
                                SEQUENCE LISTING

<110> Wyeth and Elbion Gmbh

<120> Pyrido[3,2-E]Pyrazines, Process For Preparing The Same, And Their Use
 As Inhibitors Of Phosphodiesterase 10

<130> 20743-0022WO1

<150> US 61/004,954      
<151> 2007-11-30  

<160> 14

<170> FastSEQ for Windows Version 4.0

<210> 1
<211> 26
<212> DNA
<213> Artificial Sequence

<220> 
<223> Primer

<400> 1
tgcatctaca gggttaccat ggagaa                                      26

<210> 2
<211> 29
<212> DNA
<213> Artificial Sequence

<220> 
<223> Primer

<400> 2
tatccctgca ggccttcagc agaggctct                                   29

<210> 3
<211> 28
<212> DNA
<213> Artificial Sequence

<220> 
<223> Primer

<400> 3
ttcacatgga tatgcgacgg taccttct                                    28

<210> 4
<211> 31
<212> DNA
<213> Artificial Sequence

<220> 
<223> Primer

<400> 4
ctgtgaagaa gaactatcgg cgggttcctt a                                31

<210> 5
<211> 967
<212> DNA
<213> Sus scrofa

<400> 5
tgcatctaca gggttaccat ggagaagctg tcctaccaca gcatttgtac cgcggaagag 60
tggcaaggcc tcatgcgctt caaccttccc gtccgtcttt gcaaggagat tgaattgttc 120
cacttcgaca ttggtccttt tgaaaacatg tggcctggaa tctttgtcta tatggttcat 180
cgcttctgtg ggacggcctg ctttgagctt gaaaagctgt gtcgttttat catgtctgtg 240
aagaagaact atcgtcgggt tccttaccac aactggaagc acgcggtcac ggtggcacac 300
tgcatgtacg ccatcctcca gaacagccac gggctcttca ccgacctcga gcgcaaagga 360
ctgctaatcg cgtgtctgtg ccacgacctg gaccacaggg gcttcagcaa cagctacctg 420
cagaaattcg accaccccct ggccgctctc tactccacgc ccaccatgga gcagcaccac 480
ttctcccaga ccgtgtccat cctccagttg gaagggcaca acatcttctc caccctgagc 540
tccagtgagt acgagcaggt gcttgagatc atccgcaaag ccatcattgc cacagacctc 600
gctttgtact ttggaaacag gaaacagttg gaggagatgt accagaccgg atcgctaaac 660
cttaataacc agtcacatag agaccgcgtc attggtttga tgatgactgc ctgtgatctc 720
tgttccgtga caaaactgtg gccagtaaca aaactgacgg caaatgatat atatgcggaa 780
ttctgggccg agggcgatga ggtgaagaag ctgggaatac agcctattcc catgatggac 840
agagacaaga aggacgaagt cccacaaggc cagctcggat tctacaacgc ggtagctatc 900
ccctgctaca ccaccctcac ccagatcttc ccgcccacag agcctcttct gaaggcctgc 960
agggata                                                           967

<210> 6
<211> 732
<212> DNA
<213> Guinea pig

<400> 6
ctgtgaagaa gaactatcgg cgggttcctt accacaactg gaagcatgca gtcacggtgg 60
cgcactgcat gtacgccata cttcaaaaca acaatggcct cttcacagac cttgagcgca 120
aaggcctgct aattgcctgt ctgtgccatg acctggacca caggggcttc agtaacagct 180
acctgcagaa attcgaccac cccctggctg cgttgtactc cacctccacc atggagcaac 240
accacttctc ccagacggtg ttcatcctcc agctggaagg acacaacatc ttctccaccc 300
tgagctccag cgagtacgag caggtgctgg agatcatccg caaagccatc atcgccactg 360
acctcgcact gtactttggg aacaggaagc agttggagga gatgtaccag acagggtcgc 420
tgaacctcaa taaccagtcc catcgagacc gcgtcatcgg cttgatgatg actgcctgcg 480
atctttgctc tgtgacgaaa ctatggccag ttacaaaatt gacagcaaat gatatatatg 540
cagagttctg ggctgagggg gatgagatga agaagttggg gatacagccc atccctatga 600
tggacagaga caagaaggat gaagtccctc aaggacagct tggattctac aatgctgtgg 660
ccatcccctg ctataccacc ctgacgcaga tcctcccacc cacagagcct ctgctgaagg 720
cctgcaggga ta                                                     732

