What is NSI-189 Phosphate?

NSI-189 Phosphate ((4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)-3-pyridinyl]methanone phosphate, also called amdiglurax phosphate and NSI-189 H₃PO₄; CAS 1270138-41-4) is the phosphoric acid salt of NSI-189, a small synthetic benzylpiperazine–aminopyridine amide. Its free base, NSI-189 (amdiglurax, CAS 1270138-40-3), links a 2-(3-methylbutylamino)pyridine-3-carbonyl group to 1-benzylpiperazine through a single amide bond. NSI-189 Phosphate is not a peptide and not an amino acid, even though it is often listed beside research peptides. Its salt chemistry comes from the basic benzylpiperazine nitrogen, which accepts a proton from phosphoric acid.

The synthesis patent reports the mono-phosphate as crystalline by XRPD, with one DSC endotherm at 179 °C consistent with a melt and water solubility above 36 mg/mL under ambient conditions (US 9,278,933). That is what NSI-189 Phosphate is at the bench: a characterized crystalline salt of a lipophilic amide base, whose free base PubChem computes at XLogP3 4.2 (PubChem CID 50922681).

Batch-verified at Modern Aminos, NSI-189 Phosphate is supplied in one laboratory format:

• Dry-fill capsules, 60 per capsule bottle

Laboratories building neurochemistry and nootropic structure-activity panels often place NSI-189 Phosphate next to other public reference listings such as PRL-8-53, 9-Me-BC and TAK-653, as well as Semax and Noopept. For a closer look at the phosphate salt and the free base, see What Is NSI-189? Phosphate Salt vs. Freebase Explained.

Chemical and Molecular Data for NSI-189 Phosphate

Identity fields are drawn from PubChem CID 50922680 (phosphate) and PubChem CID 50922681 (free base); the certificate is published in the Certificate of Analysis tab.

What are the Mechanisms of Action?

The structural chemistry and pathway logic of NSI-189 Phosphate in laboratory research include:

• Benzylpiperazine–aminopyridine amide scaffold: The free base joins a 2-(3-methylbutylamino)pyridine-3-carbonyl group to 1-benzylpiperazine through an amide bond, giving C₂₂H₃₀N₄O with no stereocenters (PubChem CID 50922681). Because the carbonyl sits at position 3 of the pyridine ring, the core is a nicotinic acid–derived amide, which is how the synthesis patent describes the class: piperazines “derivatized with nicotinic acid and a benzyl moiety” (US 9,278,933).
• Patent classification and the receptor-data gap: The synthesis patent describes the compound and its salts as neurogenesis agents (US 9,278,933). It does not report a receptor subtype, K_i, EC₅₀ or IC₅₀, and the ChEMBL activity records for the free base are single-concentration screening percentages rather than binding constants (ChEMBL CHEMBL4302505). At the target level, NSI-189 is a classified but molecularly uncharacterized reference compound.
• Acid-addition salt chemistry: The benzyl-substituted piperazine nitrogen is a tertiary amine that accepts a proton, so the free base forms acid-addition salts. The patent lists sulfate, phosphate, hydrohalide, citrate, fumarate, tosylate and besylate salts and notes that both mono and bis salts may be formed (US 9,278,933). PubChem records NSI-189 Phosphate as the 1:1 phosphate, raising the hydrogen-bond donor count from 1 to 4 and the topological polar surface area from 48.5 to 126 Ų (PubChem CID 50922680; PubChem CID 50922681).
• Phosphate salt formation and crystal form: In the patented process the free base is dissolved in ethanol containing 5% water at 75 °C, a 1 M solution of phosphoric acid in ethanol is added, and the solution is seeded with the phosphate and cooled at 20 °C per hour. The patent reports that seeding was essential to establishing the proper crystal form (US 9,278,933, Example 6).
• Solid-state profile of the mono-phosphate: The patent describes the mono-phosphate as crystalline by XRPD, with one DSC endotherm at 179 °C consistent with a melt and water solubility above 36 mg/mL under ambient conditions. Moisture sorption analysis classed it as moderately hygroscopic, adsorbing 4.4 wt% water at 60% RH and 11.2 wt% at 90% RH, and ion chromatography gave free base-to-counter-ion ratios of 1:1.6 to 1:2.3 in different batches (US 9,278,933).
• Synthetic route: 2-Chloronicotinic acid is coupled with N-Boc-piperazine (with TBTU, or through the acid chloride made with thionyl chloride), the Boc group is removed with HCl in 2-propanol, the free piperazine nitrogen is benzylated, and isoamylamine (3-methylbutylamine) then displaces the 2-chloro group at 80–90 °C. Building the benzyl group on late means the route does not start from 1-benzylpiperazine, and the patent reports HPLC purities as area percent at 226 nm (US 9,278,933).

What Does Published Research Show for NSI-189?

Patent and database literature on NSI-189 Phosphate and its free base centers on synthesis, salt formation, solid-state properties, and chemical identity:

• Synthesis and purification route (US 9,278,933 B2): The patent, originally assigned to Neuralstem, Inc., describes a five-step route from 2-chloronicotinic acid and N-Boc-piperazine to the free base and its phosphate, with heptane slurry purification of the free base and HPLC monitoring at 226 nm (US 9,278,933).
• Phosphate salt formation and crystal form (US 9,278,933 B2, Example 6): Phosphoric acid in ethanol at 70–75 °C with seeding gave the crystalline phosphate; a four-reaction screen compared 1.0 and 1.25 equivalents of acid in ethanol with and without 5% water (US 9,278,933).
• Physical properties of the mono-phosphate (US 9,278,933 B2): Crystalline by XRPD, a single DSC endotherm at 179 °C, water solubility above 36 mg/mL, moderate hygroscopicity, and batch-to-batch counter-ion ratios of 1:1.6 to 1:2.3 by ion chromatography (US 9,278,933).
• Bioactivity records (ChEMBL): ChEMBL lists the free base as CHEMBL4302505 and the phosphate as CHEMBL4297309; the free base activity entries are single-concentration screening percentages, with no receptor binding constant (ChEMBL CHEMBL4302505).
• Chemical Directory & Structure Verification (PubChem): Phosphate: CAS 1270138-41-4, C₂₂H₃₃N₄O₅P, 464.5 g/mol, InChIKey LWHMGALTTIYPJU-UHFFFAOYSA-N, UNII HX0VO60T62 (PubChem 50922680). Free base: CAS 1270138-40-3, C₂₂H₃₀N₄O, 366.5 g/mol, InChIKey DYTOQURYRYYNOR-UHFFFAOYSA-N, UNII YVE9U408ZL, ChEBI CHEBI:228696, DSSTox DTXSID901025668, nonproprietary name amdiglurax (PubChem 50922681).
• Analytical Quality: Why chromatographic testing matters for reference materials is covered in Modern Aminos’ note on HPLC testing.

How does NSI-189 compare to other compounds?

To map salt chemistry and neurochemistry targets, researchers compare NSI-189 Phosphate against its own free base and against amine, β-carboline, adamantane and allosteric-modulator reference compounds, including several available at Modern Aminos:

Frequently Asked Questions (FAQs)