|
|
CCC#CC(C)C1(C(=O)NC(=O)N(C1=O)C)CC=C |
Approved |
|
GABAA receptors
|
Unknown,
GABA A receptor binding,
Muscarinic receptor binding
|
Song, Y., Liu, Y., Yuan, Y., Jia, X., Zhang, W., Wang, G., Jia, Y., Wang, X., Liu, L., Li, W. and Li, X., 2021. Effects of general versus subarachnoid anaesthesia on circadian melatonin rhythm and postoperative delirium in elderly patients undergoing hip fracture surgery: a prospective cohort clinical trial. EBioMedicine, 70.
|
|
|
C1=CC(=CC=C1N)S(=O)(=O)N |
not approved |
Regulates Flowering Time through Expression of the Circadian Clock Gene LUX
|
LUX (GENE)
|
Affects flowering rhythms (LUX)
|
Hirohata, A., Yamatsuta, Y., Ogawa, K., Kubota, A., Suzuki, T., Shimizu, H., Kanesaka, Y., Takahashi, N. and Endo, M., 2022. Sulfanilamide regulates flowering time through expression of the circadian clock gene LUX. Plant and Cell Physiology, 63(5), pp.649-657.
|
|
|
CCC1C(C(C(C(=O)C(CC(C(C(C(C(C(=O)O1)C)OC2CC(C(C(O2)C)O)(C)OC)C)OC3C(C(CC(O3)C)N(C)C)O)(C)OC)C)C)O)(C)O |
Approved |
Improvement in daytime sleepiness in patients with GABA-related hypersomnia
|
Microbiota
|
Unknown
|
Trotti, L.M., Saini, P., Freeman, A.A., Bliwise, D.L., García, P.S., Jenkins, A. and Rye, D.B., 2014. Improvement in daytime sleepiness with clarithromycin in patients with GABA-related hypersomnia: clinical experience. Journal of psychopharmacology, 28(7), pp.697-702.
|
|
|
C1CC(=O)NC2=C1C=CC(=C2)OCCCCN3CCN(CC3)C4=C(C(=CC=C4)Cl)Cl |
Approved |
Disrupts cellular synchrony in suprachiasmatic nucleus
|
D2R (dopamine receptor)
|
Dopamine receptor binding
|
Li, R., Masuda, K., Ono, D., Kanbayashi, T., Hirano, A. and Sakurai, T., 2023. Aripiprazole disrupts cellular synchrony in the suprachiasmatic nucleus and enhances entrainment to environmental light–dark cycles in mice. Frontiers in Neuroscience, 17, p.1201137.
|
|
|
C1=CC(=CC=C1C(C(CO)NC(=O)C(Cl)Cl)O)[N+](=O)[O-] |
Approved |
shortened the period length of the circadian rhythm by 2 hours
|
Mitochondrial translation machine
|
Chloramphenicol can inhibit both bacterial and mitochondrial protein synthesis
|
Feldman, J.F. and Dunlap, J.C., 1983. Neurospora crassa: a unique system for studying circadian rhythms. In Photochemical and Photobiological Reviews: Volume 7 (pp. 319-368). Boston, MA: Springer US.
|
|
|
C[C@H]1/C=C/C=C(\C(=O)NC2=C(C(=C3C(=C2O)C(=C(C4=C3C(=O)[C@](O4)(O/C=C/[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)C)O)O)/C=N/N5CCN(CC5)C)/C |
Approved |
Rifampicin lengthened the circadian period under darkness in plants.
|
organellar transcription
|
Lenghthen the circadian period
|
Philippou, K., Davis, A.M., Davis, S.J. and Sánchez-Villarreal, A., 2020. Chemical perturbation of chloroplast-related processes affects circadian rhythms of gene expression in Arabidopsis: salicylic acid application can entrain the clock. Frontiers in physiology, 11, p.429.
|
|
|
C1CN(CCN1CCC=C2C3=CC=CC=C3SC4=C2C=C(C=C4)Cl)CCO |
Approved |
|
Unknown
|
Unknown
|
Herberger, S., Ruether, E. and Hajak, G., 2021. Somnologics: Medicines for the Treatment of Sleep Disorders. In NeuroPsychopharmacotherapy (pp. 1-39). Cham: Springer International Publishing.
