Synthesis and structure-activity relationships for anticipated molluscicidal activity of some 2-amino-5-substituted pyridine derivatives

Article abstract of DOI:10.1002/(SICI)1096-9063(199912)55:12<1203::AID-PS82>3.0.CO;2-9

A series of 2-amino-5-substituted pyridine derivatives was synthesized and their molluscicidal activity against white garden, Theba pisana (Muller), and brown garden, Helix aspersa (Muller), snails was investigated by two methods of application. Some of t

Full text of DOI:10.1002/(SICI)1096-9063(199912)55:12<1203::AID-PS82>3.0.CO;2-9

Pesticide Science
Pestic Sci 55:1203±1209 (1999)
Synthesis and structure–activity relationships
for anticipated molluscicidal activity of some
2-amino-5-substituted pyridine derivatives
Saad R El-Zemity* and Mohamed A Radwan
Pesticide Chemistry Department Faculty of Agriculture (Chatby), University of Alexandria, Alexandria, Egypt
Abstract: A series of 2-amino-5-substituted pyridine derivatives was synthesized and their
È
molluscicidal activity against white garden, Theba pisana (Muller), and brown garden, Helix aspersa
(Muller), snails was investigated by two methods of application. Some of these compounds showed
È
strong activity under laboratory conditions against the two types of snail. T pisana was more sensitive
to the tested compounds than H aspersa. The most effective compounds were 2-amino-5-(benzo-
triazole-1-ylmethyl)-3-methylpyridine, 2-amino-5-[1-(benzotriazole-1-yl)nonyl]-3-methylpyridine
and 2-[(1,2,4-triazole-1-ylmethyl)amino]-3-methylpyridine which exhibited high molluscicidal activ-
ity. The toxicity results are discussed in relation to the chemical structures.
# 1999 Society of Chemical Industry
Keywords: 2-amino-5-substituted pyridines; molluscicidal activity; structure±activity relationship; Theba pisana;
Helix aspersa
1
INTRODUCTION
commercial molluscicides. Thus, we have synthesized
a series of 2-amino-5-substituted pyridine derivatives
according to our recently reported and versatile
procedure,14 in order to evaluate their possible
molluscicidal activity under laboratory conditions by
two methods of application, discussing aspects of the
relationship between chemical structure and mollusci-
cidal activity.
Terrestrial gastropod mollusca continue to be serious
agricultural pests. Today, control of these pests with
chemical substances is still regarded as the most
successful method, particularly over large areas. Of
the many substances which have been of®cially tested
for the control of land gastropods, metaldehyde and
methiocarb are the most useful and form the active
ingredients of many commercial formulations.1 How-
ever, the problems associated with the use of metalde-
hyde have not yet been solved, and so many
commercial pesticides and experimental compounds
have been investigated for their molluscicidal effects
under laboratory and ®eld conditions to try to identify
a potential replacement.2±4
2
EXPERIMENTAL METHODS
2.1 General experimental procedures
[1H] and [13C]NMR spectra were recorded on a
Varian spectrometer at 300MHz and 75MHz respec-
tively using tetramethylsilane as an internal reference
for [1H] spectra in hexadeutero dimethyl sulfoxide;
melting points were measured with a Ko¯er hot-stage
apparatus and were uncorrected. A Carlo Erba-1106
instrument (CHN analysis) and a AEL MS-30 mass
spectrometer were also used.
