Field of the Invention
In general, the present invention relates to the field of products related to neurodegenerative diseases. More particularly, the present invention directed to novel Thiazole compounds and their conjugates, process for preparing the same and use thereof in various pharmaceutical formulations.

Background of the Invention
Neurological disease has a destructive impact on society, healthcare costs, patients and their care providers. Alzheimer disease is one of them. It is a progressive neurological disorder in the elderly aged for which no cure exists. According to WHO report in 2015 an approximately 44 million people worldwide have Alzheimer disease (AD) and this number will be increased up to approximately 65 million in 2030 and 131 million in 2050. From the static data shown in 2015 it is clear that Asian country being the most affected country by this disease, an approximately 22 million people only in Asia, suffered from this disease which is almost half of the worldwide and this number will have increased up to 38 million in 2030 and 67 million in 2050. The AChE, BuChE and JNK3 are attractive targets for the treatment of AD.

People have synthesized several heterocyclic molecules such as coumarin derivatives, tacrin-coumarine conjugates, tacrine-8-hydroxyquinoline hybrid, benzylpiperidine-linked diarylthiazoles, berberine-phenyl-benzoheterocyclic, tacrine-phenylbenzoheterocyclic hybrids, pyridazine derivatives, tacrine-triazole-based inhibitors, 4-aminoquinoline derivatives, 1,3,4-thiadiazole analogues, 2,4-disubstituted pyrimidine derivatives, piperidine-hydrazone derivatives, pyridonepezil derivatives. Examples of JNK3 inhibitors includes aminopyrazoles, anilinoindazoles, pyroroloimidazoles, aminopyrimidines, pyridine carboxamides, benzothiazole-2-yl acetonitriles, benzothien-2-yl-amides and so on.

1,2,4-Triazole and its derivatives are an important class of compounds which possess diverse agricultural, industrial and biological activities, including anti-microbial, sedative, anticonvulsant, anticancer, anti-inflammatory, diuretic, antibacterial, hypoglycemic, antitubercular and antifungal activities. In recent years, the synthesis of these heterocyclic compounds has received considerable attention. This wide range of applications has been covered by more than sixty papers in the literature, many in the form of patents inhibitor.

Thiazole is a well-known five-membered heterocyclic compound. Various methods have been worked out for its synthesis. In the last few decades, a lot of work has been done on thiazole ring in order to find new compounds related to this scaffold acting as an antioxidant, analgesic, anti-inflammatory, anti-microbial, antifungal, antiviral, diuretic, anticonvulsant, neuroprotective and antitumor or cytotoxic drugs with lesser side effects.

Cholinesterase inhibitors are used for the treatment of various diseases such as pancreatitis, thrombosis, type-2 diabetes, and Alzheimer’s disease (AD). The JNK3 inhibitors are used for the treatment of Alzheimer’s disease, Parkinson’s disease, Huntington's disease and stroke.

Cholinesterase is an enzyme and is a family of serine hydrolases because it has an ability to hydrolyze substrate using an active site nucleophillic serine residue. The serine hydrolases super family belongs to a large group of proteins which involved in many important physiological processes e.g. blood coagulation, digestion, and neurotransmission, and therefore many of these enzymes linked to various diseases such as pancreatitis, thrombosis, and Alzheimer’s disease (AD). Therefore, cholinesterase is an attractive target for the drug discovery.

On the other hand, c-Jun N-terminal kinases (JNKs) have been recognized as important enzymes in cellular function. JNK3, which is predominantly found in CNS neurons, has been implicated in several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington's disease and stroke.

Various known medicines have been developed for neurodegenerative diseases such as Donepezil, Galantamine, Rivastigmine are FDA approved drugs for the treatment of AD which inhibits cholinesterase enzyme. However, the said drugs show side effects like headache, seizures, insomnia, fatigue, aggression, chest pain, hypertension, atrial fibrillation, bradycardia, AV block etc.

Summary of the Invention
One object of the present invention is to provide a compound of N-Benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide derivatives as AChE, BuChE and JNK3 inhibitor.

Another object of the present invention is to provide a compound of 3-[2-(4-Phenylthiazol-2-ylamino)-acetyl]-chromen-2-one derivatives as AChE, BuChE and JNK3 inhibitor.

In accordance with one embodiment of the present invention, there is provided a novel compound N-benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide of formula 1, wherein R1, R2 & R3 are selected from a group comprising H, F, Cl, Br, CN, OCH3, OH, NH2, NO2, alkyl, allyl, N-alkyl, N-aryl, N-piperazine, N-morpholine and wherein said substituents are interchangeable.

In accordance with another embodiment of the present invention, there is provided a novel compound N-benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide of formula 1, is prepared by reacting N-(benzo[d]thiazol-2-yl)-2-chloroacetamide (7) with substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (4).

In accordance with another embodiment of the present invention, there is provided a novel compound N-Benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide of Formula 1, is prepared by reacting N-(benzo[d]thiazol-2-yl)-2-chloroacetamide (7) with substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (4), and wherein said compound N-(benzo[d]thiazol-2-yl)-2-chloroacetamide (7) is prepared by a method comprising stirring aniline (5) in glacial acetic acid to obtained 2-aminobenzothiazole derivatives (6) and the resultant 2-aminobenzothiazole derivatives (6) is further stirred in THF and choloroacetylchloride in presence of non-nucleophilic base 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) to obtain the compound N-(benzo[d]thiazol-2-yl)-2-chloroacetamide (7).

In accordance with another embodiment of the present invention, there is provided a novel compound N-benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide of Formula 1, is prepared by reacting N-(benzo[d]thiazol-2-yl)-2-chloroacetamide (7) with substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (4) and wherein said compound substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (4) is prepared by a method comprising stirring substituted aromatic esters (1) in presence of ethanol and hydrazine hydrate to obtain benzohydrazide (2), the resultant benzohydrazide is further stirred with CS2 and KOH in presence of absolute ethanol to obtain 2-benzoylhydrazine-1-carbodithioate (3), which is refluxed with stirring in presence of water and hydrazine hydrate to obtain a compound of substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (4).

In accordance with another embodiment of the present invention, there is provided a novel compound N-benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide of Formula 1, wherein a pharmaceutical formulation is prepared comprising the compound of formula (1) along with pharmaceutically acceptable excipients, wherein said pharmaceutical formulation is in a form of any pharmaceutically acceptable doses form.

In accordance with another embodiment of the present invention, there is provided a novel compound 3-[2-(4-phenylthiazol-2-ylamino)acetyl]chromen-2-one of Formula 2, wherein R1,& R2 are selected from a group comprising H, F, Cl, Br, NO2, CN, OH, O-alkyl, NH2, N-alkyl, N-aryl, N-piperazine, N-morpholine, allyl and wherein said substituents are interchangeable.

