)-thiocarbamoyl] imidazole (0.72 g, 2.5 mmol) and 2-(4-chlorophenyl)ethylamine (0.40 g, 2.5 mmol) in N,N-dimethylformamide (15 mL) was stirred at 100°C for 1 h. 20 The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by chromatography on silica gel to provide 0.32 g (34%) of the titled 25 product: mp 147-150°C; IR (KBr, cm"1) 3170, 3020, 1608, 1507, 1348, 1180, 745, 642; XH NMR (300 MHz, DMSO-d6) 8 11.6 (br s, 1H), 8.4 (br s, 30 1H), 7.44 (s, 1H), 7.3 (d, J=8 Hz, 2H), 7.2 (d, J=8 Hz, 2H), 3.7 (m, 2H), 2.8 (t, J=7 Hz, 2H); X-8571A 26 0 A 0 MS (FD) m/e 377, 379 (M+); UV (EtOH) 296nm (e=14604), 259 nm (e=12656), 201 nm (6=28845).

Example 185 N-f 2 -(2-methoxyphenyl)ethvl1-N'-f 2-(5-bromo)thiazolvl1 thiourea A solution of 1-[(2-[5-bromo]thiazolyl)-thiocarbamoyl] imidazole (0.72 g, 2.5 mmol) and 2-(2-10 methoxyphenyl)ethylamine (0.41 g, 2.5 mmol) in N,N- dimethylformamide (15 mL) was stirred at 100 °C for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer 15 was concentrated and the residue purified by chromatography on silica gel to provide 0.38 g (41%) of the titled product: IR (KBr, cm"1) 3164, 2960, 1563, 1513, 1241, 1182, 1030, 757, 682; !h NMR (300 MHz, DMSO-d6) 8 11.6 (br s, 1H), 8.4 (br s, 1H), 7.43 (s, 1H), 7.4-7.0 (m, 4H), 3.73 (s, 3H), 3.7 (m, 2H) , 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 371, 373 (M+); UV (EtOH) 291nm (e=16746), 261 nm (£=13112), 202 nm 25 (6=31492).

X-8571A 260 29 Example 186 N- r 2 - (3 -methoxyphenyl) ethvl 1 -N1 - \ 2- (5-brome) thiazolvl 1 thiourea A solution of 1-[(2-[5-bromo]thiazolyl)-5 thiocarbamoyl] imidazole (0.72 g, 2.5 mmol) and 2-(3-methoxyphenyl)ethylamine (0.41 g, 2.5 mmol) in N,N-dimethylformamide (15 mL) was stirred at 100°C for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, 10 saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by chromatography on silica gel to provide 0.53 g (57%) of the titled product1: IR (KBr, cm"1) 3174, 1558, 1510, 1339, 1238, 1175, 1041, 15 785, 688; !h NMR (300 MHz, DMSO-c?6) 8 11.6 (br S, 1H), 8.4 (br s, 1H), 7.44 (s, 1H), 7.3-6.8 (m, 4H), 3.7 (s, 3H), 3.7 (m, 2H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 371, 373 (M+); UV (EtOH) 294nm (£=15068), 260 nm (e=12248), 202 nm (£=35594).

Example 187 N-r 2 -(4-methoxyphenyl)ethvl1-N'-f 2-(5-hromo)thiazolvl1 thiourea A solution of 1-[(2-[5-bromo]thiazolyl)-thiocarbamoyl] imidazole (0.72 g, 2.5 mmol) and 2-(3-methoxyfchenyl)ethylamine (0.41 g, 2.5 mmol) in N,N-dimethylformamide (15 mL) was stirred at 100°C for 1 h. The 30 reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, X-8571A 2 6 0 p a i.WI saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by chromatography on silica gel to provide 0.42 g (45%) of the titled product': IR (KBr, cm"1) 3170, 1558, 1512, 1343, 1246, 1163, 1082, 824; XH NMR (300 MHz, BMS0-d6) 8 11.6 (br s, 1H), 8.4 (br s, 1H), 7.44 (s, 1H), 7.1 (d, 0=8 Hz, 2H), 6.8 (d, J=8 Hz, 2H), 3.67 (s, 3H), 3.63 (m, 2H), 2.9 (t, J=7 Hz, 2H); 10 MS (FD) m/e 371, 373 (M+); UV (EtOH) 295nm (£=15314), 260 nm (e=13349), 222 nm (£=19619), 202 nm (£=30379).

Example 188 N- r 2 - (l-rrvclohexenvl) ethvl 1 -N' - f 2 - (5-hromo) thiazolvl 1 thiourea A solution of l-[(2-[5-bromo]thiazolyl)-thiocarbamoyl] imidazole (0.72 g, 2.5 mmol) and 2-(l-cyclohexenyl)ethylamine (0.32 g, 2.5 mmol) in N,N-20 dimethylformamide (15 mL) was stirred at 100°C for 1 h.

The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from 25 methylene chloride to provide 0.157 g (18%) of the titled product: IR (KBr, cm-1) 3170, 2928, 1559, 1510, 1478, 1344, 1228, 1182, 1096, 834; XH NMR (300 MHz, DMSO-dg) 8 H-6 (br s, 1H), 8.3 (br s, 30 1H), 7.4 (s, 1H), 5.4 (s, 1H), 3.5 (m, 2H), 2.15 (t, J=7 Hz, 2H) , 1.9 (m, 4H) , 1.5 (m, 4H); 2 6 0 2 - ku X-8571A -289- MS (FD) m/e 345, 347 (M+) ; UV (EtOH) 295nm (8=15533), 259 nm (e=11792), 201nm (£=21261).

Anal. Calcd for Ci2Hi6N3S2Br: ^ 5 Theory: C, 41.62; H, 4.66; N, 12.13.

Found: C, 41.87; H, 4.91; N, 12.21.

Example 189 N- f2 - (1-CvrlnhevenvT ) ehhvll -N1 - f2- (5-hrnmr)) nvririvl 1 thiourea A stirred solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10 mmol) and 2-amino-5-bromopyridine (1.73 g, 10 mmol) in W-methylpyrrolidinone (20 mL) was heated to 100°C. After 17 h, the reaction was 15 cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, water (2x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl 20 acetate to provide 1.08 g of the titled product (32%) as an off-white crystalline solid: mp 166-167°C; IR (KBr, cm"*) 3159, 2927, 1595, 1561, 1531, 1475, 1310, 1228, 1092; NMR (300 MHZ, DMSO-dg) 8ll.09 (br s, 1H),-10.64 (s, 1H), 8.20 (d, J=2.4 Hz, 1H), 7.93 (dd, 25 J=8.9, 2.4 Hz, 1H), 7.09 (d, J=9.0 Hz, 1H), 5.47 (s, 1H), 3.62-3.58 (m, 2H), 2.19 (t, J=6.7 Hz, 2H), 2.00-1.90 (m, 4H), 1.55-1.44 (ra, 4H); MS (FD) m/e 339 (M+), 341 (M+2); UV (EtOH) 305nm (e= 14037), 274nm (©=25281).

Anal. Calcd for Ci4Hi8BrN3S: C, 49.42; H, 5.33; N, 12.35. 30 Found: C, 49.22; H, 5.28; N, 12.32.

X-8571A *60-03 Example 190 N- (2-Phenethvl )-N' - f 2- (4-methvl) pvridvl 1 thiourea A stirred solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol, 1.5 mL) and 2-amino-4-methylpyridine 5 (1.08 g, 10 mmol) in N-methylpyrrolidinone (20 mL) was heated to 100°C. After 16.75 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, water (3x) and brine. The organic layer was dried over sodium sulfate, 10 filtered and concentrated. The solid obtained was purified by recrystallization from ethyl acetate/hexanes to provide 1.69 g of the titled product (62%) as a white crystalline solid: mp 151-153°C? IR (KBr, cm"1) 3225, 1616, 1534, 1486, 1313, 1192, 1037; 1H NMR (300 MHZ, DMSO-d$> 811.72 (br s, 1H) , 10.42 (s, 1H) , 7.87 (d, J=5.3 Hz, 1H), 7.31-7.15 (m, 5H), 6.88 (s, 1H), 6.80 (d, J=5.2 Hz, 1H), 3.81-3.76 (m, 2H), 2.88 (t, J=7.0 Hz, 2H) , 2.20 (s, 3H) ; MS (FD.V m/e 271 (M+) ; 20 UV (EtOH) 290nm (£=15080), 266nm (£=15528), 247nm (£= 13132), 202nm (£=21819).

Anal. Calcd for C15H17N3S: C, 66.38; H, 6.31; N, 15.48. Found: C, 66.09; H, 6.34; N, 15.71.

Example 191 N-(2-Phenethvl)—W-f2-t4.fi-dimethyl)pvridvl1 thiourea A stirred solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol, 1.5 mL) and 2-amino-4,6-dimethylpyridine (1.22 g, 10 mmol) in W-methylpyrrolidinone (20 mL) was 30 heated to 100°C. After 16 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic 2 X-8571A -291- C 0 0 9 ( phase was washed with IN hydrochloric acid, water (3x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl acetate/hexanes to provide 1.81 g of the titled product (63%) as an off-white crystalline solid: mp 165-167°C; IR (KBr, cm-1) 3219, 1618, 1543, 1342, 1215; ^■H NMR (300 MHZ, DMSO-dff) 8 11.83 (br s, 1H) , 10.35 (s, 1H) , 7.25-7.16 (m, 5H), 6.69 (s, 1H), 6.63 (s, 1H), 3.88-3.82 (m, 2H), 2.89 (t, J=6.8 Hz, 2H), 2.14 (s, 3H), 2.09 (s, 3H); MS (FD) m/e 285 (M+); UV (EtOH) 294nm (£=17405), 266nm (£=15904), 247nm (e= 14348), 203niri (£=23896).

Anal. Calcd for C16H19N3S: C, 67.33; H, 6.71; N, 14.72. Found: C, 67.11; H, 6.63; N, 14.71.

Example 192 N-(2-PhfinPthvl)-N'-f2-(3-hydroxy)pvridvll thiourea A stirred solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol, 1.5 mL) and 2-amino-3-hydroxypyridine (1.10 g, 10 mmol) in W-methylpyrrolidinone (20 mL) was heated to 100°C. After 65.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, water (3x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (5% ethyl acetate/dichloromethane to 10% ethyl acetate) to provide 1.51 g of the titled product (55%). This material was recrystallized from ethyl acetate to provide 1.05 g of the titled product as an off-white crystalline solid: X-8571A 2 6 v.? 9 3 mp 168-169°C; IR (KBr, cm"1) 3377, 1613, 1561, 1534, 1347, 1288, 1152; ^■H NMR (300 MHZ, DMSO-dff) 611.43 (br s, 1H) , 10.94 (s, 1H) , 8.32 (s, 1H), 7.54-7.52 (m, 1H), 7.28-7.14 (m, 6H), 6.90-5 6.86 (m, 1H), 3.84-3.77 (m, 2H), 2.90 (t, J=7.0 Hz, 2H); MS (FD) m/e 273 (M+); UV (EtOH) 309nm (e= 17349), 261nm (e= 11851), 245nm (e= 17252), 204nm (e= 23596).

Anal. Calcd for C14H15N3OS: C, 61.51; H, 5.53; N, 15.37. 10 Found: C, 61.46; H, 5.52; N, 15.35.

Example 193 N-r2-(2-Methoxyphenyl)ethv!1-N'-f2-(5-bromo)pvridvll thiourea A stirred solution of N-(thioimidazoyl)—2 —(2 — methoxyphenyl)ethyl amine (2.61 g, 10 mmol) and 2-amino-5-bromopyridine (1.73 g, 10 mmol) in N,N-dimethylformamide (25 mL) was heated to 90°C. After 65 h, the reaction was cooled to room temperature and poured into ethyl acetate. 20 The organic phase was washed with IN hydrochloric acid (2x), water (2x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl acetate to provide 1.78 g of the titled product (49%) as an 25 off-white crystalline solid: mp 147-148°C; IR (KBr, cm"1) 3224, 1596, 1530, 1492, 1459, 1229, 1191, 1038; X-8571A -293- 2 f) 0 NMR (300 MHZ, DMSO-dff) 8 11.10 (br S, 1H) , 10.63 (s, 1H) , 8.11 (d', J=2.3 Hz, 1H) , 7.90 (dd, J=8.9, 2.6 Hz, 1H) , 7.21-7.16 (m, 2H), 7.06 (d, J=8.9 Hz, 1H), 6.94-6.83 (m, 2H), 3.78-3.73 (m, 2H) , 3.72 (s, 3H), 2.86 (t, J=6.8 Hz, 2H) ; MS (FD) m/e 365 (M+), 367 (M+2); UV (EtOH) 305nm (fi= 13279), 274nm (£=26971), 202nm (e= 28527).

Anal. Calcd for Ci5Hi6BrN30S: C, 49.19; H, 4.40; N, 11.47. Found: C, 48.97; H, 4.36; N, 11.66.

Example 194 N-r 2-(2-Chlorophenyl)ethvl1-N'-\2-(5-bromo)pvridv11 thiourea A stirred solution of N-(thioimidazoyl)-2- (2-chlorophenyl)ethyl amine (2.65 g, 10 mmol) and 2-amino-5-bromopyridine (1.73 g, 10 mmol) in JV,N-dimethylformamide (20 mL)'was heated to 90°C. After 64.75 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with water (4x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl acetate/hexaines to provide 1.52 g of the titled product (41%) as a tan crystalline solid: mp 160-161°C; IR (KBr, cm"1) 3220, 1594, 1562, 1534, 1474, 1338, 1222, 1165, 1088; X-8571A -294- 26 a *H NMR (300 MHZ, DMSO-dg) 811.16 (br s, 1H) , 10.69 (s, 1H) , 8.15 (d, J=2.2 Hz, 1H), 7.93 (dd, J=8.9, 2.4 Hz, 1H), 7.41-7.38 (m, 2H), 7.28-7.23 (m, 2H), 7.08 (d, J=8.9 Hz, 1H), 3.86-3.80 (m, 2H), 3.04 (t, J=6.9 Hz, 2H); MS (FD) m/e 369 (M+), 371 (M+2); UV (EtOH) 306nm (e= 14321), 275nra (e=24813), 257nm (£= 16728), 201nm (e= 27700).

Anal. Calcd for Ci4Hi3BrClN3S: C, 45.36; H, 3.53; N, 11.33. Found: C, 45.13; H, 3.60; N, 11.17.

Example 195 N- (2-Phenpthvl) -N' - f2- (4-n-propvl) thiazolvl 1 thiourea A stirred solution of 2-phenethyl isothiocyanate (1.38 g, 8.44 mmol, 1.26 mL) and 2-amino-4-n-propylthiazole (1.2 g, 8.44 mmol) in N-methylpyrrolidinone (20 mL) was heated to 100°C. After 17 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl acetate/hexanes to provide 1.39 g of the titled product (54%) as a yellow crystalline solid: mp 135-137°C; IR (KBr, cm-1) 3175, 3027, 1562, 1529, 1507, 1216; iH NMR (300 MHZ, DMSO-dg) 811.50 (br s, 1H) , 9.93 (br s, 1H), 7.29-7.15 (m, 5H), 6.60 (s, 1H), 3.79-3.73 (m, 2H) , 2.85 (t, J=6.9 Hz, 2H), 2.40 (t, J=7.4 Hz, 2H), 1.53-1.41 (m, 2H), 0.82 (t, J=7.3 Hz, 3H) ; MS (FD) m/e 305 (M+); X-8571A 26 0 2 Uo UV (EtOH) 292iun (£=19216), 257nm (£= 10283), 202nm (6= 20314) .

Anal. Calcd for C15H19H3S2: C, 58.98; H, 6.27; N, 13.76. Found: C, 59.17; H, 6.08; N, 13.55.

Example 196 N- (2-Phenethv 1) -N' -T2 - (3. 5-dir.hloro)nvridvn thiourea A stirred solution ef 2-phenethyl isothiocyanate (1.63 g, 10 mmol, 1.5 mL) and 2-amino-3,5-dichloropyridine (3.26 g, 20 mmol) in W-methylpyrrolidinone (20 mL) was heated to 125°C. After 16.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with water (5x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (20% hexanes/dichloromethane) and then recrystallized from ethyl acetate/hexanes to provide 581 mg of the titled product (18%) as a white crystalline solid: mp 102-104°C; IR (KBr, cm"1) 3409, 3040, 1560, 1508, 1429, 1147, 1057; 2H NMR (300 MHZ, DMSO-dg) 810.66 (S, 1H) , 8.71 (s, 1H) , 8.27 (d, J=2.2 Hz, 1H), 8.12 (d, J=2.2 Hz, 1H), 7.32-7.19 (m, 5H), 3.82-3.76 (m, 2H), 2.90 (t, J=7.1 Hz, 2H); MS (FD) m/e 325 (M+), 327 (M+2); UV (EtOH) 311nm (6=8820), 276nm (£=16571), 257nm (£= 13676), 203nm (£=19245).

Anal. Calcd for C14H13CI2N3S: C, 51.54; H, 4.02; N, 12.88. Found: C, 51.32; H, 4.12; N, 12.69.

X-8571A sxample 197 N-(2-Phenethvl)-N1 -f 2-(4-n-butvl)thiazolvl1 thiourea A stirred solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol, 1.5 mL) and 2-amino-4-n-butylthiazole (1.56 g, 10 mmol) in N-methylpyrrolidinone (20 mL) was heated to 100°C. After 16.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl acetate/hexanes to provide 1.63 g of the titled product (51%) as a yellow crystalline solid: mp 100-102°C; IR (KBr, cm-1) 3027, 1560, 1529, 1262, 1212; XH NMR (300 MHZ, DMSO-dg) 811.52 (br s, 1H) , 9.89 (br s, 1H), 7.29-7.15 (m, 5H), 6.59 (s, 1H), 3.79-3.73 (m, 2H), 2.86 (t, J=6.9 Hz, 2H), 2.45-2.40 (m, 2H), 1.50-1.40 (m, 2H), 1.29-1.19 (m, 2H), 0.84 (t, J=7.3 Hz, 3H); MS (FD) m/e 319 (M+); UV (EtOH) 292nm (e= 19193), 258nm (e= 10262), 203nm (e= 20024).

Anal. Calcd for C3.6H21N3S2: C, 60.15; H, 6.62; N, 13.15. Found: C, 59.86; H, 6.62; N, 12.99.

Example 198 N-T 2-(l-Cvclohexenvl)ethvl1-N'-f 2-(4-n-nronvl)thiazolvl1 thiourea A stirred solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10 mmol) and 2-amino-4-n-propylthiazole (1.42 g, 10 mmol) in JV-methylpyrrolidinone X-8571A 2 6 0 ° o - - • 1 *-' (20 mL) was heated to 100°C. After 40.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x) and brine. The organic layer was dried 5 over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl acetate/hexanes to provide 1.26 g of the titled product (41%) as a yellow crystalline solid: mp 152-153°C; IR (KBr, cm"1) 3175, 2930, 1561, 1529, 1507, 1203; iH NMR (300 MHZ, DMSO-dg) 811.49 (br s, 1H) , 9.90 (br s, 1H), 6.63 (s, 1H), 5.42 (s, 1H), 3.60-3.54 (m, 2H), 2.49-2.45 (m, 2H), 2.16 (t, J=6.5 Hz, 2H), 1.95-1.88 (m, 4H), 1.60-1.43 (m, 6H), 0.84 (t, J=7.3 Hz, 3H); MS (FD) m/e 309 (M+); UV (EtOH) 292nm, 257nm, 201nm.

Anal. Calcd for C15H23N3S2: C, 58.21; H, 7.49; N, 13.58. Found: C, 58.29; H, 7.58; N, 13.37.

Example 199 N- T 2- (1 -Cvcilohexenvl) ethvl 1 -N' - \ 2 - (4 -n-butvl) thiazolvl 1 thiourea A stirred solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10 mmol) and 2-amino-4-n-25 butylthiazole (1.56 g, 10 mmol) in tf-methylpyrrolidinone (20 mL) was heated to 100°C. After 18 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x) and brine. The organic layer was dried 30 over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl X-8571A -298- ~ v*7 u'l 2 6 0 acetate/hexanes to provide 1.02 g of the titled product (32%) as a yellow crystalline solid: mp 92-94°C; IR (KBr, cm"1) 3174, 2927, 1583, 1532, 1507, 1466, 1203; XH NMR (300 MHZ, DMSO-dg) 8 11.73 (br s, 1H), 10.14 (br s, 1H), 6.86 (s, 1H), 5.65 (s, 1H), 3.83-3.78 (m, 2H), 2.75-2.70 (m, 2H), 2.42-2.38 (m, 2H), 2.18-2.10 (m, 4H), 1.81-1.65 (m, 6H), 1.55-1.43 (m, 2H), 1.08 (t, J=7.3 Hz, 3H) ; MS (FD) m/e 323 (M+); UV (EtOH) 292nm (8=19266), 257nm (e=9555), 201nm (e= 15788).

Anal. Calcd for C16H25N3S2: C, 59.40; H, 7.79; N, 12.99. Found: C, 59.56; H, 7.94; N, 13.00.

Example 2QQ N-r 2-(1-Cvclohexenvl)ethvl1-N'-r2-(4-i-nropvl)thiazolvl1 thiourea A stirred solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10 mmol) and 2-amino-4-i-propylthiazole (1.42 g, 10 mmol) in Jtf-methylpyrrolidinone (20 mL) was heated to 100°C. After 15.75 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl acetate/hexanes to provide 1.01 g of the titled product (33%) as a pale yellow crystalline solid: mp 110-112°C; IR (KBr, cm"1) 3164, 2936, 1562, 1525, 1463, 1321, 1214; X-8571A 2 6 0 - : ^ \J XH NMR (300 MHZ, DMSO-dg) 811.50 (br s, 1H), 9.84 (br s, 1H), 6.61 (s, 1H), 5.41 (s, 1H), 3.61-3.55 (m, 2H) , 2.82-2.76 (m, 1H), 2.17 (t, J=6.4 Hz, 2H) , 1.94-1.88 (m, 4H), 1.56-1.41 (m, 4H), 1.14 (d, J=6.8 Hz, 6H); MS (FD)' m/e 309 (M+) ; UV (EtOH) 291nm (e=20249), 256nm (e=9969), 201nm (e= 15S80).

Anal. Calcd for C15H23N3S2: C, 58.21; H, 7.49; N, 13.58. Found: C, 58.50; H, 7.63; N, 13.38.

Example 201 N-(2-Phenethvl)-N'-f2-(4-i-oropvl)thiazolvll thiourea A stirred solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol, 1.5 mL) and 2-amino-4-i-propylthiazole 15 (1.42 g, 10 mmol) in W-methylpyrrolidinone (20 mL) was heated to 100°C. After 17 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with N/10 hydrochloric acid (2x), water (2x) and brine. The organic layer was dried over 20 sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl acetate/hexanes to provide 1.42 g of the titled product (46*) as a yellow crystalline solid: mp 155-156°C; IR (KBr, cm~l) 3172, 2962, 1581, 1525, 1467, 1350, 1290, 1210; XH NMR (300 MHZ, DMSO-dg) 811.52 (br s, 1H) , 9.89 (br s, 1H), 7.29-7.14 (m, 5H), 6.58 (s, 1H), 3.80-3.74 (m, 2H), 2.87 (t, J=6.9 Hz, 2H) , 2.76-2.71 (m, 1H), 1.07 (d, J=6.8 30 Hz, 6H) ; X-8571A -300 MS (FD) m/e 305 (M+); UV (EtOH) 292nm (£=19882), 257nm (e= 10580), 203nm (e= 20047).

Anal. Calcd for C15H19N3S2: C, 58.98; H, 6.27; N, 13.76. 5 Found: C, 58.95; H, 6.39; N, 13.72.

Example 202 N-(2-Phenethvl)-N'-f2-((4-alvoxvlic acid)thiazolvl)1 thiourea A solution of N-(2-phenethyl)-N'-[2-((4- ethylglyoxylate)thiazolyl)] thiourea (1.30 g, 3.58 mmol) in ethanol (30 mL) was treated with IN sodium hydroxide and heated to reflux. After 1 h, the reaction was cooled to room temperature, diluted with water and washed wtih ethyl 15 acetate (2x). The aqueous layer was acidified to pH 1 with hydrochloric acid and extracted with dichloromethane (2x). The organic layers were combined, washed with brine, dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by triturating with ethyl acetate to 20 yield 390 mg of the titled product (32%) as a light brown solid: mp >170°C (d) ; IR (KBr, cm-1) 3024, 1705, 1669, 1565, 1323, 1146; !h NMR (300 MHZ, DMSO-dg) 8 12.2 (br S, 1H) , 9.07 (s, 1H) , 8.01 (s, 1H), 7.28-7.14 (m, 5H), 3.71-3.64 (m, 2H), 2.84 (t, J=7.3 Hz, 2H); MS (FD) m/e 336 (M+l); HRMS (FAB) m/e (M+l) calcd 336.0477, obs 336.0474; UV (EtOH) 284nm (6=17301), 203nm (£=18110) . 2, 6 0 ? 0 t / o X-8571A -301- 26 0 Example 203 N- (2-Phenethvl) -N' - f 2- (4-methoxvhenzothiazolvl) 1 thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 2-amino-4-methoxybenzothiazole (3.60 g, 20 mmol) in JV,W-dimethylformamide (50 mL) was heated to 100°C. After 64 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (2x), and brine. The organic layer was filtered directly to provide 3.87 g of the titled product (56%) as a white solid: mp 209-211°C; IR (KBr, cm"1) 3171, 2938, 1570, 1527, 1331, 1191, 1044; !h NMR (300 MHZ, DMSO-dtf) 8 11.88 (s, 1H) , 9.86 (s, 1H) , 7.49-6.93 (m, 8H), 3.86 (s, 3H), 3.77-3.70 (m, 2H), 2.89 (t, J»7.1 Hz, 2H); MS (FD) m/e 343 (M+); HRMS (FAB) m/e (M+l) calcd 344.0891, obs 344.0884; UV (EtOH) 290nm, 248nm, 210nm.

Example 204 N-(2-Phenethvl)-N'-r2-((5-tri fluoromethyl1-1.3.4-thiadiazolvl)1 thiourea A solution of 2-phenethyl isothiocyanate (3.26 g, 20 mmol, 3.0 mL) and 2-amino-5-trifluoromethyl-l,3,4-thiadiazole (3.38 g, 20 mmol) in W,iV-dimethylformamide (50 mL) was heated to 100°C. After 40 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with water (3x) and brine (2x). The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified X-8571A *6 0 ? by flash chromatography on silica gel (5% ethyl acetate in dichloromethane) and then recrystallized from ethyl acetate to provide 171 mg of the titled product (3%) as a white solid: mp 212-213°C; IR (KBr., cm"1) 3336, 2788, 1629, 1534, 1494, 1398, 1327, 1148, 1038; iH NMR (300 MHZ, DMSO-dff) 8 12.6 (br s, 1H) , 8.51 (s, 1H) , 7.30-7.15 (m, 5H), 3.73-3.66 (m, 2H), 2.85 (t, J=7.3 Hz, 2H) ; MS (FD) m/e 332 (M+); UV (EtOH) 322nm (e=5240) , 261nm (e= 11025), 204nm (e=28776) . Anal. Calcd for C12H11F3N4S2: C, 43.36; H, 3.34; N, 16.86. Found: C, 43.20; H, 3.44; N, 16.86.

Example 2Q5 N- (2-Phenethvl) -N' - T2- I M-narhnyvHr acid) fchiazolvin thiourea A solution of N-(2-phenethyl)-N'-[2-(4-cyano)thiazolyl] thiourea (250 mg, 0.867 mmol) in glacial acetic acid (10 mL) and 5N hydrochloric acid (10 mL) was heated to reflux. After 16 h, the reaction was cooled to room temperature, diluted with acetonitrile and concentrated to dryness (2x). The solid obtained was purified by flash chromatography on silica gel (2% acetic acid in ethyl acetate) and then recrystallized from methanol/ethyl acetate to provide 13 mg of the titled product. The mother liquor was concentrated and triturated with ethyl acetate to provide another 34 mg of the titled product, for a total yield of 47 mg (18%) as a white solid: mp >230°C; X-8571A. 26 o n r IR (KBr,cm"1) 3275, 1603, 1531, 1394, 1268; !h NMR (300 MHZ, DMSO-dtf) 8 7.26-7.14 (m, 6H) , 3.71-3.65 (m, 2H), 2.87 (t, J=7.2 Hz, 2H); MS (FD) m/e 307 (M+); HRMS (FAB) m/e (M+l) calcd 309.0527, obs 309.0528; UV (EtOH) 288nm, 260nm, 206nm.

Examnle 206 N- (2-(1-Cvclnhexenvl)ethvl) -N' -f 2-(6-fluorobenzothiazolvl)1 thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.66 g, 9.93 mmol) and 2-amino-6-fluorobenzothiazole (1.67 g, 9.93 mmol) in dimethyl sulfoxide (10 mL) was heated to 125°C. After 20 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, water (3x), and brine. The organic layer was dried over sodium sulfate# filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (1% ethyl acetate in dichloromethane) and then recrystallized from ethyl acetate to provide 1.04 g of the titled product (31%) as a yellow crystalline solid: mp 200-201°C; IR (KBr, cm-1) 3451, 3177, 3044, 2924, 2832, 1560, 1533, 1462, 1215, 1198; !h NMR (300 MHZ, CDCl3)8 10.83 (s, 1H) , 10.33 (br s, 1H) , 7.61-7.56 (m, 1H), 7.41-7.37 (m, 1H), 7.17-7.10 (m, 1H), 5.65 (s, 1H), 3.87-3.81 (m, 2H), 2.38 (t, J=6.5 Hz, 2H), 2.03-2.00 (m, 4H), 1.67-1.52 (m, 4H); MS (FD) m/e 335 (M+); X-8571A 2 6 0 2 9 UV (EtOH) 301nm, 218nm, 201nm.

Anal. Calcd for CI6HI8FN3S2: C, 57.29; H, 5.41; N, 12.53. Found: C, 57.58; H, 5.44; N, 12.42.

Example 2Q7 N-12-Phenethvl)-N■-f 2-(5-chlorothiazolvl)1 thiourea 2-Amino-5-chlorothiazole hydrochloride (1.71 g, 10 mmol) was slurried with dichloromethane and shaken with a slight excess of sodium hydroxide solution. The layers were separated and the aqueous washed with dichloromethane. The combined organics were dried over sodium sulfate, filtered and concentrated. To the resulting solid was added 2-phenethyl isothiocyanate (1.63 g, 10 mmol. 1.5 mL) and W-methyl-pyrrolidinone (20 mL). The resulting solution was heated to 100°C. After 20 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, water (4x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (2% ethyl acetate in dichloromethane) and then recrystallized twice from 1:1 ethyl acetate/hexanes to provide 187 mg of the titled product (6%) as a light brown crystalline solid: mp 163-164°C; IR (KBr, cm-1) 3312, 3028, 2925, 1607, 1527, 1513, 1438, 1377, 1348, 1314, 1026; 1h NMR (300 MHZ, DMSO-dg) 8 11.60 (br S, 1H) , 8.41 (s, 1H) . 7.39 (s, 1H), 7.30-7.15 (m, 5H), 3.70-3.63 (m, 2H), 2.82 (t, J=7.2 Hz, 2H); MS (FD) m/e 297 (M+), 299 (M+2); UV (EtOH) 296nm (£=14487), 260nm (6=12442), 206nm (e=27427).

X-8571A 26 0 2 Laja Anal. Calcd for C12H12CIN3S2: C, 48.40; H, 4.06; N, 14.11. Found: C, 48.40; H, 4.16; N, 13.85.

Example 20fl N-T 2- (1-Cvclohexenvl)ethvl1-N'-T 2-((4- trifluoromethyl)thiazolvl)1 thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10 mmol) and 2-amino-4-trifluoromethylthiazole (1.68 g, 10 mmol) in N-10 methylpyrrolidinone (20 mL) was heated to 125°C. After 20 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (3x) , and brine. The organic layer was dried over sodium sulfate, filtered and 15 concentrated. The solid obtained was purified by flash chromatography on silica gel (1% ethyl acetate in dichloromethane) and then recrystallized from 1:1 ethyl acetate/hexanes to provide 139 mg of the titled product (4%) as an off-white solid: mp 153-154°C; IR (KBr,cm"l) 3168, 2932, 1562, 1513, 1472, 1438, 1219, 1175, 1081; !h NMR .(300 MHZ, DMSO-dff) 5 11.95 (s, 1H) , 8.21 (s, 1H) , 7.71 (s, 1H), 5.41 (s, 1H), 3.55-3.49 (m, 2H), 2.14 (t, 25 J=6.7 Hz, 2H), 1.93-1.83 (m, 4H) , 1.56-1.41 (m, 4H); MS (FD) m/e 335 (M+); HRMS (FAB) m/e (M+l) calcd 336.0816, obs 336.0842; UV (EtOH) 285nm ^6=15215), 258nm (e=12868), 203nm (e=20271) . 2 6 0 ° o > .5 X-8571A -306- 7 Example 2Q9 N-f 2-(2-Chlorophenyl)ethyl 1 -N'-f 2 -(14 - trif lunrnmgf.hvl) thiazolvl) 1 thiourea A solution of 2-(2-chlorophenyl)ethyl amine 5 (1.56 g, 10 mmol,1.41 mL) and N-(thioimidazoyl)-2-amino-4- trifluoromethylthiazole (3.0 g, 10.8 mmol) in N,N-dimethylformamide (20 mL) was heated to 90-100°C. After 2 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN 10 hydrochloric acid (2x), water (2x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (1% ethyl acetate in dichloromethane) and then recrystaiJized from 1:1 ethyl 15 acetate/hexanes to provide 870 mg of the titled product (24%) as a white crystalline solid: mp 187-188°C; IR (KBr,cm"1) 3169, 3018, 1569, 1512, 1245, 1220, 1154, 1133, 1080; 1h NMR (300 MHZ, DMSO-dtf) 8 11.92 (s, 1H) , 8.32 (s, 1H) , 7.71 (s, 1H), 7.41-7.22 (m, 4H), 3.76-3.69 (m, 2H), 2.97 (t, J=7.1 Hz, 2H); MS (FD) m/e 365 (M+); UV (EtOH) 285nm (e=13758), 257nm (£=14164) , 202nm (£=30204) . 25 An=il. Calcd for C13H11F3CIN3S2: C, 42.68; H, 3.03; N, 11.49. Found: C, 42.82; H, 3.14; N, 11.68.

X-8571A -307- ^ C b 2 6 0 P a Example 21Q N-r 2-(4-Chloronhenvl)ethvl1-N'-f 2 -(14- trifluoromethyl)thiazolvl)1 thiourea A solution of 2-(4-chlorophenyl)ethyl amine 5 (1.56 g, 10 mmol, 1.40 mL) and N-(thioimidazoyl)-2-amino-4- tr if luoromethylthiazole (3.0 g, 10.8 mmol) in N,N-dimethylformamide (20 mL) was heated to 90-100°C. After 2 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN 10 hydrochloric acid (2x), water (2x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (1% ethyl acetate in dichloromethane) and then recrystallized from 1:1 ethyl 15 acetate/hexanes to provide 570 mg of the titled product (16%) as a white crystalline solid: mp 196-197°C; IR (KBr, cm'1) 3167, 3021, 1562, 1516, 1469, 1445, 1184, 1173, 1126, 1083; XH NMR (300 MHZ, DMSO-d£) 8 11.91 (s, 1H) , 8.27 (s, 1H) , 7.71 (s, 1H), 7.32 (d, J=8.4 Hz, 2H), 7.23 (d, J=8.4 Hz, 2H), 3.72-3.65 (m, 2H), 2.83 (t, J=7.0 Hz, 2H); MS (FD) m/e 365 (M+); UV (EtOH) 236nm (e=11309), 257nm (e=11445), 202nm (e=21815) . 25 Anal. Calcd for C13H11F3CIN3S2: C, 42.68; H, 3.03; N, 11.49. Found: C, 42.87; H, 3.05; N, 11.46. 9 20 ^ 25 2 8 no X-8571A -308- " — 0 3 Example 211 N-T2-(3-Chlorophenyl)ethvl1-N'- \2- ( (4- trifluoromethyl)thiazolyl?1 thiourea A solution of 2-(3-chlorophenyl)ethyl amine (1.56 g, 10 mmol, 1.40 mL) and N-(thioimidazoyl)-2-amino-4-trifluoromethylthiazole (3.0 g, 10.8 mmol) in N,N-dimethylformamide (20 mL) was heated to 90-100°C. After 2 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (1% ethyl acetate in dichloromethane) and then recrystallized from 1:1 ethyl acetate/hexanes to provide 407 mg of the titled product (11%) as a white crystalline solid: mp 159-160°C; IR (KBr, cm"1) 3176, 3017, 1567, 1517, 1224, 1133, 1080; ^■H NMR (300 MHZ, DMSO-dg') 8 11.93 (s, 1H) , 8.28 (s, 1H) , 7.72 (s, 1H) , 7.33-7.17 (m, 4H), 3.73-3.67 (m, 2H), 2.85 (t, J=7.0 Hz, 2H); MS (FD) m/e 365 (M+), 367 (M+2); UV (EtOH) 285nm (£=14175), 257nm (£=14293), 202nm (6=31514). Anal. Calcd for C13H11F3CIN3S2: C, 42.68; H, 3.03; N, 11.49. Found: C, 42.72; H, 3.09; N, 11.79.

Example 212 N-r 2-(2-Methoxyphenyl)ethyl1-N' -f 2- ((4- trifluoromethyl)thiazolvl)1 thiourea A solution of 2-(2-methoxyphenyl)ethyl amine (1.51 g, 10 mmol, 1.46 mL) and N-(thioimidazoyl)-2-amino-4- X-8571A 2 6 0 ° n y trifluoromethylthiazole (3.0 g, 10.8 mmol) in N,N-dimethylformamide (20 mL) was heated to 90-100°C. After 2 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN 5 hydrochloric acid (2x), water (2x) , and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (2% ethyl acetate in dichloromethane) and then recrystallized from 1:1 ethyl 10 acetate/hexanes to provide 872 mg of the titled product (24%) as a white crystalline solid: mp 184-184.5°C; IR (KBr, cm'1) 3168, 2973, 1571, 1514, 1244, 1221, 1168, 1127, 1077; lH NMR -(300 MHZ, DMSO-dg) 8 11.87 (s, 1H) , 8.24 (s, 1H) , 7.71 (s, 1H), 7.18-7.10 (m, 2H), 6.94-6.82 (m, 2H), 3.74 (s, 3H), 3.68-3.61 (m, 2H), 2.80 (t, J=7.0 Hz, 2H); MS (FD) m/e 361 (M+); UV (EtOH) 280nm (£=16781), 259nm (£=15202)/ 203nm (£=32863). 20 Anal. Calcd for C14H14F3N3OS2: C, 46.53; H, 3.90; N, 11.63. Found: C, 46.52; H, 3.94; N, 11.52.

Example 213 N-r 2-(3-Methnxvnhenv3)ethvl1-N' -T 2- ( (4-25 trifluoromethyl)thiazolvl)1 thiourea A solution of 2-(3-methoxyphenyl)ethyl amine (1.51 g, 10 mmol, 1.45 mL) and N-(thioimidazoyl)-2-amino-4-trifluoromethylthiazole (3.0 g, 10.8 mmol) in N,N-dimethylformamide (20 mL) was heated to 90-100°C. After 2 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN 26 Q p X-8571A -310- hydrochloric acid (2x), water (2x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (2% ethyl acetate in dichloromethane) and then recrystallized from 1:1 ethyl acetate/hexanes to provide 1.32 g of the titled product (36%) as a white solid: mp 139-140°C; IR (KBr, cm"1) 3215, 3018, 1598, 1582, 1544, 1490, 1299, 1242, 1180, 1081; % NMR (300 MHZ, DMSO-dg) 8 11.93 (s, 1H) , 8.26 (s, 1H) , 7.71 (s, 1H), 7.18 (t, J=8.0 Hz, 1H), 6.79-6.74 (m, 3H), 3.73-3.66 (m, 2H), 3.69 (s, 3H), 2.80 (t, J=7.0 Hz, 2H); MS (FD) m/e 361 (M+); UV (EtOH) 281nm (£=15384), 258nm (£=14389), 202nm (£=35020). Anal. Calcd for C14H14F3N3OS2: C, 46.53; H, 3.90; N, 11.63 Found: C, 46.76; H, 3.91; N, 11.52.

Example 214 N-r 2-(4-Methoxyphenyl)ethyl 1 -w'-f 2-((4- trifluoromethyl)thiazolvl) 1 thiourea A solution of 2-(4-methoxyphenyl)ethyl amine (1.51 g, 10 mmol, 1.46 mL) and N-(thioimidazoyl)-2-amino-4 trifluoromethylthiazole (3.0 g, 10.8 mmol) in N,N~ dimethylformamide (20 mL) was heated to 90-100°C. After 2 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (2% ethyl acetate in P ft n X-8571A -311- *• V U1 dichloromethane) and then recrystallized from 1:1 ethyl acetate/hexanes to provide 893 mg of the titled product (25%) as a white crystalline solid: mp 169-170°C; IR (KBr, cm"1) 3173, 3025, 1565, 1515, 1240, 1181, 1127, 1083; NMR (300 MHZ, DMSO-dg) S 11.90 (s, 1H) , 8.26 (s, 1H) , 7.71 (s, 1H), 7.12 (d, J=8.5 Hz, 2H), 6.83 (d, J=8.5 Hz, 2H), 3.67 (s, 3H), 3.67-3.61 (m, 2H), 2.76 (t, J=7.1 Hz, 2H) ; MS (FD) m/e 361 (M+); UV (EtOH) 284nm (£=15865) , 258nm (6=14872), 224nm (£=16821), 201nm (&=29323) .

Anal. Calcd for C14H14F3N3OS2: C, 46.53; H, 3.90; N, 11.63. Found: C, 46.70; H, 3.89; N, 11.50.

Example 215 N-f2-(l-CYClohexenYl)ethyn -W'-f2- f (4 r 5- dimethvl)thiazolvl)1 thiourea 2-Amino-4,5-dimethylthiazole hydrochloride (1.65 g, 10 mmol) was slurried with dichloromethane and shaken with a mixture of sodium hydroxide/saturated sodium bicarbonate solution. The organics were washed with brine, dried over sodium sulfate, filtered and concentrated. To the resulting solid was added 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10 mmol) and W-methylpyrrolidinone (20 mL). The resulting solution was heated to 105° C.

After 20 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x), and brine. The organic layer was dried over sodium sulfate, filtered and X-8571A concentrated. The solid obtained was purified by recrystallization from 2:1 ethyl acetate/hexanes to provide 1.57 g of the titled product (53%) as a light yellow crystalline solid: mp 162-164°C; IR (KBr, cm"1) 3170, 2917, 1583, 1554, 1514, 1433, 1325, 1255, 1215; ^H NMR (300 MHZ, DMSO-dg) S 11.35 (s, 1H) , 9.83 (br S, 1H) , 5.43 (s, 1H), 3.58-3.52 (m, 2H), 2.17-2.11 (m, 5H), 2.07 (s, 3H), 1.94-1.89 (m, 4H), 1.57-1.44 (m, 4H); MS (FD) m/e 295 (M+) ; UV (EtOH) 297nm (6=18557), 256nm (6=9443) , 201nm (6=16880) . Anal. Calcd for C14H21N3S2: C, 56.91; H, 7.16; N, 14.22. Found: C, 57.10; H, 7.28; N, 14.36.

Example 216 N-T2 - (3-Ethoxv-4-methoxvphenvl) ethvl 1 -N.' - (2-thiazolvl) thiourea A solution of 2-(3-ethoxy-4-methoxyphenyl)ethyl amine (1.00 g, 5.12 mmol) and N-(thioimidazoyl)-2-aminothiazole (1.08 g, 5.12 mmol) in N,N- dime thyl formamide (20 mL) was heated to 90-100°C. After 16 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with In hydrochloric acid (2x), water (2x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from dichloromethane/ethyl acetate to provide 471 mg of the titled product (27%) as an off-white solid: mp 150-152°C; X-8571A 26c ' ^ ■■J IR (KBr, cm-1) 3176, 3112, 3040, 1575, 1514, 1469, 1261, 1235, 1140, 1042; NMR (300 MHZ, DMSO-dg) 811.51 (s, 1H) , 9.73 (br s, 1H) , 7.28 (d, J=3 .6 Hz, 1 H), 7.07 (s, 1H), 6.90-6.78 (m, 2H) , 5 6.72 (d, J=8.2 Hz, 1H), 4.00-3.88 (m, 2H), 3.80-3.67 (m, 5H), 2.76 (t, J=6.9 Hz, 2H), 1.25 (t, J=6.9 Hz, 3H); MS (FD) m/e 337 (M+); UV (EtOH) 287nm (e=21828), 259nm (e=11770) , 205nm (e=35881) . Anal. Calcd for C15H19N3O2S2: C, 53.39; H, 5.67; N, 12.45. 10 Found: C, 53.10; H, 5.64; N, 12.22.

