Biguanide derivatives and their rearrangement products for use in the treatment of cancer

Abstract

The present disclosure relates to biguanide derivatives of formula (I) and their rearrangement products. The present disclosure also relates to the use of these compounds in a method for treating cancer, in particular melanoma. ##STR00001##

Claims

1. A compound of formula (II) or (III) ##STR00163## wherein Y′ is —SR.sub.4 or —OR.sub.5, R.sub.4 is selected from C.sub.1-C.sub.6 alkyl and protecting groups selected from any group linked by a disulfide function, thioesters, alkyl, alkenyl and alkynyl thioethers, benzyl thioethers, alkylarylmethyl thioethers, and triarylmethylthioethers; R.sub.5 is selected from protecting groups selected from esters, silylated ethers, alkoxymethyl ethers, benzyl ethers tetrahydropyranyl ethers, pentoses, and hexoses; each R′ is independently selected from halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkyl, —OH, —NR″R′″, —NO.sub.2, —CN and —(CO)—R; n is 0 to 4; R.sub.3 is selected from C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, heterocyclyl having 5 to 10 ring atoms, aryl having 6 to 10 ring atoms, heteroaryl having 5 to 10 ring atoms and C.sub.7-C.sub.16 aralkyl, said alkyl, cycloalkyl, haloalkyl, alkenyl, alkynyl, heterocyclyl, aryl, heteroaryl and aralkyl being optionally substituted with one or more substituents independently selected from halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6haloalkyl, —OH, —NR″R″, —NO.sub.2, —CN and —(CO)—R; each R is independently selected from H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy and —NR″R″ ‘; each R″ and R’ is independently selected from H and C.sub.1-C.sub.6 alkyl.

2. The compound of claim 1, wherein Y′ is —SR.sub.4, R.sub.4 being selected from C.sub.1-C.sub.6 alkyl; each R′ is independently selected from halogen and C.sub.1-C.sub.6 alkoxy; n is 0 to 1; R.sub.3 is selected from C.sub.1-C.sub.6 haloalkyl, aryl having 6 to 10 ring atoms, heteroaryl having 5 to 10 ring atoms, and C.sub.7-C.sub.16 aralkyl, said aryl, heteroaryl and aralkyl being optionally substituted with one or more substituents independently selected from halogen, C.sub.1-C.sub.6 alkoxy, and —CN.

3. The compound of claim 1, wherein the compound is ##STR00164## ##STR00165## ##STR00166## ##STR00167## ##STR00168## ##STR00169## ##STR00170## ##STR00171## ##STR00172##

4. The compound of claim 1, wherein the compound is selected from ##STR00173## ##STR00174## ##STR00175##

5. A pharmaceutical composition comprising a compound of claim 1, and a pharmaceutically acceptable carrier.

Description

FIGURES LEGENDS

(1) In all the figures, the bars indicate the mean±SEM: *p<0.05; **p<0.01; ***p<0.001.

(2) FIG. 1A represents the cell viability of A375 S cells treated with 5 μM of CRO15 or PLX4032 at time indicated on the graph.

(3) FIG. 1B represents the cell viability of A375 S cells treated with different concentrations of CRO15 or with 5 μM PLX4032 for 48 hours.

(4) FIG. 1C represents the viability of different melanoma cells with various mutations treated with 5 μM CRO15 for 48 hours. Mutations are specified next to name of melanoma cell lines. Mutated proteins are symbolized with “*”.

(5) FIG. 1D represents the viability of patient melanoma cells treated with 5 μM CRO15 for 48 hours. Mutated proteins are symbolized with “*”

(6) FIG. 1E represents the viability of normal cells treated with 5 μM CRO15 for 48 hours.

(7) FIG. 2 represents the results of the western blot assays.

(8) FIG. 3A represents the evolution of the tumoral volume of xenograft mice inoculated subcutaneously with A375 sensitive melanoma cells and treated with CRO15 or PLX4032.

(9) FIG. 3B represents the tumoral weight of xenograft mice inoculated subcutaneously with A375 sensitive melanoma cells and treated with CRO15 or PLX4032, after mice euthanasia.

(10) FIG. 4A represents the viability of both sensitive and resistant A375 melanoma cells treated with CRO15 or PLX4032.

(11) FIG. 4B represents the evolution of the tumoral volume of xenograft mice inoculated subcutaneously with A375 resistant melanoma cells and treated with CRO15 or PLX4032.

(12) FIG. 4C represents the tumoral weight of xenograft mice inoculated subcutaneously with A375 resistant melanoma cells and treated with CRO15 or PLX4032, after mice euthanasia.

(13) FIG. 5 represents the cell viability of DR6 cells treated with different concentrations of CRO15 or with 1 μM of vemurafenib and 0.5 μM of cobimetinib for 24 hours.

(14) FIG. 6A represents the evolution of the tumoral volume of xenograft mice inoculated subcutaneously with A375 resistant melanoma cells and treated with MTF319 or PLX4032.

(15) FIG. 6B represents the tumoral weight of xenograft mice inoculated subcutaneously with A375 resistant melanoma cells and treated with MTF319 or PLX4032, after mice euthanasia.

(16) FIG. 7A represents the evolution of the tumoral volume of allograft mice inoculated subcutaneously with murine melanoma cells and treated with CRO15.

(17) FIG. 7B represents the cell viability of WM9 cells after treatment for 8 weeks with PLX4032, CRO15 or MTF255 and stimulation with 10 μM of each drug for 48 h.

EXAMPLES

Experimental Procedures

(18) Chemical Synthesis and Characterization

(19) Methanol, ethyl acetate, diethyl ether and dichloromethane were purchased from Carlo Erba, and used as received. Anhydrous DMF (99.8% stored under septum) was purchased from Sigma Aldrich, and used as received. All chemicals were purchased from Aldrich, Fisher or Alfa Aesar and used without further purification. Thin layer chromatography (TLC) was performed on precoated Merck 60 GF254 silica gel plates and revealed first by visualization under UV light (254 nm and 360 nm) .sup.1H and .sup.13C NMR spectra were recorded on a Bruker Advance 200 MHz spectrometer or a Bruker Advance 400 MHz or a Bruker Advance 500 MHz. Mass spectra (ESI-MS) were recorded on a Bruker (Daltonics Esquire 3000+). HRMS spectra were recorded on a ThermoFisher Q Exactive (ESI-MS) at a resolution of 140 000 at m/z 200. The purity of compounds was further assayed by HPLC analysis on a JASCO PU-2089 apparatus with Supelco analytical column Ascentis Express C18, 100 mm×46 mm 5 μM. Eluent A: water with 1‰ formic acid. Eluent B: CH.sub.3CN with 1‰ formic acid. Method 1: 30% B for 1 min, 30% B to 100% B over 5 min, 100% B for 2.5 min then from 100% B to 30% B over 30 sec, 30% B for 7 min (16 min in total). Method 2: 30% B for 1 min, 30% B to 100% B over 5 min, 100% B for 20 min then from 100% B to 30% B over 1 min, 30% B for 4 min (31 min in total). Method 3: 30% B for 1 min, 30% B to 100% B over 5 min, 100% B for 2.5 min then from 100% B to 30% B over 30 sec (9 min in total). Method 4: 10% B for 10 min: 10% B to 95% B over 8 min, 95% B for 2 min, then from 95% B to 10% B over 4 min, 10% B for 1 min (25 min in total).

(20) Synthetic Procedures and Characterizations:

General Procedure (A) for the Formation of Biguanides of Formula I

(21) To a solution of the corresponding guanidine (1 equiv) in N,N-dimethylformamide (25 mL/g of guanidine) was added sodium hydride (60% dispersion in mineral oil, 1.5 eq.) and the mixture was stirred for 30 min at r.t. To this solution was added the corresponding nitrile (1 equiv) in one portion. The reaction was stirred overnight at room temperature and monitored by TLC. After completion of the reaction, the mixture was poured into water (200 mL/g of guanidine) and the precipitate was collected and washed with water, methanol and diethyl ether.

General Procedure (B) for the Formation of N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-aryl/hetaryl-1,3,5-triazine-2,4-diamines) of formula II and III (B)

(22) A solution of the corresponding biguanide (1 equiv) in technical grade ethanol (approx. 25 mL/100 mg of biguanide) was stirred at reflux temperature and monitored by LCMS. After full conversion (approx 6-7 hours), the precipitate formed was filtered and washed with technical grade ethanol.

General Procedure (C) for the formation of N2,N2′-(disulfanediylbis(4-alkyl/hal-2,1-phenylene))bis(6-(trichloromethyl)-1,3,5-triazine-2,4-diamines) of Formula II and III

(23) To a solution of the corresponding guanidine (1 equiv) in technical grade ethanol (approx. 10 mL/g of guanidine), trichloroacetonitrile (2 equiv) was added and the reaction mixture was stirred at reflux temperature and monitored by LCMS. After full conversion (approx 6-7 hours), the precipitate formed was filtered and washed with technical grade ethanol and diethyl ether.

General Procedure (D) for the formation of 2-((6-imino-4-(trichloromethyl)-1,6-dihydro-1,3,5-triazin-2-yl)amino)phenols

(24) To a solution of corresponding guanidine (1 equiv.) in technical grade ethanol (25 mL/g of guanidine) trichloroacetonitrile (10 equiv.) was added and the reaction mixture was stirred in a sealed tube under argon atmosphere at 60° C. After full conversion (approx. 18 hours), the mixture was concentrated to dryness. The residue was purified by silica gel flash chromatography.

General Procedure (E) for the formation of 2-(4-amino-6-phenyl-1,3,5-triazin-2-yl)amino)phenols

(25) To a solution of corresponding guanidine (1 equiv.) in N,N-dimethylformamide (25 mL/g of guanidine) sodium hydride (60% dispersion in mineral oil, 1.1 equiv.) was added and the reaction mixture was stirred in a sealed tube under argon atmosphere. When the gas evolution stopped to this solution was added corresponding nitrile (1 equiv.) and the tube was sealed. The resulting solution was then stirred at 80° C. After full conversion (approx. 18 hours), the mixture was concentrated to dryness. The residue was purified by silica gel flash chromatography.

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(trichloromethyl)-1,3,5-triazine-2,4-diamine) (CRO15)

(26) A solution of 1-(benzo[d]thiazol-2-yl)guanidine (10.0 g, 52 mmol) and trichloroacetonitrile (10.0 mL, 1.92 mmol) in technical grade ethanol (100 mL) was stirred at 75° C. After 1 h, a large amount of white precipitate appeared in the yellow solution. After reaction completion (TLC monitoring, about 3 h), the suspension was cold down to r.t. and filtered. The precipitate was washed with little amount of cold ethanol and dried at air. Recrystallization from acetone/diethyl ether afforded the desired compound as a white solid (10.03 g, 57.5%). TLC: R.sub.f (Et.sub.2O/PE, 1/1, v/v)=0.23. .sup.1H NMR (200 MHz, Acetone-d6): δ 8.54 (s, 1H), 7.96 (d, J=8.0 Hz, 1H), 7.58 (dd, J=7.8, 1.6 Hz, 1H), 7.35 (td, J=7.8, 1.6 Hz, 1H), 7.22-6.93 (m, 3H). .sup.13C NMR (101 MHz, Acetone-d6): δ 174.00, 168.98, 166.37, 139.05, 133.76, 130.58, 129.92, 126.33, 125.34, 97.43. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.20H.sub.15Cl.sub.6N.sub.10S.sub.2.sup.+, 668.90482; Found: 668.90497. HPLC (λ.sub.280): Purity 97.4%; t.sub.R: 7.958 min (method 2).

N2,N2′-(disulfanediylbis(4-methoxy-2,1-phenylene))bis(6-(trichloromethyl)-1,3,5-triazine-2,4-diamine) (MTF-232)

(27) Synthesized following the general procedure C using 1-(6-methoxybenzo[d]thiazol-2-yl)guanidine (300 mg, 1.35 mmol) to afford the titled compound as a green powder (418 mg, 85%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.64 (s, 1H), 7.59 (s, 1H), 7.45 (s, 1H), 7.20 (d, J=8.7 Hz, 1H), 7.10 (s, 1H), 6.84 (dd, J=8.7, 2.8 Hz, 1H), 3.70 (s, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.28, 167.38, 166.07, 158.26, 135.44, 129.22, 128.28, 113.08, 112.20, 96.77, 55.48. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 7.433 min (method 3).

N2,N2′-(disulfanediylbis(4-chloro-2,1-phenylene))bis(6-(trichloromethyl)-1,3,5-triazine-2,4-diamine) (MTF-233)

(28) Synthesized following the general procedure C using 1-(6-chlorobenzo[d]thiazol-2-yl)guanidine (300 mg, 1.32 mmol) to afford the titled compound as a white powder (454 mg, 93%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.66 (s, 1H), 7.71 (s, 1H), 7.58 (s, 2H), 7.40 (d, J=8.5 Hz, 1H), 7.35 (dd, J=8.5, 2.3 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.39, 167.34, 165.59, 135.71, 134.89, 131.29, 129.12, 127.91, 127.52, 96.63. HPLC (λ.sub.280): Purity 95.1%; t.sub.R: 13.767 min (method 1).

N2,N2′-(disulfanediylbis(4-fluoro-2,1-phenylene))bis(6-(trichloromethyl)-1,3,5-triazine-2,4-diamine) (MTF-234)

(29) Synthesized following the general procedure C using 1-(6-fluorobenzo[d]thiazol-2-yl)guanidine (300 mg, 1.42 mmol) to afford the titled compound as a white powder (457 mg, 91%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.06 (br. s., 2H), 7.69 (br. s., 1H), 7.57 (br. s., 1H), 7.45-7.30 (m, 2H), 7.14 (t, 1H, J=8.6 Hz, H1). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.42, 167.38, 165.94, 160.87 (d), 136.40, 131.93, 130.04, 114.76 (d), 113.61 (d), 96.69. HPLC (λ.sub.280): Purity 98.7%; t.sub.R: 6.858 min (method 3).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-bromobenzimidamide (MTF-242)

(30) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 3-bromobenzonitrile (0.95 g, 5.20 mmol) to afford the titled compound as a white-yellowish powder (708 mg, 36%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.29 (br. s, 1H), 9.36 (br. s, 1H), 8.94 (br. s, 1H), 8.26 (s, 1H), 8.11 (s, 1H), 8.03 (d, J=7.9 Hz, 1H), 7.80 (d, J=7.7 Hz, 1H), 7.76 (dd, J=7.9, 1.1 Hz, 1H), 7.66 (d, J=8.0 Hz, 1H), 7.47 (t, J=7.9 Hz, 1H), 7.39-7.30 (m, 1H), 7.24-7.15 (m, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.23, 161.94, 160.52, 151.47, 137.42, 134.08, 131.23, 130.43, 126.51, 125.66, 122.86, 121.70, 121.15, 119.78. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.12BrN.sub.5S.sup.+, 374.00696; Found: 374.00797. HPLC (λ.sub.280): Purity 99.3%; t.sub.R: 6.775 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-chlorobenzimidamide (MTF-243)

(31) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 3-chlorobenzonitrile (715 mg, 5.20 mmol) to afford the titled compound as a yellow powder (206 mg, 12%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.30 (br. s, 1H), 9.37 (br. s, 1H), 8.90 (br. s, 1H), 8.12 (t, br. s, J=1.8 Hz, 2H), 7.99 (d, J=7.9 Hz, 1H), 7.80 (d, J=7.7 Hz, 1H), 7.66 (d, J=7.9 Hz, 1H), 7.65-7.60 (m, 1H), 7.54 (t, J=7.9 Hz, 1H), 7.38-7.30 (m, 1H), 7.22-7.17 (m, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.22, 161.95, 160.57, 151.47, 137.26, 133.22, 131.23, 131.20, 130.20, 127.53, 126.14, 125.67, 122.87, 121.16, 119.79. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.12ClN.sub.5S.sup.+, 330,05747; Found: 330,05774. HPLC (λ.sub.280): Purity 99.2%; t.sub.R: 6.792 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2-chlorobenzimidamide (MTF-244)

(32) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 2-chlorobenzonitrile (715 mg, 5.20 mmol) to afford the titled compound as a white powder (326 mg, 19%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.14 (br. s, 1H), 9.30 (br. s, 1H), 8.81 (br. s, 1H), 8.09 (br. s, 1H), 7.80 (d, J=7.5 Hz, 1H), 7.65 (d, J=7.7 Hz, 1H), 7.53 (br. s, 2H), 7.50-7.40 (m, 2H), 7.34 (t, J=7.1 Hz, 1H), 7.20 (t, J=7.1 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.40, 162.90, 162.00, 151.45, 136.67, 131.23, 130.66, 130.29, 129.56, 129.46, 126.97, 125.63, 122.82, 121.16, 119.74. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.12CN.sub.5S.sup.+, 330.05747; Found: 330.05783. HPLC (λ.sub.280): Purity 96.6%; t.sub.R: 6.500 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-chlorobenzimidamide (MTF-245)

(33) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 4-chlorobenzonitrile (715 mg, 5.20 mmol) to afford the titled compound as a white-yellowish powder (721 mg, 42%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.27 (br. s, 1H), 9.36 (br. s, 1H), 8.85 (br. s, 1H), 8.06 (d, br.s, J=8.6 Hz, 3H), 7.79 (d, J=7.4 Hz, 1H), 7.66 (d, J=7.9 Hz, 1H), 7.59 (d, J=8.6 Hz, 2H), 7.34 (t, J=7.7 Hz, 1H), 7.19 (t, J=7.6 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.22, 162.00, 160.95, 151.47, 136.28, 134.00, 131.21, 129.44, 128.36, 125.65, 122.83, 121.15, 119.74. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.12ClN.sub.5S.sup.+, 330.05747; Found: 330.05743. HPLC (λ.sub.280): Purity 98.8%; t.sub.R: 6.800 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-methylbenzimidamide (MTF-246)

(34) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and p-tolunitrile (609 mg, 5.20 mmol) to afford the titled compound as a beige powder (145 mg, 9%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.28 (br. s, 1H), 9.34 (br. s, 1H), 8.74 (br. s, 1H), 7.96 (d, br. s, J=7.9 Hz, 3H), 7.79 (d, J=7.7 Hz, 1H), 7.65 (d, J=7.9 Hz, 1H), 7.33 (dd, J=18.6, 7.7 Hz, 3H), 7.19 (t, J=7.5 Hz, 1H), 2.37 (s, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.21, 161.99, 161.33, 151.46, 137.15, 134.68, 131.21, 129.49, 125.64, 122.82, 121.13, 119.74, 99.13. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.15N.sub.5S.sup.+, 310.11209; Found: 310.11218. HPLC (λ.sub.280): Purity 97.9%; t.sub.R: 6.592 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-iodobenzimidamide (MTF-247)

(35) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 4-iodobenzonitrile (1.19 g, 5.20 mmol) to afford the titled compound as a beige powder (832 mg, 38%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.24 (br. s, 1H), 9.34 (br. s, 1H), 8.82 (br. s, 1H), 8.03 (br. s, 1H), 7.90 (d, J=8.5 Hz, 2H), 7.82 (d, J=8.5 Hz, 2H), 7.79 (d, J=7.8 Hz, 1H), 7.65 (d, J=7.9 Hz, 1H), 7.34 (t, J=7.6 Hz, 1H), 7.19 (t, J=8.0 Hz, 1H). .sup.13C NMR (126 MHz, DMSO-d6): δ 172.20, 161.97, 161.31, 151.45, 137.13 (2C), 134.68, 131.20, 129.47 (2C), 125.62, 122.79, 121.11, 119.72, 99.09. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.12IN.sub.5S.sup.+, 421.99309; Found: 421.99316. HPLC (λ.sub.280): Purity 98.8%; t.sub.R: 6.900 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)benzimidamide (MTF-248)

(36) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and benzonitrile (0.54 mL, 5.20 mmol) to afford the titled compound as a beige powder (430 mg, 28%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.28 (br. s, 1H), 9.35 (br. s, 1H), 8.80 (br. s, 1H), 8.03 (d, br. s, J=7.3 Hz, 3H), 7.79 (d, J=7.6 Hz, 1H), 7.66 (d, J=7.9 Hz, 1H), 7.60-7.54 (m, 1H), 7.51 (t, J=7.2 Hz, 2H), 7.34 (t, J=7.4 Hz, 1H), 7.19 (t, J=7.4 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.37, 162.29, 162.21, 151.57, 135.28, 131.44, 131.26, 128.28, 127.60, 125.67, 122.82, 121.15, 119.75. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.13N.sub.5S.sup.+, 296.09644; Found: 296.09659. HPLC (λ.sub.280): Purity 97.9%; t.sub.R: 6.358 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2-fluorobenzimidamide (MTF-249)

