OSDDMalaria:GSK Arylpyrrole Series:desired compounds: Difference between revisions

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The decisions about the compounds discussed below is being carried out at [http://www.thesynapticleap.org/node/409 The Synaptic Leap]
The decisions about the compounds discussed below is being carried out at [http://www.thesynapticleap.org/node/409 The Synaptic Leap]


== Finalised List ==
== Finalised List ==


This finalised list of desired synthetic compounds is the result of the [http://www.thesynapticleap.org/node/409 compounds consultation]. The descriptors "sA" etc are temporary and will be replaced with appropriate designators when acquired in reality.  
This finalised list of desired synthetic compounds is the result of the [http://www.thesynapticleap.org/node/409 compounds consultation]. The descriptors "sA" etc are temporary and will be replaced with appropriate designators when acquired in reality. We are also interested in the secondary and tertiary amide analogues of these compounds as well. for compound sH, other heterocycles would be of interest.
 
[[Image:Top_10_Synthetics_final.png|thumb|none|600px|Desired compounds]]
The .cdx file is available via a [https://dl.dropbox.com/u/3557122/Top%2010%20Synthetics_final.cdx public dropbox]


=== SMILES/InChi ===
=== Synthetic SMILES/InChi ===


sA: FC1=CC=C(N2C(C)=CC(C(OC(C)(C)C(N)=O)=O)=C2C)C=C1
sA: FC1=CC=C(N2C(C)=CC(C(OC(C)(C)C(N)=O)=O)=C2C)C=C1
Line 16: Line 20:
InChI=1S/C16H14FN3O2/c1-9-7-13(16-19-14(8-22-16)15(18)21)10(2)20(9)12-5-3-11(17)4-6-12/h3-8H,1-2H3,(H2,18,21)
InChI=1S/C16H14FN3O2/c1-9-7-13(16-19-14(8-22-16)15(18)21)10(2)20(9)12-5-3-11(17)4-6-12/h3-8H,1-2H3,(H2,18,21)


sC: FC1=CC=C(N2C(C)=CC(C(N(C)C(C)C(N)=O)=O)=C2C)C=C1
 
sC (alanine derivative shown): FC1=CC=C(N2C(C)=CC(C(N(C)C(C)C(N)=O)=O)=C2C)C=C1
InChI=1S/C17H20FN3O2/c1-10-9-15(17(23)20(4)12(3)16(19)22)11(2)21(10)14-7-5-13(18)6-8-14/h5-9,12H,1-4H3,(H2,19,22)
InChI=1S/C17H20FN3O2/c1-10-9-15(17(23)20(4)12(3)16(19)22)11(2)21(10)14-7-5-13(18)6-8-14/h5-9,12H,1-4H3,(H2,19,22)


sD: FC1=CC=C(N2C(C)=CC(COCC(N)=O)=C2C)C=C1
sD: FC1=CC=C(N2C(C)=CC(COCC(N)=O)=C2C)C=C1
InChI=1S/C15H17FN2O2/c1-10-7-12(8-20-9-15(17)19)11(2)18(10)14-5-3-13(16)4-6-14/h3-7H,8-9H2,1-2H3,(H2,17,19)
InChI=1S/C15H17FN2O2/c1-10-7-12(8-20-9-15(17)19)11(2)18(10)14-5-3-13(16)4-6-14/h3-7H,8-9H2,1-2H3,(H2,17,19)


sE: FC1=CC=C(N2C(C)=CC(S(N(C)CC(N)=O)(=O)=O)=C2C)C=C1
sE: FC1=CC=C(N2C(C)=CC(S(N(C)CC(N)=O)(=O)=O)=C2C)C=C1
InChI=1S/C15H18FN3O3S/c1-10-8-14(23(21,22)18(3)9-15(17)20)11(2)19(10)13-6-4-12(16)5-7-13/h4-8H,9H2,1-3H3,(H2,17,20)
InChI=1S/C15H18FN3O3S/c1-10-8-14(23(21,22)18(3)9-15(17)20)11(2)19(10)13-6-4-12(16)5-7-13/h4-8H,9H2,1-3H3,(H2,17,20)