Example 217 N-r 2-(3-Methoxv-4-isonropoxvphenvl)ethvl1-N'-(2-thiazolvl) thiourea A solution of 2-(3-methoxy-4-isopropoxy- phenyl)ethyl amine (1.00 g, 4.78 mmol) and N-(thioimidazoyl)-2-aminothiazole (1.00 g, 4.78 mmol) in N,N-dimethylformamide (20 mL) was heated to 90-95°C. After 24 h, the reaction was cooled to room temperature and poured 20 into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl acetate to provide 891 mg of 25 the titled product (53%) as yellowish needles. A sample was recrystallized a second time from ethyl acetate: mp 140-141°C; IR (KBr, cm"1) 3165, 2971, 1560, 1516, 1466, 1266, 1182, 1144; X-8571A 2 6 Q On •> o? j !h NMR (300 MHZ, DMSO-dg) S11.53 (s, 1H) , 9.71 (br s, 1H) , 7.28 (d, J=3.6 Hz, 1H), 7.06 (s, 1H), 6.84-6.81 (m, 2H) , 6.71-6.68 (m, 1H) , 4.45-4.37 (m, 1H), 3.74-3.66 (m, 5H) , 2.77 (t, J=7.0 Hz, 2H), 1.17 (d, J=6.0 Hz, 6H); MS (FD) m/e 351 (M+); UV (EtOH) 286nm, 258nm, 204nm.

Anal. Calcd for C16H21N3O2S2: C, 54.68; H, 6.02; N, 11.96. Found: C, 54.79; H, 6.11; N, 12.21.

Example 218 N-r 2-(3.4-dichlorophenyl)ethvl1-N1 -(2-thiazolvl) thiourea 2-(3,4-Dichlorophenyl)ethyl amine hydrochloride (1.00 g, 4.41 mmol) was slurried in dichloromethane and shaken with a slight excess of sodium hydroxide solution.

The layers were separated and the organics were dried over sodium sulfate, filtered and concentrated. N-(thioimidazoyl)-2-aminothiazole (928 mg, 4.41 mmol) and W,W-dimethylformamide (20 mL) were added to the resulting oil. This solution was heated to 90-100°C. After 18 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (2% ethyl acetate/dichloromethane) to provide 1.0 g of 3 (68%) as a white solid. This solid was recrystallized from ethyl acetate to provide 700 mg of the titled product as a white crystalline solid: mp 159.5-160°C; X-8571A 26 0 29 IR (KBr, cm-1) 3175, 1577, 1515, 1472, 1328, 1190, 1029; ^■H NMR (300 MHZ, DMSO-dg) 811.55 (s, 1H) , 9.63 (br S, 1H) , 7.54-7.48 (m, 2H), 7.30-7.21 (m, 2H), 7.06 (s, 1H), 3.77-3.70 (m, 2H), 2.87 (t, J=6.9 Hz, 2H); MS (FD) m/e 331 (M+); UV (EtOH) 289nm (8=19623), 265nm (8=11818), 204nm (8=36059) . Anal. Calcd for C12HHCI2N3S2: C, 43.38; H, 3.34; N, 12.65. Found: C, 43.14; H, 3.36; N, 12.63.

Example 219 N-T2-(2-methvl-1-trifluorompthvlnhenvl)ethvl1-M1-(2- thiazQlYl) thiourea 2-(2-Methyl-3-trifluoromethylphenyl)ethyl amine hydrochloride (1.00 g, 4.17 mmol) was slurried in 15 dichloromethane and shaken with a slight excess of sodium hydroxide solution. The layers were separated and the organics were dried over magnesium sulfate, filtered and concentrated. N-(thioimidazoyl)-2-aminothiazole (877 mg, 4.17 mmol) and w,J\7-dimethylformamide (20 mL) were added to 20 the resulting oil. This solution was heated to 90-100°C.

After 65 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water, and brine. The organic layer was dried over sodium sulfate, filtered and 25 concentrated. The solid obtained was purified by flash chromatography on silica gel (2% ethyl acetate/dichloromethane) and then recrystallized from ethyl acetate (1st crop) or 1:1 ethyl acetate/hexanes (2nd crop) to provide 581 mg of the titled product (40%) as a white 30 solid: X-8571A -316- 26 0 29 3 mp 158-159°C; IR (KBr,cm-l) 3178, 3130, 2994, 1566, 1514, 1473, 1321, 1161, 1120; NMR (300 MHZ, DMSO-dg) 811.60 (s, 1H) , 9.76 (br s, 1H) , 7.52-7.47 (m, 2H) , 7.33-7.28 (m, 2H), 7.07 (s, 1H), 3.75-3.68 (m, 2H), 2.98 (t, J=7.4 Hz, 2H), 2.40 (s, 3H); MS (FD) m/e 345 (M+); UV (EtOH) 289nm (e=19176) , 258nm (e=11507), 203nm (e=21953). Anal. Calcd for C14H14F3N3S2: C,48.68; H,4.08; N,12.16. Found: C,48.89; H,4.06; N,12.14.

Example 22 Q N-r 2- (3 - (3 . 3 .3 -tri fluoro)propvlphenvl)ethvl1-N■-(2- thiazolvl) thiourea 2-(3 - (3,3,3-trifluoro)propylpheny1)ethyl amine tosylate (1.00 g, 2.57 mmol) was slurried in dichloromethane and shaken with a slight excess of sodium hydroxide solution. The layers were separated and the aqueous was extracted with dichloromethane. The combined organics were dried over magnesium sulfate, filtered and concentrated. N-(thioimidazoyl)-2-aminothiazole (540 mg, 2.57 mmol) and JV,w-dimethylformamide (20 mL) were added to the resulting oil. This solution was heated to 90-95°C.

After 1 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x), and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from 40% ethyl acetate/hexanes to provide m X-8571A 260 2 9 508 mg of the titled product (55%) as an off-white crystalline solid: mp 138-139°C; IR (CHCI3, cm-1) 3192, 3058, 2979, 1567, 1514, 1259, 1139; 5 3-H NMR (300 MHZ, DMSO-dg) 811.53 (S, 1H) , 9.73 (br S, 1H) , 7.29-7.06 (m, 6H) , 3.75-3.69 (m, 2H), 2.83 (t, J=7.0 Hz, 2H), 2.77-2.71 (m, 2H), 2.57-2.45 (m, 2H) ; MS (FD) m/e 359 (M+); UV (EtOH) 288nm (e=19255), 257nm (6=11152), 203nm (e=21782) . 10 Anal. Calcd for C15H16F3N3S2: C, 50.13; H, 4.49; N, 11.69. Found: C, 50.36; H, 4.45; N, 11.46.

Example 221 N-(2-(1-Cvclohexenvl)ethvl)-N'-f2-pvridvl1 thiourea 15 A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10 mmol) and 2-aminopyridine (941 mg, 10 mmol) in W-methylpyrrolidinone (20 mL) was heated to 100°C. After 16.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic 20 phase was washed with water (4x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The solid obtained was purified by recrystallization from ethyl acetate to provide 1.31 g of the titled product (50%) as a white crystalline solid: 25 mp 153-155°C; IR (KBr, cm"1) 3219, 2921, 1605, 1569, 1537, 1481, 1319, 1235, 1181, 1092; X-8571A 260 2 1H NMR (300 MHZ, DMSO-dg) 511.55 (s, 1H) , 10.47 (s, 1H) , 8.09 (d', J=3.9 Hz, 1H) , 7.74-7.68 (m, 1H) , 7.09 (d, J=8.3 Hz, 1H), 7.00-6.96 (m, 1H), 5.47 (s, 1H), 3.65-3.59 (m, 2H), 2.19 (t, J=6.6 Hz, 2H), 1.94-1.90 (m, 4H), 1.55-1.43 5 (m, 4H); MS (FD) m/e 261 (M+) ; UV (EtOH) 292nm (©=15926), 265nm (e=17724), 247nm (e=15198) . Anal. Calcd for C14H19N3S: C, 64.33; H, .7.33; N, 16.08. Found: C, 64.12; H, 7.33; N, 15.89.

Example 222 N-(2-Phenethvl)-N'-T2-(5-bromo1nvridvl1 thiourea A solution of 2-phenethyl isothiocyanate (1.63 g, 10 mmol, 1.5 mL) and 2-amino-5-bromopyridine (1.73 g, 10 15 mmol) in W-methylpyrrolidinone (20 mL) was heated to 100°C.

After 22 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid (2x), water (2x) and brine. The organic layer was dried over sodium sulfate, filtered and 20 concentrated. The solid obtained was purified by recrystallization from ethyl acetate/hexanes to provide 1.20 g of the titled product (36%) as a white crystalline solid: mp 160-162°C; IR (KBr, cm-1) 3028, 1595, 1559, 1531, 1475, 1311, 1228, 1092; XH NMR (300 MHZ, DMSO-dg) 811.16 (S, 1H), 10.65 (s, 1H), 8.11 (d, J=2.1 Hz, 1H), 7.93-7.90 (m, 1H), 7.29-7.18 (m, 5H), 7.05 (d, J=8.8 Hz, 1H), 3.82-3.77 (m, 2H), 2.88 (t, 30 J=7.0 Hz, 2H); X-8571A * o o ? • MS (FD) m/e 335 (M+), 337 (M+2); UV (EtOH) 305nm (6=14171), 275nm (6=24881), 201nm (6=21601) . Anal. Calcd for Ci4Hi4BrN3S: C, 50.01; H, 4.20; N, 12.50. Found: C, 49.93; H, 4.19; N, 12.52.

Example 223 N-f 2-(1-Cvclohexenvl1ethvl1-N'-\2 -(5-cvano)Pvridvl1 thiourea A stirred solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.36 g, 8.14 mmol) and 2-amino-5-cyanopyridine (0.97 g, 8.14 mmol) in W-methylpyrrolidinone (20 mL) was heated to 100°C. After 5 days, the reaction was cooled to room temperature and poured into EtOAc. The organic phase was washed with H2O (4x) and brine. The organic layer was dried over Na2S04, filtered and concentrated. The solid obtained was purified by flash chromatography on silica gel (2% EtOAc/CH2CI2), followed by recrystallization with EtOAc/hexanes to provide 78 mg of the titled product (3%) as an off-white solid: mp 195-197°C; IR (KBr, cm"1) 2927, 2224, 1605, 1570, 1533, 1487, 1369, 1228, 1165; *H NMR '(300 MHZ, DMSO-dg) 8 11.17 (br s, 1H) , 10.96 (s, 1H), 8.57 (d, J=1.9 Hz, 1H), 8.12 (dd, J=8.8, 2.1 Hz, 1H), 7.20 (d, J=8.8 Hz, 1H), 5.47 (s, 1H), 3.66-3.59 (m, 2H), 2.20 (t, J=6.6 Hz, 2H) , 1.94-1.89 (m, 4H), 1.54-1.43 (m, 4H) ; MS (FD) m/e 286 (M+); UV (EtOH) 308nm, 202nm.

Anal. Calcd for C15H18N4S: C, 62.91; H, 6.34; N, 19.56. Found: C, 62.70; H, 6.42; N, 19.42.

X-8571A 26 0 r i • V Example 224 N- (2-phenethvl1-N'-f2-(4-(4-biphenvl)thiazolvl1 thiourea A solution of 2-phenethyl isothiocyanate (0.82 g, 5 mmol, 0.75 mL) and 2-amino-4-(4-biphenyl)thiazole (1.26 g, 5 mmol) in W,JV-dimethylforniamide (12.5 mL) was heated to 100°C. After 19.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic solution was washed with IN hydrochloric acid. The mixture was filtered and the filtrate was separated and the organic phase washed with saturated sodium bicarbonate solution, water (4x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The materia^, was purified by flash chromatography on silica gel (1% ethyl acetate in dichloromethane to 2% ethyl acetate in dichloromethane) to provide 372 mg of the titled product (18%). The yellow solid was recrystallized from ethyl acetate: mp 208.5-209°C; IR (KBr, cm"1) 3437, 3172, 3029, 1570, 1553, 1511, 1211, 1060, 738; lH NMR (300 MHz, DMSO-c?6) 8 11.72 (s, 1H) , 9.54 (br s, 1H) , 7.86-7.80 (m, 2H), 7.78-7.68 (m, 4H), 7.58 (s, 1H), 7,52-7.44 (m, 2H), 7.41-7.35 (m, 1H), 7.34-7.29 (m, 4H), 7.27-7.20 (m, 1H), 3.92-3.84 (m, 2H), 2.98 (t, J=3 Hz, 2H); MS (FD) m/e 415 (M+); UV (EtOH) 293nm, 212nm.

Anal. Calcd for C24H21N3S2: C, 69.36; H, 5.09; N, 10.11. Found: .C, 69.08; H, 5.10; N, 9.99.

X-8571A •321- 26 0 2 Example 225 N-(2-Phenethvl)-N'-2 -f 4-(4-pvridvl)thiazolvl 1 thiourea 2-Amino-4-(4-pyridyl)thiazole hydrobromide was slurried with methylene chloride and shaken with saturated 5 sodium bicarbonate solution. The layers were separated and the aqueous washed with methylene chloride and ethyl acetate. The combined organic layers were concentrated. To the solid (1.0 g, 5.6 mmol) was added 2-phenethyl isothiocyanate (0.91 g, 5.6 mmol, 0.83mL) in N,N-10 dimethylformamide (12.5 mL). The resulting suspension was heated to 100°C. After 20.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with water (4x) and brine. The organic layer was dried over sodium sulfate, filtered and 15 concentrated. The resulting solid was recrystallized from ethyl acetate (3x) to provide 133 mg (7%) of the titled product: mp 196.5°C; IR (KBr-, cm"1) 3250, 2939, 1723, 1604, 1506, 1223, 670, 20 664; lH NMR (300 MHz, DMSO-d6) 8 11.72 (s, 1H) , 9.21 (br s, 1H) , 8.54 (d, J=6 Hz, 2H), 7.82 (s, lH), 7.63 (d, J=6 Hz, 2H), 7.30-7.15 (m, 5H), 3.84-3.77 (m, 2H), 2.89 (t, J=7 Hz, 2H); MS (FD) m/e 340 (M+); HRMS (FAB) m/e (M+) calcd 341.0895, obs 341.0909; UV (EtOH) 294nm (e=23935), 231nm (e=16356), 203nm (e=25793).

» X-8571A -322- 26 0 Example 226 N- (2-Phenethvl) -N' -2- f4- (1- (1-ethvoxvcarbonvl)-(3-t-butoxvcarbnnvlmethoxv> imlno)thiazolvl1 thiourea 2-Amino-4-(1-(1-ethoxycarbonyl)-(3-t-butoxycarbonylmethoxy)imino)thiazole (2.64 g, 8 mmol) and 2-phenethyl isothiocyanate (1.31 g, 8 mmol, 1.2 mL) in N,N-dimethylformamide (20 mL) were heated to 100°C. After 24 h, the reaction was cooled to room temperature and poured into ethyl acetate. ve organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The resulting solid was triturated with ethyl acetate to provide 801 mg (20%) of the titled product: mp 188.5°C; IR (KBr, cm"1) 3293, 2975, 1749, 1594, 1543, 1453, 1382, 1231, 1154, 1054, 748, 698; !h NMR (300 MHz, DMSO-dg) 8 11.85 (S, 1H), 8.46 (br s,lH), 7.29-7.17 (m, 5H), 4.59 (s, 2H), 4.31-4,24 (q, J=7.1 Hz, 2H), 3.70-3.64 (m, 2H), 2.82 (t, J=7.1Hz, 2H), 1.36 (s, 9H>, 1.23 (t, J= 7.1 HZ, 3H); Mi; (FD) m/e 492 (M+); UV (EtOH) 292nm, 257nm (e=16356), 203nm.

Anal. Caicd for C22H28N4O5S2: C, 53.64; H, 5.73; N, 11.37. Found: C, 53.67; H, 5.83; N, 11.34.

Example 227 N- (2-Phenethvl) -N'-2- f4-f:-butvl-5-methvlthiazolvll thiourea 2-Amino-4-t-butyl-5-methylthiazole (1.87 g, 11 mmol) and 2-phenethyl isothiocyanate (1.80 g, 11 mmol, 1.64 mL) in N,itf-dimethylformam.^cie (25 mL) were heated to 100°C.

X-8571A 260 " o ? L * After 1&.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer was 5 dried over sodium sulfate, filtered and concentrated. The resulting solid was triturated with ether to provide 1.02 g (28%) of the titled product: mp 153-153.5°C; IR (KBr, cm"1) 3171, 2966, 1474, 1534, 1510, 1455, 1346, 10 1221, 1186, 755, 704; iH NMR (300 MHz, DMSC)-d6) 8 11.28 (BR S, lH) , 9.90 (BR S, 1H), 7.28-7.14 (M, 5H), 3.78-3.34 (M, 2H), 2.84 (T, J=7 Hz, 2H), 2.27 (s, 3H), 1.16 (s, 9H); MS (FD) m/e 333 (M+) ; UV (EtOH) 297nm (£=19835), 257nm (£=9954), 202nm (£=21059).

Anal. Calcd for C17H23N3S2: C, 61.22; H, 6.95; N, 12.60. Found: C, 61.42; H, 6.92; N, 12.55. fixamnle 228 N-(2-Phenethvl)-N'-2-f4-(4-bromophenvl)-5-ethvlthiazolvl1 thiourea 2-Amino-4-(4-bromophenyl)-5-ethylthiazole (848 mg, 3 mmol) and 2-phenethyl isothiocyanate (490 mg, 3 mmol, 0.45 mL) in W, JV-dimethylformamide (7.5 mL) were heated to 25 100°C. After 22.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with IN hydrochloric acid, saturated sodium bicarbonate solution, water (3x) and brine. The organic layer was dried over sodium sulfate, filtered and 30 concentrated. The resulting solid was recrystallized from X-8571A *60Zc, ethyl acetate and toluene to provide 146 mg (11%) of the titled product: mp 169-170°C; IR (KBr, cm"1) 3169, 3025, 2969, 2930, 1581, 1558, 1520, 5 1234, 1168, 1009; ^ NMR '(300 MHZ, DMSO-C?6) 8 11.54 (S, 1H) , 9.40 (br s, lH) , 7.57 (d, J=8.3 Hz, 2H), 7.36 (d, J=8.3 Hz, 2H), 7.21-7.14 (m, 5H) , 3.75-3.73 (m, 2H), 2.87-2.82 (m, 2H), 2.80 (q, J=7.8 Hz, 2H), 1.17 (t, J-l.8 Hz, 3H); MS (FD) m/e 445 (M+), 447 (M+2); UV (EtOH) 291nm, 263nm, 237nm, 203nm.

Anal. Calcd for C20H20BrN3s2: C, 53.81; H, 4.52; N, 9.41; Found: C, 53.71; H, 4.61; N, 9.39.

Example 229 N-(2-phenethyl)-N'-r2-pvriflinof2,3-tf1thiazolyl thiourea A solution of 2-phenethyl isothiocyanate (1.33 g, 8.13 mmol, 1.21 mL) and 2-aminopyridiont2,3-d]thiazole (1.23 g, 8.13 mmol) in W-dimethylformamide (15 mL) was 20 heated to 105°C. After 46.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic solution was washed with water (6x) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The material was purified by flash 25 chromatography on silica gel (5% ethyl acetate in dichloromethane to 10% ethyl acetate in dichloromethane) to provide 330 mg of the titled product (13%). The white powder was recystallized from ethyl acetate: mp 202-202.5°C; IR (KBr, cm"1) 3445, 3171, 3025, 1565, 1551, 1510, 1382, 1201, 1150; X-8571A 26 Q p a C*. Vy XH NMR (300 MHz, DMSO-c?6) 8 11.91 (br s, 1H) , 9.76 (br s, 1H), 8.37 (m, 1H), 7.88 (m, 1H), 7.43 (dd, J= 3 and 6 Hz, 1H), 7.33-7.20 (m, 5H), 3.82-3.79 (m, 2H), 2.89 (t, J=7 Hz, 2H) ; MS (FAB) m/e 315 (M+l); UV (EtOH) 312nm (6=22468), 211nm (6=19194).

Anal. Calcd for Ci5Hi4N4S2: C, 57.30; H, 4.49; N, 17.82.

Found: C, 57.20; H, 4.49; N, 17.66.

Example 230 N-(2-Phenethvl)-N'-f 2-(3-ethvl)pvridvl1 thiourea A) 2-£-Butoxvcarbonvlamino-3-ethvlovridine 2-t-Butoxycarbonylaminopyridine (10 g, 51.5 mmol) was dissolved in tetrahydrofuran (80 mL), and cooled 15 to -78° C. N-butyllithium (80 mL of 1.49 M in hexanes, 120 mmol) was added dropwise over a period of 1 h. After stirring for an additional 15 min at -78°C and then for 2.5 hours at -10°C, the solution was then recooled back down to -78°C and iodoethane (77.2 mmol, 6.18 mL) was added 20 dropwise over a period of 15 min via syringe. The solution was allowed to warm to room temperature. The reaction was quenched with 100 mL of a saturated ammonium chloride and extracted with ethyl acetate (3x). The organic layers were collected, dried over magnesium sulfate, and concentrated. 25 The resulting solid was purified by flash chromatography on silica gel (25% ethyl acetate/hexanes) to provide the 4.9 g (43%) of the titled product as a light brown solid: mp 101-102°C; IR (KBr,cm"l) 3174, 2968, 1725, 1594, 1519, 1442, 1278, 30 1249, 1156; X-8571A -326- w Vi . v, 2 !h NMR '(300 MHZ, DMSO-dg) b 8.98 (s, 1 H), 8.17 (m, lH) , 7.61 (m, 1H), 7.15 (m, lH), 2.52 (q, J=7.5 Hz, 2H), 1.39 (S, 9H), 1.08 (t, J=7.5 Hz, 3H) ; MS (FD) m/e 222 (M+); UV (EtOH) 270nm (e= 4398), 223nm (6= 6745) .

Anal. Calcd for C12HI8N2O2: C, 64.84; H, 8.16; N, 12.60. Found: C, 64.91; H, 8.34; N, 12.42.

B) Preparation of 3-Ethvl-2-aminopvridine. 2-t-Butoxycarbonylamino-3-ethylpyridine (4.9 g, 19.8 mmol) was dissolved in 90 ml of 3N HCl/Acetic acid and stirred for two hours. The sloution was neutralized with 2N NaOH to pH 7 and then extracted with ethyl acetate (2x 400 ml). The organics were dried over magnesium sulfate 15 and concentrated giving 2.3 g (95%) of a yellowish solid. This solid was used in the next reaction without further purification.

C) N-(2-Phenethvl)-N'-T2-(3-ethvl)pvridvl1 thiourea A solution of phenethyl isothiocyanate (3.61 g, 18.8 mmol, 3.3 mL) and 2-amino-3-ethylpyridine (2.3 g, 18.8 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90-95°C for 3 h. The solution was cooled to room temperature, poured into ethyl acetate (150 mL), and washed with 0.1N 25 hydrochloric acid (2x), water (3x), and brine. The organics were dried over sodium sulfate, riltered, and concentrated. The resulting solid was purified by flash chromatography on silica gel (1.5% ethyl acetate/dichloromethane) and then recrystallized (30% ethyl X-8571A 26:} ' acetate/ hexanes) to give 1.1 g (21%) of the titled product as a white solid : mp 57-58°C; IR (KBr, cm"1) 3433, 2932, 1561, 1516, 1452, 1433, 1328, 5 1237, 760; XH NMR (300 MHZ, DMSO-dg) 511.58 (br S, 1H) , 8.66 (s, lH) , 7.92-7.90 (m, 1H), 7.6-7.58 (m, 1H), 7.30-7.15 (m, 5H), 7.02-6.98 (m, 1H), 3.83-3.77 (m, 2H), 2.89 (t, J=6 Hz, 2H), 2.64 (q, J=7.5 Hz, 2H), 1.09 (t, J=7.5 Hz, 3 H); 10 MS (FD) m/e 285 (M+); UV (EtOH) 293nm (£= 16632), 265nm (e= 14930), 244nm (e= 16594), 202nm (e= 21127) .

Anal. Calcd for C16H19N3S: C, 67.33; H, 6.71; N, 14.72. Found: C, 67.17; H, 6.88; N, 14.51.

Example 231 N- (2 -Phenet-.hvl) -N' - f 2 - (3 -bromo) pvr idvl 1 thiourea A) 2-fc-Butoxvcarbonvlamino-3-bromoovridine 20 2-fc-Butoxycarbonylaminopyridine (10 g, 51.5 mmol) was dissolved in tetrahydrofuran (80 mL), and cooled to -78° C . N-butyllithium (120 mmol, 80 mL of 1.49 M in hexanes) was added dropwise over a period of 1 h . After stirring for an additional 15 min at -78°C and then for 2.5 25 h at -10°C, the solution was recooled back down to -78°C and 1,2-dibromoethane (77.2 mmol, 6.65 mL) was added dropwise over a period of 15 min via syringe. The solution was allowed to warm to room temperature. The reaction was quenched with 100 mL of saturated ammonium chloride and was 30 extracted with ethyl acetate (3x). The organic layers were collected, dried over magnesium sulfate, filtered, and X-8571A. 2 6 0 9 Q v J? concentrated. The resulting solid was purified by flash chromatography on silica gel (25% ethyl acetate/hexanes) giving 4.5 g (32%) of the titled product as a light brown solid: mp 120-121°C; IR (KBr, cm"1) 3191, 2980, 1729, 1521, 1442, 1365, 1272, 1166, 1032; NMR (300 MHZ, DMSO-dg) 8 9.28 (s, 1H) , 8.34 (m, 1H) , 8.05 (m, 1H), 7.15 (m, 1H), 1.39 (s, 9H); MS (FD) m/e 272 (M+), 274 (M+2); UV (EtOH) 280nm (£=4047), 230nm (e=9067), 204nm (6=16385).

B) Preparation of 3-Bromo-2-aminopvridine. 3-Bromo-2-t-butoxycarbonylaminopyridine (3.8 g,13.9 15 mmol) was dissolved up in 70 ml of 3N HCl/ Acetic acid and stirred for two hours. The solution was neutralized with 2N NaOH to pH 7 and then extracted with ethyl acetate (3x 300 ml). The organics were dried over magnesium sulfate and concentrated giving a brown oil. 20 This was put on vacuum overnight giving 2.4 g (100%) solid crystals. This was used in the next reaction without further purification: mp 57-59*C; !h NMR (300 MHZ, DMSO-dg) 8 7.9 (m,lH), 7.65 (m,lH), 6.5-25 6.4 (m, lH), 6.2-6.l(s, 2H).

C) N-(2-Phenethvl)-N'-f2-(3-bromo)nvridvl1 thiourea A solution of phenethyl isothiocyanate (1.89g, 11.6 mmol, 1.73 mL) and 2-amino-3-bromopyridine (2.0 g, 30 11.6 mmol) in N,JV-dimethylformamide was stirred at 90-95°C for 3 h. The solution was cooled to room temperature, X-8571A 26 0 2 9 poured into ethyl acetate (150 mL), and washed with 0.1N hydrochloric acid (2x), water (3x), and brine. The organics were dried over sodium sulfate, filtered, and concentrated. The resulting solid was purified by flash chromatography on silica gel (30% ethyl acetate/hexanes) to yield 0.5 g (13%) of the titled product as a white solid: mp 95-96°C; IR (KBr, cm"1) 3403, 3021, 1591, 1564, 1548, 1514, 1435, 1150, 750, 700; 1H NMR (300 MHZ, DMSO-dg) 811.2 (s, lH) , 8.45 (s, 1H) , 8.13-8.06 (m, 2H), 7.29-7.18 (m, 5H), 7.04-7.0 (m, 1H) , 3.86-3.8 (m, 2H), 2.91 (t, J=6 Hz, 2H); MS (FD) m/e 335 (M+), 337 (M+2); UV (EtOH) 298nm (£=13404), 272nm (e= 16029) , 250nm (e= 17186) , 203nm (£=22974) .

Anal. Calcd for Ci4Hi4N3S2Br: C, 50.01; H, 4.20; N, 12.50. Found: C, 49.77; H, 4.21; N, 12.37.

Example 232 N-(4-Bromonhenethvl)-N'-T2-(4-ethvl)thiazolvl1 thiourea 4-Bromophenethylamine hydrochloride (1 g, 4.22 mmol) was slurried with dichloromethane and water. Sodium hydroxide (0.17g, 4.22 mmol) dissolved in water was added to this mixture and stirred. The organics were separated, washed v' " " rine, dried over sodium sulfate, filtered, and concentrated. The resulting solid was added to N-(thioimidazoyl)-2-amino-4-ethylthiazole (1.0 g, 4.22 mmol) in N,N-dimethyl-formamide (20 mL) and stirred for 3 h at 90-95°C. The solution was cooled to room temperature and added to 150 mL of ethyl acetate, washed with 0.1N hydrochloric acid (2x), water (3x), and brine. The X-8571A 26 Q ? a o- \j organics were dried over sodium sulfate, filtered, and concentrated. The solid was recrystallized (50% ethyl acetate/ hexanes) providing 0.7 g (45%) of the titled product as a yellow solid : mp 156-157°C; IR (KBr, cm"1) 2963, 1560, 1527, 1259, 1212, 1011, 802, 743; l-H NMR (300 MHZ, CDCI3) 6 10.94 (br s, 1H) , 9.77 (br s, 1H), 7.41 (d, J=8.3 Hz, 2H), 7.24 (d, J=8.2 Hz, 2H), 6.33 10 (s, 1H), 4.03-3.97 (m, 2H) , 2.97 (t, J=6.8 Hz, 2H), 2.49 (q, J=7.5 Hz, 2H), 1.13 (t, J=7.5 Hz, 3H); MS (FD) m/e 369 (M+), 371 (M+2); UV (EtOH) 292nm (€=10803) , 257nm (e= 6300) .

Anal. Calcd for Ci4Hi6N3SBr: C, 45.41; H, 4.35; N, 11.35. 15 Found: C, 45.53; H, 4.42; N, 11.49.

Example 233 N- (3-Phenoxvphenethvl) -N' - f2- (4-ethvl ) thiazolvll thiourea 3-Phenoxyphenethylamine hydrochloride (1.0 g, 20 4.0 mmol) was slurried with dichloromethane and water.

Sodium hydroxide (0.16 g, 4.0 mmol) dissolved in water was added and stirred. The organics were separated, washed with brine, dried over sodium sulfate, filtered, and concentrated. The resulting solid was added to N-25 (thioimidazoyl)-2-amino-4-ethylthiazole (1.0 g, 4.22 mmol) in j7,W-dimethyl-formamide (20 mL) and stirred for 3 h at 90-95°C. The solution was cooled to room temperature, added to 150 mL of ethyl acetate and washed with 0.1N hydrochloric acid (2x), water (3x), and brin®. The 30 organics were dried over sodium sulfate, filtered, and concentrated. The oil was put on vacuum overnight and X-8571A 260 recrystallized (50% ethyl acetate / hexanes) providing 0.6 g (42%) of the titled product as a white solid : mp 124°C; IR (KBr, cm"1) 3177, 2966, 1563, 1534, 1509, 1491, 1446, 1349, 1287, 1260, 1218, 1158, 773; iH NMR (300 MHZ, CDCI3) 810.99 (br s, 1H), 9.87 (br s, lH), 7.31-7.23 (m, 3H), 7.09-6.84 (m, 6H), 6.32 (s, 1H), 4.03-3.97 (m, 2H), 2.99 (t, J=6.8 Hz, 2H), 2.53 (q, J=7.5 Hzi 2H), 1.14 (t, J=7.5 Hz, 3H); MS (FD) m/e 383 (M+); UV (EtOH) 293nm (e= 19262), 258nm (e= 11356), 205nm (6=37212). Anal. Calcd for C20H21N3OS2: C, 62.63; H, 5.52; N, 10.96. Found: C, 62.69; H, 5.61; N, 11.06.

Example 234 N- (2-NitrnnhPTiethvl) -N' -T2-(4-ethvl)thiazolvl1 thiourea 2-Nitrophenethylamine tosylate (0.97g, 3.0 mmol) was slurried with dichloromethane and water. Sodium hydroxide (0.12 g, 3 mmol) dissolved in water was added and stirred. The organics were separated, washed with brine, dried over sodium sulfate, filtered, and concentrated. The resulting solid was added to N-(thioimidazoyl)-2-amino-4-ethylthiazole [BK8-6TT-074] (0.71 g, 3 mmol) in N,N-dimethylformamide (20 mL). and stirred for 3 h at 90-95°C.

The solution was allowed to cool to room temperature and then was added to 150 mL of ethyl acetate and washed with 0.1N hydrochloric acid (2x), water (3x), and brine. The organics were dried over sodium sulfate, filtered, and concentrated. The solid was recrystallized (50% ethyl acetate/ hexanes) providing 0.5g (54%) of the titled product as a white solid : X-8571A 26 0 mp 132-133°C; IR (KBr, cm"1) 3171, 2966, 1586, 1531, 1509, 1341, 1215; 1H NMR (300 MHZ, CDCI3) 811.06 (br S, 1H) , 9.76 (br S, lH) , 7.98 (d', J=8.1 Hz, 1H), 7.56-7.35 (m, 3H) , 6.35 (s, 1H) , 4.13-4.02 (m, 2H), 3.33 (t, J=7 Hz, 2H), 2.56 (q, J=7.4 Hz, 2H), 1.16 (t, J=7.4 Hz, 3H); MS (FD) m/e 336 (M+); UV (EtOH) 292nm (e=20546), 258nm (e= 14748) , 203nm (e= 24932) . Anal. Calcd for C14H16N4O2S2: C, 49.98; H, 4.79; N, 16.65. Found: C, 49.95; H, 4.86; N, 16.59.

Example 235 N-r 6-(2-Phenvlbenz oxa z ole)1ethvl1-N1 -f 2- ethvIthiazolvl1 thiourea 2-[6-(2-phenylbenzoxazole)] ethylamine hydrochloride (0.88 g, 3.2 mmol) was slurried with dichloromethane and water. Sodium hydroxide (0.13 g, 3.2 mmol) dissolved in water was added and stirred. The organics were separated, washed with brine, dried over sodium sulfate, filtered, and concentrated. The resulting solid was added to N-(thioimidazoyl)-2-amino-4-ethylthiazole (0.71 g, 3 mmol) in W, JV-dimethylformamide (20 mL) and stirred for 3 h at 90-95°C. The solution was cooled to room temperature, added to 150 mL of ethyl acetate and washed with 0.1N hydrochloric acid (2x), water (3x), and brine. The organics were dried over sodium sulfate, filtered, and concentrated. The solid was recrystallized (50% ethyl acetate/ hexanes) providing 0.64 g (49%) of the titled product as a white solid : mp 183°C; X-8571A 26 0 n IR (KBr, cm-1) 3178, 3035, 1578, 1533, 1506, 1253, 1214, 701; iH NMR (300 MHZ, CDCI3) 810.96 (br s, 1H), 9.7 (br s, 1H) , 8.25-8.21 (m, 2H), 7.69 (d, J=8.1 Hz, 1H), 7.53-7.48 (m, 4H), 7.29 (m, 1H), 6.28 (s, 1H), 4.13-4.06 (m, 2H), 3.17 (t, J=6.6 Hz, 2H), 2.39 (q, J=7.5 Hz, 2H), 1.0 (t, J=7.5 Hz, 3H); MS (FD) m/e 408 (M+); UV (EtOH) 294nm (e= 12603), 201nm (e= 14517) .

Anal. Calcd for C21H20N4OS2: C, 61.74; H, 4.93; N, 13.71.

Found: C, 61.99; H, 5.18; N, 13.85.

Example 236 N-(2-Phenoxvphenethvll-N'-T2-(ethvl)thiazolvl! thiourea 2-phenoxyphenethylamine hydrochloride (0.97 g, 3.9 mmol) was slurried with dichloromethane and water. Sodium hydroxide (0.13 g, 3.9 mmol) dissolved in water was added and stirred. The organics were separated, washed with brine, dried over sodium sulfate, filtered, and concentrated. The resulting solid was added to N-(thioimidazoyl)-2-amino-4-ethylthiazole (0.929 g, 3.9 mmol) in W,A7-dimethylformamide (20 mL) and stirred for 3 h at 90-95°C. The solution was cooled to room temperature, added to 150 mL of ethyl acetate and washed with 0.1N hydrochloric acid (2x), water (3x), and brine. The organics were dried over sodium sulfate, filtered, and concentrated. The resulting solid was recrystallized (50% ethyl acetate/ hexanes) providing 0.73 g (49%) of the titled product as a white solid : mp 168°C; X-8571A 260 IR (KBr, cm"1) 3168, 3013, 1581, 1532, 1487, 1237, 1209, 753; XH NMR (300 MHZ, CDCI3) 810.93 (br s, 1H), 9.67 (br s, lH), 7.35-7.24 (m, 3H), 7.21-7.16 (m, 1H) , 7.08-7.02 (m, 2H), C.94-6.86 (m, 3H), 6.31 (s, 1H), 4.05-4.0 (m, 2H), 3.05 (t, J=6.9 Hz, 2H), 2.5 (q, J=7.5 Hz, 2H), 1.12 (t, J=7.5 Hz, 3H) ; MS (FD) m/e 383 (M+); UV (EtOH) 292nm (£=19052), 258nm (£= 11450) , 204nm (£= 38534) . Anal. Calcd for C20H21N30S2: C, 62.63; H, 5.52; N, 10.96. Found: C, 62.91; H, 5.67; N, 11.22.

Example 237 N- f f (4-met-.hvl-2-thiazolvl) amino 1 thioxomethvll -DL-nhenvlalanine methvl ester A solution of 1-[(2-[4-methyl]thiazolyl) thiocarbamoyl] imidazole (0.45 g, 5.0 mmol) and DL-phenylalanine methyl ester hydrochloride (0.43 g, 2.0 mmol) in W,W-dimethylformamide (50 mL) was heated at 110*C for 12 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, recrystallized from ethyl ether-hexanes to provide 118 mg (18%) of the titled product: mp 131-132*C; IR (KBr, cm-1) 3179, 3027, 1578, 1579, 1533,1224; XH NMR (300 MHz, DMSO-d6) 8 11.80 ( br s, 1H), 10.20 (br s, 1H), 7.20-7.38 (m, 5H), 6.63 (s, 1H), 5.10 (q, 1H), 3.63 (s, 3H), 3.03-3.22 (m, 2H), 2.12 (s, 3H); MS (FD) m/e 335(M+); UV (EtOH)294nm (£=18428), 257nm (£=9852), 202nm (£=21796).

X-8571A -335- " r- -A' \ i._.. > 26 Anal. Calcd for C15H17N3O2S2: C, 53.71; H, 5.11; N, 12.53. Found: C, 53.47; H, 5.11; N, 12.75.

Example 23fi (+-) -3- (4-methvl-2-thia7nlvU-5-(phenvlmethvl)-2-thinxr>-4- imldazolidinnne A solution of N-[[(4-methyl-2-thiazolyl)amino]thioxomethyl]-DL-phenylalanine methyl ester (0.94 g, 2.80 mmol) and p-toluene sulfonic acid hydrate 10 (0.20 g 1.05 mmol) in toluene (80 mL) was refluxed with a Dean-Stark trap for 24 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and saturated sodium chloride, dried 15 over magnesium sulfate, and concentrated under reduced pressure. The resulting product was recrystallized from ethyl acetate-hexanes to provide 216.1 mg (25%) of the titled product: mp 169-171*C; IR (KBr", cm"l) 3153, 1776, 1539, 1280, 1195, 744, 303; !h NMR (300 MHz, DMSO-d6) 8 10.85 ( S, 1H), 7.40 (d, 1H) , 7.30(m, 3H), 7.11(m, 2H), 4.83 (t, 1H), 3.50 (d, 2H), 2.35 (s, 3H); MS (FD) m/e 303(M+); UV(EtOH) 265nm (e=16902) , 203nm (£=17971).

Anal. Calcd for C14H13N3OS2: C, 55.42; H.4.32; N,13.85. Found: C,55.63; H, 4.45; N, 13.91.

X-8571A -336- ' ' •. V Example 239 N-f (2-thlazolvlaminr)) thioxomethvll -DL-phenvlalanine methvl eater A solution of 1-[(2-thiazolyl) thiocarbamoyl] 5 imidazole (4.21 g, 20.0 mmol) and DL-phenylalanine methyl ester hydrochloride (4.31 g, 20.0 mmol) in N,N-dimethylformamide (150 mL) was heated at 90*C for 3 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, recrystalllized from ether-hexanes 10 to provide 3.26 g (51%) of the titled product: IR (KBr, cm"1) 3184, 3029, 1735 1569, 1510, 1223,1189 ; NMR (300 MHz, DMSO-d6) 5 11.90 (s, 1H), 7.40 (d, 1H), 7.20-7.38 (m, 5H), 7.17 (d, 1H), 5.30 (q, 1H), 3.63 (s, 3H), 3.02-3.22 (m, 2H); MS (FD) m/e 321(M+); UV (EtOH) 291nm (6=18235), 255 nm (£=10773), 202nm (e=20575) .

Anal. Calcd for C14H15N3O2S2: C, 52.31; H, 4.70; N, 13.07.

Found: C, 52.24; H, 4.61; N, 13.18.

Rxamnlp 240 DL-5-(nhenvImpthv1)-3-(2-thiazolvl)-2-thioxo-4- thiazolidinone A solution of N-[(2-thiazolylamino)thioxomethy1]-DL-phenylalanine methyl ester (0.47 g, 2.23 mmol) and p-25 toluene' sulfonic acid hydrate (0.20 g 1.05 mmol) in toluene (50 mL) was refluxed with a Dean-Stark trap for 12 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and saturated 30 sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting product <6 0 r X-8571A -337- 26 0 2 Q ?vr was recrystallized from ethyl ether-hexanes to provide 0.243g (58%) of the titled product: mp 164-165 *C; IR (KBr, cm"1) 3099, 2985, 2873, 1775,1532, 1440, 1398, 5 1329, 1251, 1208, 737 ; XH NMR (300 MHZ, DMSO-d6) 6 10.90 ( S, 1H) , 7.83 (d, 1H) , 7.80 (d, 1H), 7.50 (m, 3H), 7.20 (m, 2H), 4.90 (t, 1H) , 3.17 (d, 2H); MS (FD) m/e 289(M+); UV (EtOH) 264nm (£=16108), 202nm (£=17275) .

Anal. Calcd for C13H11N3OS2: C, 53.96; H, 3.83; N,14.52. Found: C,54.22; H, 3.96; N, 14.30.

Example 241 N-f (2 -benzothiazol vlaminn) thioxonethvll-DL-phenvlalanine methvl ester A solution of 1-[(2-benzothiazolyl) thiocarbamoyl] imidazole (1.30 g, 5.0 mmol) and DL-phenylalanine methyl ester hydrochloride (1.08 g, 5.0 mmol) 20 in N,N-dimethylformamide (50 mL) was heated at 90*C for 3 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, recrystalllized from ethyl ether-hexanes to provide 1.31 g (70%) of the titled product: mp 168-169'C; IR (KBr, cm"1) 3168, 3030, 1732, 1548, 1525, 1206,1193; iH NMR (300 MHz, DMSO-d6) 5 10.30 (br s, 1H) , 7.88 (d, 1H) , 7.62 (d, 1H), 7.32 (t, 1H), 7.20-7.29 (m, 6H), 5.18 (q, 1H), 3.70 (s, 3H), 3.22 (m, 2H); MS (FD) - m/e 371(M+); UV (EtOH) 303nm (e=25329), 247 nm (e=12095), 203nm (£=28990).

X-8571A -338- O «eo2 Anal. Calcd for C18H17N3O2S2s C, 58.20; H, 4.61; N, 11.31. Found: C, 58.19; H, 4.70; N, 11.30.

Example 242 DL-3-(2-benzothiazolyl)-5-(phenvlmethvl)-2-thloxo-4- thi azolidinone A solution of N-[(2-benzothiazolylamino)thioxomethyl]-DL-ph?nylalanine methyl ester (1.0 g, 2.69 mmol) and p-toluene sulfonic acid 10 hydrate (0.20 g 1.05 mmol) in toluene (80 mL) was refluxed with a Dean-Stark trap for 36 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and saturated sodium chloride, dried 15 over magnesium sulfate, and concentrated under reduced pressure. The resulting product was recrystallized from ethyl acetate-hexanes to provide 74.9 mg (8%) of the titled product: mp 187-189*C; IR (KBr, cm"1) 3250, 1766, 1522, 1489; !h NMR (300 MHz, DMSO-d6) 8 11.00 (s, 1H), 8.18 (d, 1H) , 8.02 (d, 1H), 7.08-8.00 (m, 2H), 7.37 (m, 3H), 7.23 (d, 2H), 4.97 (t, 1H), 3.18 (d, 2H); MS (FD) m/e 339(M+); UV (EtOH) 300nm (e=7355), 265nm (e=19454), 217nm (e*=26558 ), 203nm (e=31150) .

Anal. Calcd for C17H13N3OS2: C, 60.16; H.3.86; N.12.38. Found: C, 60.33; H, 4.14; N, 12.25.

X-8571A -339- 260 Example 243 N- f f (6-f luoro-2-benzothiaznlvl) amino! thioxomethvll -DT.- pheriYlalanine methvl ester A solution of 1-[(2-[6-fluoro]benzothiazolyl) thiocarbamoyl] imidazole (1.40 g, 5.0 mmol) and DL-phenylalanine methyl ester hydrochloride (1.08 g, 5.0 mmol) in NfN-dimethy1,formamide (175 mL) was heated at 90 °C for 3 h. The reaction was cooled to room temperature, solvent 10 removed under reduced pressure, recrystalllized from ethyl ether-hexanes to provide 900 mg (46%) of the titled product: iH NMR (300 MHz, DMSO-d6) 6 10.03 (br s, lH) , 7.82 (q, 1H) , 7.60 un, 1H), 7.20-7.32 (m, 6H) , 5.10 (q, 1H), 3.63 (s, 15 3H), 3.20 (t, 2H); MS (FD) m/e 389 (M+) .

