Review article on 2, 5-Disubstituted-1, 3, 4-Thiadiazole Derivatives and its Pharmacological Activities

 

Preety Mishra, Arvind Kumar Singh*, Rohit Tripathi, Alok Giri

Kashi Institute of Pharmacy, MS-23 Varanasi-Allahabad Highway, Mirzamurad, Varanasi (UP)

*Corresponding Author E-mail: adi_arv26@rediffmail.com

Heterocyclic compounds are the nucleus of the compound that provides life to the compound. It occupies the central position. In recent years it has been found that 1,3,4-thiadiazole and derivatives had gained many importance because of having extensive pharmacological activities, possibly due to the presence of toxophoric N₂C₂S moiety. It possess unique anti-inflammatory, analgesic, antimicrobial, anticonvulsant, antidiabetic, antitumor, antiviral activities. In the pursuit and design of new drugs, the development of hybrid molecules through the combination of different molecules in one frame may lead to compounds with interesting biological profiles. This review presents the recently synthesized 1,3,4-thiadiazole derivatives having important biological activities.

 

 

INTRODUCTION:

Many compounds bearing 5-membered heterocyclic ring in their structure have an extensive spectra of pharmacological activities. ¹Chemical properties of 1,3,4-thiadiazole have been received in last few years. However, the usefulness of 1,3,4-thiadiazole as a privileged system in medicinal chemistry has prompted the advances in therapeutic potential. ²They occur in nature in four forms as 1,2,3-thiadiazole; 1,2,5-thiadiazole; 1,2,4-thiadiazole and 1,3,4-thiadiazole. Compounds bearing 1,3,4-thiadiazole nucleus is known to have unique antimicrobial, anti-inflammatory and analgesic properties. ³On substitution it have been found to have other interesting pharmacological responses such as antimicrobial, antitubercular, anticonvulsant, anti-hepatitis B- viral, analgesic. A summary of review of 1,3,4-thiadiazole derivatives associated with large no. of biological responses is presented in table.

 

 

