Non MedChem-Friendly SMARTS
Structural alerts or "toxicophores" are substructures found in chemicals that are highly correlated with undesirable properties typically associated with human or environmental toxicity. A number of studies over the past 20 years have provided descriptions of individual chemical substructures associated with particular pharmacological endpoints, typically in the format of a Daylight SMARTS description. Moreover when such substructures are used to filter medicinally unfriendly compounds out of the drug discovery pipeline, a significant reduction in compound failure rates in the clinic has been observed. For a comprehensive and freely accessible source of structural alerts please go to the OCHEM toxalerts database.
Below are the SMARTS descriptions used by SureChEMBL that would indicate whether a compound would match one or more structural alerts and hence considered to have a MedChem unfriendly status.
| Chemical_Group | SMARTS |
|---|---|
| 2,2-dimethyl-4,5-dicarboxy-dithiole | C1(C)(C)SC(C(=O)O)=C(C(=O)O)S1 |
| 2,3,4_trihydroxyphenyl | c([OH])c([OH])c([OH]) |
| 2,3,5_trihydroxyphenyl | c([OH])c([OH])cc([OH]) |
| acid_anhydrides | C(=O)OC(=O) |
| acid_halides | [S,C](=[O,S])[F,Br,Cl,I] |
| Acridine | c1c2cc4ccccc4nc2ccc1 |
| Active_Phosphate | P(=S)([OH1,O$(O[#6])])([OH1,O$(O[#6])])[S,O] |
| acyl_cyanide | C(=O)-C#N |
| Adjacent_Ring_Double_Bonds | [*;R]=[*;R]=[*;R] |
| Aldehyde | [#6][C!H0]=O |
| Aliphatic_Triflate | COS(=O)(=O)C(F)(F)F |
| AlkylEnamine | [C;H1$(C([#6;!$(C=O)])),H0$(C([#6;!$(C=O)])[#6;!$(C=O)])]=[CH1]!@N([#6;!$(C(=O))])[#6;!$(C(=O))] |
| Allene | *=C=* |
| Alpha_Halo_Carbonyl | [C;!$(C[N])](=O)!@[C;h1,h2;H1,H2][F,Cl,Br,I] |
| amidotetrazole | c1nnnn1C=O |
| Amino_Naphtalimide | c1(N)ccc(C(=O)NC3(=O))c(c3ccc2)c21 |
| Aminonitrile | NC#N |
| Anhydride | [#6]C(=O)OC(=O)[#6] |
| Any_Carbazide | O=*N=[N+]=[N-] |
| aromatic_azides | cN=N=N |
| Azanitrone | N=[N+]([O-])C |
| azoalkanals | [N;R0]=[N;R0]CC=O |
| Azobenzene | c1ccccc1[N!r]=[N!r]c2ccccc2 |
| Azocyanamide | [N;R0]=[N;R0]C#N |
| b-Carbonyl_Quaternary_Nitrogen | C(=O)CC[N+,n+] |
| benzylic_quaternary_nitrogen | cC[N+,NX4] |
| beta-carbonyl_quaternary_nitrogen | C(=O)C[N+,n+,NX4,nX4] |
| Beta-Fluoro-ethyl-ON | [C;H2$(CF),H1$(C(F)F)]!@[CH2][N,O] |
| biotin_analogue | C12C(NC(N1)=O)CSC2 |
| carbazides | C(=O)N=N=N |
| carbodiimides | N=C=N |
| CCl3-CHO_releasing | C(Cl)(Cl)(Cl)C([O,S])[NX3] |
| Chloramidine | [Cl]C([C&R0])=N |
| Conjugated_Dithioether | SC(=[!r])S |
| Crown_Ether_12CRO4 | O1CCOCCOCCOCC1 |
| Crown_Ether_15CRO5 | O1CCOCCOCCOCCOCC1 |
| Crown_Ether_16CRO6 | O1CCOCCOCCOCCOCCOCC1 |
| crown_ethers | [O;R1][C;R1][C;R1][O;R1][C;R1][C;R1][O;R1] |
| cyanamide | N[CH2]C#N |
| Cyanophosphonate | P(OCC)(OCC)(=O)C#N |
| Cyanohydrin | N#CC[OH1] |
| di_and_triphosphates | P(=O)([OH])OP(=O)[OH] |
| Diacetylene | C#CC#C |
| Diazoalkane | C=[N+]=[N-] |
