Constrained 7-fluorocarboxychromone-4-aminopiperidine based Melanin-concentrating hormone receptor 1 antagonists: The effects of chirality on substituted indan-1-ylamines

Article abstract of DOI:10.1016/j.bmcl.2006.11.061

The incorporation of constrained tertiary amines into an existing class of N-benzyl-4-aminopiperidinyl chromone-based MCHr1 antagonists led to the identification of a series of chiral racemic compounds that displayed good to excellent functional potency, binding affinity, and selectivity over the hERG channel. Further separation of two distinct chiral racemic compounds into their corresponding pairs of enantiomers revealed a considerable selectivity for MCHr1 for one configuration, in addition to a striking difference in oral exposure between one pair of enantiomers in diet-induced obese mice. Oral administration of the most potent compound in this class in the same animal model led to significant reduction of fat mass in a semi-chronic model for weight loss.

Full text of DOI:10.1016/j.bmcl.2006.11.061

Bioorganic & Medicinal Chemistry Letters 17 (2007) 884–889
Constrained 7-fluorocarboxychromone-4-aminopiperidine based
Melanin-concentrating hormone receptor 1 antagonists: The
effects of chirality on substituted indan-1-ylamines
Andrew J. Souers,a,* Rajesh R. Iyengar,a Andrew S. Judd,a David W. A. Beno,c Ju Gao,a
Gang Zhao,a Michael E. Brune,a James J. Napier,b Mathew M. Mulhern,a John K. Lynch,a
Jennifer C. Freeman,a Dariusz Wodka,a Chong J. Chen,b H. Doug Falls,a Sevan Brodjian,a
Brian D. Dayton,a Gilbert J. Diaz,c Eugene N. Bush,a Robin Shapiro,a Brian A. Droz,a
Victoria Knourek-Segel,a Lisa E. Hernandez,c Kennan C. Marsh,c Regina M. Reilly,a
Hing L. Sham,a Christine A. Collinsa and Philip R. Kyma
aMetabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
bProcess Chemistry, Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
cExploratory Pharmacokinetics, Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park,
IL 60064, USA
Received 20 October 2006; revised 14 November 2006; accepted 20 November 2006
Available online 1 December 2006
Abstract—The incorporation of constrained tertiary amines into an existing class of N-benzyl-4-aminopiperidinyl chromone-based
MCHr1 antagonists led to the identification of a series of chiral racemic compounds that displayed good to excellent functional
potency, binding affinity, and selectivity over the hERG channel. Further separation of two distinct chiral racemic compounds into
their corresponding pairs of enantiomers revealed a considerable selectivity for MCHr1 for one configuration, in addition to a strik-
ing difference in oral exposure between one pair of enantiomers in diet-induced obese mice. Oral administration of the most potent
compound in this class in the same animal model led to significant reduction of fat mass in a semi-chronic model for weight loss.
Ó 2006 Elsevier Ltd. All rights reserved.
Melanin-concentrating hormone1 (MCH) is a neuropep-
tide that plays a role in multiple physiologic processes,
including the regulation of feeding behavior and energy
balance. Multiple lines of evidence support the role of
MCH in the regulation of body weight in rodents,2 as
a single injection of MCH into the CNS stimulates food
intake,3 and chronic administration leads to increased
body weight.4 Additionally, transgenic mice over-
expressing the MCH gene are susceptible to insulin resis-
tance and obesity,5 while mice lacking the gene encoding
MCH are hypophagic, lean, and maintain elevated met-
abolic rates.6 Genetically altered mice that lack the gene
encoding the MCH receptor similarly maintain elevated
metabolic rates and thus remain lean despite hyperpha-
gia on a normal diet.7 Finally, multiple reports of small
molecule antagonists that confer a reduction of body
weight and/or food intake8 in rodents have been report-
ed recently, providing validation of MCHr1 blockade as
a possible pharmacotherapy for obesity.
Keywords: MCHr1; Obesity.
*
Figure 1. N-benzyl-4-aminopiperidine-based orally active MCHr1
antagonist 1.
