1-(2-Aminoethyl)-3-(arylsulfonyl)-1H-pyrrolopyridines are 5-HT6 receptor ligands

Article abstract of DOI:10.1016/j.bmcl.2009.10.067

1-(2-Aminoethyl)-3-(arylsulfonyl)-1H-pyrrolopyridines were prepared. Binding assays indicated they are 5-HT₆ receptor ligands, among which 6f and 6g showed high affinity for 5-HT₆ receptors with K_i = 3.9 and 1.7 nM, respectively.

Full text of DOI:10.1016/j.bmcl.2009.10.067

Bioorganic & Medicinal Chemistry Letters 19 (2009) 6935–6938
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
1-(2-Aminoethyl)-3-(arylsulfonyl)-1H-pyrrolopyridines are 5-HT6
receptor ligands
b
b
b
b
Ronald C. Bernotas a, , Schuyler A. Antane , Steven E. Lenicek , Simon N. Haydar , Albert J. Robichaud ,
*
Boyd L. Harrison b, Guo Ming Zhang c, Deborah Smith c, Joseph Coupet c, Lee E. Schechter c
a Chemical Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
b Chemical Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA
c Neuroscience, Wyeth Research, CN 8000, Princeton, NJ 08543, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
1-(2-Aminoethyl)-3-(arylsulfonyl)-1H-pyrrolopyridines were prepared. Binding assays indicated they are
5-HT6 receptor ligands, among which 6f and 6g showed high affinity for 5-HT6 receptors with Ki = 3.9 and
1.7 nM, respectively.
Received 28 August 2009
Revised 14 October 2009
Accepted 15 October 2009
Available online 20 October 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Serotonin
5-HT6 receptor
Pyrrolo[2,3-c]pyridine
Pyrrolo[3,2-b]pyridine
Pyrrolo[3,2-c]pyridine
Agonist
Antagonist
Sulfone
The 5-hydroxytryptamine-6 (5-HT6) receptor is believed to play
a role in learning and memory and therefore its modulation has
been investigated as a potential therapeutic target.1 Intense inter-
est in 5-HT6 receptors has led to the discovery of several classes of
to explore the synthesis and pharmacology of the regioisomeric
pyrrolopyridines, which result from moving the nitrogen around
to the various positions of the six-membered ring (4, 5 and 6). In
high affinity ligands2 including 1-arylsulfonyl-tryptamines
1
NR1R2
NR1R2
(Fig. 1) reported by Glennon and others.3 One approach to the
development of novel serotonergic ligands has been to reverse
the relative roles of the 1- and 3-positions on the indole ring of this
compound class. On this basis, we initially identified compounds 2
in which the location of the aminoethyl side chain is ‘flipped’ from
the indole 3-position, as in serotonin, to the indole nitrogen.4 Many
of these compounds were high affinity 5-HT6 ligands and served as
the genesis of several ensuing novel derivative classes.
N
N
SO2Ar
SO2Ar
1
2
Figure 1. ’Flipped’ 5-HT6 ligands.
Further modification of the core heterocycle led to the identifi-
cation of 5-HT6 ligands exemplified by 3 (Fig. 2).5 Here, substitut-
ing a pyrrolo[2,3-b]pyridine for an indole afforded ligands which
had high affinity for the 5-HT6 receptor, and showed an interesting
variation in their functional efficacy. Depending on the substitu-
ents, these compounds behaved as either potent agonists or antag-
onists in a cyclase functional assay. These promising results led us
NR1R2
NR1R2
N
N
N
X
Y
Z
SO2Ar
SO2Ar
3
4
5
6
X = N; Y, Z = CR
X, Z = CR;Y = N
X, Y = CR; Z = N
* Corresponding author.
E-mail address: bernotr@wyeth.com (R.C. Bernotas).
Figure 2. Regioisomeric 1-(2-aminoethyl)-3-arylsulfonyl-pyrrolopyridines.
0960-894X/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2009.10.067

6936
R. C. Bernotas et al. / Bioorg. Med. Chem. Lett. 19 (2009) 6935–6938
this Letter, we describe the preparation and biological activity of
representative examples of these series.