The high insecticidal activity of pyridine alkaloids,
nicotine, nornicotine and anabasine,5 has led to the
synthesis and examination of many analogues and in
particular to a study of the effects of nuclear and side-
chain substitution on biological activity. The patent
literature contains an enormous number of pyridine
derivatives that have diverse pesticidal activity, includ-
ing insecticides,6 fungicides,7 bactericides,8 herbi-
cides,9 nematicides,10 acaricides11 and algicides.12
No trials on the molluscicidal activity of pyridines
against land gastropods have been reported, and only
4-aminopyridine has been tested on the freshwater
snail, Limnaea stagnalis (L) for blocking of the fast
potassium current.13 However, no other pyridine
derivatives have been screened and/or developed as
2.2. Synthesis
The sequence of the reactions leading to the synthesis
of 2-amino-5-substituted pyridine derivatives in this
study is outlined in Fig 1. 1-Hydroxymethyl-1H-
benzotriazole (1) was reacted with 2-aminopyridines
in presence of acetic acid and a catalytic amount of
p-toluenesulfonic acid to give the benzotriazole adduct
2. The methylene group of 2 can be mono- or di-
lithiated and subsequently substituted by various
* Correspondence to: Saad R El-Zemity, Pesticide Chemistry Department, Faculty of Agriculture (Chatby), University of Alexandria,
Alexandria, Egypt
(Received 7 May 1999; accepted 23 August 1999)
# 1999 Society of Chemical Industry. Pestic Sci 0031±613X/99/$17.50
1203

SR El-Zemity, MA Radwan
Figure 1. Overall synthetic routes to 2-amino-5-subsituted pyridine derivatives.
2.2.2 General procedure for synthesis of compounds 4a±h
and 5a±d
electrophiles. The benzotriazole moiety in both the
primary products 2 and in their methylene substituted
derivatives 4 and 5, is displaced by alkyl, aryl, and or
alkoxy anions, as described in our previous paper.14
To
a solution of 2-amino-5-(benzotriazole-1-yl-
methyl)pyridine (2b, 2c or 2e; 5mmol) in tetrahydro-
furan (THF; 100ml) at 78°C was added butyl
lithium (for 5a±d, 15mmol; for compounds 4a±h,
10mmol) under nitrogen. The mixture developed an
intense greenish±blue colour immediately. The solu-
tion was stirred for 15min at this temperature and the
electrophile (for 5a±d, 10mmol and for 4a±h, 5mmol
of the appropriate alkyl halide; for 4® and 4®i,
benzaldehyde; 4g benzophenone, and 4h, acetone)
was added. The mixture was kept at this temperature
for a further 15min. Water (50ml) was then added to
the mixture at 78°C, and the solution was extracted
with diethyl ether (3Â150ml), washed with water and
dried over magnesium sulfate. Evaporation of the
solvent gave a residue which was chromatographed on
silica gel with methylene chloride‡hexane (1‡1 by
volume) as the eluent. In the case of 5b, lithiation was
carried out in a stepwise procedure: 2 equiv of BuLi
2.2.1 General procedure for the synthesis of compounds
2a±e and 9
A mixture of 1-(hydroxymethyl)-1H-benzotriazole
(3.75g, 25mmol), the corresponding 2-aminopyridine
or 2-(dimethylamino)pyridine (25mmol) and a cata-
lytic amount of toluene-p-sulfonic acid in acetic acid
(25ml) was heated under re¯ux for 72h. The acetic
acid was removed under reduced pressure, and aque-
ous sodium carbonate was added to the residue. The
product was extracted with ethyl acetate (4Â80ml),
washed with aqueous sodium hydroxide, then water
(80ml), and dried over magnesium sulfate. The
solvent was removed under reduced pressure, and
the solid was chromatographed with chloroform‡
ethyl acetate (10‡1 by volume) to give the pure
compounds.
1204
Pestic Sci 55:1203±1209 (1999)

SARs and molluscicidal activity of 2-amino-5-substituted pyridines
2.2.7 Synthesis of 2-[(benzotriazole-1-ylmethyl)amino]-4-
methylpyridine 11
were added to the solution of 2b and 1 equiv of ethyl
bromide. After 15min, a further 1 equiv of BuLi and 1
equiv of propyl bromide were added. The temperature
for the whole process was kept at 78°C and the work-
up was as described above.
A mixture of 1-hydroxymethylbenzotriazole 1 (3.75g,
25mmol) and 2-amino-4-methylpyridine 12c (2.70g,
25mmol) was heated in ethanol (50ml) under re¯ux
for 20h. The solvent was distilled off, and the solid
product was recrystallized from ethanol.
