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It is understood that the 2-aminoimidazole occupies an important region of chemical space as its hydrogen bond donor-acceptor pattern is capable of recreating that of the guanidine. 74 More importantly, it occupies a unique pKa range between the more acidic 2-aminopyridinium ion 75 and less acidic guanidinium ion 76 (Fig.1.8.2). Furthermore, the pKa’s of 2-aminoimidazolium ions show a predictable trend with substitution, allowing it to be finely tuned for medicinal applications as illustrated in the examples below. 77 2-Aminopyridine 2-aminobenzimidazole H N N NH 2 N pK a = 6.71 7.18 N NH 2 NH 2-aminoimidazole Me N NH 2 NH Me N NH 2 pK a = 8.46 8.65 9.21 HN NH 2 HN NH 2 Me NH amidine guanidine NH 2 pK a = 12.4 13.4 NH 2 Fig.1.8.2 pKa’s of common guanidine mimetics This dramatic difference in the pKa of 2-aminoimidazoles (~4 pKa units) with that of guanidine has led to some debate concerning the ability of the 2-aminoimidazole to directly mimic a guanidine. These arguments, based on a lowered pKa and electronic dissimilarity are, however, precisely what makes the 2-aminoimidazole a unique guanidine mimic for medicinal chemistry.- 77-78 Most importantly, their pKa range (pKa ~7-9) allows a significant fraction of compound to be uncharged at physiological pH thus increasing the likelihood of cellular penetration. It also permits this unique heterocycle to cross the blood brain barrier and may decrease the susceptibility of these compounds to Pgp mediated efflux vide infra. 79
1.9 2-Aminoimidazole Alkaloids The 2-aminoimidazole framework is emerging as an important pharmacophore, 80 and is widely found in numerous biologically active marine alkaloids. Over the last 25 years, several hundreds of diverse 1-unsubstituted and 1-substituted 2aminoimidazoles have been characterized. 1-Unsubstituted 2-aminoimidazole alkaloids (Fig. 1.9.1) have been isolated essentially from various species of marine sponges (Phylum Porifera) of Caribbean and South Atlantic regions. 81 Oroidin (1) and the dimeric sceptrin (3) are the most abundant members of the pyrrole-imidazole family. H 2N H 2N H 2N N N H H N N N Oroidin (1) HN O HN N H O Sceptrin (3) H N HN H2N HO N N H HN N H H2N Cl Palau'amine (5) H N HN O NH 2 O N H N H Br Br Br Br H 2N N H N HO O H 2N H 2N Me HN H N N N H HN N N H Cl N H OH Girolline (2) N Br Br Ageladine A (4) O NH 2 NH Dragmacidin E (6) Fig.1.9.1 Some representative 1-unsubstituted 2-aminoimidazoles from marine sponges. Br
Page 1 and 2: Saurashtra University Re - Accredit
Page 3: JANUARY-2011 Statement under O. Ph.
Page 7 and 8: Acknowledgment This thesis arose in
Page 9 and 10: since I was a child. My Mother Hans
Page 11 and 12: CHAPTER - 2 Microwave Assisted Synt
Page 13 and 14: 5.5 Results and discussion 156 5.6
Page 15 and 16: Ms Mesyl MW Microwave NBS N-bromosu
Page 17 and 18: 1. Microwave Assisted Organic Synth
Page 19 and 20: 1.4 Heating Mechanism In microwave
Page 21 and 22: 1.5. Effects of solvents Every solv
Page 23 and 24: 1.7 Application of microwave in org
Page 25: aromatic amines, Lancini’s group
Page 29 and 30: Recently group of Erik 83 described
Page 31 and 32: 1.10 Methods for the preparation of
Page 33 and 34: R 1 O X R 2 NH 2 H 2N NAc R 1 HN R
Page 35 and 36: this manifold, was reported in 1925
Page 37 and 38: Another route to 4(5)-acyl-2-amino-
Page 39 and 40: this series of compounds against th
Page 41 and 42: documented. Extra care is needed be
Page 43 and 44: Very recently the research group of
Page 45 and 46: OH a,b O N H2N N Boc N 3 H N R N N
Page 47 and 48: 1.12.2 Biofilm Growth Cycle 1) Plan
Page 49 and 50: can survive both the onslaught of a
Page 51 and 52: [26] Leadbeater, N. E. (2004) Chemi
Page 53 and 54: [86] Kreutzberger, A. (1962) J. Org
Page 55 and 56: Microwave Assisted Synthesis & Stru
Page 57 and 58: 2.1 Introduction As described in ch
Page 59 and 60: 2.3 Proposed Mechanism: Regarding t
Page 61 and 62: No. 12 60 120 traces 84 a All react
Page 63 and 64: the development of biofilm related
Page 65 and 66: In first instance, a series of 2-hy
Page 67 and 68: Br N N N R 1 OH Br N N N R 1 OH Fig
Page 69 and 70: do have a very strong effect agains
Page 71 and 72: 2.6 Conclusion In the present study
Page 73 and 74: 2.8 Biological assays 2.8.1 Static
Page 75 and 76: 2.9 Experimental protocol: 2.9.1 Ge
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temperature of 80 °C and a maximum
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29.5,29.4, 29.2, 27.0, 22.6, 14.1.