Example 244 DL-3-(6-fluoro-2-benzofchiazolvl)-5-(phenvlmethvl)-2-thioxo- 4-imidazolidinone 20 A solution of N- [ [ (6-fluoro-2- benzothiazolyl)amino]thioxomethyl]-DL-phenylalanine methyl ester (0.90 g, 2.31 mmol) and p-toluene sulfonic acid hydrate (0.20 g 1.05 mmol) in toluene (80 mL; was refluxed with a Dean-Stark trap for 48 h. The reaction was cooled 25 to room temperature, solvent removed under reduced pressure, residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and sat\-rated sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting product was recrystallized 30 front ethyl ether-hexanes to provide 251mg (31%) of the titled product: 2 0 .5 X-8571A 26 0 p 0 :ap 223-224*C; IR (KBr, cm"1) 3173, 1767, 1538, 1453, 1388, 1267; XH NMR (300 MHZ, DMSO-d6) 8 11.02 (S, 1H) , 8.00-8.12 (m, 2H), 7.40-7.50 (m, 1H), 7.20-7.39 (m, 5H), 4.97 (t, 1H), 5 3.20 (d, 2H); MS (FD) m/e 357(M+); UV (EtOH) 265nm (e=15680) , 223nxn (e=19505), 201nm (e=23665) . Anal. Calcd for C17H12FN3OS2: C, 57.13; H,3.38; N, 11:76. Found: C,56.89; H, 3.43; N, 11.60.

Example 245 N-f f(4.5-dimethvl-2-thiazolvl)amino1thioxomethvll-DL-phenvlalanine methvl ester A solution of 1-[(2-[4,5-dimethyl]thiazolyl) 15 thiocarbamoyl] imidazole '1.80 g, 7.5 mmol) and DL- phenylalanine methyl ester hydrochloride (1.60 g, 7.5 mmol) in N, W-dimethylformamide (50 mL) was heated at 90'C for 4 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, recrystalllized from ether-20 hexanes to provide 1.91 g (72%) of the titled product: IR (KBr, cm"1) 3178, 3029, 1756, 1552, 1505, 1219 ; !h NMR (300 MHz, DMSO-d6) 8 11.65 (br s, 1H) , 7.20-7.38 (m, 5H), 5.10 (q, 1H), 3.65 (s, 3H), 3.05-3.21 (m, 2H), 2.20 (s, 3H), 2.08 (s, 3H); MS (FD) m/e 349(M+); UV (EtOH) 300nm (e=17248) , 257 nm (e=9202), 203nm (£=22444) . Anal. Calcd for C16H19N3O2S2: C, 54.99; H, 5.48; N, 12.02. Found: C, 55.16; H, 5.57; N, 12.01.

X-8571A 2 6 0 p Example 24 6 DL-3- (4. 5-dimethvl-2-thiazolvl) -5- (phenvlmethvl) -2-thinoxr>- 4-imidazolidinonfe A solution of N- <4,5-dimethyl-2-thiazolyl)amino]thioxomethyl]-DL-phenylalanine (1.00 g, 2.86 mmol) and p-toluene sulfonic acid hydrate (0.20 g, 1.05 mmol) in toluene (50 mL) was refluxed with a Dean-Stark trap for 48 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and saturated sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting product was recrystallized from ethyl ether-hexanes to provide 0.545 g (60%) of the titled product: mp 205-207*C; IR (KBr, cm"1) 3161, 1783, 1527, 1287, 1164? !h NMR (300 MHz, DMSO-d6) 8 10.80 (s, 1H) , 7.30 (m, 3H) , 7.20 (m, 2H) , 4.83 (t, 1H), 3.10 (d, 2H), 2.32 (s, 3H) , 2.21 (s, 3H)); MS (FD) rn/e 317 (M+); UV (EtOH) 266nm (e=16921) , 201 nm (e=17995) .

Anal. Calcd for C15H15N3OS2: C, 56.76; H, 4.76; N, 13.24.

Found: C, 56.53; H, 4.94; N, 13.49.

Example 247 N-f r(4-cvano-2-thiazolvl)aminolthioxomethvl1-DL-phenvlalanine methvl ester A solution of 1-[(2-[4-cyano]thiazolyl) thiocarbamoyl] imidazole (1.76 g, 7.5 mmol) and DL-phenylalanine methyl ester hydrochloride (1.62 g, 7.5 mmol) # X-8571A 2®0?9.J in N,.N-dimethylformamide (50 mL) was heated at 90°C for 5 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, recrystallized from ethyl ether-hexanes to provide 1.42 g (55%) of the titled 5 product: IR (KBr, cm"1/ 3011, 2220, 1742, 1672, 1586,1455, 1372; % NMR (300 IIHz, DMSO-d6) 6 7.12-7.38 (m, 5H) , 7.40 (s, 1H) , .05 (q, 1H), 3.63 (s, 3H), 3.03-3.22 (m, 2H); MS (FD) m/e 346 (M+); UV (EtOH)287nm (e=7404), 257nm (e=12260) , 206nm (e=30014) .

Example 248 DL-3-(4-cvano-i-thiazolvll-5-(nhenvlmethvl)-2-thioxo-4- imidflSQlidinone A solution of N-[[(4-cyano-2- thiazolyl)amino]thioxomethyl]-DL-phenylalanine methyl ester (1.42 g, 4.10 mmol) and p-toluene sulfonic acid hydrate (0.20 g 1.05 mmol) in toluene (80 mL) was refluxed with a Dean-Stark trap for 24 h. The reaction was cooled to room 20 temperature, solvent removed under reduced pressure, residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and saturated sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting product was recrystallized from 25 ethyl ether-hexanes to provide 170.1 mg (10%) of the titled product: mp 214-216*C; IR (KBr, cm"1) 3294, 3092, 2246, 1781, 1505, 1381, 1325, 1244; *H NMR (300 MHz, DMSO-dg) 8 11.08 (s, 1H) , 8.90 (s, 1H) , 30 7.22-7.80 (m, 3H), 7.20-7.22 (m, 2H), 4.83 (t, 1H), 3.17 (d, 2H); X-8571A -343- ^ ^ Q 2 9 MS (FD) m/e 314(M+); UV (EtOH) 259nm (e=15097), 205nm (£=26419).

Anal. Calcd for C14H10N4OS2 '• C, 53.49; H, 3.21; N,17.82.

Found: C, 53.75; H, 3.43; N, 17.62.

Example 249 N-f r(4-trifluoromethvl-2-thiazolvl)aminolthioxomethyl1-DL- phenvlalanine methvl ester A solution of 1-[(2-[4-trifluoromethyl]thiazolyl) 10 thiocarbamoyl] imidazole (1.60 g, 5.8 mmol) and DL- phenylalanine methyl ester hydrochloride (1.24 g, 5.8 mmol) in N,W-dimethylformamide (50 mL) was heated at 90*C for 5h. The reaction was cooled to room temperature, solvent removed under reduced, recrystallized ethyl ether-hexanes 15 to provide 2.22 g (99%) of the titled product: IR (CHCI3, cm-1) 3000, 1744, 1672,1554, 1523, 1226; l-H NMR (300 MHz, DMSO-d6) 8 8.64 (d, 1H) , 7.82 (s, 1H) , 7.21-7.38 (m, 3H) , 7.19-7.21 (d, 2K), 5.05 (q, 1H), 3.63 (s, 3H), 3.02-3.22 (m, 2H); MS (FD) m/e 389(M+); UV (EtOH) 287nm (e=11327) , 256nm (e=11674) , 203nm (e=24532) . Anal. Calcd for C15H14F3N3O2S2: C, 46.27; H, 3.62; N, 10.79. Found: C, 46.55; H, 3.57; N, 11.06.

Example 25Q DL-3-(4-trifluoromethvl-2-thiazolvl)-5-(phenvlmethvl)-2- thioxo-4-imidazolirilnone X-8571A 26 0 ? Q * - W J A solution of N-[[(4-trifluoromethyl-2-thiazolyl)amino]thioxomethyl]-DL-phenylalanine methyl este--(2.09 g, 5.38 mmol) and p-toluene sulfonic acid hydrate (0.20 g 1.05 mmol) in toluene (80 mL) was refluxed 5 with a Dean-Stark trap for 48 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and saturated sodium chloride, dried over magnesium sulfate, and concentrated under 10 reduced pressure. The resulting product was recrystallized from ethyl ether-hexanes to provide 1.01 g (53%) of the titled product: mp 187-189*C; IR (CHCI3. cm-1) 3431, 3008, 1782, 1495, 1369, 1328, 1242, 15 1178, 1149, 1085; XH NMR (300 MHZ, DMSO-d6) 8 11.02 (s, ^H), 8.59 (s, 1H) , 7.22-7.80 (m, 3H) , 7.20-7.22 (m, 2H) , 4.83. (t, 1H) , 3.17 (d, 2H); MS (FD) m/e 357 (M+) ; UV (EtOH) 263nm (e=13898), 202nm (e=19355) .

Anal. Calcd for C14H10F3N3OS2: C, 47.05; H,2.82; N.11.76. Found: C,47.33; H, 2.86; N, 11.67.

Example 251 N- (2-f1-cvclohexenvl1ethvl)-N'-f 2-(6-bromo)pvridjnvl1 thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10 mmol) and 2-amino-6-bromopyridine (1.73 g, 10 mmol) in JV/N-dimethylformamide 30 (100 mL) was heated at 100'C for 96 h. The reaction was cooled to room temperature, solvents removed under reduced X-8571A 26 0 P pressure, taken up in ethyl acetate washed with IN HCl. The organic layer was concentrated and the residue purified by HPLC (elution with hexanes-EtOAc) to afford 70.1 mg (2.1%) of the titled product: mp 174-175*C; IR (CHC13, cm-1) 2936, 1592, 1512, 1448, 1203 ; NMR (300 MHz, DMSO-d6) 5 10.79 (s,lH), 10.65 (m, 1H) , 7.70 (t, 1H) , 7.28 (d, 1H), 7.19 (d, 1H), 5.60 (s, 1H) , ' 3.70 (q, 2H), 2.23 (t, 2h), 1.95 (s, 4H) , 1.62-1.42 (m, 4H) MS (FD) rn/e 341 (M+); UV (EtOH) 303nm (e=19786), 269nm (e=18279) , 252nm (e=18006) , 201nm (6=17992) .

Anal. Calcd for Ci4Hi8BrN3S: C, 49.42 H, 5.33; N, 12.35. 15 Found: C, 49.69; H, 5.36; N, 12.09.

Example 252 N- (2-f 1-cvclohexenvll ethvl) -N' - f (4-is jpropvDpvridinvl1 thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (0.36 g, 2.2 mmol) and 2-amino-4-isopropylpyridine (0.36 g, 2.2 mmol) in N,N-dime thyl formamide (20 mL) was heated at 100'C for 96 h. The reaction was cooled to room temperature, solvents 25 removed under reduced pressure, taken up in ethyl acetate, washed with IN aqueous HCl. The organic layer was concentrated and the residue purified by HPLC (elution with hexanes-EtOAc) to afford 169 mg (5.6%) of the titled product: mp 105-106*C; IR (KBr, cnr1) 3215, 2931, 1614 1556, 1534, 1487, 1199; X-8571A 26 o p iH NMR (300 MHz, DMSO-<?6) 8 11.65 (t, 1H) , 10.40 (s, lH) , 8.30 (d, 1H), 7.20 (s, lH), 6.93 (d, 1H), 5.52 (s, lH), 3.63 (q, 2H), 2.80 (m, 1H), 2.22 (t, 2H), 1.95 (m, 4H), , 1.62-1.42 (m, 4H), 1.18 (d, 6H); MS (FD) m/e 303 (M+); UV (EtOH) 290nm (6=17565), 266nm (©=18863), 247nm (£=15125) , 203nm(e=23091).

Anal. Calcd for C17H25N3S: C, 67.28;H, 8.30; N, 13.85. Found: C, 67.55; H, 8.48; N, 13.94.

Example 253 N-(2-Tl-cvclohexenvl1ethvl)-N'-(2-T6-methvlthiolbenzothiazolyl1 thiourea A solution of 2-(l-cyclohexenyl)ethyl 15 isothiocyanate (1.67g, 10 mmol) and 2-amino-6- methylthiobenzothiazole (1.96 g, 10 mmol) in N,N-dimethylformamide (20 mL) was heated at 100'C for 96 h. The reaction was cooled to room temperature, a precipitate formed,' collected, washed with ethyl acetate to provide 20 1.22 g (54%) of the titled product: mp 186-187*C; IR (KBr, cm-1) 3171, 3036, 2918, 1548, 1522, 1251, 1214; !h NMR (300 MHz, DMSO-dg) 8 11.82 (br s, 1H) , 10.20 (br s, 1H), 7.88 (s, 1H), 7.6-7.5 (m, 1H), 7.4-7.3 (q, 1H), 5.55 25 (s, 1H), 3.67 (q, 2H), 2.4 (s, 3H) , 2.25 (t, 2H), 1.95 (s, 4H), 1.62-1.42 (m, 4H); MS (FD) m/e 363 (M+); UV (EtOH) 318nm (6=14538), 256 nm (e=6742), 224nm (6=13749), 201 nm (6=11940) .

X-8571A 26 0 p q» Anal. Calcd for C17H21N3S3: C, 56.16; H, 5.82; N, 11.56. Found: C, 56.40; H# 5.94; N, 11.76.

Example 254 N- (2- n -cvelohexenvllethvl) -N'•> T2- (4-f 4- bromo1Phenyl)thiazolyl1 thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10 mmol) and 2-amino-[4-(4-bromophenyl)]thiazole (2.55 g, 10 mmol) in N,N~ 10 dimethylformamide (2u mL) was heated at 100'C for 72 h. The reaction was cooled to room temperature, solvent removed under reduced, recrystallized from ethyl acetate-hexanes to provide 455 mg (11%) of the titled product: mp 219-220*C; IR (KBr, cm-1) 3171, 2927, 1566, 1516, 1301, 1211, 1071, 1110; 1H NMR (300 MHz, DMSO-d6) 8 11.70 (s, 1H) , 9.30 (br s, 1H) , 7.80 (d, 2H), 7.60 (m, 3H), 5.43 (s, 1H), 3.67 (q, 2H), 2.25 (t, 2H), 1.95 (s, 4H), 1.62-1.42 (m, 4H); 20 MS (FD) m/e 421 (M+); UV (EtOH) 285nm (6=27781), 245 nm (e=17426), 202nm (6=31192).

Anal. Calcd for Ci8H20BrN3S2: C, 51.18; H, 4.77; N, 9.95. Found: C, 51.08; H, 4.47; N, 9.91. f'l 1 X-8571A -348- u & 26 Example 255 N- (2-ri-cyclQhexenynethyl) -N'-f2- (4 - f 2- fhexadecvloxv)phenyl!) t-.hiazolvl! thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (840 mg, 5 mmol) and 2-amino-4-(2-[hexadecyloxy]phenyl)thiazole (2.10 g, 5 mmol) in N,N-dimethylformamide (20 mL) was heated at 100 °C for 72 h. The reaction was cooled to room temperature, solvent removed under reduced, recrystallized from ethyl acetate-hexanes to provide 900 mg (31%) of the titled product: mp 98-99*C; IR (KBr, cm"1) 2919, 1567, 1473, 1222,1062, 681; !h NMR (300 MHz, DMSO-dg) 8 11.62 (s, 1H) , 9.62 (br s, 1H) , 7.95 (d> 1H), 7.56 (s, lH), 7.30 (t, lH), 7.12 (d, 1H), 7.0 (t, 1H), 5.43 (s, 1H), 4.10 (t, 2H), 3.65 (q, 2H), 2.25 (t, 2H), 1.95 (br s, 2H), 1.83 (t, 3H), 1.94-1.73 (m, 4H), 1.40-1.38 (m, 2H), 1.23 (s, 28H) ; MS (FD) m/e 583 (M+); UV (EtOH) 299nm (e=21244), 263 nm (e=21549), 202nm (£=30773). Anal. Calcd for C34H53N3OS2: C, 69.93; H, 9.15; N, 7.19. Found: C, 69.70; H, 8.99; N, 7.28.

Example 256 N- r (2-thiazolvl)amino!thioxomethyl-DL-2-fluorophenvlalanine methvl ester A solution of 1-[(2-thiazolyl) thiocarbamoyl] imidazole (3.15 g, 15 mmol) and DL-2-fluorophenylalanine methyl ester hydrochloride u.51 g, 15 mmol) in N,N-dimethylformamide (100 mL) was heated at 80*C for 8 h. The reaction was cooled to room temperature, the solvent removed under reduced pressure, and the residue X-8571A -349- £ h (1 O 26 recrystallized from ethyl ether-hexanes to provide 1.89 g (37%) of the titled product: IR (KBr, cm"1) 3187, 3122, 3090, 3037, 2950, 1739, 1566, 1495, 1209, 1182; XH NMR '(300 MHz, DMSO-d6) 8 11.61 (br S, 1H) , 7.39 (d, lH) , 7.26 (m, 2H), 7.18 (m, 3H), 5.16 (q, 1H), 3.64 (s, 3H), 3.28 (m, 2H); MS (FD) m/e 339 (M+); UV (EtOH) 290nm (6=18548) , 256 nm (6=10899) , 203nm (e=19927) . 10 Anal. Calcd for C14H14FN3O2S2: C, 49.67; H, 3.87; N, 12.42. Found: C, 49.45; H, 4.07; N, 12.40.

F.xamnle 257 DL-3-(2-thiazolvll-5-f O.-fluoro1nhenvlmethvll-S-thinxo-d- imidazolidinone A solution of N-[(2-thiazolyl)amino]thioxomethyl-DL-2-fluorophenylalanine methyl ester (1.0 g, 2.95 mmol) and p-toluenesulfonic acid hydrate (0.20 g 1.05 mmol) in toluene (100 mL) was refluxed with a Dean-Stark trap for 48 20 h. The reaction was cooled to room temperature, solvent removed under reduced pressure, residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and saturated sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting 25 product was recrystallized from ethyl acetate-hexanes to provide 305 mg (23%) of the titled product: IR (KBr, cm"1) 3104, 2870, 1781, 1531, 1438, 1330, 1255, 1204; % NMR (300 MHz, DMSO-d6) 8 10.95 (br s, lH) , 7.85 (d, 1H), 30 7.78 (d, 1H), 7.30 (m, 2H), 7.18 (m, 2H), 4.83 (t, lH), 3.18 (d, 2H); X-8571A -350- e\ 26 0 MS (FD) m/e 307(M+); UV (EtOH)397 (6=586), 263nm (©=16615), 201nm (©=15980) Anal Calcd for C13H10N2 FOS2: C, 50.80; H,3.28; N,13.67. Found: C, 50.84; H, 3.33; N, 13.38.

Example 258 N-f(2-thiazolyl)amino1thioxomethyl-PL-3.5-bis(trifluoremethyl)phenylalanine methyl ester A solution of 1-[(2-thiazolyl) thiocarbamoyl] 10 imidazole (0.46 g, 2.19 mmol) and DL-3,5- ditrifluorometliy lpheny lalanine methyl ester hydrochloride (0.77 g, 2.19 mmol) in N,N- dime thyl formamide (75 mL) was heated at 80'C for 7 h. The reaction was cooled to room temperature, thp solvent removed under reduc d pressure, 15 and the residue recrystallized from ethyl ether-hexanes to provide 203 mg (20%) of the titled product: IR (KBr, cm"1) 3179, 3022, 1745, 1568, 1379, 1291, 1212; iH NMR (300 MHz, DMSO-c?6) 8 11.82 (br s, lH) , 7.98 (s, 3H) , 7.10 (m, 1H), 5.12 (m, 1H), 3.31 (s, 3H), 3.08 (m, 2H); 20 MS (FD) m/e 457 (M+); UV (EtOH) 291 (©=18895), 255nm (e=10490), 202nm (£=19571) Anal. Calcd for C16H13F6N3O2S2: C, 42.01; H, 2.86; N, 9.19. Found: C, 41.90; H, 2.74; N, 9.36.

Example 259 DL-3-(2-thiazolvl)-5-f (3 . 5-bis ftrifluoromethyl1)phenvlmethvll-2-thioxo-4- imidazoliflinone A solution of N-[ (2-thiazolyl) amino] thioxomethyl-30 DL-3,5-bis trif luoromethy lpheny lalanine methyl ester (0.15 X-8571A 26 0 2 g, 0.32 mmol) and p-toluene sulfonic acid hydrate (0.10 g 0.53 mmol) in toluene (65 mL) was refluxed with a Dean-Stark trap for 48 h. The reaction was cooled to room temperature, the solvent removed under reduced pressure, and the residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and saturated sodium chloride, dried over magnesium sulfate, concentrated under reduced pressure to provide 39 mg (29%) of the titled product. IR (KBr, cm"1) 3105, 1771, 1535, 1500, 1444, 1380, 1278, 1217; lH NMR (300 MHz, DMSO-d6) 8 10.93 (br s, 1H) , 8.03 (s, 1H) , 7.96 (s, 2H), 7.89 (d, 1H), 7.80 (d, lH), 5.01 (t, 1H), 3.37 (d, 2H) ; MS (FD) m/e 425 (M+); UV (EtOH) 44Cnm (e=1169), 264nm (£=14109) .

Anal. Calcd for C15H9F6N3OS2: C, 42.35; H,2.13; N,9.88.

Found: C, 42.60; H, 2.33; N, 9.63 .

N-f(2-thiazolvl)amino1thi oxomethvl-PL-2-chlorophenvlalanine methvl ester A solution of 1-[(2-thiazolyl) thiocarbamoyl] imidazole (1.5 g, 7.1 mmol) and DL-2-chlorophenylalanine methyl ^ster hydrochloride (1.78 g, 7.1 mmol) in N,N-dimethylformamide (65 mL) was heated at 80°C for 7 h. The reaction was cooled to room temperature, the solvent removed under reduced pressure, and the residue recrystallized from ethyl ether-hexanes to provide 280 mg (12%) of the titled product: 1h NMR (300 MHz, DMSO-d6) 8 7.38 (m, 3H) , 7.23 (m, 2H) , 7.08 X-8571A 260 2 9 (br s, 1H), 5.17 (q, 1H), 3.62 (s, 3H), 3.21 (m, 2H); MS (FD) m/e 355 (M+).

Example 261 N- f (2-thiaznlvl) amino! fchioxomefchvl-DL-4-chlornphenvlalar.lne methyl ester A solution of 1-[ (2-thiazolyl) thiocarbamoyl] imidazole (1.5 g, 7.1 mmol) and DL-4-chlorophenylalanine methyl ester hydrochloride (1.78 g, 7.1 mmol) in N,N-10 dimethyiformamide (65 mL) was heated at 80*C for 6 h. The reaction was cooled to room temperature, the solvent removed under reduced pressure, and the residue recrystallized from ethyl ether-hexanes to provide 8-10 mg (20%) of the titled product: IR (KBr, cm"1 ) 3176, 3025, 1735, 1562, 1510, 1493, 1467, 1452, 1387, 1353, 1306, 1202, 1191; ifi NMR (300 MHZ, DMSO-C?6) 6 11.81 (br S, lH) , 7.39 (m, 3H) , 7.26 (d, 2H), 7.18 (br s, 1H), 5.09 (q, 1H), 3.64 (s, 3H), 3.18 (m, 2H); MS (FD) m/e 355(M+); UV (EtOH) 291nm (e=18545), 255 nm (e=11222) , 220nm (e=16171), 201 (£=18545).

Anal. Calcd for C12H14CIN3O2S2: C, 47.25; H, 3.96; N, 11.81. Found: C, 47.28; H, 3.94; N, 11.88.

Example 262 DL-3-(2-thiazolvl)-5-f(4-chloro)phenvlmethvl!-2-thioxo-4- imidazolidi;.one A solution of N-[(2-thiazolyl)amino]thioxomethyl-30 DL-4-chlorophenylalanine methyl ester (0.84 g, 2.36 mmol) and p-toluene sulfonic acid hydrate (0.20 g, 1.05 mmol) in X-8571A' -353- 2 Q Q O toluene (100 mL) was refluxed with a Dean-Stark trap for 48h. The reaction was cooled to room temperature, the solvent removed under reduced pressure, residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and saturated sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting product was recrystallized from ethyl acetate-hexanes to provide 176 mg (23%) of the titled product: 1h NMR (300 MHz, DMSO-d6) 5 7.83 (d, 1H) , 7.78 (d, 1H) , 7.38 (d, 2H), 7.22 (d, 2H), 4.85 (t, 1H), 3.11 (d, 2H); MS (FD) m/e 323 (M+).

Example 263 N- f(2-thiazolvl)amino!thioxomethvl-DL-4-tr if luoromethy 1. phenylalanine methvl eflter A solution of 1-[(2-thiazolyl) thiocarbamoyl] imidazole (1.03 g, 4.1 mmol) and DL-4-trifluoromethylpheny lalanine methyl ester hydrochloride (1.15 g, 4.1 mmol) in ^w-dimethylformamide (75 mL) was heated at 80'C for 6 h. The reaction was cooled to room temperature, the solvent removed under reduced pressure, and the residue recrystallized from ethyl ether-hexanes to provide 389 mg (24%) of the titled product: IR (KBr, cm"1 ) 3178, 3020, 1747, 1577, 1509, 1325, 1278, 1185? !h NMR (300 MHz, DMSO-d6) 5 11.82 (br s, 1H), 9.82 (br s, 1H) , 7.63 (d, 2H), 7.39 (d, 2H), 7.35 (d, 1H), 7.13 (s, 1H), 5.18 (q, 1H), 3.62 (s, 3H), 3.31 (m, 2H); MS (FD) m/e 389 (M+); UV (EtOH) 291nm (e=18127), 255 nm (e=10867), 201nm (8=20712).

X-8571A 260 2 9 Anal. Calcd for C15H14N3F3O2S2: C, 46.26? H, 3.62; N, 10.79. Found: C, 46.21; H, 3.69; N, 11.00.

Example 264 DL-3-(2-thia^alvl)-5-f(4-trifluoromethyl)phenvlmethvll-2- thloxo-4-imldazolidinone A solution of N-[(2-thiazolyl)amino]thioxomethyl-DL-4-trifluoromethylphenylal.inine methyl ester (0.34 g, 0.87 mmol) and p-toluene sulfonic acid hydrate (0.20 g 0.106 mmol) in toluene (100 mL) was refluxed with a Dean-Stark trap for 48 h. The reaction was cooled to room temperature, the solvent removed under reduced pressure, and the residue taken up in ethyl acetate, washed with saturated sodium bicarbonate and saturated sodium chloride, dried over magnesium sulfate, concentrated under reduced pressure to provide 145 mg (46%) of the titled product. IR (KBr, cm'l) 3176, 1779, 1619, 1532, 1508, 1432, 1327, 1270, 1194, 1129? lH NMR (300 MHz, BMSO-de) 8 10.90 (br s, 1H) , 7.83 (d: lH) , 7.79 (d, 1H), 7.65 (d, 2H). 7.41 (d, 2H), 4.88 (t, 1H), 3.22 (d, 2H) ; MS (FD) m/e 357(M+); UV (EtOH) 264nm (e=15626), 201nm (e=16341) .

Anal. Calcd for C14H10F3N3OS2: C, 47.05; H, 2.82; N,11.76.

Found: C, 47.17; H, 2.82; N, 11.53.

Example 265 N-f(2-thiazolvl)amino]thioxomethyl-DL-2.6-difluoronhenvlalanine methvl ester A solution of 1-[(2-thiazolyl) thiocarbamoyl] imidazole (0.65 g, 3.08 mmol) and DL-2,6- X-8571A £f) 0 2 difluorophenylalanine methyl ester hydrochloride (0.78 g, 3.08 mmol) in w, tf-dimethylformamide (75 mL) was heated at 80*c for 7 h. The reaction was cooled to room temperature, the solvent removed under reduced pressure, and the residue 5 recrystallized from ethyl ether-hexanes to provide 413 mg (38%) of the titled product: IR (KBr4 cm-1) 3205, 3036, 1737, 1625, 1554, 1511, 1468, 1442, 1388, 1265; lH NMR (300 MHz, DMSO-dg) 5 11.83 (br S, 1H) , 7.37 (q, 2H) , 10 7.08 (m, 2H), 5.21 (q, 1H), 3.62 (s, 3H), 3.31 (m, 2H); MS (FD) m/e 357(M+); UV (EtOH) 291nm (e=18495), 256 nm (e=10695), 202nm (e=20082) . Anal. Calcd for C14H13F2N3O2S2: C, 47.05; H, 3.67; N, 11.76. Found: " 47.08; H, ?.76; N, 11.93.

Example 266 N- f 2- (1- CYClohexenvl) ethvl 1 -N' - f,4.5«6«7 - tetrahvdrnhenzothiazolvl1 thlom*a A solution of 2-(l-cyclohexenyl)ethyl 20 isothiocyanate (1.67 g, 10 mmol) and 2-amino-4,5,6,7-tetrahydrobenzothiazole (1.54 g, 10 mmol) in N,N-dimethylformamide (100 mL) was heated at 100'C for 120 h. The reaction was cooled to room temperature, the solvent removed under reduced pressure, the residue taken up in 25 ethyl acetate and washed with IN HCl. The organic layer was concentrated and the residue recrystallized from ethyl acetate-hexanes to pre vide 426 mg (13 %) of the titled product: X-8571A- 26 0 - a IR (KBr, cm"1) 3169, 3031, 2931, 1580, 1258, 1198 ; ^•H NMR (300 MHz, DMSO-d6) 6 11.41 (br s, lH) , 10.05 (br S, 1H), 5.43 (s, 1H), 3.58 (m, 2H), 2.6-1.9 (m, 10H), 1.7 (m, 4H) , 1.5 (m, 4H) ; MS (FD) m/e 321 (M+); UV (EtOH) 298nm (£=12157), 257nm (e=6569), 201nm (e=12172) .

Anal. Calcd for C16H23N3S2: C, 59.97 H, 7.21; N, 13.07. Found: C, 60.06; H, 6.95; N, 12.82.

Example 267 N-T 2-(1-rvclohexenvl)ethvll-N'-f 2-(5-chloro)nvrazinvll thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (2.30 g, 13.7 mmol) and 2-amino-5-15 chloropyrazine (1.75 g, 13.7 mmol) in W,.N-dimethylformamide (40 mL) was heated at 100*C for 192 h. The reaction was cooled to room temperature, the solvent removed under reduced pressure, and the residue taken up in ethyl acetate and washed with IN aqueous HCl. The organic layer was 20 concentrated and the resulting product was recrystallized from ethyl acetate-hexanes to provide 64 mg (1.6%) of the titled product: IR (KBr, cm"1) 3192, 2931, 1588, 1515, 1457, 1320, 1251, 1153; !h NMR (300 MHz, DMSO-d6) 6 11.01 (br s, 1H) , 10.45 (t, 1H) , 8.38 (d, 1H), 8.29 (d, 1H), 5.50 (br s, 1H), 3.63 (q, 2H), 2.21 (t', 2H), 1.95 (m, 4H) , 1.52 (m, 4H) ; MS (FD) m/e 296 (M+); UV (EtOH) 330nm (£=9176), 273nm (£=21432), 201nm (£=10972).

X-8571A 2 6 0 2 93 Anal. Calcd for C13H17N4SCI: C, 67.28; H, 8.30; N, 13.85. Found: C, 67.55; H, 8.48; N, 13.94.

F.xample 268 N-T2-fl-cvclohexenvl)ethvll -N'-(2-T4-(3.4- rii rhlnronhpnvl)1thiazolvl) thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10 mmol) and 4-(3,4-dichlorophenyl)-2-thiazolamine (2.45 g, 10 mmol) in N,N-10 dimethyiformamide (50 mL) was heated at 100'C for 120 h.

The reaction was cooled to room temperature, the solvent removed under reduced pressure, and the residue taken up in ethyl acetate and washed with IN HCl. The organic layer was concentrated and the residue recrystallized from ethyl 15 acetate-hexanes to provide 933 mg (2.3%) of the titled product: IR (KBr, cm-1) 3169, 2927, 1573, 1558, 1523, 1460, 1393, 1295, 1214 ; !h NMR (300 MHz, DMSO-d6) 5 11.72 (br s, 1H) , 9.11 (br s, 20 1H), 8.07 (d, 1H), 7.83 (m, 1H), 7.62 (m, 2H), 5.45 (m, 1H) , 3.60 (m, 2H), 2.21 (m, 2H), 1.85 (m, 4H) , 1.43 (m, 4H) ; MS (FD) m/e 411 (M+); UV (MeOH) 287nm (6=25040), 241nm (6=16142), 205nm (e=29362) . 25 Anal. Calcd for C18H19N3S2CI2: C, 52.42; H, 4.64; N, 10.19. 'found: C, 52.63; H, 4.48; N, 10.21.

Example 26? 1-(2-r2-methoxyphenyl1ethvl)thiocarbamoyl imidazole 30 A solution of 1,1'-thiocarbonyldiimidazole (1.78 g, 10 mmol) and 2-methoxyphenethylamine (1.51 g, 10 mmol) X-8571A 260 in acetonitrile (25 mL) was stirred at room temperature for 20 h. The resulting precipitate was collected by filtration to provide 1.40 g (53%) of the titled product: IR (KBr, cm-1) 2944, 1563, 1493, 1409, 1282, 1246, 1031, 755; iH NMR (300 MHz, DMSO-d6) 8 12.0 (br S, lH), 7.65 (S, 1H), 7.25 (m-, 2H) , 7.05-6.9 (m, 4H), 3.8 (m, 2H) , 3.8 (s, 3H) , 2.95 (t, J=7 Hz, 2H); MS (FD) m/e 261 (M+); UV (EtOH) 278nm (8=7083), 216 nm (e?=12683), 203 nm (e=22221) .

Example 270 N-r 2-(2-methoxypheny1)ethvl 1 -N1 -(2-pvridvl) thiourea A solution of 1— (2—[2 — methoxyphenyl]ethyl)thiocarbamoyl imidazole (0.52 g, 2 mmol) and 2-aminopyridine (0.19 g, 2 mmol) in N,N-dime thyl formamide (5 mL) was stirred at 90'C for 4 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 0.25 g (44%) of the titled product: IR (KBr, cm"1) 3219, 3048, 1607, 1557, 1236, 1036, 756; l-H NMR '(300 MHz, DMSO-d6) 8 11.65 (m, 1H) , 10.55 (br s, lH) , 8.1 (m, 1H), 7.75 (m, 1H), 7.3-6.9 (m, 6H), 3.8 (m, 2H), 3.78 (s, 3H), 2.9 (t, J=7 Hz, 2H); MS (FD) m/e 287 (M+); UV (EtOH) 290nm (6=10141), 267nm (6=13121), 247 nm (6=10959), 202 nm (6=24078).

X-8571A -359- « 26 Q c L.. . , Example 271 N-f 2-(1-cvclnhexenvl)ethvl1-N'-f 2 -(6-methvl)nvridvl1 thiourea A solution of 2-(l-cyclohexenyl)ethyl 5 isothiocyanate (1.67 g, 10.0 mmol) and 2-amino-6- methylpyridine (1.08 g, 10.0 mmol) in JV,2y-dime thyl formamide (25 mL) was heated at 90'C for 20 h. The reaction was cooled to room temperature and the solvent removed under reduced pressure. The resulting product was recrystallized 10 from ethyl acetate-hexanes to provide 1.04 g (38%) of the titled product: IR (KBr, cm"1) 3230, 2920, 1608, 1572, 1540, 1457, 1378, 1317, 1235, 1164; !h NMR (300 MHz, DMSO-dg) 8 11.7 (br t, 1H) , 10.45 (s, lH) , 15 7.62 (t, 1H), 6.95 (d, lH), 6.90 (d, lH), 5.50 (br s, 1H), 3.7 (q, 2H), 2.4 (s, 3H), 2.25 (t, 2H), 1.95 (m, 4H), 1.55 (m, 4H); MS (FD) m/e 275 (M+); UV (EtOH) 296nm (e=17669), 265nm (e=16667), 247nm (e=15266) . 20 Anal. Calcd for C15H21N3S: C, 65.42; H, 7.69; N, 15.26. Found: C, 65.42; H, 7.75; N, 15.20.

Example 272 N-f 2-(1-cvclohexenvl)ethvl1-N'-\2-(5-methvl)pvri dvll 25 thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10.0 mmol) and 2-amino-5-methylpyridine (1.08 g, 10.0 mmol) in J^N-dimethylformamide (25 mL) was heated at 90'C for 20 h. The reaction was 30 cooled to room temperature and the solvent removed under reduced pressure. The resulting product was recrystallized ® 25 X-8571A -360- 26 from ethyl acetate-hexanes to provide 1.06 g (39%) of the titled product: IR (KBr, cm"1) 3225, 2933, 1596, 1569, 1532, 1494, 1344, 1311, 1232, 827; !h NMR (300 MHz, DMSO-dg) 8 11.55 (br t, 1H) , 10.45 (s, 1H) , 7.95 (br s, 1H), 7.6 (dd, lH), 7.05 (d, 1H), 5.5 (br s, 1H), 3.7 (q, 2H), 2.3 (m, 5H), 1.95 (m, 4H), 1.55 (m, 4H); MS (FD) m/e 275 (M+); UV (EtOH) 298nm (6=13 663) , 268nm (£=21631) , 249nm (6=14893) . Anal. Calcd for C15H21N3S: C, 65.42; H, 7.69; N, 15.26. Found: C, 65.15; H, 7.75; N, 15.33.

Example 273 N-T2-(1-cvclohexenvl)ethvl1-N'-T2-(4-methvl)pvridyll thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10.0 mmol) and 2-amino-4-methylpyridine (1.08 g, 10.0 mmol) in N,W-dimethylformamide (25 mL) was heated at 90'C for 16 h. The reaction was cooled to room temperature and the solvent removed under reduced pressure. The resulting product was purified by HPLC to provide 1.67 g (61%) of the titled product; IR (KBr, cm"1) 3220, 2935, 1617, 1535, 1487, 1322, 1188, 866; NMR (300 MHz, DMSO-dg) 8 11.65 (br t, 1H) , 10.45 (s, 1H) , 8.0 (d, 1H), 6.95 (s, 1H), 6.85 (d, 1H), 5.5 (br s, 1H) , 3.65 (q, 2H) , 2.3 (m, 5H) , .1.95 (m, 4H) , 1.55 (m, 4H) ; MS (FD) m/e 275 (M+); UV (EtOH) 289nm (6=16865), 266nm (6=17870), 247nm (6=14179), 202nm (6=20105) .

X-8571A -361- 26 Q 2 Anal. Calcd for C15H21N3S: C, 65.42; H, 7.69; N, 15.26. Found: C, 65.16; H, 7.55; N, 15.30.

Example 274 N-r 2-(1-cvclohexenvl)ethvl1-N'-f2-(3-methvl)pvridvl1 thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10.0 mmol) and 2-amino-3-methylpyridine (1.08 g, 10.0 mmol) in N,lV-dimethyl formamide (25 mL) was heated at 90*C for 16 h. The reaction was cooled to room temperature and the solvent removed under reduced pressure. The resulting product was purified by HPLC to provide 1.8 g (65%) of the titled product; IR (KBr, cm"1) 3220, 2931, 1589, 1513, 1462, 1325, 1164; lH NMR (3 00 MHz, DMSO-d6) 8 11.6 (br t, 1H) , 8.65 (s, 1H) , 8.05 (d, 1H), 7.65 (d, 1H), 7.05 (dd, 1H), 5.5 (br s 1H), 3.65 (g, 2H), 2.3 (s, 3H), 2.25 (t, 2H), 1.95 (m, 4H), 1.55 (m, 4H); MS (FD) m/e 275 (M+); UV (EtOH) 293nir. (8=16693) , 264nm (8=14464), 244nm (e=14762) , 201nm (8=16723) .

Example 275 N-f 2-(1-cvclohexenvl)ethvll-N'-\2-(6-ethvl)nvridvl1 thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10.0 mmol) and 2-amino-6-ethylpyridine (1.22 g, 10.0 mmol) in N,N-dimethylformamide (25 mL) was heated at 90*C for 20 h. The reaction was cooled to room temperature and the solvent removed under X-8571A 260 2 reduced pressure. The resulting product was purified by HPLC to provide 1.55 g (54%) of the titled product; IR (KBr, cm-1) 3230, 2930, 1604, 1533, 1450, 1211, 1157; ^-H NMR (300 MHz, DMSO-d6> 5 11.8 (br t, 1H) , 10.45 (s, lH) , 7.62 (t, 1H), 6.95 (d, 1H), 6.90 (d, 1H), 5.45 (br s, 1H), 3.7 (q, 2H), 2.7 (q, 2H), 2.25 (t, 2H), 1.95 (m, 4H), 1.55 (m, 4H), 1.2 (t, 3H); MS (FD) m/e 289 (M+); UV (EtOH) 296nm (e=17903), 265nm (e=16556), 247nm (e=14932) , 201nm (£=14174) .

Anal. Calcd for C16H23N3S: C, 66.40; H, 8.01; N, 14.52. Found: C, 66.40; H, 8.00; N, 14.75.

Example 27 6 N-r 2-(1-cvclnhexpnvl)ethvl1-N'-r2-(4-ethvl)pvridvl 1 thiourea A solution of 2-(l-cyclohexenyl)ethyl isothiocyanate (1.67 g, 10.0 mmol) and 2-amino-4-ethylpyridine (1.22 g, 10.0 mmol) in N,N-dimethylformamide (25 mL) was heated at 90'C for 16 h. The reaction was cooled to room temperature and the solvent removed under reduced pressure. The resulting product was purified by HPLC to provide 1.2 g (42%) of the titled product; IR (KBr, cm"1) 3215, 2931, 1615, 1535, 1407, 1334, 1198, 843; XH NMR (300 MHz, DMSO-d6) 8 11.68 (br t, 1H) , 10.45 (s, 1H) , 8.0 (d, 1H), 7.0 (s, 1H), 6.9 (d, 1H), 5.5 (br s, 1H), 3.65 (q, 2H), 2.6 (q, 2H), 2.25 (t, 2H), 1.95 (m, 4H), 1.55 (m, 4H), 1.15 (t, 3H); MS (FAB) m/e 290 (M+H); X-8571A -363- 2 6 0 P 9 3 UV (EtOH) 289nm (6=17378), 26631111(6=18654), 247nm (6=14847), 202nm (6=23101) .

Anal. Calcd for C3.6H23N3S: C, 66.40; H, 8.01; N, 14.52. Found: C, 66.45; H, 7.99; N, 14.26.

Example 277 N-r2-(1-cvclohexenvl)ethvl1-N'-f 2- (5-trifluoromethyl)ovridvl1 thiourea A solution of 2-(l-cyclohexenyl)ethyl 10 isothiocyanate (1.67 g, 10.0 mmol) and 2-amino-5- trifluoromethylpyridine (1.62 g, 10.0 mmol) in N,N-dime thyl formamide (25 mL) was heated at 90 "C for 72 h. The reaction was cooled to room temperature and the solvent removed under reduced pressure. The resulting product was 15 purified by HPLC to provide 0.33 g (10%) of the titled product; IR (KBr, cm"1) 3220, 2929, 1618, 1551, 1500, 1324, 1238, 1132, 1078, 828; ^ NMR (300 MHz, DMSO-d6) 5 11.4 (br t, 1H) , 10.95 (s, lH) , 20 8.5 (br s, lH) , 8.15 (dd, 1H) , 7.3 (d, 1H) , 5.55 (br s, 1H) , 3.7 (q, 2H) , 2.3 (t, 2H) , 1.95 (m, 4H) , 1.55 (m, 4H) ; MS (FD) m/e 329 (M+); UV (EtOH) 296nm (6=17058), 255nm (6=14250).

Anal. Calcd for C15H18N3F3S: C, 54.70; H, 5.51; N, 12.76. 25 Found: C, 54.98; H, 5.67; N, 12.59.

X-8571A 2 6 0 9 Q ? \J Example 278 N- (2-f cvclohexanvl1ethvl)-N'-\2-(4-methvl)thiazolvl1 thiourea A solution of l-[(2-[4-methyl]thiazolyl) 5 thiocarbamoyl] imidazole (1.0 g, 4.46 mmol) and 2-cyclohexanylethylamine (0.567 g, 4.46 mmol) in N,N-dimethylformamide (25 mL) was stirred at 90'C for 16 h, the reaction was cooled to room temperature and the solvent removed" in vacuo. The residue was crystallized from ethyl 10 acetate to provide 0.72 g (57%) of the titled product: IR (KBr, cm-1) 3220, 2922, 1565, 1505, 1227, 1168; !h NMR (300 MHz, DMSO-d6) 8 11.5 (br s, 1H) , 9.9 (br s, 1H) , 6.65 (s, 1H), 3.55 (m, 2H), 2.25 (s, 3H), 1.8-0.8 (m, 13H); MS (FD) m/e 283 (M+); UV (EtOH) 291nm (e=5315), 257nm (e=2711) .