<210> 7
<211> 266
<212> DNA
<213> Artificial Sequence

<220> 
<223> Synthetically generated oligonucleotide

<400> 7
tagagcctct gctgaaggcc tgcagggata acctcaatca gtgggagaag gtaattcgag 60
gggaagagac agcaatgtgg atttcaggcc cagcaactag caaaagcaca tcagggaagc 120
cgaccaggaa ggtcgatgac tgatcctgag gtgatgtctg cctagcaact gactcaacct 180
gcttctgtga cttcgttctt tttattttta tttttttaac ggggtgaaaa cctctctcag 240
aaggtaccgt cgcatatcca tgtgaa                                      266

<210> 8
<211> 993
<212> DNA
<213> Artificial Sequence

<220> 
<223> Consensus sequence

<400> 8
acccgagatg gcaaggcctc atgccttcaa ctccgcgttg cggaatgatt tccacttgac 60
attggtcctt tgaaacatgt ggcctggatc tttgtctaat gtcatcgttg tgggaccctg 120
ttttgacttg aaaatgtgct tttatcatgt ctgtgaagaa gaactatcgg cgggttcctt 180
accacaactg gaagcatgca gtcacggtgg cgcactgcat gtacgccata cttcaaaaca 240
acaatggcct cttcacagac cttgagcgca aaggcctgct aattgcctgt ctgtgccatg 300
acctggacca caggggcttc agtaacagct acctgcagaa attcgaccac cccctggctg 360
cgttgtactc cacctccacc atggagcaac accacttctc ccagacggtg tccatcctcc 420
agctggaagg acacaacatc ttctccaccc tgagctccag cgagtacgag caggtgctgg 480
agatcatccg caaagccatc atcgccactg acctcgcact gtactttggg aacaggaagc 540
agttggagga gatgtaccag acagggtcgc tgaacctcca caaccagtcc catcgagacc 600
gcgtcatcgg cttgatgatg actgcctgcg atctttgctc tgtgacgaaa ctatggccag 660
ttacaaaatt gacagcaaat gatatatatg cagagttctg ggctgagggg gatgagatga 720
agaagttggg gatacagccc atccctatga tggacagaga caagcgagat gaagtccctc 780
aaggacagct tggattctac aatgctgtgg ccatcccctg ctataccacc ctgacgcaga 840
tcctcccacc cacagagcct ctgctgaagg cctgcaggga taacctcaat cagtgggaga 900
aggtaattcg aggggaagag acagcaatgt ggatttcagg cccagcaact agcaaaagca 960
catcggaagc cgaccaggaa ggtcgatgac tga                              993

<210> 9
<211> 845
<212> DNA
<213> Guinea pig

<400> 9
ctgtgaagaa gaactatcgt cgggttcctt accacaactg gaagcacgcg gtcacggtgg 60
cacactgcat gtacgccatc ctccagaaca gccacgggct cttcaccgac ctcgagcgca 120
aaggactgct aatcgcgtgt ctgtgccacg acctggacca caggggcttc agcaacagct 180
acctgcagaa attcgaccac cccctggccg ctctctactc cacgcccacc atggagcagc 240
accacttctc ccagaccgtg tccatcctcc agttggaagg gcacaacatc ttctccaccc 300
tgagctccag tgagtacgag caggtgcttg agatcatccg caaagccatc attgccacag 360
acctcgcttt gtactttgga aacaggaaac agttggagga gatgtaccag accggatcgc 420
taaaccttaa taaccagtca catagagacc gcgtcattgg tttgatgatg actgcctgtg 480
atctctgttc cgtgacaaaa ctgtggccag taacaaaact gacggcaaat gatatatatg 540
cggaattctg ggccgagggc gatgaggtga agaagctggg aatacagcct attcccatga 600
tggacagaga caagaaggac gaagtcccac aaggccagct cggattctac aacgcggtag 660
ctatcccctg ctacaccacc ctcacccaga tcttcccgcc cacagagcct cttctgaagg 720
cctgcaggga taacctcaat cagtgggaga aggtaattcg aggggaagag acagcaatgt 780
ggatttcagg cccagcaact agcaaaagca catcagggaa gccgaccagg aaggtcgatg 840
actga                                                             845

