Ilantimod

It's only fair to share...

Ilantimod

CAS 2242464-44-2

MF C18H18ClN5O3 MW 387.82

6-(4-chlorophenyl)-N-[(2S)-1-hydroxypropan-2-yl]-2-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

(S)-6-(4-chlorophenyl)-N-(1-hydroxypropan-2-yl)-2-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydropyridazine-4-carboxamide
immunomodulator, BAY-2416964, BAY 2416964, Y87V4WXQ4Z

Ilantimod is an orally available formulation containing a small molecule antagonist of the aryl hydrocarbon receptor (AhR; class E basic helix-loop-helix protein 76; bHLHe76) with potential immunomodulating and antineoplastic activities. Upon oral administration, ilantimod specifically binds to AhR, inhibits AhR activation, and prevents AhR-mediated signaling. Abrogation of AhR activation prevents the activation of immune-tolerant dendritic cells (DCs) and regulatory T-cells (Tregs) in the tumor microenvironment (TME). This may restore the immune response against tumor cells. AhR, a member of the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) family of transcription factors, has important roles in regulating immunity and cellular differentiation. AhR can exhibit both pro-oncogenic and tumor suppressor-like functions depending on the tumor type; therefore, its expression may serve as a negative or positive prognostic factor.

A Study to Learn How Safe the Study Drug BAY 2416964 (AhR Inhibitor) in Combination With the Treatment Pembrolizumab is, How This Combination Affects the Body, the Maximum Amount That Can be Given, How it Moves Into, Through and Out of the Body and Its Action Against Advanced Solid Cancers in AdultsCTID: NCT04999202Phase: Phase 1Status: TerminatedDate: 2025-02-10
A First-in-Humans Dose Finding Study for an Aryl Hydrocarbon Receptor Inhibitor (AhRi) in Patients With Advanced CancerCTID: NCT04069026Phase: Phase 1Status: CompletedDate: 2024-03-06

SYN

WO-2018146010

https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2018146010&_cid=P11-MHAFJG-41587-1

Example 17

6-(4-Chlorophenyl)-/V-[(2S)-1 -hydroxypropan-2-yl]-2-(1 -methyl-1 H-pyrazol-4-yl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

A solution of 80 mg intermediate 1 1 , 29.1 mg (2S)-2-aminopropan-1 -ol, 1 10 mg HATU and 0.1 mL ethyldiisopropylamine in 5 mL of DMF was stirred at room temperature for 14 hours. Then the reaction was quenched by water, and the mixture was extracted with dichloromethane two times. The combined organic phases were dried over sodium sulfate and evaporated to dryness. The residue was subjected to RP-HPLC ((column: X-Bridge C18 5μηι 100x30mm, mobile phase: acetonitrile / water (0.1 vol% formic acid)-gradient)) to yield 50 mg 6-(4-chlorophenyl)-/V-[(2S)-1 -hydroxypropan-2-yl]-2-(1 -methyl-1 H-pyrazol-4-yl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

¹H-NMR (400 MHz, CDC ): δ [ppm] = 1.34 (d, 3H); 2.73-2.82 (m, 1 H); 3.66-3.73 (m, 1 H); 3.77-3.84 (m, 1 H); 3.98 (s, 3H); 4.26-4.36 (m, 1 H); 7.49 (d, 2H); 7.87 (d, 2H); 8.12 (s, 1 H); 8.33 (s, 1 H); 8.69 (s, 1 H); 9.82 (bd, 1 H).

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US438191125&_cid=P11-MHAFQQ-47913-1

SEE EX 17

PAT