Anal. Calcd for C13H21N3S2: C, 55.09 H, 7.47; N, 14.82. Found: C, 55.29; H, 7.60; N, 14.64.

Example 279.

N-T2-(2-methoxvnhenvl)ethvl 1 -N'-f2-(5-methvllPvridyll thiourea A solution of l-(2-[2-methoxyphenyl 3 ethyl) thiocarbamoyl imidazole (0.7 g, 2.68 mmol) and 2-amino-5-methylpyridine (0.29 g, 2.68 mmol) in 25 N,N-dimethyiformamide (5 mL) was stirred at 90'C for 16 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 0.62 g (77%) of the titled product: IR (KBr, cm"1) 3227, 2932, 1612, 1534, 1493, 1273, 1037; !h NMR (300 MHz, DMSO-d6) 8 11.55 (br t, 1H) , 10.45 (s, 1H) , 9 20 9 25 2 6 0 ? Q .7 X-8 571A -365- w w 7.9 (br s, 1H), 7.6 (m, 1H), 7.2-6.9 (m, 5H), 3.8 (m, 5H), 2.9 (t, J=7 Hz, 2H), 2.2 (s, 3H); MS (FAB) m/e 302 (M+H); UV (EtOH) 298nm (e=13316), 268nm (e=23132), 249 nm (£=15574), 202 nm (£=25460) .

Anal. Calcd for C16H19N3OS: C, 63.76; H, 6.35; N, 13.94. Found: C, 63.71; H, 6.34; N, 13.79.

Example 280 1-\2-(2-Chlorophenyl)ethvl1-thiocarbamoyl imidazole A solution of 1,1'-thiocarbonyldiimidazole (1.8 g, 10 mmol) and 2-(2-chlorophenyl)ethyl amine (1.56 g, 10 mmol) in acetonitrile (100 mL) was stirred at room temperature for 3 h. The solution was concentrated to about 50 ml and was placed in the freezer for 4 days. The resulting crystals were collected by filtration to provide 2.37 g (89%) of crude title product. mp 74-78*C.

IR (KBr, cm-1) 3134, 2924, 1564, 1529, 1474, 1448, 1411, 1353, 1287, 1215; MS (FD) m/e 266 (M+); UV (EtOH) 278nm (£=5421), 247 nm (£=5655), 202 nm (£=22240).

Example 281 N- r2-(2-chlorophenyl)ethvl1-N'-f 2-(5-methvl)pvridvl1 thiourea A solution of 1— (2— £2 — chlorophenyl]ethyl)thiocarbamoyl imidazole (1.0 g, 3.76 mmol) and 2-amino-5-methylpyridine (0.41 g, 3.76 mmol) in JV, N-dimethylformamide (10 mL) was stirred at 90*C for 16 h.

X-8571A 260293 the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 0.92 g (80%) of the titled product: IR (KBr, cm"1) 3226, 1597, 1532, 1491, 1273, 1050; 5 !h NMR "(300 MHz, DMSO-d6) 8 11.6 (br t, 1H) , 10.5 (s, 1H) , 7.9 (br s, 1H), 7.6-7.0 (m, 6H), 3.9 (q, 2H), 3.1 (t, J=7 Hz, 2H), 2.2 (s, 3H); MS (FD) m/e 305 (M+); UV (EtOH) 298nm (e=14145), 268nm (6=21034), 249 nm (e=15757), 10 202 nm (e=23053) .

Anal. Calcd for C15H16N3CIS: C, 58.91; H, 5.27; N, 13.74. Found: C, 58.65; H, 5.39; N, 13.77.

Example 282 1-ft2-(d-ethvl)thiazolvl)thionarbamovll imidazole A solution of 1,1'-thiocarbonyldiimidazole (11.9 g, 60 mmol) and 2-amino(4-ethyl)thiazole (8.0 g, 60 mmol) in acetonitrile (250 mL) was stirred at room temperature for about 5 h. The resulting precipitate was collected by 20 filtration to provide 12.0 g (85%) of the titled product, mp. 198-200*C; IR (KBr, cm"1) 2970, 2637, 1609, 1529, 1461, 1398, 1357, 1226, 1262; iH NMR (300MHz, DMSO-d6) 8 8.6 (s, 1H), 7.9 (s, 1H), 7.0 (s, 1H), 6.9 (s, 1H), 2.6 (q, J=7 Hz, 2H) , 1.2 (t, J=7 Hz, 25 3H); MS (FD) rn/e 238 (M+); UV (EtOH) 361 nm (6=11223), 290 nm (6=8828) , 203 nm (6=20303) .

Anal. Calcd for C9H10N4S2: C, 45.36 H, 4.23; N, 23.51. 30 Found: C, 45.51; H, 4.20; N, 23.53.

X-8571A 260 2 F.xamr>le 283 N-(2-f 2-pvririvl1ethvl)-N■-T 2-(4-ethvl)thiazolvl1 thiourea A solution of 1-1(2-[4-ethyl]thiazolyl)thiocarbamoyl] imidazole (1.00 g, 4.2 mmol) 5 and 2-(2-aminoethyl)pyridine (0.51 g, 4.2 mmol) in N,N- dimethylformamide (25 mL) was stirred at 90"C for 3 h, the reaction was cooled to room temperature and uie solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 0.75 g (61%) of the titled product: 10 IR (KBr-, cm""1) 3163, 1557, 1524, 1222, 757; iH NMR (300 MHz, DMSO-dfi) 8 11.3 (br s, 1H) , 10.0 (br s, 1H), 8.5 (m, 1H), 7.7 (m, 1H), 7.25 (m, 2H), 6.6 (s, 1H), 3.9 (m, 2H), 3.05 (m, 2H), 2.45 (q, J=7 Hz, 2H), 1.05 (t, J=7 Hz, 3H); MS (FD) m/e 292 (M+) ; UV (EtOH) 292nm (£=17803), 261nm (e=12919), 201 nm (6=17809).

Anal. Calcd for C13H16N4S2: C, 53.40 H, 5.51; N, 19.16. Found: C, 53.64; H, 5.51; N, 19.02.

Example 284 N- (2 - ri-cvclohexenvll p.thvl* -N' - T2 - (4-ethvl) thi zolvll thiourea A solution of 1-[(2-[4-ethyl]thiazolyl) thiocarbamoyl] imidazole (0.75 g, 3.15 mmol) and 2-(l-cyclohexenyl)ethylamine (0.39 g, 3.15 mmol) in N,N-25 dimethyiformamide (15 mL) was stirred at 90*C for 4 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 0.77g (83%) of the titled product: MP 155-156'C; IR (KBr, cm"1) 3172, 2914, 1560, 1507, 1202, 30 710; 260 pg X-8571A -368- w l-H NMR (300 MHz, DMSO-d6) 8 11.5 (br s, lH) , 9.8 (br s, 1H), 6.6 (s, 1H), 5.42 (s, 1H), 3.56 (q, J=7 Hz, 2H), 2.45 (m, 2H), 2.16 (m, 2H), 1.9 (m, 4H>, 1.5 (m, 4H), 1.12 (t, J=7 Hz, 3H); MS (FD) m/e 295 (M+); UV (EtOH) 291nm (e=19227), 257nm (e=9628), 201 nm (e=15736) . Anal, ''alcd for C14H21N3S2: C, 56.91 H, 7.16; N, 14.22. Found? C, 57.20; H, 7.22; N, 14.16.

Example 285 N- f 2-f2-chlorophenyl)ethyl1-N'-f 2 -(4-ethvl)thiazolyl1 thiourea A solution of 1-[ (2-[4-ethyl]thiazolyl) thiocarbamoyl] imidazole (0.75 g, 3.15 mmol) and 2-(2-chlorophenyl)ethylamine (0.49 g, 3.15 mmol) in N,N-dimethylformamide (15 mL) was stirred at 90*C for'2 h, the reaction was cooled to room temperature arid the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 0.85 g (83%) of the titled product: MP 153-155'C; IR (KBr, cm"1) 3167, 3018, 1570, 1505, 1215, 749, 599; !h NMR (300 MHz, DMSO-d6) 8 11.65 (br s, 1H) , 9.85 (br s, 1H) , 7.5-7.2 (rn, 4H) , 6.65 (s, 1H), 3.85 (m, 2H) , 3.05 (t, J=7 Hz, 2H), 2.55 (q, J=7 Hz, 2H), 1.1 (t, J=7 Hz, 3H); MS (FD) m/e 325 (M+); UV (EtOH) 292nm (6=19154), 257nm (e=10451) , 202 nm (8=24308). Anal. Calcd for C14H16N3S2CI: C, 51.60; H, 4.95; N, 12.87. Found: C, 51.75; H, 4.98; N, 12.79.

X-8571A 2 6 0 2 Example 286 N- r 2-(2-methoxypheny1)ethvl1-N'-f 2-(4-ethvl)thiazolvl1 thiourea A solution of 1-t(2-[4-ethyl]thiazolyl) thiocarbamoyl] imidazole (0.70 g, 2.94 mmol) and 2-(2-methoxyphenyl)ethylamine (0.44 g, 2.94 mmol) in N,N-dimethylformamide (15 mL) was stirred at 95'C for 2 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 0.67 g (71%) of the titled product: MP 166-167.5*C; IR (KBr, cm-1) 3173, 3025, 1528, 1248, 1209, 755, 677; !h NMR (300 MHz, DMSO-d6) 8 11.5 (br s, 1H) , 9.85 (br s, 1H), 7.2-6.8 (m, 4H), 6.57 (s, 1H), 3.7 (m, 5H), 2.82 (t, J=7 Hz, 2H), 2.4 (q, J=7 Hz, 2H), 1.06 (t, J=7 Hz, 3H); MS (FD) m/e 321 (M+) ; UV (EtOH) 291nm (£=12114), 259nm (e=6792) , -201 nm (£=18914). Anal. Calcd for C15H19N3OS2: C, 56.04; H, 5.96; N, 13.07. Found: C, 55.83; H, 6.00; N, 13.08.

Example 287 N-r 2-(3-methoxyphenyl)ethvl1-N'-f 2-(4-ethvl)thiazolvl1 thiourea A solution of 1-[ (2-[4-ethyl]thiazolyl) thiocarbamoyl] imidazole (0.70 g, 2.94 mmol) and 2 — (3-methoxyphenyl)ethylamine (0.44 g, 2.94 mmol) in N,N-dimethylformamide (15 mL) was stirred at 90*C for 2 h, the reaction was cooled to room temperature and the solvent removed in vacuo. The residue was crystallized from ethyl acetate to provide 0.76 g (80%) of the titled product: MP 123-125'C; X-8571A 0 £ pi ^ IR (KBr, cm"1) 3167, 3027, 1587, 1207, 699; 1H NMR (300 MHz, DMSO-d6) 8 11.5 (br s, 1H), 9.9 (br s, 1H), 7.2-6.8 (m, 4H), 6.58 (s, 1H), 3.75 (m, 2H), 3.67 (s, 3H), 2.84 (t, J=7 Hz, 2H), 2.45 (q, J=7 Hz, 2H) , 1.05 (t, J=7 Hz, 3H); MS (FD) m/e 321 (M+); UV (EtOH) 292nm (e=19113), 258nm (e=10607) , 202 nm (e=29289) . Anal. Calcd for C15H19N3OS2: C, 56.04; H, 5.96; N, 13.07. Found: C, 56.08; H, 5.96; N, 13.16.

Example 288 1-r(2-r4-cvannl thiazolvl)thiocarbamoyl1 imidazole A solution of 1,1'-thiocarbonyldiimidazole (3.2 g, 16 mmol) and 2-amino-4-cyanothiazole (2.0 g, 16 mmol) in acetonitrile (40 mL) was stirred at room temperature for 72 h and heated at 60'C for 24 h. The resulting precipitate was collected by filtration to provide 2.74 g (73%) of the titled product: IR (KBr, cm"1) 3097, 2230; iH NMR (300 MHz, DMSO-d6) 8 11.99 (br s, 1H) , 8.76 (s, 1H) , 8.67 (s, 1H), 8.07 (s, 1H), 7.92 (s, 1H) ; MS (FAB) m/e 236 (M+H).

Example 289 N-r 2-(2-Chlorophenyl)ethvl1-N'-T 2-(4-cvano)thiazolvl1 thiourea A solution of 1—[(2—[4-cyano]thiazolyl)thiocarbamoyl] imidazole (0.66 g, 2.8 mmol) and 2-(2-chlorophenyl)ethylamine (0.45 g, 2.8 mmol) in N,N-dimethylformamide (15 mL) was stirred at 100'C for 2 h.

X-8571A 26 0 2 Q The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by chromatography on silica gel to provide 0.24 g (26%) of the titled product: mp 165-168*C; IR (KBr, cm"1) 3119, 2955, 2232, 1577, 1505, 1461, 1328, 1299, 1221, 1053, 826; l-H NMR (300 MHz, DMSO-d6) 5 11.8 (br s, 1H), 8.5 (br s, 1H), 8.1 (s, 1H), 7.2-7.4 (m, 4H), 3.74 (m, 2H), 2.98 (t, J=7 Hz, 2H); MS (FD) m/e 322 (M+); UV (EtOH) 287nm (e=10082), 258 nm (©=15462), 205 nm (e=31601) .

Example 290 N-r2- (3-chlorophenyl)ethvl1-N'-f 2-(4-cvano)thiazolvl1 thiourea A solution of l-[(2-[4-cyano]thiazolyl)thiocarbamoyl] imidazole (0.66 g, 2.8 mmol) and 2-(3-chlorophenyl)ethylamine (0.44 g, 2.8 mmol) in N,N-dime thyl formamide (15 mL) was stirred at 90 "C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueons HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from methylene chloride to provide 0.21 g (23%) of the titled product as a tan solid: mp 180-185'C; IR (KBr, cm-1) 2955, 2239, 1559, 1522, 1331, 1251, 1206, 1168, 823; X-8571A 26 0 ^-H NMR (300 MH7, DMSO-d6) 5 11.8 (br s, 1H), 8.4 (br s, 1H), 8.1 (s, 1H), 7.1-7.3 (m, 4H), 3.71 (m, 2H), 2.86 (t, J=7 Hz, 2H); MS (FD) m/e 322 (M+), 324; UV (EtOH) 287nm (e=10684), 258 nm (e=16406), 207 nm (8=33113) .

Example 291 N-f 2-(2-methoxyphenyl)ethvl1-N■-\2-(4-cvano)thiazolvl1 io thiourea A solution of 1—[(2—14— cyano]thiazolyl)thiocarbamoyl] imidazole (0.66 g, 2.8 mmol) and 2-(2-methoxyphenyl)ethylamine (0.46 g, 2.8 mmol) in W, iV-dimethylformamide (15 mL) was stirred at 90'C for 2 h. 15 The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by chromatography on silica gel to provide 0.21 g (23%) of the titled 20 product as a yellow solid: mp 159-161*C; IR (KBr, cm"1) 2937, 2235, 1566, 1454, 1301, 1243, 1208, 1173, 754; !h NMR (300 MHz, DMSO-d6) 8 11.8 (br s, 1H) , 8.4 (br s, 1H) , 25 8.1 (s, 1H), 6.8-7.2 (m, 4H), 3.73 (s, 3H), 3.66 (m, 2H), 2.81 (t, J=7 Hz, 2H); MS (FD) m/e 318 (M+); UV (EtOH) 279nm (8=12102), 259 nm (e=16281), 203 nm (8=33347) .

X-8571A -373- 26 0 n O 0 Example 292 N- r2- (3-methoxyphenyl) ethvll -N' - T2 - (4-cvano) thiazolvl 1 thiourea A solution of 1- [ (2-[4-5 cyano]thiazolyl)thiocarbamoyl] imidazole (0.66 g, 2.8 mmol) and 2-(3-methoxyphenyl)ethylamine (0.44 g, 2.8 mmol) in N,N-dimethylformamide (15 mL) was stirred at 90'C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue purified by chromatography on silica gel to provide 0.21 g (23%) of the titled product- as a yellow solid: mp 151-153*C; IR (KBr, cm"1) 3065, 2235, 1564, 1515, 1295, 1250, 1209, 1155, 1058, 874, 768, 748, 684; !h NMR (300 MHZ, DMSO-C?6) 8 11.8 (br S, 1H) , 8.4 (br s, 1H) , 8.1 (s, 1H), 7.18 (m, 1H), 6.77 (m, 3H), 3.68 (m, 5H) , 2.80 (t, J=7 Hz, 2H); MS (FD) m/e 318 (M+) ; UV (EtOH) 280nm (e=11770), 258 nm (£=16613), 204 nm (£=34785) .

Example 293 n-t 2-(l-cyclohexenyl)ethyl1-n'-^' jb. cvano)thiazolvl1 thiourea A solution of l-[(2-[4-cyano]thiazolyl)thiocarbamoyl] imidazole (0.82 g, 3.5 mmol) and 2-(l-cyclohexenyl)ethylamine (0.45 g, 3.5 mmol) in N,N- dimethyiformamide (15 mL) was stirred at 90*C for 1.5 h.

The reaction was cooled to room temperature, poured into X-8571A 26 0 y 0 7 ♦ n ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was purified by chromatography on silica gel to provide 0.27 g (26%) of the 5 titled product as a pale yellow solid: mp 176-178 *C; IR (KBr, cm"1) 3169, 3075, 2924, 2233, 1556, 1513, 1330, 1298, 1260, 1217, 1200, 1167, 1145, 983, 922; ^■H NMR (300 MHz, DMSO-d6) 8 11.87 (br s, 1H) , 8.40 (br s, 1H), 8.11 (s, 1H), 5.42(br s, lH), 3.52 (m, 2H), 2.14 (t, J=7 Hz, 2H), 1.90 (m, 4H), 1.49 (m, 4H); MS (FD) m/e 292 (M+); UV (EtOH) 288nm (e=11250) , 258 nm (e=16113), 206 nm (6=25473) Anal. Calcd for C13H16N4S2: C, 53.40; H, 5.52; N, 19.16. Found: C, 53.10; H, 5.55; N, 18.96.

Example 294 1- r (2 - f'4- (3-chlorophenyl 1 thiazolvl) thiocarbamoyl 1 imidazole 20 A solution of 1,1'-thiocarbonyldiimidazole (2.52g, 12 mmol) and 4-(3-chlorophenyl)-2-thiazoleamine (2.14 g, 12 mmol) in acetonitrile (35 mL) was stirred at room temperature for 30 hours. The resulting precipitate was collected by filtration to provide 2.77 g (72%) of the 25 titled product: MS (FAB) m/e 321 (M+H).

X-8571A 2 6 0 9 Q - " f Example 295 N-T 2-(2-chlorophenyl)ethvl1-N'-f2-f4-(3- chloronhenv1)11thiazolvl thiourea A solution of 1—[(2—[4— (3 — 5 chlorophenyl]thiazolyl)thiocarbamoyl] imidazole (0.92 g, 2.86 mmol) and 2-(2-chlorophenyl)ethylamine (0.46 g, 2.86 mmol) in W,jy-dimethylformamide (15 mL) was stirred at 90'C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous 10 HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 1.0 g (86%) of the titled product as yellow needles: mp 193-195*C; IR (KBr, cm-1) 3018, 1560, 1515, 1470, 1291, 1210, 1065, 935, 785, 757, 716; iH NMR (300 MHz, DMSO-c?6) 8 11.66 (br s, 1H) , 9.29 (br s, 1H), 7.79 (s, 1H), 7.63 (m, 2H), 7.35 (m, 4H), 7.23 (m, 2H), 3.83 (m, 2H) , 3.02 (t, J=7 Hz, 2H); MS (FD) m/e 407 (M+), 409 (M+2); UV (EtOH) 285nm (e=22709), 266 nm (6=20608), 202 nm (6=37861) .

Anal. Calcd for CI8H15N3S2CI2: C, 52.94; H, 3.70; N, 10.29. Found: C, 52.96; H, 3.74; N, 10.49.

Example 296 N-T2-(3-methoxyphenyl)ethy11-N'-f2-f4- (3- chlorophenyl)11thiazolyl thiourea A solution of l-[(2-[4-(3-30 chlorophenyl]thiazolyl)thiocarbamoyl] imidazole (0.92 g, 2.86 mmol) and 2-(3-methoxyphenyl)ethylamine (0.45 g, 2.86 2 6 0 On X-8571A -376- ^ C y mmol) in iV, iV-dimethylformamide (15 mL) was stirred at 90'C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 0.85 g (74%) of the titled product as a white solid: mp 183-185"C; IR (KBr, cm'1)3172, 3024, 1569, 1515, 1466, 1319, 1287, 1260, 1220, 1067, 996, 775, 728, 604; iH NMR (300 MHz, DMSO-d6) 5 11.66 (br s, 1H) , 9.20 (br s, 1H) , 7.81 (s, 1H), 7.63 (m, 2H), 7.35 (m, 2H), 7.16 (m, 1H), 6.73 (m, 3H), 3.77 (m, 2H), 3.64 (s, 3H), 2.86 (t, J=7 Hz, 2H); MS (FD) m/e 403 (M+), 405 (M+2); UV (EtOH) 280nm (e=23880), 202 nm (e=42912) .

Anal. Calcd for C19H18N3OS2CI: C, 56.49; H, 4.49; N, .40. Found: C, 56.62; H, 4.50; N, 10.58.

Example 297 N-T2-(l-cyclohexenvl)ethyn-N'-T2-f4-(3- chlorophenyl)11thiazolyl thiourea A solution of 1—[(2-[4—(3-chlorophenyl]thiazolyl)thiocarbamoyl] imidazole (0.92 g, 2.86 ramol) and 2-(l-cyclohexenyl)ethylamine (0.37 g, 2.86 mmol) in i^-N-dimethylformamide (15 mL) was stirred at 90'C for 0.5 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was X-8571A 260 2 3 crystallized from EtOAc to provide 0.7 g (65%) of the titled product as a white solid: mp 196-197'C; IR (KBr, cm"1) 2939, 1557, 1514, 1469, 1287, 1202, 1062, 5 881, 784, 719, 661; 2H NMR (300 MHz, DMSO-d6) 8 11.66 (br s, 1H), 9.17 (br s, 1H), 7.85 (s, 1H), 7.76 (m, lH), 7.61 (s, 1H), 7.37 (m, 2H), 5.41(br s, lH), 3.60 (m, 2H), 2.20 (t, J=7 Hz, 2fc) , 1.87 (m, 4H), 1.46 (m, 4H); MS (FD) m/e 377 (M+), 379 (M+2); UV (EtOH) 285nm (e=23385), 232 nm (e=18756), 202 nm (e=31779) Anal. Calcd for C18H20N3S2CI: C, 57.20; H, 5.33; N, 11.12. Found: C, 57.04; H, 5.32; N, 11.09.

Example 298 1- r (2 - T4- <3-nifcroohenvll thiazolvl) thiocar-hamovll imidazole A solution of 1,1'-thiocarbonyldiimidazole (0.41g, 2.3mmol) and 4-(3-nitrophenyl)-2-thiazoleamine 20 (0.5g, 2.3 mmol) in acetonitrile (25 mL) was stirred at room temperature for 72 h and heated at 60'C for 72 h. The resulting precipitate was collected by filtration to provide 0.51 g (68%) of the titled product: MS (FAB) m/e 332 (M+H).

Anal. Calcd for C13H9N5O2S2: C, 47.12; H, 2.73; N, 21.13. Found: C, 47.35; H, 2.69; N, 21.03.

X-8571A. 26 0 9 Example 299 M- r 2-(1-cvclohaxenvl)ethvl1-N'-f2-r4-(3- nitrophenvl)11thiazolvl thiourea A solution of 1-[(2- [4- (3-nitrophenyl]thiazolyl)thiocarbamoyl] imidazole (0.5g, 1.5 mmol) and 2-(l-cyclohexenyl)ethylamine (0.19 g, 1.5 mmol) in N,N- dime thyl formamide (15 mL) was stirred at 90'C for 0.75 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 0.37 g (63%) of the titled product as a yellow solid: mp 218-221*C; IR (KBr, cm-1). 3165, 3017, 2922, 1569, 1513, 1465, 1352, 1265, 1216, 1167, 1065, 877, 788, 713, 676; % NMR (300 MHz, DMSO-<?6) 8 11.76 (s, 1H) , 8.85 (br S, lH) , 8.61 (s, 1H), 8.25 (d, J=8 Hz, 1H), 8.11 (d, J=8 Hz, 1H), 7.77 (s, 1H), 7.67 (m, 1H), 5.42(br s, lH), 3.58 (m, 2H), 2.20 (t, J=7 Hz, 2H), 1.89 (m, 4H) , 1.46 (m, 4H); MS (FD) m/e 388 (M+); UV (EtOH) 286nm (6=22903), 265nm (6=23582), 237 nm (e=17806) , 202 nm (6=24107) Anal. Calcd for CI8H20N4O2S2: C, 55.65; H, 5.19; N, 14.42. Found: C, 55.45; H, 5.14; N, 14.51.

Example 3Q0 N-r 2-(4-chlorophenyl)ethvl1-N'-f2-(4-cvano)thiazolvl1 thiourea A solution of 1—[(2-[4-cyano] thiazolyl) thiocarbamoyl] imidazole (0.71 g, 3.0 mmol) X-8571A 260 2 9 and 2-(4-chlorophenyl)ethylamine (0.48 g, 3.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90*C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 0.4 g (41%) of the titled product as a tan solid: mp 188-190*C; IR (KBr, cm"1) 3396, 3110, 2226, 1586, 1518, 1490, 1353, 1248, 1087, 808, 766, 649, 517; !h NMR (300 MHz, DMSO-d6) 5 11.8 (s, 1H) , 8.43 (br s, 1H) , 8.12 (s, 1H), 7.33 (d, J= 8Hz, 2H), 7.24 (d, J= 8Hz, 2H), 3.69 (m, 2H), 2.84 (t, J=7 Hz, 2H); MS (FD) m/e 322 (M+); UV (EtOH) 287nm (e=10775), 257 nm (6=17025), 206 nm (6=31350) .

Example 3Q1 N-r 2-(4-methoxvohenvl)ethvl1-N'-f 2-(4-cvano)thiazolvl1 thiourea A solution of 1- [ (2—[4— cyano]thiazolyl)thiocarbamoyl] imidazole (0.9 g, 3.8 mmol) and 2-(4-methoxyphenyl)ethylamine (0.59 g, 3.8 mmo1) in N,N- dime thyl formamide (25 mL) was stirred at 90 *C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 0.66 g (55%) of the titled product as a yellow solid: X-8571A -380- 2 6 0 2 P 3 mp 185-190"C; IR (KBr, cm"1) 3208, 3064, 2236, 1547, 1514, 1259, 1201, 1164, 1033, 886, 775, 748, 680; iH NMR (300 MHz, DMSO-d6) 8 11.8 (br s, lH), 8.4 (br s, 1H), 5 8.1 (s, 1H), 7.13 (d, J= 9Hz, 2H), 6.83 (d, J= 9Hz, 2H), 3.68 (s, 3H), 3.64 (m, 2H), 2.77 (t, J=7 Hz, 2H); MS (FD) m/e 318 (M+); UV (EtOH) 284nm (£=12158), 258 nm (8=17248), 204 nm (£=30994) .

Example 3Q2 1-r(2-benzimidazolyl)thiocarbamoyl1 imidazole A solution of 1,1'-thiocarbonyldiimidazole (8.91g, 50 mmol) and 2-aminobenzimidazole (6.66g, 50 mmol) 15 in acetonitrile (50 mL) was stirred at room temperature for 19 hours. The resulting precipitate was collected by filtration to provide 8.92 g (73%) of the titled product: IR (KBr, cm"1) 3058, 2621, 1623, 1580, 1509, 1469, 1445, 1355, 1290, 1252, 1212, 1153, 1099, 1081, 1048, 925, 898, 20 746, 659; l-H NMR (300 MHz, DMSO-d6) 8 13.24 (br s, 2H) , 8.52 (s, 1H) , 7.87 (s, 1H), 7.57 (m, 2H), 7.33 (m, 2H), 6.96 (s, 1H); MS (FAB) m/e 244 (M+l); UV (EtOH) 351nm (8^18204), 283nm (£=13099), 227 nm (8=17339), 25 204 nm (£=31915) .

Example 303 N-f2-U-chlorophenyl)ethv!1-N'-(2-benzimidazolyl) thiourea A solution of 1—[ (2 — 30 benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5.0 mmol) and 2-(2-chlorophenyl)ethylamine (0.81 g, 5.0 mmol) in N,N- X-8571A 2 6 Q p g dimethyiformamide (20 mL) was stirred at 90'C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer 5 was concentrated and the resultant solid was crystallized from EtOAc to provide 0.67 g (40%) of the titled product as a white solid: mp 166-169*C; IR (KBr, cm-1) 3235, 1656, 1554, 1459, 1248, 1224, 1192, 10 754, 737, 629; !h NMR (300 MHz, DMSO-d6) 8 11.95 (br s, 1H) , 10.82 (br s, 1H), 7.42 (m, 5H), 7.25 (m, 2H), 7.12 (m, 2H), 3.83 (m, 2H), 3.05 (t, J=7 Hz, 2H); MS (FD)' m/e 330 (M+) ; TJV (EtOH) 301nm (£=18044), 293 nm (£=18559), 266 nm (6=11113), 260nm (£=10441), 239 nm (£=8428), 206 nm (£=27620).

Example 3Q4 N-r2-(3-Chlorophenyl)ethvl1-N'-(2-benzimidazolyl) thiourea 20 A solution of l-[(2- benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5.0 mmol) and 2-(3-chlorophenyl)ethylamine (0.79 g, 5.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90'C for 2 h. The reaction was cooled to room temperature, poured into ethyl 25 acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 0.24 g (14%) of the titled product as a white" solid: mp 171-177*C; X-8571A -382- i a f * ^ ^ 26 0 : IR (KBr, cm-1) 3387, 1574, 1539, 1461, 1426, 1237, 1175, 734, 699, 477; 1H NMR (300 MHz, DMSO-<?6) 8 11.18 (m, 2H) , 7.28 (m, 8H) , 7.06 (m, 1H), 3.83 (m, 2H), 2.94 (t, J=7 Hz, 2H); 5 MS (FD) m/e 330 (M+); UV (EtOH) 293 nm (e=17219), 266 nm (e=9969), 260nm (e=9196), 240 nm (e=8196) , 203 nm (e=27483) .

Example 305 N-\2-(4-Chlorophenyl)ethvl1-N'-(2-benzimidazolyl) thiourea A solution of l-[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5.0 mmol) and 2-(4-chlorophenyl)ethylamine (0.79 g, 5.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90 °C for 2 h. 15 The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 1.31 g (79%) of the titled product as 20 a white solid: mp 173-182 * C; IR (KBr, cm-1) 3168, 3031, 1668, 1562, 1494, 1470, 1327, 1221, 1174, 1090, 817, 777, 742, 657, 526, 457; ^-H NMR (300 MHz, DMSO-d6) 8 12.18 (br s, 1H), 10.36 (br s, 1H), 7.52 (m, 2H), 7.22-7.38 (m, 7H), 3.76 (m, 2H), 2.89 (t, J=7 Hz, 2H); MS (FD) m/e 330 (M+), 332 (M+2); UV (EtOH) 301nm (e=21672), 293 nm (©=22296), 266 nm (£=13408), 260nm (6=12591), 206 nm (£=29310).

X-8571A 26 0 ?0? O Example 306 N-T2-(2-methoxvohenvl)ethvl1-N'-(2-benzimidazolyl) thiourea A solution of 1—[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5.0 mmol) 5 and 2-(2-methoxyphenyl)ethylamine (0.82 g, 5.0 mmol) in w,tf-dimethylformamide (20 mL) was stirred at 90 *C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer 10 was concentrated and the resultant solid was crystallized from EtOAc to provide 0.62 g (38%) of the titled product as a white solid: mp 176-184*C; IR (KBr, cm-1) 3035, 1644, 1539, 1495, 1463, 1331, 1246, 15 1203, 1025, 750, 454; l-H NMR (300 MHz, DMSO-d6) 5 11.95 (br s, 1H) , 10.32 (br s, 1H), 7.52 (m, 2H), 7.20 (m, 5H), 6.88 (m, 2H), 3.75 (s, 3H) 3.70 (m, 2H), 2.88 (t, J=7 Hz, 2H); MS (FD) m/e 326 (M+); UV (EtOH) 301nm (6=20950), 293 nm (£=21508), 265 nm (6=14212), 239 nm (e=9552), 204 nm (6=30277).

Example 307 N-r 2-(3-methoxyphenyl)ethvl1-M'-(2-benzimidazolyl) thiourea 25 A solution of 1— [ (2- benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5.0 mmol) and 2-(3-methoxyphenyl)ethylamine (0.78 g, 5.0 mmol) in W,w-dimethylformamide (20 mL) was stirred at 90 *C for 2 h. The reaction was cooled to room temperature, poured into 30 ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer X-8571A -384- ^ £* 2 6 0 ? was concentrated and the resultant solid was purified by chromatography on silica gel to provide 1.2 g (73%) of the titled product as a white solid: mp 161-167'C; IR (KBr, cm-1) 2932, 1574, 1541, 1460, 1230, 1152, 1016, 737, 694, 577, 461; NMR (300 MHz, DMSO-d6> 8 11.14 (br s, 1H) , 10.95 (br s, lH), 7.30 (m, 2H), 7.16 (m, 1H), 7.06(m, 2H), 6.87 (m, 2H), 6.75 (m, 2H), 3.83 (m, 2H) 3.80 (s, 3H), 2.89 (t, J=7 Hz, 2H) ; MS (FD) rn/e 326 (M+) ; UV (EtOH) 301nm (6=23757), 293 nm (£=24495), 265 nm (£=16068), 260 nm (6=14682), 239 nm (£=11477), 204 nm (£=36963).

Example 3P8 N-r2- (4-methoxypheny1)ethv11-N1-(2-benzimidazolyl) thiourea A solution of l-[(2-benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5.0 mmol) and 2-(4-methoxyphenyl)ethylamine (0.77 g, 5.0 mmol) in i^W-dimethylformamide (20 mL) was stirred at 90*C for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was purified by chromatography on silica gel to provide 1.1 g (67%) of the titled product as a white solid: mp 166-172*C; IR (KBr, cm"1) 3416, 3195, 3065, 1575, 1543, 1511, 1464, 1243, 1176, 1037, 747, 442; X-8571A 2 6 0 ? a * tv xj !h NMR (300 MHz, DMSO-d6) 8 11.11 (br s, 1H) , 10.95 (br s, 1H), 7.36 (m, 2H), 7.20 (d, J=8 Hz, 2H), 7.08(m, 3H), 6.82 (d, J=8 Hz, 2H), 3.78 (m, 2H) 3.67 (s, 3H), 2.85 (t, J=7 Hz, 2H); MS (FD) m/e 326 (M+) ; UV (EtOH) 301nm (e=24618), 293 nm (£=25247), 265 nm (£=16716), 260 nm (e=15557), 203 nm (£=35060).

Example 3Q9 N-f2-(1-cvclohexenvl)ethvlj-N'-(2-benzimidazolyl) thiourea A solution of 1—[ (2— benzimidazolyl)thiocarbamoyl]imidazole (1.22 g, 5.0 mmol) and 2-(l-cyclohexenyl)ethylamine (0.64 g, 5.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90'C for 2 h. The 15 reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 0.82 g (55%) of the titled product as 20 yellow needles: mp 178-180 *C; IR (KBr, cm"1) 3182, 2922, 1576, 1540, 1421, 1271, 1232, 1033, 740, 450; !h NMR (300 MHz, DMSO-d6) 5 11.08 (br s, 1H), 11.07 (br s, 25 1H), 11.02 (br s, lH), 7.36 (m, 2H) , 7.06(m, 2H), 5.51 (s, 1H), 3.66 (m, 2H), 2.21 (t, J=7 Hz, 2H) , 1.93 (m, 4H), 1.51 (m, 4H) ; MS (FD) m/e 300 (M+); X-8571A -386- ^ Q Q 2 Q 7 ^ \J UV (EtOH) 301nm (6=25279), 292 nm (©=26214), 265 nm (©=15965), 259 nm (e=14734), 239 nm (6=11012), 206 nm (6=30007).

Anal. Calcd for C16H20N4S: C, 63.97; H, 6.71; N, 18.65. Found: C, 64.25; Hf 6.99; N, 18.63.

Example 31Q 1-r(2-ovridvl)thiocarbamoyl1 imidazole A solution of 1,1'-thiocarbonyldiimidazole (9.9 g, 50 mmol) and 2-aminopyridine (4.75 g, 50 mmol) in acetonitrile (50 mL) was stirred at room temperature for 72 h. The resulting solution was evaporated to a black oil and triturated with hexane. The remaining oily residue was placed under vacuum to provide 13.6 g of crude titled product as a black solid: !h NMR (300 MHz, DMSO-d6) 8 8.89 (br s, 1H) , 8.58 (m, 1H) , 8.35 (m, 1H), 7.80 (m, 2H), 7.40 (m, lH), 7.15 (m, 1H), 6.95 (m, lH); MS (FAB) m/e 204 (M+, weak) Example 311 N-r 2-(2-Chlorophenyl)ethvl1-N'-(2-pvridvl)thiourea A solution of l-[(2-pyridyl)thiocarbamoyl] imidazole (1.02 g, 5.0 mmol) and 2-(2-chlorophenyl)ethylamine (0.81 g, 5.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90*C for 24 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant oil was purified by X-8571A -387- chromatography on silica gel to provide 0.21 g (14%) of the titled product as a yellow solid: mp 116-122*C; IR (KBr, cm"1) 3235, 1606, 1592, 1558, 1537, 1477, 1439, 1332, 1259, 1234, 1212, 1185, 1150, 1088, 1057, 861; % NMR (300 MHZ, DMSO-C?6) 8 11.63 (m, 1H) , 10.53 (s, 1H) , 8.03 (m, 1H), 7.68 (m, 1H), 7.41 (m, 2H), 7.30 (m, 2H), 7.07 (m, 1H), 6.96 (m, 1H), 3.84 (ir., 2H), 3.04 (t, J=7 Hz, 2H) ; MS (FD) m/e 291 (M+) ; UV (EtOH) 293 nm (e=14959), 266 nm (e=15723), 246nm (e=15174) , 201 nm (e=23340) .

Example 312 2- (2 . 6-Dif luorophenyl') ethylamine 2, 6-Difluorophenylacet.onitrile (15.8g, 100 mmol)was dissolved in tetrahydrofuran (75 mL) at room temperature. The solution was cooled in an ice bath and borane*THF complex (lOOmL, 100 mmol) was added dropwise over 15 minutes under nitron n atmosphere. The ice bath was removed after borane addition was complete and the mixture was stirred at room temperature for 23 hours under nitrogen atmosphere. Saturated aqueous ammonium chloride solution (20 mL) was added dropwise with stirring over 30 minutes. The reaction mixture was filtered through diatomaceous earth, concentrated to an oil, redissolved in ethyl acetate/water, and adjusted to pH 1.0 with concentrated hydrochloric acid. The mixture was filtered through diatomaceous earch and the ethyl acetate layer extracted with IN hydrochloric acid (4 x 10 mL). The combined acidic aqueous extracts were washed with ethyl X-8571A 2 6 0 ? acetate (2 x 50 ml). Solid sodium chloride was added to the acidic aqueous extracts, adjusted to pH 9.0 with solid sodium bicarbonate and 5N sodium hydroxide solution, and the mixture extracted with methylene chloride (7 x 50 mL). The combined methylene chloride extracts were washed with brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated to yield 10.6g (68%) of the titled product as a nearly colorless oil: IR (KBr, cirT1) 2967, 2876, 1626, 1590, 1469, 1265, 1236, 1213, 1157, 1128, 1085, 1051, 1016, 956, 843; !h NMR (300 MHz, CDCI3) 8 7.13 (m, 1H) , 6.83 (m, 2H) , 2.89 (m, 2H), 2.80 (t, J=7 Hz, 2H), 1.19 (s, 2H); MS (FD) m/e 157 (M+, weak); UV (EtOH) 265nm (£=650), 260nm (e=674), 204nm (£=7922) ; TITRATION (66% DMF/H2O) pKa 9.06 Anal. Calcd for C8H9F2N: C, 61.14; H, 5.77; N, 8.91. Found: C, 60.88; H, 5.88; N, 8.63.

Example 313 N-T2-(2.6-difluorophenyl)ethvl1-N'-T2-(4-ethvl)thiazclvl1 thiourea A solution of 2-(2, 6-difluorophenyl)ethylamine(0.16 g, 1 mmol) and l-[(2-[4-ethyl]thiazolyl) thiocarbamoyl] imidazole (0.24g, 1 mmol) in J^JV-dime thyl formamide (15 mL) was stirred at 90 *C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 0.29 g (89%) of the titled product as a pale yellow solid: X-8571A -389- 2 6 Q 9 mp 157-158*C; IR (KBr, cnT1) 3178, 2972, 1584, 1502, 1469, 1340, 1351, 1293, 1267, 1212, 1075, 1014, 953, 787, 726. 672? NMR {300 MHz, DMSO-d6) 8 11.54 (br s, 1H), 9.75 (br s, 1H), 7.29 (m, 1H), 7.01 (m, 2H), 6.58 (s, 1H), 3.77 (m, 2H), 2.92 (t, J=7 Hz, 2H), 2.45 (q, J=8 Hz, 2H), 1.05 (t, J=8 Hz, 3H); MS (FD) m/e 327 (M+); UV (EtOH) 292nm (£=18786), 257nm (8=10109), 202nm (£=19042) Anal, Calcd for C14H15F2N3S2: C, 51.36; H, 4.62; N, 12.83. Found: C, 51.60; H, 4.78; N, 13.08.

Example 314 N- T2- (2 . 6-difluorophenyl)ethvl1 -N' - (2-pvridvl) thiourea A solution of 2-(2,6-difluorophenyl)ethylamine (0.43 g, 2.7 mmol) and 1-[(2-pyridyl)thiocarbamoyl] imidazole (0.55 g, 2.7 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90'C for 27 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant oil was purified by chromatography on silica gel to provide 0.08 g (10%) of the titled product as a pale yellow solid: mp 157-160*C; IR (KBr, cm-1) 3226, 1605, 1539, 1466, 1332, 1260, 1236, 1188, 1100, 974, 899, 861, 774, 725, 635, 516; iH NMR (300 MHz, DMSO-d6) 8 11.68 (br s, 1H) , 10.53 (br s, 1H), 7.99 (m, 1H), 7.70 (m, 1H), 7.28 (m, 1H), 7.04 (m, 4H) , 3.82 (m, 2H), 2.97 (t, J=7 Hz, 2H); X-8571A 2 60° o ^ • • O MS (FD) m/e 293 (M+); UV (EtOH) 292nm (e=15506), 266nm (6=16020), 245nm (6=14709) Example 315 l-r(2-(2.6-difluoroohenvl)ethvl)thiocarbamoyl 1 imidazole A solution of 1,1'-thiocarbonyldiimidazole (9.5 g, 48 mmol) and 2-(2,6-difluorophenyl)ethylamine (7.54 g, 48 mmol) in acetonitrile (100 mL) was stirred at room temperature for 20 h. The solution was concentrated under 10 reduced pressure and the resulting precipitate was collected by filtration and triturated with hexane to provide 16 g of crude titled product as a brown solid: IR (KBr, cm"1) 3129, 1565, 1468, 1355, 1259, 1203, 1120, 1065, 1031, 937, 900, 827, 787, 751, 664, 621, 499; 15 !h NMR (300 MHz, DMSO-d6) 8 10.50 (br s, 1H) , 8.29 (s, 1H) , 7.71 (s, 1H), 7.35 (m, 1H), 7.04 (m, 3H), 3.85 (m, 2H), 3.0 (m, 2H); MS (FAB) m/e 268 (M+H); UV(EtOH) 280nm (£=4068), 250nm (e=4341), 201nm (£=15062) Example 316 N-f 2-(1-cyclohexenyl)ethyl1-N'-f 2-(6- chloro)pyrazinvllthiourea A solution of 2-amino-6-chloropyrazine (2.59 g, 25 20 mmol) and 2-(l-cyclohexenyl)ethylisothiocyanate (3.34 g, 20 mmol) in N,W-dimethylformamide (25 mL) was stirred at 95 °C for 27 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The 30 organic layer was concentrated and the resultant solid was X-8571A 260 2 93 purified by chromatography on silica gel and crystallized from EtOAc to provide 0.44 g (7%) of the titled product or white needles: mp 170-171*C; IR (KBr, cm"1) 3207, 2926, 1584, 1514, 1414, 1295, 1161, 1005, 866, 714, 459; XH NMR (300 MHz, DMSO-dg) 8 11.08 (br s, 1H), 10.02 (br s, 1H), 8.49 (s, 1H), 8.29 (s, 1H), 5.48 (br s, 1H), 3.64 '(m, 2H), 2.21 (t, J=7 Hz, 2H), 1.90 (m, 4H), 1.49 (m, 4H); MS (FD) m/e 296 (M+), 298 (M+2); UV (EtOH) 327nm (e=12429), 266 nm (©=17577) Anal. Calcd for C13H17N4SCI: C, 52.60; H, 5.77; N, 18.87. Found: C, 52.89; H, 5.89; N, 19.11.