NO2
a, b
X
c, d
N
N
SO2Ph
To simplify SAR comparisons, we chose to initially target only
compounds with 2-(dimethylamino)ethyl side chains. We knew
from our previous work5 that this side chain was easy to install
and generally provided high affinity ligands. This group also did
not seem to interfere with agonist activity determinations in the
5-HT6 cyclase functional assay. Because direct alkylation of 3-aryl-
sulfonyl-1H-pyrrolopyridines should provide compounds 4–6,
these core heterocycles became our penultimate targets. Several
different routes were used to prepare the target compounds and
are described here.
O
O
e
12
13 X = NO2 (74%)
14 X = NH2 (50%)
NMe2
H
N
N
N
N
SO2Ph
15 (57%, 2 steps)
SO2Ph
5 (35%)
The most versatile route to 3-arylsulfonyl-1H-pyrrolopyridines
relied heavily on the vicarious nucleophilic substitution (VNS) ap-
proach developed by Makosza.6 To prepare 4, we started with 2-
chloro-5-nitropyridine (7a) which when reacted with PhSO2CH2Cl7
in the presence of base provided a mixture of separable regioisom-
ers 8 and 9a, favoring the undesired 4-substitution product 9a
(Scheme 1).8 Nonselective nitro reduction using prolonged hydro-
genation of 8 gave aniline 10a in which the 2-chloro substituent
was cleaved from the pyridine ring.9 An alternative reduction uti-
lizing tin metal in acidic medium provided chloroaniline 10b.
Heating aniline 10a with excess triethylorthoformate and p-TsOH
in 1,2-dichloroethane gave an iminoether, which was treated with
a slight excess of 1.0 M KOtBu in THF to afford 11a. This one-pot
approach to ring formation generally provided product in good
yields. Alkylation with 2-(dimethylamino)ethyl chloride hydro-
chloride provided unsubstituted target 4a. Application of the same
sequence to 10b provided additionally functionalized 4b.
The regioisomeric pyrrolo[3,2-c]pyridine (15) was prepared by
an analogous VNS route. Reaction of commercial 12 with
PhSO2CH2Cl in DMSO using KOH as base provided 13 (Scheme 2).
The substitution product was reduced to aniline 14 on prolonged
hydrogenation using ammonium formate as the hydrogen source.
Cyclization to form 15 and subsequent alkylation completed the
sequence to derivative 5.
Scheme 2. Reagents and conditions: (a) PhSO2CH2Cl, DMSO, KOH, 0 °C, 45 min; (b)
10% palladium on carbon, NH4CO2H (7 equiv), MeOH, 50 °C to reflux, 54 h; (c)
HC(OEt)3 (5 equiv), p-tolunesulfonic acid monohydrate (0.1 equiv), DCE, reflux, 7 h;
(d) 1.0 M KOtBu in THF (1.3–1.5 equiv), THF, rt, 2 h; (e) Me2N(CH2)2ClÁHCl, NaH,
DMF, rt, 24 h.
H
NO2
Cl
NO2
CN
N
a, b
c, d, e
N
N
N
X
R
t
16
17 R = CO2 Bu
19 X = H (68%)
20 X = I (98%)
21 X = 3-FPhS (59%)
18 R = H (73%, 2 steps)
NMe2
H
N
g
N
f
N
N
SO2Ar
SO2Ar
22a Ar = 3-FPh (75%)
6b Ar = 3-FPh (73%)
Scheme 3. Reagents and conditions: (a) NCCH2CO2tBu, K2CO3, THF, reflux, 22 h; (b)
p-TsOH hydrate (0.1 equiv), toluene, reflux, 2 h; (c) 10% Pd on carbon, AcOH, EtOH,
hydrogen (55 psi), rt, 24 h; (d) I2, KI, aq EtOH, rt, 4 h; (e) 3-FPhSH, Pd(PPh3)4,
NaOtBu, EtOH, reflux, 17 h; (f) OXONETM
Me2N(CH2)2ClÁHCl, NaH, DMF, rt, 24 h.
