Structure stability/activity relationships of sulfone stabilized N,N-dichloroamines

Article abstract of DOI:10.1016/j.bmcl.2011.04.084

Structure stability/activity relationships (SXR) of a new class of N,N-dichloroamine compounds were explored to improve antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans while maintaining aqueous solution stability. This study identified a new class of solution-stable and topical antimicrobial agents. These agents are sulfone-stabilized and possess either a quaternary ammonium or sulfonate appendages as a water solubilizing group. Several unique challenges were confronted in the synthesis of these novel compounds which are highlighted in the discussion.

Full text of DOI:10.1016/j.bmcl.2011.04.084

Bioorganic & Medicinal Chemistry Letters 21 (2011) 3682–3685
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Structure stability/activity relationships of sulfone stabilized
N,N-dichloroamines
Eddy Low, Bum Kim, Charles Francavilla, Timothy P. Shiau, Eric D. Turtle, Donogh J. R. O’Mahony,
Nichole Alvarez, Ashley Houchin, Ping Xu, Meghan Zuck, Chris Celeri, Mark B. Anderson,
⇑
Ramin (Ron) Najafi, Rakesh K. Jain
NovaBay Pharmaceuticals Inc., 5980 Horton St., Suite 550, Emeryville, CA 94608, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Structure stability/activity relationships (SXR) of a new class of N,N-dichloroamine compounds were
explored to improve antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida
albicans while maintaining aqueous solution stability. This study identified a new class of solution-stable
and topical antimicrobial agents. These agents are sulfone-stabilized and possess either a quaternary
ammonium or sulfonate appendages as a water solubilizing group. Several unique challenges were con-
fronted in the synthesis of these novel compounds which are highlighted in the discussion.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 14 March 2011
Revised 13 April 2011
Accepted 19 April 2011
Available online 24 April 2011
Keywords:
Antimicrobial
N-Chloroamine
Many antimicrobial compounds used for the prevention or
treatment of infections have been rendered less effective through
evolved bacterial drug resistance. This has engendered both an ur-
gent need and widespread interest in new, fast-acting, broad spec-
trum, topical antimicrobials with reduced potential for inducing
resistance.1
the process of elucidating the MOA and our studies so far indicate
a very rapid inactivation of sulfur containing proteins resulting in
their dysfunction, dysregulation or shedding from the membrane
leading to the death of the pathogen. A dichloroamine compound
identified from this program, NVC-4225 (3) is currently in phase
2 clinical trials for impetigo and viral conjunctivitis.
The chlorinated derivatives of taurine, N-chlorotaurine (1) and
N,N-dichlorotaurine (2) (Fig. 1) are part of the innate mammalian
response to infection, produced as antimicrobials to destroy invad-
ing microorganisms and protect the body.2 Myeloperoxidase
(MPO; EC 1.11.1.7) in human granulocytes and monocytes uses
hydrogen peroxide and chloride to generate hypochlorous acid,
which reacts with taurine to produce the longer lived antimicrobial
N-chlorotaurine.
In previous SXR (structure stability/activity relationship) stud-
ies of N,N-dichloroamine compounds,6a,c we replaced the sulfonate
portion of 3 with alternative water solubilizing groups, such as tri-
alkylammonium (4),6c dimethylsulfonium, pyridinium, and other
positively charged heterocycles. Only
a limited number of
O
O
O
O
Cl
S
N-Chlorotaurine has evolved as
a natural antimicrobial
Cl
S
N
H
compound with no known bacterial resistance,3a and provides a
unique starting point for novel antibiotic drug development. Nagl
et al., have previously reported the anti-microbial activity of
N-chlorotaurine.3b–g However, its commercial utility may be lim-
ited due to its short shelf-life in solution.4 Fortunately, we have
determined that key properties of chloramine-based antimicrobi-
als can be tailored through the molecule’s core targeting moiety
(CTM), allowing us to regulate the biological activity, toxicity,
and physiochemical properties such as reactivity, stability, and sol-
ubility. These N,N-dichloramines are a promising class of antimi-
crobials with a unique mechanism of action (MOA). We are in
OH
N
OH
1
2
Cl
Cl
CTM
N
X
O
O
Cl
S
Cl
N+
Cl-
N
ONa
N
3
Cl
Cl
4
⇑
Corresponding author.