(37) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 2-fluorobenzonitrile (0.56 mL, 5.20 mmol) to afford the titled compound as a red powder (179 mg, 11%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.16 (s, 1H), 9.31 (s, 1H), 8.69 (s, 1H), 8.05 (s, 1H), 7.80 (d, J=7.7 Hz, 1H), 7.72 (td, J=7.6, 1.4 Hz, 1H), 7.65 (d, J=7.9 Hz, 1H), 7.55 (ddd, J=9.4, 7.3, 1.6 Hz, 1H), 7.37-7.28 (m, 3H), 7.20 (t, J=7.5 Hz, 1H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.30 (s), 161.95 (s), 159.34 (d, J=250.6 Hz), 160.01 (s), 151.43 (s), 132.26 (d, J=8.6 Hz), 131.21 (s), 130.39 (d, J=2.6 Hz), 125.62 (s), 124.59 (d, J=13.0 Hz), 124.28 (d, J=3.4 Hz), 122.82 (s), 121.14 (s), 119.73 (s), 116.09 (d, J=21.9 Hz). .sup.19F NMR (377 MHz, DMSO-d6): δ −114.77. HPLC (λ.sub.280): Purity 97.4%; t.sub.R: 6.792 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2-bromobenzimidamide (MTF-250)

(38) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 2-bromobenzonitrile (946 mg, 5.20 mmol) to afford the titled compound as a beige powder (136 mg, 7%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.26 (s, 1H), 7.67 (d, J=7.9 Hz, 1H), 7.54 (d, br. s, J=7.0 Hz, 2H), 7.44 (t, J=7.3 Hz, 2H), 7.35 (t, J=7.1 Hz, 1H), 7.28-7.04 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d6): δ 173.15, 166.81, 165.00, 139.47, 136.49, 133.16, 132.85, 130.48, 130.28, 128.84, 127.32, 127.03, 126.48, 126.12, 120.08. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.12BrN.sub.5S.sup.+, 374.00696; Found: 374.00702. HPLC (λ.sub.280): Purity 97.8%; t.sub.R: 4.158 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)picolinimidamide (MTF-251)

(39) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 2-pyridinecarbonitrile (541 mg, 5.20 mmol) to afford the titled compound as a white-yellowish powder (955 mg, 62%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.10 (br. s, 1H), 9.40 (br. s, 1H), 8.92 (br. s, 1H), 8.72 (ddd, J=4.7, 1.6, 0.9 Hz, 1H), 8.37 (dt, J=7.9, 1.0 Hz, 1H), 8.03 (br. s, td, J=7.7, 1.7 Hz, 2H), 7.81 (dd, J=7.8, 0.8 Hz, 1H), 7.73-7.58 (m, 2H), 7.35 (td, J=7.7, 1.4 Hz, 1H), 7.20 (td, J=7.6, 1.2 Hz, 1H). .sup.13C NMR (101 MHz, DMSO-d6): δ 170.26, 167.51, 165.72, 154.24, 149.29, 136.70, 133.47, 128.60, 127.35, 126.57, 126.22, 125.45, 123.31. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.14H.sub.12N.sub.6S.sup.+, 291.09169; Found: 291.09174. HPLC (λ.sub.280): Purity 98.6%; t.sub.R: 6.075 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)nicotinimidamide (MTF-252)

(40) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol), 3-pyridinecarbonitrile (541 mg, 5.20 mmol) to afford the titled compound as a white-yellowish powder (1.49 g, 97%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.20 (br. s, 1H), 9.34 (br. s, 1H), 9.17 (dd, J=2.2, 0.6 Hz, 1H), 8.95 (br. s, 1H), 8.74 (dd, J=4.8, 1.6 Hz, 1H), 8.37-8.28 (m, 1H), 8.11 (br. s, 1H), 7.66 (dd, J=8.0, 0.6 Hz, 1H), 7.55 (ddd, J=8.0, 4.8, 0.8 Hz, 1H), 7.35 (td, J=7.7, 1.4 Hz, 1H), 7.20 (td, J=7.6, 1.2 Hz, 1H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.18, 161.92, 160.34, 151.88, 151.43, 148.75, 135.10, 131.24, 130.86, 125.61, 123.24, 122.82, 121.11, 19.75. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.14H.sub.12N.sub.6S.sup.+, 297.09169; Found: 297.09174. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 5.592 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)isonicotinimidamide (MTF-253)

(41) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 4-pyridinecarbonitrile (541 mg, 5.20 mmol) to afford the titled compound as a white-yellowish powder (1.12 g, 73%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.15 (br. s, 1H), 9.35 (br. s, 1H), 8.96 (br. s, 1H), 8.76 (dd, J=4.6, 1.5 Hz, 2H), 8.15 (br. s, 1H), 7.91 (dd, J=4.6, 1.5 Hz, 2H), 7.81 (dd, J=7.7, 0.7 Hz, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.42-7.30 (m, 1H), 7.27-7.14 (m, 1H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.12, 161.90, 160.07, 151.38, 150.07, 142.53, 131.28, 125.64, 122.88, 121.43, 121.13, 119.81. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.14H.sub.12N.sub.6S.sup.+, 297.09169; Found: 297.09177. HPLC (λ.sub.280): Purity 95.9%; t.sub.R: 5.308 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-methoxybenzimidamide (MTF-254)

(42) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 4-methoxybenzonitrile (692 mg, 5.20 mmol) to afford the titled compound as a beige powder (135 mg, 8%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.27 (br. s, 1H), 9.30 (br. s, 1H), 8.69 (br. s, 1H), 8.03 (d, J=5.9 Hz, 2H), 7.92 (br. s, 1H), 7.78 (d, J=5.4 Hz, 1H), 7.64 (d, J=5.8 Hz, 1H), 7.33 (s, 1H), 7.18 (s, 1H), 7.05 (d, J=5.6 Hz, 2H), 3.83 (s, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.33, 162.14, 161.96, 161.71, 151.58, 131.16, 129.40, 127.19, 125.62, 122.72, 121.10, 119.64, 113.56, 55.41. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.15N.sub.5OS.sup.+, 326.10701; Found: 326.10718. HPLC (λ.sub.280): Purity 95.3%; t.sub.R: 6.592 min (method 1).

3-acetyl-N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)benzimidamide (MTF-255)

(43) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 3-acetylbenzonitrile (755 mg, 5.20 mmol) to afford the titled compound as a red powder (228 mg, 13%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.25 (br. s, 1H), 9.33 (br. s, 1H), 8.98 (br. s, 1H), 8.58 (t, J=1.6 Hz, 1H), 8.30-8.22 (m, 1H), 8.20-7.97 (m, 2H), 7.81 (dd, J=7.8, 0.8 Hz, 1H), 7.68 (t, J=7.7 Hz, 2H), 7.35 (td, J=7.7, 1.4 Hz, 1H), 7.20 (td, J=7.6, 1.2 Hz, 1H), 2.66 (s, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 197.59, 172.28, 162.07, 161.35, 151.50, 136.86, 135.70, 132.04, 131.24, 131.07, 128.79, 127.31, 125.67, 122.85, 121.16, 119.77, 26.89. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.17H.sub.15N.sub.5OS.sup.+, 338.10701; Found: 338.10701. HPLC (λ.sub.280): Purity 95.2%; t.sub.R: 6.283 min (method 1).

3-bromo-N—(N-(4-phenylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-256)

(44) Synthesized following the general procedure A using 1-(4-phenylthiazol-2-yl)guanidine (1.00 g, 4.58 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 275 mg, 6.87 mmol) and 3-bromobenzonitrile (833 mg, 4.58 mmol) to afford the titled compound as a yellow powder (715 mg, 39%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.36 (br. s, 1H), 9.15 (br. s, 1H), 8.79 (br. s, 1H), 8.25 (s, 1H), 8.02 (d, J=7.8 Hz, 1H), 7.88 (d, br. s, J=7.3 Hz, 3H), 7.76 (dd, J=7.9, 1.0 Hz, 1H), 7.47 (dd, J=9.1, 6.6 Hz, 2H), 7.43 (t, J=7.7 Hz, 2H), 7.31 (t, J=7.3 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.11, 160.69, 160.04, 149.88, 137.62, 134.52, 133.94, 130.38, 128.71, 127.61, 126.46, 125.61, 121.73, 106.53. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.17H.sub.14BrN.sub.5S.sup.+, 400.02261; Found: 400.02213. HPLC (λ.sub.280): Purity 98.7%; t.sub.R: 7.033 min (method 1).

3-bromo-N—(N-(4-(3-nitrophenyl)thiazol-2-yl)carbamimidoyl)benzimidamide (MTF-257)

(45) Synthesized following the general procedure A using 1-(4-(3-nitrophenyl)thiazol-2-yl)guanidine (1.00 g, 3.80 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 228 mg, 5.70 mmol) and 3-bromobenzonitrile (692 mg, 3.80 mmol) to afford the titled compound as a yellow powder (711 mg, 42%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.21 (s, 1H), 8.78 (s, 2H), 8.62 (s, 1H), 8.34 (d, J=7.5 Hz, 1H), 8.23 (s, 1H), 8.19 (br. s, 1H), 8.15 (d, J=7.8 Hz, 1H), 8.01 (d, J=7.5 Hz, 1H), 7.80 (s, 1H), 7.76 (d, J=7.7 Hz, 1H), 7.72 (t, J=7.9 Hz, 1H), 7.48 (t, J=7.8 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.32, 160.75, 159.98, 148.31, 147.48, 137.51, 136.01, 133.95, 131.81, 130.37, 130.20, 126.47, 121.99, 121.66, 119.77, 109.28. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.17H.sub.13BrN.sub.6O.sub.2S.sup.+, 445.00768; Found: 445.00806. HPLC (λ.sub.280): Purity 99.1%; t.sub.R: 7.100 min (method 1).

N—(N-(4-(3-nitrophenyl)thiazol-2-yl)carbamimidoyl)picolinimidamide (MTF-259)

(46) Synthesized following the general procedure A using 1-(4-(3-nitrophenyl)thiazol-2-yl)guanidine (1.00 g, 3.80 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 228 mg, 5.70 mmol) and 2-pyridinecarbonitrile (366 mL, 3.80 mmol) to afford the titled compound as a yellow powder (796 mg, 57%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.03 (br. s, 1H), 9.08 (br. s, 1H), 8.78 (br. s, 1H), 8.71 (d, J=4.2 Hz, 1H), 8.66-8.61 (m, 1H), 8.38 (d, J=7.9 Hz, 1H), 8.35 (d, J=7.9 Hz, 1H), 8.16 (dd, J=8.1, 1.5 Hz, 1H), 8.02 (td, J=7.8, 1.6 Hz, 1H), 7.91 (br. s, 1H), 7.82 (s, 1H), 7.73 (t, J=8.0 Hz, 1H), 7.63 (ddd, J=7.4, 4.8, 1.0 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.49, 161.02, 158.37, 150.67, 148.58, 148.29, 147.51, 137.39, 135.99, 131.78, 130.16, 126.39, 122.10, 121.99, 119.78, 109.31. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.13N.sub.7O.sub.2S.sup.+, 368.09242; Found: 368.09274. HPLC (λ.sub.280): Purity 99.2%; t.sub.R: 6.850 min (method 1).

N—(N-(4-(3-nitrophenyl)thiazol-2-yl)carbamimidoyl)nicotinimidamide (MTF-260)

(47) Synthesized following the general procedure A using 1-(4-(3-nitrophenyl)thiazol-2-yl)guanidine (1.00 g, 3.80 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 228 mg, 5.70 mmol) and 3-pyridinecarbonitrile (395 mg, 3.80 mmol) to afford the titled compound as a yellow powder (656 mg, 47%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.14 (br s, 1H), 8.84 (br. s, 2H), 8.75 (d, J=5.8 Hz, 2H), 8.63 (s, 1H), 8.34 (d, J=7.8 Hz, 1H), 8.15 (dd, J=8.0, 1.4 Hz, 1H), 7.91 (d, J=5.8 Hz, 2H), 7.86 (br. s, 1H), 7.82 (s, 1H), 7.72 (t, J=8.0 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.23, 160.74, 159.55, 150.07, 148.33, 147.49, 142.64, 136.00, 131.80, 130.20, 122.01, 121.49, 119.79, 109.48. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.13N.sub.7O.sub.2S.sup.+, 368.09242; Found: 368.09283. HPLC (λ.sub.280): Purity 95.1%; t.sub.R: 6.350 min (method 1).

N—(N-(4-(3-nitrophenyl)thiazol-2-yl)carbamimidoyl)isonicotinimidamide (MTF-261)

(48) Synthesized following the general procedure A using 1-(4-(3-nitrophenyl)thiazol-2-yl)guanidine (1.00 g, 3.80 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 228 mg, 5.70 mmol) and 4-pyridinecarbonitrile (395 mg, 3.80 mmol) to afford the titled compound as a yellow powder (544 mg, 39%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.14 (br. s, 1H), 9.17 (d, J=1.6 Hz, 1H), 8.81 (br. s, 2H), 8.73 (dd, J=4.7, 1.4 Hz, 1H), 8.63 (s, 1H), 8.33 (t, J=8.4 Hz, 2H), 8.15 (dd, J=8.1, 1.5 Hz, 1H), 7.81 (s, 1H), 7.76 (br. s, 1H), 7.72 (t, J=8.0 Hz, 1H), 7.54 (dd, J=7.8, 4.8 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.30, 160.78, 159.84, 151.81, 148.78, 148.32, 147.48, 136.02, 135.13, 131.79, 130.97, 130.19, 123.25, 121.99, 119.79, 109.31. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.13N.sub.7O.sub.2S.sup.+, 368.09242; Found: 368.09283. HPLC (λ.sub.280): Purity 96.8%; t.sub.R: 6.367 min (method 1).

4-methoxy-N—(N-(4-phenylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-262)

(49) Synthesized following the general procedure A using 1-(4-phenylthiazol-2-yl)guanidine (1.00 g, 4.58 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 275 mg, 6.87 mmol) and 4-methoxybenzonitrile (610 mg, 4.58 mmol) to afford the titled compound as a beige powder (32 mg, 2%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.30 (br. s, 1H), 9.05 (br. s, 1H), 8.55 (s, 1H), 8.01 (d, J=8.9 Hz, 2H), 7.87 (d, J=7.3 Hz, 2H), 7.68 (br. s, 1H), 7.46 (s, 1H), 7.43 (t, J=7.7 Hz, 1H), 7.31 (t, J=7.3 Hz, 1H), 7.04 (d, J=8.9 Hz, 2H), 3.83 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 173.16, 161.77, 161.07, 160.84, 149.72, 134.54, 129.21, 128.64, 127.50, 127.36, 125.51, 113.46, 106.11, 55.37, 38.89. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.18H.sub.17N.sub.5OS.sup.+, 352.12266; Found: 352.12268. HPLC (λ.sub.280): Purity 95.1%; t.sub.R: 6.842 min (method 1).

N—(N-(4-phenylthiazol-2-yl)carbamimidoyl)picolinimidamide (MTF-263)

(50) Synthesized following the general procedure A using 1-(4-phenylthiazol-2-yl)guanidine (1.00 g, 4.58 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 275 mg, 6.87 mmol) and 2-pyridinecarbonitrile (441 mL, 4.58 mmol) to afford the titled compound as a yellow powder (369 mg, 25%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.16 (br. s, 1H), 9.19 (br. s, 1H), 8.79 (br. s, 1H), 8.70 (d, J=3.6 Hz, 1H), 8.38 (d, J=7.7 Hz, 1H), 8.01 (t, J=7.4 Hz, 1H), 8.19-7.70 (m, 4H), 7.88 (d, br. s, J=7.4 Hz, 4H), 7.66-7.57 (m, 1H), 7.50 (s, 1H), 7.43 (t, J=7.3 Hz, 2H), 7.32 (t, J=7.0 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.20, 160.91, 158.35, 150.73, 149.86, 148.61, 137.40, 134.50, 128.70, 127.61, 126.38, 125.59, 122.04, 106.61. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.14N.sub.6S.sup.+, 323.10734; Found: 323.10770. HPLC (λ.sub.280): Purity 98.0%; t.sub.R: 6.692 min (method 1).

3-bromo-N—(N-(6-methoxybenzo[d]thiazol-2-yl)carbamimidoyl)benzimidamide (MTF-264)

(51) Synthesized following the general procedure A using 1-(6-methoxybenzo[d]thiazol-2-yl)guanidine (1.00 g, 4.50 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 270 mg, 6.75 mmol) and 3-bromobenzonitrile (819 mg, 4.50 mmol) to afford the titled compound as a dark gray powder (146 mg, 8%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.29 (br. s, 1H), 9.24 (br. s, 1H), 8.84 (br. s, 1H), 8.23 (s, 1H), 8.01 (d, br. s, J=7.5 Hz, 2H), 7.77 (d, J=7.2 Hz, 1H), 7.56 (d, J=8.6 Hz, 1H), 7.48 (t, J=7.8 Hz, 1H), 7.42 (s, 1H), 6.95 (d, J=8.5 Hz, 1H), 3.79 (s, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 170.29, 161.45, 160.30, 155.69, 145.55, 137.47, 134.03, 132.39, 130.45, 130.36, 126.46, 121.68, 120.37, 113.92, 104.89, 55.55. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.14BrN.sub.5OS.sup.+, 404.01752; Found: 404.01733. HPLC (λ.sub.280): Purity 95.2%; t.sub.R: 6.825 min (method 1).

3-bromo-N—(N-(6-methylbenzo[d]thiazol-2-yl)carbamimidoyl)benzimidamide (MTF-265)

(52) Synthesized following the general procedure A using 1-(6-methylbenzo[d]thiazol-2-yl)guanidine (1.00 g, 4.85 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 291 mg, 7.28 mmol) and 3-bromobenzonitrile (883 mg, 4.85 mmol) to afford the titled compound as a beige powder (207 mg, 11%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.30 (br. s, 1H), 9.32 (br. s, 1H), 8.87 (br. s, 1H), 8.24 (s, 1H), 8.01 (d, br. s, J=7.6 Hz, 2H), 7.77 (d, J=7.7 Hz, 1H), 7.60 (s, 1H), 7.54 (d, J=8.1 Hz, 1H), 7.48 (t, J=7.8 Hz, 1H), 7.16 (d, J=8.0 Hz, 1H), 2.37 (s, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 171.42, 161.76, 160.43, 149.40, 137.44, 134.05, 132.22, 131.30, 130.41, 126.86, 126.47, 121.69, 120.95, 119.45, 20.93. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.14BrN.sub.5S.sup.+, 388.02261; Found: 388.02313. HPLC (λ.sub.280): Purity 98.3%; t.sub.R: 6.992 min (method 1).

3-chloro-N—(N-(4-phenylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-267)

(53) Synthesized following the general procedure A using 1-(4-phenylthiazol-2-yl)guanidine (1.00 g, 4.58 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 275 mg, 6.87 mmol) and 3-chlorobenzonitrile (630 mg, 4.58 mmol) to afford the titled compound as a white-yellowish powder (749 mg, 46%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.36 (br. s, 1H), 9.15 (br. s, 1H), 8.78 (br. s, 1H), 8.10 (t, J=1.7 Hz, 1H), 7.98 (d, J=7.9 Hz, 1H), 7.88 (d, br. s, J=7.2 Hz, 3H), 7.63 (dd, J=8.0, 1.2 Hz, 1H), 7.54 (t, J=7.9 Hz, 1H), 7.48 (s, 1H), 7.43 (t, J=7.7 Hz, 2H), 7.31 (t, J=7.3 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.05, 160.66, 160.04, 149.85, 137.43, 134.51, 133.20, 131.03, 130.14, 128.69, 127.59, 127.46, 126.08, 125.58, 106.53. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.17H.sub.14ClN.sub.5S.sup.+, 356.07312; Found: 356.07321. HPLC (λ.sub.280): Purity 98.0%; t.sub.R: 7.008 min (method 1).

