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# Copyright (C) 2002 Rational Discovery LLC
#Code Description SMARTS MOE_SMARTS Notes
##########
# Oxygens
##########
fr_C=O "Number of carbonyl O" [CX3]=[OX1] C=O "Includes carboxylic acids, esters, amides, etc."
fr_C=O_noCOO "Number of carbonyl O, excluding COOH" [C!$(C-[OH])]=O [C!$(C-[OH])]=O "Excludes COOH but not COO- (assumes no formal charge) hydroxyls. Includes esters, amides, etc."
fr_Al_OH "Number of aliphatic hydroxyl groups" [C!$(C=O)]-[OH] [C!$(C=O)]-[OH] "Excludes COOH but not COO- (assumes no formal charge) hydroxyls"
fr_Ar_OH "Number of aromatic hydroxyl groups" c[OH1] c[OH1]
fr_methoxy "Number of methoxy groups -OCH3" [OX2](-[#6])-[CH3] O(-[#6])-CH3 "Aliphatic. Includes esters. Includes OMe groups on aromatic rings."
fr_oxime "Number of oxime groups" [CX3]=[NX2]-[OX2] C=N-O
fr_ester "Number of esters" [#6][CX3](=O)[OX2H0][#6] C(=O)O-C
fr_Al_COO "Number of aliphatic carboxylic acids" C-C(=O)[O;H1,-] "C-C(=O)[OH] or C-C(=O)[O-]"
fr_Ar_COO "Number of Aromatic carboxylic acide" c-C(=O)[O;H1,-] "c-C(=O)[OH] or c-C(=O)[O-]"
fr_COO "Number of carboxylic acids" [#6]C(=O)[O;H,-1] "[#6]C(=O)[OH] or [#6]C(=O)[O-]"
fr_COO2 "Number of carboxylic acids" [CX3](=O)[OX1H0-,OX2H1] "[#6]C(=O)[OH] or [#6]C(=O)[O-]"
fr_ketone "Number of ketones" [#6][CX3](=O)[#6]
fr_ether "Number of ether oxygens (including phenoxy)" [OD2]([#6])[#6]
fr_phenol "Number of phenols" [OX2H]-c1ccccc1
fr_aldehyde "Number of aldehydes" [CX3H1](=O)[#6]
############
# Nitrogens
############
fr_quatN "Number of quarternary nitrogens" [$([NX4+]),$([NX4]=*)] [NX4]
fr_NH2 "Number of Primary amines" [NH2,nH2] [NH2] "Include aromatic Ns"
fr_NH1 "Number of Secondary amines" [NH1,nH1] "[NH1] or [nH1]"
fr_NH0 "Number of Tertiary amines" [NH0,nH0] "[NH0] or [nH0]"
fr_Ar_N "Number of aromatic nitrogens" n n
fr_Ar_NH "Number of aromatic amines" [nH]
fr_aniline "Number of anilines" c-[NX3]
fr_Imine "Number of Imines" [Nv3](=C)-[#6] [Nv3](=C)-[#6] "Aliphatic. Excludes aromatic sp2 nitrogens."
fr_nitrile "Number of nitriles" [NX1]#[CX2] C#N
fr_hdrzine "Number of hydrazine groups" [NX3]-[NX3] [NX3]-[NX3] "Includes primary, secondary hydrazines, carbazides, cyclic hydrazines. Excludes hydrazones"
fr_hdrzone "Number of hydrazone groups" C=N-[NX3] C=N-[NX3] "Includes cyclic hydrazones"
fr_nitroso "Number of nitroso groups, excluding NO2" [N!$(N-O)]=O [N!$(N-O)]=O "Includes N-N=O"
fr_N-O "Number of hydroxylamine groups" [N!$(N=O)](-O)-C [N!$(N=O)](-O)-C
fr_nitro "Number of nitro groups" [$([NX3](=O)=O),$([NX3+](=O)[O-])][!#8] N(=O)(O)[#6]
#fr_nitro "Number of nitro groups" N(=O)(O)[#6] N(=O)(O)[#6]
fr_azo "Number of azo groups" [#6]-N=N-[#6] [#6]-N=N-[#6] "Both nitrogens must be attached to a C. Excludes azides."