E-mail address: rjain@novabaypharma.com (R.K. Jain).
Figure 1. Examples of stabilizing core targeting moieties.
0960-894X/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2011.04.084

E. Low et al. / Bioorg. Med. Chem. Lett. 21 (2011) 3682–3685
3683
derivatives could be prepared with acceptable levels of solution
stability, leaving little room for SAR expansion in this series. We
observed that an electron withdrawing (EW) group proximal to
the nitrogen is required to stabilize the N–Cl bond, and developed
methods to prepare new derivatives with EW functional groups,
such as esters, amides, ethers or sulfones, within the scaffold.6a,c
In particular, a sulfone analog showed good aqueous stability
prompting us to explore this functionality further. In the present
study, we modified the structural elements of the CTM by varying
the linkages between stabilizing, solubilizing and reactive func-
tionalities to monitor their effects on stability and the in vitro
anti-microbial activity towards Gram-negative and Gram-positive
bacteria as well as fungi.
a,b
61 %
N
c,d
O2N
NO2
quant
9
10
N+
I-
Cl
N+
Cl-
e,f
98 %
H2N
N
Cl
12
11
Scheme 2. Reagents and conditions: (a) N,N-dimethylacrylamide, BnN+Me3OHꢁ,
dioxane, 100 °C, 1 h; (b) BH3ꢂTHF, 70 °C, 2 h; (c) MeI, MeOH, 20 °C, 48 h; (d) Raney
Ni, H2 (500 psi), MeOH-H2O, 20 °C, 72 h; (e) Ag2O, aq HCl, 1 h; (f) MeOH, t-BuOCl,
0–10 °C.
The relationship of compound stability and activity vs the place-
ment of electron withdrawing functionalities within the CTM was
examined in both sulfone and quaternary ammonium series. Ini-
tially a series of homologous quaternary ammonium compounds
was prepared. The synthesis of 8, a one carbon homolog of 4, is pre-
sented in Scheme 1.
Intermediate 7 was synthesized through the amidation of acid
chloride (6) with dimethylamine, reduction of the azide and amide,
N-protection of the primary amine as the benzyloxycarbonyl, and
quaternization with methyl iodide. Halogen exchange with silver
oxide converted an iodide salt, 7, to a chloride salt which was more
amenable for hydrogenation. The resulting free amine was chlori-
nated with t-BuOCl to obtain dichloroamine product 8.
The synthesis of the two carbon homolog 12 is shown in
Scheme 2. Intermediate 10 was synthesized by a modified version
of the reported procedure7 wherein a conjugate addition of 2-
nitropropane to N,N-dimethylacrylamide was employed, followed
by reduction of the amide with borane, to provide the amine. N-
Methylation and reduction of the nitro group provided the key
intermediate 11. The nitro group required high pressure hydroge-
nation for both the chloride or iodide counter ions. Although re-
moval of the iodide was not necessary for reduction to occur, it
was necessary to prevent the formation of mixed dihaloamines
during the N-chlorination reaction with t-BuOCl to afford 12.
The synthesis of sulfone analogs is presented in Scheme 3. A
common intermediate 14 allowed the preparation of compounds
having either a sulfonic acid or a trimethylammonium moiety as
a terminal water solubilizing group. Compound 14 was prepared
from the previously synthesized6a azido carboxylic acid 13 in five
steps. Alkylation of thiol 14 with the appropriate bromo-
chloroalkane, a common step for analogs 15, 17, and 19, followed
by reaction with KSAc and oxidation with formic peracid (from
hydrogen peroxide in formic acid) gave the desired sulfone-
containing sulfonic acid derivatives, with the exception of 19
which required a repeat of steps f and d prior to oxidation. The syn-
theses of 21 and 23 were accomplished by treating 14 with the
appropriate bromoalkyltrimethylammonium salt. Oxidation of
the intermediate thioethers gave the desired sulfones 21 and 23,
respectively. The bromide counter ion was converted to bromine
during oxidation and was distilled off while concentrating the
reaction mixture. Removal of the Cbz group from 21 was accom-
plished with HBr in acetic acid followed by halogen exchange in
the presence of acetic acid. Acetic acid was beneficial in that it both
assisted in the dissolution of the Ag2O and kept the solution acidic.
