• The Korean Journal of Pesticide Science
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• v.5 no.2
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• pp.13-17
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• 2001

A synthesis of new 2-phenylimino-1,3-thiazolines 2 for the purpose of development of new agrochemical fuugicide was described. Reaction of chlorine with diketene followed by treatment of benzylamine without isolation of intermediate 8a gave ${\gamma}-chloro-{\beta}-keto$ benzylamide 10a. Thioureas 4 obtained from the reaction of methyl isothiocyanate with aniline derivatives were subjected to 10a in acetone solution to afford the corresponding 2-phenylimino-1,3-thiazoline hydrochloric acid salts 2 through unisolable inltermediates 11 and 12. The plausible reaction mechanism including nucleophilic attack of sulfur assisted neighboring nitrogen lone pair electron on phenyl of thiourea 4 was discussed.

• Bulletin of the Korean Chemical Society
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• v.33 no.5
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• pp.1703-1706
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• 2012

Rice blast is the most serious disease of rice due to its harmfulness and its world wide distribution. $Magnaporthe$ $grisea$ is the cause of rice blast disease and destroys rice enough to feed several tens of millions of people each year. Fungicides are commonly used to control rice blast. But $M.$ $grisea$ acquires resistance to chemical treatments by genetic mutations. 2-Phenylimino-1,3-thiazolines were proposed as a novel class of fungicides against $M.$ $grisea$ in the previous study. To develop compounds with a higher biological activity, a new series of 2-phenylimino-1,3-thiazolines was synthesized and its fungicidal activity was determined against $M.$ $grisea$. The QSAR analysis was carried out on a series of 2-phenylimino-1,3-thiazolines. The QSAR results showed the dependence of fungicidal activity on the structural and physicochemical features of 2-phenylimino-1,3-thiazolines. Our results could be used as guidelines for the study of the mode of action and further design of optimal fungicides.

• The Korean Journal of Pesticide Science
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• v.7 no.1
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• pp.51-57
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• 2003

For the purpose of a development of new agrochemical fungicides, new compound 4 in which 1,3-thiazoline scaffold as well as urea moiety in the structure was designed through molecular modification of lead compound, 2-imino-1,3-thiazone based on isosterism. The reaction of N-alkylthiourea 5 and bromoacetonitrile in ethanol gave 2,4-diimino-1,3-thiazolidine hydrobromide 6 regioselectively, which was treated with isocyanates gave the corresponding 8 which is tautomer of 4. Antifungal screening (in vivo) of the synthesized compound 8 against typical plant diseases, which include rice blast, rice sheath blight, cucumber gray mold, tomato late blight, wheat leaf rust, and barley powdery mildew, was carried out. Antifungal activities against rice blast of the compound 8 were weaker than those of 2-phenylimino-1,3-thiazoline 1. Some compounds showed weak antifungal activities against wheat leaf rust.

• The Korean Journal of Pesticide Science
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• v.10 no.3
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• pp.165-171
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• 2006

A new 3-amino-1,3-thiazoline chemical library was synthesized through parallel synthetic technology and in vivo antifungal activity of the compounds were investigated against the typical 6 plant diseases (100 ppm). The characteristic feature of these derivatives was that both a benzyl moiety in C-2 imino and an amino group in C-3 of 2-imino-1,3-thiazoline scaffold were substituted in the molecule respectively. Some compounds showed antifungal activity with selectivity against tomato late blight and rice blast. The fungitoxicity would be attributed to 3,4-dichlorophenyl moiety of the benzyl group.

• The Korean Journal of Pesticide Science
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• v.8 no.3
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• pp.168-174
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• 2004

In a course of the process for a lead optimization of 2-imino-l,3-thiazolines 1 which show a selective in vivo antifungal activity against rice blast, new compounds 2 in which C-5 was substituted by methyl group of the lead compound were synthesized and tested for the biological activity. Bromination of $\beta$-keto ester 7 followed by the reaction with thiourea and hydrolysis gave 2-imino-5-methyl-l,3-thiazoline carboxylic acid 3. Coupling reactions of 3 with aniline derivatives afforded 17 kinds of the corresponding 2-imino-5-methyl-l,3-thiazoline carboxanilides 2. Their in vivo antifungal activity against rice blast was weaker than that of 1, indicating that the in vivo antifungal activity of 2-imino-l,3-thiazolines was affected by the substituent at C-5. These results would be an important data for the molecular design in the lead optimization process of this series.