S.No	Compounds	Derivatives	Biological Activities
1	Methylene bridged benzofuranyl imidazo[2,1-b][1,3,4]-thiadiazole1	R= Br, Cl, NO2	Anti-inflammatory and analgesic4
2	4,5-dihydro-1,5-diaryl-1H-pyrazole-3-substituted[1,3,4]thiadiazole derivatives2	R= H, SO2, NH2 R1= SCH3	Anti-inflammatory and analgesic5
3	4-(4-substituted phenyl) –N-(5-phenyl-1,3,4-thiadiazol-2-yl)-1H-pyrrole-3-carboxamide3	R= C6H5, 4-Br-C6H4, 4-NO2-C6H4, 4-F-C6H4, 4-I-C6H4, 4-Cl-C6H4	Anti-inflammatory and analgesic.6
4	Schiff’s bases of 2-amino-5-aryl-1,3,4-thiadiazole.4	Comp. R R1 A OCH3 OH B OH OH C Cl OH D NO2 OH E N(CH3)2 OH F OCH3 NO2 G OH NO2 H Cl NO2 I NO2 NO2 J N(CH3)2 NO2	Anti-inflammatory
5	2-p-aminophenyl-4-phenyl-5-imino-D2-1,3,4-thiadiazole5		Anti-inflammatory and analgesic
6	2-p-aminophenyl-4-phenyl-5-imino-D2-1,3,4-thiadiazole6		Anti-inflammatory7
7	3,6-disubstituted-1,2,4-triazolo[3,b-b]-1,3,4-thiadiazole7	Comp A B R H OCH3 R1 H CH3 R2 5-methoxy-3, indolylmethyl 5-methoxy-2-methyl-3-indolyl methyl	Anti-inflammatory and analgesic.8
8	3-(4-((5-amino-1,3,4-thiadiazol-2-yl) methoxy)-3-methoxy phenyl)-5-(substituted)-4,5-dihydro-1H-pyrazole-1-carboxamide.8	R= a. H; b. 2-OCH3; c. 2,4-diCl; d. 3-NH2; e. 3-NO2 ; f. 4-OCH3;  g. 4-F; h. 4-Na; i. 4-Br; j. 4-CH3; k. 3-OH; l. 2-OH; m. 4-Cl; n. 2-NO2; o. 2,4-diOH; p. 4-NH2; q. 2-Cl; r. 4-OH; s. 3-CH3	Antimicrobial9
9	N-{5-[(2-methyl-1H-benzimidazol-1-yl)-1,3,4-thiadiazol-2-yl}-N4-(4-substituted benzaldehyde)-semicarbazone(a-f)9	a.        R=H; R’=H b.        R=H; R’=4-NO2 c.        R=H; R’=4-OH d.        R=H; R’=4-CH3 e.        R=H; R’=4-OCH3 f.         R=H; R’=4-Cl	Antimicrobial10
10	(3,5-dichloro-4-((5-aryl-1,3,4-thiadiazol-2-yl)methoxy)phenyl)arylmethanones(a-f)10	a.        R=H; R’=H b.        R=H; R’=Cl c.        R=H; R’=Me d.        R=Me; R’=H e.        R=Me; R’=Cl f.         R=Me; R’=Me	Anti-microbial11
11	2-aryl-5-(6’-chloro-1’,3’- benzothiazol-2-yl-amino)-1,3,4-thiadiazoles11	R= a) Phenyl; b) 4-chlorophenyl; c) 2,4-dichlorophenyl; d) 4-nitrophenyl; e) 2-amino phenyl; f)2,4-dichloro phenoxymethyl; g)2- naphthylmethyl; h)4-methoxyphenyl; i) 2- acetoxyphenol; j) 3-pyridyl	Antimicrobial
12	Mannich Bases of 5-(4-chlorophenyl amino)-2-mercapto-1,3,4-thiadiazole12	R= 2-Chloro; 3-methoxy-4-hydroxy	Anti-bacterial12
13	6-(aryl/heteryl)-3-(5-methyl-1-phenyl-1H-4-pyrazolyl)[1,2,4]triazoly[3,4-b][1,3,4]-thiadiazole13	Ar= phenyl, 4-methyl phenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-chlorophenyl,4-aminophenyl, 4-hydroxyphenyl, 4-nitrophenyl, 3-pyridyl, 4-pyridyl	Anti-microbial13
14	Fluorobenzothiazole incorporated with 1,3,4-thiadiazole derivative14	R= a. Morphine       b. Piperazine	Anti-microbial14
15	2-(3’-chloro-5’-phenoxybenzo[b]thiophen-2’-yl)-5-arylamino-1,3,4-thiadiazole derivatives15	R= a. C6H5; b. 3-ClC6H4; c. 4-ClC6H4; d. 2-CH3C6H4; e. 4 –CH3C6H4; f. 2-OCH3C6H4; g.4-OCH3C6H4; h. 2-NO2C6H4	Anti-microbial15
16	5-(p-methoxyphenyl)-[ 2-substituted benzylidenylimino]1,3,4-thiadiazole16	R= a. 4-OHC6H4; b. 4-OCH3 C6H4; c. C6H5; d. 4-ClC6H4 e. 4-N(CH3)2C6H4	Anti-microbial16
