US 12491169 B1Patent grantUnited States

Schiff-Base Candidates for PD-L1 Research

Official patent title

1-naphthalenyl aminoethyl Schiff base and use as a death ligand-1 inhibitor

Arabic title: قاعدة شيف 1-نفثالينيل أمينوإيثيل واستخدامها كمثبط لربيطة الموت المبرمج 1

Invention

Problem

The PD-1/PD-L1 immune-checkpoint interaction can suppress antitumor immune responses, creating demand for experimentally validated inhibitor candidates with suitable selectivity and safety.

Why it matters

Small-molecule checkpoint candidates could complement biologic research, but patent-stated binding metrics alone do not demonstrate cellular activity, therapeutic efficacy, or clinical safety.

Approach

The disclosure prepares substituted 1-naphthalenyl aminoethyl Schiff bases and proposes contacting PD-L1 with a compound to inhibit its binding to PD-1; it states binding metrics alongside spectroscopic characterization, but the assay basis is unclear.

Who may benefit

Potential beneficiaries include medicinal-chemistry researchers, immuno-oncology laboratories, biochemical-assay developers, computational-chemistry groups, and early preclinical discovery teams.

Potential value

The patent supplies a substituted Schiff-base compound series, a synthesis route, spectroscopic characterization, and stated PD-L1 binding values that can frame independent preclinical testing.

Background

Programmed death protein 1 and its ligand PD-L1 form an immune checkpoint that can reduce T-cell activity. Blocking this interaction is an established research strategy, but a new chemical scaffold must be supported by reproducible target-binding assays, functional immune-cell evidence, and selectivity against unintended targets. The publication describes naphthalenyl aminoethyl Schiff-base compounds and gives patent-stated binding percentages and affinity values. The supplied material does not clearly establish whether those values are experimental or computational, and reports no cellular, normal-cell, animal, pharmacokinetic, toxicology, or clinical evidence.

Technology overview

N-(naphthyl)-ethylenediamine dihydrochloride is reacted with an aldehyde in ethanol and sodium bicarbonate, including reflux for 3–7 h; other disclosed reaction conditions include 20–25 °C for 1–3 h. The compound series varies aromatic substituents and is characterized by FTIR and 1H/13C NMR. Patent-stated PD-L1 binding percentages include at least 60% and at least 75%, with examples such as 85–90% and 75–80%; stated affinity values include at least −6 and −6.5 kcal/mol.

Potential applications

Early-stage PD-L1 ligand-candidate screening.
Schiff-base medicinal-chemistry library development.
Independent biochemical and biophysical binding studies.
Structure-activity and computational-model validation research.

Evidence-supported advantages

A defined naphthalenyl aminoethyl Schiff-base scaffold is disclosed.
Multiple aromatic substituent variants are described.
A practical condensation synthesis and isolation route is provided.
FTIR and 1H/13C NMR characterization is included.

Development stage

Compound synthesis, spectroscopic characterization, and patent-stated binding metrics are described; assay basis, cellular activity, selectivity, toxicology, animal efficacy, pharmacokinetics, and clinical validation were not established.

Commercial opportunity

The compounds are early-stage research candidates, not established therapies. Progress requires independent confirmation of direct PD-L1 binding and PD-1 competition, cellular checkpoint activity, normal-cell selectivity, off-target profiling, exposure, metabolism, formulation, toxicology, animal efficacy, scalable synthesis, and regulatory studies. Clinical benefit and safety cannot be inferred from the disclosed metrics.

Patent classifications

WIPO IPC

A61K31/15Preparations for medical, dental or toiletry purposes

CPC

A61K31/15Preparations for medical, dental or toiletry purposes

Inventors

First inventorAmin Osman Elzupir
InventorSondos A. J. Almahmoud

Keywords

Schiff base
PD-L1
PD-1
immune checkpoint
naphthalenyl aminoethyl
medicinal chemistry
binding affinity
preclinical candidate

Patent document and drawings

The patent publication is mapped to this record. Patent drawings remain within that publication; no separately cleared public media package has been supplied.