In accordance with another embodiment of the present invention, there is provided a novel compound 3-[2-(4-phenylthiazol-2-ylamino)acetyl]chromen-2-one of Formula 2, wherein the compound 3-[2-(4-phenylthiazol-2-ylamino)acetyl]chromen-2-one of Formula 2 is prepared by reacting 2-amino-4-phenylthiazole (14) with 3-(2-Bromo-acetyl)-chromen-2-one (11).

In accordance with another embodiment of the present invention, there is provided a novel compound 3-[2-(4-phenylthiazol-2-ylamino)acetyl]chromen-2-one of Formula 2, wherein the compound 3-[2-(4-phenylthiazol-2-ylamino)acetyl]chromen-2-one of Formula 2 is prepared by reacting 2-amino-4-phenylthiazole (14) with 3-(2-bromoacetyl)-chromen-2-one (11) and wherein the compound 3-(2-bromoacetyl)-chromen-2-one (11) is prepared by a process comprising reacting ethylacetoacetate (9) with salicayldehyde (8) to obtain 3-acetylchromen-2-one (10), wherein the resultant 3-acetylchromen-2-one (10) further stirred in presence of Br2/CHCl3 to obtain 3-(2-bromoacetyl)-chromen-2-one (11).

In accordance with another embodiment of the present invention, there is provided a novel compound 3-[2-(4-phenylthiazol-2-ylamino)acetyl]chromen-2-one of Formula 2, wherein the compound 3-[2-(4-phenylthiazol-2-ylamino)acetyl]chromen-2-one of Formula 2 is prepared by reacting 2-amino-4-phenylthiazole (14) with 3-(2-bromoacetyl)-chromen-2-one (11) and wherein the compound 2-amino-4-phenylthiazole (14) is prepared by reacting substituted phenacyl bromide (12) with thiourea (13) in THF.

In accordance with another embodiment of the present invention, there is provided a novel compound 3-[2-(4-phenylthiazol-2-ylamino)acetyl]chromen-2-one of Formula 2, wherein a pharmaceutical formulation is prepared comprising the compound of Formula (2) along with pharmaceutically acceptable excipients, wherein said pharmaceutical formulation is in a form of any pharmaceutically acceptable doses form.

These and other embodiments of the invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.

Description of the Invention
The particulars shown herein are by way of example and for purposes of illustrative discussion of the various embodiments of the present invention only and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual embodiments/aspects of the invention. In this regard, no attempt is made to show details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.

While this specification concludes with claims particularly pointing out and distinctly claiming that, which is regarded as the invention, it is anticipated that the invention can be more readily understood through reading the following detailed description of the invention and study of the included examples.

One object of the present invention is to provide a compound of N-Benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide derivatives as AChE, BuChE and JNK3 inhibitors.

Another object of the present invention is to provide a compound of 3-[2-(4-Phenyl thiazol-2-ylamino)-acetyl]-chromen-2-one derivatives as AChE, BuChE and JNK3 inhibitors.

In accordance with one embodiment of the present invention, there is provided a compound of formula 1;

Formula 1
wherein R1, R2 & R3 are selected from a group comprising H, F, Cl, Br, CN, OCH3, OH, NH2, NO2, alkyl, allyl, N-alkyl, N-aryl, N-piperazine, N-morpholine and wherein the said groups are interchangeable as a substituent on R1, R2 & R3 considering desired results;
wherein R1, R2 & R3 are Hydrogen;
wherein R1 and R3 are H and R2 is X selected from F, Cl or Br;
wherein R1 is X, preferably Br and R2 and R3 are H;
wherein R1 and R3 are H and R2 is selected from OCH3, NO2 or CH3;
wherein R1, R2 & R3 are OCH3;

In accordance with another embodiment of the present invention, there is provided a compound of formula 2;

Formula 2
wherein R1,& R2 are selected from a group comprising H, F, Cl, Br, NO2, CN, OH,
O-alkyl, NH2, N-alkyl, N-aryl, N-piperazine, N-morpholine, allyl and wherein the said groups are interchangeable as a substituent on R1 & R2 considering desired results;
wherein R1, R2 are Hydrogen;
wherein R1 is H and R2 is selected from H, Br, NO2 or OCH3;
wherein R2 is H and R1 is selected from H, F, Cl, Br, CN, OCH3, NO2 or CH3;
wherein R1 & R2 are Cl;

In accordance with one other embodiment of the present invention, there is provided a method for preparing a compound N-benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide derivatives (8) of Formula 1, wherein said method comprises reacting N-(benzo[d]thiazol-2-yl)-2-chloroacetamide (7) with substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (4);

In accordance with one other embodiment of the present invention, there is provided a method for preparing a compound N-(benzo[d]thiazol-2-yl)-2-chloroacetamide (7), wherein said compound is prepared by stirring aniline (5) in glacial acetic acid to obtained 2-aminobenzothiazole derivative (6), the resultant 2-aminobenzothiazole derivative (6) is further stirred in THF and choloroacetylchloride in presence of non-nucleophilic base DBU to obtain the compound N-(benzo[d]thiazol-2-yl)-2-chloroacetamide (7).

In accordance with one other embodiment of the present invention, there is provided a method for preparing a compound of substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (4), wherein said compound is prepared by a method comprising stirring substituted aromatic esters (1) in presence of ethanol and hydrazine hydrate to obtain benzohydrazide (2), further the resultant benzohydrazide derivatives are converted into their corresponding salts by reaction with CS2 in ethanolic solution of KOH. The reaction mixture is agitated continuously for a period of 15 hours. It was then diluted with anhydrous ether and the precipitated potassium dithiocarbazinate is collected by filtration to obtain 2-benzoylhydrazine-1-carbodithioate (3), The salt thus obtained is dissolved in water and refluxed with hydrazine hydrate to obtain a compound of substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (4).

In accordance with another embodiment of the present invention, there is provided novel triazole-thiazole conjugate of formula 1, wherein said conjugate is produced by a method as shown in the following reaction sequence.

wherein R1, R2 & R3 are selected from a group comprising H, F, Cl, Br, CN, OCH3, OH, NH2, NO2, alkyl, allyl, N-alkyl, N-aryl, N-piperazine, N-morpholine and wherein the said groups are interchangeable as substituents on R1, R2 & R3 considering desired results;
wherein R1, R2 & R3 are Hydrogen;
wherein R1 and R3 are H and R2 is X selected from F, Cl or Br;
wherein R1 is X, preferably Br and R2 and R3 are H;
wherein R1 and R3 are H and R2 is selected from OCH3, NO2 or CH3;
wherein R1, R2 & R3 are OCH3;
In accordance with one other embodiment of the present invention, there is provided a method for preparing a compound 3-[2-(4-phenylthiazol-2-ylamino) acetyl]chromen-2-one of Formula 2, wherein said method comprises reacting 2-amino-4-phenylthiazole (14) with 3-(2-bromo-acetyl)-chromen-2-one (11).