Example 317 N-F 2-(2.6-difluorophenyl)ethvl1-N'-F2-(6- methvl)pyridyl1 thiourea A solution of 1— [ (2—(2,6-difluorophenyl)ethyl)thiocarbamoyl]imidazole (0.53 g, 2 mmol) and 2-amino-6-methylpyridine (0.22g, 2 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90*C for 3 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 0.14 g (23%) of the titled product as nearly colorless prisms: mp 187-189 *C; IR (KBr, cm"1) 3195, 1612, 1544, 1468, 1451, 1380, 1293, 1269, 1230, 1192, 1160, 1072, 950, 788, 722, 635, 501; X-8571A r) A -"y c o 0 9 1h NMR .(300 MHz, DMSO-d6) 8 11.83 (br s, 1H), 10.44 (br s, 1H), 7.56 (t, J=8 Hz, 1H), 7.26 (m, 1H), 6.98 (m, 2H), 6.87 (d, J=8 Hz, 1H), 6.79 (d, J=8 Hz, lH), 3.87 (m, 2H), 2.94 (t, J=7 Hz, 2H), 2.11 (s, 3H); MS (FD) m/e 307 (M+); UV (EtOH) 296nm (6=12052), 265nm (6=10578) , 246nm (6=10257) Anal. Calcd for C15H15F2N3S: C, 58.62; H, 4.92; N, 13.67. Found: C, 58.35; H, 4.98; N, 13.39. example 318 N-r 2-(1-cvclohexenvl)ethyl1-N'-T 2-(3.5- dimethvl)pvrazinvl1 thiourea A solution of 2-amino-3,5-dimethylpyrazine (0.62 g, 5 mmol) and 2-(l-cyclohexenyl)ethylisothiocyanate (0.84 g, 5 mmol) in jy,W-dimethylformamide (20 mL) was stirred at 90*C for 24 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant oil was purified by chromatography on silica gel to provide 0.27 g (19%) of the titled product as an off-white solid: mp 100-103 *C; IR (KBr, cm-1) 3387, 2929, 1515, 1329, 1214, 1164, 1014, 966, 907; !h NMR (300 MHz, DMSO-d6) 8 10.57 (br s, 1H), 9.12 (br s, 1H), 7.91 (s, 1H), 5.44 (br s, 1H), 3.61 (m, 2H), 2.47 (s, 3H), 2.35 (s, 3H), 2.18 (t, J=7 Hz, 2H), 1.90 (m, 4H), 1.48 (m, 4H); MS (FD) m/e 290 (M+); X-8571A 26 0 2 9 UV (EtOH) 320nm (6=11659), 265 nm (8=16153), 201 nm (8=11795) Anal. Calcd for C15H22N4S: C, 62.03; H, 7.63; N, 18.29.

Found: C, 62.06; H, 7.65; N, 18.58.

Example 33.3 N-r 2 -(2.6-difluorophenyl)ethvl1-N'-f 2- (5 -t.rifluoromethvl)pvridvl1 thiourea A solution of 1—[(2—(2,6— difluorophenyl)ethyl)thiocarbamoyl]imidazole (1.07 g, 4 mmol) and 2-amino-5-trifluoromethylpyridine (0.65 g, 4 mmol) in W/N-dime thy If ormamide (20 mL) was stirred at 95'C for 25 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was purified by chromatography on silica gel to provide 0.26 g (18%) of the titled product as a white solid: mp 148-152*C; IR (KBr, cm"!) 3165, 3033, 1619, 1600, 1548, 1470, 1332, 1248, 1189, 1160, 1138, 1106, 1079, 964, 886, 776, 669, 603, 435; XH NMR (300 MHz, DMSO-d6) 8 11.42 (br s, 1H) , 10.94 (br s, 1H), 8.36 (s, 1H), 8.08 (m, 1H), 7.28 (m, 2H), 7.02 (m, 2H) , 3.82 (ra, 2H) , 2.98 (t, J=7 Hz, 2H) ; MS (FD) m/e 361 (M+); UV (EtOH) 297nm (8=18455), 253nm (8=14782) , 2Olnm (8=15765) Anal. Calcd for C15H12F5N3S: C, 49.86; H, 3.35; N, 11.63. Found: C, 49.59; H, 3.28; N, 11.35 X-8571A -394- 26 0 Example 37.0 N-f2-(2.6-difluorophenyl)ehhvll-M1-12-(5- chlorp)pyridyl! thiourea A solution of l-[(2-(2,6-5 difluorophenyl)ethyl)thiocarbamoyl] imidazole (1.07 g, 4 mmol) and 2-amino-5-chloropyridine (0.53 g, 4 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90'C for 22 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 0.65 g (50%) of the titled product as a tan solid: mp 172-175'C; IR (KBr, cm-1). 3233, 1597, 1557, 1529, 1468, 1340, 1308, 1265, 1231, 1190, 1112, 1072, 950, 857, 834; ^-H NMR (300 MHZ, DMSO-C?6> 8 11.19 (m, 1H) , 10.67 (s, 1H) , 8.03 (s, 1H), 7.82 (m, 1H), 7.30 (m, lH), 7.13 (m, lH) , 7.03 (m, 2H), 3.79 (m, 2H), 2.96 (t, J=7 Hz, 2H); MS (FD) m/e 327 (M+), 329 (M+2); UV (EtOH) 304nm (6=13180), 274nm (e=23154), 253 nm (£=15998), 201 nm (£=19019) Example 321 N-T2-(2,6-difluorophenvl)ethvll-N'-T2-f^- methvl )pvridvl1 thiourea A solution of l-[(2-(2,6-difluorophenyl)ethyl)thiocarbamoyl]imidazole (1.33 g, 5 mmol) and 2-amino-5-methylpyridine (0.54 g, 5 mmol) in N,N- dimethyiformamide (20 mL) was stirred at 90'C for 7 h. The reaction was cooled to room temperature, poured into ethyl X-8571A -395- 2 6 V n 0 "? ^ \J acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was conbentrated and the resultant solid was crystallized from EtOAc to provide 0.83 g (86%) of the titled product as 5 yellow crystals: mp 195-196'C; IR (KBr, cm"1) 3230, 1611, 1535, 1492, 1468, 1334, 1274, 1236, 1190, 1111, 1065, 957, 821, 777, 716, 657, 608, 513; 1h NMR (300 MHz, DMSO-d6) 8 11.59 (br s, 1H) , 10.44 (br s, 1H), 7.83 (br s, 1H), 7.53 (d, J=8 Hz, 1H), 7.30 (m, 1H), 7.02 (m, 3H), 3.80 (m, 2H), 2.96 (t, J=7 Hz, 2H), 2.16 (s, 3H) ; MS (FD) m/e 307 (M+); UV(EtOH) 297nm (e=5129), 268nm (e=7508) , 247nm (e=5383) 15 Anal. Calcd for C15H15F2N3S: C, 58.62; H, 4.92; N, 13.67. Found: C, 58.36; H, 4.98; N, 13.73.

Example 322 N- T2-(2.6-difluorophenyl)ethvll-N'-f2-(5-20 bromo)pvrazinvl1 thiourea A solution of 1—[(2—(2,6— difluorophenyl)ethyl)thiocarbamoyl] imidazole (1.33 g, 5 mmol) and 2-amino-5-bromopyrazine (0.87 g, 5 mmol) in N,N-dimethylformamide (20 mL) was stirred at 95*C for 26 h. 25 The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was purified by chromatography on silica gel to provide 0.31 g (17%) of the 30 titled product as a white solid: mp 175-178*C; X-8571A 26 0 n IR (KBr, cm"1) 3200, 1596, 1560, 1526, 1469, 1441, 1324, 1259, 1179, 1161, 1114, 1012, 962, 899, 874, 788, 780, 667, 601; NMR (300 MHz, DMSO-d6) 8 10.98 (br s, lH) , 10.51 (br s, 1H), 8.33 (s, 1H), 8.24 (s, lH), 7.31 (m, 1H), 7.04 (m, 2H), 3.81 (m, 2H), 2.97 (t, J=7 Hz, 2H); MS (FD) m/e 372 (M+), 374 (M+2); UV (EtOH) 333nm (6=10125), 275nm (£=22570), 201 nm (£=16801) Anal. Calcd for Ci3HnBrF2N4S: C, 41.84; H, 2.97; N, 15.01. Found: C, 42.10; H, 3.12; N, 14.73.

Example 323 N-f 2-(2.6-difluoroohenvl)ethvl1-N'-f 2-(6- ethyl)pyridyl1 thiourea A solution of l-[(2-(2,6-difluorophenyl)ethyl)thiocarbamoyl]imidazole (1.33 g, 5 mmol) and 2-amino-6-ethylpyridine (0.61 g, 5 mmol) in N,N-dimethylformamide (20 mL) was stirred at 95'C for 21 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 0.63 g (39%) of the titled product as dense yellow crystals: mp 147-148*C; IR (KBr, cm-1) 2972, 1609, 1541, 1468, 1344, 1292, 1265, 1225, 1155, 1073, 951, 804, 786, 727, 692, 635, 501; !h NMR (300 MHz, DMSO-d6) 8 11.97 (m, lH) , 10.48 (br s, 1H) , 7.59 (t, J=8 Hz, 1H), 7.27 (m, 1H), 6.98 (m, 2H), 6.89 (d, X-8571A -397- V \J O 26 0 J=8 Hz, 1H), 6.80 (d, J=8 Hz, 1H), 3.87 (m, 2H), 2.95 (t, J=7 Hz, 2H), 2.44 (q, J=8 Hz, 2H), 0.93 (t, J= 8 Hz, 3K); MS (FD) m/e 321 (M+); UV(EtOH) 296nm (©=17512), 266nm (e=15047 ) , 246nm (6=14627) , 5 201nm (e=16211) Anal. Calcd for C16H17F2N3S: C, 59.80; H, 5.33; N, 13.07.

~£S> Found: C, 60.04; H, 5.38; N, 13.22.

Example 324 NT— \1- (2. 6-dif luorophenyl) ethvll-N' - T2- (6- chloro)pyrazinvl1 thiourea A solution of l-t(2-(2,6-difluorophenyl)ethyl)thiocarbamoyl] imidazole (4.0 g, 15 mmol) and 2-amino-6-chloropyrazine (1.96 g, 15 mmol) in 15 W, JV-dimethylformamide (25 mL) was stirred at 95*C for 18 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was purified by 20 chromatography on silica gel to provide 0.7 g (14%) of the titled product as a light yellow solid: mp 175-180*C; IR (KBr, cm"1) 3232, 1588, 1512, 1468, 1414, 1296, 1240, 1163, 1097, 1004, 981, 869, 777, 714, 659, 459; 25 XH NMR (300 MHz, DMS0-d6) 8 11.07 (br s, 1H) , 10.07 (br s, 1H), 8.50 (s, 1H), 8.28 (s, lH), 7.28 (m, lH) , 7.00 (m, 2H), 3.85 (m, 2H), 2.95 (t, J=7 Hz, 2H); MS (FD) m/e 328 (M+), 330 (M+2); UV (EtOH) 327nm (e=10851), 265nm (£=14817), 201 nm (8=16442) X-8571A 260 p q Example 325 N-f 2-(2-pvridvl)ethvll-N'-r2-(4-cvano)thiazolvl 1 thiourea A solution of 1— t(2—[4-cyano]thiazolyl)thiocarbamoyl] imidazole (2.35 g, 10 mmol) 5 and 2-(2-pyridyl)ethylamine (1.29 g, 10 mmol) in N,N- dimethylformamide (25 mL) was stirred at 95'C for 2 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the 10 residue purified by chromatography on silica gel to provide 0.4 g (14%) of the titled product as a yellow solid: mp 160'C; IR (KBr, cm"1) 3165, 3100, 2996, 2234, 1540, 1489, 1433, 1305, 1266, 1219, 1159, 1132, 999, 904, 817, 758, 574, 435; 15 !h NMR (300 MHz, DMSO-dg) 8 11.88 (br s, 1H) , 8.67 (br s, 1H) , 8.49 (d, J=4 Hz, 1H), 8.11 (s, 1H), 7.69 (m, 1H), 7.23 (m, 2H), 3.87 (m, 2H), 3.01 (t, J=7 Hz, 2H); MS (FD) m/e 289 (M+); UV (EtOH) 288nm (e=10826), 257 nm (£=19925), 205 nm 20 (£=28658.) .

Example 326 N-r 2-(2.6-di fluorophenyl)ethvl1-N'-\2-(4-methyl) pyridyl 1 thii onraa 25 A solution of l-[{2-(2,6- difluorophenyl)ethyl)thiocarbamoyl]imidazole (1.33 g, 5 mmol) and 2-amino-4-methylpyridine (0.54 g, 5 mmol) in N,N-dimethylformamide (20 mL) was stirred at 90'C for 3 h. The reaction was cooled to room temperature, poured into ethyl 30 acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer X-8571A 26 0 " was concentrated and the resultant solid was crystallized from EtOAc to provide 0.49g (32%) of the titled product as yellow needles: mp 168-170*C; IR (KBr, cm"1) 3233, 1616, 1536, 1465, 1335, 1262, 1191, 1104, 959, 815, 783, 719, 653, 442; % NMR (300 MHz, DMSO-c?6) 8 11.74 (br s, 1H) , 10.44 (br s, 1H) , 7.85 (d, J=5 Hz, 1H), 7.27 (m, 1H), 7.02 (m, 2H), 6.88 (s, 1H), 6.80 (d, J=5 Hz, 1H), 3.80 (m, 2H), 2.96 (t, J=7 Hz, 2H), 2.20 (s, 3H); MS (FD)• m/e 307 (M+); UV (EtOH) 290nm (e=16210) , 266nm (£=15920), 246nm (£=13211), 202nm (e=13211) Example 327 N- [2- (2.6-flifluorophenyl)ethyl!-N' - T2- (4- ethvl)pvridvl1 thiourea A solution of 1—[(2—(2,6-difluorophenyl)ethyl)thiocarbamoyl]imidazole (1.33 g, 5 mmol) and 2-amino-4-ethylpyridine (0.61 g, 5 mmol) in N,N-dimethylformamide (20 mL) was stirred at 95'C for 3 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was crystallized from EtOAc to provide 0.32 g (20%) of the titled product as a light brown solid: mp 140-142'C; IR (KBr, cm-1) 2939, 1616, 1590, 1536, 1469, 1341, 1267, 1189, 1104, 1064, 960, 868, 826, 781, 759, 721, 668, 652; X-8571A -400- 26 0 C !h NMR (300 MHz, DMSO-d6) 8 11.74 (br s, 1H), 10.42 (br s, 1H), 7.87 (d, J=5 Hz, 1H), 7.29 (m, lH), 6.99 (m, 2H), 6.85 (s, 1H), 6.84 (d, J=5 Hz, 1H), 3.81 (m, 2H), 2.95 (t, J=7 Hz, 2H), 2.49 (q, J=8 Hz, 2H), 1.09 (t, J=8 Hz, 3H); MS (FD) m/e 321 (M+); UV(EtOH) 290nm (£=18247), 266nm (£=18045), 246nm (£=15212), 202nm (£=27817) Anal. Calcd for C16H3.7F2N3S: C, 59.79; H, 5.33; N, 13.07. Found: C, 59.50; H, 5.31; N, 12.87.

Example 328 1-r(2-(2-pvridvl)ethvl)thiocarbamoyl 1 imidazole A solution of 1,1'-thiocarbonyldiimidazole (9.9 g, 50 mmol) and 2-(2-pyridyl)ethylamine (6.43 g, 50mmol) in acetonitrile (120 mL) was stirred at room temperature for 24 h. The solution was concentrated under reduced pressure and the resulting brown oil was triturated with ethyl ether. The remaining oil was placed under vacuum to provide 10.7 g of crude titled product as a black solid: IR (KBr, cm-1) 3125, 2930, 2098, 1548, 1477, 1437, 1363, 1329, 1284, 1221, 1098, 1063, 1030, 925, 828, 750, 661, 620; !h NMR (300 MHz, DMSO-dg) 8 10.35 (br s, 1H) , 8.48 (in, 1H) , 8.33 (s, 1H), 7.76 (s, 1H), 7.72 (m, 2H), 7.25 (m, 2H), 3.95 (m, 2H), 3.1 (m, 2H) ; MS (FAB> m/e 233 (M+H); UV (EtOH) 267nm (£=5516) , 261nm (£=6306) , 256nm (6=6220) . 203nm (£=14929) X-8571A I 2^0 2 9 Example 329 N- r 2 - (2 -pvr idvl) ethvl 1 -N' - \ 2 - (5 -bromo) nvraainvl 1 thiourea A solution of 1-[(2—(2-pyridyl)ethyl)thiocarbamoyl] imidazole (1.16 g, 5 mmol) and 5 2-amino-5-bromopyrazine (0.87 g, 5 mmol) in N,N- dimethylformamide (20 mL) was stirred at 95'C for 27 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, saturated sodium bicarbonate, and brine. The organic layer was concentrated 10 and the residue purified by chromatography on silica gel and crystallized from EtOAc to provide 0.13 g (7%) of the titled product as a tan solid: mp 185-190 * C; IR (KBr, cm"l) 3186, 1588, 1558, 1517, 1479, 1439, 1356, 15 1325, 1289, 1268, 1220, 1185, 1156, 1100, 1083, 1013, 996, 900, 876, 800, 760, 716, 569, 511, 431; iH NMR (300 MHz, DMSO-c?6) 5 10.93 (br s, lH) . 10.74 (br s, 1H), 8.54 (d, J=5 Hz, 1H), 8.31 (s, 1H) , 8.28 (s, 1H), 7.69 (m, 1H), 7.28 (m, 1H), 7.21 (m, 1H) , 3.96 (m, 2H), 3.05 (t, 20 J=7 Hz, 2H); MS (FD) m/e 337 (M+), 339 (M+2); UV (EtOH) 333nm (e=10984) , 270 nm (£=25064) .

Anal. Calcd for Ci2Hi2BrN5S: C, 42.61; H, 3.58; N, 20.71. Found: C, 42.41; H, 3.83; N, 20.54 .

Example 33Q N- T2- (2 . 6 - di f luor ophenv 1) et-.hv 1 "I -N' -\2- (5- chloro)pyrazinyl1 thiourea A solution of 1-t(2-(2,6-30 difluorophenyl)ethyl)thiocarbamoyl] imidazole (1.33 g, 5 mmol) and 2-amino-5-chloropyrazine (0.65 g, 5 mmol) in N,N- X-8571A 2 6 0 2 9 dimethyiformamide (20 mL) was stirred at 95'C for 24 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the resultant solid was purified by chromatography on silica gel and crystallized from EtOAc to provide 0.1 g (6%) of the titled product as a white solid: mp 170-171*C; IR (KBr, cm"1) 3199, 3070, 1593, 1563, 1529, 1468, 1443, 1418, 1327, 1263, 1184, 1166, 1128, 1016, 779; !h NMR (300 MHz, DMSO-d6) 8 11.00 (br s, 1H) , 10.53 (br s, 1H), 8.33 (s, 1H), 8.19 (s, 1H), 7.30 (m, 1H), 7.04 (m, 2H), 3.81 (m, 2H), 2.96 (t, J=7 Hz, 2H); MS (FD) m/e 328 (M+), 330 (M+2); UV (EtOH) 332nm (8=10097) , 274nm (e=22879) Anal. Calcd for C13H11CIF2N4S: C, 47.49; H, 3.37; N, 17.04. Found: C, 47.54; H, 3.45; N, 17.19.

Example 331 1-r(2-(5-ethoxv carbonvl)thiazolvl)thiocarbamoyl1 imidazole A solution of 1,11-thiocarbonyldiimidazole (8.9 g, 50 mmol) and 2-amino(5-ethoxy carbonyl)thiazole (8.9 g, 50 mmol) in acetonitrile (600 mL) was stirred at 50'C for 20 h. The resulting precipitate was collected by filtration to provide 6.5 g (40%) of the titled product, mp 208-210'C (d).

IR (KBr, cm'1) 3205, 3176, 3146, 3115, 1708, 1557, 1470, 1352, 1298, 1244, 1225; !h NMR (300 MHz, DMSO-d6) 8 13.2 (br s, 1H) , 8.1 (s, lH) , 7.9 (s, 1H), 7.6 (s, 1H), 7.1 (s, 1H), 4.2 (q, 2H), 1.3 (t, 3H) ; x"e57iA -403- 2 6 0 o o MS (FD) m/e (no correct pk) (M+); UV (EtOH) 349 nm (e=4746), 269 nm (£=8713), 209 nm (6=21033). Anal. Calcd for C10H10N4O2S2: C, 42.54 H, 3.57? N, 19.84. Found: C, 42.37; H, 3.55; N, 19.59.

Example 332 N- r 2- (l-cvrlnhexprivl) ethyl 1 -N' - f 2- (5-f>thr>xv carbonv1)thiazolvl1 thiourea A solution of 1-t(2-[5-ethoxy carbonyl]thiazolyl)thiocarbamoyl] imidazole (1.12 g, 4.0 mmol) and 2-(l-cyclohexenyl)ethylamine (0.5 g, 4.0 mmol) in itf,JV-dimethylformamide (40 mL) was stirred at 90 °C for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue recrystallized from ethyl acetate to provide 0.790 g (56%) of the titled product: mp. 197-198"C; IR (KBr*, cm-1) 3243, 3121, 3044, 2991, 2925, 1707, 1582, 1543, 1458, 1190; XH NMR (300 MHz, DMSO-d6) 5 12.0 (br s, lH) , 8.5 (br s, 1H) , 7.9 (s, 1H), 5.5 (s, 1H), 4.3 (q, 2H), 3.6 (m, 2H), 2.2 (t, J=7 HZ, 2H), 1.9 (m, 4H), 1.5 (m, 4H), 1.3 (t, J=7 Hz, 3H) ; MS (FD) m/e 339 (M+); UV (EtOH) 262nm (£=17510), 205 nm (6=19237).

Anal. Calcd for C15H21N3O2S2: C, 53.07; H, 6.23; N, 12.38. Found: C, 53.31; H, 6.44; N, 12.42.

X-8571A 2 6 0 ? o * . <.

Example 333 N- (2-phenethyl)-N' -\2-(5-ethoxy carbonyl)thiazolvll thiourea A solution of 1-[ (2-[5-ethoxy carbonyl]thiazolyl)thiocarbamoyl] imidazole (1.1 g, 4.0 mmol) and 2-(1-phenyl)ethylamine (0.6 g, 4.0 mmol) in N,N-dimethylformamide (40 mL) was stirred at 90'C for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water, IN aqueous HCl, water, saturated sodium bicarbonate, and brine. The organic layer was concentrated and the residue crystallized from ethyl acetate to provide 1.07 g (80%) of the titled product: mp. 174-175'C; IR (KBr, cm"1) 3340, 3253, 3124, 3056, 1707, 1682, 1579, 1537, 1454, 1252, 1222; !h NMR (300 MHz, DMSO-dg) 5 12.0 (br s, 1H) , 8.7 (br s, 1H) , 7.9 (s, 1H), 7.3 (m, 5H), 4.3 (q, 2H), 3.8 (m, 2H), 2.9 (t, J=7 Hz, 2H), 1.3 (t, J=7 Hz, 3H); MS (FD) m/e 335 (*J+) ; UV (EtOH) 262nm (e=19184), 206 nm (e=26117) .

Anal. Calcd for C15H17N3O2S2: C, 53.71; H, 5.11; N, 12.53.

Found: C, 53.48; H, 5.10; N, 12.68.

Example 334 N-f 2-(1-cvclohexenvl)ethvl1-N'-f 2-(5-chloro)ovridvll thiourea A solution of 2-amino-5-chloropyridine (1.28 g, 10.0 mmol) and 2-(l-cyclohexenyl)ethylisothiocyanate (1.67 g, 10.0 mmol) in J7,J^-dimethylformamide (30 mL) was stirred at 90'C for 1 h. The reaction was cooled to room temperature, concentrated under vacuum to remove solvent.

X-8571A -405- 2 6 0 P The residue was purified by HPLC to provide 0.560 g (19%) of the titled product: rap. 166-167'C; IR (KBr, cm"1) 3455, 3159,1599, 1555, 1534, 1476; iH NMR (300 MHz, DMSO-d6) 8 11.1 (br s, 1H) , 10.7 (s, 1H) , 8.2 (d, 1H) , 7.9 (m, 1H) , 7.2 (d, 1H) , 5.5 (s, 1H) , 3.6 (in, 2H), 2.2 (t, J=7 Hz, 2H), 1.9 (m, 4H), 1.5 (m, 4H) ; MS (FD) m/e 295 (M+); UV (EtOH) 305nm (6=12139), 273nm (6=15905), 244 nm (e=25052). Anal. Calcd for C14H18N3SCI C, 56.84; H, 6.13; N, 14.20. Found: C, 56.59; H, 6.00; N, 14.09.

Example 335 N-r 2 -(2-chlorophenyl)ethyl1-w'-f 2-(5-chloro)pyridyl1 thiourea A solution of N-[2-(2-chlorophenyl)ethyl]-N'-thiocarbamoyl imidazole (1.3 g, 5.0 mmol) and 2-amino-5-chloro pyridine (0.65 g, 5.0 mmol) in JV,.W-dimethylfonnamide (25 mL) was stirred at 100'C for 1 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water and brine. The organic layer was concentrated and the residue triturated with hexane to provide 0.83 g (55%) of the titled product: mp 178-179*C; !h NMR (300 MHz, DMSO-dg) 8 11.2 (m, 1H) , 10.7 (s, 1H) , 8.1 (m, 1H), 7.5 (m, 1H), 7.4 (m, 2H), 7.2 (m, 2H), 7.1 (d, 1H), 3.8 (m, 2H), 3.1 (t, J=7 Hz, 2H) ; MS (FD) m/e 325 (M+); UV (EtOH) 305nm (6=12931), 273 nm (6=22583), 253 nm (6=16558) 201 nm (e=25277) .

X-8571A -406- 2 6 0^93 Anal. Calcd for C14H13N3SCI: C, 51.54; H, 4.02; N, 12.88. Found: C, 51.26; H, 3.99; N, 12.79.

Example 336 N-f 2-(1-evciohaxenvl)ethvl1-N'-f 3 -(6-chloro)pvridazinvl1 thiourea A solution of 3-amino-6-chloropyridazine (1.3 g, 10.0 mmol) and 2-(l-cyclohexenyl)ethylisothiocyanate (1.67 g, 10.0 mmol) in N,N- dime thyl formamide (20 mL) was stirred at 90 °C for 1.5 h. The reaction was cooled to room temperature and concentrated under vacuum to remove solvent. The residue was purified by HPLC to provide 0.220 g (7.5%) of the titled product: mp. 149-153'C; pKa in (66% DMF) 12.8; IR (KBr, cm~l) 3203, 3072, 2935, 1599, 1565, 1520, 1424, 1351, 1308, 1280, 1184, 1147, 1073; lH NMR (300 MHz, DMSO-dg) 6 11.1 (m, lH) , 10.9 (s, lH) , 7.8 (d, 1H), 7.6 (d, 1H), 5.5 (S, 1H), 3.7 (m, 2H), 2.2 (t, J=7 Hz, 2H), 1.9 (m, 4H), 1.5 (m, 4H) ; MS (FD) m/e 296 (M+); UV (EtOH) 275nm (e=23066).

Anal. Calcd for C13H17N4SCI C, 52.60; H, 5.77; N, 18.87. Found: C, 52.85; H, 5.84; N, 19.15.

Example 337 N-f2 - (2. 6-difluorophenvl)ethvl1-N'-f3-16-chloro)pvridazinvl1 thiourea A solution of N-[2-(2, 6-difluorophenyl)ethyl]-N'-thiocarbamoyl imidazole (1.33 g, 5.0 mmol) and 3-amino-6-chloropyridazine (0.65 g, 5.0 mmol) in N,N- X-8571A 26 0 "■ o dimethyiformamide (20 mL) was stirred at 80'C for 19 h. The reaction was cooled to room temperature, poured into ethyl acetate, washed with water and brine. The organic layer was concentrated and the residue was purified by HPLC 5 to provide 0.12 g (7.5%) of the titled product: mp 187-189'C; IR (KBr, cm"1) 3199, 3055, 1626, 1593, 1555, 1522, 1469, 1425, 1348,1313, 1263; XH NMR (300 MHz, DMSO-d6) 8 11.2 (m, 1H), 10.9 (s, lH) , 7.9 10 (d, 1H), 7.6 (d, 1H), 7.3 (m, 1H), 7.1 (m, 2H), 3.9 (m, 2H), 3.0 (t, J=7 Hz, 2H); MS (FD) m/e 328 (M+); pKa in (66% DMF) 12.73; UV (EtOH) 277nm (6=20141), 252 nm (©=12935) , 201 nm 15 (£=17891) .

Example 338 N-F2-(2. 6-difluorgphenvl)ethvl(6- mefchoxv) mrridazinv11 thiourea 20 A solution of N-[2-(2, 6-difluorophenyl)ethyl]- N'-thiocarbamoyl imidazole (0.8 g, 3.0 mmol) and 3-amino-6-methoxy pyridazine (0.4 g, 3.0 mmol) in N,N-dimethylformamide (20 mL) was stirred at 70'C for 19 h. The reaction was cooled to room temperature, poured into 25 ethyl acetate, washed with water and brine. The organic layer was concentrated and the residue was precipitated with diethyl ether to provide 0.235 g (24%) of the titled product: mp 193-196'C; IR (KBr, cm"1) 3222, 3084, 1628, 1586, 1560, 1531, 1468, 1423, 1356, 1310, 1266; X-8571A 2 6 9 $ iH NMR (300 MHz, DMSO-d6) 5 11.45 (m, 1H) , 10.7 (s, 1H) , 7.42 (d, J=10 Hz, lH), 7.28 (m, 1H), 7.21 (d, J=10 Hz, 1H), 7.0 (t,J=8 Hz, 2H) , 3.9 (s, 3H), 3.85 (m, 2H) , 3.0 (t, J=7 Hz, 2H); MS (FD) m/e 324 (M+)j UV (EtOH) 269nm (e=18845), 235 nm (8=10636), 201 nm (8=16622).

Example 339 N-f 2-(2-pyridyl)ethvl1-N1 - 13 -<6-chloro)nvridazinvl1 thiourea A solution of 1,1'-thiocarbonyldiimidazole (1.83 g, 10.0 mmol) and 3-amino-6-chloro pyridazine (1.3 g, 10.0 mmol) in acetonitrile (100 mL) was stirred at room temperature for 288 h. To this solution was added 2-(2-aminoethyl) pyridine (1.22 g, 10 mmol) and the resultant mixture stirred at room temperature for 48 h. The solvent was removed in vacuo and the residue purified by HPLC to provide 0.300 g (10.0%) of the titled product: mp 197-199*C; R (KBr, cm-1) 3172, 3045, 1583, 1562, 1511, 1478, 1428, 1345,1313, 1280; !h NMR (300 MHz, DMSO-C?6) 8 11.3 (m, 1H) , 10.9 (s, 1H) , 8.6 (d, J=5 Hz, 1H), 7.8 (d, J=10 Hz, 1H), 7.7 (m, 1H), 7.55 (d, J=10 Hz, 1H), 7.3 (d, J=8 Hz, lH), 7.2 (m, 1H), 4.0 (m, 2H), 3.1 (t, J=7 Hz, 2H) ; MS (FD) m/e 293 (M+); pka (66% DMF) is 4.17, 12.32; UV (EtOH) 275nm (e=21715), 270 nm (e=2183 6) , 221 nm (e=9867) .

X-8571A 2 6 0 ° o■ y <■ r . '1 Anal. Calcd for C12H12N5SCI2: C, 49.06; H, 4.12; N, 23.84. Found: C, 48.91; H, 4.14; N, 23.76.

Example 340 N-f2-f2.fi-Difluorophenyl)ethvl1-N'-f 2-(5-bromo)pvridvl1 thiourea A stirred solution of N-(thioimidazoyl)-2-(2,6-difluorophenyl)ethyl amine (2.67 g, 10 mmol) and 2-amino-5-bromopyridine (1.73 g, 10 mmol) in l-methyl-2-10 pyrrolidinone (20 mL) was heated to 90"c. After 16.5 h, the reaction was cooled to room temperature and poured into ethyl acetate. The organic phase was washed with H20 (2x), IN HCl, H2O and brine. The organic layer was dried over Na2S04, filtered and concentrated. The solid 15 obtained was purified by recrystallization from 1:1 EtOAc/hexanes to provide 1.6 g (43%) of the titled product. This material was recrystallized again from 70% EtOAc/hexanes to provide 1.16 g of the titled product as a light brown crystalline solid: mp 174-175°C; IR (KBr, cm'1) 3229, 1593, 1558, 1529, 1468, 1265, 1188, 1071, 832; ^H NMR (300 MHZ, DMSO-dg) 811.20 (s, lH) , 10.68 (s, 1H) , 8.11 (s', 1H) , 7.95-7.91 (m, 1H) , 7.33-7.28 (m, 1H) , 7.09-25 7.01 (m, 3H), 3.83-3.77 (m, 2H), 2.98-2.94 (m, 2H); MS (FD) m/e 371 (M+), 373 (M+2); UV (EtOH) 306nm (e=12790), 275nm (e=22096), 257nm (8=14120), 201nm (8=17270).

Anal. Calcd for Ci4Hi2BrF2N3S: C, 45.17; H, 30 3.25; N, 11.29. Found: C, 44.56; H, 3.29; N, 11.21.

X-8571A 260po? Example 341 2-nvanomethv1-3-ethoxvovr id 1 n<* A solution of thionyl chloride (3.26 g, 27.4 mmol, 2.0 mL) in CH2CI2 (10 mL) was added dropwise with 5 stirring to a solution of 2-ethoxy-3- hydroxymethylpyridine (3.0 g, 19.6 mmol) in CH2CI2 (20 mL) at 0°c. The ice bath was removed and the reaction stirred 2 h at RT. The reaction was concentrated in vacuo and redissolved in MeOH (30 mL). Potassium cyanide 10 (3.82 g, 58.7 mmol) was dissolved in H2O (10 mL) and added to the reaction in one amount. The reaction was heated to reflux and stirred for 66 h, then quenched with saturated Na2CC>3 solution. The reaction was diluted with H2O and extracted with Et20 (3x). The combined organic 15 extracts were washed with brine, dried over Na2S04, filtered and concentrated to yield 2.84 g (89%) of the titled product as a brownish oil. A small sample was further purified by flash chromatography (40% EtOAc/hexanes) to provide a clear, colorless oil: 20 IR (KBr, cm-1) 3020, 2988, 2536, 1579, 1450, 1397, 1282, 1122, 1041; ^H NMR (300 MHZ, CDCI3) 6 8.17-8.15 (m, 1H) , 7.25-7.15 (m, 2H), 4.09 (q, J=7 Hz, 2H) , 3.90 (s, 2H) , 1.47 (t, J=7 Hz, 3H) ; MS (FD) m/e 162 (M+) ; UV (EtOH) 278nm (e= 5241), 220nm (e= 7490).

X-8571A 260 29 3 Example 342 N-r 2 -(3-ethoxvpvridvl)ethvl1-N'-T 2-(5-bromo)ovridvl1 thiourea A solution of 2-cyanomethyl-3-ethoxypyridine 5 (22.03 g, 136 mmol) in EtOH (475 mL) and 5N HCl (3 mL) was treated with Pt02 catalyst (4.5 g) under 60 psi of H2. The reaction was stirred overnight at RT, then filtered. The crude reaction was concentrated and redissolved in H20 and EtOAc. The aqueous layer was made 10 basic with 5N NaOH and extracted with EtOAc. The organic layer was washed with brine, dried on Na2S04, filtered and concentrated to give 16.89 g of a yellow oil. This crude product was dissolved in 1-methyl-2-pyrrolidinone (175 mL) and N-(thioimidazoyl)-2-amino-5-bromopyridine 15 (36 g, 127 mmol) was added. The reaction was heated to 100°C and stirred for 68 h. The crude reaction was cooled and poured into EtOAc. The organic layer was washed with H20 (4x), brine, dried on Na2S04, filtered and concentrated. The resulting solid was again 20 dissolved in EtOAc and extracted with IN HCl (3x). The acid extracts were stirred with CH2CI2, made basic with 5N NaOH and extracted with CH2CI2 (2x). The CH2CI2 extracts were combined, washed with brine, dried on MgS04, filtered and concentrated. The crude product was 25 purified by flash chromatography (10% EtOAc/CH2Cl2), followed by trituration with 1:1 EtOAc/hexanes to provide 3.76 g of the titled product (7%) as a white crystalline solid: mp 170-172°C; ^H NMR (300 MHZ, DMSO-d$) 8 11.39 (s, 1H) , 10.59 (s, 1H) , 8.13-8.11 (m, 2H), 7.92-7.87 (m, 1H), 7.30 (d, J=8.1 Hz, X-8571A -412- ' r* ' " ^ 2 6 c9 3 1H), 7.22-7.18 (m, 1H) , 7.05 (d, J=8.9 Hz, lH), 4.05-3.95 (m, 4H), 3.00 (t, J=6.3 Hz, 2H), 1.29 (t, J=6.9 Hz, 3H); MS (FD) m/e 380 (M+), 382 (M+2); UV (EtOH) 305nm (e= 16291), 276nm (e= 36829).

Example 343 N-T2 - (3-pf.hnwnvririvl) ethvl 1 -N' - f 2- (5-hrnmr))pvridvl1 thiourea hydrochloride N-[2-(3-ethoxypyridyl)et.hyl]-N,-[2- (5-bromoJpyridyl] thiourea (5.17 g, 13.5 mmol) was dissolved in a saturated solution of methanolic HCl (100 mL) with stirring. After complete dissolution, a precipitate started to form. The solution was poured into Et20 (400 mL) with stirring, and the resulting white solid was filtered. The crude product was triturated with 10% MeOH/EtOAc to provide 5.47 g of the titled product (97%) as a white solid: mp 203-205°C (d); IR (KBr, cm"1) 3226, 3007, 2306, 1593, 1565, 1530, 1472, 1290, 1197, 1172; ^H NMR (300 MHZ, DMSO-dff) 611.24-11.20 (m, 1H) , 10.65 (s, 1H), 8.29 (d, J=5.3 Hz, lH), 8.17 (d, J=2.3 Hz, 1H), 7.96-7.88 (m, 2H) , 7.73-7.68 (m, 2H), 7.08 (d, J=8.9 Hz, 1H), 4.10-4.03 (m, 4K), 3.24 (t, J=6.0 Hz, 2H), 1.27 (t, J=6.9 Hz, 3H); MS (FD) m/e 380 (M+), 382 (M+2); UV (EtOH) 304nm (e=13635), 276nm (e=28876) .

Anal. Calcd for Ci5Hl8BrClN40S: C, 43.13; H, 4.34; N, 13.41. Found: C, 42.90; H, 4.36; N, 13.11. 9 X-8571A -413- ^ v ™ S 2 6 Example 344 1-f(2-amino-5-bromopvridvl)thiocarbamoyl 1 imidazole A solution of l,l'-thiocarbonyldiimidazole (17.8G, 0.1m) and 2-amino-5-bromopyridine (17.3g, 0.1m) in acetonitrile (150 mL) was stirred at room temperature for 2 hours. To this suspension was added the material described below.

Example 345 N-f2-(2-pyridyl) ethyl)1-N'-(2-anuno-5-bromopyri<ayl) thiourea To the above solution of 1-[(2-amino-5-bromopyridy 1) thiocarbamoyl ] imidazol e was added 2 - (2 -aminoethyl)pyridine (14.7g, 0.12m) stirred at r.t. for 2 hours and at 50*C 12 hours. The reaction was cooled to room temperature, filtered, washed with acetonitrile. The resultant solid was dissolved in methanol, filtered, hydrogen chloride gas was bubbled into this solution with cooling. Solvents removed under reduced pressure and the resulting residue was recrystallized from methanol ethyl ether to provide 24.8g (76%) of the titled product as a white solid: mp 215-216*C; IR (KBr, cm~l) 3015, 2576, 1634, multiple peaks between (1633-400) ; NMR (300 MHz, DMSO-(?6) 8 11.30 (S, 1H) , 10.75 (s, 1H) , 10.78 (S,1H), 8.80 (d, 1H), 8.40 (t, 1H), 8.22 (s, 1H), 7.97-8.00 (g, 1H), 7.82-7.90(d, 1H) , 7.80(t, lH), 7.10 (d, 1H), 4.10(q, 2H), 3 .35 (t, 2H); MS (FD) m/e 338(M+); X-8571A- 26 0 p o7 ■ c ,j UV (EtOH) 305nm (£=13565), 274nin (£=24201), 201 nm (£=17628) .

Anal. Calcd for Ci3Hi4N4BrClS: C, 41.78; H, 3.78; N, 14.99. Found: C, 42.02; H, 3.86; N, 15.16.

Example 346 N- f2- ( (3-Methoxv) pvr idvl) ethyl! -N' -\7-(5-bromo)ovridvl1 thiourea hydrochlcrjde A) Preparation of 2-Bvdroxvmethvl-3-methoxv pyridine.

Potassium hydroxide (41.66g ,0.744 mol) was ground under nitrogen and stirred in DMSO (130 ml, anhydrous) for 20 min. 3-Hydroxy-2-hydroxymethyl pyridine hydrochloride [Aldrich] (47 g, 0.248 mol) was 15 added and stirred for 30 min in an ice bath. Methyl iodide (35.2 g, 0.248 mol, 15.43 ml) in DMSO (20 ml) was added dropwise to the solution and then allowed to stir overnight at room temperature. 5N HCl was added to pH 1 and the solution was extracted with dichloromethane (5X 20 500ml) . The aqueous was then basified with 5N NaOH \.o pH 14 and extracted with dichloromethane (3X 500 ml). The organics (base wash) were dried over sodium sulfate, and concentrated leaving tan colored crystals. The solid was recrystallized (50% ethyl acetate/hexanes) providing 10.B 25 g (32%) of the titled product as light tan crystals: mp 72°C; IR (KBr, cm-"1) 3080, 1575, 1459, 1424, 1278, 1218, 1066, 809; X-8571A 26 0 o 1-H NMR (300 MHZ, DMSO-dff) 8 8.5 (d,J=4.5Hz,1H), 7.3 (d,J=8.3Hz,1H), 7.25 (dd,J=8.2,4.6 Hz,lH), 4.77 (t,J=5.74Hz,lH), 4.48 (d,J=5.6Hz,2H), 3.77 (s,3H); MS (FD) m/e 139(M+); UV (EtOH) 278nm (£=4909), 220nm (£=6984).

Anal. Calcd for C7H9NO2: C,60.42; H,6.52; N,10.07.

Found: C, 60.32; H,6.54; N,10.23.

B) Preparation of 2-T (3-methoxv)pvridvl1acetonitrile.

Thionylchloride (100 ml) was added dropwise to 2-Hydroxymethyl-3-methoxy pyridine (13.9 g, 0.1 mol) while stirring in an ice bath. After initial fuming subsided, the thionyl chloride was added more rapidly. The solution was then heated to reflux for 2 h. After cooling, the thionyl chloride was removed under reduced pressure leaving brown crystals. The solid was taken up in 190 ml methanol and potassium cyanide (19.4 g, 0.298 mol) dissolved in 80 ml of water was added to the methanolic solution. This solution was heated to reflux and allowed to reflux overnight. The solution was cooled down and 150 ml of saturated sodium carbonate was added and then poured into diethyl ether (500 ml). The solution was extracted 3 more times with 500 ml diethyl ether. The collected organics were washed with brine and saturated sodium bicarbonate. The organics were dried over sodium sulfate and concentrated giving 12.1 g (81.7%) of brown crystalline solid. This solid was used in the reduction without further purification: mp 71°C; 26 Q p X-8571A -416- IR (KBr, cm-1) 3074, 2949, 2253, 1578, 1459, 1286, 1017, 821; l-H NMR (300 MHZ, DMSO-dtf) 8 8.07 (m, 1H) , 7.43 (m,lH), 7.35 (m,lH), 4.0 (s,2H), 3.8 (s,3H); MS (FD) m/e 148(M+); UV (EtOH) 278nm (e=5407), 219nm (e=7435) .

Anal. Calcd for C8H8N2O: C,64.85; H,5.44; N,18.91 .

Found: C, 64.62; H,5.50; N,19.0.

C) Preparation of 2-Ethvlamine-3-methoxvPvridine. 2-[(3-methoxy)pyridyl]acetonitrile (2.0 g, 13 mmol) in 25 ml ethanol was reduced at room temperature under 60 p.s.i. for 24 h using platinum oxide (0.5 g) and 5N HCl (0.2 ml) as catalyst. The organics were concentrated and then taken up in ethyl acetate and water. IN NaOH was added to pH 12 and the amine was extracted out (2x300 ml ethyl acetate). The organics were th?n washed with brine and saturated sodium bicarbonate and then dried over sodium sulfate. The solution is filtered and concentrated giving 1.5 g of oily material. This is used without further purification.