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Yield: 78 %. 1 H NMR (300 MHz, CDCl
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N Br N N C 14H 29 OH Yield: 72 %. 1
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(75.5 MHz, CDCl3): δ = 167.7, 154.
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N Br N N C 14H 29 OH Cl Yield: 90 %
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2-(3,4-Dichlorophenyl)-2-hydroxy-1-
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N Br N N C 8H 17 OH NO 2 Yield: 49
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C3H7 HN N N H Cl Cl Yield : 70 %. 1
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(s, 1H), 3.16 (s, 3H), 1.80 (m, 2H)
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5-(4’-Nitrobiphenyl-4-yl)-N-octyl
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2.11 Representative NMR spectra 2.1
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2.11.3 10.4329 0.7429 151.5720 10.0
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[21] Matz C, McDougald D, Moreno A.
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Chapter-3 Structure Activity Relati
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imidazoles, where the addition of a
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3.4 Result and Discussion It was fo
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No. H 2N Compound Code N N C8H17 R1
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medium used in the set-up to monito
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H 2N N N N H2N N R R Figure-1 Effec
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3.5.3 Cyclo-alkyl 2-aminoimidazoles
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3.6. Conclusion In the present stud
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3.8. Experimental protocols 3.8.1 G
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122.6, 54.6, 33.3(×2), 27.3 (×2),
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5-(4-Chlorophenyl)-1-cyclooctyl-1H-
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Yield: 50 %. Mp: 76-78 ° C. 1 H NM
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5-(4-Chlorophenyl)-1-cyclobutyl-1H-
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Yield: 66%. 1 H NMR (300 MHz, CDCl3
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3.10 Representative NMR spectra 3.1
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3.11 References [1] (a) Alvi K. A,
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Copper Catalyzed Microwave Assisted
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4.1 Introduction There are only a f
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(Table-1, No- 6). Next reaction tem
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No. Product, Yield b (%) No. Produc
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4.4 Possible Mechanism Regarding th
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4.7 Experimental protocols 4.7.1 Ge
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1-(3-Azidopropyl)-2-(3,4-dichloroph
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Yield: 84 %. 1 H NMR (300 MHz, DMSO
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1H), 1.66 (m, 6H), 1.70 (m, 2H). 13
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5.48 Hz, 2H), 3.59 (m, 2H), 3.16 (d
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4.10 References [1] For a general r
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Crystal and Molecular Structure Ana
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5.1 Introduction The membrane efflu
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oscillation range of 5˚ and proces
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C12-C13 1.372(4) C32-C37 1.390(3) C
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Fig.-3: Packing of the molecules wh
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1 H NMR (400 MHz CDCl3): δ = 7.57-
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5.9.2 13 C spectra of bs-DP-7
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SUMMARY The work represented in the
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CONFERENCES/SEMINARS/WORKSHOPS ATTE
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PUBLICATIONS [1] One-Pot Microwave-
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Scheme 2 Competitive formation of 1
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Table 2 continued 9 10 11 12 N hydr
Page 204:
8. Colson G, Raboult L, Lavelle F,
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