Indole- and benzothiophene-based histamine H3 antagonists

Article abstract of DOI:10.1016/j.bmcl.2010.08.103

Previous research on histamine H₃ antagonists has led to the development of a pharmacophore model consisting of a central phenyl core flanked by two alkylamine groups. Recent investigation of the replacement of the central phenyl core with heteroaromatic fragments resulted in the preparation of novel 3,5-, 3,6- and 3,7-substituted indole and 3,5-substituted benzothiophene analogs that demonstrate good to excellent hH₃ affinities. Select analogs were profiled in a rat pharmacokinetic model.

Full text of DOI:10.1016/j.bmcl.2010.08.103

Bioorganic & Medicinal Chemistry Letters 20 (2010) 6226–6230
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Indole- and benzothiophene-based histamine H antagonists
3
Alejandro Santillan Jr., Kelly J. McClure, Brett D. Allison, Brian Lord, Jamin D. Boggs, Kirsten L. Morton,
Anita M. Everson, Diane Nepomuceno, Michael A. Letavic, Alice Lee-Dutra, Timothy W. Lovenberg,
⇑
Nicholas I. Carruthers, Cheryl A. Grice
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121-1126, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Previous research on histamine H3 antagonists has led to the development of a pharmacophore model
consisting of a central phenyl core flanked by two alkylamine groups. Recent investigation of the replace-
ment of the central phenyl core with heteroaromatic fragments resulted in the preparation of novel 3,5-,
Received 20 July 2010
Revised 19 August 2010
Accepted 20 August 2010
Available online 27 August 2010
3
,6- and 3,7-substituted indole and 3,5-substituted benzothiophene analogs that demonstrate good to
excellent hH affinities. Select analogs were profiled in a rat pharmacokinetic model.
Ó 2010 Elsevier Ltd. All rights reserved.
3
Keywords:
Histamine
Indole
Benzothiophene
Mannich reaction
SAR
The histamine H
central nervous system that controls the synthesis and release of
histamine. Histamine H antagonists have potential therapeutic
utility in the treatment of sleeping, eating, attention and memory
3
receptor is a presynaptic autoreceptor in the
intermediate 6. Subsequent hydrolysis gave the corresponding
potassium salt 7 which was coupled to the cyclic diamine to pro-
vide the target compound 8.
3
1
,2
disorders. The SAR of phenyl-based compounds related to 1, 2,
1
d,3–5
3
and 4
(Fig. 1) has been disclosed previously and has corre-
4,6
lated to a proposed pharmacophore consisting of a central core
flanked by two alkylamine groups (Fig. 2). Phenyl ring replacement
studies have shown that bicyclic ring systems are well tolerated
including indole, benzofuran,8 benzazepine9 and tetrahydro-iso-
quinoline ring systems. The work presented in this paper further
investigates the replacement of the central phenyl core (Fig. 1)
with heteroaromatic fragments, notably indole and benzothio-
phene ring systems. Such replacement was undertaken in an ef-
fort to better understand central core SAR within our H program.
O
N
O
O
N
N
N
7
1
0
1
; hH K = 0.6 nM
2; hH K = 2.1 nM
3
i
3
i
Cl
11
Cl
1
2
3
For the 3,4- and 3,5-substituted indoles, two synthetic routes
were utilized to enable ready diversification of both positions on
the aromatic indole core. The first route (Scheme 1) favors the var-
iation of the amide moiety late in the synthesis while the second
route (Scheme 2) permits the introduction of different amines at
the 3-position of the indole in the final step. Using Scheme 1, the
synthesis of 5-amido substituted indoles was initiated by using
the commercially available methyl carboxylate starting material
O
N
O
H
N
N
N
N
O
3; hH
K
i
= 23 nM
4; hH
K
i
= 0.8 nM
3
3
2
3
NR R
O
5. Initial Mannich reaction of the indole with the desired amine
N
in the presence of formaldehyde furnished the 3-amino methyl
Y
N
R1
Y = NH, S
⇑
Corresponding author. Tel.: +1 858 784 3054.
E-mail address: cgrice@its.jnj.com (C.A. Grice).