2.2.3 General procedure for the synthesis of compounds 3b
and 6b
The yields and melting points of the above
compounds are given in Table 1.
To butanol or ethanol (20ml) was added sodium
metal (2.3g, 100mmol). On complete dissolution of
the metal, the benzotriazole adduct 2d or 5a (5mmol)
was added in one portion and the solution was re¯uxed
for 5h. Evaporation of the solvent gave a residue which
was dissolved in water and extracted with ethyl acetate
(3Â60ml). The organic extracts were washed with
water (50ml) and dried over magnesium sulfate.
Evaporation of the solvents gave a residue which was
chromatographed with hexane‡dichloromethane
(1‡1 by volume) to give the desired product.
2.3 Molluscicidal tests
2.3.1 Test animals
Specimens of the herbivorous snails, Theba pisana
(MuÈller) and Helix aspersa (MuÈller) were collected
during autumn 1998, from untreated nursery plants
and farms in Alexandria governorate, Egypt. The snail
species used in these studies were selected on the basis
of their geographical distribution and economy of the
crops they damage and identi®ed according to the key
given by Godan.1 Adult animals were chosen and
allowed to acclimatize to laboratory conditions for
three weeks and were fed on bran bait ad libitum.
2.2.4 General procedure for the synthesis of compounds 3a,
6a and 8
To a solution of benzotriazole adducts 2b, 5a or 4g
(5mmol) in THF (50ml) under nitrogen was added
butyl magnesium bromide (Grignard reagent
40mmol); in diethyl ether (20ml). The diethyl ether
was distilled off and the mixture was re¯uxed for 8h.
The reaction was monitored by TLC until the starting
material had been consumed. The reaction mixture
was then allowed to cool, poured into ice-water
(30ml), acidi®ed to pH 9 with hydrochloric acid
(2M) and extracted with diethyl ether (3Â60ml). The
ether solution was washed with saturated aqueous
sodium hydrogen carbonate (2Â100ml) and dried
over magnesium sulfate. Evaporation of the solvent
gave a residue which was puri®ed by column chroma-
tography with hexane‡dichloromethane (1‡1 by
volume).
2.3.2 Test chemicals
Stock solutions of each compound, including methio-
carb as a reference, were prepared in dimethyl
sulfoxide (DMSO), which causes little distress to slugs
and has been shown to be the most appropriate solvent
for the topical application,16 and serially diluted with
the same solvent to achieve the desired concentrations.
2.3.3 Bioassay techniques
2.3.3.1 Topical application. (Contact toxicity). The
method of Hussein et al17 was used because it is easy,
reproducible, and allows rapid screening of large
numbers of chemicals that may be used by spray
application. Preliminary experiments were carried out
to establish the range of dosage of the tested chemicals.
Six different concentrations, ranging from 5.0 to 25g
1
2.2.5 Synthesis of 2-amino-5-(1-ethylprop-1-enyl)-3-
methylpyridine 7
litre for each compound were prepared and three
replicates (10 animals for each) were kept in 0.5-litre
glass jars covered with cloth netting and secured with a
rubber band to prevent snails from escaping. Control
snails were treated with DMSO. The tested dose was
gently applied to the surface of the snail body inside
the shell using a micropipet containing 30ml in the case
of H aspersa and 5ml in the case of T pisana. Snails were
provided with lettuce leaves to feed on 24h after
treatment. Dead animals were detected 24, 48, and
72h after treatment by loss of response to a thin
stainless steel needle according to the WHO proce-
dure.18 Pure methiocarb (Mesurol, Bayer Co) was
used as a standard molluscicide.
To a solution of 2-amino-5-[1-(benzotriazol-1-yl)-1-
ethylpropyl]-3-methylpyridine 5a (1.50g, 5mmol) in
THF (40ml) was added NaH (0.24g, 10mmol) in one
portion. The solution was re¯uxed for 4h, cooled to
room temperature and water (30ml) added. The
solution was extracted with ethyl acetate (3Â30ml),
washed with aqueous sodium hydrogen carbonate,
and dried over magnesium sulfate. Evaporation of the
solvent gave a residue which was chromatographed
with hexane‡dichloromethane (3‡1 by volume) to
give the desired product as a yellowish oil.