4-chloro-N—(N-(5-phenylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-268)

(54) Synthesized following the general procedure A using 1-(4-phenylthiazol-2-yl)guanidine (1.00 g, 4.58 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 275 mg, 6.87 mmol) and 4-chlorobenzonitrile (630 mg, 4.58 mmol) to afford the titled compound as a yellow powder (717 mg, 44%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.35 (br. s, 1H), 9.14 (br. s, 1H), 8.73 (br. s, 1H), 8.05 (d, J=8.6 Hz, 2H), 7.87 (d, J=7.2 Hz, 2H), 7.73 (br. s, 1H), 7.58 (d, J=8.6 Hz, 2H), 7.47 (s, 1H), 7.43 (t, J=7.7 Hz, 2H), 7.31 (t, J=7.3 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.07, 160.72, 160.43, 149.82, 136.13, 134.52, 134.17, 129.37, 128.69, 128.31, 127.58, 125.57, 106.47. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.17H.sub.14ClN.sub.5S.sup.+, 356.07312; Found: 356.07318. HPLC (λ.sub.280): Purity 99.1%; t.sub.R: 6.925 min (method 1).

N—(N-(4-phenylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-272)

(55) Synthesized following the general procedure A using 1-(4-phenylthiazol-2-yl)guanidine (1.00 g, 4.58 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 275 mg, 6.87 mmol) and benzonitrile (0.471 mL, 4.58 mmol) to afford the titled compound as a beige powder (486 mg, 33%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.33 (br. s, 1H), 9.13 (br. s, 1H), 8.67 (br. s, 1H), 8.02 (d, J=7.2 Hz, 2H), 7.88 (d, J=7.3 Hz, 2H), 7.72 (br. s, 1H) 7.56 (t, J=7.2 Hz, 1H), 7.49 (dd, J=14.9, 7.7 Hz, 3H), 7.43 (t, J=7.7 Hz, 2H), 7.31 (t, J=7.3 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.16, 161.66, 160.90, 149.80, 135.41, 134.54, 131.26, 128.71 (2C), 128.22 (2C), 127.57, 127.50 (2C), 125.57 (2C), 106.37. HPLC (λ.sub.280): Purity 82.0%; t.sub.R: 6.850 min (method 1).

N—(N-(4-phenylthiazol-2-yl)carbamimidoyl)nicotinimidamide (MTF-273)

(56) Synthesized following the general procedure A using 1-(4-phenylthiazol-2-yl)guanidine (1.00 g, 4.58 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 275 mg, 6.87 mmol) and 3-cyanopyridine (477 mg, 4.58 mmol) to afford the titled compound as a yellowish powder (694 mg, 47%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.30 (br. s, 1H), 9.17 (d, br. s, J=1.6 Hz, 2H), 8.82 (br. s, 1H), 8.73 (dd, J=4.7, 1.4 Hz, 1H), 8.33 (d, J=8.0 Hz, 1H), 7.88 (d, br. s, J=7.3 Hz, 3H), 7.54 (dd, J=7.8, 4.8 Hz, 1H), 7.49 (s, 1H), 7.43 (t, J=7.6 Hz, 2H), 7.32 (t, J=7.3 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.07, 160.68, 159.88, 151.80, 149.86, 148.77, 135.10, 134.52, 131.05, 128.71, 127.60, 125.59, 123.25, 106.58. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.14N.sub.6S.sup.+, 323.10734; Found: 323.10764. HPLC (λ.sub.280): Purity 96.9%; t.sub.R: 6.075 min (method 1).

N—(N-(4-phenylthiazol-2-yl)carbamimidoyl)isonicotinimidamide (MTF-274)

(57) Synthesized following the general procedure A using 1-(4-phenylthiazol-2-yl)guanidine (1.00 g, 4.58 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 275 mg, 6.87 mmol) and 4-pyridinecarbonitrile (477 mg, 4.58 mmol) to afford the titled compound as a yellowish powder (871 mg, 59%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.30 (br. s, 1H), 9.20 (br. s, 1H), 8.86 (br. s, 1H), 8.75 (dd, J=4.5, 1.6 Hz, 2H), 7.92 (dd, J=4.5, 1.6 Hz, 2H), 7.88 (d, br. s, J=7.2 Hz, 3H), 7.50 (s, 1H), 7.43 (t, J=7.7 Hz, 2H), 7.32 (t, J=7.3 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.00, 160.64, 159.63, 150.09, 149.90, 142.74, 134.50, 128.72, 127.63, 125.61, 121.49, 106.75. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.14N.sub.6S.sup.+, 323.10734; Found: 323.10757. HPLC (λ.sub.280): Purity 95.2%; t.sub.R: 6.058 min (method 1).

2-chloro-N—(N-(4-(3-nitrophenyl)thiazol-2-yl)carbamimidoyl)benzimidamide (MTF-276)

(58) Synthesized following the general procedure A using 1-(4-(3-nitrophenyl)thiazol-2-yl)guanidine (1.00 g, 3.80 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 228 mg, 5.70 mmol) and 2-chlorobenzonitrile (523 mg, 3.80 mmol) to afford the titled compound as a brown powder (30 mg, 2%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.08 (br. s, 1H), 8.83 (br. s, 1H), 8.70 (br. s, 1H), 8.62 (s, 1H), 8.34 (d, J=7.7 Hz, 1H), 8.15 (d, J=7.4 Hz, 1H), 8.03-7.64 (br. s, 1H), 7.81 (s, 1H), 7.72 (t, J=7.7 Hz, 1H), 7.52 (t, J=7.8 Hz, 2H), 7.49-7.37 (m, 2H). .sup.13C NMR (101 MHz, DMSO-d6): δ 173.55, 162.25, 160.72, 148.36, 147.36, 136.69, 136.00, 131.76, 130.52, 130.25 (2C), 129.51, 129.39, 126.87, 121.95, 119.70, 109.25. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.17H.sub.13ClN.sub.6O.sub.2S.sup.+, 401.05820; Found: 401.05820. HPLC (λ.sub.280): Purity 95.2%; t.sub.R: 6.858 min (method 1).

3-chloro-N—(N-(4-(3-nitrophenyl)thiazol-2-yl)carbamimidoyl)benzimidamide (MTF-277)

(59) Synthesized following the general procedure A using 1-(4-(3-nitrophenyl)thiazol-2-yl)guanidine (1.00 g, 3.80 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 228 mg, 5.70 mmol) and 3-chlorobenzonitrile (523 mg, 3.80 mmol) to afford the titled compound as a brown powder (457 mg, 30%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.22 (br. s, 1H), 8.77 (br. s, 1H), 8.62 (s, 1H), 8.34 (d, J=7.7 Hz, 1H), 8.23-7.91 (br. s, 1H), 8.15 (d, J=8.0 Hz, 1H), 8.09 (s, 1H), 7.97 (d, J=7.7 Hz, 1H), 7.80 (s, 1H), 7.72 (t, J=8.0 Hz, 1H), 7.63 (d, J=7.9 Hz, 1H), 7.54 (t, J=7.9 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.31, 160.75, 160.02, 148.34, 147.48, 137.34, 136.02, 133.17, 131.83, 131.05, 130.24, 130.17, 127.45, 126.11, 122.02, 119.78, 109.32. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.17H.sub.13ClN.sub.6O.sub.2S.sup.+, 401.05820; Found: 401.05835. HPLC (λ.sub.280): Purity 95.5%; t.sub.R: 7.025 min (method 1).

4-chloro-N—(N-(4-(3-nitrophenyl)thiazol-2-yl)carbamimidoyl)benzimidamide (MTF-281)

(60) Synthesized following the general procedure A using 1-(4-(3-nitrophenyl)thiazol-2-yl)guanidine (1.00 g, 3.80 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 228 mg, 5.70 mmol) and 4-chlorobenzonitrile (523 mg, 3.80 mmol) to afford the titled compound as a yellow powder (640 mg, 42%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.15 (br. s, 1H), 8.74 (br. s, 2H), 8.68-8.60 (m, 1H), 8.55-7.90 (br. s, 1H), 8.39-8.30 (m, 1H), 8.16 (ddd, J=8.2, 2.3, 0.8 Hz, 1H), 8.10-7.97 (m, 2H), 7.82 (s, 1H), 7.72 (t, J=8.0 Hz, 1H), 7.66-7.48 (m, 2H). .sup.13C NMR (50 MHz, DMSO-d6): δ 173.37, 160.84, 160.46, 148.30, 147.47, 136.17, 136.04, 134.10, 131.77, 130.16, 129.40 (2C), 128.29 (2C), 121.96, 119.77, 109.19. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.17H.sub.13ClN.sub.6O.sub.2S.sup.+, 401.05820; Found: 401.05820. HPLC (λ.sub.280): Purity 96.7%; t.sub.R: 7.033 min (method 1).

N—(N-(4-methylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-283)

(61) Synthesized following the general procedure A using 1-(4-methylthiazol-2-yl)guanidine (1.00 g, 6.41 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 384 mg, 9.61 mmol) and benzonitrile (0.66 mL, 6.41 mmol) to afford the titled compound as a brown powder (382 mg, 23%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.42 (br. s, 1H), 9.11 (br. s, 1H), 8.61 (br. s, 1H), 8.02-7.96 (m, 2H), 7.57-7.52 (m, 1H), 7.85-7.39 (br. s, 4H), 7.51-7.46 (m, 2H), 6.57 (d, J=1.0 Hz, 1H), 2.24 (d, J=0.9 Hz, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.99, 161.63, 160.69, 147.64, 135.50, 131.20, 128.21, 127.45, 105.64, 17.56. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.12H.sub.13N.sub.5S.sup.+, 260.09644; Found: 260.09653. HPLC (λ.sub.280): Purity 95.7%; t.sub.R: 5.167 min (method 1).

2-chloro-N—(N-(4-methylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-284)

(62) Synthesized following the general procedure A using 1-(4-methylthiazol-2-yl)guanidine (1.00 g, 6.41 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 384 mg, 9.61 mmol) and 2-chlorobenzonitrile (881 mg, 6.41 mmol) to afford the titled compound as a white powder (132 mg, 7%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.27 (br. s, 1H), 9.06 (br. s, 1H), 8.63 (br. s, 1H), 7.63 (br. s, 1H), 7.46 (m, 4H), 6.57 (s, 1H), 2.24 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.87, 162.18, 160.47, 147.49, 136.79, 130.49, 130.27, 129.55, 129.40, 126.88, 105.69, 17.46. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.12H.sub.12ClN.sub.5S.sup.+, 294.05747; Found: 294.05747. HPLC (λ.sub.280): Purity 95.0%; t.sub.R: 5.500 min (method 1).

3-chloro-N—(N-(4-methylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-285)

(63) Synthesized following the general procedure A using 1-(4-methylthiazol-2-yl)guanidine (1.00 g, 6.41 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 384 mg, 9.61 mmol) and 3-chlorobenzonitrile (881 mg, 6.41 mmol) to afford the titled compound as a white-yellowish (1.24 g, 66%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.43 (br. s, 1H), 9.13 (br. s, 1H), 8.71 (br. s, 1H), 8.11-8.05 (m, 1H), 7.95 (d, J=7.9 Hz, 1H), 7.64-7.59 (m, 1H), 7.58 (br.s, 1H), 7.53 (t, J=7.9 Hz, 1H), 6.59 (d, J=0.9 Hz, 1H), 2.25 (d, J=0.5 Hz, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.82, 160.44, 159.91, 147.64, 137.47, 133.18, 130.97, 130.15, 127.39, 126.00, 105.82, 17.53. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.12H.sub.12ClN.sub.5S.sup.+, 294.05747; Found: 294.05768. HPLC (λ.sub.280): Purity 95.0%; t.sub.R: 5.933 min (method 1).

4-chloro-N—(N-(4-methylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-286)

(64) Synthesized following the general procedure A using 1-(4-methylthiazol-2-yl)guanidine (1.00 g, 6.41 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 384 mg, 9.61 mmol) and 4-chlorobenzonitrile (881 mg, 6.41 mmol) to afford the titled compound as a white-yellowish (923 mg, 49%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.42 (br. s, 1H), 9.13 (br. s, 1H), 8.67 (br. s, 1H), 8.01 (d, J=8.6 Hz, 2H), 7.57 (d, br. s J=8.6 Hz, 3H), 6.57 (d, J=1.0 Hz, 1H), 2.24 (d, J=0.7 Hz, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.87, 160.50, 160.37, 147.63, 136.08, 134.23, 129.30, 128.29, 105.74, 17.53. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.12H.sub.12ClN.sub.5S.sup.+, 294.05747; Found: 294.05762. HPLC (λ.sub.280): Purity 95.3%; t.sub.R: 5.958 min (method 1).

2-bromo-N—(N-(4-methylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-287)

(65) Synthesized following the general procedure A using 1-(4-methylthiazol-2-yl)guanidine (1.00 g, 6.41 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 384 mg, 9.61 mmol) and 2-bromobenzonitrile (1.17 g, 6.41 mmol) to afford the titled compound as a white-yellowish (499 mg, 23%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.27 (br. s, 1H), 9.07 (br. s, 1H), 8.63 (br. s, 1H), 7.67 (d, br. s, J=7.9 Hz, 2H), 7.46-7.43 (m, 2H), 7.36 (ddd, J=8.1, 6.0, 3.2 Hz, 1H), 6.57 (s, 1H), 2.24 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.89, 163.29, 160.49, 147.50, 138.85, 132.49, 130.57, 129.44, 127.37, 119.62, 105.68, 17.46. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.12H.sub.12BrN.sub.5S.sup.+, 338.00696; Found: 338.00705. HPLC (λ.sub.280): Purity 95.8%; t.sub.R: 5.192 min (method 1).

3-bromo-N—(N-(4-methylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-288)

(66) Synthesized following the general procedure A using 1-(4-methylthiazol-2-yl)guanidine (1.00 g, 6.41 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 384 mg, 9.61 mmol) and 3-bromobenzonitrile (1.17 g, 6.41 mmol) to afford the titled compound as a white-yellowish (1.11 g, 51%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.42 (s, 1H), 9.12 (s, 1H), 8.72 (s, 1H), 8.21 (t, J=1.7 Hz, 1H), 7.98 (d, J=8.0 Hz, 1H), 7.75 (dd, br. s, J=8.0, 1.1 Hz, 2H), 7.46 (t, J=7.9 Hz, 1H), 6.59 (d, J=0.9 Hz, 1H), 2.24 (d, J=0.8 Hz, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.80, 160.42, 159.83, 147.63, 137.63, 133.86, 130.38, 130.27, 126.35, 121.66, 105.81, 17.53. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.12H.sub.12BrN.sub.5S.sup.+, 338.00696; Found: 338.00760. HPLC (λ.sub.280): Purity 95.1%; t.sub.R: 6.042 min (method 1).

N—(N-(4-methylthiazol-2-yl)carbamimidoyl)picolinimidamide (MTF-289)

(67) Synthesized following the general procedure A using 1-(4-methylthiazol-2-yl)guanidine (1.00 g, 6.41 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 384 mg, 9.61 mmol) and 2-pyridinecarbonitrile (0.617 mL, 6.41 mmol) to afford the titled compound as a yellow powder (1.05 g, 63%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.20 (s, 1H), 9.15 (s, 1H), 8.77 (s, 1H), 8.73-8.65 (m, 1H), 8.34 (d, J=8.5 Hz, 1H), 8.00 (td, J=7.8, 1.7 Hz, 1H), 7.61 (ddd, J=7.4, 4.8, 1.1 Hz, 2H), 6.60 (d, J=1.0 Hz, 1H), 2.25 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.90, 160.61, 158.17, 150.75, 148.52, 147.60, 137.32, 126.26, 121.87, 105.82, 17.46. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.11H.sub.12N.sub.6S.sup.+, 261.09169; Found: 261.09174. HPLC (λ.sub.280): Purity 95.7%; t.sub.R: 5.708 min (method 1).

N—(N-(4-methylthiazol-2-yl)carbamimidoyl)nicotinimidamide (MTF-290)

(68) Synthesized following the general procedure A using 1-(4-methylthiazol-2-yl)guanidine (1.00 g, 6.41 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 384 mg, 9.61 mmol) and 3-pyridinecarbonitrile (0.667 mg, 6.41 mmol) to afford the titled compound as a yellow powder (751 mg, 45%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.39 (br. s, 1H), 9.15 (d, br. s, J=1.7 Hz, 2H), 8.77 (br. s, 1H), 8.71 (dd, J=4.7, 1.5 Hz, 1H), 8.36-8.23 (m, 1H), 7.65 (br. s, 1H), 7.52 (dd, J=7.5, 4.8 Hz, 1H), 6.59 (d, J=0.7 Hz, 1H), 2.25 (s, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.84, 160.46, 159.79, 151.75, 148.72, 147.67, 135.03, 131.09, 123.24, 105.89, 17.54. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.11H.sub.12N.sub.6S.sup.+, 261.09169; Found: 261.09171. HPLC (λ.sub.280): Purity 97.1%; t.sub.R: 5.508 min (method 1).

N—(N-(4-methylthiazol-2-yl)carbamimidoyl)isonicotinimidamide (MTF-291)

(69) Synthesized following the general procedure A using 1-(4-methylthiazol-2-yl)guanidine (1.00 g, 6.41 mmol), sodium hydride (60% dispersion in mineral oil, 384 mg, 9.61 mmol) and 4-pyridinecarbonitrile (0.667 mg, 6.41 mmol) to afford the titled compound as a yellow powder (985 mg, 59%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.37 (br. s, 1H), 9.15 (br. s, 1H), 8.80 (br. s, 1H), 8.74 (dd, J=4.5, 1.6 Hz, 2H), 7.89 (dd, J=4.5, 1.6 Hz, 2H), 7.68 (br. s, 1H), 6.60 (d, J=0.9 Hz, 1H), 2.25 (d, J=0.8 Hz, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.77, 160.43, 159.58, 150.08, 147.74, 142.81, 121.45, 106.08, 17.54. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.11H.sub.12N.sub.6S.sup.+, 261.09169; Found: 261.09174. HPLC (λ.sub.280): Purity 99.5%; t.sub.R: 4.525 min (method 1).

4-methoxy-N—(N-(4-methylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-292)

(70) Synthesized following the general procedure A using 1-(4-methylthiazol-2-yl)guanidine (1.00 g, 6.41 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 384 mg, 9.61 mmol) and 4-methoxybenzonitrile (0.853 mg, 6.41 mmol) to afford the titled compound as a beige powder (167 mg, 9%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.40 (br. s, 1H), 9.06 (br. s, 1H), 8.50 (br. s, 1H), 7.98 (d, J=8.9 Hz, 2H), 7.49 (br. s, 1H), 7.02 (d, J=8.9 Hz, 2H), 6.55 (d, J=0.8 Hz, 1H), 3.83 (s, 3H), 2.24 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.97, 161.71, 160.99, 160.62, 147.51, 129.13, 127.43, 113.43, 105.33, 55.34, 17.48. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.13H.sub.15N.sub.5OS.sup.+, 290.10701; Found: 290.10709. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 5.308 min (method 1).

2-bromo-N—(N-(4,5-dimethylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-295)

(71) Synthesized following the general procedure A using 1-(4,5-dimethylthiazol-2-yl)guanidine (1.00 g, 5.88 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 353 mg, 8.82 mmol) and 2-bromobenzonitrile (1.07 g, 5.88 mmol) to afford the titled compound as a brown powder (746 mg, 36%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.28 (br. s, 1H), 9.01 (br. s, 1H), 8.58 (br. s, 1H), 7.70-7.30 (br. s, 1H), 7.67 (d, J=7.9 Hz, 1H), 7.44 (dd, J=8.1, 5.2 Hz, 2H), 7.40-7.33 (m, 1H), 2.21 (s, 3H), 2.14 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.26, 163.14, 160.22, 142.62, 138.85, 132.48, 130.54, 129.44, 127.36, 119.64, 116.98, 14.58, 10.71. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.13H.sub.14BrN.sub.5S.sup.+, 352.02261; Found: 352.02289. HPLC (λ.sub.280): Purity 97.8%; t.sub.R: 5.717 min (method 1).

2-bromo-N—(N-(4,5-dimethylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-296)

(72) Synthesized following the general procedure A using 1-(4,5-dimethylthiazol-2-yl)guanidine (1.00 g, 5.88 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 353 mg, 8.82 mmol) and 3-bromobenzonitrile (1.07 g, 5.88 mmol) to afford the titled compound as a brown powder brown powder (746 mg, 36%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.45 (br. s, 1H), 9.01 (br. s, 1H), 8.70 (br. s, 1H), 8.20 (t, J=1.7 Hz, 1H), 8.06-7.28 (br. s, 1H), 7.97 (d, J=8.0 Hz, 1H), 7.74 (ddd, J=7.9, 1.9, 0.8 Hz, 1H), 7.46 (t, J=7.9 Hz, 1H), 2.21 (s, 3H), 2.15 (s, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 169.14, 160.12, 159.63, 142.74, 137.65, 133.81, 130.41, 130.18, 126.29, 121.61, 117.13, 14.63, 10.76. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.13H.sub.15BrN.sub.5S.sup.+, 352.02261; Found: 352.02377. HPLC (λ.sub.280): Purity 97.3%; t.sub.R: 5.767 min (method 1).

