#/**********************************************************************
#Copyright (C) 2000-2007, 2010 by OpenEye Scientific Software, Inc.
#***********************************************************************/
MIN_MOLWT      0
MAX_MOLWT      350
MIN_NUM_HVY    0
MAX_NUM_HVY    15

#count ring degrees of freedom = (#BondsInRing) - 4 - (RigidBondsInRing) - (BondsSharedWithOtherRings)
#must be >= 0, from JCAMD 14:251-265,2000.
ADJUST_ROT_FOR_RING     true      "BOOLEAN for whether to estimate degrees of freedom in rings"

MIN_ROT_BONDS    0      "Minimum number of rotatable bonds"
MAX_ROT_BONDS    12      "Maximum number of rotatable bonds"

MIN_UNBRANCHED   0      "Minimum number of connected unbranched non-ring atoms"
MAX_UNBRANCHED   6      "Maximum number of connected unbranched non-ring atoms"

MIN_UNBRANCHED_C 0      "Minimum number of connected unbranched non-ring carbon"
MAX_UNBRANCHED_C 6      "Maximum number of connected unbranched non-ring carbon"

MIN_HBOND_DONORS  0      "Minimum number of hydrogen-bond donors"    
MAX_HBOND_DONORS  10     "Maximum number of hydrogen-bond donors"    

MIN_HBOND_ACCEPTORS  0      "Minimum number of hydrogen-bond acceptors"    
MAX_HBOND_ACCEPTORS  10     "Maximum number of hydrogen-bond acceptors"    

MIN_COUNT_FORMAL_CRG    0      "Minimum number formal charges"
MAX_COUNT_FORMAL_CRG    4      "Maximum number of formal charges"

MIN_SUM_FORMAL_CRG   -2      "Minimum sum of formal charges"
MAX_SUM_FORMAL_CRG    2      "Maximum sum of formal charges"

MIN_CHIRAL_CENTERS   0   "Minimum chiral centers"
MAX_CHIRAL_CENTERS   8   "Maximum chiral centers"

ALLOWED_ELEMENTS  *,H,C,N,O,F,S,Cl,Br,I #No P!
ELIMINATE_METALS Sc,Ti,V,Cr,Mn,Fe,Co,Ni,Cu,Zn,Y,Zr,Nb,Mo,Tc,Ru,Rh,Pd,Ag,Cd

#specific, undesirable functional groups

RULE  1  quinone
RULE  0  pentafluorophenyl_esters
RULE  0  paranitrophenyl_esters
RULE  0  HOBT_esters
RULE  0  triflates
RULE  0  lawesson_s_reagent
RULE  0  phosphoramides
RULE  1  beta_carbonyl_quat_nitrogen
NEWRULE acylhydrazide 1 [N;R0;$(*[!a&!#1])][N;R0]C(=O)
#RULE  1  acylhydrazide
RULE  0  cation_C_Cl_I_P_or_S
RULE  0  alkyl_phosphate
RULE  1  phosphinic_acid
RULE  1  phosphanes
RULE  0  phosphoranes
RULE  0  imidoyl_chlorides
RULE  0  nitroso
RULE  0  N_P_S_Halides
RULE  0  carbodiimide
RULE  0  isonitrile
RULE  0  triacyloxime
RULE  0  cyanohydrins
RULE  0  acyl_cyanides
RULE  0  sulfonylnitrile
RULE  0  phosphonylnitrile
RULE  0  azocyanamides
RULE  0  beta_azo_carbonyl
RULE  2  polyenes
RULE  0  saponin_derivatives
RULE  1  cytochalasin_derivatives
RULE  4  cycloheximide_derivatives
RULE  1  monensin_derivatives
RULE  1  squalestatin_derivatives

#functional groups which often eliminate compounds from consideration
RULE  0  azide
RULE  1  azo
RULE  0  aldehyde
RULE  0  phosphonic_acid
RULE  0  phosphonic_ester
RULE  0  phosphoric_acid
RULE  0  phosphoric_ester
RULE  0  phosphoryl

RULE  0  acid_halide
RULE  6  alkyl_halide
RULE  0  anhydride
RULE  2  di_peptide
RULE  1  michael_acceptor
RULE  0  beta_halo_carbonyl
RULE  3  nitro
RULE  0  oxygen_cation
RULE  0  peroxide
RULE  1  sulfonic_acid
RULE  0  sulfonic_ester
RULE  0  tricarbo_phosphene
RULE  1  epoxide
RULE  0  sulfonyl_halide
RULE  0  halopyrimidine
RULE  0  perhalo_ketone
RULE  0  aziridine
RULE  1  oxalyl
RULE  0  alphahalo_amine 
RULE  0  halo_amine 
RULE  1  halo_alkene
RULE  0  acyclic_NCN
RULE  0  acyclic_NS
RULE  0  SCN2
RULE  0  terminal_vinyl
RULE  0  hetero_hetero
RULE  1  hydrazine
RULE  0  N_methoyl
RULE  2  NS_beta_halothyl
RULE  0  propiolactones
RULE  0  iodoso
RULE  0  iodoxy
RULE  1  noxide