In accordance with one other embodiment of the present invention, there is provided a method for preparing a compound 3-(2-bromo-acetyl)-chromen-2-one (11), wherein said method comprises reacting ethylacetoacetate (9) with salicayldehyde (8) to obtain 3-acetylchromen-2-one (10), wherein the resultant 3-acetylchromen-2-one (10) further stirred in presence of Br2/CHCl3 to obtain 3-(2-bromoacetyl)-chromen-2-one (11).

In accordance with one other embodiment of the present invention, there is provided a method for preparing a compound 2-amino-4-phenylthiazole (14), wherein said method comprises reacting substituted phenacyl bromide (12) with thiourea (13).

In accordance with another embodiment of the present invention, there is provided novel coumarin-thiazole conjugate of formula 2, wherein said conjugate is produced by a method as shown in the following reaction sequence.

wherein R1 & R2 are selected from a group comprising H, F, Cl, Br, NO2, CN, OH,
O-alkyl, NH2, N-alkyl, N-aryl, N-piperazine, N-morpholine, allyl and wherein the said groups are interchangeable as substituents on R1 & R2 considering desired results;
wherein R1, R2 are Hydrogen;
wherein R1 is H and R2 is selected from H, Br, NO2 or OCH3;
wherein R2 is H and R1 is selected from H, F, Cl, Br, CN, OCH3, NO2 or CH3;
wherein R1 & R2 are Cl;

In accordance with one other embodiment of the present invention, there is provided a pharmaceutical formulation comprising a compound of formula (1) along with pharmaceutically acceptable excipients.

In accordance with one other embodiment of the present invention, there is provided a pharmaceutical formulation comprising a compound of formula (2) along with pharmaceutically acceptable excipients.

Below are the various examples for preparing different compounds according to the present invention. However, the below examples are not limited and will be worked on within the scope of the current invention and filed during the complete application.

Example 1
Synthesis of Benzohydrazide (2)
In 100 ml round bottom flask substituted aromatic esters (1, 0.1 M) are dissolved in 30 ml ethanol, and hydrazine hydrate (0.1 M) is added dropwise to the mixture with stirring. The resulting mixture is allowed to reflux for 6 hrs. The completion of the reaction is monitored by thin layer chromatography (TLC) by using ethyl acetate and petroleum ether (1:1) as the eluent. After completion of reaction excess ethanol is distilled out and the contents are allowed to cool. The crystals formed are filtered which is washed thoroughly with water, and dried. The formed compound is characterized by IR, NMR and M.P.

Example 2
Synthesis of potassium 2-benzoylhydrazine-1-carbodithioate (3)
In 100 ml round bottom flask KOH (0.15 M) is dissolved in absolute ethanol (200 ml). To the above solution, aryl acid hydrazide (2, 0.1 M) is added and the solution cooled on ice. To this, carbon disulfide (0.15 M) is added in small portions with constant stirring. The reaction mixture is stirred continuously for a period of 15 hrs. After completion of reaction ether is added to the reaction mixture and stirred vigorously for 15-30 min., the solid salt which is precipitated is further filtered and dried on reduced pressure. The potassium salt thus obtained is in quantitative yield and is used in the next step without further purification.

Example 3
Synthesis of substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (4)
A suspension of substituted potassium 2-benzoylhydrazine-1-carbodithioate (3, 0.1 M) in water (5 ml) and hydrazine hydrate (15 ml, 0.3 M) is refluxed for 24 hrs with stirring. The color of the reaction mixture changed to green with the evolution of hydrogen sulfide gas. A homogeneous reaction mixture is obtained during the reaction process. The reaction mixture is cooled to room temperature and diluted with water (100 ml). On acidification with concentrated hydrochloric acid, the required substituted triazole is precipitated out. It is filtered, washed thoroughly with cold water, and recrystallized from ethanol.

Example 4
Synthesis of 2-aminobenzothiazole (6)
2-Amino benzothiazole is synthesised by well established protocol. To 9 ml glacial acetic acid solution (precooled to 5oC), KSCN (20 mmol) and aniline (5, 5 mmol) are added. The mixture is placed in freezing mixture of ice and salt and mechanically stirred. Then Br2 (5 mmol) in 4 ml glacial acetic acid is added from dropping funnel at such rate the temperature does not raise beyond 0-5oC. After all bromine has been added the solution is stirred for overnight at room temperature. The progress of reaction is monitored by TLC. After completion of reaction, the resulting crude solid product is filtered and washed with water. The filtrate is neutralised by adding ammonia. The resulting precipitate is dried and purified by crystallisation. White solid pure product is obtained.

Example 5
Synthesis of N-(benzo[d]thiazol-2-yl)-2-chloroacetamide (7)
A solution of 2-aminobenzothiazole (33.3 mmol) in 15 mL THF (Tetrahydrofuran) is taken in 100 mL round-bottom flask. Further, DBU (6.6 mmol) is added to the solution. The reaction mixture is kept at 0oC. A dropping funnel is fitted to the flask, and a solution of chloroacetylchloride (3.2 mL, 40 mmol, in 2 mL THF) is taken in a dropping funnel and added drop wise to the reaction mixture. The solution is stirred at room temperature for 6 hrs. After completion which is monitored by TLC a crude solid product was obtained. The formed product was characterised by spectroscopic technique.

Example 6
Synthesis of N-Benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide derivatives (8)
N-(Benzo[d]thiazol-2-yl)-2-chloroacetamide (7, 0.1 M) are dissolve in DMF and then added substituted triazole (4, 0.1 M) and 0.5 ml of triethyl amine. The reaction mixture is stirred at 50oC for 4 hrs. The progress of reaction is monitored by TLC. After completion of reaction, the reaction mixture is extracted by ethyl acetate. The solvent is removed under reduced pressure and reaction mixture was extracted with ethyl acetate (3×40 mL). The organic layer is dried over anhydrous sodium sulphate, and the excess of solvent is removed under reduced pressure. The crude product is purified by column chromatography on silica gel (60-120 mesh) using chloroform: methanol 3:1 v/v) as eluent. The formation of obtained acetamide derivative products are further confirmed by elemental analysis and spectroscopic techniques as detailed below:

N-Benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide (R1 = R2 = R3 = H, 8a): Yield: 75%; Mp.: 221-224oC; FTIR (KBr): 3361, 3064, 2995, 2064, 1682, 1597, 1553, 1485, 1318, 1256, 1082, 756 cm-1; 1H NMR (DMSO-d6, 400 MHz,) d: 2.67 (s, 2H, CH2), 3.50 (s, 1H, SH), 7.31-8.00 (m, 9H, ArH), 12.82 (bs, 1H, NH);13C NMR (DMSO-d6, 100 MHz) d:36, 121, 122, 123, 124, 126 (3C of Ar), 129 (2C of Ar), 132 (2C of Ar), 163, 165, 167 (C=O); Anal. calc. for C17H14N6OS2: C, 53.39; H, 3.69; N, 21.97; S, 16.77; found C, 53.32; H, 3.64; N, 21.93; S, 16.71.