sF: FC1=CC=C(N2C(C)=CC(C3=NOC(C(N)=O)=N3)=C2C)C=C1
sF: FC1=CC=C(N2C(C)=CC(C3=NOC(C(N)=O)=N3)=C2C)C=C1
InChI=1S/C15H13FN4O2/c1-8-7-12(14-18-15(13(17)21)22-19-14)9(2)20(8)11-5-3-10(16)4-6-11/h3-7H,1-2H3,(H2,17,21)
InChI=1S/C15H13FN4O2/c1-8-7-12(14-18-15(13(17)21)22-19-14)9(2)20(8)11-5-3-10(16)4-6-11/h3-7H,1-2H3,(H2,17,21)


sG: FC1=CC=C(N2N=CC(C3=NC(C(N)=O)=CO3)=C2C)C=C1
sG: FC1=CC=C(N2N=CC(C3=NC(C(N)=O)=CO3)=C2C)C=C1
InChI=1S/C14H11FN4O2/c1-8-11(14-18-12(7-21-14)13(16)20)6-17-19(8)10-4-2-9(15)3-5-10/h2-7H,1H3,(H2,16,20)
InChI=1S/C14H11FN4O2/c1-8-11(14-18-12(7-21-14)13(16)20)6-17-19(8)10-4-2-9(15)3-5-10/h2-7H,1H3,(H2,16,20)


sH: O=C1CCCN1CC(C=C(N2C3=CC=CC=C3)C)=C2C
sH: O=C1CCCN1CC(C=C(N2C3=CC=CC=C3)C)=C2C
InChI=1S/C17H20N2O/c1-13-11-15(12-18-10-6-9-17(18)20)14(2)19(13)16-7-4-3-5-8-16/h3-5,7-8,11H,6,9-10,12H2,1-2H3
InChI=1S/C17H20N2O/c1-13-11-15(12-18-10-6-9-17(18)20)14(2)19(13)16-7-4-3-5-8-16/h3-5,7-8,11H,6,9-10,12H2,1-2H3


sI: FC1=CC=C(N2C(C=CN=C3OCC(N)=O)=C3C=N2)C=C1
sI: FC1=CC=C(N2C(C=CN=C3OCC(N)=O)=C3C=N2)C=C1
InChI=1S/C14H11FN4O2/c15-9-1-3-10(4-2-9)19-12-5-6-17-14(11(12)7-18-19)21-8-13(16)20/h1-7H,8H2,(H2,16,20)
InChI=1S/C14H11FN4O2/c15-9-1-3-10(4-2-9)19-12-5-6-17-14(11(12)7-18-19)21-8-13(16)20/h1-7H,8H2,(H2,16,20)