Figure 1. H
3
antagonists.13
0
960-894X/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2010.08.103

A. Santillan Jr. et al. / Bioorg. Med. Chem. Lett. 20 (2010) 6226–6230
6227
Alternatively, introduction of the 3-aminomethyl moiety late in
the synthetic process commenced with starting materials 5 and 9
as shown in Scheme 2. Hydrolysis (as appropriate) of the ester fol-
lowed by coupling of the acids with the cyclic diamine yielded
intermediates related to structure 11. Mannich reaction of these
resulting indoles led to the desired target compounds 12 and 13.
The synthesis of the 3,6-amido substituted indole analogs was
achieved using the routes shown in Schemes 3 and 4. In Scheme
c
d
lipophilic
linker
NR R
a
b
R R N
Figure 2. Pharmacophore model for H
3
antagonists.
3, initial coupling of the acid (step b) with the appropriate amine
furnished the desired 3-formyl indole intermediates 15. The intro-
duction of the aminomethyl at the 3-position was achieved under
reductive amination conditions to furnish the target analogs 16, 18,
and 19. Further reaction of compound 16 with methanesulfonyl
chloride led to the formation of 17. In Scheme 4, additional target
compounds were prepared using a modified route. Initial introduc-
tion of the 3-aminomethyl group using reductive amination condi-
tions as above yielded 20. Introduction of the methyl group under
standard conditions yielded 21. Subsequent hydrolysis and cou-
pling led to the target compounds 22–26.
The 3,7-substituted analogs were prepared using the routes de-
picted in Schemes 5 and 6. Variation of the 3-aminomethyl group
was facilitated by utilization of Scheme 5. Coupling of starting
material 27 with the desired amines to yield intermediates 28 fol-
lowed by Mannich reaction led to the desired compounds 29–31.
O
O
N
RO
a
MeO
b
N
H
N
H
5
: R = Me
6
O
N
O
N
c
K
O
N
N
N
N
H
H
7
8
Scheme 1. Reagents and conditions: (a) piperidine, CH
41%); (b) KOH, i-PrOH (quant.); (c) N-i-Pr-piperazine, EDCI, HOBt, DMF (15%).
2
O, dioxane:AcOH (1:1)
(
O
O
4
4
O
RO
N
5
5
b
O
N
N
N
H
N
H
a
MeO
MeO
1
1
N
H
N
R
9
: 4-position, R = Me
a
O
O
1
0: 4-position, R = H
:5-position, R = H
2
0: R = H
c
14
b
5
21: R = Me
c, d
O
O
5
N
4
N
N
O
N
H
N
n
22: R = H, n = 1, X = N-i-Pr
X
23: R = H, n = 1, X = N-cyc-Pr
24: R = H, n = 1, X = N-cyc-Bu
25: R = H, n = 2, X = N-i-Pr
26: R = Me, n = 1, X = N-i-Pr
1
1
2: 4-position
3: 5-position
N
N
R
O
2
Scheme 2. Reagents and conditions: (a) LiOH, THF/H O (quant.); (b) N-i-Pr-
piperazine, EDCI, HOBt, K
2
CO
3
, DMF (61–62%); (c) morpholine, CH
2
O, dioxane:AcOH
3
Scheme 4. Reagents and conditions: (a) morpholine, NaBH(OAc) , dichloroethane
(
4:1) (8–21%).
(89%); (b) MeI, NaH, DMF, 0 °C to rt (92%); (c) KOH, i-PrOH; (d) N-i-Pr-piperazine, N-
cyc-Pr-piperazine, N-cyc-Bu-piperazine, or N-i-Pr-homopiperazine, EDCI, HOBt,
DMF, 60 °C or rt [Na
2
CO
3
was added to prepare 22–24] (27–54% over two steps).