N-Benzothiazol-2-yl-2-[3-(4-fluorophenyl)-5-mercapto-[1,2,4]triazol-4-ylamino]acetamide (R1 = R3 = H, R2 = F, 8b): Yield: 68%; Mp.: 242-246oC; FTIR (KBr): 3320, 3164, 2958, 2012, 1679, 1610, 1548, 1480, 1324, 1276, 1086, 750 cm-1; 1H NMR (DMSO-d6, 400 MHz,) d: 2.67 (s, 2H, CH2), 3.38 (s, 1H, SH), 7.19-8.26 (m, 8H, ArH); 13C NMR (DMSO-d6, 100 MHz) d: 38, 114, 117, 120, 122, 123, 125, 127, 131, 148, 155, 162, 164, 169, 173; Anal. calc. for C17H13N6OS2F: C, 50.99; H, 3.27; N, 20.99; S, 16.01; found C, 50.93; H, 3.13; N, 20.96; S, 15.99.

N-Benzothiazol-2-yl-2-[3-(4-chlorophenyl)-5-mercapto-[1,2,4]triazol-4-ylamino]acetamide (R1 = R3 = H, R2 = Cl, 8c): Yield: 62%; Mp.: 258-260oC; FTIR (KBr): 3332, 3176, 3062, 2938, 1928, 1673, 1620, 1555, 1476, 1439, 1417, 1234, 1093, 829, 746, 718, 677 cm-1; 1H NMR (DMSO-d6, 400 MHz) d: 2.74 (s, 2H, CH2), 3.33 (s, 1H, SH), 7.26-8.19 (m, 8H, ArH), 12.65 (bs, 1H, NH); 13C NMR (DMSO-d6, 100 MHz) d: 36, 116, 122, 124, 126, 127, 129, 131, 133, 149, 152, 166, 169, 172; Anal. calc. for C17H13N6OS2Cl: C, 48.98; H, 3.14; N, 20.16; S, 15.38; found C, 49.94; 3.08; N, 20.10; S, 15.32.

N-Benzothiazol-2-yl-2-[3-(4-bromophenyl)-5-mercapto-[1,2,4]triazol-4-ylamino]acetamide (R1 = R3 = H, R2 = Br, 8d): Yield: 58%, Mp.: 278-281oC; FTIR (KBr): 3321, 3165, 3042, 2942, 1936, 1686, 1612, 1548, 1472, 1430, 1232, 1086, 832, 735, 694 cm-1; 1H NMR (DMSO-d6, 400 MHz) d: 2.82 (s, 2H, CH2), 3.42 (s, 1H, SH), 7.21-8.02 (m, 8H, ArH), 12.63 (bs, 1H, NH); 13C NMR (DMSO-d6, 100 MHz) d: 39, 117, 120, 122, 124, 126, 131, 132, 133, 150, 165, 169, 175; Anal. calc. for C17H13N6OS2Br: C, 44.26; H, 2.84; N, 18.22; S, 13.90; found C, 44.21; H, 2.80; N, 18.19; S, 13.86.

N-Benzothiazol-2-yl-2-[3-(3-bromophenyl)-5-mercapto-[1,2,4]triazol-4-ylamino]acetamide (R1 = Br, R3 = R2 = H, 8e): Yield: 53%, Mp.: 241-245oC; FTIR (KBr): 3329, 3156, 3048, 2947, 1948, 1678, 1618, 1568, 1478, 1236, 1094, 746, 675 cm-1; 1H NMR (DMSO-d6, 400 MHz) d: 2.67 (s, 2H, CH2), 3.56 (s, 1H, SH), 7.19-8.06 (m, 8H, ArH), 12.78 (bs, 1H, NH); 13C NMR (DMSO-d6, 100 MHz) d: 38, 118, 120, 122, 123, 125, 126, 127, 129, 131, 132, 136, 152, 154, 166, 169, 173; Anal. calc. for C17H13N6OS2Br: C, 44.26; H, 2.84; N, 18.22; S, 13.90; found C, 44.23; H, 2.80; N, 18.21; S, 13. 83.

N-Benzothiazol-2-yl-2-[3-(4-methylphenyl)-5-mercapto-[1,2,4]triazol-4-ylamino]acetamide (R1 = R3 = H, R2 = CH3, 8f): Yield: 62%, Mp.: 232-236oC; FTIR (KBr): 3346, 3168, 3036, 2946, 1928, 1688, 1626, 1540, 1465, 1245, 1087, 766, 640 cm-1; 1H NMR (DMSO-d6, 400 MHz) d: 2.32 (s, 3H, CH3), 2.86 (s, 2H, CH¬2), 3.46 (s, 1H, SH), 7.14-8.21 (m, 8H, ArH), 12.78 (bs, 1H, NH); 13C NMR (DMSO-d6, 100 MHz) d: 20, 36, 119, 122, 125, 126, 128, 130, 131, 132, 151, 154, 167, 168, 172; Anal. calc. for C18H16N6OS2: C, 54.53; H, 4.07; N, 21.20; S, 16.17; found C, 54.48; H, 3.98; N, 21.19; S, 16.15.

N-Benzothiazol-2-yl-2-[3-(4-methoxylphenyl)-5-mercapto-[1,2,4]triazol-4-ylamino]acetami -de (R1 = R3 = H, R2 = OCH3, 8g): Yield: 57%, Mp.: 256-258oC; FTIR (KBr): 3336, 3146, 3028, 2968, 1967, 1679, 1614, 1529, 1457, 1240, 1076, 748, 656 cm-1; 1H NMR (DMSO-d6, 400 MHz) d: 2.72 (s, 2H, CH2), 3.67 (s, 1H, SH), 3.83 (s, 3H, OCH3), 7.36-8.12 (m, 8H, ArH), 12.72 (bs, 1H, NH); 13C NMR (DMSO-d6, 100 MHz) d: 38, 52, 115, 119, 122, 123, 125, 126, 129, 131, 150, 159, 168, 173; Anal. calc. for C18H16N6O2S2: C, 52.41; H, 3.91; N, 20.37; S, 15.54; found C 52.38; H, 3.87; N 20.32; S, 15.48.
N-Benzothiazol-2-yl-2-[3-(4-nitrophenyl)-5-mercapto-[1,2,4]triazol-4-ylamino]acetamide (R1 = R3 = H, R2 = NO2, 8h): Yield : 48%, Mp.: 296-298oC; FTIR (KBr): 3340, 3160, 2958, 1950, 1685, 1618, 1542, 1473, 1352, 1248, 1056, 773, 642 cm-1; 1H NMR (DMSO-d6, 400 MHz) d: 2.85 (s, 2H, CH2), 3.67 (s, 1H, SH), 7.34-8.14 (m, 8H, ArH), 12.89 (bs, 1H, NH); 13C NMR (DMSO-d6, 100 MHz) d: 39, 120, 123, 126, 127, 129, 132, 138, 149, 153, 155, 169, 171, 176; Anal. calc. for C17H13N7O3S2: C, 47.77; H, 3.07; N, 22.94; S, 15.00; found C, 47.72; H, 3.04; N, 22.90; S, 14.96.