sJ: FC1=CC=C(N2N=CC(C(OCC(N)=O)=O)=C2)C=C1
sJ: FC1=CC=C(N2N=CC(C(OCC(N)=O)=O)=C2)C=C1
InChI=1S/C12H10FN3O3/c13-9-1-3-10(4-2-9)16-6-8(5-15-16)12(18)19-7-11(14)17/h1-6H,7H2,(H2,14,17)
InChI=1S/C12H10FN3O3/c13-9-1-3-10(4-2-9)16-6-8(5-15-16)12(18)19-7-11(14)17/h1-6H,7H2,(H2,14,17)
== Commercially available analogues of desired compounds ==
This is a list of commercially available analogues of the above compounds.  The cores of each of the different classes in the above list were searched by eMolecules.com and by supplier websites. Partial search carried out by via Molport.
The consultation did not largely change the desired commercial compounds. The thiazolidinone type compounds were discounted. The list of Smiles/InChi strings below reflects the desired commercial compounds
[[Image:Desiredcompounds_commercial.png|thumb|none|600px|Desired compounds]]
The .cdx file is available via a [https://dl.dropbox.com/u/3557122/desiredcompounds_commercial.cdx public dropbox]
=== Commercial Smiles/InChi list ===
cA: O=C(N(C)C)CNCC1=C(C)N(C(C)=C1)C2=CC=CC=C2
InChI=1S/C17H23N3O/c1-13-10-15(11-18-12-17(21)19(3)4)14(2)20(13)16-8-6-5-7-9-16/h5-10,18H,11-12H2,1-4H3
cB: FC1=CC=C(N2C(C)=CC(C(OCC(N)=O)=O)=C2C)C=C1
InChI=1S/C15H15FN2O3/c1-9-7-13(15(20)21-8-14(17)19)10(2)18(9)12-5-3-11(16)4-6-12/h3-7H,8H2,1-2H3,(H2,17,19)
cC: O=C(N1CCNC(C1)=O)C2=C(C)N(C(C)=C2)C3=CC=CC=C3
InChI=1S/C17H19N3O2/c1-12-10-15(17(22)19-9-8-18-16(21)11-19)13(2)20(12)14-6-4-3-5-7-14/h3-7,10H,8-9,11H2,1-2H3,(H,18,21)
cD: O=C(NC)CN(C)CC1=C(C)N(C(C)=C1)C2=CC=C(Br)C=C2
InChI=1S/C17H22BrN3O/c1-12-9-14(10-20(4)11-17(22)19-3)13(2)21(12)16-7-5-15(18)6-8-16/h5-9H,10-11H2,1-4H3,(H,19,22)
cE: O=C(NC1=CC=CC(OC)=C1)CSC2=NN=C(O2)C3=C(C)N(C(C)=C3)C4=CC=CC=C4
InChI=1S/C23H22N4O3S/c1-15-12-20(16(2)27(15)18-9-5-4-6-10-18)22-25-26-23(30-22)31-14-21(28)24-17-8-7-11-19(13-17)29-3/h4-13H,14H2,1-3H3,(H,24,28)
cF: FC1=CC=C(N2C(C)=CC(C(N(CC)CC(NC3=C(F)C=CC=C3F)=O)=O)=C2C)C=C1
InChI=1S/C23H22F3N3O2/c1-4-28(13-21(30)27-22-19(25)6-5-7-20(22)26)23(31)18-12-14(2)29(15(18)3)17-10-8-16(24)9-11-17/h5-12H,4,13H2,1-3H3,(H,27,30)
cG: O=C(NC1=NOC(C)=C1)CN(C)C(C2=C(C)N(C(C)=C2)C3=CC(C)=CC=C3)=O
InChI=1S/C21H24N4O3/c1-13-7-6-8-17(9-13)25-14(2)10-18(16(25)4)21(27)24(5)12-20(26)22-19-11-15(3)28-23-19/h6-11H,12H2,1-5H3,(H,22,23,26)
cH: ClC1=CC=C(N2C(C)=CC(CNC3CCN(CC(NC)=O)CC3)=C2C)C=C1
InChI=1S/C21H29ClN4O/c1-15-12-17(16(2)26(15)20-6-4-18(22)5-7-20)13-24-19-8-10-25(11-9-19)14-21(27)23-3/h4-7,12,19,24H,8-11,13-14H2,1-3H3,(H,23,27)
cI: O=C(NCC)[C@H](C[C@@H](N)C1)N1CC2=C(C)N(C(C)=C2)C3=CC=CC=C3Cl
InChI=1S/C20H27ClN4O/c1-4-23-20(26)19-10-16(22)12-24(19)11-15-9-13(2)25(14(15)3)18-8-6-5-7-17(18)21/h5-9,16,19H,4,10-12,22H2,1-3H3,(H,23,26)/t16-,19+/m1/s1
cJ: CCC1=CC=C(N2C(C)=CC(CN3CCC(C(O)=O)CC3)=C2C)C=C1
InChI=1S/C21H28N2O2/c1-4-17-5-7-20(8-6-17)23-15(2)13-19(16(23)3)14-22-11-9-18(10-12-22)21(24)25/h5-8,13,18H,4,9-12,14H2,1-3H3,(H,24,25)
cK (additional): FC1=CC=C(N2C(C)=CC(C(OCC(N(C)C)=O)=O)=C2C)C=C1
InChI=1S/C17H19FN2O3/c1-11-9-15(17(22)23-10-16(21)19(3)4)12(2)20(11)14-7-5-13(18)6-8-14/h5-9H,10H2,1-4H3