, aq NaHCO3, acetone, rt, 3 h; (g)
3-Arylsulfonyl-pyrrolo[3,2-b]pyridines 22wereproduced bytwo
different routes. The first began with the synthesis of pyrrolo[3,2-
b]pyridine (19) from 2-chloro-3-nitropyridine 16 (Scheme 3). Katz
and Voyle described the introduction of tert-butyl cyanoacetate un-
der basic conditions to give 17 followed by hydrolysis and decarbox-
ylation to afford 18.10 Hydrogenation of 18 provided 19 for
subsequent transformations. Direct iodination gave 3-iodopyrrol-
o[3,2-b]pyridine (20) which was converted to 21 by a palladium-
mediated reaction using 3-fluorothiophenol. Oxidation11 of 21 gave
sulfone 22a, which was in turn alkylated to final product 6b.
Alternatively, we utilized a VNS route to pyrrolo[3,2-b]pyridines
22, allowing further substitution on the pyridyl ring (Scheme 4).
Employing 7a or 7b as starting materials, VNS reaction with chlo-
romethylarylsulfones provided 9a–e. These sulfones were reduced
to 3-aminopyridines 23a–f and cyclized to pyrrolo[3,2-b]pyridines
22b–g in a manner analogous to the previous syntheses. Alkylation
gave the desired derivatives (6a, 6c–g). The VNS approach utilized
here allowed for variations in the arylsulfonyl based on the chlo-
romethylarylsulfone employed. The chloromethylarylsulfones
were conveniently prepared in one-pot from the corresponding
arylsulfonyl chloride, as described previously.7
SO2Ph
NO2
a
NO2
SO2Ph
NO2
N
N
N
+
Cl
Cl
Cl
7a
8 (23%)
9a (50%)
NH2
SO2Ph
b or c
d, e
N
R1
10a R1 = H (39%)
10b R1 = Cl (63%)
NMe2
H
f
N
N
N
N
R1
R1
SO2Ph
SO2Ph
4a R1 = H (60%)
4b R1 = Cl (79%)
Preparation of primary amines 6 (R1, R2 = H) was accomplished
by a three-step sequence, which used a nitrile as the amine precur-
sor (Scheme 5).5 Alkylation of 19 with bromoacetonitrile instead of
2-(dimethylamino)ethyl chloride provided 24, which was sub-
jected to arylsulfonylation in the presence of silver triflate to pro-
vide 25.5 Subsequent reduction of the nitrile with borane gave
targeted primary amines 6h–k.
11a R1 = H (68%)
11b R1 = Cl (95%)
Scheme 1. Reagents and conditions: (a) PhSO2CH2Cl, THF, 1 M KOtBu in THF,
À65 °C to 0 °C over 1.5 h, then AcOH; (b) Sn (4.4 equiv), 6 M aq HCl, MeOH, 45 °C,
4–6 h; (c) 10% palladium on carbon, hydrogen (55 psi), NaOAc, MeOH, 3 d; (d)
HC(OEt)3 (2–5 equiv), p-tolunesulfonic acid monohydrate (0.1 equiv), DCE, reflux,
7 h; (e) 1.0 M KOtBu in THF (1.3–1.5 equiv), THF, rt, 5–30 min; (f)
Me2N(CH2)2ClÁHCl, (1.1 equiv), NaH (2.0 equiv), DMF (11a: 80 °C, overnight; 11b:
rt, 22 h, then 55 °C, 4 h).
Final compounds were tested for 5-HT6 affinity in a radioligand
binding assay12 using human-cloned 5-HT6 receptors (Table 1).

R. C. Bernotas et al. / Bioorg. Med. Chem. Lett. 19 (2009) 6935–6938
6937
NO2
NH2
NO2
SO2Ar
a
CN
X
N
R1
N
N
R1
N
b
c
N
7a R1 = Cl
9a R1 = Cl, Ar = Ph
N
N
N
7b R1 = OMe
9b R1 = OMe, Ar = Ph
SO2Ar
SO2Ar
9c R1 = OMe, Ar = 3-FPh
9d R1 = OMe, Ar = 4-BrPh
9e R1 = OMe, Ar = 1-naphthyl
19 X = H
24 X = CH2CN
25a Ar = 3-FPh
25b Ar = 3-ClPh
25c Ar = 3-MePh
6h-k
a
25d Ar = 6-Cl-imidazo[2,1-b][1,3]thiazo-5-yl
NH2
d, e
b or c
Scheme 5. Reagents and conditions: (a) NaH, BrCH2CN, DMF, rt, 16 h; (b) ArSO2Cl,
AgOTf, PhNO2, 100 °C, 3–5 h (28–52%); (c) BH3 (1.0 equiv), THF, rt, 18–24 h, then
0 °C, 1 M aqueous HCl (51–71%).