<210> 10
<211> 1032
<212> DNA
<213> Rattus norvegicus

<400> 10
acctctgagg aatggcaagg cctcatgcac ttcaacttgc cagcacgcat ctgccgggac 60
atcgagctat tccactttga cattggtcct ttcgagaaca tgtggcctgg gatctttgtc 120
tacatgatcc atcggtcttg tgggacatcc tgttttgaac ttgaaaaatt gtgccgtttt 180
atcatgtctg tgaagaagaa ctataggcgg gttccttacc acaactggaa gcatgcagtc 240
acggtggcgc actgcatgta cgccatactt caaaacaaca atggcctctt cacagacctt 300
gagcgcaaag gcctgctaat tgcctgtctg tgccatgacc tggaccacag gggcttcagt 360
aacagctacc tgcagaaatt cgaccacccc ctggctgcgt tgtactccac ctccaccatg 420
gagcaacacc acttctccca gacggtgtcc atcctccagc tggaaggaca caacatcttc 480
tccaccctga gctccagcga gtacgagcag gtgctggaga tcatccgcaa agccatcatc 540
gccactgacc tcgcactgta ctttgggaac aggaagcagt tggaggagat gtaccagaca 600
gggtcgctga acctccacaa ccagtcccat cgagaccgcg tcatcggctt gatgatgact 660
gcctgcgatc tttgctctgt gacgaaacta tggccagtta caaaattgac agcaaatgat 720
atatatgcag agttctgggc tgagggggat gagatgaaga agttggggat acagcccatc 780
cctatgatgg acagagacaa gcgagatgaa gtccctcaag gacagcttgg attctacaat 840
gctgtggcca tcccctgcta taccaccctg acgcagatcc tcccacccac agagcctctg 900
ctgaaggcct gcagggataa cctcaatcag tgggagaagg taattcgagg ggaagagaca 960
gcaatgtgga tttcaggccc agcaactagc aaaagcacat ctgagaagcc gaccaggaag 1020
gtcgatgact ga                                                     1032

<210> 11
<211> 329
<212> PRT
<213> Sus scrofa

<400> 11
Ile Arg Leu Cys Ile Tyr Arg Val Thr Met Glu Lys Leu Ser Tyr His
 1               5                  10                  15      
Ser Ile Cys Thr Ala Glu Glu Trp Gln Gly Leu Met Arg Phe Asn Leu
            20                  25                  30          
Pro Val Arg Leu Cys Lys Glu Ile Glu Leu Phe His Phe Asp Ile Gly
        35                  40                  45              
Pro Phe Glu Asn Met Trp Pro Gly Ile Phe Val Tyr Met Val His Arg
    50                  55                  60                  
Phe Cys Gly Thr Ala Cys Phe Glu Leu Glu Lys Leu Cys Arg Phe Ile
65                  70                  75                  80  
Met Ser Val Lys Lys Asn Tyr Arg Arg Val Pro Tyr His Asn Trp Lys
                85                  90                  95      
His Ala Val Thr Val Ala His Cys Met Tyr Ala Ile Leu Gln Asn Ser
            100                 105                 110         
His Gly Leu Phe Thr Asp Leu Glu Arg Lys Gly Leu Leu Ile Ala Cys
        115                 120                 125             
Leu Cys His Asp Leu Asp His Arg Gly Phe Ser Asn Ser Tyr Leu Gln
    130                 135                 140                 
Lys Phe Asp His Pro Leu Ala Ala Leu Tyr Ser Thr Pro Thr Met Glu
145                 150                 155                 160 
Gln His His Phe Ser Gln Thr Val Ser Ile Leu Gln Leu Glu Gly His
                165                 170                 175     
Asn Ile Phe Ser Thr Leu Ser Ser Ser Glu Tyr Glu Gln Val Leu Glu
            180                 185                 190         
Ile Ile Arg Lys Ala Ile Ile Ala Thr Asp Leu Ala Leu Tyr Phe Gly
        195                 200                 205             
Asn Arg Lys Gln Leu Glu Glu Met Tyr Gln Thr Gly Ser Leu Asn Leu
    210                 215                 220                 
Asn Asn Gln Ser His Arg Asp Arg Val Ile Gly Leu Met Met Thr Ala
225                 230                 235                 240 
Cys Asp Leu Cys Ser Val Thr Lys Leu Trp Pro Val Thr Lys Leu Thr
                245                 250                 255     
Ala Asn Asp Thr Tyr Ala Glu Pro Trp Ala Glu Gly Asp Glu Val Lys
            260                 265                 270         
Lys Leu Gly Ile Gln Pro Ile Pro Met Met Asp Arg Asp Lys Lys Asp
        275                 280                 285             
Glu Val Pro Gln Gly Gln Leu Gly Phe Tyr Asn Ala Val Ala Ile Pro
    290                 295                 300                 
Cys Tyr Thr Thr Leu Thr Gln Ile Phe Pro Pro Thr Glu Pro Leu Leu
305                 310                 315                 320 
Lys Ala Cys Arg Asp Lys Ala Glu Phe
                325                 