N—(N-(4,5-dimethylthiazol-2-yl)carbamimidoyl)picolinimidamide (MTF-297)

(73) Synthesized following the general procedure A using 1-(4,5-dimethylthiazol-2-yl)guanidine (1.00 g, 5.88 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 353 mg, 8.82 mmol) and 2-pyridinecarbonitrile (0.566 mL, 5.88 mmol) to afford the titled compound as a yellow powder (726 mg, 45%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.19 (br. s, 1H), 9.09 (br. s, 1H), 8.68 (d, br. s. J=4.1 Hz, 2H), 8.33 (d, J=7.9 Hz, 1H), 7.99 (td, J=7.7, 1.3 Hz, 1H), 7.60 (dd, br. s, J=6.5, 5.0 Hz, 2H), 2.21 (s, 3H), 2.15 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.29, 160.32, 158.01, 150.80, 148.50, 142.71, 137.28, 126.19, 121.80, 117.16, 14.56, 10.69. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.12H.sub.14N.sub.6S.sup.+, 275.10734; Found: 275.10742. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 5.475 min (method 1).

N—(N-(4,5-dimethylthiazol-2-yl)carbamimidoyl)nicotinimidamide (MTF-298)

(74) Synthesized following the general procedure A using 1-(4,5-dimethylthiazol-2-yl)guanidine (1.00 g, 5.88 mmol), sodium hydride (60% dispersion in mineral oil, 353 mg, 8.82 mmol) and 3-pyridinecarbonitrile (612 mg, 5.88 mmol) to afford the titled compound as a yellow powder (742 mg, 46%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.43 (br. s, 1H), 9.04 (br. s, 1H), 8.67 (br. s, 1H), 8.20 (t, J=1.6 Hz, 1H), 7.97 (d, J=8.0 Hz, 1H), 7.80-7.70 (m, 1H), 7.88-7.29 (br. s, 1H), 7.46 (t, J=7.9 Hz, 1H), 2.21 (s, 3H), 2.15 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.13, 160.11, 159.55, 151.63, 148.60, 142.72, 134.89, 131.06, 123.17, 117.16, 14.57, 10.69. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.12H.sub.14N.sub.6S.sup.+, 275.10734; Found: 275.10736. HPLC (λ.sub.280): Purity 97.0%; t.sub.R: 5.458 min (method 1).

N—(N-(4,5-dimethylthiazol-2-yl)carbamimidoyl)isonicotinimidamide (MTF-299)

(75) Synthesized following the general procedure A using 1-(4,5-dimethylthiazol-2-yl)guanidine (1.00 g, 5.88 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 353 mg, 8.82 mmol) and 4-pyridinecarbonitrile (612 mg, 5.88 mmol) to afford the titled compound as a yellow powder (548 mg, 34%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.40 (br. s, 1H), 9.09 (br. s, 1H), 8.73 (d, br. s., J=5.7 Hz, 3H), 7.88 (d, J=5.5 Hz, 2H), 7.61 (br. s, 1H), 2.21 (s, 3H), 2.15 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.05, 160.06, 159.33, 149.98, 142.78, 121.31, 117.38, 14.55, 10.68. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.12H.sub.14N.sub.6S.sup.+, 275.10734; Found: 275.10739. HPLC (λ.sub.280): Purity 99.5%; t.sub.R: 5.108 min (method 1).

2-chloro-N—(N-(4,5-dimethylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-300)

(76) Synthesized following the general procedure A using 1-(4,5-dimethylthiazol-2-yl)guanidine (1.00 g, 5.88 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 353 mg, 8.82 mmol) and 2-chlorobenzonitrile (809 mg, 5.88 mmol) to afford the titled compound as a yellow powder (109 mg, 6%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.30 (br. s, 1H), 9.01 (br. s, 1H), 8.59 (br. s, 1H), 7.46 (m, 5H), 2.21 (s, 3H), 2.14 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.26, 162.01, 160.22, 142.63, 136.82, 130.47, 130.28, 129.56, 129.39, 126.88, 117.00, 14.58, 10.71. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.13H.sub.14CN.sub.5S.sup.+, 308.07312; Found: 308.07318. HPLC (λ.sub.280): Purity 95.4%; t.sub.R: 5.425 min (method 1).

3-chloro-N—(N-(4,5-dimethylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-301)

(77) Synthesized following the general procedure A using 1-(4,5-dimethylthiazol-2-yl)guanidine (1.00 g, 5.88 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 353 mg, 8.82 mmol) and 3-chlorobenzonitrile (809 mg, 5.88 mmol) to afford the titled compound as a yellow powder (416 mg, 23%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.44 (br. s, 1H), 9.04 (br. s, 1H), 8.68 (br. s, 1H), 8.08-8.03 (m, 1H), 7.93 (d, J=7.9 Hz, 1H), 7.61 (ddd, J=8.0, 2.1, 0.9 Hz, 1H), 7.78-7.39 (br. s, 1H), 7.52 (t, J=7.9 Hz, 1H), 2.21 (s, 3H), 2.15 (s, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 169.15, 160.14, 159.71, 142.73, 137.49, 133.13, 130.91, 130.15, 127.31, 125.93, 117.14, 14.62, 10.75. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.13H.sub.14CN.sub.5S.sup.+, 308.07312; Found: 308.07321. HPLC (λ.sub.280): Purity 95.2%; t.sub.R: 6.075 min (method 1).

4-chloro-N—(N-(4,5-dimethylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-302)

(78) Synthesized following the general procedure A using 1-(4,5-dimethylthiazol-2-yl)guanidine (1.00 g, 5.88 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 353 mg, 8.82 mmol) 4-chlorobenzonitrile (809 mg, 5.88 mmol to afford the titled compound as a yellow powder (90 mg, 5%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.44 (br. s, 1H), 9.04 (br. s, 1H), 8.64 (br. s, 1H), 8.01 (d, J=8.6 Hz, 2H), 7.57 (d, br. s, J=8.6 Hz, 3H), 2.22 (s, 3H), 2.15 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.15, 160.16, 160.11, 142.66, 135.93, 134.23, 129.19 (2C), 128.22 (2C), 117.02, 14.57, 10.70. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.13H.sub.14ClN.sub.5S.sup.+, 308.07312; Found: 308.07315. HPLC (λ.sub.280): Purity 98.0%; t.sub.R: 6.267 min (method 1).

N—(N-(4,5-dimethylthiazol-2-yl)carbamimidoyl)benzimidamide (MTF-303)

(79) Synthesized following the general procedure A using 1-(4,5-dimethylthiazol-2-yl)guanidine (1.00 g, 5.88 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 353 mg, 8.82 mmol) and benzonitrile (0.605 mL, 5.88 mmol) to afford the titled compound as a yellow powder (113 mg, 7%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.45 (s, 1H), 8.94 (s, 1H), 8.61 (s, 1H), 7.98 (dd, J=7.9, 1.7 Hz, 2H), 7.84-7.31 (m, 4H), 2.21 (d, J=0.6 Hz, 3H), 2.15 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.26, 161.31, 160.33, 142.65, 135.47, 131.06, 128.12, 127.30, 116.88, 14.58, 10.70. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.13H.sub.15N.sub.5S.sup.+, 274.11209; Found: 274.11212. HPLC (λ.sub.280): Purity 97.5%; t.sub.R: 5.408 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2,2,2-trichloroacetimidamide (MTF-305)

(80) A solution of 1-(benzo[d]thiazol-2-yl)guanidine (500 mg, 2.6 mmol) and trichloroacetonitrile (260 μL, 2.6 mmol) in technical grade ethanol (5 mL) was stirred at r.t. under argon atmosphere for 22 h. The precipitate that formed was filtered, washed with little amount of cold ethanol, then with a very little amount of diethyl ether, dried quickly at air (the compound oxidized over time at air) and stored under argon. Yellow solid (100 mg, 11%). TLC: R.sub.f (CHCl.sub.3/MeOH, 95/5, v/v)=0.90. .sup.1H NMR (400 MHz, Acetone-d6): δ 10.71 (s, 1H), 9.84 (s, 1H), 8.39 (s, 1H), 7.80 (dd, J=7.9, 1.3 Hz, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.66 (s, 1H), 7.38 (td, J=8.2, 7.8, 1.3 Hz, 1H), 7.25 (td, J=7.6, 1.2 Hz, 1H). .sup.13C NMR (101 MHz, Acetone-d6): δ 206.12, 126.63, 124.28, 121.93, 121.33. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.10H.sub.9Cl.sub.3N.sub.5S.sup.+, 335.96388; Found: 335.96420. HPLC (λ.sub.254): Purity 99.7%; t.sub.R: 7.983 min (method 1).

N2-(2-(methylthio)phenyl)-6-(trichloromethyl)-1,3,5-triazine-2,4-diamine (MTF-316)

(81) To suspension of N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(trichloromethyl)-1,3,5-triazine-2,4-diamine) CRO15 (150 mg, 0.225 mmol) in methanol (10 mL) was added mercaptoethanol (350 μL, 4.5 mmol) and the mixture stirred at r.t. After 10 min stirring, total solubility was reached. TLC and LCMS showed total conversion into the reduced thiophenol. After 20 h stirring at r.t., K.sub.2CO.sub.3 (62.1 mg, 0.45 mmol) was added and the mixture sonicated until total solubilisation. Then MeI (28 μL, 0.45 mmol) was added and the solution stirred for 5 h at r.t. (reaction time not optimized). TLC and LCMS showed total conversion into two new compounds (ratio 2/1). The mixture was extracted with EtOAc twice and the combined organic layers were dried with Na.sub.2SO.sub.4 and evaporated under reduced pressure. Purification by silicagel flash chromatography (cyclohexane/EtOAc, 10/0 to 7/3, v/v) afforded the desired compound as white crystals (27.0 mg, 34% over 2 steps). .sup.1H NMR (200 MHz, Acetone-d6): S 8.04 (s, 1H), 7.73 (d, J=7.9 Hz, 1H), 7.11 (dd, J=7.7, 1.7 Hz, 1H), 7.01-6.57 (m, 4H), 2.05 (s, 3H). .sup.13C NMR (50 MHz, Acetone-d6): δ 174.04, 168.91, 166.25, 138.04, 131.38, 130.32, 128.05, 125.84, 124.21, 97.43. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.11H.sub.11Cl.sub.3N.sub.5S.sup.+, 349.97953; Found: 349.97983. HPLC (λ.sub.254): Purity 97.6%; t.sub.R: 10.483 min (method 2).

6-(dichloromethyl)-N2-(2-(methylthio)phenyl)-1,3,5-triazine-2,4-diamine (MTF-317)

(82) To suspension of N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(trichloromethyl)-1,3,5-triazine-2,4-diamine) CRO15 (150 mg, 0.225 mmol) in methanol (10 mL) was added mercaptoethanol (350 μL, 4.5 mmol) and the mixture stirred at r.t. After 10 min stirring, total solubility was reached. TLC and LCMS showed total conversion into the reduced thiophenol. After 20 h stirring at r.t., K.sub.2CO.sub.3 (62.1 mg, 0.45 mmol) was added and the mixture sonicated until total solubilisation. Then MeI (28 μL, 0.45 mmol) was added and the solution stirred for 5 h at r.t. (reaction time not optimized). TLC and LCMS showed total conversion into two new compounds (ratio 2/1). The mixture was extracted with EtOAc twice and the combined organic layers were dried with Na.sub.2SO.sub.4 and evaporated under reduced pressure. Purification by silicagel flash chromatography (cyclohexane/EtOAc, 10/0 to 7/3, v/v) afforded the titled compound as white crystals (12.7 mg, 18% over 2 steps). .sup.1H NMR (200 MHz, Acetone-d6): δ 8.27 (s, 1H), 8.19-8.07 (m, 1H), 7.49 (dd, J=7.6, 1.7 Hz, 1H), 7.32-7.23 (m, 1H), 7.16 (td, J=7.5, 1.5 Hz, 1H), 6.90 (s, 2H), 6.54 (s, 1H), 2.43 (s, 3H). .sup.13C NMR (50 MHz, Acetone-d6): δ 173.85, 168.61, 166.05, 138.23, 131.54, 130.28, 128.11, 125.67, 124.06, 71.59, 17.73. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.11H.sub.12Cl.sub.2N.sub.5S.sup.+, 316.01850; Found: 316.01892. HPLC (λ.sub.254): Purity 97.3%; t.sub.R: 10.658 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(3-methoxyphenyl)-1,3,5-triazine-2,4-diamine (MTF-318)

(83) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-methoxybenzimidamide (325 mg, 1 mmol) to afford the titled compound as a white powder (272 mg, 84%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.25 (s, 2H), 7.82 (dd, J=8.1, 5.1 Hz, 4H), 7.61 (dd, J=7.7, 1.4 Hz, 2H), 7.44-7.33 (m, 4H), 7.27 (td, J=7.5, 1.4 Hz, 2H), 7.22-6.97 (m, 8H), 3.78 (s, 6H). .sup.13C NMR (50 MHz, DMSO-d6): δ 169.95, 167.28, 165.48, 159.19, 138.15, 136.69, 133.74, 129.31, 128.36, 127.63, 126.62, 126.32, 120.25, 117.26, 112.78, 55.10. HRMS-ESI (m/z): [M+H]+ calc. for C.sub.15H.sub.12BrN.sub.5S.sup.+, 374.00696; Found: 374.00797. HPLC (km): Purity 100.0%; t.sub.R: 11.458 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(3-ethoxyphenyl)-1,3,5-triazine-2,4-diamine) (MTF-319)

(84) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-ethoxybenzimidamide (339 mg, 1 mmol) to afford the titled compound as a white powder (291 mg, 86%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.24 (s, 2H), 7.83 (d, J=8.8 Hz, 4H), 7.62 (dd, J=7.6, 1.1 Hz, 2H), 7.37 (t, J=7.8 Hz, 4H), 7.32-7.23 (m, 2H), 7.22-7.15 (m, 2H), 7.14-6.98 (m, 6H), 4.04 (q, J=6.9 Hz, 4H), 1.33 (t, J=6.9 Hz, 6H). .sup.13C NMR (50 MHz, DMSO-d6): δ 169.98, 167.28, 165.48, 158.46, 138.12, 136.73, 133.68, 129.30, 128.39, 127.64, 126.61, 126.29, 120.13, 117.81, 113.27, 63.06, 14.68. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.34H.sub.33N.sub.10O.sub.2S.sub.2.sup.+, 677.22239; Found: 677.22253. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 13.058 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(3-fluorophenyl)-1,3,5-triazine-2,4-diamine (MTF-320)

(85) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-fluorobenzimidamide (313 mg, 1 mmol) to afford the titled compound as a white powder (237 mg, 76%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.32 (s, 2H), 8.08 (d, J=7.6 Hz, 2H), 7.93 (d, J=9.7 Hz, 2H), 7.62 (d, J=7.7 Hz, 2H), 7.57-7.45 (m, 2H), 7.45-7.06 (m, 12H). .sup.19F NMR (188 MHz, DMSO-d6): δ −113.29. .sup.13C NMR (50 MHz, DMSO-d6): δ 168.98, 167.26, 165.51, 164.58, 159.75, 139.31 (d, J=7.7 Hz), 136.52, 133.76, 130.39 (d, J=7.8 Hz), 128.22, 127.66, 126.62 (d, J=16.1 Hz), 123.79, 118.23 (d, J=20.5 Hz), 114.11 (d, J=22.6 Hz). HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.30H.sub.23F.sub.2N.sub.10S.sub.2.sup.+, 625.15112; Found: 625.15125. HPLC (λ.sub.280): Purity 97.5%; t.sub.R: 12.817 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(pyridin-2-yl)-1,3,5-triazine-2,4-diamine) (MTF-321)

(86) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)picolinimidamide (296 mg, 1 mmol) to afford the titled compound as a white powder (266 mg, 90%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.39 (s, 1H), 8.74-8.64 (m, 1H), 8.20 (d, J=7.8 Hz, 1H), 7.93 (td, J=7.7, 1.8 Hz, 1H), 7.61 (dd, J=7.6, 1.5 Hz, 1H), 7.51 (ddd, J=7.5, 4.7, 1.2 Hz, 1H), 7.39 (dd, J=7.7, 1.4 Hz, 1H), 7.35-7.08 (m, 4H). .sup.13C NMR (50 MHz, DMSO-d6): δ 170.30, 167.53, 165.79, 154.32, 149.29, 136.74, 136.57, 133.61, 128.25, 127.64, 126.88, 126.47, 125.48, 123.33. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.28H.sub.23N.sub.12S.sub.2.sup.+, 591.16048; Found: 591.16048. HPLC (λ.sub.280): Purity 95.3%; t.sub.R: 6.483 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(3-chlorophenyl)-1,3,5-triazine-2,4-diamine) (MTF-322)

(87) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-chlorobenzimidamide (329 mg, 1 mmol) to afford the titled compound as a white powder (260 mg, 79%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.33 (s, 2H), 8.24 (s, 2H), 8.16 (d, J=7.6 Hz, 2H), 7.58 (ddd, J=20.7, 9.4, 4.5 Hz, 6H), 7.44-7.08 (m, 10H). .sup.13C NMR (50 MHz, DMSO-d6): δ 168.82, 167.23, 165.50, 138.80, 136.49, 133.81, 133.18, 131.14, 130.31, 128.22, 127.66, 127.45, 126.79, 126.51, 126.27. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.30H.sub.23Cl.sub.2N.sub.10S.sub.2.sup.+, 657.09201; Found: 657.09222. HPLC (λ.sub.280): Purity 96.9%; t.sub.R: 12.867 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(3-bromophenyl)-1,3,5-triazine-2,4-diamine) (MTF-323)

(88) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-bromobenzimidamide (374 mg, 1 mmol) to afford the titled compound as a white powder (339 mg, 91%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.34 (s, 2H), 8.40 (s, 2H), 8.20 (d, J=7.8 Hz, 2H), 7.74 (ddd, J=8.0, 2.0, 1.0 Hz, 2H), 7.62 (dd, J=7.5, 1.6 Hz, 2H), 7.46 (t, J=7.9 Hz, 2H), 7.40-7.13 (m, 10H). .sup.13C NMR (50 MHz, DMSO-d6): δ 168.73, 167.22, 165.49, 138.97, 136.48, 134.02, 133.83, 130.60, 130.43, 128.22, 127.66, 126.81, 126.63, 126.55, 121.69. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.30H.sub.23Br.sub.2N.sub.10S.sub.2.sup.+, 744.99098; Found: 744.99098. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 17.600 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(4-methoxyphenyl)-1,3,5-triazine-2,4-diamine) (MTF-324)

(89) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-methoxybenzimidamide (325 mg, 1 mmol) to afford the titled compound as a white powder (263 mg, 81%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.13 (s, 2H), 8.20 (d, J=8.8 Hz, 4H), 7.62 (dd, J=7.8, 1.2 Hz, 2H), 7.40 (d, J=7.2 Hz, 2H), 7.32-7.22 (m, 2H), 7.22-7.12 (m, 2H), 7.01 (d, J=8.8 Hz, 8H), 3.82 (s, 6H). .sup.13C NMR (50 MHz, DMSO-d6): δ 169.77, 167.19, 165.36, 161.99, 136.91, 133.33, 129.62 (2C), 128.90, 128.61, 127.72, 126.36, 126.10, 113.57 (2C), 55.30. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.32H.sub.29N.sub.10O.sub.2S.sub.2.sup.+, 649.19109; Found: 649.19116. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 10.800 min (method 2).