SO2Ar
N
R1
23a R1 = H, Ar = Ph
23b R1 = Cl, Ar = Ph
Both 3a and its 3-fluoro analog 3b had good to excellent affinity for
the target receptor with the 3-fluoro group increasing binding al-
most fivefold. Moving the nitrogen of pyridyl ring to the adjacent
position on the ring provided derivatives 4a and 4b. Compound
4b had little affinity for the target receptor. Similarly, shifting the
nitrogen to the next position to afford 5 provided a compound with
weak affinity for the 5-HT6 receptor. It is plausible that differences
in the basicity of 4b and 5, relative to 3, were responsible for the
reduced affinity.
The first example (6a) of the final regioisomers, arylsulfonyl-1H-
pyrrolo[3,2-b]pyridines 6, had modest affinity for the receptor but
still had nearly 10-fold weaker binding compared to the
comparably unsubstituted 3a of the lead series. Encouragingly,
introduction of a 3-fluoro group on the aryl ring modestly increased
affinity, though the magnitude was less than the increase in affinity
going from 3a to 3b. Similarly, a chloro substituent on the pyridyl
ring improved affinity somewhat (compare 6a to 6c) and switching
from a chloro substituent (6c) to a methoxy (6d) further improved
affinity. Combining fluoro substitution on the arylsulfonyl ring with
methoxy substitution on the pyridyl ring further increased affinity
(6e) of this series. Replacement of the 3-fluorophenyl with 4-bromo-
phenyl (6f) and then with 1-naphthyl (6g) continued the improve-
23c R1 = OMe, Ar = Ph
23d R1 = OMe, Ar = 3-FPh
23e R1 = OMe, Ar = 4-BrPh
23f R1 = OMe, Ar = 1-naphthyl
NMe2
H
f
N
N
R1
N
R1
N
SO2Ar
SO2Ar
22b R1 = H, Ar = Ph
6a, c-g
22c R1 = Cl, Ar = Ph
22d R1 = OMe, Ar = Ph
22e R1 = OMe, Ar = 3-FPh
22f R1 = OMe, Ar = 4-BrPh
22g R1 = OMe, Ar = 1-naphthyl
Scheme 4. Reagents and conditions: (a) ArSO2CH2Cl, THF, KOtBu, À65 °C to À20 °C
over 1 h, then AcOH quench; (b) 10% Pd on carbon, H2 (55 psi), NaOAc, MeOH, rt, 3 d
(59%); (c) Sn (4.4 equiv), 6 M aq HCl, MeOH, 45 °C, 4–6 h; (d) HC(OEt)3 (2–5 equiv),
p-tolunesulfonic acid monohydrate (0.1 equiv), ClCH2CH2Cl, reflux, 6–24 h; (e)
1.0 M KOtBu in THF (1.3–1.5 equiv), THF, rt, 0.5–2 h; (f) Me2N(CH2)2ClÁHCl, NaH,
DMF, rt, 18–24 h.