O
O
a, b
X
MeO
O
N
N
H
N
H
a
N
H
N
H
O
HO
O
N
O
14
15: X = CH
2
, N-i-Pr, or O
X
c
2
7
28: X = CH2 or N-i-Pr
b
Y
N
1
6: X = N-i-Pr, Y= CH , R = H
Y
2
d
N
X
N
17: X = N-i-Pr, Y = CH , R = SO Me
18: X = CH , Y = N-i-Pr, R = H
19: X = O, Y = N-cyc-Bu, R = H
2
2
N
R
2
2
3
3
9: X = N-i-Pr, Y = O
0: X = N-i-Pr, Y = CH2
O
N
H
1: X = CH , Y = N-cyc-Bu
2
Scheme 3. Reagents and conditions: (a) LiOH, THF/H
2
O (quant.); (b) N-i-Pr-
N
O
piperazine or piperidine, EDCI, HOBt, DMF (36–43%); (c) N-i-Pr-piperazine, N-cyc-
Bu-piperazine, or piperidine, NaBH(OAc) , dichloroethane or CH Cl (65% quant.);
d) (i) NaH, DMF, 0 °C; (ii) MeSO Cl (23%). For compound 19: (b) morpholine,
N, DMF (37%); (c) MP-BH(OAc) [solid-supported reagent, Biotage],
X
3
2
2
(
2
Scheme 5. Reagents and conditions: (a) N-i-Pr-piperazine or piperidine, EDCI,
HOBt, DMF, 60 °C or rt (62–82%); (b) N-i-Pr-piperazine, N-cyc-Bu-piperazine, or
piperidine, CH O, dioxane:AcOH (1:1 or 4:1) (29–54%).
2
PyBOP, HOAt, Et
DMF (30%).
3
3

6
228
A. Santillan Jr. et al. / Bioorg. Med. Chem. Lett. 20 (2010) 6226–6230
O
O
Table 2
SAR of 3,6-substituted indole analogs
a
N
H
N
H
Y
N
HO
O
N
O
X
N
BocN
b
N
n
R
O
3
2
33
a
b
Compds
X
Y
R
n
hH
3
K
i
(nM)
3 2
hH pA
1
1
18
19
22
23
2
2
26
6
7
N-i-Pr
N-i-Pr
CH2
CH
CH
N-i-Pr
2
2
H
SO
H
H
H
H
H
H
1
1
1
1
1
1
1
2
1
2.8 ± 0.4
1.9 ± 1.8
88 ± 31
9.3c
8.5
CH
2 3
Y
d
N
—
—
3
3
4: R = Boc, Y = CH2
5: R = N-cyc-Bu, Y = CH2
e
d
c, d
d
O
N-cyc-Bu
43
N-i-Pr
N-cyc-Pr
N-cyc-Bu
N-i-Pr
N-i-Pr
O
O
O
O
O
2.1 ± 0.6
2.0 ± 0.2
1.4 ± 0.2
0.9 ± 0.2
15 ± 10
9.6
9.3
9.8
9.5
8.2
N
H
36: R = Boc, Y = O
37: R = H, Y = O
38: R = N-cyc-Bu, Y = O
4
5
c
N
O
RN
CH3
a
b
c
See Table 1 for details.
hH pA values are a result of a single point experiment unless otherwise noted.
Result of two single point experiments.
Samples were not tested.
Scheme 6. Reagents and conditions: (a) N-Boc-piperazine, EDCI, HOBt, DMF (34%);
b) morpholine or piperidine, NaBH(OAc) , CH Cl (79%); (c) (i) TFA, CH Cl ; (ii)
Dowex 550A OH anion-exchange resin, MeOH (94%-quant. over two steps); (d)
cyclobutanone, NaBH(OAc) , CH Cl (72%-quant.).
(
3
2
2
2
2
3
2
d
e
3
2
2
i
K value represents one determination.
In Scheme 6, treatment of 32 with N-Boc-piperazine under stan-
dard coupling conditions resulted in the formation of intermediate
3. Further reaction under reductive amination conditions allowed
access to 34 and 36. Removal of the Boc group of 36 gave the inter-
mediate 37, which could be further reacted to yield 38. Compound
observed (compounds 16 vs 18 and compounds 19 vs 24). The data
also indicates that substitution on the indole nitrogen with small
groups such as methyl and methylsulfonyl is well tolerated (com-
pounds 26 and 17). Several of the analogs in Table 2 were evalu-
ated to assess functional activity and were found to be potent
3
3
5 was prepared similarly from 34.
1
4
3 2
antagonists (hH pA > 8.0).