Under basic conditions 21 is prone to beta elimination to pro-
duce a vinyl sulfone side product. While hydrogenation of 21 over
Pd/C also caused the elimination of trimethylamine, compound 23
proved to be stable to these conditions and the resultant amine
was chlorinated to give dichloroamine product 24. Compound 25
was synthesized through alkylation of 14 with 8-bromo-octan-1-
ol, mesylation of the resulting alcohol, thioacetate displacement
of the mesylate and oxidation of the thioether to produce the sul-
fone-containing sulfonic acid 25, which was deprotected and chlo-
rinated to give 26. Compound 27 was synthesized from 14 via the
thioether mesylate intermediate, analogous to 25, where the mes-
ylate was then displaced with potassium phthalimide. The thioe-
ther was oxidized to the sulfone followed by N-phthalimide
deprotection of the amine with hydrazine. Methylation of the
amine to the trimethylammonium salt, then halogen exchange
and N-chlorination gave 28. The two-carbon homolog of the sul-
fone sulfonic acid 30 was obtained from the key intermediate 29.
Michael addition of 2-nitropropane to methyl acrylate followed
by reduction of the nitro ester to a nitro alcohol, which was mesy-
lated and reacted with sodium 2-mercaptoethanethiolate resulted
in an inseparable mixture of disulfides. Oxidation of the crude
mixture with formic peracid gave the desired sulfone-containing
sulfonic acid in low yield. Hydrogenation of the nitro group under
high pressure followed by N-chlorination gave 30. The data in
Table 1 summarizes the antimicrobial activity as MBC or MFC val-
ues against Escherichia coli, Staphylococcus aureus, and Candida albi-
cans, as well as aqueous solution stability at 40 °C for pH 4
(acetate) and pH 7 (phosphate) buffered saline solutions. All ana-
logs showed comparable antibacterial activity, with no significant
difference between the in vitro activities for Gram-positive versus
Gram-negative organisms. Activity against C. albicans was the most
O
O
variable for the compounds tested, ranging from 8
case of 26 to 1024 g/mL for compound 18.
lg/mL in the
a,b
c,d,e,f
70 %
l
OH
N3
Cl
The quaternary ammonium series (QA) (4, 8, and 12) exhibited
excellent solution stabilities where 12 ꢀ 8 < 4. The general trend
where solution stability increased as an EW group was moved
closer to the N–Cl bond was also observed in a related sulfonic acid
series, where 3 was more stable than the corresponding homologs
for m = 2 and 3.6a This observation may be explained through the
inductive effect of the EW group, which was consistent with both
cationic and anionic EWGs. The reactivity and stability of the
N–Cl bond may be related to the electronegativity of the nitrogen.
One might expect that the inductive effect of nearby EW group
would weaken the N–Cl bond and decrease stability, but this was
86 %
5
6
I-
N+
Cl-
N+
Cbz
Cl
g,h,i
36 %
N
H
N
Cl
8
7
Scheme 1. Reagents and conditions: (a) NaN3, AcOH, H2O, 95 °C, 48 h; (b) SOCl2,
DCE, reflux, 4 h; (c) dimethylamine, DCM, ice-cooled, 2 h; (d) LAH, THF, 70 °C, 8 h;
(e) THF, Cbz-OSu, 20 °C, 16 h; (f) MeI, EtOH, 20 °C, 16 h; (g) Ag2O, water, 0.5 h; then
aq HCl; (h) 10% Pd/C, MeOH, H2, 20 °C, 16 h; (i) MeOH, t-BuOCl, 0–20 °C, 1 h.