2.2.6 Synthesis of 2-[(1,2,4-triazole-1-ylmethyl)amino]-3-
methylpyridine 10
2.3.3.2 Toxic baits (Stomach toxicity). Bran baits con-
taining 10 and 20g kg 1 of the tested pyridine deriva-
tives were used for trials, after preliminary tests had
A mixture of 1-hydroxymethyl-1,2,4-triazole 13 (2g,
20mmol) and 2-amino-3-methylpyridine 12b (2.70g,
25mmol) was heated in ethanol (50ml) under re¯ux
for 20h. The solvent was distilled off, and the solid
product was recrystallized from ethanol.
1
revealed that more than 20g kg baits discouraged
feeding by snails. The preparation of the bran baits was
carried out according to the method of El-Sebae et al19
Pestic Sci 55:1203±1209 (1999)
1205

SR El-Zemity, MA Radwan
Compound
R
R1
R2
Yield (%) mp (°C)
2a
2b
2c
2d
2e
3a
3b
4a
4b
4c
4d
4e
4fi
4fii
4g
4h
5a
5b
5c
5d
6a
6b
7
H
±
±
±
±
±
±
53
73
60
62
61
77
70
60
78
61
65
59
36
17
72
69
85
60
78
81
83
72
58
70
56
85
90
183±185
174±175
213±214
208±210
247±249
Oil
3-CH3
4-CH3
6-CH3
4,6-(CH3)2
3-CH3
6-CH3
3-CH3
3-CH3
3-CH3
3-CH3
±
±
±
±
C4H9
OC4H9
C2H5
iC3H9
45±47
±
152±153
192±193
136±137
106±107
183±184
223±225
262±264
280±281
227±230
161±162
78±81
±
(CH2)2CH(CH3)2
C8H17
±
±
4,6-(CH3)2 C2H5
±
3-CH3
3-CH3
3-CH3
3-CH3
3-CH3
3-CH3
4-CH3
3-CH3
3-CH3
3-CH3
3-CH3
3-CH3
H
C6H5CH(OH)
±
C6H5CH(OH)
(C6H5)2COH
(CH3)2COH
C2H5
±
±
±
C2H5
C2H5
C3H7
(CH2)2CH (CH3)2 (CH2)2CH (CH3)2
180±181
100±101
34±36
C8H17
C8H17
C2H5
C2H5
C2H5
C2H5
44±46
C2H5
±
±
±
±
±
Oil
8
9
10
11
a
±
±
±
±
168±170
164±165
157
3-CH3
4-CH3
163b
See Fig 1 for structures.
Table 1. Characteristics of 2-amino-5-substituted
pyridine derivativesa
b Literature (Reference 15) 157±158°C.
and they were tested for molluscicidal activity against
T pisana snails. For each treatment, three glass jars
(0.5litre) containing 10 adult snails per jar, and tightly
covered with cloth netting secured with a rubber band
were used. Three jars were also prepared for the
control group containing bran bait free of chemicals.
Two millilitres of water were added daily into each jar
to provide suitable humidity for snail activity. Mortal-
ity counts were recorded daily up to 10 days and the
dead snails were removed.
The results of tests on 2-amino-5-substituted
pyridine derivatives which are presented in Table 2
against the two tested snails by topical application
showed that there are some promising compounds
which could be developed in this area. Most of the
tested compounds showed excellent activity particu-
larly against T pisana. The structure±activity relation-
ship studies of pyridine derivatives revealed that
methyl substitution on the pyridine ring, particularly
at the 3-position (2b), increased the activity against H
aspersa except for the 4-methyl analogue (2c), but, the
activity was decreased against T pisana snails, when
compared with the unsubstituted compound (2a),
apart from 2b, which showed increased activity over
methiocarb in both tests, indicating that the 3-position
is necessary for molluscicidal activity. On the other
hand, 4,6-dimethyl substitution (2e) showed, moder-
ate toxicity, ranking between compounds 2d and 2c
against H aspersa but 2e was the least effective ana-
logue among compounds of type 2 against T pisana.