<210> 12
<211> 280
<212> PRT
<213> Guinea pig

<400> 12
Val Lys Lys Asn Tyr Arg Arg Val Pro Tyr His Asn Trp Lys His Ala
 1               5                  10                  15      
Val Thr Val Ala His Cys Met Tyr Ala Ile Leu Gln Asn Ser His Gly
            20                  25                  30          
Leu Phe Thr Asp Leu Glu Arg Lys Gly Leu Leu Ile Ala Cys Leu Cys
        35                  40                  45              
His Asp Leu Asp His Arg Gly Phe Ser Asn Ser Tyr Leu Gln Lys Phe
    50                  55                  60                  
Asp His Pro Leu Ala Ala Leu Tyr Ser Thr Ser Thr Met Glu Gln His
65                  70                  75                  80  
His Phe Ser Gln Thr Val Phe Ile Leu Gln Leu Glu Gly His Asn Ile
                85                  90                  95      
Phe Ser Thr Leu Ser Ser Ser Glu Tyr Glu Gln Val Leu Glu Ile Ile
            100                 105                 110         
Arg Lys Ala Ile Ile Ala Thr Asp Leu Ala Leu Tyr Phe Gly Asn Arg
        115                 120                 125             
Lys Gln Leu Glu Glu Met Tyr Gln Thr Gly Ser Leu Asn Leu Asn Asn
    130                 135                 140                 
Gln Ser His Arg Asp Arg Val Ile Gly Leu Met Met Thr Ala Cys Asp
145                 150                 155                 160 
Leu Cys Ser Val Thr Lys Leu Trp Pro Val Thr Lys Leu Thr Ala Asn
                165                 170                 175     
Asp Thr Tyr Ala Glu Pro Trp Ala Glu Gly Asp Glu Met Lys Lys Leu
            180                 185                 190         
Gly Ile Gln Pro Ile Pro Met Met Asp Arg Asp Lys Lys Asp Glu Val
        195                 200                 205             
Pro Gln Gly Gln Leu Gly Phe Tyr Asn Ala Val Ala Ile Pro Cys Tyr
    210                 215                 220                 
Thr Thr Leu Thr Gln Ile Leu Pro Pro Thr Glu Pro Leu Leu Lys Ala
225                 230                 235                 240 
Cys Arg Asp Asn Leu Asn Gln Trp Glu Lys Val Ile Arg Gly Glu Glu
                245                 250                 255     
Thr Ala Met Trp Ile Ser Gly Pro Ala Thr Ser Lys Ser Thr Ser Glu
            260                 265                 270         
Lys Pro Thr Arg Lys Val Asp Asp
        275                 280 


<210> 13
<211> 343
<212> PRT
<213> Rattus norvegicus

<400> 13
Thr Ser Glu Glu Trp Gln Gly Leu Met His Phe Asn Leu Pro Ala Arg
 1               5                  10                  15      
Ile Cys Arg Asp Ile Glu Leu Phe His Phe Asp Ile Gly Pro Phe Glu
            20                  25                  30          
Asn Met Trp Pro Gly Ile Phe Val Tyr Met Ile His Arg Ser Cys Gly
        35                  40                  45              
Thr Ser Cys Phe Glu Leu Glu Lys Leu Cys Arg Phe Ile Met Ser Val
    50                  55                  60                  
Lys Lys Asn Tyr Arg Arg Val Pro Tyr His Asn Trp Lys His Ala Val
65                  70                  75                  80  
Thr Val Ala His Cys Met Tyr Ala Ile Leu Gln Asn Asn Asn Gly Leu
                85                  90                  95      
Phe Thr Asp Leu Glu Arg Lys Gly Leu Leu Ile Ala Cys Leu Cys His
            100                 105                 110         
Asp Leu Asp His Arg Gly Phe Ser Asn Ser Tyr Leu Gln Lys Phe Asp
        115                 120                 125             
His Pro Leu Ala Ala Leu Tyr Ser Thr Ser Thr Met Glu Gln His His
    130                 135                 140                 
Phe Ser Gln Thr Val Ser Ile Leu Gln Leu Glu Gly His Asn Ile Phe
145                 150                 155                 160 
Ser Thr Leu Ser Ser Ser Glu Tyr Glu Gln Val Leu Glu Ile Ile Arg
                165                 170                 175     
Lys Ala Ile Ile Ala Thr Asp Leu Ala Leu Tyr Phe Gly Asn Arg Lys
            180                 185                 190         
Gln Leu Glu Glu Met Tyr Gln Thr Gly Ser Leu Asn Leu His Asn Gln
        195                 200                 205             
Ser His Arg Asp Arg Val Ile Gly Leu Met Met Thr Ala Cys Asp Leu
    210                 215                 220                 
Cys Ser Val Thr Lys Leu Trp Pro Val Thr Lys Leu Thr Ala Asn Asp
225                 230                 235                 240 
Ile Tyr Ala Glu Phe Trp Ala Glu Gly Asp Glu Met Lys Lys Leu Gly
                245                 250                 255     
Ile Gln Pro Ile Pro Met Met Asp Arg Asp Lys Arg Asp Glu Val Pro
            260                 265                 270         
Gln Gly Gln Leu Gly Phe Tyr Asn Ala Val Ala Ile Pro Cys Tyr Thr
        275                 280                 285             
Thr Leu Thr Gln Ile Leu Pro Pro Thr Glu Pro Leu Leu Lys Ala Cys
    290                 295                 300                 
Arg Asp Asn Leu Asn Gln Trp Glu Lys Val Ile Arg Gly Glu Glu Thr
305                 310                 315                 320 
Ala Met Trp Ile Ser Gly Pro Ala Thr Ser Lys Ser Thr Ser Glu Lys
                325                 330                 335     
Pro Thr Arg Lys Val Asp Asp
            340             