3684
E. Low et al. / Bioorg. Med. Chem. Lett. 21 (2011) 3682–3685
f,d,g
h,i
Cl
SO3H
Cbz
SO3H
N
S
N
H
S
78 %
71 %
16
O
S
O
15
O
S
O
Cl
f,g
Cbz
h,i
Cl
N
H
SO3H
N
SO3H
70 %
93 %
17
O
O
18
O
O
Cl
f,d,e,
f,d,g
O
O
O
O
O
h,i
Cb z
S
Cl
S
O
N
H
S
SO3H
N
S
SO3H
37 %
11 %
19
O
O
20
O
O
O
Cl
N3
OH
Cbz
N+
13
N+
Cl-
j,g
Cl
k,l,i
N
H
S
-
N
S
HCO2
61 %
76 %
21
a,b,c,d,e
O
34 %
SH
22
O
Cl
Cl-
N+
m,g,l
32 %
Cl-
N+
h,i
Cbz
Cl
Cb z
N
S
N
S
quant
N
H
H
23
O
O
24
O
O
Cl
14
Cl
Cl
SO3H
f,c,d,g
62 %
Cbz
SO3H
h,i
70 %
N
S
N
S
S
7
H
7
7
26
28
O
O
O
Cl
25
27
O
O
O
f,c,n,g,
o,p,l
N+
Cl-
Cbz
O2N
N+
Cl-
h,i
75 %
N
S
N
H
7
21 %
O
S
O
Cl
O
O
Cl
q,r,c,s
42 %
S
g,t,i
N
SO3H
NO2
SH
30
29
Cl
24 %
10
Scheme 3. Reagents and conditions: (a) LAH, ether, 0–25 °C, 16 h; (b) Cbz-OSu, isopropanol–H2O, 16 h; (c) MeSO2Cl, CH2Cl2, Et3N, 0 °C, 2 h; (d) KSAc, DMF, 20–70 °C, 16 h; (e)
MeOH, aq NaOH, 1 h; (f) 1-bromo-2-chloroethane for 15 and 19, sodium 3-bromopropane-1-sulfonate for 17, 1-bromo-octan-8-ol for 25 and 27, Cs2CO3, DMF–water, 20 °C,
16 h; (g) HCO2H, 30% H2O2, 20 °C, 2 h; (h) 10% Pd/C, MeOH, H2, 20 °C, 16 h; (i) t-BuOCl, 0–10 °C, 1 h; (j) 2-bromo-N,N,N-trimethylethan-1-ammonium bromide, Cs2CO3, DMF–
water, 20 °C, 16 h; (k) 33% HBr AcOH; (l) Ag2O, AcOH, water, 0.5 h; then aq HCl; (m) 3-bromo-N,N,N-trimethylpropan-1-ammonium bromide, Cs2CO3, DMF–water, 20 °C, 16 h;
(n) KPhthalimide, DMF, 50 °C; (o) NH2NH2, EtOH, reflux 6 h; (p) MeI, EtOH, 20 °C; (q) methyl acrylate, BnN+Me3OHꢁ, dioxane, 100 °C, 1 h; (r) LiBH4, MeOH, 20 °C, 16 h; (s)
sodium 2-mercaptoethanethiolate, EtOH, 90 °C, 0.5 h; (t) Raney Ni, H2 (500 psi), MeOH–H2O, 20 °C, 72 h.
Table 1
Biological activity of compound 3 and its analogs
Cl
X
m
W
n
g/mL)a
Solution stability (days)c
N
Cl
MBC or MFC (
l
Compds
m
X
n
W
E. coli ATCC 25922
S. aureus ATCC 29213
C. albicans ATCC 10231
t1/2 pH 4 (saline)
t1/2 pH 7 (phosphate)
3
1
1
2
3
2
2
2
2
2
2
2
3
1
n/a
n/a
n/a
n/a
SO2
SO2
0
0
0
0
2
3
2
2
3
8
8
2
2
SO3H
NMe3
2
16
2
8
8
2
2
8
8
2
8
8
4
2
8
2
2
2
2
4
2
2
4
8
2
8
32
128
64
256
16
1024
32
32
32
8
32
>730
>325
>281
ꢃ80
>342
>112
>73
6
>160
182
127
45
>300
>396
>210
56
44c
8
þ
þ
NM3þ
12
16
18
20
22
24
26
28
30
313a
NM3
SO3H
SO3H
SO3H
>342
85
SO2CH2CH2SO2
14b
0
þ
SO2
SO2
SO2
SO2
SO2
SO2
NM3þ
70b
70b
74
NM3
SO3H
þ
NM3
SO3H
SO3H
128
64
45b
1
>93
a
Minimum Bactericidal Concentration (MBC) was determined using a modified standard method described in CLSI M26-A whereby isotonic saline at pH 4 is substituted for
Mueller-Hinton broth (MHB) to compensate for the reactivity of chlorine to certain components of MHB. Due to the rapid cidal nature of chlorinated derivatives, the assay
was shortened from 16 to 20 h at 35 °C to 1 h at room temperature.
b
In 0.6% borate buffer pH 7.