Corresponding author. Tel.: +1 847 937 5312; fax: +1 847 938
1674; e-mail: andrew.souers@abbott.com
0960-894X/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2006.11.061

A. J. Souers et al. / Bioorg. Med. Chem. Lett. 17 (2007) 884–889
885
A previous report from these laboratories described the
7-fluorinated chromone analog 1, which showed a
promising combination of MCHr1 affinity, functional
potency, and hERG selectivity (Fig. 1) while demon-
strating oral efficacy in a chronic model for weight loss
in diet-induced obese mice (DIO).9 In an effort to further
capitalize on the encouraging properties of antagonist 1,
we explored the N-benzyl piperidine region of this mol-
ecule with the hopes of further improving the functional
potency and hERG selectivity.
diimidazole or bromoacetylbromide to afford the 5,6
and 6,6 substituted esters 4 and 6, respectively.
Saponification furnished the corresponding propionic
acid derivatives and set the stage for cyclization.
Unfortunately, these acids proved to be highly resis-
tant to Lewis acid-mediated cyclization, and multiple
attempts under several reaction conditions resulted
in little or no conversion. Harsh treatment with phos-
phoric acid-based reagents was also attempted, yet led
to decomposition with little conversion to the desired
compounds in all cases. Faced with this challenge, we
then attempted a melt procedure, employing solid
aluminum chloride in the absence of solvent at
140 °C for 2 h. Fortuitously, this protocol furnished
the desired ketones 5 and 7 in 70% and 78%, respec-
tively, as single regioisomers.
In the course of our search for more potent analogs, we
focused on the piperonyl region of the molecule, and
reasoned that incorporation of an appropriately placed
constraint could enhance functional antagonism by
locking the molecule into a highly active conformation,
an effect that could also improve the selectivity profile
against other receptors and ion channels. We were addi-
tionally interested in the incorporation of more polar
benzylic amine moieties in order to probe for greater
hERG selectivity. To this end, several novel constrained
compounds were designed, synthesized, and evaluated in
both in vitro and in vivo assays.
Finally, the acetamide 9 was prepared according to
Scheme 1. Nitration of 1-indanone afforded a regioiso-
meric mixture of 8a and 8b, which could be separated
via column chromatography. Intermediates 8a and 8b
were then individually subjected to iron-mediated nitro
reduction followed by acylation to afford the desired
ketones.
The indanone building blocks were generally prepared
from the corresponding propionic acid derivatives
(Scheme 1). These intermediates, in turn, were elabo-
rated from the appropriately functionalized benzalde-
hyde derivatives via a Horner–Wadsworth–Emmons
(HWE) homologation followed by a reduction/cycliza-
tion sequence. Both methylenedioxyphenyl indanone
regioisomers were prepared according to Nichols
et al.10 A similar sequence was utilized for the prep-
aration of the benzoxazine derivatives 5 and 7.
HWE homologation of 3-hydroxy-4-nitro-benzalde-
hyde followed by exhaustive reduction afforded the
intermediate 3, which was then reacted with carbonyl
The final compounds were prepared according to
Scheme 2. Briefly, Ti(iOPr)4-mediated enamine forma-
tion using 4-N-boc-aminopiperidine and the desired ke-
tone was followed by treatment with NaBH(OAc)3 to
afford the corresponding intermediate amines. Acid-
mediated deprotection and amide coupling with 7-fluo-
ro-4-oxo-4H-chromene-2-carboxylic acid9 furnished the
final products.
As demonstrated in Table 1, the chiral racemic analog
12 was a high-affinity ligand to MCHr1, and showed
functional antagonism that was nearly equal to that of
CO2Me
CO2Me
O
O
a, b
c
e, f
HO
O
HO
O
N
H
O
O
O
N
H
O2N
H2N
2
3
4
5
CO2Me
d
O
e, f
O
O
N
H
O
N
H
6
7
O
O
O
O
g
h, i
O2N
AcHN
+
NO2
8a
8b
9
Scheme 1. Reagents and conditions: (a) Triethyl phosphonoacetate, NaOtBu, DMF; (b) H2, Pd/C, EtOH/EtOAc; (c) CDI, THF, 50 °C; (d)
Bromoacetylbromide, K2CO3, rt then 50 °C; (e) LiOH, THF/H2O (3:1); (f) AlCl3, LiCl, 140 °C, 2 h; (g) HNO3; (h) Fe, NH4Cl, 80% EtOH, 60 °C; (i)
AcOH, EDCI.