17	5-substituted-[1,3,4-thiadiazole-2-yl]benzamide17	R= a. C6H5; b. 2-ClC6H4; c. 3-ClC6H4; d. 4-ClC6H4; e. 2- NO2C6H4; f. 3-NO2C6H4;     g. 4-NO2C6H4	Anti-microbial17
18	6-substituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole18	R= a. C6H5; b. 2-ClC6H4; c. 2,4-ClC6H3; d. 2-CH3C6H4; e. 2-OCOCH3C6H3; f. OC6H5;     g. 4-NO2C6H4	Anti-microbial18
19	5-(8-quinolinoxy methyl)-1,3,4-thidiazoles19	R= 3-OCH3; 4-OH; 2-OH; 4-OCH3; 3-OCH3, 4-N,N-dimethyl, 2-Cl, 4-NO2, -H	Anti-microbial19
20	2-(4-fluoro-3-nitrophenyl)-6-(4-methoxy phenyl)imidazo[2,1-b]-1,3,4-thiadiazole20		Anti-microbial20
21	2,4-thiazolidinediones der. bearing imidazo[1,2-b][1,3,4]-thiadiazole moiety21	R= Ar= C6H5; 4-CH3C6H4; 4-OCH3C6H4; 4-NO2C6H4; 4-Br-C6H4; 4-Cl-C6H4; 2,5-(OCH3)-C6H3	Anti-bacterial and antifungal21
22	2-substituted-5,6-diarylsubstituted imidazo[2,1-b]-1,3,4-thiadiazole22	Compd R R’ A CF3 H B SO2NO2 OCH3	Selective COX-2 Inhibitor22
23	2,5-disubstituted-1,3,4-thiadiazole23	Compd R R’ A CH2COOH CH2COOH A	Anti-microbial23
24	[2-(substitutedaryl)-3-{5-(substituted phenyl)1,3,4-thiadiazole}]-4-oxo-thiazolidines24	Compd R Ar A 4-ClC6H4 3-NO2C6H4 B 4-ClC6H4 2,4-ClC6H4 C 4OCH3C6H4 C6H5 D 4OCH3C6H4 4OCH3C6H4	Anti-bacterial and anti-fungal24
25	2-(biphenyl-4-yl)-6-substituted[2,1-b][1,3,4]-thiadiazole25	R= a. H; b. 4’Cl; c. 4’F; d. 2’,4diCl;       e. 4’NH2; f. 2’,4’diOH; g. 4’Br        h. 2’OH	Anti-bacterial and antifungal25
26	2-[3’,4’-dihydro-6’,7’-diethoxyisoquinoline-1’-methylidene]-3,5-disubstituted-1,3,4-thiadiazole.26	Compd R R’ A C6H5 C6H5 B C2H5OCO C6H5 C C6H5CH=CH C6H5 D 2-thienyl 4NO2C6H5	Antiviral26
27	2-arylsulfonamido-5-(benzthiazol-2’yl-thiamethyl)-1,3,4-thiadiazole27	R= a. Phenyl; b. 4-chlorophenyl;       c. 4-iodophenyl; d. 4-anisyl;  e. 3- carboxyphenyl; f. 3-carboxy-4-chlorophenyl; g.3-carboxy-6- chlorophenyl; h. 3-carboxy-4-methoxyphenyl	Antibacterial and antifungal27
28	4-amino-2{5-[(4-substituted phenyl) amino]-1,3,4-thiadiazole-2-yl} phenol28	Ar= a. 4-methylphenyl; b. 4-methoxy phenyl; c. 4-chlorophenyl; d. 2,5-dimethylphenyl; e. 3-chloro -4-fluorophenyl; f. 4-bromophenyl	Anti-bacterial and antifungal28
29	Methylene bridged benzisoxazolyl imidazo[2,1-b][1,3,4]-thiadiazoles29	R= Br, NO, SCN	Anti-bacterial and antifungal29
30	2-benzamido-5-substituted-N-(5-substituted phenyl)-(1,3,4-thiadiazol-2-yl)benzamide30	R= -H, 2-Cl, 2,4-Cl, 4-Cl, 4-F	Anti-convulsant30

 

 

 

CONCLUSION:

The synthesis of 1,3,4-thiadiazole heterocyclic that have been reported to date illustrates different approaches to the challenge of preparing these bioactive products and allows the synthesis of many novel chemical derivatives. The literature review reveals that 1,3,4-thiadiazole has diverse biological activity. It has shown good analgesic and anti-inflammatory activities.

 

ACKNOWLEDGEMENT:

The authors would like to express gratitude and thanks to Faculty of Pharmacy, KNIMT, Sultanpur and Kashi institute of Pharmacy Varanasi (UP) for providing necessary literature to carry out this research work.    

 

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Received on 03.03.2015         Modified on 19.03.2015

Accepted on 08.04.2015         © AJRC All right reserved