#functional groups which are allowed, but may not be wanted in high quantities
#common functional groups

RULE  6  alcohol
RULE  5  alkene
RULE  4  amide
RULE  4  amino_acid
RULE  3  amine
RULE  4  primary_amine
RULE  4  secondary_amine
RULE  4  tertiary_amine
RULE  2  carboxylic_acid
RULE  6  halide
RULE  4  iodine
RULE  3  ketone
RULE  4  phenol
RULE  2  imine
RULE  1  methyl_ketone
RULE  1  alkylaniline
RULE  4  sulfonamide 
RULE  1  sulfonylurea 
RULE  0  phosphonamide 
RULE  1  alphahalo_ketone
RULE  0  oxaziridine
RULE  2  cyclopropyl
RULE  2  guanidine
RULE  0  sulfonimine
RULE  0  sulfinimine
RULE  1  hydroxamic_acid
RULE  0  sulfinylthio
RULE  0  disulfide
RULE  0  enol_ether
RULE  2  enamine
RULE  0  organometallic
RULE  1  dithioacetal
RULE  1  oxime
RULE  0  isothiocyanate
RULE  0  isocyanate
RULE  3  lactone
RULE  3  lactam
RULE  1  thioester
RULE  2  carbonate
RULE  2  carbamic_acid
RULE  1  thiocarbamate
RULE  1  triazine
RULE  1  malonic

#other functional groups

RULE  2  alkyne
RULE  4  aniline
RULE  4  aryl_halide
RULE  2  carbamate
RULE  3  ester
RULE  6  ether
RULE  1  hydrazone
RULE  1  nonacylhydrazone
RULE  1  hydroxylamine
RULE  2  nitrile
RULE  3  sulfide
RULE  2  sulfone
RULE  2  sulfoxide
RULE  1  thiourea
RULE  1  thioamide
RULE  2  thiol
RULE  2  urea

RULE  0  hemiketal 
RULE  0  hemiacetal
RULE  0  ketal
RULE  0  acetal
NEWRULE aminal 0 [C;$(*(-[O!$(**=O)][#6])-[N!$(**=O)][#6]);!$(*=*)]
#RULE  0  aminal
NEWRULE hemiaminal 0 [C;$(*(-[O;!$(*([!#1])[!#1])])-[N!$(**=O)][#6]);!$(*=*)]
#RULE  0  hemiaminal
NEWRULE labile 0 [R;O,N,S;!$(*=O)]@[R;O,N,S;!$(*=O)]

#protecting groups

RULE  1  benzyloxycarbonyl_CBZ
RULE  1  t_butoxycarbonyl_tBOC
RULE  0  fluorenylmethoxycarbonyl_Fmoc
RULE  1  dioxolane_5MR
RULE  1  dioxane_6MR
RULE  1  tetrahydropyran_THP
RULE  1  methoxyethoxymethyl_MEM
RULE  2  benzyl_ether
RULE  2  t_butyl_ether
RULE  0  trimethylsilyl_TMS
RULE  0  t_butyldimethylsilyl_TBDMS
RULE  0  triisopropylsilyl_TIPS
RULE  0  t_butyldiphenylsilyl_TBDPS
RULE  1  phthalimides_PHT
RULE  2  arenesulfonyl