|
|
|
CN(C)CCCN1C2=CC=CC=C2SC3=C1C=C(C=C3)Cl |
Approved |
|
NPAS2
|
Unknown
|
Nagayama, H., Takagi, A., Sakurai, Y., Nishiwaki, K. and Takahashi, R., 1978. Chronopharmacological study of neuroleptics: II. Circadian susceptibility rhythm to chlorpromazine. Psychopharmacology, 58, pp.49-53.
|
|
|
CN(C)C(=O)NC1CCC(CC1)CCN2CCN(CC2)C3=C(C(=CC=C3)Cl)Cl |
Approved |
|
D2R (dopamine receptor)
|
Dopamine receptor binding
|
Nyitrai, G., et al. 2021. Cariprazine modulates sleep architecture in rats. Journal of Psychopharmacology, 35(3), pp.303-310.
|
|
|
C1CN(CCC1N2C3=CC=CC=C3NC2=O)CCCC(=O)C4=CC=C(C=C4)F |
Approved |
|
D2R (dopamine receptor)
|
Dopamine receptor binding,
Dopamine receptor agonist
|
Altenhofen, S. and Bonan, C.D., 2022. Zebrafish as a Tool in the Study of Sleep and Memory-related Disorders. Current neuropharmacology, 20(3), pp.540-549.
|
|
|
CN1CC2C(C1)C3=C(C=CC(=C3)Cl)OC4=CC=CC=C24 |
Approved |
Induces resless legs syndrome
|
5-HT7
|
5-HT7 binding
|
Delcourte, S., Abrial, E., Etiévant, A., Rovera, R., Arnt, J., Didriksen, M. and Haddjeri, N., 2017. Asenapine modulates mood‐related behaviors and 5‐HT 1A/7 receptors‐mediated neurotransmission. CNS Neuroscience & Therapeutics, 23(6), pp.518-525.
,
Colita, C.I., Hermann, D.M., Filfan, M., Colita, D., Doepnner, T.R., Tica, O., Glavan, D. and Popa-Wagner, A., 2024. Optimizing Chronotherapy in Psychiatric Care: The Impact of Circadian Rhythms on Medication Timing and Efficacy. Clocks & Sleep, 6(4), pp.635-655.
,
McCall, W.V., Riley, M.A., Hodges, C., McCloud, L., Phillips, M. and Rosenquist, P.B., 2014. Asenapine-induced restless legs syndrome: differentiation from akathisia. Journal of Clinical Sleep Medicine, 10(12), pp.1341-1342.
|
|
|
C1=CC=C2C3=C4C(=CC=C3)C5=CC=CC=C5C4=CC2=C1 |
None |
|
mPer2
,
mPer1
,
CRY1-PER2 complex
,
CRY1
,
CLOCK-BMAL1
|
Disruption of circadian clock,
Bmal1,
Interferes with CLOCK–BMAL1,
Targets BMAL1–CLOCK DNA-binding activity,
aryl hydrocarbon receptor (AhR) binding
|
Schmitt, E. E., Barhoumi, R., Metz, R. P., & Porter, W. W. (2017). Circadian Regulation of Benzo[a]Pyrene Metabolism and DNA Adduct Formation in Breast Cells and the Mouse Mammary Gland. Molecular Pharmacology, 91(3), 178–188.
|
|
|
COCCOC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=CC(=C3)C#C)OCCOC |
Approved |
potential period alteration via EGFR/JAK2 inhibition
|
CLOCK-BMAL1
,
BMAL1 expression (induction)
,
JAK2
,
EGFR
|
inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase
|
Tamai, T.K., Nakane, Y., Ota, W., Kobayashi, A., Ishiguro, M., Kadofusa, N., Ikegami, K., Yagita, K., Shigeyoshi, Y., Sudo, M. and Nishiwaki‐Ohkawa, T., 2018. Identification of circadian clock modulators from existing drugs. EMBO molecular medicine, 10(5), p.e8724.
|
|
|
CC1=CC2=C(S1)NC3=CC=CC=C3N=C2N4CCN(CC4)C |
Approved |
|
Unknown
|
Disruption of circadian clock,
Unknown
|
Romo‐Nava, F., Buijs, F.N., Valdés‐Tovar, M., Benítez‐King, G., Basualdo, M., Perusquía, M., Heinze, G., Escobar, C. and Buijs, R.M., 2017. Olanzapine‐induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin. Journal of Pineal Research, 62(4), p.e12402.