N-Benzothiazol-2-yl-2-[3-(3,4,5-trimethoxyphenyl)-5-mercapto-[1,2,4]triazol-4-ylamino] acetamide (R1 = R3 = R2 = OCH3, 8i): Yield: 44%, Mp.: 241-245oC; FTIR (KBr): 3397, 3156, 2942, 1939, 1681, 1606, 1560, 1448, 1241, 1046, 765, 637 cm-1; 1H NMR (DMSO-d6, 400 MHz) d: 2.88 (s, 2H, CH2), 3.66 (s, 1H, SH), 3.72 (s, 3H, OCH3), 3.84 (s, 6H, OCH3), 7.31-8.14 (m, 6H, ArH), 12.92 (bs, 1H, NH); 13C NMR (DMSO-d6, 100 MHz) d: 36, 59, 115, 118, 120, 123, 124, 125, 126, 129, 148, 152, 164, 166, 171; Anal. calc. for C20H20N6O4S2: C, 50.84; H, 4.27; N, 17.79; S, 13.57; found C, 50.79; H, 4.21; N, 17.71; S, 13.55.

Cholinesterase inhibition assay:
Inhibition of acetyl-cholinesterase (AChE) and butyl-cholinesterase (BuChE) activity assay:
The resultant products are tested for AChE and BuChE inhibitory activity, wherein enzyme inhibition assay is performed in a 96-well plate by using DTNB method. Briefly, 25 µL AChE/BuChE (25 mU in 100 µM PBS) is incubated with 75 µL DTNB (100 µM PBS containing 600 µM NaHCO3) for 5 min at room temperature. To this, 25 µL of test compounds (1 – 1000 µM) and 50 µL PBS (pH 7.4) are added. Reaction mixture is then incubated for 15 min at room temperature. Reaction is initiated by adding 25 µL of acetylthiocholine iodide and butrylthiocholine (75 mM in PBS) for AChE and BuChE inhibitory assay respectively. Change in absorbance is recorded spectrophotometrically with experimental duration of 4 min at 412 nm by using UV-spectrophotometer. A blank reaction is run simultaneously with 25 µL solvent (1% DMSO) in place of drugs. Percent inhibition of AChE or BuChE activity is calculated by using following equation.

In vitro cholinesterase inhibitory activity:
The in-vitro inhibition activities of substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol derivatives (4) and N-benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide derivatives (8) are studied. The IC50 values and selectivity indices of (4) and (8) as well as the reference drug donepezil are summarized in Table 1 below.

Table 1
IC50 value & docking score of compounds 4 & 8 against AChE & BuChE:
Comp. No MW IC50 (µM) Selectivity for BChE*
AChE# BuChE#
4a 192 1320.4 ± 140.09 604.25 ± 110.08 2.18
4b 210 974.86± 130.99 168.47 ± 56.24 5.78
4c 226.5 643.56 ± 9.47 1548.52 ±68.89 0.41
4d 269 216.06 ± 7.84 1200.91 ± 103.98 0.17
4e 269 671.28 ± 71.53 1023.59 ± 23.28 0.65
4f 206 501.41 ± 0.82 1525.55 ± 366.47 0.32
4g 222 1247.40 ± 374.15 1441.27 ± 218.14 0.86
4h 237 748.89 ± 343.53 1382.56 ± 5.69 0.54
4i 282 789.87 ± 21.55 1141.64 ± 466.62 0.69
8a 382 606.43 ± 21.60 25.18 ± 22.10 24.08
8b 400 542.67 ± 60.02 95.52 ± 10.34 5.68
8c 416.5 261.25 ± 19.31 403.66 ± 4.95 0.64
8d 459 534.36 ± 43.06 181.73 ± 60.56 2.94
8e 459 859.40 ± 32.62 479.80 ± 14.71 1.79
8f 396 975.42 ± 81.72 83.25 ± 16.74 11.71
8g 412 788.59 ± 27.59 ND ND
8h 427 3449.1 ± 556.77 318.01 ± 64.73 10.84
8i 472 520.67 ± 65.25 472.75 ± 0.04 1.10
Donepezil 0.042 ± 0.010 4.66 ± 0.503 155.30
#AChE = Acetylcholiesterase, BuChE = Butrylcholinesterase, ND = Not determined; * IC50(AChE)/IC50(BuChE)
Example 7
Synthesis of 3-acetyl-2H-chromen-2-one (10)
A solution of ethylacetoacetate (9, 23.5 mmol) in ethanol (15 mL) is taken in a round bottom flask (250 mL). The solution is kept at 0oC and further piperidine (2.0 mmol) is added. The resulting mixture is stirred at 0oC for 5 min followed by addition of salicylaldehyde (8, 23.5 mmol). The reaction mixture is allowed to come at room temperature and stirred for 3 hrs. The progress of the reaction is monitored by TLC (Hexane: ethylacetate, 7:3). A crude yellow solid is obtained. The reaction mixture is filtered and product is washed with ice cold water-ethanol (7:3, v/v) mixture. The product is further recrystalized by using ethanol. Yellow pure solid of 3-acetyl-2H-chromen-2-one is obtained which is characterized by IR, NMR and melting point.

Example 8
Synthesis of 3-(2-Bromo-acetyl)-chromen-2-one (11)
A solution of 3-acetyl-2H-chromen-2-one (10, 28.2 gm, 150 mmol) in 150 mL of alcohol free chloroform is taken in round bottom flask (250 mL). The solution is kept at 0oC and further Br2 (7.6 mL in 20 mL CHCl3, 150 mmol) is added with the help of dropping funnel. After addition of all bromine the reaction mixture is allowed to come at room temperature and stirred vigorously for 6 hrs. The progress of reaction is monitored by TLC (DCM). After completion of reaction, the reaction mixture is heated on water bath for 15-20 min to expel most of the HBr and for decomposition of by products. Then cool the reaction mixture. Solid product is separated which is further filtered and washed with ether. The product is further recrystallized by using glacial acetic acid. Solid colourless needle shaped crystal is obtained which is characterized by IR, NMR and melting point.

Example 9
Synthesis of 2-amino-4-phenyl thiazole and its derivatives (14)
A solution of substituted phenacyl bromide (12, 20.0 mmol) in 6 mL THF is taken in round bottom flask (100 mL). The solution is kept at room temperature and added thiourea (13, 24.0 mmol). Stirred the reaction mixture at room temperature for 30 min. The progress of reaction mixture is monitored by TLC (Hexane: ethylacetate, 7:3). After completion of reaction the solid product is separated, which is filtered and washed with water. The products are further crystalized by using ethanol. Solid product is dried and characterized by IR, NMR and melting point.

