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MedKoo Cat#: 555338 | Name: BI-409306
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Osoresnontrine, also known as BI-409306, and SUB 166499, is a potent and selective PDE9A inhibitor with an IC50 of 52 nM. PDE9A is a drug target for cognitive decline in Alzheimer's and other diseases because this enzyme reduces brain levels of the second messenger cyclic guanosine monophosphate. cGMP transduces signals by the neurotransmitters nitric oxide and glutamate.

Chemical Structure

BI-409306
BI-409306
CAS#1189767-28-9

Theoretical Analysis

MedKoo Cat#: 555338

Name: BI-409306

CAS#: 1189767-28-9

Chemical Formula: C16H17N5O2

Exact Mass: 311.1382

Molecular Weight: 311.35

Elemental Analysis: C, 61.72; H, 5.50; N, 22.49; O, 10.28

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,450.00 Ready to ship
1g USD 3,450.00 Ready to ship
2g USD 5,650.00 Ready to ship
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Related CAS #
1189767-28-9
Synonym
BI-409306; BI 409306; BI409306; SUB 166499; SUB-166499; SUB166499; Osoresnontrine;
IUPAC/Chemical Name
6-(pyridin-2-ylmethyl)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one
InChi Key
BZTIJCSHNVZMES-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H17N5O2/c22-16-13-10-18-21(12-4-7-23-8-5-12)15(13)19-14(20-16)9-11-3-1-2-6-17-11/h1-3,6,10,12H,4-5,7-9H2,(H,19,20,22)
SMILES Code
O=C1C2=C(N(C3CCOCC3)N=C2)N=C(CC4=NC=CC=C4)N1
Appearance
Solid powder
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
>3 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
2934.99.03.00
More Info
Biological target:
BI 409306 (SUB 166499) is a potent and selective inhibitor of human and rat PDE9A with mean IC50 of 65 nM and 168 nM, respectively.
In vitro activity:
BI 409306 demonstrated both potent and selective inhibition of human PDE9A activity, with a calculated mean (S.D.) IC50 of 65 (11) nM (Supplementary Fig. 1; Table 1). The IC50 for inhibition of rat PDE9A was 168 nM (Table 1). IC50 values of 1.45 and 1.17 μM were calculated for PDE1A and PDE1C, respectively, and no inhibitory activity was observed for PDE2A, 3A, 4B, 5A, 6AB, 7A, and 10A with BI 409306 up to a concentration of 10 μM (Table 1). There was no significant activity of BI 409306 at 10 μM against 95 non-PDE targets (Supplementary Table 1). Reference: J Pharmacol Exp Ther. 2019 Dec;371(3):633-641. https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=31578258
In vivo activity:
Following microdialysis, the mean (S.E.M.) basal extracellular cGMP concentration in the rat prefrontal cortex was 4.08 (0.51) fmol/100 μl. At 20 minutes post-intraperitoneal injection of BI 409306 1.5–15 mg/kg, a significant dose-dependent increase in extracellular cGMP levels was observed (Χ2 = 13.95; P < 0.01; df = 3; N = 5 animals per group), which peaked after 20 minutes and gradually returned to control values approximately 100 minutes after the injection (Fig. 2A). At 20 minutes, the mean (S.E.M.) percentage increase in extracellular cGMP levels relative to baseline was 187.9% (49.2) for BI 409306 7.5 mg/kg and 97.6 (49.2) for BI 409306 15 mg/kg (P < 0.05). With BI 409306 15 mg/kg, significant increases over control values were also observed 40 and 180 minutes after BI 409306 administration. The 1.5 mg/kg dose did not significantly increase extracellular cGMP over baseline at any time point. cGMP levels in rat CSF increased in a dose-dependent manner following BI 409306 administration, as determined by high-performance LC-MS/MS. Compared with vehicle control, significant increases in cGMP were induced by BI 409306 3 and 10 mg/kg (N = 2–6 animals per group; P < 0.001) but not by the lower doses of 0.3 and 1 mg/kg (Fig. 2B). Mean CSF concentration of BI 409306 30 minutes after oral administration of BI 409306 0.3 mg/kg in these rats was 67 nM. On the basis of the potency of BI 409306 against the rat PDE9 enzyme, a 50% increase in CSF cGMP was achieved at a CSF BI 409306 exposure of approximately 40% of the IC50 against PDE9. Oral treatment of mice with BI 409306 at all doses tested (0.007–2.5 mg/kg) led to an attenuation or reversal of the MK-801-induced reduction in spontaneous alternation compared with the MK-801-treated group (N = 10 animals per group; P < 0.05; Fig. 5A). On the basis of the mean plasma concentration of BI 409306 measured in mice 1 hour after administration of BI 409306 1.5 mg/kg, the extrapolated plasma exposure levels of mice in the T-maze at most effective doses (0.02–0.5 mg/kg intraperitoneal) would be in the range of 67–1675 nM. These extrapolated plasma exposures correspond to BI 409306 concentrations in CSF of 13–335 nM, which is approximately 0.1- to 2-fold of the PDE9A IC50 on the basis of potency against the rat enzyme. Since the IC50 value for inhibition of PDE1 isoforms by BI 409306 is >1 μM, the memory-improving efficacy of BI 409306 can be attributed solely to the inhibition of PDE9. Reference: J Pharmacol Exp Ther. 2019 Dec;371(3):633-641. https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=31578258
Solvent mg/mL mM comments
Solubility
DMSO 62.0 199.14
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 311.35 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.