Surprisingly, linkage of methyl to the amino group or
linking the benzotriazole at this point reduced mollus-
cicidal activity (2a versus 9 & 2c versus 11). On the
other hand, replacing the benzotriazole in compound
11 with a triazole ring led to a potent compound, 10,
with LD50=89.26 and 260.77mg per snail against T
pisana and H aspersa, respectively. The corresponding
LD50 values for methiocarb were 107.34 and
210.27mg per snail. Substitution with a straight or
2.3.3.3 Statistical procedure. Percentage mortality was
corrected by Abbott's formula.20
LD50 (mg per snail) values with ®ducial limits for
each treatment were determined by the probit-analysis
method of Finney.21
3
RESULTS AND DISCUSSION
The performance of molluscicides against terrestrial
gastropods is greatly affected by the method of appli-
cation, which determines their ability to penetrate to
the sites of action,22 and by species-speci®c differences
in the effect of the molluscicidal itself.23
The molluscicidal activity of 2-amino-5-substituted
pyridine derivatives has been evaluated by a contact
method against H aspersa and T pisana (Table 2) and
as toxic baits against T pisana (Table 3) and compared
with methiocarb as a standard.
1206
Pestic Sci 55:1203±1209 (1999)

SARs and molluscicidal activity of 2-amino-5-substituted pyridines
LD50 (mg per snail) at 48h with 95% Fiducial Limitsa
Compound
H aspersa
T pisana
2a
2b
2c
2d
2e
635.02
118.78
674.70
354.16
539.76
560.32
544.81
(573.95±702.60)
(106.32±132.81)
(600.38±758.26)
(295.16±424.90)
(459.59±633.93)
(509.24±616.52)
(490.91±604.62)
>750
81.14
60.65
(73.96±97.52)
(50.22±73.23)
(92.45±145.55)
106.92
132.47 (116.32±150.17)
217.11 (137.48±381.70)
3a
58.10
65.74
47.30
98.06
(37.19±76.71)
(59.82±79.49)
(37.27±59.95)
(81.22±118.34)
3b
4ab
4b
342.97
136.81
306.50
(223.79±479.78)
(106.74±230.22)
(266.75±386.31)
>750
4c
165.13 (104.46±180.41)
4d
81.70
85.77
72.53
(65.49±89.29)
(76.04±96.75)
(54.82±95.86)
4eb
4fi
518.59
(424.67±633.31)
>750
4fiib
4g
178.93 (137.62±227.61)
614.46 (502.83±751.15)
629.47
336.68
(561.72±705.42)
(289.11±392.04)
>750
4h
104.18
83.18
(89.34±130.45)
(78.13±97.73)
(93.35±112.25)
5ab
5b
460.72
342.02
(418.82±506.79)
(238.68±454.40)
>750
109.88
5c
235.89 (202.96±274.13)
330.89 (296.02±481.44)
5db
6a
376.99
524.33
317.13
582.05
(339.26±418.91)
(432.15±637.75)
(265.35±473.67)
(473.44±615.67)
>750
96.77
76.29
59.68
(79.83±117.25)
(69.10±93.07)
(48.22±79.86)
6b
7
8
129.00 (105.50±157.66)
121.47 (106.61±150.74)
9b
10
260.77
210.72
(216.18±314.54)
>750
89.26
365.79 (337.60±444.55)
107.34 (87.83±124.35)
(66.24±103.29)
11b
Methiocarb
Control
a
(189.20±244.90)
0% mortality at 48h
n =30, in three replicates of 10 each.