Example 10
Synthesis of 3-[2-(4-phenylthiazol-2-ylamino)acetyl]chromen-2-one derivatives (15)
A solution of substituted 2-amino-4-phenylthiazole (14, 2.84 mmol) in 3 mL DMF are taken in round bottom flask (50 mL) then added 3-(2-bromoacetyl) chromen-2-one (11, 2.84 mmol) and K2CO3 (0.72 mmol). The reaction mixture is stirred at 60oC for 3 hrs and the progress of reaction is monitored by TLC (Hexane: ethylaceate, 7:3). After completion of reaction the reaction mixture is quenched by water and extracted with ethylacetate (3×50 mL). After extraction the organic layer is washed with water (3×50 mL) and dried over anhydrous sodium sulphate and is concentrated under reduced pressure. The residue obtained is purified by silica gel (60-120 mesh) column chromatography using petroleum ether-ethylacetate (4:1) as a mobile phase to give the pure products. The resultant products are characterized by IR, NMR and melting point as detailed below:

3-[2-(4-Phenylthiazol-2-ylamino)acetyl]chromen-2-one (R1 = R2 = H, 15a): Brown solid; yield:458 mg (67%); Mp.:190-195oC; FTIR (KBr): 3436, 1705, 1604, 1532, 1518, 1483, 1442, 1332, 1148, 1039, 845, 714 cm.-1; 1H NMR (DMSO-d6, 400 MHz):d 4.21 (s, 2H, CH2), 7.07 (s,1H, H of thiazole), 7.11-7.91 (m,8H, ArH), 8.53 (s,1H, H of pyran); 13C NMR (DMSO-d6, 100 MHz):d 51, 102, 111, 113, 118, 124, 125, 129, 131, 136, 147, 150, 155, 159, 168, 195;Anal. calc. for C20H14N2O3S:C, 66.28; H, 3.89; N, 7.73; S, 8.85; found C, 66.20; H, 3.81; N, 7.68; S, 8.80.

3-{2-[4-(4-Fluorophenyl)thiazole-2-ylamino]acetyl}chromen-2-one (R1 = F, R2 = H, 15b): Orange solid; yield: 455 mg (64%); Mp.:125-130oC; FTIR (KBr): 3441, 2923, 2853, 1701, 1625, 1538, 1488, 1384, 1261, 1095, 801, 730 cm-1; 1H NMR (DMSO-d6, 400 MHz)d: 4.52 (s,2H, CH2), 6.98 (s,1H, H of thiazole), 7.20 (d, 2H, J = 8.8 Hz, ArH), 7.45-7.62 (m, 4H, ArH), 7.90 (d, 2H, J= 8.8 Hz, ArH), 8.68 (s, 1H, H of pyran); 13C NMR (DMSO-d6, 100 MHz) d: 51, 104, 116, 126, 127, 129, 131, 135, 147, 158, 162, 168, 198; Anal. calc. for C20H13FN2O3S: C, 63.15; H, 3.44; N, 7.36; S, 8.43; found C, 63.09; H, 3.40; N, 7.28; S, 8.39.

3-{2-[4-(4-Chlorophenyl)thiazole-2-ylamino]acetyl}chromen-2-one (R1 = Cl, R2 = H, 15c): Yellow solid; yield: 489 mg (67%); Mp.: 182-186oC; FTIR (KBr): 3438, 3283, 3111, 2962, 1708, 1633, 1535, 1477, 1401, 1261, 1088, 820, 730 cm-1; 1H NMR (DMSO-d6, 400 MHz)d: 4.75 (s, 2H, CH2), 6.73 (s, 1H, H of thiazole), 7.16-7.21 (m, 2H, ArH), 7.37 (d, 2H, J = 8.4 Hz, ArH), 7.67-7.70 (m, 2H, ArH), 8.17 (d, 2H, J = 8.4 Hz, ArH); 8.73 (s, 1H, H of pyran); 13C NMR (DMSO-d6, 100 MHz)d: 48, 103, 114, 124, 128, 130, 133, 136, 145, 155, 161, 167, 195; Anal. calc. for C20H13ClN2O3S: C, 60.53; H, 3.30; N, 7.06; S, 8.08; found C, 60.49; H, 3.26; N, 6.98; S, 8.01.

3-{2-[4-(4-Bromophenyl)thiazol-2-ylamino]acetyl}chromen-2-one (R1 = Br, R2 = H, 15d): Yellow solid; yield: 503 mg (61%); Mp.: 210-215oC; FTIR (KBr): 3425, 2926, 1720, 1611, 1532, 1458, 1342, 1225, 1075, 1045, 990, 895 cm-1; 1H NMR (DMSO-d6, 400 MHz)d: 4.72 (s, 2H, CH2), 7.11 (s, 1H, H of thiazole), 7.52-7.62 (m, 2H, ArH), 7.72 (d, 2H, J = 6.8 Hz, ArH), 7.78-7.90 (m, 2H, ArH), 8.07 (d, 2H, J = 8.4 Hz), 8.67 (s, 1H, H of pyran); 13C NMR (DMSO-d6, 100 MHz)d: 50, 106, 112, 123, 129, 131, 133, 136, 149, 153, 160, 166, 192; Anal. calc. for C20H13BrN2O3S: C, 54.43; H, 2.97; N, 6.35; S, 7.27; found C, 54.40; H, 2.92; N, 6.31; S, 7.24.

3-{2-[4-(4-Methylphenyl)thiazol-2-ylamino]acetyl}chromen-2-one (R1 = CH3, R2 = H, 15e): Yellow solid; yield: 443 mg (63%) ; Mp.: 156-160oC; FTIR (KBr): 3450, 3295, 2921, 2853, 1715, 1633, 1530, 1487, 1359, 1331, 1222, 1033, 820, 728 cm-1; 1H NMR (DMSO-d6, 400 MHz) d: 2.29 (s, 3H, CH3), 4.40 (s, 2H, CH2), 6.91 (s, 1H, H of thiazole), 7.04-7.17 (m, 2H, ArH), 7.23 (d, 2H, J = 8.0 Hz, ArH), 7.68 (d, 2H, J = 8.0 Hz, ArH), 7.78-7.88 (m, 2H, ArH), 8.52 (s, 1H, H of pyran); 13C NMR (DMSO-d6, 100 MHz)d: 23, 54, 109, 114, 120, 128, 132, 135, 138, 147, 156, 162, 167, 197; Anal. calc. for C21H16N2O3S: C, 67.00; H, 4.28; N, 7.44; S, 8.52; found C, 66.96; H, 4.20; N, 7.42; S, 8.48.

