Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C24H20ClN5O3 |
| Molecular Weight | 461.9 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC=C(CNC(=O)C2=CC(=CN=C2C3=NC=CC=C3)C4=CN=CC(Cl)=C4)N=C1OC
InChI
InChIKey=CKTWQGHVNRYNCM-UHFFFAOYSA-N
InChI=1S/C24H20ClN5O3/c1-32-21-7-6-18(30-24(21)33-2)14-29-23(31)19-10-16(15-9-17(25)13-26-11-15)12-28-22(19)20-5-3-4-8-27-20/h3-13H,14H2,1-2H3,(H,29,31)
| Molecular Formula | C24H20ClN5O3 |
| Molecular Weight | 461.9 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
MK-1064 is an orexin 2 receptor antagonist patented by pharmaceutical company Merck & Co for the treatment of insomnia. MK-1064decreases the amount of time spent in active wake and increases the time spent in rapid eye movement (REM) sleep and slow-wave sleep (SMS) in mice, rats, dogs, and rhesus monkeys. MK-1064, even at the very high dose did not show signs of an enhanced predisposition to cataplexy in the food-elicited cataplexy test. MK-1064 has now completed two Phase I studies focused on pharmacokinetics, safety and sleep in healthy volunteers. The effects of MK-1064 on sleep parameters were moderate, but statistically significant, representing the first demonstration of PSG-quantified sleep induced in humans by an OX2R antagonist. MK-1064 at 50, 120 and 250 mg decreased latency to persistent sleep and wake after sleep onset, and increased total sleep time and sleep efficiency.
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.37 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
0.42 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
1.06 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
2.09 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
3.6 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
3.83 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
6.78 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
8.28 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.95 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
1.67 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
5.22 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
9.45 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
20.93 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
23.5 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
48.93 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
51.48 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
11.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
6.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
7.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
8.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27256922/ |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
MK-1064 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
| Substance Class |
Chemical
Created
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Edited
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| Record UNII |
O812716S9E
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| Record Status |
Validated (UNII)
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| Related Record | Type | Details | ||
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ACTIVE MOIETY |
Originator: Merck Sharp & Dohme; Class: Amide, Pyridine, Sleep disorder therapy, Small molecule
Mechanism of Action: Orexin receptor type 2 antagonist; Orphan Drug Status: No; On Fast track: No; New Molecular Entity: Yes; Highest Development Phase: No development reported for Insomnia;
Most Recent Event: No Data Available
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ACTIVE MOIETY |
This article highlights structural modifications the team utilized to drive compound design, as well as in vivo characterization of our 2-SORA clinical candidate, 5-chloro-N-((5,6-dimethoxypyridin-2-yl)methyl)-2,2:5,3-terpyridine-3-carboxamide (MK-1064), in mouse, rat, dog, and rhesus sleep models.
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