| Diazonium_Salt | [N+]#N |
| Diene | C!@=[CH1]-C!@=[CH1]-[CX3](=O) |
| Dinitrobenzene_1 | c1c([N+](=O)[O-])c([N+](=O)[O-])ccc1 |
| Dinitrobenzene_2 | c1c([N+](=O)[O-])ccc([N+](=O)[O-])c1 |
| Dinitrobenzene_3 | c1c([N+](=O)[O-])cc([N+](=O)[O-])cc1 |
| disulfides | [SX2][SX2] |
| Dithiocarbamate | NC(=S)S |
| Dithiole-2-thione | S1SC=CC1=S |
| Dithiole-3-thione | S1C=CSC1=C |
| Dithiomethylene_acetal | S[C;!$(C=*)]S |
| Enyne | C=!@CC#C |
| epoxides,_thioepoxides,_aziridines | C1[O,S,N]C1 |
| ester_of_HOBT | C(=O)Onnn |
| Flavin | c1cccc(NC(=NC(=[N,S,O])NC(=O)3)C3=N2)c12 |
| Fluorescein | c1cc(O)cc(OC(=CC(=O)C=C3)C3=C2)c12 |
| Fluorinated_Carbon_1 | C(C(CF)F)F |
| Fluorinated_Carbon_2 | C(C(F)F)(F)F |
| four_member_lactones | C1(=O)OCC1 |
| geminal_amines | [NH1;!r][CX4][NH1;!r] |
| geminal_dinitriles | N#CCC#N |
| halo-pyridine,_-diazoles_and_-triazoles | [Cl,Br,I]c1[c,n][c,n][c,n][c,n]n1 |
| hydrazothiourea | N=NC(S)N |
| Imidazolium | c1[n+]([#6])ccn1([#6]) |
| Imine2 | [#6,#8,#16]-[CH1]=[NH1] |
| imines_(not_ring) | [#6][C;R0](=[N;R0,O0])[#6] |
| isocyanates_&_isothiocyanates | N=C=[S,O] |
| isonitrile | [N+]#[C-] |
| ketene | C=C=O |
| Lawesson_Reagent_Derivatives | P(=S)(S)S |
| methylidene-1,3-dithiole | S1C=CSC1=S |
| Michael_Phenyl_Ketone | c1ccccc1C(=O)C=!@CC(=O)!@* |
| N-halo | [NX3,NX4][F,Cl,Br,I] |
| Nitrobenz-azadiazole_1 | c1ccc(n[o,s]n2)c2c1[N+](=O)[O-] |
| Nitrobenz-azadiazole_2 | c1c([N+](=O)[O-])cc(n[o,s]n2)c2c1 |
| nitrosamine | N-[N;X2](=O) |
| nitroso | [N&D2](=O) |
| noname | N1=C[S,NH1]C(=[C,N,P][C,N,O,P])C1(=O) |
| N-Oxide_aliphatic | [N+!$(N=O)][O-X1] |
| N-S_(not_sulfonamides) | [#6][S;O0][N;H0] |
| Orthoester | C(O)(O)[OH] |
| o-tertbutylphenol | c1c([OH1])c(C(C)(C)C)ccc1 |
| Oxobenzothiepine | C1(=O)C=CCSC=C1 |
| P_or_S_Halides | [P,S][Cl,Br,F,I] |
| p-Aminoaryl_diazo | Nc1aaa(N!@=N)aa1 |
| PCP | PCP |
| paranitrophenyl_esters | C(=O)Oc1ccc(N(=O)=O)cc1 |
| pentahalophenyl | c1c([F,Cl])c([F,Cl])c([F,Cl])c([F,Cl])c1([F,Cl]) |
| pentafluorophenyl_esters | C(=O)Oc1c(F)c(F)c(F)c(F)c1(F) |
| peroxide | [#8]~[#8] |
| Phenanthrene | c12cccc3c1c4c(cc3)cccc4cc2 |
| phosphonate_esters | [#6]P(=O)(~O)O[#6] |
| phosphoramides | NP(=O)(N)N |
| phosphorane | C=P |
| Phosphorus_Halide | [S,P][F,Cl,Br,I] |
| Polyene | C=!@CC=!@C |
| polyenes | C=CC=CC=CC=C |
| polyene_chain_between_aromatics | cC=CC=CC=Cc |
| polyines | CC#CC#CC |
| Polynuclear_Aromatic_1 | c1cccc(cc(cccc2)c2c3)c13 |
| Polynuclear_Aromatic_2 | c1cccc(c(cccc2)c2cc3)c13 |
| Polysulfide | *[SX2][SX2][SX2]* |
| Sulphur_Halide | [#16][F,Cl,Br,I] |
| pyrene_fragments | c1c2cccc3c2c4c(cc3)cccc4c1 |
| Pyrylium | c1ccc[o+]c1 |
| reactive_carbonyls | [C;!r](=[O,S])[S;!r] |
| reactive_carbonyls | [C;!r](=[O,S])[CX2;!r][F,Br,Cl] |
| Ring_Triple_Bond | [C,c;R]#[C,c;R] |
| S=N_(not_ring) | [S;R0]=[N;R0] |
| Sulfonate_Ester | O=[SX4](=O)OC |
| sulfonyl_cyanide | S(=O)(=O)C#N |