3-{2-[4-(4-Methoxyphenyl)thiazol-2-ylamino]acetyl}chromen-2-one (R1 = OCH3, R2 = H, 15f): Light yellow solid; yield: 477 mg (65%); Mp.:224-228oC; FTIR (KBr): 3411, 3120, 2940, 1712, 1698, 1594, 1528, 1486, 1284, 1263, 1188, 1045, 862, 785 cm-1; 1H NMR (DMSO-d6, 400 MHz) d: 3.87 (s, 3H, OCH3), 4.67 (s, 2H, CH2), 6.58 (s, 1H, H of thiazole), 6.92-6.98 (m, 4H, ArH), 7.34 (d, 2H, J = 8.4 Hz, ArH), 7.71 (d, 2H, J = 8.4 Hz, ArH), 8.23 (s, 1H, H of pyran); 13C NMR (DMSO-d6, 100 MHz)d: 52, 55, 115, 118, 125, 129, 134, 140, 148, 159, 164, 169, 190 ; Anal. calc. for C21H16N2O4S: C, 64.27; H, 4.11; N, 7.14; S, 8.17; found C, 64.23; H, 4.08; N, 7.10; S, 8.11.

3-{2-[4-(4-Nitrophenyl)thiazol-2-ylamino]acetyl}chromen-2-one (R1 = NO2, R2 = H, 15g): Orange solid; yield: 411 mg (54%); Mp.: 302-306oC; FTIR (KBr): 3399, 3306, 3146, 1708, 1642, 1593, 1537, 1502, 1324, 1108, 1039, 853, 719 cm-1; 1H NMR (DMSO-d6, 400 MHz)d: 4.78 (s, 2H, CH2), 7.22 (s, 1H, H of thiazole), 8.03-8.31 (m, 8H, ArH), 8.56 (s, 1H, H of pyran) ; 13C NMR (DMSO-d6, 100 MHz)d: 56, 105, 111, 120, 124, 130, 136, 137, 142, 149, 158, 161, 170, 198; Anal. calc. for C20H13N3O5S: C, 58.96; H, 3.22; N, 10.31; S, 7.87; found C, 58.94; H, 3.19; N, 10.27; S, 7.83.

3-{2-[4-(4-Cyanophenyl)thiazol-2-ylamino]acetyl}chromen-2-one (R1 = CN, R2 = H, 15h): Yellow solid; yield: 421 mg (58%); Mp.: 286-290oC; FTIR (KBr): 3375, 3114, 2227, 1716, 1642, 1603, 1540, 1453, 1341, 1230, 1173, 1042, 837, 752 cm-1; 1H NMR (DMSO-d6, 400 MHz)d: 4.54 (s, 2H, CH2), 7.12 (s, 1H, H of thiazole), 7.54-7.56 (m, 2H, ArH), 7.63 (d, 2H, J= 8.4 Hz, ArH), 7.74-7.81 (m, 2H, ArH), 7.86 (d,2H, J= 8.4 Hz, ArH ), 8.54 (s, 1H, H of pyran); 13C NMR (DMSO-d6, 100 MHz)d: 52, 102, 113, 119, 120, 125, 131, 138, 142, 146, 151, 159, 163, 168, 199; Anal. calc. for C21H13N3O3S: C, 65.11; H, 3.38; N, 10.85; S, 8.28; found C, 65.07; H, 3.35; N, 10.83; S, 8.21.

3-{2-[4-(3-Bromophenyl)thiazol-2-ylamino]acetyl}chromen-2-one (R1 = H, R2 = Br, 15i): Orange solid; yield: 503 mg (61%); Mp:156-158oC; FTIR (KBr): 3435, 2998, 2830, 1709, 1609, 1528, 1455, 1339, 1227, 1070, 1047, 897, 756 cm-1; 1H NMR (DMSO-d6, 400 MHz)d: 4.68 (s, 2H, CH2), 7.19 (s, 1H, H of thiazole), 7.30-7.34 (m, 4H, ArH), 7.62-7.65 (m, 4H, ArH), 8.57 (s, 1H, H of pyran); 13C NMR (DMSO-d6, 100 MHz)d: 51, 107, 112, 122, 129, 132, 135, 139, 148, 154, 159, 168, 193; Anal. calc. for C20H13BrN2O3S: C, 54.43; H, 2.97; N, 6.35; S, 7.27; found C, 54.38; H, 2.94; N, 6.32; S, 7.19.

3-{2-[4-(3-Nitrophenyl)thiazol-2-ylamino]acetyl}chromen-2-one (R1 = H, R2 = NO2, 15j): Orange solid; yield: 388 mg (51%); Mp.: 215-220oC; FTIR (KBr): 3447, 3240, 3114, 1714, 1635, 1579, 1537, 1513, 1342, 1204, 1052, 869, 714 cm-1; 1H NMR (DMSO-d6, 400 MHz)d: 4.76 (s, 2H, CH2), 7.24 (s, 1H, H of thiazole), 7.68-7.98 (m, 4H, ArH), 8.02-8.28 (m, 4H, ArH), 8.67 (s, 1H, H of pyran); 13C NMR (DMSO-d6, 100 MHz)d: 54, 118, 120, 124, 131, 136, 143, 148, 157, 160, 171, 199; Anal. calc. for C20H13N3O5S: C, 58.96; H, 3.22; N, 10.31; S, 7.87; found C, 58.92; H, 3.18; N, 10.29; S, 7.82.

3-{2-[4-(3-Methoxyphenyl)thiazol-2-ylamino]acetyl}chromen-2-one (R1 = H, R2 = OCH3, 15k): Yellow solid; yield: 484mg (66%); Mp.:120-125oC; FTIR (KBr): 3400, 2942, 1715, 1598, 1537, 1523, 1488, 1464, 1281, 1048, 863, 783 cm-1; 1H NMR (DMSO-d6, 400 MHz)d: 3.85 (s, 3H, OCH3), 4.68 (s, 2H, CH2), 6.78 (s, 1H, H of thiazole), 6.93-7.12 (m, 4H, ArH), 7.42-7.45 (m, 4H, ArH), 8.46 (s, 1H, H of pyran); 13C NMR (DMSO-d6, 100 MHz)d: 53, 56, 109, 116, 120, 126, 130, 136, 141, 149, 161, 166, 170, 196; Anal. calc. for C21H16N2O4S: C, 64.27; H, 4.11; N, 7.14; S, 8.17; found C, 64.23; H, 4.07; N, 7.12; S, 8.12.