D) Preparation of N-f 2 - ((3-Methoxv)pvridv1)ethv11-N' — T2 — (5-bromo)pyridyl 1 thiourea Thiocarbonyldiimidazole (5 g, 28 mmol) was taken up in acetonitrile (50 ml, anhydrous) and stirred. 2-Amino-5-bromopyridine [Aldrich] (4.85 g, 28 mmol) and 30 ml acetonitrile was added to the solution. The solution was allowed to stir overnight forming a X-8571A. 260 precipitate. The cream colored solid was filtered off and used in the next reaction without further purification. (6.89 g, 87%) The cream colored solid (2.88 g, 10.3 mmol) was taken up in l-methyl-2~pyrrolidinone [Aldrich]. 2-Ethylamine-3-methoxypyridine was added and the solution was heated to 100°C overnight. The solution was poured into ethyl acetate and washed with water and saturated sodium bicarbonate (3x 200 ml). The organics were then dried over sodium sulfate and concentrated. The crude material was purified by flash chromatography on silica gel using 40% ethyl acetate /hexanes, giving lOOmg (3%) of needle-like crystals: mp 178°C; IR (KBr, cm"1) 3157, 3037, 1595, 1562, 1534, 1314, 1275, 1178, 1023, 825; NMR (300 MHZ, DMSO-dg) 811.53 (s,lH), 8.5 (s,lH), 8.17-8.12 (m,2H), 7.68-7.65 (dd, J=8.75, 8.73Hz, 1H), 4.24-4.18 (m,2H), 3.8 (s,3H), 3.2-3.17 (t, J=6.63Hz, 2H) MS (FD) m/e 366(M+), 368(M+l), 369 (M+2) ; UV (EtOH) 305nm (8=13005), 275nm (e=28998) .

Anal. Calcd for Ci4HisN40SBr: C,45.78; H,4.12; N,15.25 Found: C,45.85; H,4.12; N, 15.12.

E) Preparation of N-T2- ((3-Methoxv)ovridvl)ethvll-N1-T2-(5-bromo)pyridvllthiourea hydrochloride N-[2-((3-MethoxyJpyridyl)ethyl]-N'-[2-(5-bromoJpyridyl]thiourea (70 mg, 0.02 mmol) was taken up i a solution of methanol saturated with HCl. The solid immediately went into solution and then came back out as a white solid. More of the solid was crashed out with 26 0 X-8571A -418- diethyl ether. This solid was filtered providing 65 mg (84%) of the hydrochloride salt.

Example 347 N-(2- (2-Flur>ro-6-methoxv) -phenethvl)-N'-(2-thiazolvl) thiourea 3-Fluoro-anisole (10 ml, 88 mmol) was dissolved in dry THF (200 ml). The solution was cooled to -75° C and n-BuLi (52 ml, 105 mmol) was added slowly. The pale yellow solution was stirred at -70°C for 10 minutes. DMF (20 ml) was added and the solution was warmed to ambient temperature. Toluene (200 ml) was added and the solution was washed with water and evaporated to dryness. The product formed crystals. The aldehyde was transformed into the corresponding titled thiazolyl-thiourea product according to the procedure in Example 151. l-H NMR,CDC13 8 2.9-3.0 (2H, t) 3.7-3.9 (2H, t) 6.7-6.9 (2H, q, m) 7-7.1 (1H, d, ) 7.15-7.3 (lH, q) 7.4 (1H, d) .

Example 348 Cis-(D.L)-2-phenylcvclopropvlamine Styrene (100 ml, 873 mmol), Cul (10 mg, 0.05 mmol) and Pd(OAc)2 (10 mg, 0.045 mmol) in 1,2- dichloroethane (100 ml) was heated to reflux. Ethyl diazoacetate (50 ml, 475 mmol) in styrene (100 ml, 873 mmol) was added over 30 minutes. The solution was refluxed for an additional 5 minutes. The solution was cooled and filtered through a short column of alumina which was eluted with ethyl acetate/hexane 26 Q O n y, X-8571A -419- (1:9). The solvents including styrene were evaporated. The residual oil contained a cis-trans mixture (3:7). The oil was dissolved in methanol (200 ml>, and potassium hydroxide (30 g, 535 mmol) in water 5 (50 ml) was added. The solution was refluxed for 2 hours. The solution was cooled and diluted with toluene (100 ml) and water (100 ml).

The water-phase was separated and acidified with hydrochloric acid. The solution was extracted 10 with toluene. The organic phase was dried with sodium sulphate, filtered and evaporated, yielding a pale brown solid. The solid (70 g, 430 mmol) was dissolved in acetone (400 ml) with mechanical stirring under an atmosphere of N2~gas. Triethylamine (70 ml, 502 mmol) 15 was added. The solution was cooled to 5° C and ethyl chloroformate (41 ml, 430 mmol) was added during 20 minutes. The solution was stirred for an additional 5 minutes. Sodium azide (30 g, 460 mmol) in water (100 ml) was added and the solution was stirred for 30 20 minutes. Toluene (400 ml) was added and a thick, white precipitate formed. The solution was decanted to remove the precipitate and dried with sodium sulphate (50 g). The solution was evaporated to 1/4 of the original volume. The solution was diluted with 25 1,2-dichloro-ethane (400 ml) and was refluxed for 3 hours wi*-.h evolution of nitrogen gas.

To the solution was added a mixture of hydrochloric acid (conc. aq.) (100 ml), water (100 ml) and dioxane (200 ml) . The solution was refluxed for 3 30 hours with evolution of CO2 gas. The solution was diluted with water (200 ml), the water-phase was X-8571A 2 separated and washed with 1,2-dichloroethane, basified with ammonia (conc. aq.) and extracted with dichloromethane (3 x 100 ml). The organic-phase was washed with water (100 ml), dried with sodium-sulphate, filtered and evaporated. 50 g of the residual oil was separated on 1000 ml silica-gel, by elution with ethyl acetate, the product (cis) is the faster-eluting component. The pure cis-fractions were evaporated to yield an oil (14g).

^H-NMR CDC13 8ppm 0.8-0.9 (1H, CH2 , m) 1.1-1.2 (lH, CH2, m) 2.-2.1 (1H, PhCH, q) 2.6-2.7 (1H, CiJNH2m. ) 7.1-7.4 (5H, Ph.).

Example 349 N-(cis-(D.L)-2-phenvlcvclopropvl)-N'-(2-thiazolvl)- thiourea The product cis-(D,L)-2-phenylcyclopropylamine from Example 348 was transformed into the titled product according to the procedure in Example 151.

^H-NMR CDCI3 8ppm 1.2-1.3 (lH, CH2, m) 1.5-1.6 (1H, m) 2.4-2.5 (1H, q, PhCfl) 3.6-3.7 (lH, m) 6.6-6.7 (lH, d) 6.8-6.9 (1H, d) 7.2-7.4 (5H, m) Example 35Q N-(ris- (D.L)-2-phenvlcvclobutvl)-N'-(2-thiazolvl)- thiourea A cis/trans mixture of 2-phenylcyclobutylamine (C. Beard, A. Burger, JOC, 27, 2 6 Q o n 7 X-8571A -421- ' . d 3 1647 (1962)) (0.150 g, 1 mmol) was condensed with 165 mg of the product of Example 103 according to the procedure of Example 105. The solution was put into a refrigerator (-10°C) over night and the crystals were collected on a filter and washed with CH3CN. The stereochemistry was determined with NOE-difference NMR. The crystals were pure cis. iH-NMR CDCI3 8ppm 2.2-2.4 (3H, m) 2.6-2.7 (1H, m) 3.9-4.0 (1H, q) 5.1-5.2 (1H, q) 6.6-6.7 (1H, d, thiazole) 6.8-6.9 (1H, d, thiazole) 7.3-7.5 (5H, m, Ph) .

Example 351 N-(cis-(D.l)-2-methvl-2-phenvl-cvclopropvl)-N'-(4- chlorophenvl)thiourea a-Methylstyrene (Aldrich) was transformed into the corresponding amine as a cis-trans mixture according to the procedure of Example 348. The amine (300 mg', 2.04 mmol) and 4-chloro-phenylisothiocyanate were refluxed in CH3CN (5 ml) for 60 minutes. The solution was evaporated and final purification was made by flash-chromatography on silica-gel by elution with ethyl acetate/n-hexane (1:4). The collected fractions were pure cis as determined by NOE-difference NMR. !h-NMR CDCI3 81.1-1.2 (2H, m, CH2> 1.4-1.5 (3H, S, ch3), 3.2-3.4 (1H, m, CflN), 6.4-6.5 (1H, b.s., NH), 7.0-7.1 (2H, Ph), 7.3-7.5 (7H, s,+m, Ph), 7.9-8.1 (lH, b.s., NH).

X-8571A -422- 260 Example 352 N-(2-(2.fi-riifluorophenyl)ethvl)-N'-(2-pvrazlnvl)- thiourea 2,6-Difluorophenethylamine (1.0 g, 6.4 5 mmol), 2-aminopyrazine (0.61 g, 6.4 mmol) and N,N-thiocarbonyl-diimidazole (1.13 g, 6.4 mmol) were condensed according to the procedure of Example 93 to give the titled compound as crystals.

^H-NMR CDCI3 8ppm 3.1-3.2 (2H, t, PhCH2), 3.9-4.0 10 (2H, t, CH2N)/ 6.8-6.9 (2H, t, Ph), 7.1-7.3 (1H, m, Ph), 7.9-8.0 (1H, s, pyr), 8.1-8.2 (lH, d, pyr), 8.3-8.4 (1H, s, pyr?, 9.3-9.4 (1H, b.s., NH), 11.0-11.2 (1H, b.s., NH) • Example 353 N-(2- 12.6-difluoro-3-carboxamidomethvl phenyl)ethvl)-N'-(2-(5-bromonvridvl)-thiourea 2,6-Difluorobenzaldehyde (10 g, 70.4 mmol), 20 ethylene glycol (20 ml), trieLhyl-orthoformate (10 ml) and para-toluene sulphonic acid in 1,2-dichloroethane were heated to 80°C for 2 hours. The solution was neutralized with sodium hydrogen carbonate, washed with water, dried with sodium sulfate, filtered and 25 evaporated. The residual oil was dissolved in tetrahydrofurane (700 ml) under nitrogen-atmosphere. The solution was stirred and cooled to -70°C and n-BuLi (48ml, 1.6 M) was added slowly. The solution was stirred for 20 minutes. Dry-ice (20 g, 455 mmol) was 30 added as quickly as possible (foaming).

X-8571A °6 0 p The solution was slowly brought up to ambient temperature. Water was added and the solution was washed with ethyl acetate, acidified with acetic acid and extracted with ethyl acetate. 5 The organic phase was dried with sodium sulfate, filtered and evaporated. 1 g of the residual solid (4.35 mmol) and N,N-diisopropylamine (2.0 ml) were dissolved in dichloromethane (50 ml) and the solution was cooled to 0°C. 10 Thionylchloride (0.50 ml, 6.9 mmol) was added and the solution was slowly heated to ambient temperature. Methylamine (3 ml) was added. The solution was stirred for 30 minutes and was washed with water, dried with sodium sulfate, filtered and 15 evaporated.

The residue was dissolved in a mixture of water and dioxane (1:2, 20 ml) and para-toluene sulphonic acid (0.5 g, 2.63 mmol) was added. The solution was stirred and heated to 60°C for 2 hours. 20 The solution was neutralized with sodium hydrogen carbonate, extracted with ethyl acetate, dried with sodium sulfate, filtered and evaporated.

The residue was dissolved in toluene and benzyloxycarbonylmethyl triphenyl-phosphorane (1.5 g, 25 3.7 g) was added. The solution was stirred for 30 minutes at 50°C. The solution was put onto a silica- gel column. The column was eluted with ethyl acetate-hexane (1:2) and the collected fractions were evaporated. 0.15 g of the residue was hydrogenated in 30 methanol (50 ml) and acetic acid (5 ml) with Pd/C (10 X-8571A 26 Q p q %, 100 mg) and hydrogen gas, using a Parr apparatus at 1.5 bar for 1 hour.

The solution was filtered through Celite and evaporated. A part of the residue (50 mg, 0.26 mmol) 5 was dissolved in acetone at 0°C.

Triethylamine (50 ml, 0.36 mmol) was added followed by ethyl chloroformate (30 ml, 0.32 mmol). The solution was stirred for 15 minutes and sodium azide (30 mg, 0.46 mmol) in water (2 ml) was added. 10 The solution was stirred for 15 minutes, diluted with ethyl acetate, washed with water, dried with sodium sulfate, filtered and evaporated.

The residue was dissolved in toluene (20 ml) and was stirred and heated at 90° C for 1 hour. The 15 solution was evaporated and dissolved in a dioxane-water-hydrochloric acid (conc. aq.) mixture (1:3:1). The solution was stirred at ambient temperature for 20 minutes. The solution was evaporated and the residual 2 —(2,6-difluoro-3-carboxamidomethyl phenyl)ethylamine 20 hydrochloride was condensed with 1-(2-amino-5- bromopyridyl)-1'-(imidazolyl)thiocarbony1 using the procedure of Example 94.

The reaction mixture was evaporated and the residue was purified by flash chromatography on 25 silica-gel by elution with ethyl acetate-hexane (1:1). Evaporation of the collected fractions yielded the titled product. l-H-NMR CDCI3 5ppm 2.9-3.0 (3H, s, CH3) , 3.1-3.2 (2H, t, PhCH2), 4.0-4.1 (2H, t, -H2N), 6.8-6.9 (1H, d), 30 6.9-7.0 (2H, t), "i.7-7.8 (2H, m) , 8.0-8.1 (1H, s) .

X-8571A 2 6 0 2 9 Example 354 N- 12- n-acPf-amlriomethvl-2 . 6-dlfluoroohenvl) -ethvl) -N'-(2-(5-bromopvridvl))-thiourea 5 Under an atmosphere of nitrogen-gas, 2,4- difluorobenzonitrile (Aldrich) (4.6 g, 33 mmol) was dissolved in tetrahydrofurane (200 ml) with stirring under an atmosphere of nitrogen gas. The solution was cooled to -75°C and lithium-diisopropylamide (25 ml, 10 1.5 M solution) was added. The solution was stirred for 15 minutes and dimethyiformamide (10 ml) was added. The cooling was withdrawn and the solution was diluted with toluene (200 ml), washed with water, dried with sodium sulfate, filtered and evaporated. 15 The residue (4.76 g, 28.5 mmol) was dissolved in 250 ml toluene and benzyloxycarbonylmethyl triphenyl-phosphorane (14 g, 34 mmol) was added.

The solution was stirred for 40 minutes at 35°C (slightly exothermic reaction), and then put onto 20 a column of silica gel. The column was eluted with ethyl acetate-hexane 1:4, and the collected fractions were evaporated. A small part of the residue (0.5 g) was dissolved in methanol (50 ml) and acetic acid (6 ml) and 5 % - Pd/C (300 mg) was added. The mixture 25 was hydrogenated in a Parr apparatus at 1.5 bar for 1 hour.

The solution was filtered through celite and evaporated. The residue was dissolved in acetic anhydride and the solution was stirred and heated to 30 50°C for 20 minutes. Excess reagent was evaporated — - ° X-8571A -426- 2 6 0 ? and the residue was dissolved in water. The solution was heated to 60° C for 20 minutes under stirring. The residue (0.29 g, 1.14 mmol) was dissolved in acetone at 0°C.

Triethylamine (0.315 ml, 2.3 mmol) was added, followed by ethyl chloroformate (0.16 ml, 1.7 mmol). The solution was stirred for 15 minutes and sodium azide (220 mg, 3.3 mmol) in water (2 ml) was added. The solution was stirred for 15 minutes, 10 diluted with ethyl acetate, washed with water, dried with sodium sulfate, filtered and evaporated.

The residue was dissolved in toluene (20 ml) and was stirred and heated at 90°C for 1 hour. The solution was evaporated and dissolved in a dioxane-15 water-hydrochloric acid (conc. aq.) mixture (50:10:1, 50 ml). The solution was stirred at ambient temperature for 20 minutes. The solution was evaporated and the residual amine-hydrochloride was condensed with 1- (2-amino-5-bromopyridyl)-1'-20 (imidazolyl)thiocarbonyl using the procedure of Example 94.

The reacticn-mixture was evaporated and the residue was purified by flash chromatography on silica-gel by elution with ethyl acetate-hexane (1:1). 25 The collected fractions were evaporated to yield the titled product as crystals. l-H-NMR CDCI3 8ppm 1.9-2.0 (3H, s, CH3CON) , 3.0-3.1 (2H, b.s., PhCH2CH2N), 3.9-4.1 (2H, b.s., PhCH2CH2N), 4.3-4.4 (2H, s, PhCE2N), 6.8-6.9 (2H, m), 7.2-7.4 (1H, 30 m) , 7.7.-7.8 (1H, d) , 8.1-8.2 (1H, s) .

X-8571A 2 6 0 ? o x Example 355 N- (4-inefchvl-3-pentenvl) -N' - (4-methvl-2- thiazolvl) thiourea 4-Methyl-3-pentenylamine and an activated derivative of 2-amino-4-methylthiazole, i.e. l-(2-amino-4-methylthiazole)-1'-imidazole thiocarbonyl, were condensed according to the procedures of Example 105 to give the titled product.

Mp.: 164.5 - 165.5°C.

Analyses: Calculated C 51.73, H 6.71, N 16.45; Found C 52.0, H 6.9, N 16.7. 1H-NMR (CDC13 d): 1.65 (s, 3H), 1.73 (d, 3H), 2.29 (d, 3H), 2.40 (q, 2H), 3.70-3.78 (m, 2H), 5.16-5.22 (m, 15 1H), 6.36 (q, 1H), 10.14 (broads, 1H), 10.90 (broad s, 1H). 13C NMR (CDCl3d) : 17.16, 17.93, 25.83, 27.28, 45.69, 105.04, 120.53, 134.84, 147.99, 160.79, 177.28.

Example 356 N-(2-(2.6-difluoro)-phenethvl)-N'-(2 - benzimidazolyl)thiourea 2, 6-Dif luorphenetylamine and 2-aminobenzimidazole were reacted according to the 25 procedures of Examples 93 and 94, using 2- aminobenzimidazole instead of 2-aminothiazole, to give the titled product.

Mp: 195-7°C (dec) ^H-NMR (DMSO-dg d): 3.16 (t, 2H), 4.02 (q, 2H), 7.14-30 7.24 (m, 4H), 7.43-7.49 (m, 3H), 11.13 (broad s, 1H), 11.40 (broad s, 1H).

X-8571A 26 Q 9 q Example 3 57 M-(2-(3-hydroxy)-phenethvl)-N'-(5-bromo-2- pyriflinvl)thiourea 3-Hydroxyphenethylamine and 5-bromo-2-aminopyridine were reacted according to the procedures of Examples 93 and 94, using 4-bromo-2-aminopyridine instead of 2-aminothiazole, to give the titled product..

Yield: 35 %.

Mp: 176.5 - 178.0°C. l-H-NMR (DMSO-dg d) : 2.95 (t, 2H) , 3.90 (q, 2H) , 6.73-6.85 (m, 3H), 7.20-7.27 (m, 2H), 8.08 (dd, lH), 8.32 (d, 1H), 9.49 (s, 1H), 10.84 (s, H) , 11.33 (t, 1H) . 13C-NMR (DMSO-dg d): 34.01, 46.30, 111.70, 113.26, 114.41, 115.70, 119.32, 129.35, 140.41, 141.29, 145.79, 152.29, 157.34, 179.07.

Example 3 58 N- (2-M.-methvl)-2-pvrrolvlethvl)-N'-(5-chloro-2-pvridinvl)thiourea 2-(Aminoethyl)-1-methyIpyrrole and an isothiocyanate of 5-chloro-2-aminopyridine were condensed analogous to the procedures described in Example 105, to give the titled product.

Yield: 78 %.

Mp: 169.5-170.0°C. iH-NMR (DMSO-dg d): 3.01 (t, 2H), 3.67 (s, 3H), 3.93 (q, 2H), 6.00 - 6.02 (m, 2H) , 6.74 (s, 1H), 7.32 (d, X-8571A 2 6 0 o Q 1H), 7.97 (dd, 1H), 8.27 (d, 1H), 10.76 (s, 1H), 11.36 (broad s, lH). 13C-NMR (DMSO-dg d): 24.97, 33.19, 44.37, 106.22, 106.39, 114.02, 121.58, 123.70, 129.32, 138.70, 5 143.61, 152.05, 179.31.

Example 359 N-(2-(3-Methvl)phenethvl)-N'-(2-thiazolvl)thiourea (3-Methyl-phenyl)acetic acid was reduced 10 with lithium aluminum hydride in tetrahydrofurane under reflux to 2-(3-methyl-phenyl)ethanol, which was further transformed to 2-(3-methyl-phenyl)ethylamine by the procedure described in Example 106.

Condensation of this amine with the product of Example 15 103 and using the procedure described in Example 105, gave the titled product. 13C-NMR (250MHz, CDC13): 8178, 162, 138, 137, 137, 130, 128, 127, 126, 102, 47, 35, 22.

Mp: 145 - 146°C.

Example 360 N- 12-(2-Ethoxv)phenethvl)-N'-(2-(4- methvl)thiazolvl)thiourea In a manner analogous to Example 105, 2-(2-25 ethoxyphenyl)ethylamine was condensed with l-(2-amino-4-methylthiazolyl)-1'-imidazole thiocarbonyl, which was made in a similar way as described in Example 103, to give the titled product.

^H-NMR (250 MHz, DMSO): 87.32 - 6.73 (m, 5H, phenyl, 30 thiazole), 4.09 (q, 2H, OCH2CH3), 3.86 (q, 2H, CH2NH), X-8571A 260 2 9 2.97 (t, 2H, Ph-Ch2), 2.25 (s, 3H, thiazole-CH3), 1.43 (t, 3H, OCH2CH3). 13C-NMR (250 MHz, DMSO): 8176, 162, 157, 130, 128, 127, 120, 112, 107, 106, 63, 44, 29, 17, 15. 5 Mp: 188 - 189°C.

Example 361 N- (2 - (3-Efchoxv)nhpnpt.hvl) -N' - (2-thiazolvl) thiourea 3-Hydroxybenzaldehyde (3.0 g, 24.6 mmol), 10 ethyl iodide (5.9 ml, 73.8 mmol) and K2CO3 (3.4 g, 24.6 mmol) in 50 ml of acetone was stirred at +40°C for 6 h and at RT overnight. The mixture was filtered and evaporated. The product was purified by silica gel column chromatography (EtOAc/petroleum ether 15 15:100) to give 3-ethoxybenzaldehyde.

Yield 2.91 g (79%) . l-H-NMR (250 MHz, CDCI3) : 9.97 (s, lH, CHO) , 7.45 -7.14 (m, 4H, phenyl), 4.10 (q, 2H, CH2CH3), 1.44 (t, 3H, CH2CH3).

By using the procedure of Example 151, 3-ethoxybenzaldehyde was transformed to 2-(3-ethoxyphenyl)ethylamine, which was reacted with the product of Example 103, following the procedure of 25 Example 105 to give the titled product. 1H-NMR (250MHZ, DMSO): 57.60 (d, 1H, thiazole), 7.30 - 6.93 (m, 4H, phenyl), 4.08 (q, 2H, OCH2CH3), 3.87 (q, 2H, CH2-NH), 2.96 (t, 2H, phenyl-CH2>, 1.42 (t, 3H, OCH2CH3).

Mp: 169 - 170°C.

X-8571A 26 0 Example 362 M- (2- (2-F.t-hoxv-6-fluoro)nhenethvl) -N' - (2-t-.hiaozolvl) thiourea 1) 3-Fluorophenol (20.0 g, 178.4 mmol), ethyl iodide (83.5 g, 535.2 mmol) and K2CO3 (49.3 g, 356.8 mmol) in 250 ml of acetone were stirred at 50°C overnight. The mixture was filtered and evaporated to give l-ethoxy-3-fluorobenzene.

Yield 19.84 g (79%).

^H-NMR (250 MHz, CDCI3): 87.20 (q, 1H, phenyl), 6.69 - 6.57 (m, 3H, phenyl), 4.00 (q, 2H, CH2CH3), 1.40 (t, 3H, CH2CH3). 2) 1.6 M Butyl lithium in hexane (24 ml, 38.4 mmol) was added slowly (0.5 h) to a solution of l-ethoxy-3-fluorobenzene (5.0 g, 35.7 mmol) in 100 ml of dry THF at -65°C under nitrogen. The solution was stirred at -65° C for 25 min. DMF (5.22 g, 71.4 mmol) was added dropwise to the solution. The mixture was allowed to warm to room temperature. 300 ml of ice was poured to this mixture and it was extracted with diethyl ether. Diethyl ether was washed with brine, dried over Na2S04 and evaporated. The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100) to give 2-ethoxy-6-fluorobenzaldehyde.

Yield: 3.69 g (61 %).

X-8571A 260 ^H-NMR (250 MHz, CDCI3): 87.52 - 7.40, 6.80 - 6.64 (m, 3H, phenyl), 4.18(q, 2H, CH2CH3), 1.50 (t, 3H, CH2CH3).. 13C-NMR (250 MHz, CDCI3): 5188, 165, 161, 136, 109, 108, 65, 14. 3) Following the procedure of Example 151, this aldehyde was transformed to 2-(2-ethoxy-6-fluorophenyl)ethylamine, which was condensed with the product of Example 103, using the procedure of Example 105 to give the titled product. l-H-NMR (250 MHz, DMSO): 87.32 - 6.72 (m, 5H, phenyl, thiazole), 4.00 (q, 2H, CH2CH3), 3.78 (q, 2H, CH2-NH), 2.92 (t, phenyl-CH2), 1.33 (t, 3H, CH2CH3).

Example 363 N- (2- (3-Isopropoxv)phenethvl) -N' - (2-thiazolvl ) r.himirea 3-Isopropoxybenzaldehyde was prepared from 3-hydroxybenzaldehyde and isopropyl iodide analogous to the procedure described in Example 361. By using the procedure of Example 151 this aldehyde was transformed to 2-(3-isopropoxyphenyl)ethylamine, which was reacted with the product of Example 103, following the procedure of Example 105 to give the titled product. iH-NMR (250 MHz, DMSO): 8 7.44 - 6.84 (m, 6H, phenyl, thiazole), 4.69 - 4.64 (m, 1H, isopropoxy-CH), 3.87 (q, 2H, CH2NH), 2.96 (t, 2H, phenyl-CH2), 1.36 - 1.32 (m, 6H, 2CH3).

X-8571A 26 0 ? I— Example 364 N- 12- (5-Bromo-7.-et-hoxv)phenethvl -TJ' - ra-thi agr>1 vl) thiourea 1) 5-Bromo-2-hydroxybenzylalcohol (5.0 g, 24.6 mmol), ethyl iodide (11.5 g, 73.8 mmol) and K2CO3 (3.4 g, 24.6 mmol) in 50 ml of acetone was stirred at +50°c overnight. The mixture was filtered and evaporated. The product was purified by silica gel column chromatography (EtOAc/petroleum ether 30:100) 10 to give 5-bromo-2-ethoxybenzyl alcohol.

Yield: 5.24 g (92 %). l-H-NMR (250 MHz, CDCI3) : 57.42 - 7.31 (m, 2H, phenyl), 6.73 (d, 1H, phenyl), 4.67 (d, 2H, £H2"OH), 4.07 (q, 2H, £H2CH3), 1.60 (S, 1H, OH), 1.43 (t, 3H, CH2£fi3). 2) 5-Bromo-2-ethoxybenzyl alcohol (2.78 g, 12.0 mmol) and pyridinium dichromate (4.51 g, 12.0 mmol) in 120 ml of CH2CI2 was stirred at RT for 6 h. The mixture was filtered, washed with H2O, 0.5 N HCl and brine and dried over Na2£04. The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100) to give 5-bromo-2-ethoxybenzaldehyde.

Yield: 2.33 g (85 %).

^H-NMR (250 MHz, CDCI3) : 810.4 (s, 1H, CHO) , 7.91 (d, 1H, phenyl), 7.60 (dd, 1H, phenyl), 6.88 (d, 1H, phenyl), 4.14 (q, 2H, CH2CH3), 1.51 (t, 3H, CH2CH3). 3) Following the procedure of Example 151, 30 the aldehyde was transformed to 2-(5-bromo-2- X-8571A 26 0? i-oa« ethoxyphenyl)ethylamine, which was condensed with the product of Example 103, using the procedure of Example 105, to give the titled product.

^H-NMR (250 MHz, DMSO): 87.10 - 6.62 (m, 5H, phenyl, thiazole), 3.73 (q, 2H, CH2CH3), 3.52 (q, 2H, CH2NH), 2.62 (t, 2H, phenyl-CH2)/ 1.07 (t, 3H, CH2CH3).

N-(2-(2.5-Dimethoxv)phenethvl)-N'-(2-pvridvl)thiourea 10 2, 5-Dimethoxy phenethylamine (0.36 g, 2.0 mmol) in 7 ml ui: DMF was added to a solution of 1,1-thiocarbonyldiimidazole (0.36 g, 2.0 mmol) in 7 ml of DMF at 0°C. After 5 minutes 2-aminopyridine (0.19 g, 2.0 mmol) in 1 ml of DMF was added at 0°C. 15 This mixture was refluxed at 150°C for 4 hours. After cooling to room temperature it was poured into ice-water and extracted with diethyl ether, dried over Na2S04 and the solvent was evaporated. The product was purified by silica gel 20 column chromatography (EtOAc/petroleum ether 15:100). Yield: 0.24 g (39 %) .

^■H-NMR (250 MHz, CDCI3) : 58.41 (broad s, 1H, NH) , 8.04 (d, 1H, pyridine), 7.61 (t, 1H, pyridine), 6.94 - 6.67 (m, 5H, phenyl, pyridine), 4.03 (q, 2H, CH2NH), 3.78 25 (s, 3H, CH3O), 3.73 (s, 3H, CH3O), 3.00 (t, 2H, phenyl-CH2).

X-8571A 260 2 9 Example 3 66 N-(2-(2-Ethoxv)Phenethvl)-W-(2-(5- bromo)pyridyl)thiourea In a manner analogous to Example 151, 2-5 ethoxy phenethylamine was obtained from 2-ethoxybenzaldehyde. 2-Ethoxy phenethylamine (1.1 g, 6.7 mmol) in 20 ml of acetonitrile was added slowly to a mixture of 1,1-thiocarbonyldiimidazole (1.32 g, 7.4 mmol) in 20 10 ml of acetonitrile at 0°C. The mixture was warmed to RT and evaporated. 2-Amino-5-bromo-pyridine (1.63 g, 9.4 mmol) and this crude reaction mixture in 30 ml of DMF were refluxed for 6 h at 140°C. After cooling to room temperature the reaction mixture was poured into 15 ice-water and extracted with diethyl ether, dried over Na2SC>4 and the solvent was evaporated. The product was purified by silica gel column chromatography (EtOAc/petroleum ether 15/100). l-H-NMR (250 MHz, CDCI3) 5 8.73 (broad s, lH, NH) , 8.00 20 (d, 1H,. pyridine), 7.08 (dd, 1H, pyridine), 7.26 - 7.16 (m, 2H, phenyl), 6.96 - 6.82 (m, 2H, phenyl), 6.68 (d, 1H, pyridine), 4.03 (q, 2H, CH2CH3), 4.03 (q, 2H, CH2NH), 3.02, (t, 2H, phenyl-CH2), 1.42 (t, 3H, CH2CH3). 13c-nmr (250MHz, CDCl3)6l79, 157, 152, 146, 141, 131, 128, 127, 120, 113, 112, 111, 63, 46, 30, 15. 2 6 0 ^ q 7 X-8571A -436- • O Example 367 N-12-(2-Ethnxv-6-fluoro)phenethvl)-N'- 12- pyridyl)thiourea The starting material 2-(2-ethoxy-6-fluorophenyl)ethylamine was prepared as described in Example 362. Following the condensation procedure described in Example 366, and using 2-aminopyridine instead of 2-amino-5-bromopyridine, the titled product resulted. 1-H-NMR (250 MHz, CDCI3) 5 8.00 (d, lH, pyridine), 7.58 (t, 1H,. pyridine), 7.14 (q, 1H, pyridine), 6.91 - 6.59 (m, 4H, phenyl, pyridine), 3.95 (q, 2H, CH2CH3), 3.95 (q, 2H, CH2-NH), 3.09 (t, 2H, phenyl-CH2), 1.39 (t, 3H, CH2CH3). 13C-NMR (250 MHz, CDCl3)8l79, 164, 153, 145, 138, 128, 128, 117, 112, 108, 107, 107, 64, 45, 22, 15.

Example 368 N-2--Methoxv)phenethvl)-N1-(2-thiazolvl)methvlthioether Methyl iodide (0.425 g, 3.0 mmol) was added to a solution of N-(2-(2-methoxy)phenethyl)-N' - (2-thiazolyl)thiourea, (Example 94), (0.3 g 1.0 mmol) in 15 ml of DMF. The mixture was stirred at RT for 8 h. Methyl iodide was evaporated and the mixture was poured to ice, extracted with methylene chloride, dried over Na2S04 and evaporated. The product was purified by silica gel column chromatography (EtOAc/petroleum ether 10:100).

X-8571A -437- 2 6 0 p o ^-NMR (250 MHz, CDCI3): 87.25 (d, lH, thiazole), 7.24 - 7.16 (m, 2H, phenyl), 6.92 - 6.81 (m, 2H, phenyl), 6.70 (d, 1H, thiazole), 3.79 (s, 3H, CH3O), 3.57 (q, ?K, CH2NH), 2.95 (t, 2H, phenyl-^), 2,46, (s, 3H, SCH3). 13C-NMR (250 MHz, CDCI3): 8173, 162, 157, 137, 130, 127, 126, 120, 111, 110, 55, 43, 30, 13.

Example 369 N-(2-(2-Ethoxv-fi-flnoro)phenethvl)-N'-(2-<5- fflftf.hvl )wri^l) thiourea The starting material 2-(2-ethoxy-6-fluorophenyl)ethylamine was prepared as described in Example 362. . Following the condensation procedure described in Example 366 and using 2-amino-5-methyIpyridine instead of 2-amino-5-bromopyridine, the titled product resulted.

^H-NMR (250 MHz, CDCI3): 88.65 (broad s, 1H, NH) , 7.83 (s, 1H, pyridine), 7.41 (d, 1H, pyridine), 7.22 - 7.05 (q, 1H, phenyl), 6.73 - 6.58 (m, 3H, phenyl, pyridine), 3.98 (q, 2H, Cfi2CH3)' 3.98 (q, 2H, » 3.07 (t, 2H, phenyl-£H2)» 2-25 (s, 3H, CH3), 1.40 (t, 3H, CH2CH3)• 13C-NMR (250 MHz, CDCI3): 8179, 168, 152, 145, 139, 127, 127, 126, 111, 108, 108, 107, 63, 44, 22, 17, 14.

Example 370 N-Phenethv1-N'-(2-(5-chloro)pvridvl)thiourea The product from example 374 (0,3 g, 1.76 mmol) and phenethylamine (0.22 ml, 1.76 mmol) in 8 ml X-8571A 26 0 of acetonitrile was stirred at RT for 0.5 h. The mixture was filtered. The precipitate was dried and recrystallized from acetonitrile.

Mp: 152 - 153°C.

^H-NMR (250MHz, DMSO): 58.20 (d, lH, pyridine), 7.98 (dd, 1H, pyridine), 7.45 - 7.40 (m, 5H, phenyl), 7.27 (d, 1H, pyridine), 3.94 (q, 2H, CH2NH), 3.04 (t, 2H, phenyl-CH2). 13C-NMR (250 MHz, DMSO): 6179, 152, 143, 139, 139, 129, 128, 126, 124, 114, 46, 34.

Example 371 N-(cis- (D.L) -2-PhenvlcvclopropvH -N' - 12-pvridvl)thiourea -cis-(D,L)-2-Phenylcyclopropylamine (Example 348) and 2-aminopyridine were reacted according to the procedures of Examples 93 and 94, using 2-aminopyridine instead of 2-aminothiazole, to give the titled product. iH-NMR: 1.19 - 1.27 (m, 1H), 1.45 - 1.55 (m, 1H), 2.50 (q, 1H), 3.67 - 3.78 (m, 1H), 6.73 - 6.78 (m, 2H), 7.27 - 7.34 (m, 5H), 7.41 - 7.53 (m, 2H), 1.08 (broad s, 1H}.' 13C-NMR: 12.4, 21.9, 34.6, 111.8, 117.3, 126.5, 128.2, 129.1, 136.5, 138.2, 145.1, 153.0, 180.3.

Mp: 184.5 - 186.0°C.

X-8571A 2 60° n ? • • »J Example 372 N-(5-Chloro-2-pvridvl)-N'-(cis-(D.L)-2- phenvlcvclopropyl)thiourea cis-(D,L)-2-Phenylcyclopropylamine (Example 5 348) and an activated derivative of 2-amino-5- chloropyridine, i.e. 1-(2-amino-5-chloropyridine)-1*-imidazole-thiocarbonyl, were condensed using the procedures of Example 105 to give the titled product. !H-NMR (CDCI3): 1.19 - 1.26 (m, 1H), 1.46 - 1.55 (m, 1H) , 2.51 (q, 1H) , 3.64 - 3.74 (m, 1H) , 6.74 (dd, 1H) , 7.30 - 7.40 (m, 6H), 7.47 (dd, 1H), 9.2 (broad s, lH) , 10.9 (broad s, 1H). 13C-NMR (CDCI3): 12.4, 22.0, 34.7, 112.7, 124.7, 126.8, 128.4, 129.2, 136.5, 138.3, 143.9, 151.1, 15 180.2.

Mp: 194 - 195.5°C.

Example 373 N-(5-Bromo-2-pvridvl)-N' -(cAs- (D.L) -2- phenylcyclopropyl)thiourea cis- (D,L)-2-Phenylcyclopropylamine (Example 348) and 2-amino-5-bromopyridine were reacted according to the procedures of Examples 93 and 94, using 2-amino-5-bromopyridine instead of 2-25 aminothiazole, to give the titled product.

^H-NMR {CDCI3): 1.19-1.26 (m, 1H), 1.47 - 1.55 (m, 1H), 2.52 (q, 1H), 3.66 - 3.75 (m, 1H), 6.66 (dd, 1H), 7.27 - 7.41 (m, 5H), 7.47 (d, 1H), 7.60 (dd, 1H), 8.98 (broad s, lH), 10.88 (broad s, lH). 26 0 X-8571A -440- 13C-NMF (CDCI3): 12.4, 22.0, ZA.l, 112.3, 113.1, 126.C, 128.4, *129.2, 136.5, 140.9, 146.2, 151.3, 180.2.

Mp: 20.4 - 205OC 5 Anal calcd. for CisH^Br^S: C, 51.7; H, 4.05; N, 12.07. Found C, 51.5; H, 4.0; N, 12.0.

Example 374 -ChloroPvrid-2-vligothiocvanate 10 2-Amino-5-chloropyridine (10.28 g) was added in portions, with stirring, over a period of 25 minutes to a solution of thiocarbonyl diimidazole (14.26 g) in acetonitrile (100 ml) a: ambient temperature. .The stirring was continued and the 15 solution/suspension was left at ambient temperature for a few hours. The precipitate was filtered and washed with acetonitrile (3 x 25 ml). The solid residue was dissolved in hot acetone and filtered. The acetone solution was evaporated in vacuo, the 20 residue was dissolved in hot ethyl acetate and filtered through a pad of silica (diam. 7 c m x 3 cm). The silica was washed with another portion of hot ethyl acetate. The combined solutions were evaporated in vacuo to yield a crude product (5 g) of the titled 25 product. !h-NMR (DMSO): 7.54 (d, J = 8.7 Hz, lH), 8.17 (dd, J = 2.7, 8.7 Hz, 1H). 8.63 (d, J = 2.7 Hz, lH) . 13C-NMR (DMSO): 121.4, 130.1, 139.4, 140.7, 143.9, 148.6.

X-8571A 26 Q ? a Example 375 N-cis-(D.L)-(2-(3-Methoxv)-Phenylcvclopropvl)-N/(2- thiazolyl)thiourea The starting material, 3-methoxystyrene, was 5 prepared in following manner: To a mixture of 26.2 g (73.4 mmol) of methyl triphenylphosphonium bromide in 200 ml of THF cooled to 0°C, was added 42 ml (2M THF, 82 mmol) of a lithium, diisopropyl amide solution over 30 min. The 10 mixture was stirred for an additional 2 hours then 10 g (73.4 mmol) 3-methoxybenzaldehyde was added dropwise over 25 min. The reaction mixture was stirred for one hour at room temperature and then heated under reflux for 14 hours. After cooling the solvent was 15 evaporated in vacuo, the residue was diluted with 200 ml diethyl ether and the precipitate was removed by filtration. The ether solution was washed with water, dried with Na2S04 and evaporated in vacuo. The product was purified by silica gel column 20 chromatography (diethyl ether/cyclohexane).

Yield: 2.83 g (29 %). iH-NMR (CDCI3)d: 7.24 (t, J = 8.1 Hz, 1H, Ph), 7.21-6.98 (m, 1H, Ph), 6.95 (t, J = 2.3 Hz, 1H, Ph), 6.81 (ddd, J. = 8.1 Hz, 2.3Hz, 0.9 Hz, 1H, Ph), 6.69 (dd, J 25 = 17.6 Hz, 10.8 Hz, lH, C"), 5.74 (dd, J = 17.6 Hz, 0.9 Hz, 1H, CH2), 5.25 (dd, J = 10.8 Hz, 0.9 Hz, lH, CH2), 3.81 (s, 3H, CH3). 13C-NMR (CDCI3)d: 159.81 (C-3), 139.04 (C-l), 136.79 (C-a), 129.51 (C-5), 118.92 (C-6), 114.15 (C-4), 30 113.46 (C-2), 111.53 (C-b), 55.22 ,0-£H3).

X-8571A 2 6 0 o a ? J The titled compound was prepared in a manner analogous to the procedures described in Examples 348 and 349, using 3-methoxystyrene instead of styrene. ^H-NMR (CDCI3)d: 7.26-7.19 (t and d, 2H, o and thiazole), 6.90-6.69 (m, 4H, o, m, p, thiazole), 3.76 (s, 3H, OMe), 3.65 (broad s, 1H, NH-Cfl-), 2.50 (q, 1H, Ph-CH-), 1.22 (m, 2H, Cyclopropyl). 13C-NMR (CDCI3)d: 178.6 (C=S), 161.3 (thiazole), 159.8 (£-0Me), 137.8 (Ph), 137.7 (thiazole), 129.5 (Ph), 10 121.6 (Ph), 114.5 (Ph), 112.8 (Ph), 111.0 (thiazole), 55.2 (0-£H3), 44.0 (C.H-NH) , 22.0 >£H-Ph) , 12.1 (£H2) .

Example 376 N-cis- (P.P.- (2- (2-FluproPhenYl)CYclpprQPYl)-N'- (2- thiaznvl thiourea In a manner analogous to the procedures described in Examples 348 and 349 and using 2-fluorostyrene instead of styrene, the titled product was prepared.

T-H-NMR (CDCI3)d: 7.32-7.05 (m, 4H), 6.91-6.64 (m, 2H) , 3.68 (broad s, 1H, CH-NH), 2.57 (q, lH, CH-Ph), 1.70-1.40 (m, 3H), 1.31-1.18 (m, lH). 13C-NMR (CDCI3)d: 178.8 (C=S), 162.5 and 160.5 (£-F, Ph), 161.2 (thiazole), 137.4 (thiazole), 129.9 (Ph), 25 128.5 and 128.4 (m to F,Ph), 124.0 (p to F, Ph) 115.4 and 115.1 ( o to F, Ph), 111.8 (thiazole), 33.8 (CH-NH), 16.4 (£H-Ph), 12.2 (£H2)- / X-8571A -443- £6 Q o Q i Example 377 N- (2-T3- (6-rhloro-2-methoxv)pvridvllethvl) -N'- (2-(5-bromciinvridvl) thiourea The starting material, 3-(2-aminoethyl)-6-chloro-5 2-methoxypyridine, was prepared in following manner: To a solution of 1.0 g (7.0 mmol) of 2-chloro-6-methoxypyridine in 20 ml of dry THF cooled to -78°C was added 10.9 ml (1.6 M in hexanes, 17.4 mmol) n-BuLi under an atmosphere of nitrogen. The 10 temperature of the mixture was allowed to raise to -40°C before an addition of 4 ml ethylene oxide in 6 ml ether. The mixture was warmed to room temperature, 50 ml water was added and the aqueous layer was separated and extracted with 2 x 100 ml EtOAc. The 15 organic extracts were combined, washed once with water, dried with Na2S04, and concentrated in vacuo.

The crude material was purified by dry column flash chromatography (hexane/EtOAc ) to afford 0.22 g of 3-(2-hydroxyethyl)-6-chloro-2-methoxypyridine as a 20 yellowish oil.

To a solution of 0.20 g (0.8 mmol) of 3-(2-hydroxyethyl)-6-chloro-2-methoxypyridine in 10 ml of dry CH2CI2 cooled to -50°C was added 0.18 ml (0.8 mmol) trifluoromethanesulfonic anhydride under an 25 atmosphere of nitrogen. The mixture was stirred for min at this temperature and an additional 10 min at -78°C before a rapid addition of 30 ml of cold (-78°C) NH3 (1). The mixture was stirred for 15 min at room temperature, and then concentrated in vacuo to afford 30 1.0 g of crude 3-(2-aminoethyl)-6-chloro-2- X-8571A 26 0 p q ? methoxypyridine as a trifluoromethanesulfonic acid salt.

^H-NMR (CD30D)d: 7.66 (d, 1H, Py) , 7.03 (d, lH, Py) , 4.04 (s, 3H, CH3-O), 3.24 (t, 2H, CH2-N), 3.03 (t, 2H, 5 CH2-Py).