886
A. J. Souers et al. / Bioorg. Med. Chem. Lett. 17 (2007) 884–889
Following separation11 of the enantiomers of 12, in vitro
R3
R2
analysis revealed striking receptor selectivity for one
configuration, as the binding affinity of (ꢀ)-12 was near-
ly 700-fold higher than that of enantiomer (+)-12. Addi-
tionally, the functional potency of the parent racemate
resided solely in the former compound, as the oppositely
configured (+)-12 showed no activity up to the assayed
concentration. A moderate selectivity over the hERG
channel was revealed as well. Fortunately, the more po-
tent enantiomer showed decreased hERG activity, and
showed an improved relative selectivity as compared
to the parent analog 1.
O
O
N
R1
R2
a, b, c
O
O
N
H
R1
F
R3
5: R1, R2 = -OC(O)NH-
7: R1, R2 = -OCH2C(O)NH-
9: R1 = -NHC(O)CH3
12-16
10: R1, R2 = -OCH2O-
11: R1, R2 = -OCH2O-
Scheme 2. Reagents and conditions: (a) Amine, Ti(iOPr)4, THF,
50 °C, 5 h, then NaBH(OAc)3; (c) CH2Cl2, 2 N HCl/ether; (d) EDCI,
HOBt, NMM, RCO2H, DMF.
These promising data encouraged the further explora-
tion of the constrained amine derivatives in the hopes
that analogs with further gains in potency and hERG
selectivity could be identified. Since the linearly fused
5,6,5-indan-1-ylamine system proved to be critical as
demonstrated by the remarkable differences in MCHr1
and hERG activity between 12 and 13, we designed
compounds that retained the conformation of the form-
er analog. Additionally, prior efforts had demonstrated
that enhanced polarity within the N-benzyl region of
1. The presence of the indane ring had the effect of
slightly increasing the hERG affinity, although the selec-
tivity for MCHr1 was still promising. In contrast, the
regioisomeric analog 13 showed a 20-fold decrease in
MCHr1 binding affinity relative to 1, and over 100-fold
decrease in functional antagonism. Interestingly, this
constitutional isomerism had a significant effect on the
hERG binding, as 13 showed a three- and fivefold in-
crease in hERG affinity relative to 12 and 1, respectively.
Table 1. SAR of indanone-based compoundsa
O
O
F
R
O
Ca2+ IC50 (lM)
hERG IC50 (lM)
b
c
d
Compound
R
MCHr1 IC50 (lM)
N
HN
1
0.004
0.025
15
O
O
O
O
HN
12
13
0.005
0.036
2.75
11.2
5.86
N
N
O
0.076
0.001
N
H
O
H
O
N
(ꢀ)-12e
(+)-12e
0.015
>10
9.31
7.87
O
N
N
H
N
O
O
0.760
1
a All compounds were >95% pure by HPLC and characterized by H NMR and HRMS. All values are mean values SEM (n = 3 unless specified
otherwise).
b Displacement of [125I]MCH from MCHr1 expressed in IMR-32 (I3.4.2) cells (MCH binding Kd = 0.66 0.25 nM, Bmax = 0.40 0.08 pmol/mg).
c Inhibition of MCH-mediated Ca2+ release in whole IMR-32 cells (MCH EC50 = 62.0 3.6 nM).
d Displacement of [3H]dofetilide from hERG/HEK membrane homogenates at 6 concentrations, 1/2 log apart, in duplicate using a 96-well plate
design. IC50 values calculated using Graphpad Prizm software.
e See Ref. 11 for details regarding the chiral separation.

A. J. Souers et al. / Bioorg. Med. Chem. Lett. 17 (2007) 884–889
887
the molecule was effective in decreasing the hERG affin-
ity.9 We consequently designed and synthesized the
5,6,5-constrained cyclic carbamate 14 (Scheme 1), in
addition to the homologated 5,6,6 analog 15 in order
to probe the chemical space in this region.