<210> 14
<211> 339
<212> PRT
<213> Artificial Sequence

<220> 
<223> Consensus sequence

<400> 14
Thr Ala Glu Glu Trp Gln Gly Leu Met Phe Asn Leu Pro Arg Ile Cys
 1               5                  10                  15      
Lys Asp Ile Glu Leu Phe His Phe Asp Ile Gly Pro Phe Glu Asn Met
            20                  25                  30          
Trp Pro Gly Ile Phe Val Tyr Met Ile His Arg Cys Gly Thr Ser Cys
        35                  40                  45              
Phe Glu Leu Glu Lys Leu Cys Arg Phe Ile Met Ser Val Lys Lys Asn
    50                  55                  60                  
Tyr Arg Arg Val Pro Tyr His Asn Trp Lys His Ala Val Thr Val Ala
65                  70                  75                  80  
His Cys Met Tyr Ala Ile Leu Gln Asn Asn Asn Gly Leu Phe Thr Asp
                85                  90                  95      
Leu Glu Arg Lys Gly Leu Leu Ile Ala Cys Leu Cys His Asp Leu Asp
            100                 105                 110         
His Arg Gly Phe Ser Asn Ser Tyr Leu Gln Lys Phe Asp His Pro Leu
        115                 120                 125             
Ala Ala Leu Tyr Ser Thr Ser Thr Met Glu Gln His His Phe Ser Gln
    130                 135                 140                 
Thr Val Ser Ile Leu Gln Leu Glu Gly His Asn Ile Phe Ser Thr Leu
145                 150                 155                 160 
Ser Ser Ser Glu Tyr Glu Gln Val Leu Glu Ile Ile Arg Lys Ala Ile
                165                 170                 175     
Ile Ala Thr Asp Leu Ala Leu Tyr Phe Gly Asn Arg Lys Gln Leu Glu
            180                 185                 190         
Glu Met Tyr Gln Thr Gly Ser Leu Asn Leu His Asn Gln Ser His Arg
        195                 200                 205             
Asp Arg Val Ile Gly Leu Met Met Thr Ala Cys Asp Leu Cys Ser Val
    210                 215                 220                 
Thr Lys Leu Trp Pro Val Thr Lys Leu Thr Ala Asn Asp Ile Tyr Ala
225                 230                 235                 240 
Glu Phe Trp Ala Glu Gly Asp Glu Met Lys Lys Leu Gly Ile Gln Pro
                245                 250                 255     
Ile Pro Met Met Asp Arg Asp Lys Lys Asp Glu Val Pro Gln Gly Gln
            260                 265                 270         
Leu Gly Phe Tyr Asn Ala Val Ala Ile Pro Cys Tyr Thr Thr Leu Thr
        275                 280                 285             
Gln Ile Leu Pro Pro Thr Glu Pro Leu Leu Lys Ala Cys Arg Asp Asn
    290                 295                 300                 
Leu Asn Gln Trp Glu Lys Val Ile Arg Gly Glu Glu Thr Ala Met Trp
305                 310                 315                 320 
Ile Ser Gly Pro Ala Thr Ser Lys Ser Thr Ser Lys Pro Thr Arg Lys
                325                 330                 335     
Val Asp Asp
            