Table 2. Molluscicidal activity of 2-amino-5-
substituted pyridine derivatives against Helix
aspersa and Theba pisana by topical application
b LD50 values for compounds 4 (a, e & fii), 5 (a & b); 9 and 11 were not calculated because of the low
percentage mortalities, ꢀ20% at the highest dose against H aspersa.
branched carbon chain on the methylene bridge as R1
reduced activity against H aspersa compared to the
unsubstituted compound (4a±c versus 2b & 4e versus
2e). However, lengthening this chain up to C5
gradually increased the activity against H aspersa
(4a±c), but the activity (4d) decreased again with
chains greater than C5. Moreover, substitution (R1)
with phenyl ring (s) diminished the activity, as shown
in compounds 4®, 4®i versus 2b, and this activity was
highly affected by the orientation of the hydroxy group
in the two diastereoisomers 4® and 4®i. On the other
hand, when R1 was converted from two phenyls to
methyls (4g versus 4h), the molluscicidal activity, was
enhanced.
type 2 with a butyl or butoxy group (2b versus 3a or
3b), respectively, led to a reduction in the mollusci-
cidal activity except in compound 2b versus 3a against
T pisana. However, replacing the benzotriazole in
compounds of type 5 (R1, R2) with the same groups
(5a versus 6a or 6b) increased molluscicidal action.
Replacement of benzotriazole in compound 4g with a
butyl group gave compound 8, which was more active.
Table 3 shows the comparative toxicities after 10
1
days of the tested chemicals as 10 and 20g kg bran
baits against T pisana. Interpretation of the structure±
activity relationships against T pisana, indicated that
the addition of a methyl group to the pyridine ring gave
the highest level of the activity at position-3 only (2b),
and, the other analogues 2c, 2d and 2e were less active
Additional substituents on the methylene bridge as
R2 with ethyl (5a versus 4a), isopropyl (5b versus 4b),
isobutyl (5c versus 4c), and octyl groups (5d versus
4d) continuously reduced activity against H aspersa.
The activity patterns of the R1 substituents were
reversed in case of T pisana, but, additional substi-
tuents as R2 reduced the activity in the same way as
with H aspersa.
1
against T pisana, except compound 2d as 20g kg
bait, which achieved 100% mortality. As in the topical
test (Table 2), addition of methyl at the amino group
reduced activity (2a versus 9). Nevertheless, adding
hydroxymethybenzotriazole instead of methyl gave a
slight increase of acivity (2c versus 11) and replacing
benzotriazole with a triazole ring (11 versus 10)
increased the molluscicidal activity above that of
methiocarb as 20g kg 1 bait.
Removing the benzotriazole from the molecule (5a)
led to an increase in activity (7). However, replace-
ment of the benzotriazole moiety in compounds of
Substitution at the methylene bridge with an alkyl
Pestic Sci 55:1203±1209 (1999)
1207

SR El-Zemity, MA Radwan
Table 3. Efficacy of 2-amino-5-substituted pyridine deriva-
effects in the bait test (Tables 2 and 3). These results
may suggest that compounds such as 3b, 6a, 6b and 7
were more effective as a contact poison than a stomach
poison under laboratory conditions.
tives as bran bait against Theba pisana snails
Mortality of snails exposed to bran
bait (%) (ÆSE)a
In conclusion, the comparative study of the activity
of the different compounds in relation to their
structures against T pisana snails showed that the
introduction of the methyl group at pyridine ring at
position 3 seems to be necessary for activity in the two
tests used. Introducing the ethyl group as R1 increased
toxicity in topical application but decreased it in the
bran bait test (4a versus 2b), while the opposite was
found with the additional introduction of another ethyl
group as R2 (4a versus 5a). Replacement of the ethyl
group by isopropyl, isobutyl or octyl as R1 reduced
activity (4b, 4c, or 4d versus 2b) as did an octyl group
at R2 (4d versus 5b) in both tests. The results obtained
in the present study show a number of promising
compounds, eg 2b, 4d and 10, that could replace
methiocarb for land snail control when administered
topically or as a bran bait.