3,3′-(((disulfanediylbis(2,1-phenylene))bis(azanediyl))bis(6-amino-1,3,5-triazine-4,2-diyl))dibenzonitrile (MTF-325)

(90) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-cyanobenzimidamide (320 mg, 1 mmol) to afford the titled compound as a white powder (291 mg, 91%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.37 (s, 2H), 8.49 (d, J=10.9 Hz, 4H), 8.02 (d, J=7.7 Hz, 2H), 7.72 (t, J=7.8 Hz, 2H), 7.63 (dd, J=7.6, 1.4 Hz, 2H), 7.42-7.15 (m, 10H). .sup.13C NMR (50 MHz, DMSO-d6): δ 168.32, 167.24, 165.49, 137.79, 136.48, 134.74, 133.71, 132.16, 131.22, 129.88, 128.38, 127.79, 126.80, 126.59, 118.56, 111.54. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.32H.sub.23N.sub.12S.sub.2.sup.+, 639.16046; Found: 639.16064. HPLC (λ.sub.280): Purity 96.1%; t.sub.R: 11.858 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-phenyl-1,3,5-triazine-2,4-diamine) (MTF-326)

(91) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)benzimidamide (295 mg, 1 mmol) to afford the titled compound as a white powder (218 mg, 74%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.23 (s, 2H), 8.24 (d, J=6.5 Hz, 4H), 7.62 (d, J=7.3 Hz, 2H), 7.57-7.34 (m, 8H), 7.33-7.01 (m, 8H). .sup.13C NMR (50 MHz, DMSO-d6): δ 170.16, 167.29, 165.51, 136.71, 136.61, 133.59, 131.41, 128.37, 128.24 (2C), 127.82 (2C), 127.66, 126.61, 126.31. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.30H.sub.25N.sub.10S.sub.2.sup.+, 589.16996; Found: 589.16992. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 11.792 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(4-chlorophenyl)-1,3,5-triazine-2,4-diamine) (MTF-327)

(92) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-chlorobenzimidamide (329 mg, 1 mmol) to afford the titled compound as a white powder (283 mg, 86%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.27 (s, 2H), 8.22 (d, J=8.5 Hz, 4H), 7.66-7.50 (m, 6H), 7.38 (dd, J=7.6, 1.0 Hz, 2H), 7.33-7.05 (m, 8H). .sup.13C NMR (50 MHz, DMSO-d6): δ 169.18, 167.22, 165.46, 136.62, 136.20, 135.47, 133.52, 129.53 (2C), 128.42 (3C), 127.73, 126.65, 126.37. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.30H.sub.23O.sub.2N.sub.10S.sub.2.sup.+, 657.09201; Found: 657.09210. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 15.633 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(4-iodophenyl)-1,3,5-triazine-2,4-diamine) (MTF-328)

(93) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-iodobenzimidamide (421 mg, 1 mmol) to afford the titled compound as a white powder (387 mg, 92%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.26 (s, 2H), 8.00 (d, J=8.4 Hz, 4H), 7.87 (d, J=8.4 Hz, 4H), 7.61 (d, J=7.6 Hz, 2H), 7.39 (d, J=7.4 Hz, 2H), 7.33-6.99 (m, 8H). .sup.13C NMR (50 MHz, DMSO-d6): δ 169.58, 167.21, 165.45, 137.24 (2C), 136.63, 136.19, 133.49, 129.70 (2C), 128.47, 127.73, 126.61, 126.34, 99.15. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.30H.sub.23I.sub.2N.sub.10S.sub.2.sup.+, 840.96324; Found: 840.96289. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 17.833 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(pyridin-4-yl)-1,3,5-triazine-2,4-diamine) (MTF-329)

(94) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)isonicotinimidamide (296 mg, 1 mmol) to afford the titled compound as a white powder (266 mg, 90%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.41 (s, 2H), 8.73 (dd, J=4.5, 1.5 Hz, 4H), 8.05 (d, J=5.8 Hz, 4H), 7.62 (dd, J=7.4, 1.2 Hz, 2H), 7.43-7.08 (m, 10H). .sup.13C NMR (50 MHz, DMSO-d6): δ 168.77, 167.33, 165.59, 150.23 (2C), 144.04, 136.41, 133.74, 128.33, 127.75, 126.86, 126.61, 121.55 (2C). HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.28H.sub.23N.sub.12S.sub.2.sup.+, 591.16046; Found: 591.16089. HPLC (λ.sub.280): Purity 99.2%; t.sub.R: 7.742 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(pyridin-3-yl)-1,3,5-triazine-2,4-diamine) (MTF-330)

(95) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)nicotinimidamide (296 mg, 1 mmol) to afford the titled compound as a white powder (266 mg, 90%). (277 mg, 94%). .sup.1H NMR (200 MHz, DMSO-d6): δ 9.35 (s, 4H), 8.71 (dd, J=4.8, 1.7 Hz, 2H), 8.47 (d, J=8.1 Hz, 2H), 7.62 (dd, J=7.6, 1.2 Hz, 2H), 7.52 (dd, J=7.8, 4.6 Hz, 2H), 7.38 (dd, J=7.7, 1.4 Hz, 2H), 7.33-7.06 (m, 8H.sup.13C NMR (50 MHz, DMSO-d6): δ 168.81, 167.12, 165.37, 151.99, 149.09, 136.50, 135.09, 133.66, 132.00, 128.31, 127.69, 126.77, 126.49, 123.51 HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.28H.sub.23N.sub.12S.sub.2.sup.+, 591.16046; Found: 591.16052. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 7.700 min (method 2).

2-((4-amino-6-(3-bromophenyl)-1,3,5-triazin-2-yl)amino)phenol (MTF-331)

(96) Synthesized following the general procedure A using 1-(benzo[d]oxazol-2-yl)guanidine (1.00 g, 5.68 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 341 mg, 8.52 mmol) and 3-bromobenzonitrile (1.034 g, 5.68 mmol) to afford the titled compound as a brown powder (1.46 g, 72%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.97 (s, 1H), 8.44 (s, 1H), 8.36 (s, 1H), 8.26 (d, J=7.5 Hz, 1H), 7.90 (d, J=7.7 Hz, 1H), 7.76 (d, J=7.7 Hz, 1H), 7.48 (t, J=7.8 Hz, 1H), 7.29 (s, 2H), 6.99-6.92 (m, 1H), 6.89 (d, J=7.4 Hz, 1H), 6.82 (t, J=7.1 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 168.84, 167.06, 164.48, 148.30, 138.75, 133.26, 131.22, 130.38, 127.46, 126.84, 126.29, 124.12, 122.65, 118.99, 115.77. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.13BrN.sub.5O.sup.+, 358.02980 Found: 358.03094. HPLC (λ.sub.280): Purity 97.1%; t.sub.R: 9.808 min (method 1).

2-((4-amino-6-(3-chlorophenyl)-1,3,5-triazin-2-yl)amino)phenol (MTF-332)

(97) Synthesized following the general procedure A using 1-(benzo[d]oxazol-2-yl)guanidine (1.00 g, 5.68 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 341 mg, 8.52 mmol) and 3-chlorobenzonitrile (781 mg, 5.68 mmol) to afford the titled compound as a brown powder (1.45 g, 82%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.03 (s, 1H), 8.36 (s, 1H), 8.29 (s, 1H), 8.23 (d, J=7.4 Hz, 1H), 7.92 (d, J=7.5 Hz, 1H), 7.62 (d, J=7.5 Hz, 1H), 7.55 (t, J=7.8 Hz, 1H), 7.29 (s, 2H), 6.99-6.92 (m, 1H), 6.89 (d, J=7.3 Hz, 1H), 6.82 (t, J=7.1 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 168.74, 167.02, 164.48, 148.21, 138.90, 134.11, 130.67, 130.40, 126.66 (2C), 124.17, 122.79, 121.73, 119.10, 115.78. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.13ClN.sub.5O.sup.+, 314.08031; Found: 314.08066. HPLC (λ.sub.280): Purity 97.3%; t.sub.R: 9.625 min (method 1).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-benzyl-1,3,5-triazine-2,4-diamine (MTF-333)

(98) In a microwave tube, 1-(benzo[d]thiazol-2-yl)guanidine (100 mg, 0.52 mmol) was solubilized in NMP (2 mL) under argon atmosphere. The tube was subsequently cooled down to 0° C. before NaH (60% suspension in oil, 23 mg, 0.57 mmol) was added. After the gas evolution stopped, the tube was sealed and the mixture was warmed up to 110° C. under microwave irradiation for 15 min. The resulting slurry was taken in Et.sub.2O and filtered. The precipitate was then purified by silicagel flash chromatography (dichloromethane/MeOH, 10/0 to 9/1) to give the desired product as a white powder (50 mg, 31%). TLC: R.sub.f (dichloromethane/MeOH, 9/1, v/v)=0.83. .sup.1H NMR (400 MHz, DMSO-d6): δ 9.05 (s, 1H), 7.54 (dd, J=7.8, 0.9 Hz, 1H), 7.35-7.17 (m, 7H), 7.14 (t, J=7.7 Hz, 1H), 6.95 (d, J=16.0 Hz, 2H), 3.71 (s, 2H). .sup.13C NMR (101 MHz, DMSO-d6): δ 176.6, 166.9, 165.3, 151.5, 139.2, 137.9, 136.6, 129.1, 128.2, 128.0, 127.6, 126.3, 124.9, 30.4. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.32H.sub.29N.sub.10S.sub.2.sup.+617.20126, found 617.20154. HPLC (λ.sub.254): Purity 96.2%; t.sub.R: 10.742 min (method 2).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-methoxybenzimidamide (MTF-342)

(99) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 3-methoxybenzonitrile (0.635 mL, 5.20 mmol) to afford the titled compound as a white powder (914 mg, 54%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.26 (s, 1H), 9.33 (s, 1H), 8.82 (s, 1H), 8.05 (s, 1H), 7.80 (d, J=7.6 Hz, 1H), 7.73-7.52 (m, 3H), 7.48-7.29 (m, 2H), 7.17 (dd, J=14.6, 7.6 Hz, 2H), 3.83 (s, 3H). .sup.13C NMR spectrum could not be properly recorded as this compound rearranges and dimerizes into compound MTF-318 during the time of the analysis. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.16N.sub.5OS.sup.+, 326.10701; Found: 326.10706. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 6.558 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-(trifluoromethyl)benzimidamide (MTF-343)

(100) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 3-(trifluoromethyl)benzonitrile (890 mg, 5.20 mmol) to afford the titled compound as a white powder (435 mg, 23%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.33 (br. s, 1H), 9.36 (br. s, 1H), 8.93 (br. s, 1H), 8.39 (s, 1H), 8.31 (d, J=7.9 Hz, 1H), 8.16 (br. s, 1H), 7.95 (d, J=7.9 Hz, 1H), 7.86-7.72 (m, 2H), 7.67 (d, J=8.0 Hz, 1H), 7.35 (t, J=7.6 Hz, 1H), 7.20 (t, J=7.5 Hz, 1H). .sup.19F NMR (376 MHz, DMSO-d6): δ −61.04. .sup.13C NMR spectrum could not be properly recorded as this compound rearranges and dimerizes during the time of the analysis. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.13F.sub.3N.sub.5S.sup.+, 364.08383; Found: 364.08408. HPLC (λ.sub.280): Purity 97.9%; t.sub.R: 6.533 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-ethoxybenzimidamide (MTF-344)

(101) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 3-ethoxybenzonitrile (765 mg, 5.20 mmol) to afford the titled compound as a white powder (830 mg, 47%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.23 (br. s, 1H), 9.30 (br. s, 1H), 8.78 (br. s, 1H), 8.03 (br. s, 1H), 7.80 (dd, J=7.8, 0.8 Hz, 1H), 7.65 (dd, J=8.0, 0.6 Hz, 1H), 7.62-7.53 (m, 2H), 7.46-7.29 (m, 2H), 7.24-7.07 (m, 2H), 4.09 (q, J=6.9 Hz, 2H), 1.36 (t, J=6.9 Hz, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.24, 162.07, 161.82, 158.40, 151.49, 136.56, 131.16, 129.36, 125.63, 122.78, 121.13, 119.68, 119.65, 117.34, 113.64, 63.24, 14.63. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.17H.sub.18N.sub.5OS.sup.+, 340.12266; Found: 340.12296. HPLC (λ.sub.280): Purity 100.0%; t.sub.R: 6.733 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)pyrazine-2-carboximidamide (MTF-345)

(102) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and pyrazinecarbonitrile (0.465 mL, 5.20 mmol) to afford the titled compound as a yellow powder (959 mg, 62%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.13 (br. s, 1H), 9.50 (s, 1H), 9.44 (br. s, 1H), 8.99 (br. s, 1H), 8.88 (d, J=2.5 Hz, 1H), 8.79 (dd, J=2.5, 1.4 Hz, 1H), 8.26 (br. s, 1H), 7.83 (d, J=7.7 Hz, 1H), 7.69 (d, J=7.9 Hz, 1H), 7.44-7.30 (m, 1H), 7.29-7.15 (m, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.18, 161.92, 157.68, 151.39, 147.21, 145.85, 143.84, 143.44, 131.22, 125.73, 123.01, 121.22, 119.90. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.13H.sub.12N.sub.7S.sup.+, 298.08694; Found: 298.08707. HPLC (λ.sub.280): Purity 95.7%; t.sub.R: 5.508 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-fluorobenzimidamide (MTF-346)

(103) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 3-fluorobenzonitrile (0.56 mL, 5.20 mmol) to afford the titled compound as a white powder (895 mg, 55%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.26 (s, 1H), 9.34 (s, 1H), 8.89 (s, 1H), 8.09 (s, 1H), 7.95-7.76 (m, 3H), 7.70-7.51 (m, 2H), 7.50-7.28 (m, 2H), 7.19 (td, J=7.6, 1.2 Hz, 1H). .sup.19F NMR (376 MHz, DMSO-d6): δ −112.99. .sup.13C NMR spectrum could not be properly recorded as this compound rearranges and dimerizes into compound MTF-320 during the time of the analysis. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.13FN.sub.5S.sup.+, 314.08702; Found: 314.08722. HPLC (λ.sub.280): Purity 98.7%; t.sub.R: 6.442 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-cyanobenzimidamide (MTF-347)

(104) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 1,3-dicyanobenzene (667 mg, 5.20 mmol) to afford the titled compound as a white-yellowish powder (1.23 g, 74%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.27 (br. s, 1H), 9.37 (br. s, 1H), 8.97 (br. s, 1H), 8.45 (s, 1H), 8.33 (dd, J=8.0, 1.0 Hz, 1H), 8.15 (br. s, 1H), 8.06 (dd, J=7.7, 1.0 Hz, 1H), 7.89-7.62 (m, 3H), 7.35 (t, J=7.6 Hz, 1H), 7.20 (t, J=7.5 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.17, 161.83, 159.93, 151.42, 136.30, 134.69, 132.15, 131.40, 131.24, 129.67, 125.67, 122.89, 121.17, 119.81, 118.39, 111.50. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.13N.sub.6S.sup.+, 321.09169; Found: 321.09167. HPLC (λ.sub.280): Purity 96.4%; t.sub.R: 6.342 min (method 1).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(pyrazin-2-yl)-1,3,5-triazine-2,4-diamine) (MTF-348)

(105) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)pyrazine-2-carboximidamide (297 mg, 1 mmol) to afford the titled compound as a yellowish powder (279 mg, 94%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.48 (br. s, 1H), 9.33 (br. s, 1H), 8.77 (m, 2H), 7.61 (d, J=7.7 Hz, 1H), 7.38 (d, J=6.7 Hz, 2H), 7.23 (m, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 168.83, 167.37, 165.65, 149.51, 146.27, 144.58, 144.38, 136.35, 133.76, 128.18, 127.66, 127.06, 126.68. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.28H.sub.23N.sub.12S.sub.2.sup.+, 591.16046; Found: 591.16052. HPLC (λ.sub.280): Purity 99.2%; t.sub.R: 8.875 min (method 2).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-6-chloronicotinimidamide (MTF-379)

(106) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 6-chloro-3-pyridinecarbonitrile (720 mg, 5.20 mmol) to afford the titled compound as a beige powder (1.48 g, 86%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.21 (s, 1H), 9.37 (s, 1H), 9.01 (d and br. s, J=2.1 Hz, 2H), 8.38 (dd, J=8.4, 2.3 Hz, 1H), 8.12 (s, 1H), 7.80 (d, J=7.8 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H), 7.66 (d, J=8.1 Hz, 1H), 7.34 (t, J=7.6 Hz, 1H), 7.19 (t, J=7.5 Hz, 1H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.16, 161.79, 159.12, 152.70, 151.42, 149.28, 138.70, 131.29, 130.36, 125.68, 123.98, 122.91, 121.17, 119.83. HPLC (λ.sub.280): Purity 97.2%; t.sub.R: 7.033 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2-chloroisonicotinimidamide (MTF-380)

(107) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 2-chloro-4-pyridinecarbonitrile (720 mg, 5.20 mmol) to afford the titled compound as a beige powder (327 mg, 19%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.22 (br. s, 1H), 9.39 (br. s, 1H), 9.04 (br. s, 1H), 8.60 (d, J=5.1 Hz, 1H), 8.21 (br. s, 1H), 8.05 (s, 1H), 7.94 (dd, J=5.2, 1.3 Hz, 1H), 7.81 (d, J=7.3 Hz, 1H), 7.67 (d, J=7.9 Hz, 1H), 7.38-7.31 (m, 1H), 7.24-7.17 (m, 1H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.08, 161.68, 158.50, 151.36, 150.84, 150.52, 146.10, 131.31, 125.70, 122.99, 122.27, 121.20, 120.99, 119.90. HPLC (λ.sub.280): Purity 97.8%; t.sub.R: 7.108 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)thiophene-2-carboximidamide (MTF-381)

(108) Synthesized following the general procedure 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 2-thiophenecarbonitrile (0.48 mL, 5.20 mmol) to afford the titled compound as a yellowish powder (815 mg, 52%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.22 (br. s, 1H), 9.34 (br. s, 1H), 8.88 (br. s, 1H), 7.94 (dd, J=3.7, 0.9 Hz, 2H), 7.79 (d, J=6.2 Hz, 2H), 7.65 (d, J=7.9 Hz, 1H), 7.39-7.28 (m, 1H), 7.24-7.14 (m, 2H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.22, 161.71, 157.31, 151.46, 140.40, 131.89, 131.13, 128.97, 128.11, 125.65, 122.79, 121.12, 119.68. HPLC (λ.sub.280): Purity 99.2%; t.sub.R: 6.975 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3,4,5-trimethoxybenzimidamide (MTF-382)

(109) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 3,4,5-trimethoxybenzonitrile (1 g, 5.20 mmol) to afford the titled compound as a beige powder (441 mg, 22%). .sup.1H NMR (200 MHz, DMSO-d6): δ 10.22 (br. s, 1H), 9.29 (br. s, 1H), 8.77 (br. s, 1H), 8.01 (br. s, 1H), 7.80 (d, J=7.0 Hz, 1H), 7.65 (d, J=7.5 Hz, 1H), 7.39 (s, 2H), 7.38-7.27 (m, 1H), 7.19 (td, J=7.7, 1.1 Hz, 1H), 3.87 (s, 6H), 3.74 (s, 3H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.28, 161.97, 161.53, 152.51 (2C), 151.54, 140.27, 131.19, 130.33, 125.63, 122.75, 121.12, 119.66, 105.29 (2C), 60.14, 56.06 (2C). HPLC (λ.sub.280): Purity 96.1%; t.sub.R: 7.175 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)benzo[d][1,3]dioxole-5-carboximidamide (MTF-383)

(110) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and piperonylonitrile (765 mg, 5.20 mmol) to afford the titled compound as a beige powder (600 mg, 34%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.27 (s, 1H), 9.29 (s, 1H), 8.68 (s, 1H), 7.95 (s, 1H), 7.79 (d, J=7.7 Hz, 1H), 7.68-7.62 (m, 2H), 7.60 (d, J=1.6 Hz, 1H), 7.37-7.29 (m, 1H), 7.22-7.15 (m, 1H), 7.04 (d, J=8.2 Hz, 1H), 6.13 (s, 2H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.25, 161.95, 161.27, 151.52, 150.06, 147.38, 131.13, 128.99, 125.62, 122.74, 122.56, 121.11, 119.65, 107.85, 107.61, 101.80. HPLC (λ.sub.280): Purity 96.0%; t.sub.R: 7.133 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2-naphthimidamide (MTF-384)

(111) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and naphthalene-2-carbonitrile (796 mg, 5.20 mmol) to afford the titled compound as a beige powder (1.04 g, 58%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.38 (br. s, 1H), 9.42 (br. s, 1H), 8.99 (br. s, 1H), 8.64 (s, 1H), 8.16 (br. s and dd, J=8.6, 1.4 Hz, 2H), 8.08-7.96 (m, 3H), 7.81 (d, J=7.7 Hz, 1H), 7.67 (d, J=7.9 Hz, 1H), 7.66-7.57 (m, 2H), 7.40-7.31 (m, 1H), 7.25-7.15 (m, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.34, 162.16 (2C), 151.53, 134.30, 132.66, 132.15, 131.22, 128.83, 127.84, 127.75 (2C), 127.66, 126.80, 125.65, 124.55, 122.81, 121.14, 119.73. HPLC (λ.sub.280): Purity 95.7%; t.sub.R: 7.392 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-(trifluoromethyl)benzimidamide (MTF-385)