,
Vidarsdottir, S., Roelfsema, F., Frolich, M. and Pijl, H., 2009. Olanzapine shifts the temporal relationship between the daily acrophase of serum prolactin and cortisol concentrations rhythm in healthy men. Psychoneuroendocrinology, 34(5), pp.705-712.
|
|
|
CCCCCCCCCC(=O)OCCN1CCN(CC1)CCCN2C3=CC=CC=C3SC4=C2C=C(C=C4)C(F)(F)F |
Approved |
|
Unknown
|
Binding to rat brainα- andβ-adrenergic, muscarinic cholinergic, dopamine and opiate receptors
|
Naber, D., Wirz-Justice, A. and Kafka, M.S., 1982. Chronic fluphenazine treatment modifies circadian rhythms of neurotransmitter receptor binding in rat brain. Journal of Neural Transmission, 55, pp.277-288.
|
|
|
CCN1CCCC1CNC(=O)C2=C(C=CC(=C2)S(=O)(=O)N)OC |
Approved |
Modulates insulin release rhtyhms
|
D2R (dopamine receptor)
|
Dopamine receptor binding
|
Wei, H., Zapata, R.C., Lopez-Valencia, M., Aslanoglou, D., Farino, Z.J., Benner, V., Osborn, O., Freyberg, Z. and McCarthy, M.J., 2020. Dopamine D2 receptor signaling modulates pancreatic beta cell circadian rhythms. Psychoneuroendocrinology, 113, p.104551.
|
|
|
CC1=C(C(=O)N2CCCCC2=N1)CCN3CCC(CC3)C4C5=C(C=C(C=C5)F)ON4 |
Approved |
|
mPer2
,
mPer1
,
CRY1-PER2 complex
,
CRY1
,
CRY1
,
REV-ERBα
|
Core clock modulation,
PER gene exspression modulation,
CRY gene expression modulation,
BMAL1 expression modulation
|
Zapata, R.C., Silver, A., Yoon, D., Chaudry, B., Libster, A., McCarthy, M.J. and Osborn, O., 2022. Adverse effects of antipsychotic drugs on metabolism depend on drug dosing and feeding times. medRxiv, pp.2022-02.
,
Cherukalady, R., Kumar, D., Basu, P. and Singaravel, M., 2017. Risperidone resets the circadian clock in mice. Biological Rhythm Research, 48(4), pp.583-591.
|
|
|
CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2C=C(C4=CC(=O)[C@@H]5C[C@@H]5[C@]34C)Cl)C)O |
Approved |
Circadian gene modulation in human U2OS cells
|
CLOCK-BMAL1
,
Arntl (gene)
,
BMAL1 expression (induction)
|
Bmal1,
de-repressing BMAL1,
BMAL1 expression modulation,
BMAL1 expression modulation
|
Tamai, T.K., Nakane, Y., Ota, W., Kobayashi, A., Ishiguro, M., Kadofusa, N., Ikegami, K., Yagita, K., Shigeyoshi, Y., Sudo, M. and Nishiwaki‐Ohkawa, T., 2018. Identification of circadian clock modulators from existing drugs. EMBO molecular medicine, 10(5), p.e8724.
|
|
|
CC1=NC(=NC=C1OC[C@]2(C[C@H]2C(=O)NC3=NC=C(C=C3)F)C4=CC(=CC=C4)F |
Approved |
|
Orexin Receptors OX1R and OX2R
|
Orexin Receptor Antagonism
|
https://pubmed.ncbi.nlm.nih.gov/33336219/
|
|
|
C1CN(CCN1CCOCCO)C(C2=CC=CC=C2)C3=CC=C(C=C3)Cl |
Approved |
|
Histamine 1 receptor
|
Histamine 1 blocker
|
Spahr, L., Coeytaux, A., Giostra, E., Hadengue, A. and Annoni, J.M., 2007. Histamine H1 blocker hydroxyzine improves sleep in patients with cirrhosis and minimal hepatic encephalopathy: a randomized controlled pilot trial. Official journal of the American College of Gastroenterology| ACG, 102(4), pp.744-753.