| Sulphate_Ester | COS(=O)O[C,c] |
| sulphonates | COS(=O)(=O)[C,c] |
| Sulphur_Nitrogen_single_bond | [SX2H0]!@[N] |
| Tetraazinane | C1NNC=NN1 |
| Thiocyanate | SC#N |
| thioesters | C[O,S;R0][C;R0](=S) |
| thioles_(not_aromatic) | [!a][SX2;H1] |
| Thiophosphothionate | P(=S)(-[S;H1,H0$(S(P)C)])(-[O;H1,H0$(O(P)C)])(-N(C)C) |
| thiourea | [N;!r][C;!r](=S)[N;!r] |
| Three_Membered_Heterocycle | *1[O,S]*1 |
| Tri_Pentavalent_S | [#16v3,#16v5] |
| Triacyloxime | C(=O)N(C(=O))OC(=O) |
| Triazole | c1cnnn1!@C!@[NH1][#6] |
| triflate | OS(=O)(=O)(C(F)(F)(F)) |
| Triphenyl_Boranyl | B(c1ccccc1)(c2ccccc2)c3ccccc3 |
| triphenylphosphines | P(c1aaaaa1)(c1aaaaa1)(c1aaaaa1) |
| Triphenyl_Silyl | [Si](c1ccccc1)(c2ccccc2)(c3ccccc3) |
| Vinyl_Halide | [Cl,Br,I]C=[!O!R] |
| Vinyl_Sulphone | [#6][CH1]!@=[CH1][S;H1,H0$(S(C)C)](=O)(=O) |
| sulphates | [#6]S(=O)(=O)O |
| tropone | C1C(=O)C=CC=CC=1 |
| Oxime | [#6]C(=!@N[$(OC),$([OH])])[#6] |
| hydrazone | [#6]C(=!@NNa)[#6] |
| Nitrosone_not_nitro | [$(N(~!@[#6])!@O);!$([N+]([O-])=O)] |
| Thiocarbonyl_group | C=S |
| acid_anhydrides_2 | [#6]C(=O)!@OC(=!@[N,O])[#6] |
| trifluroacetate_amide | FC(F)(F)C(=O)N |
| triple_bond | [#6]C#[CH] |
| Allene | C=C=C |
| thiatetrazolidine | [$(Sc1nnn[nH,n-]1),$(Sc1nn[nH,n-]n1)] |
| oxy-amide | [#6]C(=O)!@C!@C(=O)N |
| formate_formide | O=[CH][O,N][#6] |
| pyranone | O=C1C=COC=C1 |
| Coumarin | c1cc2C=CC(=O)Oc2cc1 |
| aminothiazole | s1ccnc1[N!H0] |
| Thiazolidinone | O=C1CSCN1 |
| Thiomorpholinedione | N1C(=O)CSCC1=O |
| oxepine | O1C=CC=CC=C1 |
| cyclobutene | C1CC=C1 |
| poly_sub_atomatic | *!@c1c(!@*)c(!@*)c(!@*)c(!@*)c1 |
| Isotopes | [2H,3H,11C,11c,14C,14c,125I,32P,33P,35S] |
| Undesirable_Elements_Salts | [Ac,Ag,Am,Ar,As,At,Au,Ba,Be,Bi,Bk,Cd,Ce,Cf,Cm,Cr,Cs,Dy,Er, Eu,Fr,Ga,Gd,Ge,He,Hf,Ho,In,Ir,Kr,La,Lu,Mo,Nb,Nd,Ne,Ni, Np,Os,Pa,Pb,Pd,Pm,Po,Pr,Pt,Pu,Ra,Rb,Re,Rh,Rn,Ru,Sb,Sc, Se,Sm,Sr,Ta,Tb,Tc,Te,Th,Ti,Tl,Tm,U,V,W,Xe,Y,Yb,Zr] |
| Metal_Carbon_bond | [#6;$([#6]~[#3,#11,#12,#13,#19,#20,#26,#27,#28,#29,#30])] |
| Aromatic_N-Oxide_more_than_one | [n+][O-X1].[n+][O-X1] |
| Nitro_more_than_one | [N+](=O)[O-].[N+](=O)[O-] |
| Cyano_gte_2 | [C]-[CH0]#[NH0].[C]-[CH0]#[NH0].[C]-[CH0]#[NH0] |
| Chlor_or_Fluor_gte_5 | [Br,Cl,F].[Br,Cl,F].[Br,Cl,F].[Br,Cl,F].[Br,Cl,F].[Br,Cl,F] |
| Phosphorus_More_Than_1 | P.P |
| gte_2_N_quats | [N,n;H0;+;!$(N~O);!$(n~O)].[N,n;H0;+;!$(N~O);!$(n~O)].[N,n;H0;+;!$(N~O);!$(n~O)] |
| gte_2_sulfonic_acid | [C,c]S(=O)(=O)[O;D1].[C,c]S(=O)(=O)[O;D1].[C,c]S(=O)(=O)[O;D1] |
Details presented within this documentation reproduced from:
ToxAlerts: A Web Server of Structural Alerts for Toxic Chemicals and Compounds with Potential Adverse Reactions
Iurii Sushko, Elena Salmina, Vladimir A. Potemkin, Gennadiy Poda, and Igor V. Tetko
Journal of Chemical Information and Modeling 2012 52 (8), 2310-2316
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