الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
1. Design strategies of novel compounds related to two groups of herbicides
Forty-two compounds were synthesized based on the structure-based design
technique, thirty-four of them were a mimic to chloroacetamide herbicides group and eight compounds were designed as a mimic to pyridine carboxylic acid herbicides group.
1.1. Design strategy of novel chloroacetamide derivatives (276-309) as a mimics of chloroacetamide herbicides
Two different designs for mimics of chloroacetamide herbicides. First one, for synthesizing a novel derivatives of chloroacetamide compounds (276-297) was by replacing the aliphatic oxygenated bridge in chloroacetamide herbicides such as acetochlor (26) with aromatic part of some herbicides such as phenol ring of bromoxynil (327), methoxyphenyl of anisuron (328) and 2,4-dichlorophenyl of 2,4-D (329). The second design was based on monoterpenoid (cinnamaldehyde (274) and citral (275) moieties) as a scaffold for synthesizing a novel derivatives of chloroacetamide compounds (298-309).
1.2. Design strategy of novel pyridine derivatives (319-326) as a mimics of
Pyridine carboxylic acid herbicides
The commercial herbicide triclopyr (184) consist of two moieties 3,5,6-
trichloropyridin-2-olyl and acetic acid moieties, herein, we kept the trichloropyridin-2-
olyl moiety as a skeleton of suggested pyridine derivatives (319-326) and replaced acetic acid moiety by acetyl and chloroacetyl moieties as a mimic of acetic acid moiety and by other common commercial herbicide moieties such as propionic acid moiety of dichloprop (330), alkyl phosphonic acid moiety of glyphosate (331), alkyl phosphate
moiety of piperophos (332), methanesulfonyl moiety of ethofumesate (333), nicotinoyl moiety of imazapyr (334) and alkyl acetate moiety of elumiclorac-pentyl.
2. Chemistry The target chloroacetamide derivatives (276-309) were synthesized via acylation of imine derivatives (223-256) which synthesized by the reaction of aldehydes (271-275) and corresponding amines (257-270). The effects of substituent pattern on the
yields were studied. It was found that different aromatic substituents displayed diverse yields, and the order was as following: -N-(2,4-dichlorobenzyl) >-N-(2-hydroxybenzyl)
>N-(2-cinnamyl)>-N-(2-methoxybenzyl) >-N-(3,7-dimethylocta-2,6-dien-1-yl). The
presence of methyl group in the phenyl ring gave high yield but slowly reaction, on the other hand the presence of chlorine group on the phenyl ring gave little yield with rapid
reaction. 1H-NMR spectra and MS have confirmed the chemical structures of imine derivatives (223-256), 1H and 13C-NMR spectra and MS confirmed the chemical structures target compounds (276-309) and (319-326).
V- Summary & Conclusion
132 One the other hand, the target pyridine derivatives (319-326) were synthesized via acylation of the salt sodium 3,5,6-trichloropyridin-2-olate salt (311) by different acid
chlorides (312-318), substituent pattern of acid chlorides little effects on the yield of pyridine
3. 3D-Pharmacophore modeling.
Using DS, 3D-pharmacophore model of standard chloroacetamide herbicides was
established and investigated its features included HBA and HYD, so we kept it on the designed compounds and adding RA. Pretilachlor (43) was the highest fit value (fit value = 4) when it mapped in Hypo 1 of standard chloroacetamide herbicide.
Hypo 1 was selected as the best models of synthesized chloroacetamide derivatives (276-297). Pharmacophoric investigation features included HBA, HYD and RA also.
Compound 295 was the highest fit value (fit value = 4) when it mapped in Hypo 1 of synthesized chloroacetamide derivatives (276-297).
Hypo 1 was selected as the best models of synthesized chloroacetamide derivatives (298-309). Pharmacophoric investigation features included HBA, HYD and RA also.
Compound 307 shown the highest fit value (fit value = 4) when it mapped in Hypo 1 of synthesized chloroacetamide derivatives (298-309).
The 3D-pharmacophore model of standard pyridine carboxylic acid herbicides
(182-188) investigated its features included HBA, HYD and RA obtained hypotheses.
The top-rated Hypo 1 was selected as the best model and used to map compounds and
standard herbicides. Triclopyr (184) shows the highest fit value (fit value = 5) when it
mapped in best Hypo 1 standard pyridine carboxylic acid herbicides (182-188).
The 3D-pharmacophore model of synthesized pyridine derivatives (319-326) investigated its features included HBA, HYD and RA obtained hypotheses. The toprated Hypo 1 was selected as the best model and used to map compounds. Compound 322 shown the highest fit value (fit value = 5) when it mapped in Hypo 1 of synthesized pyridine derivatives (319-326).
4. Mapping of the test set compounds on standard pharmacophore models
All twenty-two synthesized chloroacetamide derivatives (276-297) mapped to standard chloroacetamide herbicides pharmacophore, the best-fit ligand is molecule (278), fit value = 3.77. The mapping of the standard chloroacetamide herbicides on the
Hypo 1 of synthesized chloroacetamide derivatives (276-297) showed that all of
standard herbicides mapped and the highest fit molecule was butenachlor (31), fit value = 3.33. Also, all twelve synthesized chloroacetamide derivatives (298-309) mapped to standard chloroacetamide herbicides pharmacophore except 305, the best-fit ligand is
molecule (304), fit value = 3.59. The mapping of the standard chloroacetamide
herbicides on the Hypo 1 of synthesized chloroacetamide derivatives (298-309) showed that only four standard herbicides mapped and the highest fit molecule was butachlor (30), fit value = 3.25.