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Compound Detail

CHEMBL267014

L-745870
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Clc1ccc(N2CCN(Cc3c[nH]c4ncccc34)CC2)cc1

Basic Information

ChEMBL ID CHEMBL267014
Name L-745870
Phase Preclinical
Structure Type MOL
InChI Key OGJGQVFWEPNYSB-UHFFFAOYSA-N
19
Targets
98
Activities
3
Assay Types
9
PK Parameters
20
Publications
0
Known Names

Molecular Properties

326.8
MW (Da)
3.54
ALogP
3
HBA
1
HBD
35.2
PSA (Ų)
0.80
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula C18H19ClN4
MW 326.83
Aromatic Rings 3
Heavy Atoms 23
NP-Likeness -1.76

Activity Summary

Ki 90 meas. best 9.4
IC50 6 meas. best 7.37
EC50 2 meas. best 7.57

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
D(4) dopamine receptor
CHEMBL219
Ki 9.4 9.1518 0.4 22
Unchecked
CHEMBL612545
Ki 9.37 6.8264 0.4 14
D(4) dopamine receptor
CHEMBL3361
Ki 9.37 8.9 0.4 2
D(4) dopamine receptor
CHEMBL219
EC50 7.57 6.61 27.0 2
D(4) dopamine receptor
CHEMBL219
IC50 7.37 6.748 42.7 5
Sigma non-opioid intracellular receptor 1
CHEMBL287
Ki 7.0 6.9633 100.0 3
Alpha-2B adrenergic receptor
CHEMBL1942
Ki 6.8 6.8 160.0 1
Alpha-2A adrenergic receptor
CHEMBL1867
Ki 6.77 6.77 170.0 1
5-hydroxytryptamine receptor 2A
CHEMBL224
Ki 6.7 6.52 200.0 2
Serotonin 2 (5-HT2) receptor
CHEMBL2095200
Ki 6.7 6.7 200.0 1
5-hydroxytryptamine receptor 7
CHEMBL3155
Ki 6.64 6.64 226.3 1
Alpha-2C adrenergic receptor
CHEMBL1916
Ki 6.64 6.64 230.0 1
D(3) dopamine receptor
CHEMBL234
Ki 6.42 5.3 380.2 12
D(2) dopamine receptor
CHEMBL217
Ki 6.35 5.3671 448.0 21
5-hydroxytryptamine receptor 6
CHEMBL3371
Ki 5.78 5.78 1656.2 1
Alpha-1A adrenergic receptor
CHEMBL229
Ki 5.66 5.66 2200.0 1
Alpha-1B adrenergic receptor
CHEMBL232
Ki 5.54 5.54 2900.0 1
D(2) dopamine receptor
CHEMBL3998
Ki 5.21 5.21 6100.0 1
5-hydroxytryptamine receptor 1A
CHEMBL214
Ki 5.18 5.145 6620.9 2
Voltage-gated L-type calcium channel
CHEMBL2095229
IC50 5.05 5.05 9000.0 1
D(1A) dopamine receptor
CHEMBL2967
Ki 5.0 5.0 9900.0 3

Pharmacokinetic Data

Parameter Value Units Species
F 66.0 % Rattus norvegicus
F 20.0 % Macaca mulatta
F 66.0 % Rattus norvegicus
F 20.0 % Macaca mulatta
T1/2 3.0 hr Rattus norvegicus
T1/2 2.1 hr Rattus norvegicus
T1/2 2.1 hr Rattus norvegicus
T1/2 2.8 hr Macaca mulatta
T1/2 2.8 hr Macaca mulatta

