Online computational tool finding new active substances

[Hans Meyer]

The attachments show, cited only by way of example, pharmacological relevant data of 2 LSD-derivatives and LSD itself, obtained by the online-tool “Molinspiration” (see site MolInspiration, onlinetool (http://www.molinspiration.com/cgi-bin/properties, scripts must be allowed), and infos at active links within the documents). The results can be naturally only a first screening, but may be of trendsetting valence. Since some 5-HT-receptors are also a subgroup of the G protein-coupled receptors, GPCR, the estimated GPCR-value may be a hint of being active in that way.
The range of this dimensionless biological value GPCR (and the other parameter too) is -2(unverifiable) to +2(highest possible); supposed significant values are marked light green (>0.2) to dark green (>0.5) by that tool. This tool may be suitable designing new active molecules by comparing with known ones. Around 30 to 40 % of all prescription drugs are ligands to GPCR, so I researched. The other estimated values may also be of interest (Ion channel modulator, Kinase inhibitor, Nuclear receptor ligand, Protease inhibitor, Enzyme inhibitor). Since I really do not understand much of biochemistry, I beg your understanding for renounce from requests. Hans Meyer

(the structures can be obtained, and the other informations also, by way of inserting the SMILES into the "Molinspiration property engine".)

1.) miSMILES: [H][C@@]12Cc3c[nH]c4cccc(C1=C[C@@H](C(=O)N(CC)CC)CN2C)c34
Lysergide
Molinspiration property engine v2016.10

miLogP 2.66
TPSA 39.34
natoms 24
MW 323.44
nON 4
nOHNH 1
nviolations 0
nrotb 3
volume 313.85

Molinspiration bioactivity score v2016.03
GPCR ligand 0.93
Ion channel modulator 0.32
Kinase inhibitor 0.23
Nuclear receptor ligand -0.20
Protease inhibitor 0.12
Enzyme inhibitor 0.29



2.) miSMILES:
CN2C[C@H](CS(=O)CCCF)C=C1c3cnc(F)c4[nH]cc(C[C@H]12)c34
Molinspiration property engine v2016.10

miLogP 1.35
TPSA 48.99
natoms 25
MW 365.45
nON 4
nOHNH 1
nviolations 0
nrotb 5
volume 313.95

Molinspiration bioactivity score v2016.03
GPCR ligand 1.33
Ion channel modulator 0.59
Kinase inhibitor 0.60
Nuclear receptor ligand 0.43
Protease inhibitor 0.65
Enzyme inhibitor 0.62


3.) miSMILES:
CN2C[C@H](CS(=O)CCCF)CC1c3cnc(F)c4[nH]cc(C[C@H]12)c34
Molinspiration property engine v2016.10

miLogP 1.36
TPSA 48.99
natoms 25
MW 367.46
nON 4
nOHNH 1
nviolations 0
nrotb 5
volume 320.16

Molinspiration bioactivity score v2016.03
GPCR ligand 1.26
Ion channel modulator 0.71
Kinase inhibitor 0.69
Nuclear receptor ligand 0.40
Protease inhibitor 0.81
Enzyme inhibitor 0.63

 

[Weltmeister]

DMT:

GPCR ligand 0.04
Ion channel modulator 0.17
Kinase inhibitor -0.12
Nuclear receptor ligand -0.69
Protease inhibitor -0.52
Enzyme inhibitor -0.05

Mescaline:

GPCR ligand -0.27
Ion channel modulator -0.05
Kinase inhibitor -0.30
Nuclear receptor ligand -0.82
Protease inhibitor -0.45
Enzyme inhibitor -0.09

2C-B:

GPCR ligand -0.50
Ion channel modulator -0.49
Kinase inhibitor -0.60
Nuclear receptor ligand -0.83
Protease inhibitor -0.87
Enzyme inhibitor -0.34

Heroin:

GPCR ligand 0.81
Ion channel modulator 0.49
Kinase inhibitor -0.10
Nuclear receptor ligand 0.70
Protease inhibitor 0.37
Enzyme inhibitor 0.52

Cocaine:

GPCR ligand 0.14
Ion channel modulator 0.23
Kinase inhibitor -0.33
Nuclear receptor ligand -0.10
Protease inhibitor -0.07
Enzyme inhibitor -0.01

MXE:

GPCR ligand -0.29
Ion channel modulator 0.00
Kinase inhibitor -0.89
Nuclear receptor ligand -0.53
Protease inhibitor -0.22
Enzyme inhibitor -0.11

Psilocin:

GPCR ligand 0.11
Ion channel modulator 0.11
Kinase inhibitor -0.07
Nuclear receptor ligand -0.68
Protease inhibitor -0.59
Enzyme inhibitor 0.01

Psilocybin:

GPCR ligand 0.49
Ion channel modulator 0.33
Kinase inhibitor 0.46
Nuclear receptor ligand 0.12
Protease inhibitor 0.13
Enzyme inhibitor 0.46

Methamphetamine:

GPCR ligand -0.36
Ion channel modulator -0.25
Kinase inhibitor -1.04
Nuclear receptor ligand -1.27
Protease inhibitor -0.54
Enzyme inhibitor -0.31

Ampehetamine:

GPCR ligand -0.45
Ion channel modulator -0.16
Kinase inhibitor -0.83
Nuclear receptor ligand -1.28
Protease inhibitor -0.59
Enzyme inhibitor -0.27

Caffeine:

GPCR ligand -0.53
Ion channel modulator -0.98
Kinase inhibitor -1.07
Nuclear receptor ligand -2.10
Protease inhibitor -1.23
Enzyme inhibitor -0.22

Ethanol:

GPCR ligand -3.81
Ion channel modulator -3.79
Kinase inhibitor -3.84
Nuclear receptor ligand -3.72
Protease inhibitor -3.77
Enzyme inhibitor -3.76

 

[Hans Meyer]

DMT:

Hi Weltmeister
these values does not exactly inspire confidence. etOH is completely inappropriate (normal range is -2 to +2).
It is really a pity, I fear we can forget that tool. Ligands for 5HT-receptors seem not beeing predicted in any case. What a shame!

PS. 20-08-2017: The procedure of bioactivity calculation can be seen here:
http://molinspiration.com/docu/miscreen/druglikeness.html
http://molinspiration.com/docu/miscreen/virtualscreening.html
Here you can find the reason why it not always fits the reality: it is simply the sum of active fragments contributions which themselves derives from a training set with small substructures.
It works not so well for small molecules with substructures that are sometimes active and sometimes not active.
The normal range is -2 to +2. In rare exceptions it can be < -2, it is the case when the molecule range into a unnormal uncertainty.