Represents last data point taken from for each compound.
c
not observed experimentally. Similarly, as the kinetic reactivity of
chloramines with nucleophiles is affected by proton transfer in the
transition state, it is possible that the EW groups reduce the basi-
city of the Cl–N group, limiting protonation and thereby increasing

E. Low et al. / Bioorg. Med. Chem. Lett. 21 (2011) 3682–3685
3685
kinetic stability; but again, this is not supported by experimental
evidence. Under the more acidic conditions (pH 4 vs 7), the com-
pounds are more stable in solution although they are still more
reactive towards other nucleophiles at the lower pH. Other factors
play a significant role in stabilizing the dichloroamine function. We
observe an optimal distance between the electron-withdrawing
group and the dichloroamine of about three bonds; lengthening
or shortening the chain leads to instability of the dichloroamine.
This compound instability suggests there is an associated increase
in reactivity or biological activity. Examination of the QA series (4,
8, and 12) data show similar activity for all organisms with a tight
range of 2- to 4-fold difference between these analogs and demon-
strates there is no correlation between compound stability and
biological activity for this series. Comparison of the stability of
the sulfone-containing sulfonic acids of varying (CH2)m chain
length showed compound 16, with a two-methylene spacer, was
the most stable (31 < 30 < 16), in contrast to the previous two ser-
ies where the one-carbon spacer 3 and 4 were the most stable.
When the (CH2)m chain length was held constant and the chain
length between the sulfonic acid and the sulfone were varied, 16
was again the most stable (18 ꢄ 26 < 16). Varying the chain length
from n = 3–8 did not affect aqueous stability of either the sulfonic
acid or the trimethylammonium series (18 ꢄ 26, 24 ꢄ 28). Com-
parison of the analogs when m = 2 (CH2)m while switching the
WSG showed that the sulfonic acids were generally more stable
than the ammonium salts (22 < 16, 28 < 26). When the stabilizing
group and the WSG (NMe3) are too close, the ethylene protons
are prone to b-elimination and this leads to the rapid decomposi-
tion of 22 to give trimethylamine and a vinyl sulfone.8 Inserting
a second sulfone moiety into the backbone (20) decreased stability
as compared to a simple alkyl chain (26).
While the activity of sulfone-containing sulfonic acid analogs
against C. albicans, when (CH2)n was held constant, also follows
the earlier trend, where the analog with n = 2 had the best activity
(30 < 31 < 16). This was not the case when (CH2)m was held con-
stant; there was a 32-fold difference in activity going from (18)
n = 3 to (26) n = 8. There is no obvious explanation for this observa-
tion. However, for the sulfone trimethylammonium analogs (SA)
(22, 24, and 28) their activity remained constant. This may allude
to a preferential association to C. albicans, since there is a known
negative charge on the surface of the cell wall.9 The invariance in
activity of SAs (22, 24, and 28) and dependence of QAs (4, 8, and
12) activity on chain length against C. albicans shows that it is pos-
sible to uncouple aqueous stability from activity. The factors gov-
erning stability are still under investigation.
to sodium 2-dichloramino-2-methylpropane-1-sulfonate (3). The
optimal linker length of 2 has been identified which provides solu-
tion stability in the sulfone series. This study also highlights the
significant challenges of transforming the amine precursors to
the various chloramines. Utilizing these active, stabilizing, struc-
tural elements for future dichloroamine design allows us to incor-
porate additional targeting functions or physiochemical modifying
substituents for use as new antimicrobial agents in the treatment
of resistant and non-resistant pathogens.
Acknowledgments
The authors wish to acknowledge Drs. John Bartell, Masood
Chowhan, Howard Ketelson, and David Stroman for helpful discus-
sions. This work was supported by Alcon Laboratories, Inc.
References and notes
1. (a) Brown, M. L.; Aldrich, H. C.; Gauthier, J. J. Appl. Environ. Microbiol. 1995, 61,
187; (b) Cookson, B. D.; Bolton, M. C.; Platt, J. H. Antimicrob. Agents Chemother.