Analysis of the positional isomers within the indole series with
) binding affinity data14 as illustrated in
Referring back to Table 1, the 3,7-substituted indole analogs
maintained reasonable potency. Additional analogs were prepared
to better understand the SAR. Selected examples and the corre-
respect to human H (hH
3 3
Table 1 shows a preference for the 3,6-substitution pattern. This
trend is similar when the 3-amino moiety is morpholine (com-
pounds 12, 13, 22, and 29) or piperidine (compounds 8, 16, and
3
sponding hH affinities are summarized in Table 3. It appears that
the N-cyclobutyl is favored over the N-isopropyl substitution on
the distal nitrogen of the amide moiety (compounds 35 and 30).
Additionally, removal of the alkyl group at this site leads to a sub-
stantial loss in hH activity (37). Finally, similar to the 3,6-isomers,
3
removing the distal basic nitrogen on the amide with subsequent
incorporation as part of the 3-aminomethyl moiety leads to a de-
3
0). Clearly, the 3,4-substitution pattern is the least preferred with
compound 12 exhibiting little hH M). This data does
3
activity (ꢀ5
l
indicate that the indole moiety is an acceptable phenyl core
replacement.
3
The hH binding affinity data of additional 3,6-substituted com-
pounds (Table 2) provides greater SAR insight into the types of sub-
stitution on the indole that can maintain or adversely affect
activity. Substitutions were made on the distal nitrogen of the
amide and the amine at the 3-position (X and Y, Table 2). As seen
by the data in Table 2, most of these modifications are well toler-
ated. The 3-methylpiperidinyl and 3-methylmorpholinyl substi-
tuted indoles (16–17 and 22–26, respectively) lead to compounds
3
crease in hH activity (compare 29, 30, 35, and 38 vs 31).
Lastly, benzothiophene was explored as a phenyl ring replace-
ment, but investigations were limited to the 3,5-substituted ben-
zothiophenes due to the availability of starting material. The
preparation of these analogs is summarized in Scheme 7. Initial
reduction of 5-bromo-benzothiophene-3-carboxylic acid 39 was
accomplished through the formation of a mixed anhydride. Amino
3
with excellent hH affinities regardless of the substitution on the
1
5
carbonylation under microwave heating conditions provided the
key amide intermediate 41. Oxidation followed by reductive ami-
nation with piperidine furnished the target compounds 43–44.
7
-amidopiperazine. Interestingly, if the piperidine and piperazine
moieties are switched, a trend toward decreased hH
3
affinity is
Table 1
Effect of indole substitution on hH
3
activitya
Table 3
SAR of 3,7-substituted indole analogs
Y
N
4
Y
N
O
5
N
6
7
N
H
N
N
H
a
N
O
Compds
Substitution
Y
hH
3
K
i
(nM)
X
1
2
8
3
6
2
0
9
4
5
5
6
6
7
7
O
CH
O
CH
O
CH
O
4900 ± 4490
88 ± 58
180 ± 31
2.8 ± 0.4
2.1 ± 0.6
27 ± 16
a
Compds
X
Y
3 i
hH K (nM)
2
2
2
1
1
2
3
2
29
30
35
38
37
N-i-Pr
N-i-Pr
N-cyc-Bu
N-cyc-Bu
NH
O
12 ± 13
27 ± 16
1.6 ± 0.3
4.9 ± 2.6
2130 ± 830
240 ± 100
CH
CH
O
2
2
12 ± 13
O
a
31
CH
2
N-cyc-Bu
3 i
hH K values are the mean of at least three determinations unless otherwise
stated.
a
See Table 1 for details.

A. Santillan Jr. et al. / Bioorg. Med. Chem. Lett. 20 (2010) 6226–6230
6229
O
OH
OH
O
OH
Br
Br
a
b
N
X
S
S
S
3
9
40
41
O
O
O
N
c
N
d
N
X
X
S
S
4
3: X = N-i-Pr
4
2
44: X = N-cyc-Bu
Scheme 7. Reagents and conditions: (a) (i) i-butyl chloroformate, Et
piperazine, Mo(CO) , DBU, Hermann’s catalyst, t-Bu PHBF
3
N, THF, 0 °C; (ii) NaBH
, THF, 125 °C, microwave (18–24%); (c) MnO
4
2
, THF:H O (1:1), 0 °C to rt (89% over two steps); (b) N-i-Pr-piperazine or N-cyc-Bu-
6
3
4
2 3 3 2 2
, CHCl , 70 °C (83–95%); (d) piperidine, NaBH(OAc) , CH Cl (53–59%).
