# US 11,439,608 B2 · Roles of modulators of intersectin-CDC42 signaling in Alzheimer's disease

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- Number: US 11,439,608 B2
- Document ID: US11439608B2
- Status: Granted
- Kind: B2
- Application number: 16/141,849
- Filed: 2018-09-25
- Published: 2019-03-28
- Granted: 2022-09-13
- Earliest claimed: 2017-09-25
- Assignees: Qun Lu
- Applicants: Qun Lu
- Inventors: Qun Lu; Byron Aguilar; Yi Zhu; Yan-Hua Chen
- Web page: https://patentgrep.com/patent/US11439608B2

## CPC

- A61K 31/18: Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63)
- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- A61K 31/343: condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
- A61K 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Methods of treating Alzheimer's disease and other neurodegenerative and/or neurocognitive and/or neurodevelopmental diseases are described. The methods comprise the administration of compounds that modulate an activity of cell division control protein 42 (Cdc42), such as the interaction between Cdc42 and intersectin (ITSN). Exemplary modulator compounds include thioureas, disulfonamides of fused aromatic systems (e.g., benzofuran), and acyl hydrazones, among others. Some of the modulator compounds act as activators of Cdc42, while others act as inhibitors. In some cases, the modulator compound has dual functionality and the ability of the modulator compound to act as an inhibitor or activator depends on whether or not Cdc42 is already activated in a particular disease stage or biological environment by an upstream activating signal of Cdc42.

## Claims

### Claim 1

A method of treating Alzheimer's disease in a subject in need of treatment thereof, wherein the method comprises administering to the subject a compound having the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein amyloid and tau imaging of the subject in need of treatment shows amyloid and tau accumulation.

### Claim 3 (depends on 1)

The method of claim 1, wherein the subject in need of treatment is a subject with contact avoidance, agitation, and/or psychosis.

### Claim 4 (depends on 1)

The method of claim 1, wherein brain imaging of the subject in need of treatment shows loss of neuronal spine or synaptic terminals.