== Original List Desired Analogues ==
== Original List Desired Analogues ==
Line 79: Line 146:


failed pains: 15 (62.5%)
failed pains: 15 (62.5%)
== Commercially available analogues of desired compounds ==
This is a list of commercially available analogues of the above compounds.  The cores of each of the different classes in the above list were searched by eMolecules.com and by supplier websites. Partial search carried out by via Molport.
[[Image:Desiredcompounds_commercial.png|thumb|none|600px|Desired compounds]]
The .cdx file is available via a [https://dl.dropbox.com/u/3557122/desiredcompounds_commercial.cdx public dropbox]
=== SMILES list ===
CNC(=O)COC(=O)c1cc(C)n(c2ccc(F)cc2)c1C
Fc1ccc(cc1)n1c(C)cc(C(=O)OCC(=O)N(C)C)c1C
CCN(CC(=O)Nc1c(F)cccc1F)C(=O)c1cc(C)n(c2ccc(F)cc2)c1C
O=C1NCCN(C1)C(=O)c1cc(C)n(c2ccccc2)c1C
O=C(Nc1noc(C)c1)CN(C)C(=O)c1cc(C)n(c2cccc(C)c2)c1C
CNC(=O)CN(C)C(=O)c1cc(C)n(c2ccc(Br)cc2)c1C
CN(C)C(=O)CNC(=O)c1cc(C)n(c2ccccc2)c1C
CNC(=O)CN1CCC(CC1)NCc1cc(C)n(c2ccc(Cl)cc2)c1C
COc1cccc(NC(=O)CSc2nnc(o2)c2cc(C)n(c3ccccc3)c2C)c1
O=C(CSc1nnc(o1)c1cc(C)n(c2ccccc2)c1C)Nc1cccc(C)c1C 
O=C(NCC)[C@H](C[C@@H](N)C1)N1CC2=C(C)N(C(C)=C2)C3=CC=CC=C3Cl
O=C(NC1=O)/C(S1)=C([H])/C(C=C(N2C3=CN=CC=C3)C)=C2C
O=C(NC1=O)/C(S1)=C([H])/C(C=C(N2C3=CC=NC=C3)C)=C2C
CC(N1C2=CC=CC=C2)=C(/C([H])=C(S3)/C(NC3=O)=O)C=C1C4=CC=CC=C4
CN1C=C(/C=C2C(N/C(S/2)=N\C3=CC=C(F)C=C3)=O)C4=C1C=CC=C4

Latest revision as of 21:37, 30 July 2012

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The decisions about the compounds discussed below is being carried out at The Synaptic Leap


Finalised List

This finalised list of desired synthetic compounds is the result of the compounds consultation. The descriptors "sA" etc are temporary and will be replaced with appropriate designators when acquired in reality. We are also interested in the secondary and tertiary amide analogues of these compounds as well. for compound sH, other heterocycles would be of interest.

Desired compounds

The .cdx file is available via a public dropbox

Synthetic SMILES/InChi

sA: FC1=CC=C(N2C(C)=CC(C(OC(C)(C)C(N)=O)=O)=C2C)C=C1 InChI=1S/C17H19FN2O3/c1-10-9-14(15(21)23-17(3,4)16(19)22)11(2)20(10)13-7-5-12(18)6-8-13/h5-9H,1-4H3,(H2,19,22)


sB: FC1=CC=C(N2C(C)=CC(C3=NC(C(N)=O)=CO3)=C2C)C=C1 InChI=1S/C16H14FN3O2/c1-9-7-13(16-19-14(8-22-16)15(18)21)10(2)20(9)12-5-3-11(17)4-6-12/h3-8H,1-2H3,(H2,18,21)


sC (alanine derivative shown): FC1=CC=C(N2C(C)=CC(C(N(C)C(C)C(N)=O)=O)=C2C)C=C1 InChI=1S/C17H20FN3O2/c1-10-9-15(17(23)20(4)12(3)16(19)22)11(2)21(10)14-7-5-13(18)6-8-14/h5-9,12H,1-4H3,(H2,19,22)