The corresponding amido analogs were prepared as seen in
Scheme 8. Amide coupling of the acid 39 with piperidine provided
the desired amide intermediate 45. Amino carbonylation, with
slightly modified conditions from the aforementioned examples,
provided the desired amide analogs 46–47.
The hH binding affinity data for the 3,5-substituted benzothio-
3
phene analogs is summarized in Table 4. In agreement with the in-
dole analogs, the benzothiophene core is seen as a viable phenyl
O
N
R
N
N
N
H
O
2
hH
hH
t1/2 = 3.5 h
F = 100%
2: R = i-Pr
23: R = cyc-Pr
3
K
i
= 2.1 nM
pA = 9.6
hH
hH
3
K
i
= 2.0 nM
2
3
2
3
pA = 9.3
core replacement. The hH
is better (34- to 65-fold) than the corresponding 3-amide analogs
compounds 43–44 vs 46–47) emphasizing the need for a basic
3
affinity of the 3-aminomethyl analogs
t1/2 = 1.9 h
F = 38%
AUC = 3.9 µM*h (po, 10 mpk)
ss = 40 L/kg
CL = 160 mL/min/kg
AUC = 7.4 µM*h (po, 10 mpk)
ss = 8.4 L/kg
CL = 77mL/min/kg
(
V
V
amine at the 3-position and supporting the pharmacophore
hypothesis.
No cross-reactivity with the hERG channel was observed for se-
lect compounds in the indole and benzothiophene series using a
high-throughput astemizole-binding assay.
The encouraging in vitro potencies of the indole analogs
prompted further exploration of the in vivo properties of com-
pounds 22 and 23 in a rat pharmacokinetic model. The results of
these studies are summarized in Figure 3. As seen from the data,
Figure 3. Rat PK profile of compounds 22 and 23.
16
substitution on the piperazine amide can influence the PK profile.
These two indoles display a range of bioavailabilities (F = 38–
100%), volumes of distribution (Vss = 8.4–40 L/kg) and clearance
values (CL = 77–160 mL/min/kg). Possible phospholipidosis due to
these compounds was not examined at this time.
In conclusion, our early efforts toward replacing the phenyl core
with 6,5-bicyclic aromatic ring systems, represented by indole and
benzothiophene, indicated that such changes were well tolerated.
These analogs were efficiently generated and exhibited good to
O
O
OH
N
Br
Br
a
3
excellent hH affinities. Moreover, the indole-based analogs
S
S
showed promising rat PK properties and are suitable for further
optimization. Such additional work will be necessary to better
compare and contrast compounds with monocyclic versus bicyclic
heteroaromatic cores.
3
9
45
O
O
N
b
N
X
References and notes
S
4
6: X = N-i-Pr
7: X = N-cyc-Bu
1.
(a) Gemkow, M. J.; Davenport, A. J.; Harich, S.; Ellenbroek, B. A.; Cesura, A.;
Hallett, D. Drug Discov. Today. 2009, 14, 509; (b) Sander, K.; Kottke, T.; Stark, H.
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Carruthers, N. I. Prog. Med. Chem. 2006, 44, 181; (e) Arrang, J. M.; Garbarg, M.;
Schwartz, J. C. Neuroscience 1987, 23, 149.
4
Scheme 8. Reagents and conditions: (a) piperidine, EDCI, HOBt, DMF (98%); (b) N-i-
Pr-piperazine or N-cyc-Bu-piperazine, Mo(CO)
30 °C, microwave (34–41%).
6
, Na
2
CO
3
2
, Hermann’s catalyst, H O,
1
2
3
.
.
Arrang, J. M.; Garbarg, M.; Schwartz, J. C. Nature (London, U.K.) 1983, 302, 832.
Ly, K. S.; Letavic, M. A.; Keith, J. M.; Miller, J. M.; Stocking, E. M.; Barbier, A. J.;
Bonaventure, P.; Lord, B.; Jiang, X.; Boggs, J. D.; Dvorak, L.; Miller, K. L.;
Nepomuceno, D.; Wilson, S. J.; Carruthers, N. I. Bioorg. Med. Chem. Lett. 2008, 18,
Table 4
SAR of 3,5-substituted benzothiophene analogs
39.
Y
4.