Table 1
5-HT6 Binding and adenylyl cyclase activity of 3, 4, 5 and 6a
NR1R2
W
X
N
Y
Z
SO2Ar
Compd
W
X
Y
Z
R1, R2
Ar
5-HT6 Ki (nM)
cAMP Assay for 5-HT6
EC50 or IC50 (nM) Emax or Imax (%)
3a
3b
4a
4b
5
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
N
N
CH
CH
N
CH
CH
CH
CCl
N
CH
CH
CCl
COMe
COMe
COMe
COMe
CH
CH
CH
CH
CH
CH
CH
CH
CH
N
N
N
N
N
N
N
N
N
N
N
Me, Me
Me, Me
Me, Me
Me, Me
Me, Me
Me, Me
Me, Me
Me, Me
Me, Me
Me, Me
Me, Me
Me, Me
H, H
Ph
3-FPh
Ph
Ph
Ph
Ph
3-FPh
Ph
23 ( 2)
4.9 ( 0.3)
No tested
55% @ 1
39% @ 1
368 ( 23)
200 ( 15)
214 ( 20)
56 ( 5.6)
11.3 ( 0.9)
3.9 ( 0.3)
1.7 ( 0.2)
76 ( 1)
35 ( 8)
46 ( 9)
25 ( 0.1) (ag)
7.3 ( 1.6) (ag)
—
—
—
—
—
—
94 (ag)
100 (ag)
—
—
—
—
—
—
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
N
l
l
M
M
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
Ph
—
—
3-FPh
4-BrPh
1-Naphthyl
3-FPh
3-ClPh
3-MePh
41 ( 34) (ant)
385 ( 35) (ant)
295 ( 46) (ant)
823 ( 34) (ag)
197 ( 22) (ag)
—
91 (ant)
100 (ant)
100 (ant)
51 (ag)
56 (ag)
—
H, H
H, H
H, H
6-Cl-imidazo[2,1-b][1,3]thiazo-5-yl
42 ( 3)
—
—
a
5-HT6 receptors were human clones stably expressed in Hela cells using [3H]LSD as the radioligand. EC50 and Emax values for agonists in the adenylyl cyclase assay are
indicated by ‘ag’ while for antagonists, IC50 and Imax values are indicated by ‘ant’.

6938
R. C. Bernotas et al. / Bioorg. Med. Chem. Lett. 19 (2009) 6935–6938
M. D.; Hodges, D. B.; Hogan, J. B.; Orie, A. F.; Corsa, J. A.; Barten, D. M.; Polson,
C.; Robertson, B. J.; Guss, V. L.; Gillman, K. W.; Starrett, J. E.; Gribkoff, V. K. J.
Pharmacol. Exp. Ther. 2003, 307, 682; (c) King, M. V.; Sleight, A. J.; Woolley, M.
L.; Topham, I. A.; Marsden, C. A.; Fone, K. C. F. Neuropharmacology 2004, 47, 195;
(d) Russell, M. G. N.; Dias, R. Curr. Top. Med. Chem. 2002, 2, 643.
2. For reviews on 5-HT6 receptor ligands and their biological functions, see:
Glennon, R. A. J. Med. Chem. 2003, 46, 2795; Holenz, J.; Pauwels, P. J.; Diaz, J. L.;
Merce, R.; Codony, X.; Buschmann, H. Drug Discovery Today 2006, 11, 283; Liu,
K. G.; Robichaud, A. J. Drug Dev. Res. 2009, 70, 145.
3. (a) Tsai, Y.; Dukat, M.; Slassi, A.; MacLean, N.; Demchyshyn, L.; Savage, J. E.;
Roth, B. L.; Hufesein, S.; Lee, M.; Glennon, R. A. Bioorg. Med. Chem. Lett. 2000, 10,
2295; (b) Russell, M. G. N.; Baker, R. J.; Barden, L.; Beer, M. S.; Bristow, L.;
Broughton, H. B.; Knowles, M.; McAllister, G.; Patel, S.; Castro, J. L. J. Med. Chem.
2001, 44, 3881; (c) Cole, D. C.; Lennox, W. J.; Lombardi, S.; Ellingboe, J. W.;
Bernotas, R. C.; Tawa, G.; Mazandarani, H.; Smith, D. L.; Zhang, G.; Coupet, J.;
Schechter, L. E. J. Med. Chem. 2005, 48, 353.
4. Bernotas, R. C.; Lenicek, S.; Antane, S.; Zhang, G. M.; Smith, D.; Coupet, J.;
Harrison, B.; Schechter, L. E. Bioorg. Med. Chem. Lett. 2004, 14, 5499.
5. Bernotas, R. C.; Lenicek, S.; Antane, S.; Cole, D. C.; Harrison, B.; Robichaud, A.;
Zhang, G.-M.; Smith, D. L.; Platt, B.; Lin, Q.; Li, P.; Coupet, J.; Rosenzweig-Lipson,
S.; Beyer, C. E.; Schechter, L. E. Bioorg. Med. Chem. 2009, 17, 5153.
