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Medchem design moves for generating new compounds

This repository contains a python library for exploring the medicinal chemistry design moves, as reported in publication: "The playbook of Medicinal Chemistry Design Moves, xxx-xxx-xxx" The library is adpated from original mmpdb code

Dependency

python >=3
rdkit

Dataset

please download the design moves (transformation) dataset from here. We provide the design moves from ChEMBL database at radius 3.

How to run programm

python mmpdb mmpCompoundGenerator  --tsmiles "O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N" --transformation_db "chemblDB3.sqlitdb" --replaceGroup "*S(=O)(=O)(N)" --tradius 3 --toutput output.txt --tmin-pairs 100

Output

original_smi	transformed_smi	original_frag	new_frag	rule_freq	ex_lhs_cpd_id	ex_rhs_cpd_id
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccccc2)cc1	[*]S(N)(=O)=O	[*:1][H]	1103	CHEMBL51385	CHEMBL1201104
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	COc1ccc(-n2nc(C(F)(F)F)cc2-c2ccc(C)cc2)cc1	[*]S(N)(=O)=O	[*:1]OC	607	CHEMBL51385	CHEMBL8441
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(Cl)cc2)cc1	[*]S(N)(=O)=O	[*:1]Cl	523	CHEMBL51385	CHEMBL462
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(S(C)(=O)=O)cc2)cc1	[*]S(N)(=O)=O	[*:1]S(C)(=O)=O	497	CHEMBL468367	CHEMBL507789
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(F)cc2)cc1	[*]S(N)(=O)=O	[*:1]F	491	CHEMBL3426428	CHEMBL3426432
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(C)cc2)cc1	[*]S(N)(=O)=O	[*:1]C	408	CHEMBL51385	CHEMBL274877
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(C(=O)O)cc2)cc1	[*]S(N)(=O)=O	[*:1]C(=O)O	275	CHEMBL1966874	CHEMBL2094690
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(N+[O-])cc2)cc1	[*]S(N)(=O)=O	[*:1]N+[O-]	265	CHEMBL51385	CHEMBL8682
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(O)cc2)cc1	[*]S(N)(=O)=O	[*:1]O	255	CHEMBL3632832	CHEMBL1341020
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(C(N)=O)cc2)cc1	[*]S(N)(=O)=O	[*:1]C(N)=O	215	CHEMBL3901141	CHEMBL3973258
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(Br)cc2)cc1	[*]S(N)(=O)=O	[*:1]Br	205	CHEMBL51385	CHEMBL450762
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(C#N)cc2)cc1	[*]S(N)(=O)=O	[*:1]C#N	193	CHEMBL3426428	CHEMBL3426430
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	CC(=O)Nc1ccc(-n2nc(C(F)(F)F)cc2-c2ccc(C)cc2)cc1	[*]S(N)(=O)=O	[*:1]NC(C)=O	170	CHEMBL1490019	CHEMBL1716793
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	CC(=O)c1ccc(-n2nc(C(F)(F)F)cc2-c2ccc(C)cc2)cc1	[*]S(N)(=O)=O	[*:1]C(C)=O	152	CHEMBL2163818	CHEMBL1206418
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	CCOc1ccc(-n2nc(C(F)(F)F)cc2-c2ccc(C)cc2)cc1	[*]S(N)(=O)=O	[*:1]OCC	141	CHEMBL2163818	CHEMBL1206420
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(C(F)(F)F)cc2)cc1	[*]S(N)(=O)=O	[*:1]C(F)(F)F	137	CHEMBL51385	CHEMBL501107
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	COC(=O)c1ccc(-n2nc(C(F)(F)F)cc2-c2ccc(C)cc2)cc1	[*]S(N)(=O)=O	[*:1]C(=O)OC	136	CHEMBL3695775	CHEMBL3695774
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	CCOC(=O)c1ccc(-n2nc(C(F)(F)F)cc2-c2ccc(C)cc2)cc1	[*]S(N)(=O)=O	[*:1]C(=O)OCC	132	CHEMBL285831	CHEMBL241971
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(N)cc2)cc1	[*]S(N)(=O)=O	[*:1]N	126	CHEMBL51385	CHEMBL463
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(N3CCOCC3)cc2)cc1	[*]S(N)(=O)=O	[*:1]N1CCOCC1	114	CHEMBL3679534	CHEMBL3679542
O=S(=O)(c3ccc(n1nc(cc1c2ccc(cc2)C)C(F)(F)F)cc3)N	Cc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(N(C)C)cc2)cc1	[*]S(N)(=O)=O	[*:1]N(C)C	108	CHEMBL3695775	CHEMBL3695770

note that output file contains more columns than shown above. For clearity only main columns are shown.

Input Options

parameter	meaning
--transformation_db	transformation database file
--tsmiles	input query molecule (in smiles format)
--replaceGroup	fragment to be replace in a query molecule (in smiles format). Note that it must contains * or [] to indicate attachment point. 1) single cut example N1CCOCC1, 2) double cut example N1CCOC()C1
--tradius	chemical envionment radius for design move. It must equal to radius of the transformation database. So in this case 3.
--toutput	name of output text file
--tmin-pairs	consider design moves that have at-least tmin-pairs examples. This is in other words the freqency of a design move. For instacne if we set tmin-pairs to 5: it say that consider all design moves that are derived from at-least five MMP pairs.

Output Columns Explanation

column	meaning
original_smi	smiles of a query molecule
transformed_smi	a new design molecule
constant_smi	smiles of constant part i.e. part which did not change
original_frag	fragment in a query to replace
new_frag	new suggested fragment
envsmi	chemical environment of replacementi (design move)
rule_freq	frequency of design move (transformation)
ex_lhs_cpd_id	an example of MMP (left hand compound id) from ChEMBL
ex_rhs_cpd_id	an example of MMP (right hand compound id) from ChEMBL