1. قالوا سبحانك لا علم لنا إلا ما علمتنا إنك أنت العليم الحكيم صدق الله العظيم صدق الله العظيم (سورة البقرة 32) (سورة البقرة 32)

2. SYNTHESIS AND BIOLOGICAL TESTING OF NEW 1-ADAMANTYL DERIVATIVES

4. Pharmacological Properties of Adamantane Derivatives Antiviral Activities Antimicrobial Activities Anti-inflammatory Activity CNS Activities 11  -HSD1 Inhibitory Activity Miscellaneous Activities

5. Antiviral Adamantane Derivatives Anti-Influenza and Anti-Herpes viruses

8. Anti-HIV Derivatives

9. Antimicrobial Adamantane Derivatives

13. Anti-inflammatory Adamantane Derivatives

15. CNS Activities Anti-Parkinsonian Activity The high lipophilicity of the adamantane derivatives enables them to pass through the blood brain barriers leading to the existence of high levels of these derivatives in the central nervous system The therapeutic efficacy of amantadine in the symptomatic treatment of Parkinson's disease was discovered in 1969 Amantadine is known to increase the synthesis, release and uptake of dopamine in the striatum Amantadine was found to act as blocker of brain monoamineoxidase A and as non-competitive N-methyl-D-aspartate (NMDA)-receptor antagonist thereby influencing the dopamine transmission

18. 11  -HSD1 Inhibitory Activity

23. Pharmacological Properties of 1,2,4-Triazoles 1,2,4-Triazoles (s-triazoles) and their fused heterocyclic derivatives are known for their diverse pharmacological activities. The most interesting of these are the anti- inflammatory, analgesic, antibacterial, antifungal and other activities.

24. Anti-inflammatory 1,2,4-triazole derivatives

26. Antimicrobial 1,2,4-triazole derivatives

29. 1,2,4-Triazolo[3,4-b][1,3,4]thiadiazoles

30. Pharmacological Properties of 1,3,4-Thiadiazoles 1,3,4-Thiadiazole-2-sulphonamides were early known as carbonic anhydrase inhibitors which are clinically useful in the treatment of various diseases such as glaucoma, epilepsy, congestive heart failure, mountain sickness, gastric and duodenal ulcers and other neurological disorders Antibacterial, antifungal and anti-inflammatory activities were also reported for several 1,3,4-thiadiazole derivatives

31. 1,3,4-Thiadiazoles as Carbonic Anhydrase Inhibitors

32. Antimicrobial 1,3,4-Thiadiazoles

35. RESEARCH OBJECTIVES

38. NMR data of compound 145b

39. NMR data of compound 146e

41. NMR data of compound 149c

43. NMR data of compound 150j

46. NMR data of compound 151e

49. NMR data of compound 151o

52. NMR data of compound 152i

56. NMR data of compound 154c

57. NMR data of compound 155b

59. NMR data of compound 157

61. NMR data of compound 164a

62. BIOLOGICAL TESTING In vitro antimicrobial testing (all new compounds) In vivo acute anti-inflammatory testing in rats (26 compounds) Oral acute toxicity of compounds 151l and 159 in mice.

63. Antimicrobial Activity The primary screening was carried out using the agar disc-diffusion method using Müller-Hinton agar medium for measuring the growth inhibitory activity against the standard strains of the Gram-positive bacteria: Staphylococcus aureus IFO 3060, Bacillus subtilis IFO 3007, Micrococcus luteus IFO 3232, the Gram-negative bacteria Escherichia coli IFO 3301, Pseudomonas aeuroginosa IFO 3448 and the yeast-like pathogenic fungus Candida albicans IFO 0583 The minimal inhibitory concentration (MIC) for the most active compounds against the same microorganism used in the primary screening was carried out using the microdilution susceptibility method in Müller- Hinton Broth and Sabouraud Liquid Medium

64. Diameter of Growth Inhibition Zone (mm)Ar/R Comp. No. C APAECMLBSSA ---202216C6H5C6H5 145a ---1820153-FC 6 H 4 145b ---1618134-FC 6 H 4 145c ---1318154-ClC 6 H 4 145d ---1127224-BrC 6 H 4 145e ----10-C6H5C6H5 146a ----12-3-FC 6 H 4 146b ----12-4-FC 6 H 4 146c ----11-4-ClC 6 H 4 146d ---1012-4-BrC 6 H 4 146e ---1213-NH 2 148 ----11-CH 3 NH149a ------CH 3 CH 2 NH149b ------CH 3 (CH 2 ) 3 NH149c ------CH 2 =CH-CH 2 NH149d ------C 6 H 5 CH 2 NH149e NT1920182526Gentamicin NT1617192123Ampicillin 21NT Clotrimazole