fr_diazo "Number of diazo groups" [N+]#N [N+]#N
fr_azide "Number of azide groups" [$(*-[NX2-]-[NX2+]#[NX1]),$(*-[NX2]=[NX2+]=[NX1-])] [#6]-N=[N+]=[N-]
fr_amide "Number of amides" C(=O)-N C(=O)-N "Any amide"
fr_priamide "Number of primary amides" C(=O)-[NH2] C(=O)-[NH2]
fr_amidine "Number of amidine groups" C(=N)(-N)-[!#7] C(=N)(-N)-[!#7] "Excludes guanidine"
fr_guanido "Number of guanidine groups" C(=N)(N)N C(=N)(N)N
fr_Nhpyrrole "Number of H-pyrrole nitrogens" [nH] [nH]
fr_imide "Number of imide groups" N(-C(=O))-C=O N(-C(=O))-C=O
fr_isocyan "Number of isocyanates" N=C=O N=C=O
fr_isothiocyan "Number of isothiocyanates" N=C=S N=C=S
fr_thiocyan "Number of thiocyanates" S-C#N S-C#N
###########
# Halogens
###########
fr_halogen "Number of halogens" [#9,#17,#35,#53] "F or I or Cl or Br"
fr_alkyl_halide "Number of alkyl halides" [CX4]-[Cl,Br,I,F]
##########
# Sulfurs
##########
fr_sulfide "Number of thioether" [SX2](-[#6])-C [SLp2](-[#6])-C "Aliphatic. Excludes sulfones, etc. Includes SMe groups on aromatic rings."
fr_SH "Number of thiol groups" [SH] [SH]
fr_C=S "Number of thiocarbonyl" C=[SX1] C=S "Includes thioamides, thioureas, etc."
fr_sulfone "Number of sulfone groups" S(=,-[OX1;+0,-1])(=,-[OX1;+0,-1])(-[#6])-[#6] "S(=O)(=O)(-[#6])-[#6] or S(-[O-])(-[O-])(-[#6])-[#6]" "Or charged form. Excludes sulfonamides, sulfonyl Cl, etc.."
fr_sulfone "Number of sulfone groups" S(=,-[OX1;+0,-1])(=,-[OX1;+0,-1])(-[#6])-[#6] "S(=O)(=O)(-[#6])-[#6] or S(-[O-])(-[O-])(-[#6])-[#6]" "Or charged form. Excludes sulfonamides, sulfonyl Cl, etc.."
fr_sulfonamd "Number of sulfonamides" N-S(=,-[OX1;+0,-1])(=,-[OX1;+0,-1])-[#6] "N-S(=O)(=O)-[#6] or N-S(-[O-])(-[O-])-[#6]" "Any sulfonamide"
fr_prisulfonamd "Number of primary sulfonamides" [NH2]-S(=,-[OX1;+0;-1])(=,-[OX1;+0;-1])-[#6] "[NH2]-S(=O)(=O)-[#6] or [NH2]-S(-[O-])(-[O-])-[#6]"
##################################
# Miscellaneous Functional Groups
##################################
fr_barbitur "Number of barbiturate groups" C1C(=O)NC(=O)NC1=O C1C(=O)NC(=O)NC1=O
fr_urea "Number of urea groups" C(=O)(-N)-N C(=O)(-N)-N "Includes cyclic ureas, hydroxyureas, barbiturates, etc."