1
10g kg bait
1
20g kg bait
Compound
2a
2b
2c
2d
2e
3a
3b
4a
4b
4c
4d
4e
4fi
4fii
4g
4h
5a
5b
5c
5d
6a
6b
7
8
83.33 (Æ1.67)
86.67 (Æ1.24)
23.33 (Æ3.16)
20.00 (Æ2.24)
0.00
60.00 (Æ1.29)
100
53.33 (Æ2.09)
100
30.00 (Æ3.65)
NT
NTb
0.00
20.00 (Æ3.87)
63.33 (Æ1.45)
23.33 (Æ3.16)
20.00 (Æ3.87)
46.67 (Æ3.68)
NT
40.00 (Æ2.74)
56.67 (Æ2.03)
56.67 (Æ3.07)
73.33 (Æ1.35)
NT
66.67 (Æ1.87)
13.33 (Æ1.58)
40.00 (Æ1.58)
46.67 (Æ0.84)
60.00 (Æ2.24)
43.33 (Æ2.32)
NT
73.33 (Æ1.78)
20.00 (Æ2.24)
40.00 (Æ2.74)
26.67 (Æ1.12)
83.33 (Æ1.67)
80.00 (Æ1.12)
NT
Our efforts are now directed towards optimizing the
molluscicidal activity of the most promising com-
pounds and some structural modi®cations are under
investigation that will be described in a future
publication.
40.00 (Æ1.58)
0.00
0.00
20.00 (Æ2.24)
20.00
0.00
0.00
23.33 (Æ3.16)
NT
NT
9
10
11
46.67 (Æ3.05)
63.33 (Æ0.72)
36.67 (Æ0.95)
66.67 (Æ0.71)
0.00
53.33 (Æ2.85)
100
ACKNOWLEDGEMENTS
The authors wish to express their thanks to Prof Dr
AH El-Sebae for advice and helpful suggestions
throughout this work.
56.67 (Æ0.77)
53.33 (Æ1.58)
3.33 (Æ3.16)
Methiocarb
Control
a
n =30 in three replicates of 10 each.
b
NT=Not tested.
REFERENCES
1 Godan D, Pest slugs and snails, biology and control Springer-Verlag,
Berlin. pp 191±192 (1983).
group as R1 reduced the activity in both 10 and
2 Radwan MA, El-Wakil HB and Osman KA, Toxicity and
biochemical impact of certain oxime carbamate pesticides
against terrestrial snail, Theba pisana (MuÈller). J Environ Sci
Health B 27:759±773 (1992).
1
20g kg bran baits compared to the unsubstituted
compound (4a±d versus 2b), but lengthening this alkyl
group increased activity. Furthermore, the phenyl
substituents greatly reduced the activity (4®i diaster-
eoisomer versus 2b). Additional substitution at the
methylene bridge as R2 with ethyl increased activity in
the 20g kg 1 bran bait over the standard (4a versus 5a
& 4b versus 5b), but the opposite activity was observed
in both bran baits when the octyl group was
introduced (5d). Removing or displacing of benzo-
triazole with butyl or butoxy from the molecule (2b
versus 3b and 5a versus 6a, b & 7), also reduced
activity (Table 3).
3 Miller E, Swails D, Olson F and Staten RT, White garden snail
(Theba pisana MuÈller): Ef®cacy of selected bait and sprayable
molluscicides. J Agric Entomol 5:189±197 (1988).
4 Schuytema GS, Nebeker AV and Grif®s WL, Effects of dietary
exposure to forest pesticides on the brown garden snail, Helix
aspersa (MuÈller). Arch Environ Contam Toxicol 26:23±28
(1994).
5 Yamamoto I, Kamimura H and Yamamoto R, Nicotinoids as an
insecticide. Reprinted from the Memoirs of the Tokyo Univ of
Agric, VII:67±90 (1963).
6 Alig B, Stendel W and Londershausen M, Preparation of
substituted pyridines as insecticides. (Bayer A.-G) EP
356,797 (Cl. C07d213/64), DE Appl. 3,828,820 (1988);
CA, 113: 58954g, (1990).