(112) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 4-(trifluoromethyl)benzonitrile (889 mg, 5.20 mmol) to afford the titled compound as a beige powder (1.38 g, 73%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.28 (br. s, 1H), 9.38 (br. s, 1H), 8.97 (br. s, 1H), 8.22 (d, J=8.2 Hz, 2H), 8.11 (br. s, 1H), 7.90 (d, J=8.3 Hz, 2H), 7.80 (d, J=7.3 Hz, 1H), 7.67 (d, J=7.7 Hz, 1H), 7.39-7.30 (m, 1H), 7.24-7.16 (m, 1H). .sup.19F NMR (377 MHz, DMSO-d6): δ −61.28. .sup.13C NMR (50 MHz, DMSO-d6): δ 172.11, 161.89, 160.69, 151.37, 139.09, 131.19, 131.40 (q, J=31.8 Hz), 128.36 (2C), 125.57, 125.16 (q, J=3.8 Hz, 2C), 123.91 (q, J=67.7 Hz), 122.79, 121.07, 119.72. HPLC (λ.sub.280): Purity 96.4%; t.sub.R: 7.442 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2-bromoisonicotinimidamide (MTF-386)

(113) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 2-bromo-4-cyanopyridine (952 mg, 5.20 mmol) to afford the titled compound as a yellow powder (859 mg, 44%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.19 (br. s, 1H), 9.38 (br. s, 1H), 9.04 (br. s, 1H), 8.58 (d, J=5.1 Hz, 1H), 8.18 (s and br. s, 2H), 7.96 (dd, J=5.1, 1.3 Hz, 1H), 7.81 (d, J=7.4 Hz, 1H), 7.67 (d, J=7.9 Hz, 1H), 7.39-7.32 (m, 1H), 7.24-7.17 (m, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.08, 161.67, 158.42, 151.36, 151.00, 145.67, 141.81, 131.32, 125.94, 125.71, 123.00, 121.25, 121.21, 119.91. HPLC (λ.sub.280): Purity 97.0%; t.sub.R: 7.192 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-bromothiophene-3-carboximidamide (MTF-387)

(114) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 4-bromothiophene-3-carbonitrile (978 mg, 5.20 mmol) to afford the titled compound as a brown powder (969 mg, 49%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.03 (br. s, 1H), 9.30 (br. s, 1H), 8.60 (br. s, 1H), 7.98 (br.s and d, J=3.4 Hz, 2H), 7.80 (d, J=7.7 Hz, 1H), 7.77 (d, J=3.4 Hz, 1H), 7.64 (d, J=8.0 Hz, 1H), 7.38-7.30 (m, 1H), 7.20 (d, J=7.3 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.41, 161.84, 159.08, 151.48, 137.36, 131.24, 129.06, 125.66, 125.44, 122.85, 121.16, 119.75, 108.70. HPLC (λ.sub.280): Purity 96.6%; t.sub.R: 6.967 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2,2-dimethyl-2H-chromene-6-carboximidamide (MTF-388)

(115) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (963 mg, 5.20 mmol) to afford the titled compound as a beige powder (118 mg, 6%). .sup.1H NMR (400 MHz, DMSO-d6): δ 10.25 (br. s, 1H), 9.29 (br. s, 1H), 8.66 (br. s, 1H), 7.91 (br. s, 1H), 7.84-7.75 (m, 3H), 7.64 (d, J=7.8 Hz, 1H), 7.37-7.30 (m, 1H), 7.22-7.15 (m, 1H), 6.85 (d, J=8.5 Hz, 1H), 6.45 (d, J=9.9 Hz, 1H), 5.84 (d, J=9.8 Hz, 1H), 1.41 (s, 6H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.68, 167.16, 165.32, 155.42, 136.88, 133.37, 131.25, 129.27, 129.18, 128.53, 127.69, 126.40, 126.16, 126.10, 121.61, 120.27, 115.66, 76.97, 27.93 (2C). HPLC (λ.sub.280): Purity 98.4%; t.sub.R: 7.492 min (method 1).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3,5-dichloropicolinimidamide (MTF-389)

(116) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 3,5-dichloropyridine-2-carbonitrile (900 mg, 5.20 mmol) to afford the titled compound as a brown powder (779 mg, 41%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.73 (br. s, 1H), 9.29 (br. s, 1H), 8.73 (br. s, 1H), 8.67 (d, J=1.5 Hz, 1H), 8.37 (s, 1H), 8.12 (br. s, 1H), 7.77 (d, J=7.7 Hz, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.32 (t, J=7.5 Hz, 1H), 7.18 (t, J=7.5 Hz, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.48, 161.60, 160.60, 151.43, 150.95, 145.79, 137.15, 131.46, 131.19, 129.02, 125.59, 122.77, 121.12, 119.67. HPLC (λ.sub.280): Purity 95.3%; t.sub.R: 7.192 min (method 1).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(4-(trifluoromethyl)phenyl)-1,3,5-triazine-2,4-diamine) (MTF-394)

(117) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-(trifluoromethyl)benzimidamide (363 mg, 1 mmol) to afford the titled compound as a white powder (239 mg, 66%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.34 (s, 1H), 8.42 (d, J=7.8 Hz, 2H), 7.86 (d, J=8.4 Hz, 2H), 7.64 (d, J=7.7 Hz, 1H), 7.41 (d, J=7.4 Hz, 1H), 7.25 (ddd, J=34.2, 11.4, 4.1 Hz, 4H). .sup.19F NMR (377 MHz, DMSO-d6): δ −61.24. .sup.13C NMR (101 MHz, DMSO-d6): δ 168.98, 167.28, 165.53, 140.54, 136.56, 133.57, 131.18, 128.46 (2C), 127.76, 126.75, 126.48, 125.50, 125.30 (2C), 122.80. HPLC (λ.sub.254): Purity 97.0%; t.sub.R: 16.125 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(thiophen-2-yl)-1,3,5-triazine-2,4-diamine) (MTF-396)

(118) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)thiophene-2-carboximidamide (301 mg, 1 mmol) to afford the titled compound as a white powder (250 mg, 83%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.21 (s, 1H), 7.84 (d, J=2.9 Hz, 1H), 7.75 (dd, J=5.0, 1.1 Hz, 1H), 7.61 (dd, J=7.9, 1.1 Hz, 1H), 7.37 (d, J=7.4 Hz, 1H), 7.26 (td, J=7.7, 1.2 Hz, 1H), 7.21-7.16 (m, 2H), 7.09 (d, J=15.2 Hz, 2H). .sup.13C NMR (101 MHz, DMSO-d6): δ 166.91, 166.58, 165.13, 142.40, 136.55, 133.67, 131.03, 129.34, 128.37, 128.08, 127.60, 126.68, 126.35. HPLC (λ.sub.280): Purity 97.1%; t.sub.R: 11.817 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(4-bromothiophen-3-yl)-1,3,5-triazine-2,4-diamine) (MTF-397)

(119) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-bromothiophene-3-carboximidamide (380 mg, 1 mmol) to afford the titled compound as a white powder (167 mg, 44%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.14 (s, 1H), 8.11 (d, J=3.6 Hz, 1H), 7.73 (d, J=3.6 Hz, 1H), 7.57 (d, J=7.3 Hz, 1H), 7.42 (d, J=7.7 Hz, 1H), 7.28-7.22 (m, 1H), 7.12 (t, J=7.4 Hz, 1H), 7.07 (s, 2H). .sup.13C NMR (101 MHz, DMSO-d6): δ 167.68, 166.88, 165.20, 137.92, 136.60, 133.26, 130.88, 128.44, 127.69, 126.98, 126.29, 126.03, 109.03. HPLC (λ.sub.254): Purity 97.1%; t.sub.R: 12.483 min (method 2).

N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-nitrobenzimidamide (MTF-398)

(120) Synthesized following the general procedure A using 1-(benzo[d]thiazol-2-yl)guanidine (1.00 g, 5.20 mmol), sodium hydride (60% dispersion in mineral oil, 1.5 eq., 312 mg, 7.81 mmol) and 4-nitrobenzonitrile (770 mg, 5.20 mmol) to afford the titled compound as a yellow powder (212 mg, 12%). .sup.1H NMR (500 MHz, DMSO-d6): δ 10.30 (br. s, 1H), 9.37 (br. s, 1H), 8.90 (br. s, 1H), 8.12 (t, br. s, J=1.8 Hz, 2H), 7.99 (d, J=7.9 Hz, 1H), 7.80 (d, J=7.7 Hz, 1H), 7.66 (d, J=7.9 Hz, 1H), 7.65-7.60 (m, 1H), 7.54 (t, J=7.9 Hz, 1H), 7.38-7.30 (m, 1H), 7.22-7.17 (m, 1H). .sup.13C NMR (50 MHz, DMSO-d6): δ 172.22, 161.95, 160.57, 151.47, 137.26, 133.22, 131.23, 131.20, 130.20, 127.53, 126.14, 125.67, 122.87, 121.16, 119.79. HPLC (λ.sub.280): Purity 99.2%; t.sub.R: 6.792 min (method 1).

2-((4-amino-6-(trichloromethyl)-1,3,5-triazin-2-yl)amino)phenol (MTF373)

(121) Synthesized following the general procedure D using 1-(benzo[d]oxazol-2-yl)guanidine (100 mg, 0.6 mmol) and trichloroacetonitrile (600 μL, 6 mmol) to afford the title compound as a beige powder (61 mg, 32%). .sup.1H NMR (400 MHz, Acetone-d6): δ 9.10 (s, 1H), 8.38 (br. s, 1H), 7.99 (br. s, 1H), 7.28 (br. s, 1H), 7.15 (br. s, 1H), 7.05-6.92 (m, 2H), 6.87 (td, J=7.8, 1.7 Hz, 1H). .sup.13C NMR (101 MHz, Acetone-d6): δ 174.0, 168.9, 165.8, 148.6, 127.6, 125.6, 123.2, 120.8, 117.2, 97.4. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.10H.sub.9ON.sub.5Cl.sub.3.sup.+319.98672; Found 319.98709. HPLC (λ.sub.254): 97.9%; t.sub.R: 9.108 min (method 4).

2-((4-amino-6-(trichloromethyl)-1,3,5-triazin-2-yl)amino)-4-chlorophenol (MTF374)

(122) Synthesized following the general procedure D using 2-(5-chlorobenzo[d]oxazol-2-yl)guanidine (100 mg, 0.48 mmol) and trichloroacetonitrile (450 μL, 4.8 mmol) to afford the title compound as a light pink powder (55 mg, 32%). .sup.1H NMR (400 MHz, Acetone-d6): δ 9.48 (s, 1H), 8.30 (s, 1H), 8.18 (s, 1H), 7.43 (s, 1H), 7.20 (s, 1H), 7.01-6.92 (m, 2H). .sup.13C NMR (101 MHz, Acetone-d6): δ 174.0, 168.9, 165.6, 146.6, 128.8, 124.9, 124.3, 121.9, 117.3, 97.3. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.10H.sub.8ON.sub.5Cl.sub.4.sup.+353.94775; Found 353.94830. HPLC (λ.sub.254): 97.1%; t.sub.R: 10.504 min (method 4).

2-(4-amino-6-(trichloromethyl)-1,3,5-triazin-2-yl)amino)-5-chlorophenol (MTF375)

(123) Synthesized following the general procedure D using 2-(6-chlorobenzo[d]oxazol-2-yl)guanidine (100 mg, 0.48 mmol) and trichloroacetonitrile (480 μL, 4.8 mmol) to afford the title compound as a light green powder (59 mg, 35%). .sup.1H NMR (400 MHz, Acetone-d6): δ 9.66 (br. s, 1H), 8.32 (br. s, 1H), 8.04 (br. s, 1H), 7.29 (br. s, 1H), 7.18 (br. s, 1H), 6.99 (d, J=2.2 Hz, 1H), 6.90 (dd, J=8.7, 2.1 Hz, 1H). .sup.13C NMR (101 MHz, Acetone-d6): δ 174.0, 168.9, 165.7, 149.5, 129.5, 126.7, 124.1, 120.4, 116.8, 97.3. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.10H.sub.8ON.sub.5Cl.sub.4.sup.+353.94775; Found 353.94837. HPLC (λ.sub.254): 95.3%; t.sub.R: 10.615 min (method 4).

2-((4-amino-6-(trichloromethyl)-1,3,5-triazin-2-yl)amino)-5-nitrophenol (MTF376)

(124) Synthesized following the general procedure D using 2-(6-nitrobenzo[d]oxazol-2-yl)guanidine (100 mg, 0.45 mmol) and trichloroacetonitrile (450 μL, 4.5 mmol) to afford the title compound as a light yellow powder (50 mg, 30%). .sup.1H NMR (400 MHz, MeOD): δ 8.72 (d, J=9.1 Hz, 1H), 7.78 (dd, J=9.1, 2.5 Hz, 1H), 7.70 (d, J=2.5 Hz, 1H). .sup.13C NMR (101 MHz, Acetone-d6): δ 174.3, 169.1, 165.7, 147.1, 143.7, 134.5, 120.3, 116.6, 110.4, 97.1. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.10H.sub.8O.sub.3N.sub.6Cl.sub.3.sup.+ 364.97180; Found 364.97208. HPLC (λ.sub.254): 95.1%; t.sub.R: 10.623 min (method 4).

2-((4-amino-6-(trichloromethyl)-1,3,5-triazin-2-yl)amino)-4-nitrophenol (MTF377)

(125) Synthesized following the general procedure D using 2-(5-nitrobenzo[d]oxazol-2-yl)guanidine (100 mg, 0.45 mmol) and trichloroacetonitrile (450 μL, 4.5 mmol) to afford the title compound as a light orange powder (117 mg, 71%). .sup.1H NMR (400 MHz, Acetone-d6): δ 9.29 (br. s, 1H), 8.32 (br. s, 1H), 7.91 (dd, J=8.9, 2.6 Hz, 1H), 7.54 (br. s, 1H), 7.23 (br. s, 1H), 7.11 (d, J=8.9 Hz, 1H), 6.61 (br. s, 1H). .sup.13C NMR (101 MHz, Acetone-d6): δ 174.3, 168.9, 165.6, 146.9, 143.6, 134.3, 120.3, 116.7, 110.3, 97.1. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.10H.sub.8O.sub.3N.sub.6Cl.sub.3.sup.+364.97180; Found 364.97229. HPLC (λ.sub.254): 97.7%; t.sub.R: 9.434 min (method 4).

2-((4-amino-6-phenyl-1,3,5-triazin-2-yl)amino)-4-chlorophenol (MTF409)

(126) Synthesized following the general procedure E using 1-(5-chlorobenzo[d]oxazol-2-yl)guanidine (500 mg, 2.4 mmol), sodium hydride (60% oil suspension, 104 mg, 2.6 mmol) and benzonitrile (0.25 mL, 2.4 mmol) to afford the title compound as a beige powder (210 mg, 28%). .sup.1H NMR (400 MHz, Acetone-d6): δ 9.88 (br. s, 1H), 8.41-8.37 (m, 2H), 8.16 (s, 2H), 7.56 (t, J=7.2 Hz, 1H), 7.50 (t, J=7.3 Hz, 2H), 7.01-6.92 (m, 2H), 6.81 (br. s, 2H). .sup.13C NMR (101 MHz, Acetone-d6): δ 172.1, 168.6, 165.7, 147.0, 137.3, 132.6, 129.9, 129.1 (2C), 129.0 (2C), 124.8, 124.1, 121.9, 118.4. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.13OClN.sub.5.sup.+314.08031; Found 314.08044. HPLC (λ.sub.254): 98.1%; t.sub.R: 9.916 min (method 4).

2-((6-imino-4-(trichloromethyl)-1,6-dihydro-1,3,5-triazin-2-yl)amino)-5-methylphenol (MTF410)

(127) Synthesized following the general procedure D using 1-(6-methylbenzo[d]oxazol-2-yl)guanidine (500 mg, 2.6 mmol) and trichloroacetonitrile (2.6 mL, 26 mmol) to afford the title compound as a light grey powder (480 mg, 55%). .sup.1H NMR (400 MHz, Acetone-d6): δ 9.01 (br. s, 1H), 8.31 (br. d, J=75.1 Hz, 1H), 7.79 (br. d, J=51.9 Hz, 1H), 7.25 (br. s, 1H), 7.14 (br. s, 1H), 6.79 (d, J=0.9 Hz, 1H), 6.69 (dd, J=8.1, 1.0 Hz, 1H), 2.25 (s, 3H). .sup.13C NMR (101 MHz, Acetone-d6): δ 173.8, 168.7, 165.6, 149.0, 135.8, 124.7, 123.6, 121.3, 118.0, 97.3, 20.9. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.11H.sub.11OCl.sub.3N.sub.5.sup.+334.00237; Found 334.00250. HPLC (λ.sub.254): 100%; t.sub.R: 9.948 min (method 4).

2-((4-amino-6-phenyl-1,3,5-triazin-2-yl)amino)-5-methylphenol (MTF411)

(128) Synthesized following the general procedure E using 1-(6-methylbenzo[d]oxazol-2-yl)guanidine (500 mg, 2.6 mmol), sodium hydride (60% oil suspension, 114 mg, 2.9 mmol) and benzonitrile (0.27 mL, 2.6 mmol) to afford the title compound as a beige powder (410 mg, 54%). .sup.1H NMR (400 MHz, Acetone-d6): δ 9.75 (br. s, 1H), 8.37 (d, J=7.4 Hz, 2H), 8.30 (br. s, 1H), 7.59-7.53 (m, 2H), 7.48 (t, J=7.3 Hz, 2H), 6.80 (s, 1H), 6.74 (br. s, 2H), 6.69 (d, J=8.0 Hz, 1H), 2.26 (s, 3H). .sup.13C NMR (101 MHz, Acetone-d6): δ 171.9, 168.4, 165.6, 149.1, 137.4, 135.4, 132.5, 129.1, 129.0 (2C), 125.9, 123.3, 121.3 (2C), 119.2, 20.9. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.16H.sub.16ON.sub.5.sup.+294.13494; Found 294.13495. HPLC (λ.sub.254): 99.7%; t.sub.R: 8.456 min (method 4).

2-((4-amino-6-phenyl-1,3,5-triazin-2-yl)amino)phenol (MTF412)

(129) Synthesized following the general procedure E using 1-(benzo[d]oxazol-2-yl)guanidine (500 mg, 2.8 mmol), sodium hydride (60% suspension in oil, 123 mg, 3.1 mmol) and benzonitrile (0.29 mL, 2.8 mmol) to afford the title compound as a light brown powder (53 mg, 7%). .sup.1H NMR (400 MHz, Acetone-d6): δ 9.82 (br. s, 1H), 8.39 (d, J=7.1 Hz, 2H), 8.31 (br. s, 1H), 7.83 (d, J=7.7 Hz, 1H), 7.58-7.52 (m, 1H), 7.52-7.46 (m, 2H), 7.03-6.94 (m, 2H), 6.90-6.84 (m, 1H), 6.77 (br. s, 2H). .sup.13C NMR (101 MHz, Acetone-d6): δ 172.0, 168.5, 165.7, 148.9, 137.4, 132.6, 129.1 (2C), 129.0 (2C), 128.5, 125.3, 123.1, 120.7, 118.3. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.14ON.sub.5.sup.+280.11929; Found 280.11929. HPLC (λ.sub.254): 98.9%; t.sub.R: 8.100 min (method 4).

