IUPAC/Chemical Name
(2S)-N-(3,5-dimethylphenyl)-1-(4-methoxyphenyl)sulfonylpyrrolidine-2-carboxamide
InChi Key
NHPQGZOBHSVTAQ-IBGZPJMESA-N
InChi Code
InChI=1S/C20H24N2O4S/c1-14-11-15(2)13-16(12-14)21-20(23)19-5-4-10-22(19)27(24,25)18-8-6-17(26-3)7-9-18/h6-9,11-13,19H,4-5,10H2,1-3H3,(H,21,23)/t19-/m0/s1
SMILES Code
O=C([C@H]1N(S(=O)(C2=CC=C(OC)C=C2)=O)CCC1)NC3=CC(C)=CC(C)=C3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Potent, dual orexin receptor antagonist.
In vivo activity:
In the present study, it was demonstrated that icv administration of DORA, ACT462206, a novel orexin receptor antagonist, significantly suppressed centrally administered ghrelin-induced feeding in rats. In addition, Fos immunohistochemistry revealed that centrally administered ghrelin induced Fos expression in the PVN, the Arc, and the LHA, which are areas related to feeding behavior. Fos expression was significantly inhibited by pretreatment with DORA; however, it remained significantly increased in those nuclei when compared to that after icv administration of ghrelin without DORA. It is worth noting that Fos expression of orexin-A-IR neurons induced by icv administration of ghrelin was significantly inhibited by pretreatment with DORA, but the Fos expression in orexin-A-IR neurons remained significantly increased.
Reference: J Physiol Sci. 2018; 68(2): 129–136. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394659/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
38.9 |
100.00 |
| Ethanol |
38.9 |
100.00 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
388.48
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. So M, Hashimoto H, Saito R, Yamamoto Y, Motojima Y, Ueno H, Sonoda S, Yoshimura M, Maruyama T, Kusuhara K, Ueta Y. Inhibition of ghrelin-induced feeding in rats by pretreatment with a novel dual orexin receptor antagonist. J Physiol Sci. 2018 Mar;68(2):129-136. doi: 10.1007/s12576-016-0517-5. Epub 2017 Jan 4. Erratum in: J Physiol Sci. 2019 Feb 14;: PMID: 28054308; PMCID: PMC6394659.
2. Boss C, Roch-Brisbare C, Steiner MA, Treiber A, Dietrich H, Jenck F, von Raumer M, Sifferlen T, Brotschi C, Heidmann B, Williams JT, Aissaoui H, Siegrist R, Gatfield J. Structure-activity relationship, biological, and pharmacological characterization of the proline sulfonamide ACT-462206: a potent, brain-penetrant dual orexin 1/orexin 2 receptor antagonist. ChemMedChem. 2014 Nov;9(11):2486-96. doi: 10.1002/cmdc.201402258. Epub 2014 Aug 21. PMID: 25147058.
In vivo protocol:
1. So M, Hashimoto H, Saito R, Yamamoto Y, Motojima Y, Ueno H, Sonoda S, Yoshimura M, Maruyama T, Kusuhara K, Ueta Y. Inhibition of ghrelin-induced feeding in rats by pretreatment with a novel dual orexin receptor antagonist. J Physiol Sci. 2018 Mar;68(2):129-136. doi: 10.1007/s12576-016-0517-5. Epub 2017 Jan 4. Erratum in: J Physiol Sci. 2019 Feb 14;: PMID: 28054308; PMCID: PMC6394659.
2. Boss C, Roch-Brisbare C, Steiner MA, Treiber A, Dietrich H, Jenck F, von Raumer M, Sifferlen T, Brotschi C, Heidmann B, Williams JT, Aissaoui H, Siegrist R, Gatfield J. Structure-activity relationship, biological, and pharmacological characterization of the proline sulfonamide ACT-462206: a potent, brain-penetrant dual orexin 1/orexin 2 receptor antagonist. ChemMedChem. 2014 Nov;9(11):2486-96. doi: 10.1002/cmdc.201402258. Epub 2014 Aug 21. PMID: 25147058.
1: Hoch M, van Gorsel H, van Gerven J, Dingemanse J. Entry-into-humans study with ACT-462206, a novel dual orexin receptor antagonist, comparing its pharmacodynamics with almorexant. J Clin Pharmacol. 2014 Sep;54(9):979-86. doi: 10.1002/jcph.297. Epub 2014 Apr 21. PMID: 24691844.
2: Parekh RU, White A, Leffler KE, Biancardi VC, Eells JB, Abdel-Rahman AA, Sriramula S. Hypothalamic kinin B1 receptor mediates orexin system hyperactivity in neurogenic hypertension. Sci Rep. 2021 Oct 26;11(1):21050. doi: 10.1038/s41598-021-00522-0. PMID: 34702886; PMCID: PMC8548389.
3: Boss C, Roch-Brisbare C, Steiner MA, Treiber A, Dietrich H, Jenck F, von Raumer M, Sifferlen T, Brotschi C, Heidmann B, Williams JT, Aissaoui H, Siegrist R, Gatfield J. Structure-activity relationship, biological, and pharmacological characterization of the proline sulfonamide ACT-462206: a potent, brain- penetrant dual orexin 1/orexin 2 receptor antagonist. ChemMedChem. 2014 Nov;9(11):2486-96. doi: 10.1002/cmdc.201402258. Epub 2014 Aug 21. PMID: 25147058.
4: Boss C. 20 Years of Medicinal Chemistry - Always Look at the Bright Side (of Life). Chimia (Aarau). 2020 Aug 12;74(7):549-560. doi: 10.2533/chimia.2020.549. PMID: 32778207.