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
D(4) dopamine receptor Ki = 0.4 nM 9.4 Binding affinity against human Dopamine receptor D4 by [3H]-spiperone displaceme... 15084133
D(4) dopamine receptor Ki = 0.43 nM 9.37 Displacement of [3H]-spiperone from human D4 receptor expressed in HEK293 cells ... 33422983
D(4) dopamine receptor Ki = 0.43 nM 9.37 Inhibition of human dopamine D4 receptor 28489950
Unchecked Ki = 0.43 nM 9.37 Inhibition of human dopamine D4.4 receptor 28489950
D(4) dopamine receptor Ki = 0.43 nM 9.37 Binding affinity towards human dopamine receptor D4 11170639
D(4) dopamine receptor Ki = 0.43 nM 9.37 Binding affinity towards cloned human Dopamine receptor D4 stably expressed in C... 8642550
D(4) dopamine receptor Ki = 0.43 nM 9.37 In vitro binding affinity to human Dopamine receptor D4 11378358
D(4) dopamine receptor Ki = 0.43 nM 9.37 In vitro binding affinity was measured at the cloned human Dopamine receptor D4.... 9822559
D(4) dopamine receptor Ki = 0.43 nM 9.37 Ability to displace [3H]spiperone from cloned human dopamine D4 receptor stably ... 10098669
D(4) dopamine receptor Ki = 0.43 nM 9.37 Displacement of [125I]DOI from human dopamine D4 receptor by liquid scintillatio... 19155177
D(4) dopamine receptor Ki = 0.43 nM 9.37 Displacement of [3H]N-methylspiperone from rat dopamine D4 receptor by PDSP assa... 24800940
D(4) dopamine receptor Ki = 0.5495 nM 9.26 Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane 36283180
D(4) dopamine receptor Ki = 0.6 nM 9.22 Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane 36283180
D(4) dopamine receptor Ki = 0.6 nM 9.22 Binding affinity evaluated for the displacement of [3H]spiperone against human d... 9990464
D(4) dopamine receptor Ki = 0.62 nM 9.21 In vitro binding affinity at human cloned dopamine receptor D4 stably expressed ... 11844688
D(4) dopamine receptor Ki = 0.62 nM 9.21 Displacement of [3H]spiroperidol from human cloned dopamine D4.4 receptor expres... 19481941
D(4) dopamine receptor Ki = 0.6166 nM 9.21 Displacement of [3H]spiperone from human dopamine D4.4 expressed in CHO cell mem... 17266201
D(4) dopamine receptor Ki = 0.7 nM 9.15 Displacement of [3H] Spiperone from human D4.4 receptor expressed in CHO cells b... 31613617
D(4) dopamine receptor Ki = 0.91 nM 9.04 In vitro binding affinity at human dopamine D4 receptor expressed in CHO cells b... 9873377
D(4) dopamine receptor Ki = 0.91 nM 9.04 Binding affinity at Dopamine receptor D4 in CHO cells by radioligand displacemen... 10602703

Literature References

PubMed DOI Target Context # Activities
29051383 10.1126/science.aan5468 Unchecked 12
11170639 10.1021/jm0002432 Rodentia sp. 8
36098685 10.1021/acs.jmedchem.2c00840 D(4) dopamine receptor 7
29589445 10.1021/acs.jmedchem.8b00265 D(4) dopamine receptor 5
28489950 10.1021/acs.jmedchem.7b00151 Unchecked 5
16789750 10.1021/jm060166w Rattus norvegicus 4
15084133 10.1021/jm0305669 D(4) dopamine receptor 3
28489950 10.1021/acs.jmedchem.7b00151 Rattus norvegicus 3
11844688 10.1016/s0960-894x(01)00814-9 D(4) dopamine receptor 3
28489950 10.1021/acs.jmedchem.7b00151 Rhesus monkey 3
31613617 10.1021/acs.jmedchem.9b01085 Unchecked 3
11378358 10.1016/s0960-894x(01)00241-4 D(4) dopamine receptor 2
11378358 10.1016/s0960-894x(01)00241-4 Muscarinic acetylcholine receptor M2 2
11844688 10.1016/s0960-894x(01)00814-9 D(2) dopamine receptor 2
19481941 10.1016/j.bmc.2009.05.015 D(2) dopamine receptor 2
31613617 10.1021/acs.jmedchem.9b01085 D(2) dopamine receptor 2
36098685 10.1021/acs.jmedchem.2c00840 Unchecked 2
11170639 10.1021/jm0002432 ADMET 2
29051383 10.1126/science.aan5468 D(2) dopamine receptor 2
36283180 10.1016/j.ejmech.2022.114840 Sigma non-opioid intracellular receptor 1 2

Data from ChEMBL 36 via Core Engine