2-((6-imino-4-phenyl-1,6-dihydro-1,3,5-triazin-2-yl)amino)-4-nitrophenol (MTF413)

(130) Synthesized following the general procedure E using 1-(6-nitrobenzo[d]oxazol-2-yl)guanidine (500 mg, 2.3 mmol), sodium hydride (60% suspension in oil, 100 mg, 2.5 mmol) and benzonitrile (0.24 mL, 2.3 mmol) to afford the title compound as a light yellow powder (62 mg, 8%). .sup.1H NMR (400 MHz, DMSO-d6): δ 11.39 (br. s, 1H), 8.63 (d, J=9.0 Hz, 1H), 8.36-8.30 (m, 2H), 8.26 (s, 1H), 7.80 (dd, J=9.0, 2.6 Hz, 1H), 7.70 (d, J=2.6 Hz, 1H), 7.61-7.56 (m, 1H), 7.52 (dd, J=11.4, 4.4 Hz, 2H), 7.45 (br. s, 2H). .sup.13C NMR (101 MHz, DMSO-d6): δ 170.7, 167.2, 164.2, 146.4, 141.5, 136.1, 134.5, 131.9, 128.5 (2C), 128.0 (2C), 118.9, 115.4, 108.9. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.15H.sub.13O.sub.3N.sub.6.sup.+325.10436; Found 325.10446. HPLC (λ.sub.254): 99.1%; t.sub.R: 10.242 min (method 4).

2-((6-imino-4-(pyrazin-2-yl)-1,6-dihydro-1,3,5-triazin-2-yl)amino)phenol (MTF439)

(131) Synthesized following the general procedure E using 1-(benzo[d]oxazol-2-yl)guanidine (500 mg, 2.8 mmol), sodium hydride (60% oil suspension, 123 mg, 3.08 mmol) and pyrazinecarbonitrile (250 μL, 2.8 mmol) to afford the title compound as a bright yellow powder (510 mg, 65%). The biguanide was then dissolved in DMSO and stirred for 8 h at r.t. to give the desired product as a bright yellow powder. .sup.1H NMR (400 MHz, DMSO-d6): δ 10.07 (br. s, 1H), 9.41 (s, 1H), 8.79 (s, 2H), 8.57 (s, 1H), 7.88 (dd, J=8.0, 0.6 Hz, 1H), 7.53 (br. s, 1H), 7.41 (br. s, 1H), 6.99-6.93 (m, 1H), 6.90 (dd, J=8.0, 1.4 Hz, 1H), 6.85-6.79 (m, 1H). .sup.13C NMR (101 MHz, DMSO-d6): δ 168.7, 167.2, 164.6, 149.4, 148.4, 146.4, 144.6, 144.5, 126.8, 124.4, 123.0, 119.2, 116.1. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.13H.sub.12ON.sub.7.sup.+282.10978; Found 282.10977. HPLC (λ.sub.254): 98.8%; t.sub.R: 4.209 min (method 4).

N—(N-(benzo[d]oxazol-2-yl)carbamimidoyl)pyrazine-2-carboximidamide (MTF440)

(132) Synthesized following the general procedure E using 1-(benzo[d]oxazol-2-yl)guanidine (500 mg, 2.8 mmol), sodium hydride (60% oil suspension, 123 mg, 3.08 mmol) and 3-pyridinecarbonitrile (292 mg, 2.8 mmol) to afford the title compound as a bright yellow powder (510 mg, 65%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.98 (s, 1H), 9.40 (d, J=1.4 Hz, 1H), 8.73 (dd, J=4.8, 1.7 Hz, 1H), 8.54 (d, J=8.0 Hz, 1H), 8.34 (s, 1H), 7.93 (dd, J=7.9, 1.4 Hz, 1H), 7.54 (ddd, J=8.0, 4.8, 0.5 Hz, 1H), 7.32 (s, 2H), 6.98-6.93 (m, 1H), 6.91-6.88 (m, 1H), 6.86-6.80 (m, 1H). .sup.13C NMR (101 MHz, DMSO-d6): δ 168.8, 167.0, 164.4, 152.1, 149.1, 148.1, 135.2, 132.0, 126.8, 124.1, 123.6, 122.7, 119.1, 115.7. HRMS-ESI (m/z): [M+H].sup.+ calc. for C.sub.14H.sub.13ON.sub.6.sup.+281.11454; Found 281.11450. HPLC (2.sub.254): 99.7%; t.sub.R: 4.165 min (method 4).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(naphthalen-2-yl)-1,3,5-triazine-2,4-diamine) (MTF443)

(133) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2-naphthimidamide (345 mg, 1 mmol) to afford the title compound as a white powder (299 mg, 87%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.30 (s, 1H), 8.87 (s, 1H), 8.36 (d, J=8.5 Hz, 1H), 7.99 (dd, J=19.5, 10.4 Hz, 3H), 7.68 (d, J=7.8 Hz, 1H), 7.63-7.53 (m, 2H), 7.48 (d, J=7.7 Hz, 1H), 7.29 (t, J=7.2 Hz, 1H), 7.25-7.11 (m, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 170.19, 167.33, 165.53, 136.81, 134.58, 134.17, 133.57, 132.40, 128.98, 128.66, 128.16, 127.74, 127.65 (2C), 127.51, 126.55 (2C), 126.26, 124.75. HPLC (λ.sub.280): Purity 97.3%; t.sub.R: 15.642 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(2,2-dimethyl-2H-chromen-6-yl)-1,3,5-triazine-2,4-diamine) (MTF444)

(134) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2,2-dimethyl-2H-chromene-6-carboximidamide (377 mg, 1 mmol) to afford the title compound as a white powder (241 mg, 64%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.10 (s, 1H), 8.00 (d, J=8.5 Hz, 1H), 7.95 (s, 1H), 7.61 (d, J=9.0 Hz, 1H), 7.41 (d, J=7.1 Hz, 1H), 7.27 (t, J=7.0 Hz, 1H), 7.16 (t, J=7.5 Hz, 1H), 6.99 (s, 2H), 6.81 (d, J=8.5 Hz, 1H), 6.45 (d, J=9.9 Hz, 1H), 5.80 (d, J=9.8 Hz, 1H), 1.40 (s, 6H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.67, 167.15, 165.33, 155.42, 136.86, 133.39, 131.25, 129.26, 129.18, 128.51, 127.69, 126.41, 126.16 (2C), 121.61, 120.26, 115.65, 76.97, 27.93 (2C). HPLC (λ.sub.280): Purity 95.2%; t.sub.R: 15.767 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(3-nitrophenyl)-1,3,5-triazine-2,4-diamine) (MTF445)

(135) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3-nitrobenzimidamide (340 mg, 1 mmol) to afford the title compound as a white powder (265 mg, 78%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.41 (s, 1H), 9.04 (s, 1H), 8.60 (d, J=6.8 Hz, 1H), 8.39 (dd, J=8.2, 1.4 Hz, 1H), 7.79 (t, J=8.0 Hz, 1H), 7.64 (dd, J=7.9, 0.9 Hz, 1H), 7.39 (dd, J=7.8, 0.9 Hz, 1H), 7.36-7.17 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d6): δ 168.16, 167.23, 165.49, 147.97, 138.33, 136.42, 133.75 (2C), 130.10, 128.35, 127.72, 126.82, 126.57, 125.93, 122.27. HPLC (λ.sub.280): Purity 95.3%; t.sub.R: 13.550 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(3,4,5-trimethoxyphenyl)-1,3,5-triazine-2,4-diamine) (MTF446)

(136) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3,4,5-trimethoxybenzimidamide (385 mg, 1 mmol) to afford the title compound as a white powder (358 mg, 93%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.24 (s, 1H), 7.59 (s, 3H), 7.40 (d, J=7.7 Hz, 1H), 7.27 (t, J=7.5 Hz, 1H), 7.12 (dd, J=23.2, 15.8 Hz, 3H), 3.79 (s, 6H), 3.73 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.55, 167.26, 165.29, 152.58 (2C), 140.36, 136.92, 133.81, 131.90, 128.71, 127.66, 126.37, 126.11, 105.08 (2C), 60.11, 55.74 (2C). HPLC (λ.sub.280): Purity 96.6%; t.sub.R: 10.367 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(benzo[d][1,3]dioxol-5-yl)-1,3,5-triazine-2,4-diamine) (MTF449)

(137) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)benzo[d][1,3]dioxole-5-carboximidamide (340 mg, 1 mmol) to afford the title compound as a white powder (247 mg, 73%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.14 (s, 1H), 7.87 (d, J=8.1 Hz, 1H), 7.68 (s, 1H), 7.61 (d, J=7.8 Hz, 1H), 7.39 (d, J=7.7 Hz, 1H), 7.27 (t, J=7.4 Hz, 1H), 7.17 (t, J=7.5 Hz, 1H), 7.08-6.97 (m, 3H), 6.10 (s, 2H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.41, 167.15, 165.34, 150.10, 147.37, 136.77, 133.53, 130.76, 128.41, 127.66, 126.47, 126.21, 122.88, 107.97, 107.44, 101.60. HPLC (λ.sub.280): Purity 95.1%; t.sub.R: 10.767 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(2-chlorophenyl)-1,3,5-triazine-2,4-diamine) (MTF450)

(138) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2-chlorobenzimidamide (329 mg, 1 mmol) to afford the title compound as a white powder (273 mg, 83%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.30 (s, 1H), 7.58 (dt, J=9.4, 4.8 Hz, 2H), 7.51 (dd, J=7.8, 1.0 Hz, 1H), 7.45 (td, J=7.7, 2.0 Hz, 1H), 7.41 (dd, J=7.4, 1.3 Hz, 1H), 7.38 (d, J=6.8 Hz, 1H), 7.28-7.22 (m, 1H), 7.22-7.09 (m, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.24, 166.83, 165.19, 137.48, 136.34, 133.55, 130.93, 130.50, 130.47, 129.82, 128.16, 127.59, 127.08, 126.87, 126.52. HPLC (λ.sub.280): Purity 95.1%; t.sub.R: 10.517 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(p-tolyl)-1,3,5-triazine-2,4-diamine) (MTF451)

(139) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-4-methylbenzimidamide (309 mg, 1 mmol) to afford the title compound as a white powder (179 mg, 58%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.15 (s, 1H), 8.14 (d, J=8.0 Hz, 2H), 7.61 (d, J=7.9 Hz, 1H), 7.41 (d, J=7.1 Hz, 1H), 7.26 (dd, J=8.8, 4.7 Hz, 3H), 7.17 (t, J=7.5 Hz, 1H), 7.04 (s, 2H), 2.36 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 170.14, 167.25, 165.46, 141.31, 136.80, 133.90, 133.44, 128.86 (2C), 128.52, 127.86 (2C), 127.71, 126.51, 126.21, 21.09. HPLC (λ.sub.280): Purity 96.7%; t.sub.R: 12.958 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(2-fluorophenyl)-1,3,5-triazine-2,4-diamine) (MTF452)

(140) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2-fluorobenzimidamide (313 mg, 1 mmol) to afford the title compound as a white powder (191 mg, 61%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.26 (s, 1H), 7.87 (td, J=7.7, 1.6 Hz, 1H), 7.59 (dd, J=7.9, 1.0 Hz, 1H), 7.56-7.49 (m, 1H), 7.39 (d, J=7.6 Hz, 1H), 7.30-7.23 (m, 3H), 7.20-7.10 (m, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 169.77 (d), 166.97, 165.31, 160.33 (d), 136.49, 133.54, 132.19 (d), 131.13 (d), 128.26, 127.65, 126.92, 126.46, 125.89 (d), 124.09 (d), 116.50 (d). HPLC (λ.sub.280): Purity 95.4%; t.sub.R: 10.333 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(2,6-dichlorophenyl)-1,3,5-triazine-2,4-diamine) (MTF455)

(141) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2,6-dichlorobenzimidamide (364 mg, 1 mmol) to afford the title compound as a white powder (320 mg, 88%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.44 (s, 1H), 7.55 (dd, J=13.4, 7.9 Hz, 3H), 7.45 (dd, J=9.0, 7.1 Hz, 1H), 7.33 (d, J=7.7 Hz, 1H), 7.30-7.22 (m, 3H), 7.18 (t, J=7.1 Hz, 1H). .sup.13C NMR (101 MHz, DMSO-d6): δ 170.75, 166.93, 165.40, 136.69, 135.98, 133.90, 132.08 (2C), 130.63, 128.12 (2C), 127.88, 127.50, 127.25, 126.83. HPLC (λ.sub.280): Purity 95.8%; t.sub.R: 10.150 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(3,5-dibromopyridin-4-yl)-1,3,5-triazine-2,4-diamine) (MTF456)

(142) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-3,5-dibromoisonicotinimidamide (454 mg, 1 mmol) to afford the title compound as a white powder (412 mg, 91%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.56 (s, 1H), 8.84 (s, 2H), 7.57 (d, J=7.7 Hz, 1H), 7.39 (d, J=14.8 Hz, 2H), 7.31 (d, J=7.6 Hz, 1H), 7.25 (t, J=7.2 Hz, 1H), 7.20 (d, J=5.4 Hz, 1H). .sup.13C NMR (101 MHz, DMSO-d6): δ 170.93, 166.78, 165.27, 150.32 (2C), 146.43, 135.71, 133.98, 127.70, 127.49, 127.35, 127.02, 119.05 (2C). HPLC (λ.sub.280): Purity 95.1%; t.sub.R: 9.700 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(6-bromobenzo[d][1,3]dioxol-5-yl)-1,3,5-triazine-2,4-diamine) (MTF458)

(143) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-6-bromobenzo[d][1,3]dioxole-5-carboximidamide (418 mg, 1 mmol) to afford the title compound as a white powder (300 mg, 72%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.31 (s, 1H), 7.57 (d, J=7.6 Hz, 1H), 7.38 (d, J=7.3 Hz, 1H), 7.28-7.23 (m, 2H), 7.22-7.11 (m, 4H), 6.12 (s, 2H). .sup.13C NMR (101 MHz, DMSO-d6): δ 172.43, 166.50, 165.08, 148.68, 146.86, 136.29, 133.50, 132.49, 128.17, 127.63, 127.08, 126.58, 112.81, 111.49, 109.98, 102.31. HPLC (λ.sub.280): Purity 96.1%; t.sub.R: 10.475 min (method 12).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(3-aminophenyl)-1,3,5-triazine-2,4-diamine) (MTF460)

(144) Synthesized following the general procedure B using 3-amino-N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)benzimidamide (310 mg, 1 mmol) to afford the title compound as a yellow powder (241 mg, 78%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.06 (s, 1H), 7.61 (dd, J=7.9, 1.2 Hz, 1H), 7.49 (s, 1H), 7.43 (d, J=7.8 Hz, 2H), 7.27 (td, J=7.7, 1.3 Hz, 1H), 7.17 (t, J=7.6 Hz, 1H), 7.09 (t, J=7.8 Hz, 1H), 6.98 (s, 2H), 6.71 (dd, J=7.9, 1.4 Hz, 1H), 5.18 (s, 2H). .sup.13C NMR (101 MHz, DMSO-d6): δ 170.95, 167.23, 165.44, 148.52, 137.33, 136.87, 133.20, 128.59, 128.55, 127.72, 126.43, 126.12, 116.94, 115.86, 113.34. HPLC (λ.sub.280): Purity 97.8%; t.sub.R: 7.167 min (method 2).

1,1′-((((disulfanediylbis(2,1-phenylene))bis(azanediyl))bis(6-amino-1,3,5-triazine-4,2-diyl))bis(3,1-phenylene))bis(ethan-1-one) (MTF462)

(145) Synthesized following the general procedure B using 3-acetyl-N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)benzimidamide (337 mg, 1 mmol) to afford the title compound as a white powder (225 mg, 67%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.32 (s, 1H), 8.83 (s, 1H), 8.46 (d, J=7.4 Hz, 1H), 8.13 (d, J=7.8 Hz, 1H), 7.64 (t, J=7.1 Hz, 2H), 7.40 (d, J=7.1 Hz, 1H), 7.23 (dt, J=15.3, 8.0 Hz, 4H), 2.61 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d6): δ 197.57, 169.41, 167.28, 165.49, 137.06, 136.86, 136.62, 133.74, 132.14, 131.24, 128.80, 128.46, 127.69, 127.32, 126.67, 126.40, 26.77. HPLC (λ.sub.280): Purity 96.9%; t.sub.R: 10.908 min (method 2).

N2,N2′-(disulfanediylbis(2,1-phenylene))bis(6-(2-nitrophenyl)-1,3,5-triazine-2,4-diamine) (MTF463)

(146) Synthesized following the general procedure B using N—(N-(benzo[d]thiazol-2-yl)carbamimidoyl)-2-nitrobenzimidamide (340 mg, 1 mmol) to afford the title compound as a white powder (278 mg, 82%). .sup.1H NMR (400 MHz, DMSO-d6): δ 9.29 (s, 1H), 7.92 (d, J=7.6 Hz, 1H), 7.86 (d, J=7.3 Hz, 1H), 7.77 (t, J=7.3 Hz, 1H), 7.70 (t, J=7.6 Hz, 1H), 7.57 (d, J=7.8 Hz, 1H), 7.32 (d, J=7.6 Hz, 1H), 7.28-7.07 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d6): δ 170.32, 166.77, 165.14, 149.12, 136.11, 133.49, 132.58, 132.34, 130.89, 130.51, 128.06, 127.58, 127.11, 126.63, 123.88. HPLC (λ.sub.280): Purity 98.9%; t.sub.R: 10.350 min (method 2).

(147) Cell Cultures

(148) Fresh sterile tissues were obtained from surgical waste from patients diagnosed with metastatic melanoma at the Nice CHU hospital. Epidermal cell suspensions were obtained from foreskins of Caucasian children by overnight digestion in phosphate-buffered saline containing 0.5% dispase grade II at 4° C., followed by a 20 min digestion with 0.05% trypsin-0.02% EDTA in phosphate-buffered saline (V/V) at 37° C. Human primary melanocytes were grown in MCDB153 medium supplemented with 2% FCS, 0.4 μg/ml hydrocortisone, 5 μg/ml insulin, 16 nM phorbol-12 myristate 13-acetate, 1 ng/ml basic fibroblast growth factor, 10 μg/ml bovine pituitary extract and penicillin/streptomycin (100 U/ml/50 μg/ml). Human primary keratinocytes were cultured in KSFM medium in which 0.1 ng/ml epidermal growth factor, 15 μg/ml bovine pituitary extract and penicillin/streptomycin (100 U/ml/50 μg/ml) were added. Human primary fibroblasts and melanoma cells, derived from the corresponding dermis, were grown in DMEM 7% Foetal Calf Serum (FCS) and penicillin/streptomycin (100 U/ml/50 μg/ml). Written informed consent was obtained from each patient included in this study, and the study was approved by the hospital ethics committee (Nice Hospital Center and University of Nice Sophia Antipolis, no. 210-2998).

(149) Different melanoma cell lines were purchased from the American Tissue Culture Collection: A375 and WM9 cells are mutated on B-Raf, CDKN2A and PTEN proteins; SKmel28 cells are mutated on B-Raf and P53 proteins; 1205Lu cells are mutated on B-Raf and PTEN proteins; G-361 cells are mutated on B-Raf and CDKN2A proteins; C8161 cells are mutated on B-Raf and K-Ras proteins; WM3912 cells are mutated on B-Raf and CDKN2A proteins; MeWo cells are mutated on P53 and CDKN2A proteins; WM3918 presents no mutations on characteristic proteins.

(150) Resistant melanoma cell lines A375 and SKMel28 were a gift from Professor P. Marchetti and described in Corazao-Rozas et al. (2013). Cells were grown in RPMI 1640 or in DMEM supplemented with 10% of Foetal Calf Serum (FCS) and penicillin/streptomycin (100 U/ml/50 mg/ml) at 37° C. and 5% CO2.

(151) Trypan Blue Exclusion Assay

(152) For trypan blue staining, 200 mL of cells (melanoma and normal human cells) were aseptically transferred to a 1.5 mL clear Eppendorf tube and incubated for 3 min at room temperature with an equal volume of 0.4% trypan blue solution. Viable cells were counted and the results are expressed as the percentage of the value of control cells. All the experiments are performed 3 times in triplicate.

(153) Viability Test

(154) A375 Sensitive cells were treated with different concentrations of the synthesized molecules (5.0 μM or 10 μM) for different times (24 hr or 48 hr) or with DMSO (Control) for 12 or 48 hr. At the end of the stimulation, viable cells were counted using the trypan blue dye exclusion method. The results are normalized as percentages compare to the control. The results are shown in Table 1. They show that compounds of formula (I), (II) and (III) induce a decrease of the viability of melanoma cells.

(155) Kinetic of CRO15

(156) A375 Sensitive cells were treated with 5 μM of CRO15 for different times (2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr or 48 hr) or with 5 μM of PLX4032 (B-Raf inhibitor) for 48 hr or with DMSO (Control) for 48 hr. At the end of stimulation, viable cells were counted using the trypan blue dye exclusion method. The results are normalized as percentages compare to the control and data means±SEM of three independent experiments performed in triplicate *p<0.05; **p<0.01; ***p<0.001. The results are shown in FIG. 1A. They show that CRO15 induces a decrease of the viability of melanoma cells and that the decrease of the viability after 48 hr is more important with CRO15 than with PLX4032.