The enantiomeric sets of compounds were then evalu-
ated for single dose plasma and brain penetration in
DIO mice (Table 3). Both (+)-12 and (ꢀ)-12 showed
similar in vivo properties, characterized by high plas-
ma exposure, although (+)-12 showed a twofold in-
crease in brain exposure. Both enantiomers had
prolonged plasma and brain half-lives relative to par-
ent 1, despite the observation that brain exposure
was decreased. Surprisingly, (ꢀ)-16 showed a ten-fold
higher plasma AUC and Cmax relative to the less ac-
tive enantiomer (+)-16. However, the presence of the
amide functionality had a detrimental effect on the
brain penetration for both enantiomers. The more ac-
tive (ꢀ)-16 had no measurable drug levels in the brain,
while the brain concentration of (+)-16 was very low.
That no brain penetration was observed in the face of
considerable plasma exposure for both analogs is likely
the result of the increased polarity and hydrogen-bond
capacity of the amide functionality. Additionally, the
modest CNS penetration of the less active enantiomer
while the more extensively plasma-absorbed analog
(ꢀ)-16 had none indicates that active transport mech-
anisms could play a role. Interestingly, the presence of
the indan-1-ylamine constraint had the effect of sub-
stantially increasing the plasma exposure for all of
the analogs relative to the parent 1, with the exception
of (+)-16.
As demonstrated in Table 2, analogs 14 and 15 exhibited
a decrease in both MCHr1 affinity and functional poten-
cy relative to (ꢀ)-12, yet the hERG binding was de-
creased considerably. The presence of the carbamate
and amide functionalities in these analogs appeared to
be beneficial with respect to decreasing the affinity for
the hERG channel. Additionally, the presence of the
methylene unit in 15 conferred enhanced MCHr1 activ-
ity relative to 14, and we reasoned that excision of the
aryl ether oxygen could combine the desired properties
of both compounds. To this end, the indanone 8 was
prepared (Scheme 1) and functionalized accordingly to
afford the amide 16. Gratifyingly, in vitro analysis of
this compound revealed an excellent binding affinity to-
ward MCHr1, good functional potency, and decreased
hERG activity relative to 1. Encouraged by these prop-
erties, we separated the components of 1612 to furnish
the pure enantiomers (ꢀ)-16 and (+)-16. Similar to the
enantiomeric pair (ꢀ)-12 and (+)-12, chirality had a
remarkable effect, as the binding and functional activity
of 16 resided predominantly in one isomer {(ꢀ)-16}.
Table 2. In vitro parameters of analogsa
R
N
O
F
O
O
N
H
Ca2+ IC50 (lM)
hERG IC50 (lM)
b
c
d
Compound
R
MCHr1 IC50 (lM)
H
N
14
0.011
0.173
25.0
O
O
O
H
N
15
16
0.021
0.003
0.095
0.056
14.6
34.8
O
NHAc
NHAc
NHAc
(ꢀ)-16e
(+)-16e
0.004
2.57
0.026
>10
27.2
15.6
a See Table 1, footnote a.
b See Table 1, footnote b.
c See Table 1, footnote c.
d See Table 1, footnote d.
e See Ref. 12 for details regarding the chiral separation.

888
A. J. Souers et al. / Bioorg. Med. Chem. Lett. 17 (2007) 884–889
Table 3. Selected PK properties of indanone analogs (DIO mice, 10 mg/kg po)a
Compound
1
(ꢀ)-12
140
(+)-12
(ꢀ)-16
41.6
14.6
2.3
(+)-16
Plasma AUC(lg h/mL)b
Plasma Cmax (lg/mL)b
Plasma T1/2 (h)
9.29
1.78
2.5
113
15.5
3.6
3.76
1.41
1.3
15
4.5
Brain AUC (lg h/g)b
Brain Cmax (lg/g)b
Brain T1/2 (h)
12.7
4.37
2.4
4.85
0.686
5.7
8.26
1.43
4.1
0.00
0.00
NF
0.043
0.017
NF
a Compounds are dosed in DIO mice at 10 mg/kg, po in a vehicle containing 1% Tween 80 and water.
b The three mice with highest plasma and brain concentrations were averaged to provide the peak plasma and brain concentrations (Cmax
)
SEM,
respectively. The mean plasma or brain concentration data were submitted to multi-exponential curve fitting using WinNonlin. The area under the
mean concentration-time curve from 0 to t hours (time of the last measurable concentration) after dosing (AUC0–t) was calculated using the linear
trapezoidal rule for the concentration-time profile. The residual area was extrapolated to infinity, determined as the final measured mean con-
centration (Ct) divided by the terminal elimination rate constant (b), and was added to AUC0–t to produce the total area under the curve (AUC0–1).
