MDMB-INACA: Structural Characterization and Analytical Profile of a 1H-Indazole-3-Carboxamide Synthetic Cannabinoid

MDMB-INACA (methyl N-(1H-indazole-3-carbonyl)-3-methylvalinate) is a synthetic cannabinoid belonging to the indazole-3-carboxamide class. This compound features a 1H-indazole-3-carboxylic acid core coupled with a methyl 3,3-dimethylbutanoate (MDMB) tail via an amide linkage. Structurally analogous to the ADB-5Br-INACA series but lacking halogen substitution, MDMB-INACA represents a foundational scaffold within the indazole-3-carboxamide cannabinoid family.

Molecular Identity

ParameterValue
Common NameMDMB-INACA
IUPAC NameMethyl N-(1H-indazole-3-carbonyl)-3-methylvalinate
CAS Number2709672-58-0
Molecular FormulaC₁₅H₁₉N₃O₃
Molecular Weight289.33 g/mol
InChI KeyQEXPVGIGOZJEOO-UHFFFAOYSA-N
SMILESCOC(=O)C(C(C)(C)C)NC(=O)c1n[nH]c2c1cccc2
PubChem CID165361543

Structural Overview

The molecular architecture of MDMB-INACA consists of three key structural components:

  • 1H-Indazole Core — A fused bicyclic heteroaromatic system comprising a benzene ring fused to a pyrazole ring. This core provides the primary π-stacking interaction surface for cannabinoid receptor (CB₁/CB₂) binding.
  • Carboxamide Linker — The 3-position of the indazole ring bears a carboxamide (-CONH-) functional group, which serves as the critical hydrogen-bond donor/acceptor motif responsible for receptor recognition.
  • MDMB Ester Tail — The N-(methyl 3,3-dimethylbutanoate) substituent features a bulky tert-butyl group (3,3-dimethyl) adjacent to the chiral α-carbon center. The methyl ester terminus contributes to the overall lipophilicity required for blood-brain barrier penetration.

Physicochemical Properties

  • logP (calculated): ~2.8 — Optimal lipophilicity for CNS penetration
  • Hydrogen Bond Donors: 2 (indazole N-H, amide N-H)
  • Hydrogen Bond Acceptors: 4 (amide C=O, ester C=O, indazole N, ester O)
  • Rotatable Bonds: 5 — Conformational flexibility for receptor adaptation
  • Polar Surface Area (PSA): ~84 Ų — Within the acceptable range for CNS-active compounds

Receptor Pharmacology

MDMB-INACA acts as a potent agonist at both cannabinoid receptor subtypes. The indazole-3-carboxamide scaffold, when paired with the MDMB tail, exhibits enhanced CB₁ selectivity compared to its indole-based analogs (e.g., MDMB-ICA). The absence of a 5-halogen substituent (cf. ADB-5Br-INACA or MDMB-5Br-INACA) may modulate the binding kinetics and functional selectivity profile.

Synthetic Considerations

The general synthetic route to MDMB-INACA involves activation of 1H-indazole-3-carboxylic acid (CAS 4498-67-3) via CDI or thionyl chloride, followed by amide coupling with methyl 3-amino-3,3-dimethylbutanoate hydrochloride under basic conditions (Et₃N or DIPEA in anhydrous DCM or THF). Typical yields range from 65-85% after purification by column chromatography.

Analytical Data

¹H NMR (400 MHz, CDCl₃): δ 10.85 (br s, 1H, indazole N-H), 8.25 (d, J = 8.0 Hz, 1H, Ar-H), 7.62 (d, J = 8.2 Hz, 1H, Ar-H), 7.45 (t, J = 7.6 Hz, 1H, Ar-H), 7.28 (t, J = 7.6 Hz, 1H, Ar-H), 6.95 (br d, 1H, amide N-H), 4.68 (d, J = 9.0 Hz, 1H, CH-CO₂Me), 3.78 (s, 3H, OCH₃), 1.12 (s, 9H, C(CH₃)₃).

ESI-MS: [M+H]⁺ m/z 290.2, [M+Na]⁺ m/z 312.1

HPLC Purity: ≥ 97% (area normalization, UV 254 nm, C18 reverse phase, MeCN/H₂O gradient)

References

  • Aipsin, Issue 17, May 2021: V-15
  • Aipsin, Issue 39, Mar 2023: XII-64; XII-65
  • Aipsin, Issue 41, May 2023: XII-73
  • PubChem CID 165361543
  • Project Response — MDMB-INACA, Report 2074-19

Supply Information

Sun Pharma Chemical offers high-purity MDMB-INACA (CAS 2709672-58-0) for research purposes.

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