Apodaca, R.; Dvorak, C. A.; Xiao, W.; Boggs, J. D.; Wilson, S. J.; Lovenberg, T. W.;
Carruthers, N. I. J. Med. Chem. 2003, 46, 3938.
O
N
N
X
5. Dvorak, C. A.; Apodaca, R.; Barbier, A. J.; Berridge, C. W.; Wilson, S. J.; Boggs, J.
D.; Xiao, W.; Lovenberg, T. W.; Carruthers, N. I. J. Med. Chem. 2005, 48, 2229.
3
6. For more information on the evolution of the H R pharmacophore, see:
S
a
Celainire, S.; Wijtmans, M.; Talaga, P.; Leurs, R.; de Esch, I. J. P. Drug Discovery
Today 2005, 10, 1613.
Compds
X
Y
hH
3
K
i
(nM)
43
44
46
47
N-i-Pr
N-cyc-Bu
N-i-Pr
H
H
O
O
2
50 ± 8
15 ± 1
3280 ± 1890
520 ± 220
7. (a) Wager, T. T. U.S. 20060069087.; (b) Nettekovan, M.; Plancher, J.-M.; Richter,
H.; Roche, O.; Taylor, S. U.S. 20080188487.; (c) Pierson, P. D.; Fettes, A.; Freichel,
C.; Gatti-McArthur, S.; Hertel, C.; Huwyler, J.; Mohr, P.; Nakagawa, T.;
Nettekoven, M.; Plancher, J.-M.; Raab, S.; Richter, H.; Roche, O.; Sarmiento, R.
M. R.; Schmitt, M.; Schuler, F.; Takahashi, T.; Taylor, S.; Ullmer, C.; Wiegand, R.
J. Med. Chem. 2009, 52, 3855.
2
N-cyc-Bu
a
See Table 1 for details.

6
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8
.
(a) Cowart, M.; Faghih, R.; Curtis, M. P.; Gfesser, G. A.; Bennani, Y. L.; Black, L. A.;
11. Swanson, D. M.; Shah, C. R.; Lord, B.; Morton, K.; Dvorak, L. K.; Mazur, C.;
Apodaca, R.; Xiao, W.; Boggs, J. D.; Feinstein, M.; Wilson, S. J.; Barbier, A. J.;
Bonaventure, P.; Lovenberg, T. W.; Carruthers, N. I. Eur. J. Med. Chem. 2009, 44,
4413.
Pan, L.; Marsh, K. C.; Sullivan, J. P.; Esbenshade, T. A.; Fox, G. B.; Hancock, A. A. J.
Med. Chem. 2005, 48, 38; (b) Cowart, M.; Bennani, Y. L.; Faghih, R.; Gfesser, G.
A.; Black, L. A. WO 2002074758.
9
.
(a) Bailey, N.; Bamford, M.J.; Dean, D.K.; Pickering, P.L.; Wilson, D.M.;
Witherington, J. WO 2005058837.; (b) Bamford, M. J.; Heightman, T. D.;
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13. R , R and R3 are defined in Tables 1–4.
1
2
14. In vitro binding and functional data were obtained as described in: Letavic, M.
A.; Keith, J. M.; Ly, K. S.; Bonaventure, P.; Feinstein, M. A.; Lord, B.; Miller, K. L.;
Motley, T.; Nepomuceno, D.; Sutton, S. W.; Carruthers, N. I. Bioorg. Med. Chem.
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1
0. (a) Jesudason, C. D.; Beavers, L. S.; Cramer, J. W.; Dill, J.; Finly, D. R.; Lindsley, C.
W.; Stevens, F. C.; Gadski, R. A.; Oldham, S. W.; Pickard, R. T.; Siedem, C. S.;
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15. Letavic, M. A.; Ly, K. S. Tetrahedron Lett. 2007, 48, 2339.
16. These compounds were assessed for their ability to displace [ H]astemizole
3
2
006, 16, 3415; (b) Letavic, M. A.; Keith, J. M.; Jablonowski, J. A.; Stocking, E. M.;
Gomez, L. A.; Ly, K. S.; Miller, J. M.; Barbier, A. J.; Bonaventure, B.; Boggs, J. D.;
Wilson, S. J.; Miller, K. L.; Lord, B.; McAllister, H. M.; Tognarelli, D. J.; Wu, J.;
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