NF, not found.
High Fat Vehicle
(-)-12 at 3 mg/kg
D-fenfloramine at 10 mg/kg
The introduction of polar functional groups into the in-
dan-1-ylamine portion of the molecule provided com-
pounds with similar MCHr1 activity and superior
hERG selectivity relative to 1, although the lack of acute
CNS penetration in the animal efficacy model obviated
the further assessment of these compounds. Conse-
quently, we focused on chiral non-racemic analog (ꢀ)-
12, which demonstrated the best combination of binding
and functional potency relative to any previously syn-
thesized compound within the N-benzyl-4-aminopiperi-
dine class of MCHr1 antagonists.13 Furthermore, in
receptor selectivity panels, (ꢀ)-12 showed weak affinity
(IC50 > 10 lM) for other peptide receptors that are
structurally related to MCHr1, including MCHr2,
somatostatin, and the opioid receptors, and over 100-
fold selectivity for all other GPCrs and ion channels
tested.14 While the brain/plasma ratio was decreased
compared to the non-cyclized 1, the enhanced cellular
potency of (ꢀ)-12 and its favorable CNS exposure and
half-life upon single dosing were deemed sufficient crite-
ria to predict efficacy in a semi-chronic model for weight
loss.
1
0
-1
-2
-3
-4
-5
-6
0
5
10
15
Days on Study
Figure 2. Effect of compound (ꢀ)-12 (3 mg/kg, po, bid in 1% Tween 80
in water) and D-fenfluramine (D-fen, 10mg/kg, po, qd) on the body
weight of DIO mice. Change is registered as the number of grams of
body weight difference for each measurement time point relative to day
zero. All values are mean values SEM for n = 12. **p < 0.05 for
comparisons against vehicle group.
To this end, a single oral dose of 3 mg/kg bid was
selected for (ꢀ)-12. For a two-week period, DIO mice
fed a high-fat diet ad libitum were administered this
compound, D-fenfluramine (10 mg/kg, qd) as a drug-
treated control, or vehicle. Food intake and body
weight were measured at days 1, 5, 7, 11, and 14 for
each group. In reproducible fashion, the D-fenflura-
mine treatment group was characterized by a rapid de-
crease in body weight (Fig. 2), secondary to a decrease
in food intake, followed by a characteristic rebound
that started on day 8 and continued throughout the
remainder of the study (final weight reduction and %
weight loss from day 0 were 4 g and 9%, respectively).8c
In contrast, treatment with compound (ꢀ)-12 induced
a gradual decrease in body weight that culminated in
a 7% weight reduction compared to vehicle controls
by the end of the study (3 g, p < 0.01). No significant
effect on food intake was observed at any point within
the study. Subsequent DEXA analysis revealed that the
loss of body mass was directly attributed to a selective
loss of fat mass, and that chronic treatment had no ef-
fect on lean mass (data not shown). Finally, Irwin
analysis revealed no overt behavioral abnormalities or
compound-induced effects on movement, coordination,
and muscle strength, indicating that no gross toxicity
was conferred by the administration of compound
(ꢀ)-12.
Blood samples collected at 1 and 17 h post-final-dose
determined the therapeutic (Cmax) plasma and brain
concentrations of (ꢀ)-12 to be 3680 and 530 ng/mL,
respectively (Table 4). The former value is less than
Table 4. Exposure levels of (ꢀ)-12 (3 mg/kg, bid, po) at 1 and 17 h
post-final dosea
Time (h)
Plasma (ng/mL)a
Brain (ng/g)a
1
17
3680
203
530
0.00
a Drug concentrations in plasma and in brain were determined either 1
or 17 h after the final dose. All values are mean values SEM
(n = 3).

A. J. Souers et al. / Bioorg. Med. Chem. Lett. 17 (2007) 884–889
889
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expected based upon the Cmax observed with the acute
dose of 10 mg/kg, and could reflect a gradual metabolic
induction. Interestingly, the brain Cmax was equivalent
to the measured concentration in the single dose exper-
iment, and because of the decreased plasma concentra-
tion, the brain/plasma ratio was enhanced 10-fold to
0.15 at the maximum concentration. After 17 h, the
compound was effectively cleared from the plasma and
brain, with the latter tissue containing negligible
amounts at this time point.