6. (a) Makosza, M.; Glinka, T.; Kinowski, A. Tetrahedron 1984, 40, 1863; (b)
Wojciechowski, K.; Makosza, M. Synthesis 1986, 651; (c) Wojciechowski, K.;
Makosza, M. Tetrahedron Lett. 1984, 25, 4793.
ment to provide compounds with respectable Ki values at 5-HT6
receptors (<10 nM). Compounds with a primary amine side chain
(6h–k) in place of the N,N-dimethylamine were also examined. A
modest increase in affinity was observed, comparing 6b to 6h, but
this effect was relatively weak compared to the effect of introducing
a methoxy group to the aryl ring. Incorporation of a 6-Cl-imi-
dazo[2,1-b][1,3]thiazo-5-yl-sulfonyl group, which had provided a
high affinity, potent 5-HT6 agonist in the 1-arylsulfonyl-tryptamine
series (1),12 did not improve 5-HT6 receptor affinity for 6k.
Several compounds (6e–i) with good 5-HT6 affinity were tested
in an adenylyl cyclase assay to determine the ligands’ ability to
modulate 5-HT6 function in vitro.12 We expected these com-
pounds, like regioisomeric analogs 3a–b, to function as agonists
in this assay. Instead, they proved to be only weak, full antagonists,
with the exception of the primary amines 6h and 6i, which pos-
sessed weak agonist function.
Three regioisomeric series of 1-(2-aminoethyl)-3-(arylsulfonyl)-
1H-pyrrolopyridines, based on the high affinity 1-(aminoethyl)-3-
(arylsulfonyl)-1H-pyrrolo[2,3-b]pyridines3, werepreparedusingfive
synthetic routes. Three approaches incorporated a key VNS reaction,
demonstrating the versatility of this approach. In contrast to pyrrol-
o[2,3-b]pyridines 3, pyrrolo[2,3-c]pyridine 4b and pyrrolo[3,2-c]pyr-
idine 5 had significantly weaker affinity for 5-HT6 receptors. More
promising were pyrrolo[3,2-b]pyridines 6, with optimized ligands
possessing excellent affinity for the target receptors (e.g., 6f and 6g
with 5-HT6 binding Ki = 3.9 nM and 1.7 nM, respectively). However,
these compounds were functionally weak agonists or antagonists as
demonstrated in the adenylyl cyclase assay.
7. Antane, S.; Bernotas, R.; McDevitt, R.; Yan, Y.; Li, Y. Synth. Commun. 2004, 34,
2443.
8. Makosza, M.; Chylinska, B.; Mudryk, B. Liebigs Ann. Chem. 1984, 8.
9. New compounds provided satisfactory 1H NMR (300 or 400 MHz) and MS data.
Final compounds (4a–b, 5, and 6a–k) were isolated as hydrochlorides and
generally provided satisfactory CHN analysis though often as partial hydrates
or solvates. Compounds 6h–k were analyzed by 1H NMR and MS. For additional
synthetic details, see: Bernotas, R. C.; Lenicek, S. E.; Antane, S. A. U.S. Patent
6,825,212.
10. Katz, R. B.; Voyle, M. Synthesis 1989, 314.
11. Webb, K. S. Tetrahedron Lett. 1994, 35, 3457.
12. Binding assays were performed using cloned human 5-HT6 receptors stably
transfected into HeLa cells using [3H]-LSD as the radioligand. For the adenylyl
cyclase assay, HeLa cells transfected with the human 5-HT6 receptor were
used. The% efficacy is relative to serotonin. For detailed assay conditions, see:
Cole, D. C.; Stock, J. R.; Lennox, W. J.; Bernotas, R. C.; Ellingboe, J. W.; Boikess, S.;
Coupet, J.; Smith, D. L.; Leung, L.; Zhang, G. M.; Feng, X. D.; Kelly, M. F.; Galante,
R.; Huang, P. Z.; Dawson, L. A.; Marquis, K.; Rosenzweig-Lipson, S.; Beyer, C. E.;
Schechter, L. J. Med. Chem. 2007, 50, 5535.
References and notes
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