Tovinontrine - ≥99% , Phosphodiesterase 9A inhibitor, CAS No.2062661-53-2, Phosphodiesterase 9A inhibitor

CAS: 2062661-53-2 Cat. No.: T647305 Molecular Weight: 394.47 PubChem CID: 124220601

GRADE & PURITY ≥99%

Synonyms

6-((3S,4S)-4-METHYL-1-(2-PYRIMIDINYLMETHYL)-3-PYRROLIDINYL)-3-(TETRAHYDRO-2H-PYRAN-4-YL)IMIDAZO(1,5-A)PYRAZIN-8(7H)-ONE | BDBM426313 | US10513524, Compound (P3 | 6-((3S,4S)-4-Methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)-3-tetrahydropyran-4-yl-7himidazo

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Tovinontrine (IMR-687) is a highly potent and selective phosphodiesterase-9 (PDE9) inhibitor specifically for the treatment of sickle cell disease. IC 50 s are 8.19 nM and 9.99 nM for PDE9A1 and PDE9A2, respectively

In Vitro

IMR-687 inhibits PDE9A with more than 800-fold greater potency than PDE1A3, PDE1B, PDE1C, PDE5A2, with IC 50 values of 88.4 μM, 8.48 μM, 12.2 μM, and 81.9 μM, respectively. IMR-687 (0.1-10 μM) treatment in erythroid K562 cells for 72 hours induces hemoglobin (HbF) in a dose-dependent manner. IMR-687 (0.03-10 μM) treatment for 6 hours in erythroid K562 cells increases cGMP in a dose-dependent manner. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

IMR-687 (30 mg/kg/day; after 30 days of treatment) shows a greater than 3-fold in the percent of HbF + F-cells (8.4% in vehicle treated and 27.3% in IMR-687 treated) and a corresponding 2-fold decrease in sickled red blood cells (56.3% in vehicle treated and 24.4% in IMR-687 treated) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: HbSS-Townes mice on a 129/B6 background (10-12 weeks old) Dosage: 30 mg/kg Administration: Dosed daily by gavage for 30 days Result: Resulted in fetal hemoglobin (HbF) induction, reduced hemolysis and reduced reticulocytosis.

Form:Solid

IC50& Target:PDE9A1 8.19 nM () PDE9A2 9.99 nM () PDE1A3 88.4 nM () PDE1B 8.48 nM () PDE1C 12.2 nM () PDE5A2 81.9 nM ()

Specifications

Synonyms

6-((3S, 4S)-4-METHYL-1-(2-PYRIMIDINYLMETHYL)-3-PYRROLIDINYL)-3-(TETRAHYDRO-2H-PYRAN-4-YL)IMIDAZO(1, 5-A)PYRAZIN-8(7H)-ONE | BDBM426313 | US10513524, Compound (P3 | 6-((3S, 4S)-4-Methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)-3-tetrahydropyran-4-yl-7himidazo

Specifications & Purity

≥99%

Biochemical and Physiological Mechanisms

Tovinontrine (IMR-687) is a highly potent and selective phosphodiesterase-9 (PDE9) inhibitor specifically for the treatment of sickle cell disease. IC 50 s are 8.19 nM and 9.99 nM for PDE9A1 and PDE9A2, respectively.

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Mechanism of action

Phosphodiesterase 9A inhibitor

Purity

≥99%

Product Properties

• ALogP: 0.4

Names and Identifiers

• Canonical Smiles: CC1CN(CC1C2=CN3C(=CN=C3C4CCOCC4)C(=O)N2)CC5=NC=CC=N5
• IUPAC Name: 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-3-(oxan-4-yl)-7H-imidazo[1,5-a]pyrazin-8-one
• InChIKey: GWGNPYYVGANHRJ-GDBMZVCRSA-N
• INCHI: 1S/C21H26N6O2/c1-14-10-26(13-19-22-5-2-6-23-19)11-16(14)17-12-27-18(21(28)25-17)9-24-20(27)15-3-7-29-8-4-15/h2,5-6,9,12,14-16H,3-4,7-8,10-11,13H2,1H3,(H,25,28)/t14-,16-/m1/s1
• Isomeric SMILES: C[C@@H]1CN(C[C@H]1C2=CN3C(=CN=C3C4CCOCC4)C(=O)N2)CC5=NC=CC=N5
• Alternate CAS: 2062661-53-2
• PubChem CID: 124220601
• Molecular Weight: 394.47

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Imidazo[1,5-a]pyrazines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Imidazo[1,5-a]pyrazines
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Imidazo[1,5-a]pyrazines
• Alternative Parents: Aralkylamines Pyrimidines and pyrimidine derivatives Pyrazines Oxanes N-substituted imidazoles N-alkylpyrrolidines Heteroaromatic compounds Trialkylamines Lactams Oxacyclic compounds Dialkyl ethers Azacyclic compounds Organopnictogen compounds Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Imidazo[1,5-a]pyrazine - Aralkylamine - N-alkylpyrrolidine - Pyrimidine - Pyrazine - Oxane - N-substituted imidazole - Heteroaromatic compound - Pyrrolidine - Imidazole - Azole - Tertiary aliphatic amine - Tertiary amine - Lactam - Oxacycle - Azacycle - Ether - Dialkyl ether - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Amine - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as imidazo[1,5-a]pyrazines. These are aromatic heteropolycyclic compounds containing an imidazole ring fused to and sharing one nitrogen with a pyrazine ring.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Mechanisms of Action

Chemical and Physical Properties

• Solubility: DMSO : 100 mg/mL (253.50 mM; Need ultrasonic)
• Molecular Weight: 394.500 g/mol
• XLogP3: 0.400
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 4
• Exact Mass: 394.212 Da
• Monoisotopic Mass: 394.212 Da
• Topological Polar Surface Area: 85.200 Ų
• Heavy Atom Count: 29
• Formal Charge: 0
• Complexity: 631.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 2
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1