Comparing the results of the topical application
with those of the bran bait test, compound 4a was
apparently the most effective among the tested
chemicals against T pisana in topical application
(Table 2) and gave relatively satisfactory control in
the bait test (Table 3). Also, the results obtained
showed that compounds 3b, 6a, 6b and 7, which are
free of benzotriazole, were more active than methio-
carb in topical application, but showed unimpressive
7 Nakajima T, Komyoji T, Akagi T, Nagatani K, Haga T, Matsuo
N and Suzuki K, Synthesis and fungicidal activity of N-
phenylpyridinamines. ACS Symp Ser 584:443±448 (1995).
8 Yazaki A, Niino Y, Ohshita Y, Hirao Y, Amano H, Hayashi N
and Kuramoto Y. Preparation of novel pyridonecarboxylic acid
derivatives as antibacterial agents. (Wakunaga Pharm Co Ltd)
PCT Int Appl WO 97 11,068 (Cl. C07D401/04) JP Appl 96/
178,462 (1996); CA 126: 305587g (1997).
9 Kleemann A., Preparation of heterocyclic-substituted pyridine
1208
Pestic Sci 55:1203±1209 (1999)

SARs and molluscicidal activity of 2-amino-5-substituted pyridines
selective herbicides. (Shell Int Res) PCT Int Appl WO 94
22,833 (Cl. C07D213/69), EP Appl 93/105,006 (1993); CA
122:31337g (1995).
15 Katritzky AR, Rachwal S and Rachwal B, The chemistry of
benzotriazole Part 3. The aminoalkylation of benzotriazole. J
Chem Soc Perkin Trans 1 799±804 (1987).
10 Huebl D and Pieroh EA, A method for combating nematodes
with 2-(2-pyridylimino)-1,3-dithietane or its salts. EP 310, 540
(Cl. C07D409/12), 05 DE Appl 3,733,806 (1987); CA 111:
134128s (1989).
16 Young AG and Wilkins RM, A new technique for assessing the
contact toxicity of molluscicides to slugs. J Moll Stud 55:533±
536 (1989).
17 Hussein HI, Kamel A, Abou-Zeid M, El-Sebae AH and Salah
MA, Uscharin, the most potent molluscicidal compound
tested against land snails. J Chem Ecol 20:135±140 (1994).
18 Anon, Molluscicidal screening and evaluation. WHO Bull
38:507±581 (1965).
11 Salmon R, Pearson DPJ, Parry DR and Kozakiewicz AM
Acaricidal and insecticidal penta¯uoro(phenyl)sulfur or penta-
¯uoro-(pyridinyl)sulfur compounds. (Zeneca Ltd) PCT Int
Appl WO 94 21,606 (Cl. C07D207/36) GB Appl. 93/6, 184
(1993); CA 122: 31333c (1995).
19 El-Sebae AH, El-Okda MMK and Marei AS, Local formulation
of three carbamoylated oximes as terrestrial molluscicides.
Agric Res Rev 60:85±91 (1982).
12 Oishi Y, So K, Watanabe T and Konya K, Preparation of
anilinopyridine derivatives as algicides and fouling control
agents. (Ihara Chemical Industry Co Ltd) JP 62 169,767
[87,169,767] (Cl. C07D213/74) (1987), Appl 86/11,731
(1986); CA 108:150315u (1988).
20 Abbott WS, A method of computing the effectiveness of an
insecticide. J. Econ Entomol 18:265±267 (1925).
21 Finney DJ, Probit Analysis, 3rd edn, Cambridge Univ Press,
London. p 318 (1971).
13 Alekseev SI, Blocking of the fast potassium current in Limnaea
stagnalis neurons by pyridine and its derivatives. Biol Membr
10:272±286 (1993).
22 Henderson IF and Martin AP, Control of slugs with contact
action molluscicides. Ann Appl Biol 116:273±278 (1990).
23 Radwan MA, A technique for testing the ef®cacy of molluscicidal
baits against land snails. Com In Sci. & Dev. Res 651:17±26
(1993).
14 Katritzky AR, El-Zemity S and Lang H, Conversions of 2-
aminopyridines into 5-substituted derivatives mediated by 1-
hydroxymethylbenzotriazole. J Chem Soc Perkin Trans 1 3129±
3133 (1995).
Pestic Sci 55:1203±1209 (1999)
1209