|
|
|
C1CN(CC=C1N2C3=CC=CC=C3NC2=O)CCCC(=O)C4=CC=C(C=C4)F |
Approved |
|
D2R (dopamine receptor)
|
Dopamine receptor binding,
Dopamine receptor binding,
Dopamine receptor antagonist
|
Cugini, P., Delogu, G., Casula, M.A., Gatta, L., Cascioli, C. and Di Palma, L., 1991. Anaesthesia‐induced dissociation between the circadian rhythms of blood pressure and heart rate. Biological Rhythm Research, 22(4), pp.333-340.
|
|
|
CC1=CC=C(C=C1)C2=C(N3C=C(C=CC3=N2)C)CC(=O)N(C)C |
Approved |
|
GABAA receptors
|
Hypnotic effect,
GABAergic system influence
|
Keuroghlian, A.S., Barry, A.S. and Weiss, R.D., 2012. Circadian dysregulation, zolpidem dependence, and withdrawal seizure in a resident physician performing shift work. The American Journal on Addictions/American Academy of Psychiatrists in Alcoholism and Addictions, 21(6), p.576.
,
Keating, G.M., 2005. Zolpidem: a review of its use in the management of insomnia. CNS Drugs, 19(1), pp.65-89.
,
Copinschi, G., Akseki, E., Moreno-Reyes, R., Leproult, R., L'Hermite-Balériaux, M., Caufriez, A., Vertongen, F. and Cauter, E.V., 1995. Effects of Bedtime Administration of Zolpidem on Orcadian and Sleep-Related Hormonal Profiles in Normal Women. Sleep, 18(6), pp.417-424.
|
|
|
CCC(=O)N(C1=CC=CC=C1)C2(CCN(CC2)CCC(=O)OC)C(=O)OC |
Approved |
REM sleep suppression in humans
|
Mu opioid receptor
,
OPRK1
,
OPRD1
|
Unknown,
Mu opioid receptor binding,
Kappa opioid receptor binding,
delta opioid receptor binding
|
Bonafide, C.P., Aucutt-Walter, N., Divittore, N., King, T., Bixler, E.O. and Cronin, A.J., 2008. Remifentanil inhibits rapid eye movement sleep but not the nocturnal melatonin surge in humans. Anesthesiology, 108(4), pp.627–633.
,
Wenk, M., Pöpping, D.M., Chapman, G., Grenda, H. and Ledowski, T., 2013. Long-term quality of sleep after remifentanil-based anaesthesia: a randomized controlled trial. British Journal of Anaesthesia, 110(2), pp.250–257
|
|
|
CC(CN1C2=CC=CC=C2SC3=CC=CC=C31)N(C)C |
Approved |
|
Histamine 1 receptor
|
Histamine 1 blocker
|
Masse, M., Henry, H., Cuvelier, E., Pinçon, C., Pavy, M., Beeuwsaert, A., Barthélémy, C., Cuny, D., Gautier, S., Kambia, N. and Lefebvre, J.M., 2022, January. Sleep medication in older adults: identifying the need for support by a community pharmacist. In Healthcare (Vol. 10, No. 1, p. 147). MDPI.
,
Cantisani, C., Ricci, S., Grieco, T., Paolino, G., Faina, V., Silvestri, E. and Calvieri, S., 2013. Topical promethazine side effects: our experience and review of the literature. BioMed research international, 2013(1), p.151509.
|
|
|
CC1CCC(CN1C(=O)C2=C(C=CC(=C2)C)C3=NC=CC=N3)COC4=NC=C(C=C4)F |
Not approved |
|
Orexin Receptors OX1R and OX2R
|
Orexin Receptor Antagonism
|
Hoyer, D., Dürst, T., Fendt, M., Jacobson, L.H., Betschart, C., Hintermann, S., Behnke, D., Cotesta, S., Laue, G., Ofner, S. and Legangneux, E., 2013. Distinct effects of IPSU and suvorexant on mouse sleep architecture. Frontiers in neuroscience, 7, p.235.
|