(157) IC50 of CRO15

(158) A375 Sensitive cells were treated with different concentrations of CRO15 (0.5 μM, 2.5 μM, 5.0 μM, 7.5 μM, 50 μM) for 48 hr or with 5 μM of PLX4032 (B-Raf inhibitor) for 48 hr or with DMSO (Control) for 48 hr. At the end of the stimulation, viable cells were counted using the trypan blue dye exclusion method. The results are normalized as percentages compare to the control and data means±SEM of three independent experiments performed in triplicate *p<0.05; **p<0.01; ***p<0.001. IC50 of CRO15 have been determined at 3.75 μM at 48 hr. The results are shown in FIG. 1B. They show that there is a dose-response relationship for CRO15 on melanoma cells viability.

(159) Viability Test with CRO15

(160) Different melanoma cell lines with various mutations, patient cells with various mutations and normal human cells, were treated with 5 μM of CRO15 for 48 hours or DMSO (Control). At the end of stimulation, viable cells were counted using the trypan blue dye exclusion method. The results are normalized as percentages compare to the control and data means±SEM of three independent experiments performed in triplicate *p<0.05; **p<0.01; ***p<0.001. The results are shown in FIG. 1C (melanoma cell lines with various mutations) and 1D (patient cells with various mutations) and 1E (normal human cells). They show that CRO15 induces a decrease of the viability of different melanoma cell lines with various mutations and different patient cells with various mutations, while CRO15 is not toxic for normal cells.

(161) Viability Test of CRO15 on Resistant Melanoma Cells

(162) A375 sensitive and resistant melanoma cells were treated with 5 μM of CRO15 for 48 hr or with 5 μM of PLX4032 for 48 hr or with DMSO (Control). At 48 hours, viable cells were counted using the trypan blue dye exclusion method. The results are normalized as percentages compare to the control and data means±SEM of three independent experiments performed in triplicate *p<0.05; **p<0.01; ***p<0.001. The results are shown in FIG. 4A. They show that CRO15 induces a decrease of the cell viability in both sensitive and resistant melanoma cells and that the decrease of the viability is more important with CRO15 than with PLX4032.

(163) Viability Test of CRO15 on Double Resistant Cells to BRAF and MEK Inhibitors

(164) Melanoma cell line DR6 resistant cells to B-Raf inhibitor (Vemurafenib=PLX4032) and to MEK inhibitor (Cobimetinib) were treated with DMSO (control), with 5 μM or 10 μM of CRO15 or with a combination of 1 μM of vemurafenib and 0.5 μM of cobimetinib. After 24 hours of stimulation, viable cells were counted using the trypan blue dye exclusion method. The results are normalized as percentages compare to the control. Error bars represents ±SEM of triplicate.

(165) The results are shown in FIG. 5. They show that CRO15 induces a decrease of the cell viability of melanoma cell line resistant to B-Raf inhibitor (PLX4032) and to MEK inhibitor (Cobimetinib).

(166) Western Blot Assays

(167) Western blot analyses were performed as described (Lehraiki et al., 2014). Proteins were extracted in buffer containing 50 mmol/l Tris-HCl (pH 7.5), 15 mmol/1, NaCl, 1% Triton X-100, and 1× protease and phosphatase inhibitors. Briefly, cell lysates (30 mg) were separated by SDS-PAGE, transferred onto a polyvinylidene fluoride membrane (Millipore), and then exposed to the appropriate antibodies. Proteins were visualized with the ECL System from Amersham. The western blot analyses shown are representative of at least three independent experiments.

(168) Western Blot analysis: A375 Sensitive cells were treated with 5 μM of CRO15 for different time (6 hr, 12 hr or 24 hr) or with DMSO (Control) for 24 hr.

(169) The results are shown in FIG. 2. They show that CRO15 induces an activation of AMPK.

(170) In Vivo Murine Cancer Model

(171) Animal experiments were carried out in accordance with the Declaration of Helsinki and were approved by a local ethical committee CIEPAL (Comité Institutionnel d'Ethique Pour l'Animal de Laboratoire-Azur). Female immune-deficient BALB/c nu/nu (nude) mice were obtained at 5 weeks of age from Envigo Laboratory (Gannat, France). Nude mice were inoculated subcutaneously with A375 sensitive or resistant melanoma cells (1.0×106 cells/mouse). After tumor apparition (±5 days), animals received intraperitoneal injection of Labrafil (Control), PLX4032 (0.7 mg/mouse/day) or CRO15 (0.7 mg/mouse/day) dissolved in Labrafil. The growth tumor curves were determined by measuring the tumor volume using the equation V=(L*W2)/2 (V=tumor volume, W=tumor width, L=tumor length). At the end of the experiment, mice were euthanized by cervical dislocation and tumors were taken for western blot and immunofluorescence experiments (LC3, Cleaved Caspase 3). TUNEL assay was performed using the In Situ Cell Death Detection Kit (Roche, Meylan, France). The results are shown in FIGS. 3A and 3B (A375 sensitive melanoma cells), and 4B and 4C (A375 resistant melanoma cells). They show that CRO15 reduces both the tumor volume and weight of mice inoculated with both sensitive and resistant melanoma cells.

(172) Xenograft—A375 Resistant cells (Riv)

(173) In Vivo Murine Cancer Model Animal experiments were carried out in accordance with the Declaration of Helsinki and were approved by a local ethical committee CIEPAL (Comite Institutionnel d'Ethique Pour l'Animal de Laboratoire-Azur). Female immune-deficient BALB/c nu/nu (nude) mice were obtained at 5 weeks of age from Envigo Laboratory (Gannat, France). Nude mice were inoculated subcutaneously with A375 resistant melanoma cells (1.0×106 cells/mouse). After tumor apparition (+5 days), animals received intraperitoneal injection of Labrafil (Control), PLX4032 (0.7 mg/mouse/day) or MTF319 (0.7 mg/mouse/day) dissolved in Labrafil. The growth tumor curves were determined by measuring the tumor volume using the equation V=(L*W2)/2 (V=tumor volume, W=tumor width, L=tumor length). At the end of the experiment, mice were euthanized by cervical dislocation.

(174) The results are shown in FIGS. 6A and 6B. They show a decrease in tumor volume when mice were injected with MTF319. The tumor weight also indicates that MTF319 had an effect on the tumor growth.

(175) CRO15 Inhibits Tumor Growth of Murine Melanoma BP Cells Allografted into C57BL6 Mice

(176) In Vivo Murine Cancer Model Animal experiments were carried out in accordance with the Declaration of Helsinki and were approved by a local ethical committee CIEPAL (Comite Institutionnel d'Ethique Pour l'Animal de Laboratoire-Azur). Female C57BL6/J mice were obtained at 5 weeks of age from Envigo Laboratory (Gannat, France). Mice were inoculated subcutaneously with BP melanoma cells (1×10.sup.6 cells/mouse). After tumor apparition (+5 days), animals received intraperitoneal injection of Labrafil (vehicle) or CRO15 (0.7 mg/mouse/day). The growth tumor curves were determined by measuring the tumor volume using the equation V=(L*W2)/2, (V=tumor volume, W=tumor width, L=tumor length). At the end of the experiment, mice were euthanized by cervical dislocation.

(177) The results are shown in FIG. 7A. The bars indicate the mean±SEM. *p<0.05; **p<0.01. They show that immunocompetent mice (C57BL/6) subcutaneously injected with murine melanoma cells (BP cells) showed no tumor growth when treated daily with CRO15 compared with those treated with vehicle.

(178) To study weither melanoma cells WM9 would develop resistance to CRO15, these cells were kept in culture during 8 weeks in presence of increasing concentrations of either, DMSO (control), PLX4032, CRO15 or MTF255. The starting concentration was 0.2 μM. Every 2 passages, drug concentration was slightly increased (+0.2 μM) until reaching resistance to PLX4032 when channeling with 10 μM as observed in the FIG. 7B.

(179) Along with non-treated WM9S (naive cells), drug-treated WM9S were then stimulated with 10 μM of each drug during 48 hrs. Viable cells were counted using the trypan blue dye exclusion method. The results are normalized as percentages compare to the control (DMSO). Error bars represents ±SEM of triplicate.

(180) The results are shown in FIG. 7B. They show that that PLX-treated WM9 became resistant to PLX4032 while CRO15 is still able to induce cell death in CRO15-treated WM9.

(181) TABLE-US-00001 TABLE 1 Viab Viab Viab Viab A375 A375 A375 A375 10 μM/ 5 μM/ 10 μM/ 5 μM/ ID Structure 24 h 24 h 48 h 48 h CRO15 0 23% 36% 2.6% 27% MTF 232 33.9% ±2 83.3% ±5.3 16.4 ±4.9% 24.9% ±8.5 MTF 233 7% ±0.6 13.9% ±3.6 4.7% ±1.7 8.9% ±2.1 MTF 234 9.6% ±3.2 29.6% ±6.1 7.8% ±3.6 17.4% ±3.6 MTF 242 13.4% ±4.5 29.2% ±0.0 2.9% ±4 8.1% ±3.1 MTF 243 12.1% ±3.1 22.1% ±3.8 2.7% ±1.7 7% ±11.1 MTF 244 84.9% ±9.9 81.6% ±22.6 68.4% ±13.4 68% ±26 MTF 245 83% ±16.3 95% ±9.2 79.6% ±7.8 100% ±8.5 MTF 246 94% ±58 137% ±33.7 115% ±26 91% ±7.8 MTF 247 122% ±79 100% ±33 100% ±49 135% ±39 MTF 248 0 80% ±7.2 100% ±31 138% ±59 100% ±16 MTF 249 14.4% ±1 25.4% ±8.1 8.9% ±2.9 10.6% ±6.7 MTF 250 12% ±1.5 25.4% ±4.2 2.4% ±1.2 8.9% ±5.6 MTF 251 45.1% ±3.1 48.9% ±3.6 19.5% ±7.8 44.7% ±2.9 MTF 252 12.9% ±1 8.6% ±3 2.6% ±1 5.2% ±4.6 MTF 253 14.9% ±2.5 27.8% ±7.6 4.1% ±3.5 6.9% ±5 MTF 254 100% ±31 100% ±23 100% ±12 100% ±55 MTF 255 3.2% ±1.7 IC50 = 2.3 μM 26.1% ±7.1 3.8% ±0.6 4.7% ±5.3 MTF 256 66% ±3.2 93.9% ±2.3 95.7% ±20 60% ±7.1 MTF 257 106% ±18 100% ±10 62% ±11 80.5% ±7.1 MTF 259 0 98% ±24 157% ±1.7 96.5% ±11 95.7% ±26.3 MTF 260 76.7% ±21 57% ±2.5 78% ±65 32% ±24 MTF 261 71.9% ±6.4 24.6% ±11 115% ±1.4 63.6% ±9.9 MTF 262 40.8% ±9.1 61.4% ±15.7 27.3% ±5.3 43.7% ±17.6 MTF 263 100% ±7.6 89.5% ±8.4 66% ±8 91% ±6.8 MTF 264 89% ±19 87% ±15 99% ±28 94.9% v46 MTF 265 84% ±3.8 91% ±8.7 60% ±8.4 100% ±10 MTF 267 134% ±5.4 113% ±11.9 73.3% ±39 113% ±29 MTF 268 146% ±13.7 67% ±6.1 122% ±43 47% ±5.5 MTF 272 88% ±10 100% ±6.2 54.6% ±32 81% ±21 MTF 273 0 100% ±6.6 46% ±2.9 100% ±12 48% ±8.2 MTF 274 84% ±11 83% ±5.9 89% ±20 93% ±15 MTF 276 73.9% ±24.4 91.6% ±5.1 64.9% ±7.2 95.3% ±13.9 MTF 277 76.4% ±5.2 77.6% ±16 85.8% ±10 88% ±12 MTF 281 57.4% ±4.9 79% ±15 78% ±15 112% ±2 MTF 283 100% ±9 100% ±10 150% ±4 56% ±5.6 MTF 284 104.1% ±11.4 80.1% ±3.1 76.9% ±9.2 117.3% ±13.1 MTF 285 77.8% ±8 45% ±4.5 78.7% ±3.8 100% ±8 MTF 286 65.3% ±7.3 48% ±2.3 120% ±11.5 155% ±16 MTF 287 53.7% ±3.8 60.9% ±11.7 69.5% ±14.2 86.7% ±19.8 MTF 288 0 70% ±4.6 50% ±10 53.5% ±14.9 96.7% ±17 MTF 289 78.7% ±29 81.1% ±7.2 58.2% ±12.5 90.4% ±26.5 MTF 290 50.5% ±5.6 43.4% ±8.3 14.4% ±2.4 21.6% ±15.9 MTF 291 100% ±11 100% ±12 41.3% ±1.8 95.2% ±15.9 MTF 292 141.9% ±12.9 88.1% ±8.9 71.9% ±8 83.3% ±18.7 MTF 295 66.1% ±7.2 108.9% ±18.9 39.3% ±4.2 37.3% ±15 MTF 296 21.1% ±9.5 39.4% ±7.1. 6.8% ±6.1 11.7% ±6.8 MTF 297 97.9% ±8.1 86.2% ±7.5 24.9% ±7.2 59.8% ±5.5 MTF 298 87.5% ±5.1 97.2% ±13 54.7% ±21.8 73.6% ±15.1 MTF 299 72.8% ±14.6 91.1% ±7.2 46.2% ±2.8 76.6% ±32.5 MTF 300 00 50.8% ±6.4 96% ±9.3 35.9% ±6 60% ±16.1 MTF 301 01 106.4% ±14.2 74% ±15 31.6% ±20 47% ±23 MTF 302 02 94.8% ±3.5 104.6% ±9 39.3% ±8.7 52.3% ±24.3 MTF 303 03 66.1% ±6.1 85.6% ±23.2 39.1% ±16 44.2% ±4.9 MTF 305 04 5.5% ±0 11% ±4.6 4.7% ±2.5 20.7% ±13.1 MTF 316 05 103.8% ±13.3 124.5% ±9.3 48.2% ±8.5 69.6% ±37.5 MTF 317 06 108.6% ±6.6 106.4% ±9.5 70% ±17.7 58.7% ±21.1 MTF 318 07 20.5% ±0.6 74.1% ±3.8 6.3% ±3.2 21.6% ±5 MTF 319 08 8.6% ±4 8.6% ±2.1 0.6% ±0.6 3.1% ±1.2 MTF 320 09 10.8% ±2.5 18.3% ±3.1 8.5% ±1.5 11.5% ±1.5 MTF 321 0 53.8% ±5.8 59.7% ±2.1 32.1% ±9.1 34.5% ±1.4 MTF 322 26.9% ±2.6 57.4% ±4 5.7% ±2 12.1% ±1.5 MTF 323 47.4% ±1.5 34.6% ±4.6 8.3% ±3.1 23.5% ±3.2 MTF 324 12.9% ±3 44.1% ±7.5 8.2% ±0.7 13.3% ±3.25 MTF 325 71% ±1 58.1% ±0 29.7% ±3.2 30.9% ±5.7 MTF 326 12.9% ±0 27.4% ±0.7 6.7% ±3.1 27.9% ±0.7 MTF 327 23.7% ±0.6 19.4% ±1.7 14.5% ±4.6 14.5% ±1 MTF 328 27.8% ±6.4 50% ±8.2 3.4% ±3 9.4% ±4.4 MTF 329 74.2% ±6.1 96.2% ±3.5 22.5% ±13.1 69.7% ±2.1 MTF 330 60.1% ±10.7 122.7% ±17 41.6% ±9.1 73.9% ±3.5 MTF 331 0 150.8% ±3.5 104.5% ±2.8 77.4% ±16.3 82.9% ±4.2 MTF 332 104.5% ±8.2 122% ±9.2 65.4% ±6.4 87.6% ±6.4 MTF 333 28.7% ±3.2 94.9% ±0.9 24.1% ±3.9 35.4% ±1 MTF 342 32.2% ±5.7 48.6% ±5.5 8.6% ±3.2 8.6% ±3.2 MTF 343 34.8% ±5.5 67.7% ±21 24.1% ±14.2 52.9% ±13.4 MTF 344 38.7% ±7.8 84.3% ±0.7 26.1% ±11.6 26.1% ±11.6 MTF 345 17.1% ±2.8 25.9% ±2.5 1% ±0.6 1.8% ±0.6 MTF 346 43.2% ±0 66.9% ±1.4 12.9% ±7.2 10.6% ±5.6 MTF 347 27.6% ±2.1 26.9% ±2.1 6.8% ±3.5 6.6% ±3.2 MTF 348 110% ±9.2 101.8% ±11 35.8% ±4.9 79.6% ±44.5 MTF 379 0 95.7% ±14.8 148.2% ±10.3 86.2% ±0 76.9% ±12.7 MTF 380 36.2% ±6 47.3% ±5.7 2.3% ±1 4.9% ±1.2 MTF 381 90.6% ±13.2 88.3% ±8.5 61.4% ±24.4 61.6% ±31.8 MTF 382 17.4% ±1.5 14.7% ±5.5 4.5% ±3.1 1.8% ±0.7 MTF 383 41.6% ±6.4 43.1% ±11.5 7.1% ±6.4 40.6% ±23.3 MTF 384 93.3% ±4.7 76.1% ±7.5 72.2% ±10.6 119.3% ±13.4 MTF 385 86.6% ±11.5 52.3% ±6.4 81.5% ±10.6 68.1% ±3.5 MTF 386 18.1% ±5.3 28.9% ±8.7 3.7% ±0.6 6.6% ±3.5 MTF 387 67.8% ±1.5 70.1% ±14.4 55.6% ±14 56.2% ±5 MTF 388 55.7% ±7.5 61.4% ±15.5 18.4% ±2.1 65.1% ±7.8 MTF 389 0 75.8% ±4 74.6% ±2.6 76.4% ±11.3 85.6% ±13.4 MTF 394 4.5% ±1 13.1% ±1.2 1.1% ±0.6 4.4% ±1.2 MTF 396 7.5% ±1.2 19.2% ±5.1 0% ±0 12.1% ±4.9 MTF 397 13.4% ±1 35.4% ±3.1 7.3% ±2.1 33.7% ±4 MTF 398 91% ±9.5 91.9% ±2.3 108.6% ±11.3 132.4% ±0.7 MTF 373 38.6% ±5.7 34.3% ±2.1 22.8% ±3.2 22.5% ±10.6 MTF 374 24.0% ±7.1 47.0% ±7.3 27.7% ±9.2 69.2% ±0.0 MTF 375 30.9% ±8.7 47.2% ±2.1 15.5% ±0.7 29.5% ±3.5 MTF 376 24.3% ±7.6 44.7% ±5.7 20.9% ±7.5 38.9% ±2.1 MTF 377 22.7% ±9.2 27.3% ±3.5 33.5% ±4.2 34.4% ±2.1 MTF 443 0 13.8% ±6.4 42.3% ±7.1 7.8% ±4.2 10.2% ±4.0 MTF 445 72.4% ±7.4 62.6% ±10.3 16.3% ±0.0 35.2% ±10.6 MTF 446 16.3% ±1.5 62.6% ±3.5 1.8% ±1.4 13.0% ±6.8 MTF 449 59.1% ±8.5 74.2% ±14.6 53.0% ±5.0 67.8% ±23.3 MTF 450 38.3% ±15.0 38.6% ±17.1 49.9% ±17.6 54.8% ±16.4 MTF 451 10.6% ±4.9 26.1% ±7.5 12.5% ±9.3 23.9% ±17.7 MTF 452 22.3% ±11.6 43.6% ±1.5 40.3% ±6.8 60.5% ±14.0 MTF 455 32.3% ±0.6 89.0% ±13.1 69.5% ±17.1 108.1% ±9.9 MTF 456 52.3% ±3.6 66.5% ±1.5 76.1% ±30.8 87.5% ±23.4 MTF 458 46.5% ±9.9 58.7% ±3.2 103.7% ±7.2 86.8% ±11.5 MTF 460 0 64.5% ±12.1 61.9% ±6.1 38.6% ±2.8 69.5% ±7.1 MTF 462 4.8% ±17.4 101.3% ±37.3 44.1% ±6.9 80.0% ±17.7 MTF 463 56.1% ±5.2 80.0% ±6.8 43.4% ±7.1 74.3% ±21.4