926927-61-9

Basic information

• Product Name: VTX-2337
• Synonyms: VTX-2337;VTX 378;Motolimod;2-amino-N,N-dipropyl-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepine-4-carboxamide;Motolimod(VTX-2337);Obicetrapib;2-amino-n,n-dipropyl-8-[4-(pyrrolidine-1-carbonyl)phenyl]-3h-1-benzazepine-4-carboxamide
• CAS NO: 926927-61-9
• Molecular Formula: C28H34N4O2
• Molecular Weight: 458.59516
• Mol File: 926927-61-9.mol

Chemical Properties

• Boiling Point: 718.7±70.0 °C(Predicted)
• Appearance: Solid
• Density: 1.19±0.1 g/cm3 (20 oC 760 Torr)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to at least 25 mg/ml)
• PKA: 2.47±0.40(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: VTX-2337(CAS DataBase Reference)
• NIST Chemistry Reference: VTX-2337(926927-61-9)
• EPA Substance Registry System: VTX-2337(926927-61-9)

Safety Data

• Hazardous Substances Data: 926927-61-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
VTX-2337 is used as an immune modulator for its ability to stimulate the immune system and enhance the production of cytokines, such as TNF-α and IL-12, in human peripheral blood mononuclear cells (PBMCs), monocytes, and myeloid dendritic cells. This immune-stimulating property makes it a potential candidate for the development of new therapeutic agents targeting various diseases.
VTX-2337 is also used as an antineoplastic agent for its potential to reduce tumor growth and increase tumor infiltration of monocytes and T cells. Its combination with other therapeutic agents, such as pegylated liposomal doxorubicin (PLD), has shown promising results in preclinical models of ovarian cancer, indicating its potential use in cancer treatment.

References

1) Lu?et al.?(2012),?VTX-2337 is a Novel TLR8 Agonist That Activates NK Cells and Augments ADCC;?Clin. Cancer Res.?18?499 2) Lu?et al.?(2013),?TLR8 agonist VTX-2337 enhances NKG2D-mediated cytotoxicity of NK cells;?J. Immunother. Cancer?1?P44 3) Rutman?et al.?(2015),?Motolimod,a selective TLR8 agonist, induces apoptosis in monocytic myeloid-derived suppressor cells (M-MDSC);?J. Immunother. Cancer.?3?P296 4) Ferris?et al.?(2014),?Active8: a random, double-blind, placebo-controlled study of chemotherapy plus cetuximab in combination with TLR8 agonist VTX-2337 in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN);?J. Immunother. Cancer?2P69 5) Monk?et al.?(2017),?Integrative Development of a TLR8 Agonist for Ovarian Cancer Chemo-Immunotherapy;?Clin. Cancer Res.?23?1955 6) Dietsch?et al.?(2016),?Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity;?PLoS One?11?e0148764

Upstream product

• 1226791-83-8 (tert-butoxy)-N-{4-(N,N-dipropylcarbamoyl)-8-[4-(pyrrolidinylcarbonyl)phenyl](3H-benzo[f]azepin-2-yl)}carboxamide 

Relevant articles and documents

METHODS OF SYNTHESIS OF BENZAZEPINE DERIVATIVES

The disclosure describes method of synthesis of substituted benzazepine derivatives. Preferred methods according to the disclosure allow for large-scale preparation of benzazepine compounds having low levels of metal impurities. In some embodiments, preferred methods according to the disclosure also allow for the preparation of benzazepine derivatives without the use of chromatographic purification methods and in better yield than previously used methods for preparing such compounds. The methods disclosed herein find utility in synthetic organic chemistry as well as medicinal chemistry.

8-SUBSTITUTED BENZOAZEPINES AS TOLL-LIKE RECEPTOR MODULATORS

Provided are compositions and methods useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compositions and methods have use in the treatment of autoimmunity, inflammation allergy, asthma, graft rejection, graft versus host disease, infection, sepsis, cancer and immunodeficiency.