#additional crap

NEWRULE noattachment 0 [!#0;!$(*.[#0])]
NEWRULE attach 3 [#0]
NEWRULE S 1 [#16]
#NEWRULE P 1 [#15]
#NEWRULE SnPn 1 [#15,#16]
#NEWRULE SP 0 [#15,#16]~[#15,#16]
NEWRULE HalX2 0 [#9,#17,#35,#53](~*)~*
NEWRULE UnsatHal 0 *=*[#9,#17,#35,#53]
NEWRULE F 3 [#9]
NEWRULE Fbad1 0 [#9;!$(*-C-[#9]);!$(*-c)]
NEWRULE Fbad2 0 [#9;$(*-c.[#9]),$(*-C[#9].[#9!$(*-C-[#9])])]
NEWRULE Cl 2 [#17]
NEWRULE FCl 0 [#9;$(*.[#17])]
NEWRULE Br 0 [#35]
NEWRULE I 0 [#53]
NEWRULE O 3 [#8]
NEWRULE O3 0 [#8]~[#8]~[#8]
NEWRULE N3 0 N~N~N
#NEWRULE B 0 [#5]
NEWRULE aliHH 0 [R;O,N,S;!$(*=O)]@[R;O,N,S;!$(*=O)]
NEWRULE stereo 0 [@;$(*.[@].[@].[@]),$([R0].[R0@].[R0@])]
NEWRULE SCN 0 SC-,=,#[N!$(NC=[!#6])]
NEWRULE N-N 0 [#6]-[NH2]-[N;X4H3,X3H2]
NEWRULE N=N 0 [#6;#0]-[NH]=[NH]-[#6,#0]
NEWRULE alkylBrI 0 C[Br,I]
NEWRULE n+N 0 [n+]-N
NEWRULE CN#N 0 C=N=,#N
NEWRULE unsat 0 [CR0]=[CR0]-[CR0]=[CR0]
NEWRULE hydrazineimine 0 [C;$(*=O),$(*-[#6])]NN=C
NEWRULE guanamidine 0 N~[CR0]~N~[CR0](~N)~N
NEWRULE terminalSulf 0 [S;H1-0,H0-1;$(*-,=O)]
NEWRULE badSulfur1 0 [S;!$(S-,=[O;-0H0,-1H0]);!$(S([#6,#0])[#6,#0]);!$([SR])]
NEWRULE badSulfur2 0 [S;$(S-C=*),$(S=[#6,#7]),$([S+0](*)(O)(O)O*),$(S(*)(N)(N)*)]
NEWRULE badSulfur3 0 [S;$(*[Sv4](=O)N*)]
NEWRULE NN 0 [N;!$(*(-N)-[!#1!#6!#0])]-,=[N!$(*(-N)-[!#1!#6!#0])]
NEWRULE COO 0 [C;$(*(-[OH1,OH0-1])-[OH1,OH0-1])]
NEWRULE CNNN 0 C(-N)(-N)-N
NEWRULE CNNO 0 C(-N)(-N)-O
NEWRULE nitroplus1 0 *N(=O)O*
NEWRULE nitroplus2 0 *[N+]([O-])O*
NEWRULE nitroextra1 0 *N(=O)C(=O)*
NEWRULE nitroextra2 0 *[N+]([O-])C(=O)*
NEWRULE badamide 0 *N=[CR0]([!#1])[O;H1,H0-1]
NEWRULE terminalester 0 *O[CH1]=O
#OOC
NEWRULE OO 0 [O]~[O] 
NEWRULE OS 0 [S]~[O]~[!#1] 
#[CH2][CH2][CH2][CH2,H3] 0
NEWRULE Cboring 0 [CR0H2][CH2][CH2][CH2][CH2,CH3] 
#*ON=C #*ON(C)C #*O[N+]=C
NEWRULE ON 0 O-[N;!$(*C=O);!$(*=O)] 
NEWRULE ONcarb 0 O=CN-OC=O
NEWRULE nonCHal 0 [!#6;!#0]-[#9,#17,#35,#53]
#C=C(N)NR 
NEWRULE CCNN 0 C=C([N;!$(*C=O)])[N;!$(*C=O)]  
# anilinicNCN  #should hit aminal

#questionable CC=N[OH]
#             CC=NOC
#             c1SNC(=O)c1

#odd rings
#more than 1 3 member ring
NEWRULE threemember 1 *~1~*~*1
#arom 3,4 member
NEWRULE arom3member 0 a1aa1
NEWRULE arom4member 0 a:1:a:a:a1
#unsat 3,4 member ring
NEWRULE unsat3member 0 *~1~*=,#,:*1
NEWRULE unsat4member 0 *~1~*=,#,:*~*1
NEWRULE exounsat3member 0 *=,#*~1~*~*1
#charged 3,4 member
NEWRULE crg3member 0 *~1~[!+0]~*1
NEWRULE crg4member 0 *~1~[!+0]~*~*1
#1.1.1 bicyclo 
NEWRULE bicyclo111 0 *~1~2~*~*(~*1)~*2 
#fused 3,3
NEWRULE tritri 0 *~1~*~2~*1~*2
#fused 3,4
NEWRULE triquad 0 *~1~*~2~*1~*~*2
#fused 4,4
NEWRULE quadquad 0 *~1~*~*~2~*1~*~*2
#poly-fused aromatics
NEWRULE a3 0 [aR3]:[aR3](:[aR3]):[aR3] 
#spiro 3,[anything]
NEWRULE spiro3any 0 *~1~*(@*)(@*)~*1
#fusion 3,[anything>3]
NEWRULE fusion3any 0 *~1~*(@*)~*(@*)1
#3-3
NEWRULE tribondtri 0 *~1~*~*1~*~2~*~*2
#non o,c,n 3 or 4 member ring
NEWRULE nonnco3member 0 [!#6;!#7;!#8]~1~*~*1
NEWRULE nonnco4member 0 [!#6;!#7;!#8]~1~*~*~*1
#ring triple bond
NEWRULE cyclictriple 0 *#@*