# SMARTS search

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](http://www.daylight.com/dayhtml/doc/theory/theory.smarts.html) 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](http://ochem.eu/home/show.do) 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               | <p>\[Ac,Ag,Am,Ar,As,At,Au,Ba,Be,Bi,Bk,Cd,Ce,Cf,Cm,Cr,Cs,Dy,Er,<br>Eu,Fr,Ga,Gd,Ge,He,Hf,Ho,In,Ir,Kr,La,Lu,Mo,Nb,Nd,Ne,Ni,<br>Np,Os,Pa,Pb,Pd,Pm,Po,Pr,Pt,Pu,Ra,Rb,Re,Rh,Rn,Ru,Sb,Sc,<br>Se,Sm,Sr,Ta,Tb,Tc,Te,Th,Ti,Tl,Tm,U,V,W,Xe,Y,Yb,Zr]</p> |
| 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](http://pubs.acs.org/doi/pdf/10.1021/ci300245q)


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