fr_term_acetylene "Number of terminal acetylenes" C#[CH] C#[CH]
fr_imidazole "Number of imidazole rings" n1cncc1 n1cncc1 "Includes bicyclics"
fr_furan "Number of furan rings" o1cccc1 o1cccc1 "Includes bicyclics"
fr_thiophene "Number of thiophene rings" s1cccc1 s1cccc1 "Includes bicyclics"
fr_thiazole "Number of thiazole rings" c1scnc1 c1scnc1 "Includes bicyclics"
fr_oxazole "Number of oxazole rings" c1ocnc1 c1ocnc1 "Includes bicyclics"
fr_pyridine "Number of pyridine rings" n1ccccc1 n1ccccc1 "Includes bicyclics"
fr_piperdine "Number of piperdine rings" N1CCCCC1 N1CCCCC1
fr_piperzine "Number of piperzine rings" N1CCNCC1 N1CCNCC1
fr_morpholine "Number of morpholine rings" O1CCNCC1 O1CCNCC1
fr_lactam "Number of beta lactams" N1C(=O)CC1 N1C(=O)CC1
fr_lactone "Number of cyclic esters (lactones)" [C&R1](=O)[O&R1][C&R1]
#fr_intrahbonds "Number of intramolecular H-bonds (o-OH and -C=O) + (o-NH2 and -COOH) + 8-OH/NH2 in quinolones" "c1([OH])c(C(=O))aaaa1 or c1([OH])c([NH2])aaaa1 or c1([NH2])c(C(=O)[OH])aaaa1 or n1c2c([OH])cccc2ccc1 or n1c2c([NH2])cccc2ccc1" "This is just a guess and may be missing other possible examples"
fr_tetrazole "Number of tetrazole rings" c1nnnn1 c1nnnn1
fr_epoxide "Number of epoxide rings" O1CC1 O1CC1
fr_unbrch_alkane "Number of unbranched alkanes of at least 4 members (excludes halogenated alkanes)" [R0;D2][R0;D2][R0;D2][R0;D2]
fr_bicyclic "Bicyclic" [R2][R2]
fr_benzene "Number of benzene rings" c1ccccc1
#############
# Phosphates
#############
fr_phos_acid "Number of phosphoric acid groups" [$(P(=[OX1])([$([OX2H]),$([OX1-]),$([OX2]P)])([$([OX2H]),$([OX1-]),$([OX2]P)])[$([OX2H]),$([OX1-]),$([OX2]P)]),$([P+]([OX1-])([$([OX2H]),$([OX1-]),$([OX2]P)])([$([OX2H]),$([OX1-]),$([OX2]P)])[$([OX2H]),$([OX1-]),$([OX2]P)])]
fr_phos_ester "Number of phosphoric ester groups" [$(P(=[OX1])([OX2][#6])([$([OX2H]),$([OX1-]),$([OX2][#6])])[$([OX2H]),$([OX1-]),$([OX2][#6]),$([OX2]P)]),$([P+]([OX1-])([OX2][#6])([$([OX2H]),$([OX1-]),$([OX2][#6])])[$([OX2H]),$([OX1-]),$([OX2][#6]),$([OX2]P)])]
#####################
# Topliss Metabolism
#####################
fr_nitro_arom "Number of nitro benzene ring substituents" [$(c1(-[$([NX3](=O)=O),$([NX3+](=O)[O-])])ccccc1)]
#fr_nitro_arom "Number of nitro aromatic ring substituents" c-[$([NX3](=O)=O),$([NX3+](=O)[O-])]
fr_nitro_arom_nonortho "Number of non-ortho nitro benzene ring substituents" [$(c1(-[$([NX3](=O)=O),$([NX3+](=O)[O-])])ccccc1);!$(cc-!:*)]