The crude 3-(2-aminoethyl)-6-chloro-2-methoxypyridine was condensed with N-(2-(5-bromo)pyridyl-N'-(1-imidazolyl)thiourea in a manner analogous to Example 103, to give the titled product. 10 !h-NMR (CD3OD)d: 11.25 (broad s, 1H, N-H), 10.82 (broad s, 1H, N-H), 8.31 (s, lH, Br-Py), 8.08 (d, lH, Br-Py), 7.89 (d, 1H, Cl-Py), 7.21 (m, 2H, Cl- and Br-Py), 3.96 (m, 5H, CH2-N, and CH3-O), 3.03 (t, 2H, CH2- Py) . 13C-NMR (CD3OD)d: 179.45 (C=S), 161.43 (Cl-C in Py) , 152.41 (Br-C in Py), 145.92 (Cl-Py), 145.14 (MeO-C-Py), 141.89 (Br-Py), 141.51 (Br-Py), 120.32 (Cl-Py), 116.48 (Cl-Py), 114.60 (Br-Py), 111.95 (Br-Py), 55.10 (CH3-O), 43.76 (CH2-NH), 27.89 (CH2-Ph).

Example 378 N-(2 - f 3 -(2-Fluoro)pvridvllethvl)-N'-(2- (5-bromo)pvridvl)thiourea The starting material, 3-(2-aminoethyl)-2-25 fluoropyridine, was prepared in following manner: A solution of 2.0 g (20.6 mmol) of 2-fluoropyridine in 25 ml of dry THF was cooled to -78°C was added 25 ml (1.6 M in hexanes, 41.6 mmol) n-BuLi under an atmosphere of nitrogen. The mixture was 30 stirred at this temperature for 2 hours before an addition of 4 ml ethylene oxide in 7 ml ether. The X-8571A 26 0 o g mixture was wanned to room temperature, 150 ml ether and 25 ml acetone was added. The precipitate was removed by filtration, and the filtrate was concentrated to 1/3 of volume in vacuo. The remainder 5 was washed once with brine, dried with Na2S04, and concentrated in vacuo. The crude material was purified by dry column flash chromatography (hexane/EtOAc) to afford 0.42 g of 3-(2-hydroxyethyl)-2-fluoropyridine as a brown oil. 10 To a solution of 0.20 g (1.42 mmol) of 3-P- hydroxyethyl)-2-fluoropyridine in 8 ml of dry CH2CI2 cooled to -40°C was added 0.18 ml (0.8 mmol) trifluoromethanesulfonic anhydride under an atmosphere of nitrogen. After stirring for 30 min at -40°C, 30 15 ml of cold (-78°C) NH3 (1) was added. The mixture was stirred, for 30 min at -40°C, and then concentrated in vacuo to afford 1.03 g of crude salt which was washed twice with 20 ml diethyl ether to yield 0.82 g of 3-(2-an'noethyl)-2-fluoropyridine as a 20 trifluoromethanesulfonic acid salt.

^H-NMR (CD3OD)d: 8.23 (d, 1H, Py), 7.98 (t, lH, Py), 7.40 (m, 1H, Py), 3.30 (t, 2H, CH2-N), 3.12 (t, 2H, CH2-Py).

The crude 3-(2-aminoethyl)-2-iluoroyYridine 25 was condensed with N-(2-(5-bromo)pyridyl-N'-(1- imidazolyl)thiourea in a manner analogous to example 103, to give the titled product.

^H-NMR (CD3OD) d: 8.31 (d, lH, Br-Py), 8.23 (m, lH, F-Py), 8.06 (m, 2H, Br-and F-Py), 7.45 (m, 1H, F-Py), X-8571A 26 Q p a KiJ 7.23 (d, lH, Br-Py), 4.00 (q, 2H, CH2"N) , 3.14 (m, 2H, cn2-py>• 13C-NMR (CD3OD)d: 179.59 (C=S), 163.53 and 159.78 (F-£ in Py), 152.39 (Br-Py), 145.87 (F-Py),145.63 and 5 142.38 (F-Py), 142.28 (Br-Py),141.54 (Br-Py), 122.31 and 122.26 (F-Py), 120.94 and 120.45 (F-Py), 114.59 (Br-Py)., 111.97 (Br-Py), 44.29 (£H2-NH), 27.32 (£H2- Ph) .

Example 379 N- (2 - (2. 6-difluoro)phenethvl) -NT - (2-benzothiazolyl) thiourea In a manner analogous to Example 105, 2,6-difluorophenethylamine was condensed with l-(2-15 aminobenzothiazole)-1'-imidazole thiocarbonyl which was made in similar way as described in Example 103. The titled compound crystallized from methylene chloride. iH-NMR (CDCI3 + CD3OD) d: 7.64 (m, 2H, benzo), 7.38 (m, 3H, DFPh, benzo), 7.24 (t, 2H, DFPh), 4.04 (t, 2H, CH2), 3.15 ( t, 2H, CH2).

Example 38Q N-(2-(2.6-difluoro)phenethvl)-N'-(2-(4.5-25 dimethyl)thiazolvl)thiourea In a manner analogous to Example 105, 2,6-difluorophenethylamine was condensed with l-(2-amino-4,5-dimethylthiazole)-1'-imidazole thiocarbonyl which was made in a similar way as described in Example 103.

X-8571A The titled compound crystallized from methylene chloride. iH-NMR {CDCI3) d: 7.21 (m, lH, DFPh), 7.15 (t, 2H, DFPh), 4.00 (q, 2H, CH2), 3.09 (t, 2H, CH2), 2.22 <d, J=0.5Hz, 3H, Me), 2.08 (d, J=0.6Hz, 3H, Me).

Example 381 N-(2-(2-£luoro)phenethvl) -N' - (2 - (6 - fluorobenzothiazolvl)thiourea In a manner analogous to Example 105, 2-fluorophenethylamine was condensed with 1-(2-amino-6-fluorobenzothiazole)-1'-imidazole thiocarbonyl which was made in a similar way as described in Example 103. The titled compound crystallized from methylene chloride. iH-NMJKCDCIs + CD3OD) d: 7.53-7.06 (m, 7H, benzo, FPh), 4.04 (t, 2H, CH2), 3.10 (t, 2H, CH2).

Example 382 N-(2-(2.6-difluorn)phenethvl)-KT-(2-(6-fluorobenzothiazolvl)thiourea In a manner analogous to Example 105, 2,6-difluorophenethylamine was condensed with l-(2-amino-6-fluorobenzothiazole)-1'-imidazole thiocarbonyl which was made in a similar way as described in Example 103. The titled compound crystallized from methylene chloride.

^H-NMR (CDCI3 + CD3OD) d: 7.52 (m, 1H, benzo), 7.40 (m, 1H, benzo), 7.14 (m, 2H, DFPh, benzo), 6.88 (m, 2H, DFPh), 4.02 (t, 2H, CH2), 3.14 (t, 2H, CH2).

X-8571A -448- 26 Example 383 N-12-(2-fluoro^ phenethvl1-N'-< 2- benzothiazolyl)thiourea In a manner analogous to Example 105, 2-fluorophenethylamine was condensed with l-(2-aminobenzothiazole)-1'-imidazole thiocarbonyl which was made in a similar way as described in Example 103. The titled compound crystallized from methylene chloride. !h-NMR (CDCI3 + CD3OD) d: 7.63 (q, 2H, benzo), 7.32 (m, 4H, benzo, FPh), 7.10 (q, 2H, FPh), 4.06 (t, 2H, CH2), 3.11 (t, 2H, CH2).

Example 384 N- (2-^2-fluoro)phenethvl)-N'-(2-(4-methvlthiazolvl)thiourea In a manner analogous to Example 105, 2-fluorophenethylamine was condensed with 1-(2-amino-4-methy1thiazole)-1'-imidazole thiocarbonyl which was made in a similar way as described in Example 103. The titled compound crystallized from methylene chloride.

^H-NMR (CDCI3 + CD3OD) d: 7.23 (m, 2H, FPh), 7.06 (m, 2H, FPh), 6.34 (d. T^lHz, 1H, thiazole), 3.99 ( t, 2H, CH2), 3.05 (m, 2i w.n2), 2.20 (d, J=0.9Hz, 3H, Me).

Example 385 N-(2-(2.6-difluoro)phenethy1)-N'-(2-(4-methv1thia z olv1)thiourea In a manner analogous to Example 105, 2,6-difluorophenethylamine was condensed with l-(2-amino- X-8571A 2 6 0 9 4-methylthiazole)-1'-imidazole thiocarbonyl which was made in a similar way as described in Example 103. The titled compound crystallized from methylene chloride. iH-NMR (CDCI3 + CD3OD) d: 7.19 (m, 1H, DFPh), 6.87 (t, 2H, DFPh), 6.35 (s, 1H, thiazole), 3.98 (t, 2H, CH2), 3.09 (t, 2H, CH2) , 2.22 (s, 3H, Me).

Example 386 N- (2 .2-dimethyl-2-(2-chloro-6-fluoro)phenethvl)-N'-(2- thiazolvl)thiourea A solution of 2-chloro-6-fluorophenyl acetonitrile (1.69 g, 10 mmole) in dry THF (70 ml) was cooled to -60°C, and lithium diisopropylamide (5.25 ml, 10.5 mmole) was added. After 30 min, methyl iodide (0.68 ml, 11 ml ) was added into the reaction mixture, and the reaction was slowly warmed to 0°c, and kept at 0°C for 1 hr. Then it was cooled to -60°C again, and more lithium diisopropylamide (6 ml, 12 mmole) was added. After 30 min, methyl iodide (1.87 ml, 30 mmole) was added. The reaction mixture was allowed to warm to room temperature and kept there for 2 hr after which it was poured into a sodium hydrogen carbonate solution, and extracted with chloroform.

The organic phase was washed with water, dried, and the solvent was evaporated in vacuo. The product 2,2-dimethyl-2(2-chloro-6-fluorophenyl) acetonitrile (1.07 g) was isolated by silica gel column chromatography. 1H-NMR (CDC13) d: 7.25 ( m, 2H, Ph), 7.03 ( m, 1H, Ph), 1.98 (s, 3H, Me ), 1.96 (s, 3H, Me).

X-8571A 26 The 2,2-dimethyl-2-(2-chloro-6-fluorophenyl)ethylamine was obtained by reduction of 2,2-dimethyl-2(2-chloro-6-fluorophenyl) acetonitrile with cobalt chloride and sodium borohydride according to the method described by L.s. Heizman in J. Am.

Chem. Soc., 104, p.6801, (1980). It was then condensed with 1-(2-aminothiazole)-1'-imidazole thiocarbonyl in the analogous manner to Example 105. The titled compound was isolated by silica gel column chromatography.

^-H-NMR (CDCI3) d: 7.35-7.09 (m, 3H, Ph) , 6.95 ( d, lH, thiazole), 6.73 ( d, lH, thiazole), 4.09 (d, 2H, CH2), 1.50 ( s, 6H, Me ).

Example 387 N-(2-(5-brQmo-2-methoxv)phenethvl)-N"-(2-(4-methvlthiazolvl)thiourea In a manner analogous to Example 105, 5-bromo-2-methoxyphenethylamine was condensed with 1-(2 — amino-4-methylthiazole)-1'-imidazole thiocarbonyl which was made in a similar way as described in Example 103. The titled compound crystallized from methylene chloride. iH-NMR (CDCI3 + CD3OD) d: 7.31 (d, 1H, Ph), 7.29 (s, 1H, Ph), 6.72 (d, 1H, Ph), 6.34 (s, lH, thiazole), 3.95 (t, 2H, CH2) , 3.79 (s, 3H, MeO), 2.96 (t, 2H, CH2), 2.23 (s, 3H, Me). c o u p n X-8571A -451- ' * •60 Example 38fl N-(2-(5-bromQ-2-methoxv)Phenethvlj-N'-(2-(4-cyaiiQthiazolYl) thiourecL In a manner analogous to Example 105, 5-5 bromo-2-methoxyphenethyl-amine was condensed with 1-(2-amino-4-cyanothiazole)-1'-imidazole thiocarbonyl which was made in a similar way as described in Example 103. The titled compound was purified by silica gel column chromatography.

^H-NMR (CDCI3 + CD3OD) d: 7.51 (thiazole), 7.32 (d, 1H, Ph), 7.27 (s, 1H, Ph), 6.76 (d, 1H, Ph), 3.90 (t, 2H, CH2), 3.83 (s, 3H, MeO), 2.97 (t, 2H, CH2)• N-(2-(2.6-difluoro)Phenethvl)-N'-(2- (4- cvanothiazolvl)thiourea In a manner analogous to Example 105, 2,6-difluorophenethylamine was condensed with 1-(2-amino-4-cyanothiazole)-11-imidazole thiocarbonyl which was 20 made in a similar way as described in Example 103.

The titled compound crystallized from methylene chloride.

(CDCI3 + CD3OD) d: 7.51 (s, 1H, thiazole), 7.22 (m, 1H, DFPh), 6.90 (t, 2H, DFPh), 3.93 (t, 2H, CH2), 3.08 25 (s, 2H, CH2). 26 n ~ X-8571A -452- ^ U {J 0 "7 Example 390 N-12-12.6-difluoro)phenethvl)-N'-(2-imidazolvl)thiourea In a manner analogous to Example 93, using 2,6-difluorophenethylamine and 2-aminoimidazole, the titled compound was obtained.

^H-NMR (DMSO + D20) d: 7.28 (m, lH, DFPh), 7.02 (t, 2H, DFPh), 6.78 (broad, 1H, imidazole), 6.62 (broad, 1H, imidazole), 3.79 (t, 2H, CH2), 2.97 (t, 2H, CH2).

Example 391 N-(l-amino-2-(5-imidazolyl)-ethvl)-N'- 12-(5-methvl)- thiazolvl)thiourea 1-(2-(5-methyl)-aminothiazole-11 -15 iraidazolethiocarbonyl (prepared as described in Example 103, using 2-amino-5-methylthiazole instead of 2-aminothiazole) (4.06 mmol, 910 mg) and histamine (4.05 mmol, 450 mg) in dimethyiformamide (10 ml) was heated to 50° C for 3 hrs. The mixture was concentrated and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was dried over MgS04 and concentrated to give the titled compound in 43 % yield (463 mg).

^■H NMR (250 MHz, DMSO-dg) 82.18 (s, 3 H) , 2.80 (m, 2 K), 6.57 (s, 1 H), 6.90 (s, 1 H), 7.60 (s, 1 H).

Example 392 1- (2-Amino-5-bromopvridvl) -1' - ( imiriazolvl ) t-hiocarbonvl A mixture of 2-amino-5-bromopyridine, 97% 30 (25.0 g, 140 mmol) and 1,1'-thiocarbonyldiimidazole, X-8571A 2 8 n o 0 90% (27.72 g, 140 mmol) in 300 mol of acetonitrile was stirred at ambient temperature overnight and then filtered. The precipitate was dried in vacuo to give the titled compound as a crude product which was 5 stored and used for further condensations with various phenethylamines.

Yield: 37.5 g (95 %).

Example 393 1- (5-chloroPvrid-7.-v1 -thiocarbamoyl) imidazole In a 500 ml reaction-flask, N,N-thiocarbonyl-diimidazole (60.0 g, 337 mmol) was dissolved in acetonitrile (400 ml) at 50°C with stirring. The solution was then cooled to 20°C. 2-15 Amino-5-chloropyridine (43 g, 337 mmol) was then added.

The solution was stirred for 35 minutes and kept at ambient temperature over night. The solution was filtered and the crystalline mass consisted of a 20 mixture of needles and pellets. The pellets were separated mechanically and purified by fluidization with a hair-dryer to give the titled product.

^H-NMR DMSO-dg 8ppm 7.1-7.2 (2H, s, imid) 7.5-7.6 (1H, d, orto-coupling, pyr.) 7.9-8.0 (1H, s, imid.) 8.1-8.2 25 (1H, d,d, pyr.) 8.6-8.7 (1H, d, meta-coupling, pyr.) X-8571A 2Q l - Example 394 N-2 - (2. 5-dimethoxvphenvlet-.hv 1) -N' - 12- (fi-fluorobenzothiazolvl))thiourea 450 mg 2,5-dimethoxyphenethylamine (2.5 5 mmol) and 740 mg l-((2-(6- fluoro)benzothiazolyl)thiocarbamoyl)imidazole (2.5 mmol) (Example 80) in 5 ml acetonitrile were refluxed for one half hour. The mixture was cooled, and crystals were filtered off. Recrystallization from a 10 mixture of ethanol and dimethyiformamide gave 640 mg of the pure product as very fine needles.

Mp: 196°C l-H-NMR: 3.00 2H (t) , 3.77 3H (s) , 3.84 3H (s) , 3.91 2H (m), 6.91-7.03 3H (m), 7.38 lH (m), 7.70 1H (m) , 7.94 15 1H (m), 9.9 1H broad singlet, 12.0 1H broad singlet Analysis Ci8H18FN3°2s2: calculated C 55.22 H 4.63 N 10.73; found: C 55.3 H 4.70 N 10.75 Example 395 n-2-(-2.5-dimethoxvphenvlethv1)-N'-(2-(4- methylthiazQlYl))thiourea 1000 mg (4.46 mmol) 1-(2-(4-methylthiazolyl)thiocarbamoyl)imidazole (prepared analogously to 1-(2-thiazolyl)thiocarbamoyl)imidazole 25 described in Example 103) and 800 mg 2,5- dimethoxyphenethylamine (4.42 mmol) in 7 ml acetonitrile were refluxed for one half hour. The mixture was cooled to 0°C, crystals were filtered off, rinsed with acetonitrile and dried. Recrystallization X-8571A 2 6 o p q V>' from ethanol-dimethylformamide gave 1.42 g of the pure product.

Mp: 210°C ^H-NMR (DMSO-dg): 2.27 3H (s), 2.96 2H (t), 3.78 3H 5 (s), 3.83 3H (s), 3.84 2H (m) , 6.73 1H (s), 6.85-7.04 3H (m) Analysis C15H19N3O2S2: calculated C 53.39 H 5.67 N 12.45; found: C 53.1 H 5.65 N 12.35 Example 396 N-2-(-2.5-dimethoxvphenethv1)-N'-(2- (2- benzpthiazQlyl))thiourea 556 mg 1-(2-benzothiazolyl)thiocarbamoyl) imidazole (2 mmol) (Example 66) and 362 mg 2,5-15 dimethoxyphenethylamine (2 mmol) in 5 ml acetonitrile were refluxed for one half hour. Recrystallization from ethanol-dimethylformamide gave 565 mg pure product. !h-NMR (DMSO-dg): 3.02 2H (t), 3.77 3H (s), 3.85 3H 20 (s), 3.93 2H (m), 6.92-7.04 3H (m), 7.38 1H (m), 7.53 1H (m), 7.70 1H (m), 8.01 1H (m) Analysis Ci3Hi9N302S2: calculated C 57.88 H 5.13 N 11.25; found: C 57.95 H 5.15 N 11.25 Example 397 N-2-(2.6-dichlorophenvlethvl)-N1-(2-thiazolvl)thiourea 9.3 g 2,6-Dichlorophenylacetonitrile (50 mmol) in 50 ml diethylether was added dropwise to a mixture of 5 g lithium aluminum hydride in 200 ml 30 ether. The mixture was heated to reflux, and reaction was allowed to take place for 2 hours. The mixture X-8571A 26 0 p o V/' was cooled to room temperature, and 5 ml water was added dropwise, followed by 5 ml 25 % sodium hydroxide in water. 10 ml water was then added, and the mixture was filtered. 10 ml acetic acid was added rapidly to 5 the stirred filtrate. The 2,6- dichlorophenethylammonium acetate that precipitated was filtered off and dried. 500 mg 2,6-dichlorophenethylammonium acetate (2 mmol), 10 0.42 g 1-(2-aminothiazole)-1'-imidazole thiocarbonyl (Example 103) and 0.5 g diisopropylethylamine were mixed in 5 ml acetonitrile and refluxed for 30 minutes. The mixture was then kept at 0°C for 17 hours and the crystals were filtered off. 15 Recrystallization from acetonitrile gave 265 mg of the titled product.

^■H-NMR (DMSO-dg): 3.3 2H (t), 3.9 2H (m) , 7.2 1H (d) , 7.35-7.6 4H (m).

Example 398 N-2-12.6-dichlnrophenvlethvl)-N'-(2 - (4- methYlthiasolYl))thiourea 500 mg 2,6-dichlorophenylethylammonium acetate (2 mmol) (Example 397), 0.48 g l-(2-(4-25 methylthiazolyl) thiocarbamoyl)imidazole (prepared analogously to i-(2-thiazolyl)thiocarbamoyl)imidazole described in Example 103) (2 mmol) and 0.5 g diisopropylethylamine were mixed in 5 ml acetonitrile and refluxed for 30 minutes. The mixture was cooled 30 and crystals were filtered off. Recrystallization ""^m acetonitrile gave 598 mg of the titled product. • 5 X-8571A -457- COO 9 260 iH-NMR (DMSO-dg): 2.2 3H (s), 3.3 2H (t), 4.0 2H (m), 6.7 1H (s), 7.4 1H (m), 7.5 2H (m), 9.8 1H broad singlet, 11.7 lH broad singlet Analysis C13H13CI2N3S2: calculated C 45.09 H 3.78 N 12.13; found: C 45.45 H 3.9 N 12.55 Example 399 n-1-2-(2.6-dichlorophenyl)ethvl)-N'-(2-henzot-hiazolvl) thiourea 500 mg 2,6-dichlorophenylethylammonium acetate (2 mmol) (Example 397), 0.55 g l-(2-benzothiazolyl)thiocarbamoyl) imidazole (2 mmol) (Example 66) and 0.5 g diisopropyl-ethylamine were mixed in 5 ml acetonitrile and refluxed for 30 minutes. The mixture was cooled and crystals were filtered off. Recrystallization from acetonitrile gave 497 mg of the titled product. l-H-NMR (DMSO-dg) 3.3 2H (t) , 4.0 2H (m) , 7.3- 1.1 6H (m), 8.0 lH (d), 10.0 1H broad peak, 12.1 lH broad peak.

Analysis CigHi3Cl2N3S2: calculated C 50.26 H 3.43 N 10.99; found: C 50.3 H 3.45 N 11.1 Example 4QQ N-(2- 12. 6-dichlorophenyl) ethvl) -N' -12-lC,-(fluorobenzothiazolvl))thiourea 500 mg 2,6-dichlorophenylethylammonium acetate (2 nunol) (Example 397), 0.59 g 1— ( (2— (6 — fluoro)benzothiazolyl)thiocarbamoyl) imidazole (2 mmol) (Example 80) and 0.5 g diisopropylethylamine X-8571A 2 6 0 o were mixed in 5 ml acetonitrile and refluxed for 30 minutes. The mixture was cooled and crystals were filtered off. Recrystallization from acetonitrile gave 548 mg of the titled product. 1H-NMR (DMSO-dg): 3.4 2H (t), 4.0 2H (m), 7.3-7.4 2H (m) , 7.5-7.7 2H (m), 8.0 1H (m), 9.8 1H broad peak, 12.0 1H broads peak.

Analysis CigHi2Cl2FN3s2' calculated C 48.00 H 3.02 N 10.50; found: C 48.25 H 3.1 N 10.6 Example 4Q1 N-(2-(2.6-difluoro-3-methoxypheny1)ethvl)-N'-(-2 - thiazolvl)thiourea 6.25 ml 1.6M n-butyl lithium in hexane was 15 added dropwise to a solution of 10 mmol 2,4- difluoroanisole in 30 ml diethyl ether. The mixture was kept at -65°C during the addition. 3 ml Dimethyiformamide was then added, and the mixture was slowly (lh) allowed to warm to room temperature. The 20 mixture was poured into a separation funnel concaining 50 ml ice-water. The ether layer was separated, washed with 50 ml water and dried (Na2S04). The solvent was evaporated, and the residue was redissolved in 50 ml ethaaol. 2 g Ammonium acetate 25 and 3 ml nitromethane were added and the mixture was refluxed for 3 hours. The solvent was evaporated, end the residue was partitioned between 50 ml dichloromethane and 50 ml water. The organic layer was dried, and the solvent was evaporated. 30 Crystallization from cold ethanol gave •180 mg brown X-8571A 2 6 0 p o * -J crystals of l-nitro-2(2,6-difluoro-3-methoxypheny 1) ethene. iH-NMR (CDCI3): 3.9 3H (s)1 6.9-7.1 2H (m) , 7.8 1H (d) , 8.1 1H (d) . 420 mg l-nitro-2-(2,6-difluoro-3- methoxyphenyl)ethene was dissolved in 50 ml tetrahydrofurane and added dropwise under stirring to a solution of 2 g lithium aluminum hydride in 50 ml tetrahydrofurane. The mixture was refluxed foi 3 10 hours. The product amine was worked-up by the dropwise addition of 2 ml water followed by 2 ml 25% sodium hydroxide in water followed by 4 ml water.

The mixture was then filtered. The filtrate was extracted with 2 x 20 ml 1 M HCl. The aqueous 15 layer was made basic ty the addition of 50 ml 45 % sodium hydroxide solution, and then extracted with 3 x 50 ml dichloro-methane. The 2-(2,6-difluoro-3-methoxyphenyl)ethyl-amine obtained by the evaporation of solvent was pure enough for use in the next step. 20 1-H-NMR: 1.2 2H broad singlet, 2.6 2H (m) , 2.7 2H (m) , 3.65 3H (s), 6.4-6.6 2H (m) 172 mg 2-(2,6-difluoro-3-methoxyphenyl)ethylamine (1.0 mmol) and 210 mg l-(2-aminothiazole)-1'-imidazole thiocarbonyl (1.0 mmol) in 25 5 ml acetonitrile were refluxed for one hour. The solution was cooled, and crystallization was allowed for overnight. Solid material was filtered off, and recrystallized from acetonitrile to give 138 mg of the titled product. 2 6 n ^ X-8571A -460- U U '' 0 7 «•' \) ■^■H-NMR (DMSO-dg) : 3.1 2H (t), 3.8-4.0 5H (m) , 6.9-7.2 3H (m), 7.4 1H (d), 9.8 lH broad peak, 11.7 1H broad peak Analysis C13H13F2N3OS2: calculated C 47.40% H 3.98% N 5 12.76%; found: C47.6% H 4.1% N 12.75% Example 4Q2 N-i 2-(-2-Benzptriazplyl)ethyl)-w' - (2 -thiazolvl)thiourea 10 59.5 g benzotriazole (0.50 mol) was dissolved in 700 ml dimethyiformamide. 160 g Sodium carbonate (1.5 mol) was added and then dropwise 73.5 g ethyl chloroacetate (0.60 mol). The stirred mixture was slowly heated to 40°C, and kept at that 15 temperature for 17 h. The solvent was evaporated and the residue was extracted with ethyl acetate. GC showed one major and one minor product. The minor product ethyl-2-(2-benzotriazolyl)acetate was isolated by fractional crystallization from cold mixtures of 20 ethanol and ethyl acetate. 7.1 g Of this minor product (40 mmol) was dissolved in 50 ml diethyl ether-tetrahydrofurane 1:1 and 1.5 g of lithium borohydride was added. The reaction mixture was stirred for 17 h at room 25 temperature. The solvent was removed and replaced with 50 ml butanol. 5 ml Water was added and the temperature was slowly raised to about 50°C. After 4 h at this temperature the solvent was removed and the residue was partitioned between dichloromethane and 30 water. The organic layer was dried, and the product X-8571A 0 ?g3 2-(2-benzotriazolyl)ethanol was isolated by crystallization from cold ethanol. 4.70 g Of the 2-(2-benzotriazolyl)ethanol (28.8 mmol) was dissolved in 200 ml diethyl ether and 5 2.28 g pyridine (28.8 mmol) was added. The mixture was cooled to -50°C, and 8.18 g triflie anhydride (29 mmol) was added. The mixture was removed from the cooling bath, and was allowed to reach room temperature. The mixture was filtered under dry 10 conditions and added to a cold -40°C solution of ca 150 ml ammonia in 50 ml diethyl ether. This mixture was allowed to reach room temperature, and ether was removed. 50 ml 2M HCl was added, and this mixture was washed with methylene chloride. The aqueous phase was 15 made basic by addition of 50 ml 25 % sodium hydroxide and extracted with 3 x 25 ml methylene chloride. Evaporation of the solvent gave 2.10 g 2-(2-benzotriazolyl)ethylamine (12.9 mol). This amine was used in the next step without further purification. 20 324 mg 2-(2-benzotriazolyl)ethylamine (2 mmol) and 420 mg 1-(2-aminothiazole)-1'-imidazole thiocarbonyl (2 mmol) were mixed in 3 ml acetonitrile. The mixture was slowly heated to reflux, and was then cooled to allow the product to crystalliz3. Repeated 25 crystallization from acetonitrile gave 234 mg pure N- (2-(-2-benzotriazolyl)ethyl)N'-(2-thiazolyl)thiourea. iH-NMR (DMSO-dg): 4.5 2H (m), 5.1 2H (m), 6.75 1H (d), 7.05 1H (d), 7.4 2H (m), 7.9 2H (m). 13C-NMR 47, 56, 112, 119, 127, 145, 180. 30 Analysis Ci2H12N6s2: calculated C 47.35% H 3.97% N 27.61%; found: C 47.3% H 3.95% N 27.2%' 2 6 o 9 n X-8571A -462- C/ 3 Example 403 cis/trans N-12-(2-ethoxvphenvlcvclopropanvl))-N1-(2- nvririv] )thiourea 28.56 g methyl triphenylphosphonium bromide (80 mmol) in 500 ml tetrahydrofurane was cooled to -50°C. 50 ml n-Butyllithium in hexane (about 1.6 M, 80 mmol) was added dropwise under stirring. The mixture was slowly warmed to room temperature, and kept tiiere for two hours. The mixture was then cooled tj -30°, and 12 g 2-ethoxybenzaldehyde (80 mmol) was added. The mixture was warmed to room temperature, and most of the solvent was removed and the residue was mixed with 400 ml ether and filtered. The solvent was evaporated and ethyl acetate was added to residue. The solution was passed through a pad of silica gel. This crude 2-ethoxystyrene was dissolved in 50 ml dichloroethane and used as such in the next reaction step: 0.1 g Cul was added, and the mixture was heated to reflux temperature. 8.80 g Ethyl diazoacetate in 30 ml dichloroethane was then added dropwise over a period of 1 hour. GC-analysis showed the formation of two products in a about 1:2 ratio. The two isomeric products were separated from other material by column chromatography (silica-gel, mixtures of hexane - ethyl acetate). This gave 3.1g of a cis/trans mixture of 2-(2-ethoxyphenyl)-1-carboxyethyl cyclopropanes. The product mixture was hydrolysed in a refluxing mixture of 50 ml ethanol + 10 ml water + 4 g sodium hydroxide 26 X-8571A -463- O 2 Q i (2 hours). The solvent was evaporated and the residue was made acidic with 100 ml 2M hydrochloric acid and extracted with x 50 ml dichloromethane. The organic layers were dried and solvent was evaporated. 50 ml 5 Toluene was added followed by 6 g thionyl chloride. The mixture was heated to 80°C for one hour and the solvent was then removed. 100 ml Acetone was added, the solution was cooled in an ice-bath and 4 g sodium azide in 20 ml water and 100 ml toluene was added 10 after which the mixture was washed with 3 x 50 ml water. The organic layer was dried (Na2S04), the solvent was evaporated and the residue was dissolved in 100 ml dioxane. The dioxane solution was heated slowly to reflux, and kept at reflux 30 min. 25 ml 15 Concentrated hydrochloric acid was added and the mixture was refluxed for 2 hours. The solvent was removed and the residue was partitioned between 50 ml dichloromethane and 50 ml 2M hydrochloric acid. The aqueous layer was made basic by the addition of 50 ml 20 25% sodium hydroxide solution, and extracted with 3 x 50 ml dichloromethane. The dichloromethane solvent was evaporated and the residue was purified by column chromatography (silica-gel, mixtures of ethanol and ethyl acetate to give about 1:1 mixture of cis/trans 25 2-(2-ethoxyphenyl) cyclopropyl-amines. 0.24 g 2-Aminopyridine ( 2.6 mmol) and 0.46 g thiocarbonyldiimidazole (2.6 mmol) were stirred in 5 ml acetonitrile for 2 hours. 0.41 g (2.6 mmol) of the 30 mixture of cyclopropylamines was added, and the reaction mixture was heated slowly to 70°C and stirred X-8571A 2 6 f} r> g at that temperature for 17 hours. The solvent was evaporated, and the titled product was isolated by column chromatography (silica-gel, mixtures of hexane-ethyl acetate. -l-H-NMR: 1.15-1.25 5H (m) , 2.50 1H (m), 3.42 0.55H (m) , 3.73 0.45% (m), 4.0-4.1 2H (q), 6.7-8.15 8H (m) Example 4Q4 N-(2-(2-pyridvlethvl))-N -(2 -(5- io chloropyritiYl))thiourea 1.73 g 2-Amino-5-chloropyridine (10 mmol) and 1.78 g thiocarbonyl diimidazole (10 mmol) were stirred for 2 hours in 15 ml acetonitrile. 1.47 g 2-(2-Aminoethyl)pyridine (12 mmol) was added, and the 15 mixture, was stirred at room temperature for 2 hours.

The reaction mixture was then heated to 50°C and was stirred for 17 hours. Crystals were collected by filtration after cooling of the mixture. Recrystallization from acetonitrile gave pure titled 20 product. iH-NMR (DMSO-dg): 3.2 2H (t), 4.1 2H (m), 7.2-7.5 3H (m), 7.8-8.0 2H (m), 8.2 lH (d), 8.7 lH (m), 18.0 1H (s), 11.5 1H (S) Example 4Q5 N-(2-(2-Pvridvlethvl))-N'- (2-(5-bromopvridvl))thiourea 1.28 g 2-Amino-5-bromopyridine (10 mmol) and 1.78 g thiocarbonyl diimidazole (10 mmol) were stirred for 2 hours in 15 irl acetonitrile. 1.47g 2-(2-30 Aminoethyl)pyridine (12 mmol) was added, and the mixture was stirred at room temperature for 2 hours.

X-8571A 2 6 0 0 n ^ ^ 6 The reaction mixture was then heated to 50°C and was stirred for 17 hours. Crystals were collected by filtration after cooling of the mixture. Recrystallization from acetonitrile gave pure titled 5 product. iH-NMR .(DMSO-dg) : 3.5 2H (t) , 4.2 2H (m) , 7.2 2H (d) , 7.9-8.1 3H (m) , 8.3 1H (d) ,• 8.6 lH (m) , 8.9 1H (d) 10.9 1H (s), 11.4 1H (t) Example 4Q6 N- (2- (2-pvridvlethvl) ) -N' - (2- (5-ni'hropvridvl) )thiourea 1.39 g 2-Amino-5-nitropyridine (10 mmol) was dissolved in 20 ml tetrahydrofurane. 0.68g (10 mmol) Sodium ethoxide (10 mmol) was added. The mixture was 15 heated to 50°C and stirred for 30 minutes. The mixture was cooled, and most of the liquid was decanted from the formed red precipitate. The precipitate was taken up in 20 ml acetonitrile, and added to 1.78 g thiocarbonyl diimidazole in 10 ml 20 acetonitrile. This mixture was stirred for 10 minutes at room- temperature. 1.22 g 2-(2-Amino-ethyl)pyridine was added and the mixture was stirred for one hour. 1 ml Acetic acid was added, and the solvent was evaporated. The residue was washed with water. 25 Repeated crystallizations from acetonitrile gave 1.28 g yellow crystals of the titled product. 3-H-NMR (£)MSO-d6) ' 3.1 2H (t), 3.2 2H (t>, 7.2 1H (m) , 7.3 3H (m), 7.7 lH (m), 8.4 lH (m), 8.5 1H (m), 8.9 1H (d) 26 X-8571A' -466- Examnle 407 N-(2-(2-ovridvlethvl))-N'-(2-(5- met-.hylPYridYX)) thiourea 1.78 g thiocarbonyl diimidazole (10 mmol) 5 and 1.58 g 2-amino-5-methyIpyridine (10 mmol) in 15 ml acetonitrile were stirred for 1 h at room temperature. 1.22 g 2-(2-Aminoethyl)-pyridine was added. The mixture was stirred 1 h at room temperature, and then 17 h at 50°C. The mixture was cooled and crystals 10 were collected by filtration. Recrystallization from acetonitrile gave 1.30 g pure titled product.

^■H-NMR (DMSO-dg) : 2.2 3H (s) , 3.1 2H (t), 4.0 2H (m) , 7.0 1H (d), 7.2 1H (m), 7.3 1H (d), 7.6 1H (m), 7.7 1H 15 (m) , 7.8 1H (m) , 8.6 1H (m) 13C-NMR: 17.3, 36.3, 44.0, 112.1, 121.7, 123.5, 126.7, 136.6, 139.7, 144.6, 149.2, 151.8, 159.0, 179.2 Example 40ft (M-12-(2-pvrldvlethvl))-N'-(2-(5- bromopvridvl))thiourea HCl salt) 100 mg N-(2-(2-pyridylethyl))-N'-(2-(5-bromopyridyl))thiourea (Example 405) was added to about 10 ml water. The suspension was heated to about 25 90°C and pH was adjusted to about 3 by addition of hydrochloric acid. The titled product was isolated by freeze-drying.

XH-NMR (DMSO-dg ^ : 3.6 2H (t), 4.2 2H (m), 7.2 2H (d) , 7.9-8.1 3H (m), 8.3 1H (d), 8.6 1H (m), 8.9 1H (d) 30 10.9 1H (s) , 11.4 1H (t) 2 6 0 r r - X-8571A -467- ' '■ Example 4Q3 (N-(2-(2-PYriflvlethYl))-N'-(2- (5-chloroPYridyl))thiourea HCl salt) 100 mg N-(2-(2-pyridylethyl))-N'-(2-(5-chloropyridyl))thiourea (Example 404) was added to about 10 ml water. The suspension was heated to about 90°C and pH was adjusted to about 3 by addition of hydrochloric acid. The titled product was isolated by freeze-drying.

^H-NMR (DMSO-dg): 3.6 2H (t), 4.2 2H (m) , 7.3 lH (d), 8.0-8.2 3H (m), 8.3 1H (m), 8.6 1H (m) , 9.0 1H (m), 10.9 1H (S), 11.4 1H (t).

Example 410 N-(2-(-2-Benzotriazolvl)ethvl)N'-(2-(5- bromopYridYl))thiourea 356 mg Thiocarbonyl diimidazole (2 mmol) and 346 mg 2-amino-5-bromopyridine (2 mmol) in 2 ml acetonitrile were stirred for 1 h at room temperature. 324 mg 2-(2-Benzotriazolyl)ethylamine (Example 402) (2 mmol) was then added. This mixture was stirred for 10 min, and was then heated to reflux. After 20 min 5 ml more acetonitrile and 3 ml dimethyiformamide were added to give a clear solution. The solution was cooled and the resulting precipitate was collected after centrifugation. Recrystallization from acetonitrile-dimethylformamide gave •10 mg of the pure titled product. iH-NMR (DMSO-dg): 4.44 2H (m), 5.15 2H (m), 7.18 lH (d), 7.56 2H (m), 7.90 1H (d). 8.04 3H (m), 10.93 1H (s), 11.41 1H (s) X-8571A 2 6 0 o o 7 13C-NMR: 44, 55, 114, 118, 118, 127, 142, 144, 146, 152, 180 PPM Example 411 N-(2-(2 . 6-difluoro-3-methoxypheny1)ethvl)-N'- (2-(5- feromopyridyl) )thiourea 334 mg 2- (-2,6-difluoro-3-methoxyphenyl)ethylamine (Example 401) (mw 1C7, 2 mmol) and 566 mg 1—(2- (5- bromopyridyl)thiocarbamoyl)imidazole (Example 392) (mw 283.15) (2 mmol) were mixed in 3 ml acetonitrile. The mixture was slowly heated to reflux, and was then cooled to crystallize. Repeated crystallization from acetonitrile gave 238 mg of the pure titled product. 1H-HNMR: (DMSO) 3.12 2H (t), 3.86 3H (s), 4.00 2H (m), 6.82 3H (m), 7.68-7.72 1H (m) , 8.12 1H (d), 9.16 lH (s), 11.35 1H (s) Example 412 N-(2-(3.4.5-trimethoxv)-benzvl)-N' - (2- thiazolvl)thiourea The starting material 3,4,5-trimethoxybenzylamine was prepared by reduction of 3,4,5-trimethoxybenzonitrile with cobalt chloride and sodium borohydride, according to the general method described by L.S.Heinzman in J. Am. Chew. Soc., 104, p. 6801 (1980). 3,4,5-trimethylbenzonitrile (965 mg, 5 mmole) and cobolt chloride (2.37 g, 10 mmole) were dissolved in methanol (70 ml). To the solution was X-8571A added sodium borohydride (1.89 g, 50 mmole). After 3 hrs, the reaction mixture was filtered through Celite, and concentrated to small volume. It was then taken up in chloroform and extracted with IN HCl (100 ml). The organic phase was discarded. The aqueous phase was basified with aqueous ammonia, and extracted with chloroform. The organic phase was dried over magnesium sulfate, and evaporated in vacuo to yield 3,4,5-' trimethoxybenzylamine (427 mg).

^H-NMR(CDCl3)d: 6.58 (s, 2H, TMPh), 3.85 (m, 6H, 2 x MeO), 3.82 (s, 3H, MeO), 3.80 (m, 2H, CH2) .

The titled compound was prepared analogous to Example 105. - ^H-NMR (CDCI3) d: 7.26 (d, 1H, thiazole), 6.85 (d, lH, thiazole), 6.64 (s, 2H, TMPh), 4.84 (d, J= 5.7Hz, 2H, CH2), 3.86 (m,6H, MeO), 3.85 (s, 3H, MeO). l^c-NMR(CDCI3)d: 177 (C=S), 161 (thiazole), 153 (TMPh), 138 (TMPh), 137 (thiazole), 132 (TMPh), 111 (thiazole), 104 (TMPh), 61 (MeO), 56 (MeO), 50 (CH2).

Example 413 2-FQrmvl-3-£lugrgpYridine Dry ethyl ether (500 mL), n-BuLi (1.6 M in hexane, 62.5 mL, 0.1 mol), and dry 1,4- diazabicyclo[2.2.2]octane (DABCO) (11.56 g, 0.1 mol) were introduced into a 1 L flask under a dry N2 stream at -60°C and the resulting cloudy solution was stirred for 1 hour at -20°C. 'The mixture was then cooled to -75°C and an ethyl ether (50 mL) solution of 3-fluoropyridine (9.81 g, 0.1 mol) was added dropwise and stirring continued for 1 1/2 X-8571A 26 o 2 hours at -60°C. The mixture was recooled to -75°C, dry JV,JV-dimethylformamide (8.52 mL, 0.11 mol) dissolved in ethyl ether (50 mL) was added dropwise and the mixture stirred for 2 hours at -75°C. Water (IV5 mL) was introduced slowly ac -10°C, the aqueous layer extracted with ethyl acetate (5 x 200 mL), and the combined extracts were dried over anhydrous sodium sulfate. Solvent removal produced a dark brown oil which after vacuum distillation and purification by chromatography on silica gel provided 4.4 g (35%) of the titled product as an off-white crystalline solid: mp 48-49°C; IR (CHCI3, cm-1) 3071, 3020, 2873, 2842, 1720, 1588, 1461, 1441; 1H NMR (300 MHz, C.OCI3) 8 10.21 (s, 1H) , 8.62 (m, 1H) , 7.57 (m, 2H); MS (FD) m/e 125 (M+); UV (EtOH) 263nm (6=1551), 201nm (e=2188) F.vamnlfi 414 2-Hvdroxvmethv1-^-f1noronvr i d i n p A solution of 2-formyl-3-fluoropyridine (4.0 g, 32 mmol) and sodium borohydride (309 mg, 8 mmol) in absolute ethanol (40 mL) was stirred at 0°C for 15 minutes and at room temperature for 1 hour. The reaction was quenched with saturated aqueous ammonium chloride (5 mL) and filtered through diatomaceous earth to remove solids. The filtrate was evaporated and the resultant white solid was dissolved in ethyl acetate and water. The aqueous layer was extracted with ethyl acetate (5 x 30 mL) and the combined extracts were dried over anhydrous sodium sulfate.

