# 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 quaternary 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)]

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# Toxicophores
###############