fr_dihydropyridine "Number of dihydropyridines" [$([NX3H1]1-C=C-C-C=C1),$([Nv3]1=C-C-C=C-C1),$([Nv3]1=C-C=C-C-C1),$([NX3H1]1-C-C=C-C=C1)]
#fr_readily_oxidized "Number of readily oxidized moieties: thiols+dihydropyridines"
fr_phenol_noOrthoHbond "Number of phenolic OH excluding ortho intramolecular Hbond substituents" [$(c1(-[OX2H])ccccc1);!$(cc-!:[CH2]-[OX2H]);!$(cc-!:C(=O)[O;H1,-]);!$(cc-!:C(=O)-[NH2])]
fr_Al_OH_noTert "Number of aliphatic hydroxyl groups excluding tert-OH" [$(C-[OX2H]);!$([CX3](-[OX2H])=[OX1]);!$([CD4]-[OX2H])]
fr_benzodiazepine "Number of benzodiazepines with no additional fused rings" [c&R2]12[c&R1][c&R1][c&R1][c&R1][c&R2]1[N&R1][C&R1][C&R1][N&R1]=[C&R1]2
fr_para_hydroxylation "Number of para-hydroxylation sites" [$([cH]1[cH]cc(c[cH]1)~[$([#8,$([#8]~[H,c,C])])]),$([cH]1[cH]cc(c[cH]1)~[$([#7X3,$([#7](~[H,c,C])~[H,c,C])])]),$([cH]1[cH]cc(c[cH]1)-!:[$([NX3H,$(NC(=O)[H,c,C])])])] na "Includes benzofuran and benzimidazole"
#fr_para_hydroxylation "Number of para-hydroxylation sites" [$([cH]1[cH]cc(c[cH]1)-!:[$([OX2,$(O-[H,c,C])])]),$([cH]1[cH]cc(c[cH]1)-!:[$([NX3,$(N([H,c,C])-[H,c,C])])]),$([cH]1[cH]cc(c[cH]1)-!:[$([NX3H,$(NC(=O)[H,c,C])])])]
fr_allylic_oxid "Number of allylic oxidation sites excluding steroid dienone" [$(C=C-C);!$(C=C-C-[N,O,S]);!$(C=C-C-C-[N,O]);!$(C12=CC(=O)CCC1C3C(C4C(CCC4)CC3)CC2)]
fr_aryl_methyl "Number of aryl methyl sites for hydroxylation" [$(a-[CH3]),$(a-[CH2]-[CH3]),$(a-[CH2]-[CH2]~[!N;!O]);!$(a(:a!:*):a!:*)]
fr_Ndealkylation1 "Number of XCCNR groups" [$(N(-[CH3])-C-[$(C~O),$(C-a),$(C-N),$(C=C)]),$(N(-[CH2][CH3])-C-[$(C~O),$(C-a),$(C-N),$(C=C)])]
fr_Ndealkylation2 "Number of tert-alicyclic amines (no heteroatoms, not quinine-like bridged N)" [$([N&R1]1(-C)CCC1),$([N&R1]1(-C)CCCC1),$([N&R1]1(-C)CCCCC1),$([N&R1]1(-C)CCCCCC1),$([N&R1]1(-C)CCCCCCC1)]
fr_alkyl_carbamate "Number of alkyl carbamates (subject to hydrolysis)" C[NH1]C(=O)OC
fr_ketone_Topliss "Number of ketones excluding diaryl, a,b-unsat. dienones, heteroatom on Calpha" [$([CX3](=[OX1])(C)([c,C]));!$([CX3](=[OX1])([CH1]=C)[c,C])]
fr_ArN "Number of N functional groups attached to aromatics" [$(a-[NX3H2]),$(a-[NH1][NH2]),$(a-C(=[OX1])[NH1][NH2]),$(a-C(=[NH])[NH2])]
fr_HOCCN "Number of C(OH)CCN-Ctert-alkyl or C(OH)CCNcyclic" [$([OX2H1][CX4][CX4H2][NX3&R1]),$([OH1][CX4][CX4H2][NX3][CX4](C)(C)C)]
###############
# Toxicophores
###############
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