X-8571A 2 6 0 2 9 Solvent removal provided 3.78 g (93%) of the titled product as a pale yellow oil: IR (CHCI3, cm"1) 3607, 3439, 3019, 1607, 1576, 1451, 1416, 1312, 1257, 1218, 1209, 1167, 1105, 1053, 857, 803; 5 NMR (300MHz, CDCl3) 5 8.38 (m, 1H), 7.39 (m, 1H), 7.26 (m, 1H) , 4.83 (s, 2H) , 3.73 (br s, 1H) ; MS (FD) m/e 127 (M+); UV (EtOH) 263nm (£=2796), 201nm (e=3651) Anal. Calcd for C6H6FN0: C, 56.69; H, 4.76; N, 11.02. 10 Found: C, 56.45; H, 4.97; N, 10.89 Example 415 2-chloromethvl-3-fluoropyridine hydrochloride To a solution of 2-hydroxymethyl-3 -15 fluoropyridine(3.43 g, 27 mmol) in dichloromethane (30 mL) cooled to —10°C was added neat thionyl chloride (4.4 mL, 60 mmol) dropwise over 5 minutes. The resultant pale green solution was stirred at -10°C for 3 hours followed by evaporation to dryness to provide 4.66 g (95%) of the 20 titled product as an off-white crystalline solid: IR (CHCI3, cm"1) 2984, 1732, 1551, 1470, 14:52, 1333, 1286, 1273, 1237, 1219, 1208, 1193, 1094, 905, 862, 806; !h NMR (300MHz, CDCI3) 8 8.69 (m, 1H), 8.06 (m, 1H), 7.89 (m, 1H), 5.09 (s, 2H); MS (FD) m/o 145 (M+ free base), 147 (M+2 free base) Example 416 2-cvanomethvl-3-fluoropyridinp A solution of 2-chloromethyl-3-fluoropyridine 30 hydrochloride (4.85 g, 26.7 mmol) and potassium cyanide (3.47 g, 53.4 mmol) in methanol (50 mL) and water (20 mL) X-8571A -472- 26 0 was stirred at approximately 55°C for 17 hours. The resultant black solution was concentrated to an oil under reduced pressure, redissolved in ethyl acetate and water, and adjusted to pH 11.5 with solid sodium carbonate. The 5 aqueous layer was salted with sodium chloride, extracted with ethyl acetate (7 x 40 mL), and the combined extracts were dried over anhydrous sodium sulfate. Solvent removal provided 3.6 g (99%) of (4) as a black solid: IR (CHC13, cm-1) 3019, 3011, 2977, 1708, 1603, 1578, 1454, 10 1412, 1259, 1222, 1219, 1215, 1161, 1097, 1047, 804; % NMR (300 MHz, CDC13) 8 8.43 (m, 1H), 7.42 (m, 1H), 7.33 (m, 1H), 3.97 (s, 1H), 3.96 (s, 1H); MS (FD) m/e 136 (M+); UV (EtOH) 263nm (e=3719) , 203nm (e=3707) Example 417 2-aminoethvl-3-fluoronvridine To a solution of 2-cyanomethyl-3-fluoropyridinein absolute ethanol (75 mL) and 5JJ hydrochloric acid (0.3 mL) was added platinum oxide catalyst (0.64 g) and the mixture 20 was hydrogenated at 60 psig for 1 hour in a Paar hydrogenation apparatus. Filtered off the catalyst, concentrated the filtrate under reduced pressure to a brown oil, dissolved the oil in water (40 mL) and ethyl acetate (10 mL) and adjusted to pH 0.9 with concentrated 25 hydrochloric acid. Separated the layers, extracted the ethyl acetate layer with 1H HCl (1 x 10 mL), combined the acidic aqueous extracts and washed them with ethyl acetate (4 x 30 mL). Adjusted the aqueous layer to pH 10.8, extracted with dichloromethane (6 x 30 mL), and the 30 combined extracts were dried over anhydrous sodium sulfate.

X-8571A 26 0 Solvent removal provided 1.58g (70%) of the titled product as a brown oil: IR (CHCI3, cm"1) 2969, 2873, 1632, 1602, 1575, 1550, 1450, 1414, 1359, 1246, 1219, 1212, 1203, 1169, 1093; 3-H NMR (300 MHz, CDCl^, 8 8.31 (m, 1H) , 7.29 (m, lH) , 7.13 (m, 1H), 3.03 (m, 4H), 1.80 (br s, 2H); MS(FD) m/e 140(M+); Titration (66% DMF/H2O) pKa 9.56 Example 418 1-r12-f5-chloroIpvridvl)thiocarbamoyl1 imidazole A solution of 1,1'-thiocarbonyldiimidazole (4.95g, 25 mmol) and 2-amino-5-chloropyridine (3.28g, 25 mmol) in acetonitrile (75 mL) was stirred at room temperature for 23 hours. The resulting precipitate was collected by filtration to provide 3.42 g (57%) of the titled product: IR (KBr, cm-1) 3218, 3090, 1599, 1572, 1551, 1529, 1471, 1455, 1390, 1375, 1340, 1310, 1228, 1183, 1109, 1053, 939, 831; 3-H NMR (300 MHz, DMSO-d6) 8 8.58 (m, 1H), 8.25 (m, 1H), 8.05 (br s, 1H), 8.03 (m, 1H), 7.65 (m, lH), 7.15 (d, J=8 Hz, 1H), 6.80 (s, 1H); MS (FAB) m/e 239 (M+l); UV (EtOH) 305nm (£=15141), 273nm (£=14730), 226 nm (£=11407), 203 nm (£=16456).

Example 419 1-f(2-r5-bromoIpvridvl)thiocarbamoyl1 imidazole A solution of 1,1'-thiocarbonyldiimidazole (4.95g, 25 mmol) and 2-amino-5-bromopyridine (4,46g, 25 X-8571A- -474- ' " " ; ' C 26 0 mmol) in acetonitrile (75 mL) was stirred at room temperature for 23 hours. The resulting precipitate was collected l?y filtration to provide 5.42 g (76%) of the titled product: IR (KBr, cm"1) 3218, 3088, 1594, 1565, 1550, 1465, 1387, 1370, 1340, 1309, 1251, 1196, 1182, 1096, 1053, 938, 828; *H NMR (300 MHz, DMSO-d6) 5 8.57 (m, 1H), 8.30 (m, 1H), 8.15 (m, 1H), 8.03 (br s, 1H), 7.75 (m, 1H), 7.15 (d, J»8 Hz, 1H), 6.80 (s, 1H); MS (FAB) m/e 284 (M+l); UV (EtOH) 304nm (£=13932), 274nm (e=13051) , 230 nm (6=11098), 204 nm (£=17821).

■Example. 42Q N- T2- (2-f3-flVC- - j pvr j dvl) Pf-hvl 1 -W - f 2- (5-broi. 1 ifyridvll thiourea A solution of i -L\2—[5— bromoJpyridyl)thiocarbamoyl] imidazole (7) (1.42 g, 5 mmol) and 2-aminoethyl-3-fluoropyridine (5) (0.7<j, 5 mmol) in N,N-dimethylformamide (20 mL) was stirred at 95°C for 3 hours. The reaction was cooled to room temperature, poured into ethyl acetate, and washed with water, saturated aqueous sodium bicarbonate, and brine. The organic layer was dried over anhydrous sodium sulfate, concentrated and the resultant solid was purified by chromatography on silica gel to provide 0.33 g (19%) of the titled product as a white sclxd: mp 184-187 °C; IR (KBr, cm"1) 3161, 3023, 1597, 1579, 1555, 1524, 1488, 1473, 14W, 1342, 1315, 1236, 1221, 1172, 1142, 1087, 833; X-8571A -475- / R 2 6 iH NMR (300 MHZ, DMSO-d6) 8 11.38 (m, lH) , 10.64 (s, 1H) , 8.41 (m, 1H), 8.14 (d, J=2 Hz, 1H), 7.91 (m, 1H), 7.63 (m, 1H), 7.33 (m, 1H), 7.06 (d, J=9 Hz, 1H), 4.01 (m, 2H), 3.10 (t, J=6 Hz, 2H); MS (FD) m/e 355 (M+), 357 (M+2); UV (EtOH) 305nm (6=13169), 273nm (e=25811), 201 nm (£=17493) .

Example 421 N- T2- (2- T3-f luoroIpvridv1-) ethvll -N' -\2-(5- chloro> ovridvllthiourea A solution of 1—[(2-[5— chloro]pyridyl) thiocarbamoyl] imidazole (2.39 g, 10 ntmol) and 2-aminoethyl-3-fluoropyridine(1.4g, 10 mmol) in N,N-15 dimethyiformamide (25 mL) was stirred at 95 °C for 3 hours. The reaction was cooled to room temperature, poured into ethyl acetate, and washed with water, saturated aqueous sodium bicarbonate, and brine. The organic layer was dried over anhydrous sodium sulfate, concentrated and the 20 resultant solid was purified by chromatography on silica gel to provide 0.96 g (31%) of the titled product as an off-white solid: mp 170-173 °C; IR (KBr, cm-1) 3167, 3022, 1603, 1583, 1554, 1524, 1492, 25 1474, 1449, 1367, 1342, 1317, 1238, 1222, 1173, 1142, 1087, 835, 803; iH NMR (300 MHz, DMSO-d6) 8 11.39 (m, lH) , 10.65 (s, lH) , 8.42 (m, 1H), 8.07 (d, J=2 Hz, 1H), 7.81 (m, 1H) , 7.63 (m, 1H), 7.33 (m, 1H), 7.11 (d, J=9 Hz, 1H), 4.01 (m, 2H), 3.10 (t, J=6 Hz, 2H); X-8571A 260 -r MS (FD) m/e 310 (M+), 312 (M+2); UV (EtOH) 305nm (e=11338) , 272nm (©=23394).

Example 422 ( + ) and (-) N- (cis-2-phenvlcvclopropvl) -S-nt-methoxv phenvlacetamide S-a-methoxyphenylacetic acid (2.0 g, 12 mmol) was dissolved in dichloro-methane (100 ml) and oxalylchloride (1.36 ml, 16 mmol) was added together with 2 drops of N,N-dimethylformamide. The solution was stirred under an atmosphere of nitrogen gas at ambient temperature for 120 minutes. The solvent and excess reagent were removed on a rotavapor. The oily residue was dissolved in 100 ml dichloromethane and D, L-cis-phenylcyclopropylamine (Example 202) (2.0 g, 15 mmol) in pyridine (5.0 ml) was added. The solution was stirred for 15 minutes and diethyl ether (200 ml) was added. The precipitate was filtered off and the solution was evaporated. The residual crystalline diastereoisomerical mixture was purified by flash-chromathography by elution with ethyl acetate-toluene-dichloroethane (1:2:2) . The fractions containing the faster eluting product were evaporated to yield product A. The slower eluting fractions were evaporated to yield product B.

A] ^H-NMR (35 mg in 0.6 ml CDCI3, 294 K) 0.99-1.06 (1H, m), 1.29-1.38 (1H, m) , 2.29-2.38 (1H, q), 3.00 (3H, s), 3.07-3.17 (m), 4.41 (lH, s), 6.3 (lH), 7.16-7.32 (10H, m) .

X-8571A 26 0 ;■ r - 13C-NMR: 11.18, 21.83, 27.82, 57.11, 83.68, 126.34, 126.43, 128.08, 128.18, 128.26, 128.78, 136.15, 136.85, 171.75, 171.75. calc for CigHigN: C 76.84 %, H 6.80 %, N 4.99% 5 Mp. 136.7-137.1°C B] 3-H-NMR (same conditions as for A): 1.09-1.16 (1H, q) , 1.32-1.41 (1H, q), 2.24-2.38 (1H, q), 3.10-3.20 (4H, m) , 4.45, (1H, s), 6.4 (1H), 6.95-6.99 (2H, m), 7.15-7.27 (7H, 10 m) . 13C-NMR: 10.69, 21.82, 27.85, 56.87, 83.63, 126.35, 126.87, 128.00, 128.13, 128.19, 128.83, 135.88, 136.54, 171.55.

Calc for C18H19N: C 76.84 %, H 6.80 %, N 4.99 % Mp. 143.6-144.7°C.

Example 423 (-) cig^-phenylcyclpprowlamine Compound A (1.2 g) was refluxed in a mixture of water-dioxane-hydrochloric acid conc.aq. (1:1:1) for 4 20 hours. The solution was diluted with water, washed with dichloromethane, basified with ammonium hydroxide (conc. aq.), extracted with dichloromethane, dried with sodium sulfate, filtered and evaporated to yield the titled product as an oil.

^H-NMR CDCI3 5 ppm 0.8-0.9 (1H, CH2, m) , 1.1-1.2 (1H, CH2, m) , 2.-2.1 (1H, PhCH, q), 2.6-2.7 (1H, CiJNH2, m) , 7.1-7.4 (5H, Ph).

X-8571A 26 0 ? Example 424 1+) cis-2-nhenvlcvclopropvlamine Compound B (1.2 g) was refluxed in a mixture of water-dioxane-hydrochloric acid conc. aq. (1:1:1) for 4 hours. The solution was diluted with water, washed with dichloromethane, basified with ammonium hydroxide (conc. aq.), extracted with dichloromethane, dried with sodiumsulfate, filtered and evaporated to yield the titled product as an oil.

^H-NMR CDCI3 8 ppm 0.8-0.9 (1H, CH2, m) , 1.1-1.2 (1H, CH2, m), 2.0-2.1 (1H, PhCH, q), 2.6-2.7 (1H, CHNH2, m), 7.1-7.4 (5H, Ph).

D [a] = + 62.7° (C 1, CHCI3) (-)-N-(cis-2-phenvlcvclopropvl)-N'-(5-chloropvrid-2-vl)- .thiourea (+)-N-cis-2-phenylcyclopropylamine (0.23 g, 1.7 mmol) from Example 424 was condensed with 1-(5-chloropyrid-2-yl-thiocarbamoyl)-imidazole (0.4 g, 1.7 mmol) according to the procedure of Example 372 to yield the titled product as crystals. iH-NMR CDC13 8 ppm 1.2-1.3 (lH, m, Cfl2) , 1.5-1.6 (lH, m, CH2), 2.5-2.6 (1H, q, PhCH), 3.7-3.8 (CfiN), 6.6-6.7 (1H, d, pyr), 7.2-7.5 (7H, Ph, pyr), 8.9-9.0 (1H, NH), 10.8-10.9 (1H, NH) .

X-8571A -479- 26 0 2 Mp. 189.6-191.3°C.

D [a] = - 62.7° (C 1, CHCI3) Example 426 ( + ) -N-(cis-2-phenvlcvclopropvD-N1 - (5-chloropvrid-2-vl)- thiourea (-)-N-cis-2-phenylcyclopropylamine (0.23 g, 1.7 10 mmol) from Example 423 was condensed with 1-(5-chloropyrid- 2-yl-thiocarbamoyl)-imidazole (0.4 g, 1.7 mmol) according to the procedure of Example 372 to yield the titled product as crystals. 3-H-NMR CDCI3 8 ppm 1.2-1.3 (1H, m, CE2) » 1.5-1.6 (1H, m, Ca2)/ 2.5-2.6" (1H, q, PhCH), 3.7-3.8 (CBN), 6.6-6.7 (1H, d, pyr), 7.2-7.5 (7H, Ph, pyr), 8.9-9.0 (1H, Nfl), 10.8-10.9 (1H, NH).

Mp. 189.2-191.8°C.

D [a] = + 59.3° (C 1, CHCI3) Example 427 (-)-N-(cis-2-phenvlcvclopropvl)-N'-(5-bromopvrid-2-vl)- thiourea (+)-N-cis-2-phenylcyclopropylamine from Example 424 and 2-amino-5-bromopyridine were reacted according to the procedures of Examples 93 and 94 using 2-amino-5-bromopyridine instead of 2-aminothiazole, to give the 30 titled product as crystals.

% X-8571A 26 0 p ^H-NMR (CDCI3): 1.19 - 1.26 (m, 1H), 1.47 - 1.55 (m, 1H) , 2.52 (q, 1H) , 3.66 - 3.75 (m, 1H) , 6.66 (dd, lH), 7.27 -7.41 (m, 5H), 7.47 (d, 1H), 7.60 (dd, 1H), 8.98 (broads., 5 1H), 10.88 (broad s., 1H).

Mp = 192.0 - 193.0°C D [a] = - 52.8° (C 1, CHCI3) Example 428 U) -N- (cis—2-phenvlcvcloprotTvl) -N' - (5-bromopvrid-2-vl) thiourea (-)-N-cis-2-phenylcyclopropylamine from Example 15 423 and 2-amino-5-bromopyridine were reacted according to the procedures of Examples 93 and 94 using --amino-5-bromopyridine instead of 2-aminothiazole, to give the titled product as crystals.

^H-NMR (CDCI3): 1.19 - 1.26 (m, 1H), 1.47 - 1.55 (m, 1H), 20 2.52 (q, 1H), 3.66 - 3.75 (m, 1H), 6.66 (dd, 1H), 7.27 - 7.41 (m, 5H), 7.47 (d, 1H), 7.60 (dd, 1H), 8.98 (broads., 1H), 10.88 (broad s.f 1H).

Mp = 195.5 - 196.5°C D [a] = + 50° (C 1, CHCI3) 260293

Claims (57)

WHAT WE CLAIM IS:

1. The use of a compound of the formula S R2 N C N Ri (IA) I I r4 R3 in which Ri is a stable, saturated or unsaturated, substituted or unsubstituted, 3 to 8 membered organic monocyclic ring having 0 to 4 hetero atoms selected from S, O, and N; or Ri is a stable, saturated or unsaturated, substituted or unsubstituted, 7 to 10 membered organic bicyclic ring having 0 to 5 hetero atoms selected from S, O, and N; X-8571A - 482 - 2602 R2 is a group of the formula Re R7 _I_J_ % I I R8 Rg 5 wherein R5 is Ri as defined above; or R5 is a group of the formula (RlO)y-X- whereln y1slor2;X1sN,SorO and Rjq 1s Rj as defined above; or Rio is hydrogen, C1-C6 alkyl, C2-Cg alkenyl, or C2~Cg 10 alkynyl; or R5 is hydrogen, halo, cyano, carboxy, amino, thio, hydroxy, C1-C4 alkoxy, C1-C6 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, or C2-C8 alkenoic/; and R6, R7, R8» and R9 are independently C3-C8 cycloalkyl, hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 15 alkynyl, halo, amino, nitro, cyano, C1-C5 alkoxy, hydroxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, carbamoyl, or a halo substituted Cj-Cg alkyl; or two of which Rg, R7, Rs and Rg groups; along •with the carbons to which they are attached, combine*to form a 20 stable, saturated or unsaturated, substituted or unsubstituted, 3 to 7 membered organic monocylic ring having 0 to 4 hetero atoms selected from S, O, and N; 25 N.Z. PATENT OPT 1 7 NOV 1995 260293 X-8571A " 483 - R3 and R4 are independently hydrogen, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, amino, cyano, nitro, C1-C5 alkoxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, halo-substituted (C1-C6)alkyl, or carbamoyl; or salts thereof, in the preparation of a medicament for use in inhibiting the replication of HiV.

2. The use of claim 1 wherein the compound is of formula (IA) in which R3, R4, Rg, R7t R8 and Rg are all hydrogen.

3. The use as recited in claim 2 wherein the compound is of formula (IA) in which R5 is phenyl, substituted phenyl, naphthyl, substituted naphthyl, pyridyl, substituted pyridyl, or cyclohexenyl.

4. The use as recited in claim 2 wherein the compound is of formula (IA) in which R, is thiazolyl, substituted thiazolyl, benzothiazolyl, substituted benzothiazolyl, pyrazinyl, substituted pyrazinyl, pyridyl, substituted pyridyl, pyridazinyl, substituted pyridazinyl, thiadiazolyl or substituted thiadiazolyl.

5. The use as recited in claim 1 *vherein said compound is N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea or its hydrochloride salt.

6. The use as recited in claim 1 wherein said medicament is formulated for use together with at least one other anti-HlV agent.

7. The use as recited in claim 6 wherein said other anti-HIV agent is selected from ddl (2',3'-dideoxyinosine), ddC (2,,3'-dideoxycitidine) and AZT (S'-azido.S'deoxythymidine).

8. The use of a compound of the formula N.Z. PATENT OFFICE 2! ?KS1997 RECEIVED 260293 R? N C N R, (IA) II R4 R3 in which Ri is a stable, saturated or unsaturated, substituted or unsubstituted, 3 to 8 membered organic 5 monocyclic ring having 0 to 4 hetero atoms selected from S, O, and N; or Ri is a stable, saturated or unsaturated, substituted or unsubstituted, 7 to 10 membered organic bicyclic ring having 0 to 5 hetero atoms selected from S, O, and N; 10 R2 is a group of the formula R5 C C R8 Rg wherein R5 is Ri as defined above; or R5 is a group of the 1 5 formula (RlO)y-X- wherein.y is 1 or 2; X is N, S or 0 and Rio is Rj as defined above; or Rio is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl; or R5 is hydrogen, halo, cyano, carboxy, amino, 2 0 thio, hydroxy, C1-C4 alkoxy, C1-C6 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, or C2-C8 alkenoxy; and R6, R7, R8» and Rg are independently C3-C8 cycloalkyl, hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, amino, nitro, cyano, C1-C5 alkoxy, hydroxy, N.Z. FAfciv f OFFICE 1 7 NOV 1995 roc; I X-8 571A. - 485 - 260293 carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, carbamoyl, or a halo substituted Ci-Cg alkyl; or two of which Rg. R7> Rs and R9 groups along with the carbons to which they are attached, combine to form a stable, saturated or unsaturated, substituted or unsubstituted, 3 to 7 membered organic monocylic ring having 0 to 4 hetero atoms selected from S, O, and N; R3 and R4 are independently hydrogen, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, amino, cyano, nitro, C1-C5 alkoxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, halo-substituted (C1-C6)alkyl, or carbamoyl; or pharmaceutically acceptable salts thereof, in the preparation of a medicament for use in treating or inhibiting HIV in a human.

9. The use of claim 8 wherein the compound is of formula (IA) in which R3, R4, Rg, R7i R8 and Rg are all hydrogen.

10. The use as recited in claim 9 wherein the compound is of formula (IA) in which Rs is phenyl, substituted phenyl, naphthyl, substituted naphthyl, pyridyl, substituted pyridyl, or cyclohexenyl.

11. The use as recited in claim 9 wherein the compound is of formula (IA) in which R, is thiazolyl, substituted thiazolyl, benzothiazolyl, substituted benzothiazolyl, pyrazinyl, substituted pyrazinyl, pyridyl, substituted pyridyl, pyridazinyl, substituted pyridazinyl, thiadiazolyl or substituted thiadiazolyl. N.2. PATENT OFFICE 2 I MAR 1997 . RECEIVED 260 2 X-8571A - 486 -

12. The use as recited in claim 8 wherein said compound is N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea or its hydrochloride salt.

13. The use as recited in claim 8 wherein said medicament is formulated for use together with at least one other therapeutic agent.

14. The use as recited in claim 9 wherein said other therapeutic agent is selected from ddl (^.S'-dicleoxyinosine), ddC (2',3'-dideoxycitidine) and AZT (31^-azido,3'deoxythymidine).

15. The use of a compound of the formula s II ro n c n ri (ia) I I R4 R3 in which Ri is a stable, saturated or unsatr -ated, substituted or unsubstituted, 3 to 8 membered organic monocyclic ring having 0 to 4 hetero atoms selected from S, O, and N; or Ri is a stable, saturated or unsaturated, substituted or unsubstituted, 7 to 10 membered organic bicyclic ring having 0 to 5 hetero atoms selected from S, O, and N; R2 is a group of the formula R5 I 1 R8 R9 N.Z. PATENT OFFICE 21 MAR 1997 RECEIVED 260 293 X-8571A - 487 - wherein R5 is Ri as defined above; or R5 is a group of the formula (RlO)y-X- wherein y is 1 or 2; X 1s N, S or 0 and Rio is Ri as defined above; 5 or Rio is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl; or R5 is hydrogen, halo, cyano, carboxy, amino, -iio, hydroxy, C1-C4 alkoxy, C1-C6 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, or C2-C8 alkenoxy; and Rg, R7, R8, and R9 are independently C3-C8 10 cycloalkyl, hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, amino, nitro, cyano, C1-C5 alkoxy, hydroxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, carbamoyl, or a halo substituted C1-C6 alkyl; or two of which Rg, R7, Rs and ^9 groups along 15 with the carbons to which they are attached, combine to form a stable, saturated or unsaturated, substituted or unsubstituted, 3 to 7 membered organic monocylic ring having 0 to 4 hetero atoms selected from S, O, and N; 20 R3 and R4 are independently hydrogen, hydroxy, 25 C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, amino, cyano, nitro, C1-C5 alkoxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, halo-substituted (C1-C6)alkyl, or carbamoyl; or pharmaceutically acceptable salts thereof, in the preparation of a medicament for use in treating or inhibiting acquired immunodeficiency syndrome in a human.

16. The use of claim 15 wherein the compound is of formula (IA) in which R3, R4, Re, R7) Re and Ra are all hydrogen. N.Z. PATENT OFFICE 21 MAR 1997 Rcen«EO X-8571A - 488 -

17. The use as recited in claim 16 wherein the compound is of formula (IA) in which Rs is phenyl, substituted phenyl, naphthyl, substituted naphthyl, pyridyl, substituted pyridyl, or cyclohexenyl.

18. The use as recited in claim 16 wherein the compound is of formula (IA) in which R, is thiazolyl, substituted thiazolyl, benzothiazolyl, substituted benzothiazolyl, pyrazinyl, substituted pyrazinyl, pyridyl, substituted pyridyl, pyridazinyl, substituted pyridazinyl, thiadiazolyl or substituted thiadiazolyl.

19. The use as recited in claim 15 wherein said compound is N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea or its hydrochloride salt.

20. The use as recited in claim 15 wherein said medicament is formulated for use together with at least one other therapeutic agent.

21. The use as recited in claim 20 wherein said other therapeutic agent is selected from ddl (2',3'-dideoxyinosine), ddC (2',3-dideoxycitidine) and AZT (3'-azido,3'deoxythymidine).

22. A compound of the formula below S R2 N C N Rx (IA) in which Ri is a stable* saturated or unsaturated, substituted or unsubstituted, 3 to 8 membered organic monocyclic ring having 0 to 4 hetero atoms selected from S, O, and N; or Ri is a stable, saturated or unsaturated, substituted or unsubstituted, 7 to 10 membered organic bicyclic ring having 0 to 5 hetero atoms selected from S, O, and N; N.2. PATENT OFFICE 21 MA# 1997 - RECEIVED X-8571A - 489 - 260293 R2 is a group of the formula R< R8 Rg 5 wherein R5 is Ri as defined above; or R5 is a group of the formula (RlO)y-X- wherein y is 1 or 2; X is N, S or 0 and Rjo is Rj as defined above; or Rio is hydrogen, C1-C6 alkyl, C2-C6 alkenyl,or C2-C6 10 alkynyl; or R5 is C1-C6 alkyl, halo, cyano, carboxy., amino, thio, C1-C4 alkoxy, C2-C8 alkenyl, C2-C8 alkynyl, or C2 to Cs alkenoxy; and R6 and R7 are independently C3-C8 cycloalkyl, hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, 15 amino, nitro, cyano, C1-C5 alkoxy, hydroxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, carbamoyl, or a halo substituted C1-C6 alkyl; and R8 and R9, along with the carbons to which they 20 are attached, combine to form a stable, saturated or unsaturated, substituted or unsubstituted, 3 to 7 membered organic monocylic ring having 0 to 4 hetero atoms selected from s, 0, and N; and R3 and R4 are independently hydrogen, hydroxy, 2 5 C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, amino, cyano, nitro, C1-C5 alkoxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, halo-substituted {C1-C6)alkyl, or carbamoyl; or salts thereof with the proviso that the compound is not: S II c. N" H N.Z. PATENT 1 7 MOV 1995 25 •o 260293 X-8b7lA - 490 -

23. A compound as recited in claim 22 wherein Rl is thiazolyl, substituted thiazolyl, pyridyl, substituted pyridyl, pyridazinyl, substituted pyridazinyl, pyrazinyl, or substituted pyrazinyl; R5 is pyridyl, substituted pyridyl, phenyl, or substituted phenyl; and R8 and Rg, along with the carbons to which they are attached form cyclopropyl.

24. A compound as recited in claim 22 wherein the compound is N-(2-cis-phenylcyclopropyl)-N'-2- (thiazolyl)thiourea.

25. A compound as recited in claim 22 wherein said compound is selected from: N-(2-cis-phenylcyclopropyl)-N'-[2-(5-bromo)pyridyl]thiourea; N-(2-cis-phenylcyclopropyl)-N'-[2-(5-chloro)pyridyl]thiourea; N-[2-(cis-2-pyridyl)cyclopropyl]-N'-[2-(5-bromo)pyridyl]thiourea; N-[2 - (cis-2-pyridyl)cyclopropyl]-N'-[2-(5-chloro)pyridyl]thiourea; N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N'-[2-(5-bromoJpyridyl]thiourea; N-[2-(cis-2-(6-fluoro)pyridyl)cyclopropyl]-N'-[2-(5-chloro)pyridyl]thiourea ;' N-[2-(cis-2-(6-methoxy Jpyridyl)cyclopropyl]-N'-[2-(5-bromo)pyridyl]thiourea ; N-[2-(cis-2-(6-methoxy)pyridyl)cyclopropyl]-N'-[2-(5-chloro)pyridyl]thiourea; N- [2- (cis-2- (6-ethoxy)pyi.j.dyl) cyclopropyl] -N' - [2- (5-bromo)pyridyl]thiourea- and N-[2-(cis-2-(6-etnoxyJpyridyl)cyclopropyl]-N'-[2- (5-chloro)pyridyl]thiourea; and salts thereof.

26. A composition comprising a compound as recited in claim 22 together with at least one other therapeutic agent.

27. A composition as recited in claim 26 wherein said agent is selected from ddl (2',3'-dideoxyinos1ne), ddC (2',3'-dideoxycitidine) and AZT (S'-azido^'deoxythymidine). N.Z. r.'V ■ / 1 7 NOV 1995 RLCEIVl'.d X-8571A - 491 - 260293 2€.

A pharmaceutical formulation comprising a compound o£ claim 22 associated with one or more carriers, excipients or diluents therefor.

29. A formulation as recited in claim 28 comprising at least one other therapeutic agent.

30. a formulation as recited in claim 29 wherein said agent is cldl (2' ,3'-dideoxyinos1ne), ddC (21,3'-dideoxycitidlne) and AZT (S'-azldo.S'deoxythymidlne).

31. A compound of the formula s II i*2 N C N Rx (IA) R4 R3 wherein Ri is cyclo(C3-C8)alkyl, cyclo (C3-C8) alkenyl; isothiazolyl, substituted isothiazolyl, tetrazolyl, substituted tetrazolyl, triazolyl, substituted triazolyl, pyridyl, substituted pyridyl, imidazolyl, substituted imidazolyl, naphthyl, substituted naphthyl, benzoxazolyl, substituted benzoxazolyl, benzimidazolyl, substituted benzimidazolyl,thiazolyl, substituted thiazolyl, oxazolyl, substituted oxazolyl, benzothiazolyl, substituted benzothiazolyl, pyrazinyl, substituted pyrazinyl, pyridazinyl, substituted pyridazinyl, thiadiazolyl, substituted thiadiazolyl, benzotriazolyl, substituted benzotriazolyl, pyrrolyl, substituted pyrrolyl, indolyl, substituted indolyl, benzothienyl, substituted benzothienyl, thienyl, substituted thienyl, benzofuryl, substituted benzofuryl, furyl, substituted furyl, N.Z.

PATCHT , 1 7 NOV 1995 260293 X-8571A - 492 - quinolinyl, substituted quinolinyl, isoquinolinyl, substituted isoquinolinyl, pyrazolyl, or substituted pyrazolyl; R2 is a group of the formula Re |7 TT Re Rg wherein r5 is pyridyl, substituted pyridyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, cyclohexenyl or benzyl, or R5 is a group of the formula (RlO)y-X- wherein y 1s 1 or 2; X 1s N, S or 0 and Rio 1s Ri as defined above; or Rio is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;or r5 is halo, cyano, thio, c1-c4 alkoxy, C2-C8 alkynyl, or C2-C8 alkenoxy; and R6, r7, K8, ana Rg are independently c3-C8 cycloalkyl, hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halo, amino, nitro, cyano, c1-c5 alkoxy, hydroxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-c4 alkylthio, c1-C4 alkanoyloxy, carbamoyl, or a halo-substituted C1-C6 alkyl; or R6 and Rs> or r7 and Rg, along with the carbon to which they are acw.uhed, form a stable, saturated or unsaturated, substituted or unsubstituted, 3 to 7 membered organic monocylic ring having 0 to 4 hetero atoms selected from S, O, and N; and r3 and r4 are independently hydrogen, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, amino, cyano, j~ •••• patent crr:cr I ' 7 NOV 1995 X-8571A 493 - 260293 nitro, C1-C5 alkoxy, carboxy, hydroxymethyl, aminomethyl, carboxymethyl, C1-C4 alkylthio, C1-C4 alkanoyloxy, halo-substituted C1-C6 alkyl; or carbamoyl; or salts thereof, with the proviso that the substltuents or compound are not the following: I) Rb N ( H H O Rc where R5 and Rc may be hydrogen, C1-C4 alkyl, trifluoromethyl, phenyl or substituted phenyl; II) where Rj may be hydrogen, halogen, hydroxy, C1-C5 alkyl, or Cj-C6 al kox.y; i lu I 0 1 u 1 to f L: J ri { 0 1 SB Q ' t— LU r~~ -7 ] > LU O 1 W h- as J O & N. 1 LU 1 a: Nj ~z 494 Re Re Rl N N: or 0/~n \ Rf Rf where Re and Rf must be C1-C3 alkyl; or 260293 N IV) R, = ^ or R6/ R7f R8/ and Rg are all hydrogen.

33. A compound of claim 31 wherein R5 is phenyl, substituted phenyl, pyridyl, substituted pyridyl, or cyclohexenyl.

34. A compound of claim 31 wherein Ri is pyridyl, substituted pyridyl, thiazolyl, substituted thiazolyl, benzothiazolyl, substituted benzothiazolyl, thiadiazolyl, substituted thiadiazolyl, pyrazinyl, substituted pyrazinyl, pyridazinyl, or substituted pyridazinyl.

35. A compound as recited in claim 31 wherein Rl is pyridyl, fluoropyridyl, chloropyridyl, bromopyridyl, cyanopyridyl, methylpyridy1, ethylpyridyl, trifluoromethylpyridyl, dimethylpryldyl, thiazolyl, fluorothiazolyl, chlorothiazolyl, bromothiazolyl, methylthiazolyl, ethylthiazolyl, (nitrophenyl)thiazolyl, trifluoromethylthiazolyl, dimethylthiazolyl, cyanothiazolyl, pyridylthiazolyl, benzothiazolyl, (fluorobenzo)thiazolyl, fluoropyrazinyl, chloropyrazinyl, bromopyrazinyl, cyanopyrazinyl, methylpyrazinyl, e thy lpyraz inyl, trif luoromethy lpyrazinyl, ; . • N.Z. PATENT OFFICE 1 7 NOV 1995 260293 X-8571A - 495 - dimethylpyrazinyl, pyridazinyl, fluoropyridazinyl, chloropyridazinyl, bromopyridazinyl, cyanopyridazinyl, methylpyridazinyl, ethylpyridazinyl, tr if luoromethy lpyridaz inyl, or dimethyl pyrldazl nyl; R5 is pyridyl, substituted pyridyl, cyclohexenyl, naphthyl,phenyl,or phenyl substituted 1-4 times by methoxy, ethoxy, bromo, methyl, fluoro, chloro, or azldo and R6 and Rs are independently hydrogen or Ci-Cg 10 alkyl; and salts thereof.

36. A compound as recited in claim 31 wherein said compound is selected from: N-(2-(2-methoxyphenyl)ethyl)-N'-[2-(4- 1 5 cyano)thiazolyl]thiourea ; N-(2-(2-methoxyphenyl)ethyl)—N'-[2-(4-trifluoromethyl)thiazolyl]thiourea; N-(2-(2-methoxyphenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea; 20 N-(2-(2-methoxyphenyl)ethyl)-N'-[2-(5- bromo)pyridyl]thiourea; N-(2-(2-methoxyphenyl)ethyl)-N1 -[2-(5-chloro)pyridyl]thiourea; N-(2-(3-methoxypheny1)ethyl)-N'-[2-(4- 2 5 cyano)thiazolyl]thiourea; N-(2-(3-methoxypheny1)ethyl)-N*- [2- (4-trifluoromethyl)thiazolyl]thiourea; N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea; 0 N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(5- bromo)pyridyl]thiourea; N-(2-(3-methoxyphenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea; N-(2-(2-ethoxyphenyl)ethyl)-N' — [2 —(5 — 3 5 bromo)pyridyl]thiourea; N-(2-(2-ethoxyphenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea; N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(4-cyano)thiazolyl]thiourea; N.Z. PAID :t 1 7 NOV 1995 Rl?CLI^ j I 5 10 15 20 25 30 03 5 40 45 260293 X-8571A - 496 - N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea; N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea; N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(5-bromo)pyridyl]thiourea; N-(2-[2, 6-difluorophenyl)ethyl)-N'-[2-(5-chloro)pyridyl]thiourea ; N-(2-(2,6-difluorophenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea ; N-(2-(2,6-difluorophenyl)ethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea ; N-(2-(2-fluoro-6-methoxyphenyl)ethyl)-N'-[2-(5-bromo)pyridyl]thiourea ; N-'(2- (2-fluoro-6-methoxyphenyl) ethyl) -N'.- [2 - (5-chloro)pyridyl]thiourea; N-(2-(2-chlorophenyl)ethyl)-N'-[2 -(4-cyano)thiazolyl]thiourea; N-(2-(2-chlorophenyl)ethyl)-N'-[2 -(4-ethyl)thiazolyl]thiourea; N-(2-(2-chlorophenyl)ethyl)-N'-[2 -(5-bromo)pyridyl]thiourea ; N-(2-(2-chlorophenyl)ethyl)-N'-[2 -(5-chloroJpyridyl]thiourea; N-(2-(3-chlorophenyl)ethyl)-N'-[2 -(4-cyano)thiazolyl]thiourea ; N-(2-(3-chlorophenyl)ethyl)-N'-[2 -(4-ethyl)thiazolyl]thiourea; N-(2-(3-chlorophenyl)ethyl)-N'-[2 -(5-bromo)pyridyl]thiourea; N-(2-(3-chlorophenyl)ethyl)-N'-[2 -(5-chloro)pyridyl]thiourea; N- (2 - (1 -cyclohexenyl.) ethyl) -N' - [ 2 - (4 -cyano)thiazolyl]thiourea; N- (2-(l-cyclohexenyl)ethyl)-N'-[2-(4-trifluoromethyl)thiazolyl]thiourea; N—(2-(l-cyclohexenyl)ethyl)-N'-[2-(4-ethyl)thiazolyl]thiourea ; N-(2-(l-cyclohexenyl)ethyl)-N*-[2-(5-bromo)pyridyl]thiourea ; N-(2-(l-cyclohexenyl)ethyl)-N'—[2 -(5— chloro)pyridyl]thiourea; N- (2-(l-cyclohexenyl)ethyl)-N'-[(3-(6-chloro)pyridazinyl)]thiourea ; N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(5-chloro)pyrazinyl]thiourea; N.z. r-v-Ti::. TICE 1 7 NOV 1995 RLCEIV Lu> i 5 1 0 1 5 20 25 30 45 40 45 X-8571A - 497 - 260293 N-(2-(2,5-dimethoxyphenyl)ethyl)-N'-[2-(5-bromo)pyrazinyl]thiourea ; N-12-(2-pyridyl)ethylJ —N' — [2-(5-bromo)pyridyl]thiourea; N- [2-(2-pyridyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea; N-[2-(2-pyridyl)ethyl]—N * -12-(5 — trifluoromethyl)pyridyl]thiourea; N-[2-(2-pyridyl)ethyl]-N'-[2-(5-ethyl)pyridyl]thiourea; N-[2-(2-pyridyl)ethyl]-N'-[2-(5-methyl)pyridyl]thiourea; N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea ; N-[2-(2-(6-methoxy)pyridyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea; N-[2-(2-(6-ethoxyJpyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea; N-[2-(2-(6-ethoxy)pyridyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea ; N-[2-(2-(6-fluoro)pyridyl)ethyl]-N'-[2- (5-bromo)pyridyl]thiourea; N-[2-(2-(6-fluoro)pyridyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea; N-[2-(2-(3-fluoro)pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea; N-[2-(2-(3-fluoro)pyridyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea ; N-[2-(2-(6-chloro)pyridyl)ethyl]-N'-[2- (5-bromo)pyridyl]thiourea; N-[2-(2-(6-chloro)pyridyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea; N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(5-bromoJpyridyl]thiourea; N-[2-(2-(3-methoxy-6-fluoro)pyridyl)ethyl]-N1 -[2-(5-chloro)pyridyl]thiourea; N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea; N-[2-(2-(5-ethoxy-6-fluoro)pyridyl)ethyl]-N' -[2- (5-chloro)pyridyl]thiourea ; N-[2-(2-(3-ethoxy-6-fluoro)pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea; N-[2-(2-(3-ethoxy-6-fluoroJpyridyl)ethyl]—N'— [ 2 — (5 — chloroJpyridyl]thiourea; N-[2-(2-(3,6-difluoro)pyridyl)ethyl]-N'-[2-(5-bromoJpyridyl]thiourea; N-[2-(2-(3,6-difluoro)pyridyl)ethyl]-N'-[2-(5-chloro)pyridyl]thiourea ; and 260293 X-8571A - 498 - N-[2-(2,6-difluoro-3-methoxyphenyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea; and salts thereof.

37. A composition comprising a compound as recited in claim 31 together with at least one other therapeutic agent.

38. A composition as recited in claim 37 wherein said agent 1s selected from ddl (21,3'-dideoxyinosine), ddC (2',3'-dideoxyc1tidine) and AZT (3'-azido,3'deoxythym1d1ne).

39. A pharmaceutical formulation comprising a compound of claim 31 associated with one or more carriers, excipients or diluents therefor.

40. A formulation as recited in claim 39 comprising at least one other therapeutic agent.

41. A formulation as recited in claim 40 wherein said agent 1s ddl (2',3'-d1deoxy1nos1ne), ddC (2',3'-d1deoxyc1tid1ne; and AZT (3'-azido,3'deoxythymidine).

42. A compound of the formula ?6 s A r5-c-ch,-nh n—r, 5 I 2 ,1 Rs h wherein- Ri is pyridyl, fluoropyridyl, chloropyfidyl, bromopyridyl, cyanopyridyl, methyIpyridyl, ethylpyridyl, tri fluoromethyl pyridyl, dimethy Ipyridyl, thiazolyl, fluorothiazolyl, chlorothiazolyl, bromothiazolyl, methylthiazolyl, ethylthiazolyl, (nitrophenyl)thiazolyl, trifluoromethylthiazolyl, dimethylthiazolyl, cyanothiazolyl, pyridylthiazolyl, benzothiazolyl, (fluorobenzo)thiazolyl, fluoropyrazinyl, chloropyrazinyl, bromopyrazinyl, cyanopyrazinyl, methylpyrazinyl, ethylpyrazinyl, trifluoromethylpyrazinyl, dimethylpyrazinyl, pyridazinyl, fluoropyridazinyl, n:z:.'jvrn^j office i 7 VQV 1995 X-8571A - 499 - 260 chloropyridazinyl, bromopyridazinyl, cyanopyridazinyl, methylpyridazinyl, ethylpyridazinyl, tri f luorome thy lpyr idaz inyl, or dimethyl pyri dazi nyl; R5 is pyridyl, substituted pyridyl, cyclohexenyl, naphthyl,phenyl,or phenyl substituted 1 to 4 times by methoxy, ethoxy, bromo, methyl, fluoro, chloro, or azido and R6 and Rs are independently hydrogen or C1-C6 alkyl; and salts thereof, with the proviso that the compound is not: wherein R<j may be hydrogen, halogen, hydroxy, C^-Cg alkyl or Cg alkoxy.

43. A compound as recited in claim 42 in combination with at least one other therapeutic agent.

44. A compound as recited in claim 43 wherein said agent is selected from ddl (21,3'-dideoxyinosine), ddC (2',3'-dideoxycitidine) and AZT (3'-azido,3'deoxythyniidine).

45. N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromo)pyridyl]thiourea or its hydrochloride salt. S II 260293 -500-

46. A method of disinfecting objects and surfaces in areas where maintenance of sterile conditions is important using a compound of formula (IA) as defined in any preceding claim.

47. A method as defined in claim 46 wherein the objects are glassware and dental and surgical instruments.

43. A method as defined in claim 46 wherein the surfaces are walls, floors and tables.

49. The use of a compound of the formula (IA) as defined in claim 1 or a salt thereof substantially as herein described with reference to any example thereof.

50. The use of a compound of the formula (IA) as defined in claim 8 or a pharmaceutically acceptable salt thereof substantially as herein described with reference to any example thereof.

51. The use of a compound of the formula (IA) as defined in claim 15 or a pharmaceutically acceptable salt thereof substantially as herein described with reference to any example thereof.

52. A compound of the formula (IA) defined in claim 22 or a salt thereof substantially as herein described with reference to any example thereof.

53. A pharmaceutical formulation as defined in claim 28 substantially as herein described with reference to any example thereof.

54. A compound of the formula (IA) defined in claim 31 or a salt thereof substantially as herein described with reference to any example thereof.

55. A pharmaceutical formulation as defined in claim 39 substantially as herein described with reference to any example thereof.

56. A compound of the formula defined in claim 42 or a salt thereof i ubstantially as herein described with reference to any example thereof. o ££

57. A method as defined in claim 46 of disinfecting objects substantially as olerein described with reference to any example thereof. BUI m I 9 pntn>ioi£. f\*cr ig; I END OF CLAIMS By the authorised agents —1 A J PARK&SON Per o~>a il