• The Korean Journal of Pesticide Science
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• v.13 no.2
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• pp.63-69
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• 2009

New morpholinylcarbonylmethyl-2-phenylimino-1,3-thiazolines 2(X=O) and piperidinylcarbonylmethyl-2-phenylimino-1,3-thiazolines 3(X=C) to which morpholinyl or piperidinyl functional group were introduced at C-4 side chain of the 2-phenylimino-1,3-thiazoline scaffold were synthesized to investigate the effect of NH hydrogen of 2-phenylimino-1,3-thiazoline-4-acetanilide derivatives on the antifungal property against rice blast. Synthesized 30 compounds were screened against 6 kinds of typical plant fungi. Treatment of ketene dimer with chlorine followed by the reaction of morphorine or piperidine without isolation of the intermediate acetoacetylchloride gave $\gamma$-chloro-$\beta$-keto derivatives. These were reacted with thioureas to give morpholinylcarbonylmethyl-2-phenylimino-1,3-thiazolines and piperidinylcarbonylmethyl-2-phenylimino-1,3-thiazolines respectively in good yield (27-98%). The compound 3j, in which two fluorine atoms are substituted at ortho and para position of phenyl group of 2-phenylimino moiety and piperidinyl group is substituted at C-4, showed the highest antifungal activity (100 ppm, 90%). This result suggested that the substituent at C-4 of the 2-phenylimino-1,3-thiazolines may play a supplementary role to show the antifungal activity against rice blast.

• Bulletin of the Korean Chemical Society
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• v.33 no.9
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• pp.2985-2990
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• 2012

New thiazoline derivatives 7a-c, and thiophenes 9a-c linked to indole moiety were easily prepared via the reaction of the acrylamide derivative 3 with phenacyl bromides 4a-c, depending on the reaction conditions. In addition, the reaction of compound 3 with hydrazonoyl chlorides 11a-f afforded a series of 1,3,4-thiadiazole derivatives 13a-f. Moreover, coupling of 3-(3-methyl-1H-indol-2-yl)-3-oxopropanenitrile (2) with the diazonium salts of 3-phenyl-5-aminopyrazole 16 or 3-amino-1,2,4-triazole 17 gave the corresponding hydrazones 18 and 19, respectively. Cyclization of the latter hydrazones yielded the corresponding pyrazolo[5,1-c]-1,2,4-triazine and 1,2,4-triazolo[5,1-c]-1,2,4-triazine derivatives 20 and 21, respectively. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, $^1H$ NMR and mass spectral data. All the synthesized compounds were tested for in vitro activities against certain strains of fungi such as Aspergillus niger, Aspergillus nodulans, Alternaria alternate. Compounds showed marked inhibition of fungal growth nearly equal to the standards.

• Applied Biological Chemistry
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• v.40 no.2
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• pp.139-143
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• 1997

This research aims at developing a new pesticide by means of synthesizing new 2-iminothiazoline derivatives and testing their bilolgical activity. In an effort to prepare 2-iminothiazolines, primary amines were treated to have reaction with isothiocyanate, followed by a treatment of ${\alpha}-halo$ ketone derivatives. Their antifungal activaty was tested against six different plant diseases. A compound that has a phenylimino group at C-2, methyl at C-3, phenylcarbamoylmethyl at C-4, and hydrogen at C-5 on the thiazoline skeleton was found to be most active.

• Journal of the Korean Chemical Society
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• v.54 no.1
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• pp.77-87
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• 2010

Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been an increasing problem worldwide since the initial reports over 40 years ago. To examine new drug leads with potential antibacterial activities, Various N'-[(-3-substituted-4-oxo-1,3-thiazolidin-2-ylidene]-4-hydroxy benzohydrazide (4a-4.i) and N'-[-(3,4-disubstituted)-1,3-thiazolidin-2ylidene)]-4-hydroxybenzohydrazide from (5.a-5.i) to (10.a-10.i) were synthesized using appropriate synthetic route. The entire test compounds (4.a-4.i) and from (5.a-5.i) to (10.a-10.i) were assayed in vitro against s. aureus strain. The minimum inhibitory concentration (MIC) was determined for test compounds and for reference standards. The test compounds showed significant antibacterial activity against the strains used, when tested in vitro. In general, p-hydroxybenzohydrazide ring and substituted thiazoline ring are essential for antimicrobial activity. Among the compounds tested, compounds 6.f, 7.g, 9.f and 10.f, 10 i were found to be most potent. The test compounds were found nontoxic upto the dose level of 2000 ${\mu}g$/mL. The intact compounds were then subjected for 3D-QSAR studies. 3D-QSAR study based on the principal of alignment of pharmacophoric features by Schrodinger PHASE module. The 3D-QSAR study allowed us to confirm the preferential binding mode of p-hydroxybenzohydrazide inside the active site.