Recalculate based on batch purity %
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:
In vitro protocol:
1. Rosenbrock H, Giovannini R, Schänzle G, Koros E, Runge F, Fuchs H, Marti A, Reymann KG, Schröder UH, Fedele E, Dorner-Ciossek C. The Novel Phosphodiesterase 9A Inhibitor BI 409306 Increases Cyclic Guanosine Monophosphate Levels in the Brain, Promotes Synaptic Plasticity, and Enhances Memory Function in Rodents. J Pharmacol Exp Ther. 2019 Dec;371(3):633-641. doi: 10.1124/jpet.119.260059. Epub 2019 Oct 2. PMID: 31578258.
In vivo protocol:
1. Rosenbrock H, Giovannini R, Schänzle G, Koros E, Runge F, Fuchs H, Marti A, Reymann KG, Schröder UH, Fedele E, Dorner-Ciossek C. The Novel Phosphodiesterase 9A Inhibitor BI 409306 Increases Cyclic Guanosine Monophosphate Levels in the Brain, Promotes Synaptic Plasticity, and Enhances Memory Function in Rodents. J Pharmacol Exp Ther. 2019 Dec;371(3):633-641. doi: 10.1124/jpet.119.260059. Epub 2019 Oct 2. PMID: 31578258.
1: Brown D, Nakagome K, Cordes J, Brenner R, Gründer G, Keefe RSE, Riesenberg R, Walling DP, Daniels K, Wang L, McGinniss J, Sand M. Evaluation of the Efficacy, Safety, and Tolerability of BI 409306, a Novel Phosphodiesterase 9 Inhibitor, in Cognitive Impairment in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial. Schizophr Bull. 2018 May 1. doi: 10.1093/schbul/sby049. [Epub ahead of print] PubMed PMID: 29718385. 2: Moschetti V, Kim M, Sand M, Wunderlich G, Andersen G, Feifel U, Jang IJ, Timmer W, Rosenbrock H, Boland K. The safety, tolerability and pharmacokinetics of BI 409306, a novel and potent PDE9 inhibitor: Overview of three Phase I randomised trials in healthy volunteers. Eur Neuropsychopharmacol. 2018 May;28(5):643-655. doi: 10.1016/j.euroneuro.2018.01.003. Epub 2018 Mar 19. PubMed PMID: 29567399. 3: Brown D, Daniels K, Pichereau S, Sand M. A Phase IC Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Cognitive Outcomes of BI 409306 in Patients with Mild-to-Moderate Schizophrenia. Neurol Ther. 2018 Jun;7(1):129-139. doi: 10.1007/s40120-017-0085-5. Epub 2017 Nov 24. PubMed PMID: 29177699; PubMed Central PMCID: PMC5990500. 4: Boland K, Moschetti V, Dansirikul C, Pichereau S, Gheyle L, Runge F, Zimdahl-Gelling H, Sand M. A phase I, randomized, proof-of-clinical-mechanism study assessing the pharmacokinetics and pharmacodynamics of the oral PDE9A inhibitor BI 409306 in healthy male volunteers. Hum Psychopharmacol. 2017 Jan;32(1). doi: 10.1002/hup.2569. PubMed PMID: 28120486. 5: Moschetti V, Boland K, Feifel U, Hoch A, Zimdahl-Gelling H, Sand M. First-in-human study assessing safety, tolerability and pharmacokinetics of BI 409306, a selective phosphodiesterase 9A inhibitor, in healthy males. Br J Clin Pharmacol. 2016 Nov;82(5):1315-1324. doi: 10.1111/bcp.13060. Epub 2016 Aug 22. PubMed PMID: 27378314; PubMed Central PMCID: PMC5061793. 6: Mason VL. Alzheimer's Association International Conference on Alzheimer's Disease 2015 (AAIC 2015) (July 18-23, 2015 - Washington, D.C., USA). Drugs Today (Barc). 2015 Jul;51(7):447-52. doi: 10.1358/dot.2015.51.7.2375989. PubMed PMID: 26261847.