3-{2-[4-(3,4-Dichlorophenyl)thiazol-2-ylamino]acetyl}chromen-2-one (R1 = R2 = Cl, 15l): Brown solid; Yield: 506 mg (63%); Mp.: 210-212oC; FTIR (KBr): 3432, 3316, 3142, 2921, 1716, 1608, 1560, 1523, 1463, 1376, 1229, 1050, 893, 755, 722 cm-1 ; 1H NMR (DMSO-d6, 400 MHz) d: 4.42 (s, 2H, CH2), 7.20 (s, 1H, H of thiazole), 7.52-7.94 (m, 7H, ArH), 8.32 (s, 1H, H of Pyran); 13C NMR (DMSO-d6, 100 MHz)d: 52, 58, 110, 114, 123, 128, 132, 138, 143, 151, 152, 164, 168, 172, 194; Anal. calc. for C20H12Cl2N2O3S: C, 55.70; H, 2.80; N, 6.50; S, 7.43; found C, 55.68; H, 2.77; N, 6.47; S, 7.39.

In vitro cholinesterase inhibitory activity
The inhibition activities of 3-[2-(4-phenylthiazol-2-ylamino)-acetyl]-chromen-2-one derivatives against AChE & BuChE are assessed and detailed below in Table 2.

Table 2
IC50 value & docking score of compounds 10, 11, 14 &15 against AChE & BuChE:
Compd No. IC50 (µM) Selectivity for BuChE*
#AChE #BuChE
10 906.31 ± 49.13 1151.1 ± 133.90 0.78
11 846.33 ± 25.29 346.68 ± 13.15 2.44
14a 975.48 ± 29.18 385.69 ± 24.41 2.52
14b 3112.81 ± 953.42 453.61 ± 71.11 6.86
14c 829.12 ± 38.17 1089.97 ± 89.12 0.76
14d 4824.25 ± 989.91 893.92 ± 128.12 5.39
14e 998.97 ± 40.31 585.43 ± 52.83 1.70
14f 3514.13 ± 856.19 1730.01 ± 118.59 2.03
14g 978.85 ± 14.83 1345.52 ± 150.87 0.72
14h 1859.65 ± 237.09 2280.80 ± 91.71 0.81
14i 4024.77 ± 728.16 3.54 ± 1.64 1136.94
14j 3223.9 ± 236.21 23.24 ± 6.00 138.72
14k 1681.54 ± 68.37 912.14 ± 162.74 1.84
14l 278.44 ± 83.34 405.56 ± 45.72 0.68
15a 414.27 ± 21.57 106.25 ± 9.29 3.89
15b 2008.17 ¬± 357.47 76.41 ± 4.60 26.28
15c 1354.68 ± 135.84 713.61 ± 66.48 1.89
15d 423.78 ± 30.84 321.49 ± 57.75 1.31
15e 427.83 ± 14.83 240.69 ± 39.62 1.33
15f 1016.83 ± 56.50 500.8 ± 59.22 2.11
15g 1767.56 ± 167.81 777.81 ± 49.08 2.27
15h 1659.79 ± 449.63 476.89 ± 54.96 3.48
15i 5231.54 ± 1160.8 61.64 ± 1.67 84.87
15j 1642.76 ± 136.93 46.47 ± 0.37 35.35
15k 1379.91 ± 337.62 553.59 ± 194.15 2.49
15l 1839.56 ± 209.44 107.32 ± 19.73 17.14
Donepezil 0.042 ± 0.010 4.66 ± 0.503 155.30
#AChE = Acetylcholiesterase, BuChE = Butrylcholinesterase, * IC50(AChE)/IC50(BuChE)

It is to be understood that while the invention has been described in conjunction with the preferred specific embodiments thereof, that the description and examples given above are intended to illustrate and not to limit the scope of the invention. Other aspects, advantages and modifications within the scope of the invention will be apparent to those skilled in the art to which the invention pertains. Accordingly, the appended claims are intended to cover all embodiments of the invention and modifications thereof that do not depart from the spirit and scope of the invention.

We Claim:
1. A novel compound N-Benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide of formula 1:

Formula 1
wherein R1, R2 & R3 are selected from a group comprising H, F, Cl, Br, CN, OCH3, OH, NH2, NO2, alkyl, allyl, N-alkyl, N-aryl, N-piperazine, N-morpholine and wherein said substituents are interchangeable.

2. The compound of Formula 1 as claimed in claim 1, wherein R1, R2 & R3 are Hydrogen.

3. The compound of Formula 1 as claimed in claim 1, wherein R1 and R3 are H and R2 is X selected from F, Cl or Br.

4. The compound of Formula 1 as claimed in claim 1, wherein R1 is X, preferably Br and R2 and R3 are H.

5. The compound of Formula 1 as claimed in claim 1, wherein R1 and R3 are H and R2 is selected from OCH3, NO2 or CH3.

6. The compound of Formula 1 as claimed in claim 1, wherein R1, R2 & R3 are OCH3.

7. The compound of Formula 1 as claimed in claim 1, wherein said compound N-Benzothiazol-2-yl-2-(3-mercapto-5-phenyl-[1,2,4]triazol-4-ylamino)-acetamide of Formula 1 is prepared by reacting N-(benzo[d]thiazol-2-yl)-2-chloroacetamide (7) with substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (4a-4i).

8. The compound as claimed in claim 1, wherein said compound is AChE, BuChE and JNK3 inhibitor.

9. The compound as claimed in claim 1, wherein a pharmaceutical formulation is prepared comprising the compound of formula (1) along with pharmaceutically acceptable excipients.

10. The compound as claimed in claim 9, wherein the pharmaceutical formulation is in a form of any pharmaceutically acceptable doses form.

11. A novel compound 3-[2-(4-phenylthiazol-2-ylamino)acetyl]chromen-2-one of Formula 2;

Formula 2

wherein R1,& R2 are selected from a group comprising H, F, Cl, Br, NO2, CN, OH, O-alkyl, NH2, N-alkyl, N-aryl, N-piperazine, N-morpholine, allyl and wherein said substituents are interchangeable.

12. The compound of Formula 2 as claimed in claim 11, wherein R1 & R2 are Hydrogen.

13. The compound of Formula 2 as claimed in claim 11, wherein R1 is H and R2 is selected from H, Br, NO2 or OCH3.

14. The compound of Formula 2 as claimed in claim 11, wherein R2 is H and R1 is selected from H, F, Cl, Br, CN, OCH3, NO2 or CH3.

15. The compound of Formula 2 as claimed in claim 11, wherein R1 & R2 are Cl.

16. The compound of Formula 2 as claimed in claim 11, wherein the compound 3-[2-(4-phenylthiazol-2-ylamino)acetyl]chromen-2-one of Formula 2 is prepared by reacting 2-amino-4-phenyl thiazole (14) with 3-(2-Bromo-acetyl)-chromen-2-one (11).
17. The compound as claimed in claim 11, wherein said compound is AChE, BuChE and JNK3 inhibitor.

18. The compound as claimed in claim 11, wherein a pharmaceutical formulation is prepared comprising the compound of formula (2) along with pharmaceutically acceptable excipients.

19. The compound as claimed in claim 18, wherein the pharmaceutical formulation is in a form of any pharmaceutically acceptable doses form.