sD: FC1=CC=C(N2C(C)=CC(COCC(N)=O)=C2C)C=C1 InChI=1S/C15H17FN2O2/c1-10-7-12(8-20-9-15(17)19)11(2)18(10)14-5-3-13(16)4-6-14/h3-7H,8-9H2,1-2H3,(H2,17,19)


sE: FC1=CC=C(N2C(C)=CC(S(N(C)CC(N)=O)(=O)=O)=C2C)C=C1 InChI=1S/C15H18FN3O3S/c1-10-8-14(23(21,22)18(3)9-15(17)20)11(2)19(10)13-6-4-12(16)5-7-13/h4-8H,9H2,1-3H3,(H2,17,20)


sF: FC1=CC=C(N2C(C)=CC(C3=NOC(C(N)=O)=N3)=C2C)C=C1 InChI=1S/C15H13FN4O2/c1-8-7-12(14-18-15(13(17)21)22-19-14)9(2)20(8)11-5-3-10(16)4-6-11/h3-7H,1-2H3,(H2,17,21)


sG: FC1=CC=C(N2N=CC(C3=NC(C(N)=O)=CO3)=C2C)C=C1 InChI=1S/C14H11FN4O2/c1-8-11(14-18-12(7-21-14)13(16)20)6-17-19(8)10-4-2-9(15)3-5-10/h2-7H,1H3,(H2,16,20)


sH: O=C1CCCN1CC(C=C(N2C3=CC=CC=C3)C)=C2C InChI=1S/C17H20N2O/c1-13-11-15(12-18-10-6-9-17(18)20)14(2)19(13)16-7-4-3-5-8-16/h3-5,7-8,11H,6,9-10,12H2,1-2H3


sI: FC1=CC=C(N2C(C=CN=C3OCC(N)=O)=C3C=N2)C=C1 InChI=1S/C14H11FN4O2/c15-9-1-3-10(4-2-9)19-12-5-6-17-14(11(12)7-18-19)21-8-13(16)20/h1-7H,8H2,(H2,16,20)


sJ: FC1=CC=C(N2N=CC(C(OCC(N)=O)=O)=C2)C=C1 InChI=1S/C12H10FN3O3/c13-9-1-3-10(4-2-9)16-6-8(5-15-16)12(18)19-7-11(14)17/h1-6H,7H2,(H2,14,17)

Commercially available analogues of desired compounds

This is a list of commercially available analogues of the above compounds. The cores of each of the different classes in the above list were searched by eMolecules.com and by supplier websites. Partial search carried out by via Molport.

The consultation did not largely change the desired commercial compounds. The thiazolidinone type compounds were discounted. The list of Smiles/InChi strings below reflects the desired commercial compounds

Desired compounds

The .cdx file is available via a public dropbox


Commercial Smiles/InChi list

cA: O=C(N(C)C)CNCC1=C(C)N(C(C)=C1)C2=CC=CC=C2 InChI=1S/C17H23N3O/c1-13-10-15(11-18-12-17(21)19(3)4)14(2)20(13)16-8-6-5-7-9-16/h5-10,18H,11-12H2,1-4H3


cB: FC1=CC=C(N2C(C)=CC(C(OCC(N)=O)=O)=C2C)C=C1 InChI=1S/C15H15FN2O3/c1-9-7-13(15(20)21-8-14(17)19)10(2)18(9)12-5-3-11(16)4-6-12/h3-7H,8H2,1-2H3,(H2,17,19)


cC: O=C(N1CCNC(C1)=O)C2=C(C)N(C(C)=C2)C3=CC=CC=C3 InChI=1S/C17H19N3O2/c1-12-10-15(17(22)19-9-8-18-16(21)11-19)13(2)20(12)14-6-4-3-5-7-14/h3-7,10H,8-9,11H2,1-2H3,(H,18,21)


cD: O=C(NC)CN(C)CC1=C(C)N(C(C)=C1)C2=CC=C(Br)C=C2 InChI=1S/C17H22BrN3O/c1-12-9-14(10-20(4)11-17(22)19-3)13(2)21(12)16-7-5-15(18)6-8-16/h5-9H,10-11H2,1-4H3,(H,19,22)