8. (a) Borowsky, B.; Durkin, M. M.; Ogozalek, K.;
Marzabadi, M. R.; DeLeon, J.; Lagu, B.; Heurich, R.;
Lichtblau, H.; Shaposhnik, Z.; Daniewska, I.; Black-
burn, T. P.; Branchek, T. A.; Gerald, C.; Vaysse, P. J.;
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Suzuki, N.; Nishimura, O.; Fujino, M. Eur. J. Pharma-
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Hernandez, L. E.; Marsh, K. C.; Sham, H. L.; Collins,
C. A.; Kym, P. R. J. Med. Chem. 2006, 49, 2339; (d)
Souers, A. J.; Gao, J.; Wodka, D.; Judd, A. S.;
Mulhern, M. M.; Napier, J. J.; Brune, M. E.; Bush,
E. N.; Brodjian, S. J.; Dayton, B. D.; Shapiro, R.;
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9. Lynch, J. K.; Freeman, J. C.; Judd, A. S.; Iyengar, R. R.;
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Brodjian, S.; Dayton, B. D.; Falls, H. D.; Ogiela, C.;
Reilly, R. M.; Campbell, T. J.; Polakowski, J. S.;
Hernandez, L.; Marsh, K. C.; Shapiro, R.; Knourek-
Segal, V.; Droz, B.; Bush, E.; Brune, M.; Preusser, L. C.;
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11. Chiralcell O. J., Hex/EtOH/MeOH (50/25/25), 0.8 mL/
min, UV 220 nM. Both (ꢀ)-12 and (+)-12 were purified to
enantiomeric purity within the limits of detection. The
elution times for (ꢀ)-12 and (+)-12, respectively, are 6.1
and 9.2 min.
In summary, incorporation of indan-1-ylamine-based
constraints into the N-benzyl portion of our previously
disclosed series of chromone-based MCHr1 antagonists
afforded novel chiral compounds with enhanced in vitro
and pharmacological profiles. Specifically, compound
(ꢀ)-12 demonstrated the most potent functional activity
of any compound within this class, good hERG
selectivity, and efficacy when dosed at 3 mg/kg bid in a
semi-chronic model for weight loss in DIO mice. Addi-
tionally, a remarkable effect of chirality on the in vitro
and pharmacokinetic properties of enantiomers (ꢀ)-16
and (+)-16 was manifested in significant differences in
receptor activity and oral exposure of the purified enan-
tiomers. It is quite possible that incorporation of this
type of constraint could have similar effects on other
classes of small molecules, and thus represents an addi-
tional strategy to modulate this in vivo parameter.
Acknowledgments
The authors thank Christopher Ogiela and Dennis Fry
for preparing the IMR-32 cells and aiding with the exe-
cution of the binding and functional assays, and Paul
Richardson and J. J. Jiang for MCH production.
References and notes
12. Chiralcell O. J., Hex/EtOH/MeOH (70/15/15), 0.8 mL/min,
UV 240 nM. Both (ꢀ)-16 and (+)-16 were purified to
enantiomeric purity within the limits of detection. The
elution times for (ꢀ)-16 and (+)-16, respectively, are
7.57 min and 5.43 min.
1. Saito, Y.; Nothacker, H.-P.; Civelli, O. Trends Endocrinol.
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2. Schwartz, M. W.; Woods, S. C.; Porte, D., Jr.; Selley, R.
J.; Baskin, D. G. Nature 2000, 404, 661.
13. See the following reference to 4-aminopiperidin- based
MCHR1 antagonists Kym, Philip R.; Iyengar, Rajesh;
Souers, Andrew J.; Lynch, John K.; Judd, Andrew S.;
Gao, Ju; Freeman, Jennifer; Mulhern, Mathew; Zhao,
Gang; Vasudevan, Anil; Wodka, Dariusz; Blackburn,
Christopher; Brown, Jim; Che, Jennifer Lee; Cullis,
Courtney; Lai, Su Jen; LaMarche, Matthew; Marsilje,
Tom; Roses, Jon; Sells, Todd; Geddes, Brad; Govek,
Elizabeth; Patane, Michael; Fry, Dennis; Dayton, Brian
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