65. Diameter of Growth Inhibition Zone (mm)R Comp. No. C APAECMLBSSA ----1310 H 150a ----14 2-F 150b 17--- 16 4-F 150c ----1411 2-Cl 150d ----1614 4-Cl 150e 16--14 13 4-Br 150f -1315121614 2-OH 150g -1419132519 4-OH 150h ---151815 4-CH 3 150i ------ 2-OCH 3 150j ------ 4-OCH 3 150k ----14 2-NO 2 150l ------ 4-NO 2 150m ------ 4-(CH 3 ) 2 N 150n ----1918 2,6-F 2 150o ------ 2-Cl,6-F 150p ----1614 2,6-Cl 2 150q ----1716 2,4-Cl 2 150r 12---17 3,4-Cl 2 150s ------ 3,4-(CH 3 O) 2 150t ------ 2,4-(NO 2 ) 2 150u ------ 2-NO 2,4,5- (CH 3 O) 2 150v

66. Diameter of Growth Inhibition Zone (mm)R Comp. No. C APAECMLBSSA ----1513 CH 3 151a --15-1415 C2H5C2H5 151b ----1511 COOC 2 H 5 151c ---14-- C6H5C6H5 151d -12---- 4-FC 6 H 4 151e -1118-1112 3-CF 3 C 6 H 4 151f ------ 2-CH 3 OC 6 H 4 151g 17----- C 6 H 5 CH 2 151h ----1112 CH 3 151i ----1214 C2H5C2H5 151j ----11- COOC 2 H 5 151k ------ C6H5C6H5 151l ----1213 4-FC 6 H 4 151m -1419--- 3-CF 3 C 6 H 4 151n ------ 2-CH 3 OC 6 H 4 151o ------ C 6 H 5 CH 2 151p NT1920182526Gentamicin NT1617192123Ampicillin 21NT Clotrimazole

67. Diameter of Growth Inhibition Zone (mm)R Comp. No. C APAECMLBSSA ---161912 H 152a ------ 2-F 152b --15--- 2-Cl 152c ----1511 4-CH 3 152d 13---2217 2-OH 152e 19---2622 4-OH 152f ----1115 4-OCH 3 152g 14----- 2,6-F 2 152h ----1514 2-Cl,6-F 152i ---16 12 2,6-Cl 2 152j ----1715 2,4-Cl 2 152k ----1311 3,4-Cl 2 152l -1619172420 3,4-(CH 3 O) 2 152m ------ 2-NO 2,4,5-(CH 3 O) 2 152n NT1920182526Gentamicin NT1617192123Ampicillin 21NT Clotrimazole

68. Diameter of Growth Inhibition Zone (mm)R/X Comp. No. C APAECMLBSSA -2027-13 - 153 ------ H 154a 14----- F 154b ------ Cl 154c ------ NO 2 154d ---14 13 CH 3 155a ----1312 CH 3 CH 2 155b ----14- C6H5C6H5 155c 17--162218 - 157 ---132018 - 159 11---1311 - 161 NT1920182526Gentamicin NT1617192123Ampicillin 21NT Clotrimazole

69. Diameter of Growth Inhibition Zone (mm)X Comp. No. C APAECMLBSSA ---151413 H 164a ---111914 F 164b ---122015 Cl 164c ------ - 165 NT1920182526Gentamicin NT1617192123Ampicillin 21NT Clotrimazole

70. Minimal Inhibitory Concentration (MIC,  g/ml) Comp. No. C APAECMLBSSA ND 22 145a ND 4 145b ND 12145e ND 2 12150h ND 4 150o ND 2 151n ND 4 152a ND 2 152e 8ND 12152f ND 2 12152m ND20.5ND 153 ND 2 157 ND 4 159 ND 4 164b ND 2 164c ND10.5222Gentamicin ND2220.52Ampicillin 2ND Clotrimazole

71. Anti-inflammatory Testing The acute anti-inflammatory activity of 26 representative compounds was determined in vivo following the carrageenan-induced paw oedema method in rats The selection of the representative compounds and dose levels were made after carrying out pilot experiments which showed the absence of anti-inflammatory activity in compounds 146a-e, 148 and 149a-e The compounds were tested at 20 and 40 mg/kg dose levels

72. Mean % Reduction of paw oedemaR/XComp. No. 40 mg/kg20 mg/kg 19.3721.923,4-(CH 3 O) 2 150t 39.8839.16C6H5C6H5 151d 38.3725.882-CH 3 OC 6 H 4 151g 34.7627.95C2H5C2H5 151j 50.4428.86C6H5C6H5 151l 22.9013.064-FC 6 H 4 151m 15.2723.23H152a 37.6633.022-Cl152c 31.2020.412-OH152e 35.0110.453,4-Cl 2 152l 10.6211.32C2H5C2H5 155b 32.7029.54-157 65.1950.60-159 36.837.47-161 52.79Indomethacin (5 mg/kg)

73. Oral Acute Toxicity Testing (gm/kg) LD 50 (95% Confidence limit)LD 84 LD 50 LD 16 Comp. No. 1.64 (1.23-1.89)2.881.640.82151l 2.52 (1.97-3.10)4.432.521.77159

74. Thank You