1991, 35, 1997; (c) Brooks, S. E.; Walczak, M. A.; Hameed, R.; Coonan, P. Infect.
Control Hosp. Epidemiol. 2002, 692; (d) Suller, M. T. E.; Russell, A. D. J. Antimicrob.
Chemother. 2000, 46, 11; Chuanchuen, R.; Karkhoff-Schweizer, R. R.; Schweizer,
H. P. Am. J. Infect. Control 2003, 31, 124; (e) Mori, T.; Shimizu, N.; Onishi, M.;
Sanada, S.; Koda, Y.; Inoue, M.; Kurono, S.; Okada, H. Jpn. J. Hosp. Pharm. 2000, 26,
652; (f) Russell, A. D.; Tattawasart, U.; Maillard, J.-Y.; Furr, J. R. Antimicrob. Agents
Chemother. 1998, 42, 2151; (g) McCay, P. H.; Ocampo-Sosa, A. A.; Fleming, G. T. A.
Microbiology 2010, 156, 30; Mangalappalli-Illathu, A. K.; Korber, D. R. Antimicrob.
Agents Chemother. 2006, 50, 3588.
2. Nagl, M.; Hess, M. W.; Pfaller, K.; Hengster, P.; Gottardi, W. Antimicrob. Agents
Chemother. 2000, 44, 2507.
3. (a) Nagl, M.; Gottardi, W. Hyg. Med. 1996, 21, 597; (b) Nagl, M.; Larcher, C.;
Gottardi, W. Antiviral Res. 1998, 38, 25; Nagl, M.; Hess, M. W.; Pfaller, K.;
Hengster, P.; Gottardi, W. AAC 2000, 2507; (c) Nagl, M.; Larcher, C.; Gottardi, W.
Antiviral Res. 1997, 18, 577; (d) Nagl, M.; Gottardi, W. Hyg. Med. 1992, 17, 431;
(e) Yazdanbakhsh, M.; Eckmann, C. M.; Roos, D. Am. J. Trop. Med. Hyg. 1987, 37,
110; (f) Nagl, M.; Hengster, P.; Sementiz, E.; Gottardi, W. J. Antimicrob.
Chemother. 1999, 43, 805; (g) Arnitz, R.; Sarg, Bettina.; Helmut, W. O.; Neher,
A.; Lindner, H.; Nagl, M. Proteomics 2006, 6, 865; (h) Nagl, M.; Lass-Florl, C.;
Neher, A.; Gunkel, A.; Gottardi, W. J. Antimicrob. Chemother. 2001, 47, 871.
4. N-Chlorotaurine is stable at refrigerator temperature (2–5 °C). (a) Neher, A.;
Nagl, M.; Schrott-Fischer, A.; Ichiki, H.; Gottardi, W.; Gunkel, A. R.; Stephan, K.
Arch. Otolaryngol. Head Neck Surg. 2001, 127, 530.
5. Wang, L.; Khosrovi, B.; Najafi, R. Tetrahedron Lett. 2008, 49, 2193.
6. (a) Low, E.; Nair, S.; Shiau, T.; Belisle, B.; Debabov, D.; Celeri, C.; Zuck, M.; Najafi,
R.; Georgopapadakou, N.; Jain, R. Bioorg. Med. Chem. Lett. 2009, 19, 196; (b)
Shiau, T. P.; Houchin, A.; Nair, S.; Xu, P.; Low, E.; Najafi, R.; Jain, R. Bioorg. Med.
Chem. Lett. 2009, 19, 1110; (c) Francavilla, C.; Low, E.; Nair, S.; Kim, B.; Shiau, T.
P.; Debabov, D.; Celeri, C.; Alvarez, N.; Houchin, A.; Xu, P.; Najafi, R.; Jain, R.
Bioorg. Med. Chem. Lett. 2009, 19, 2731.
7. Moffett, R. B. Org. Synth. Coll. Vol. 1963, 4, 652. ; 1952, 32, 86..
8. Kroll, F. E. K.; Morphy, R.; Rees, D.; Gani, D. Tetrahedron Lett. 1997, 38, 8573.
9. Hobden, C.; Teevan, C.; Jones, J.; O’Shea, P. Microbiology 1995, 141, 1875.
In summary, we have described the synthesis and SXR of sul-
fone-containing analogs of taurine-based chloroamines compared