cE: O=C(NC1=CC=CC(OC)=C1)CSC2=NN=C(O2)C3=C(C)N(C(C)=C3)C4=CC=CC=C4 InChI=1S/C23H22N4O3S/c1-15-12-20(16(2)27(15)18-9-5-4-6-10-18)22-25-26-23(30-22)31-14-21(28)24-17-8-7-11-19(13-17)29-3/h4-13H,14H2,1-3H3,(H,24,28)


cF: FC1=CC=C(N2C(C)=CC(C(N(CC)CC(NC3=C(F)C=CC=C3F)=O)=O)=C2C)C=C1 InChI=1S/C23H22F3N3O2/c1-4-28(13-21(30)27-22-19(25)6-5-7-20(22)26)23(31)18-12-14(2)29(15(18)3)17-10-8-16(24)9-11-17/h5-12H,4,13H2,1-3H3,(H,27,30)


cG: O=C(NC1=NOC(C)=C1)CN(C)C(C2=C(C)N(C(C)=C2)C3=CC(C)=CC=C3)=O InChI=1S/C21H24N4O3/c1-13-7-6-8-17(9-13)25-14(2)10-18(16(25)4)21(27)24(5)12-20(26)22-19-11-15(3)28-23-19/h6-11H,12H2,1-5H3,(H,22,23,26)


cH: ClC1=CC=C(N2C(C)=CC(CNC3CCN(CC(NC)=O)CC3)=C2C)C=C1 InChI=1S/C21H29ClN4O/c1-15-12-17(16(2)26(15)20-6-4-18(22)5-7-20)13-24-19-8-10-25(11-9-19)14-21(27)23-3/h4-7,12,19,24H,8-11,13-14H2,1-3H3,(H,23,27)


cI: O=C(NCC)[C@H](C[C@@H](N)C1)N1CC2=C(C)N(C(C)=C2)C3=CC=CC=C3Cl InChI=1S/C20H27ClN4O/c1-4-23-20(26)19-10-16(22)12-24(19)11-15-9-13(2)25(14(15)3)18-8-6-5-7-17(18)21/h5-9,16,19H,4,10-12,22H2,1-3H3,(H,23,26)/t16-,19+/m1/s1


cJ: CCC1=CC=C(N2C(C)=CC(CN3CCC(C(O)=O)CC3)=C2C)C=C1 InChI=1S/C21H28N2O2/c1-4-17-5-7-20(8-6-17)23-15(2)13-19(16(23)3)14-22-11-9-18(10-12-22)21(24)25/h5-8,13,18H,4,9-12,14H2,1-3H3,(H,24,25)


cK (additional): FC1=CC=C(N2C(C)=CC(C(OCC(N(C)C)=O)=O)=C2C)C=C1 InChI=1S/C17H19FN2O3/c1-11-9-15(17(22)23-10-16(21)19(3)4)12(2)20(11)14-7-5-13(18)6-8-14/h5-9H,10H2,1-4H3

Original List Desired Analogues

This is a list of compounds we are currently targeting or would like to have access to. If you happen to have some of these compounds, or their close analogues, in your labs or would like to make them then please get in touch. The compounds highlighted in red are current priority compounds, please get in touch on The Synaptic Leap with your views.

Desired compounds

The .cdx file is available via a public dropbox

The near neighbour compounds could be available from the authors of this paper


SMARTS Filter

A SMARTS filter was carried out on the above compounds with the following summary (All fail on the Alarm NMR):

total: 24

passed: 6 (25.0%)

failed: 18 (75.0%)

failed glaxo_unsuitable_leads: 0 (0.0%)

failed glaxo_unsuitable_natprod: 0 (0.0%)

failed glaxo_reactive: 0 (0.0%)

failed ursu_reactive: 0 (0.0%)

failed lint_blake-v2: 1 (4.2%)

failed oprea_filters: 1 (4.2%)

failed MLSMR_excluded: 12 (50.0%)

failed MLSMR_allowed: 1 (4.2%)

failed toxic: 0 (0.0%)

failed pains: 15 (62.5%)

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