# US 9,751,847 B2 · Methods and compositions related to neuroactive thiazoline compounds

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- Number: US 9,751,847 B2
- Document ID: US9751847B2
- Status: Granted
- Kind: B2
- Application number: 13/878,189
- Filed: 2011-10-14
- Published: 2014-01-16
- Granted: 2017-09-05
- Earliest claimed: 2010-10-14
- Assignees: University of Utah Research Foundation
- Applicants: Eric W. Schmidt; Zhenjian Lin; Rowena R. Antemano; Alan Light; Baldomero M. Olivera; Gisela P. Concepcion
- Inventors: Eric W. Schmidt; Zhenjian Lin; Rowena R. Antemano; Alan Light; Baldomero M. Olivera; Gisela P. Concepcion
- Web page: https://patentgrep.com/patent/US9751847B2

## CPC

- C07D 277/10: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A61K 31/421: 1,3-Oxazoles, e.g. pemoline, trimethadione
- A61K 31/426: 1,3-Thiazoles
- A61K 31/427: not condensed and containing further heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07D 277/12: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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)

## Abstract

In one aspect, the invention relates to compounds having a general structure: and methods of using same to modulate calcium release. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

## Claims

### Claim 1

A method for treating a disorder in a mammal, the method comprising the step of administering to the mammal an effective amount of least one compound having a structure represented by a formula:
wherein ----- is an optional covalent bond, wherein valency is satisfied;
wherein Z is selected from O and S;
wherein R1 is selected from hydrogen and optionally substituted C1-C6 alkyl;
wherein R2 is selected from nitrile, formyl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted alkoxyl, optionally substituted thioalkyl, optionally substituted alkylsulfonyl, thioamido, amino-carbonyl, and alkylamine-carbonyl;
wherein R3 is selected from hydrogen and optionally substituted C1-C6 alkyl;
wherein each of R4a, R4b,R4c, and R4d is independently selected from hydrogen, halogen, hydroxyl, nitrile, nitro, thiol, formyl, optionally substituted amino, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkoxyl, optionally substituted thioalkyl, optionally substituted alkylsulfinyl, optionally substituted alkyl sulfonyl, optionally substituted alkylamino, thioamido, amidosulfonyl, alkoxycarbonyl, carboxamide, amino-carbonyl, alkylamine-carbonyl, and optionally substituted C1-C6 alkyl;
or a pharmaceutically acceptable salt thereof,
wherein the disorder is asthma.

### Claim 2 (depends on 1)

The method of claim 1, wherein the mammal is a human.

### Claim 3 (depends on 1)

The method of claim 1, wherein the mammal has been diagnosed with a need for treatment of the disorder prior to the administering step.

### Claim 4 (depends on 1)

The method of claim 1, wherein Z is S.

### Claim 5 (depends on 1)

The method of claim 1, wherein R1 is methyl.

### Claim 6 (depends on 1)

The method of claim 1, wherein R2 is selected from formyl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, alkoxycarbonyl, amino-carbonyl, and alkylamine-carbonyl.

### Claim 7 (depends on 1)

The method of claim 1, wherein R2 has a structure represented by a formula:
wherein Y is selected from O and S;
wherein R5a and R5b together comprise ═O or ═S, or wherein each of R5a and R5b is independently selected from hydrogen and optionally substituted C1-C6 alkyl;
wherein R6 is selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, and optionally substituted benzyl.

### Claim 8 (depends on 1)

The method of claim 1, wherein R3 is hydrogen.

### Claim 9 (depends on 1)

The method of claim 1, wherein the compound has a structure represented by a formula:
wherein R1 is selected from hydrogen and optionally substituted C1-C6 alkyl;
wherein R2 is selected from nitrile, formyl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted alkoxyl, optionally substituted thioalkyl, optionally substituted alkyl sulfonyl, thioamido, amino-carbonyl, and alkylamine-carbonyl;
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

The method of claim 1, wherein the compound is selected from:

### Claim 11 (depends on 1)

The method of claim 1, wherein the compound has a structure represented by a formula:

### Claim 12

A method for treating a disorder in a mammal, the method comprising the step of administering to the mammal an effective amount of least one compound having a structure represented by a formula:
wherein Z is selected from O and S;
wherein R1 is optionally substituted C1-C6 alkyl;
wherein R2 is selected from nitrile, formyl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted alkoxyl, optionally substituted thioalkyl, optionally substituted alkyl sulfonyl, thioamido, carboxamide, amino-carbonyl, and alkylamine-carbonyl;
wherein R3 is selected from hydrogen and optionally substituted C1-C6 alkyl;
or a pharmaceutically acceptable salt thereof,
wherein the disorder is asthma.

### Claim 13 (depends on 12)

The method of claim 12, wherein the mammal is a human.

### Claim 14 (depends on 12)

The method of claim 12, wherein the mammal has been diagnosed with a need for treatment of the disorder prior to the administering step.

### Claim 15 (depends on 1)

The method of claim 1, wherein Z is S.

### Claim 16 (depends on 1)

The method of claim 1, wherein R1 is methyl.

### Claim 17 (depends on 1)

The method of claim 1, wherein R2 is selected from formyl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, alkoxycarbonyl, carboxamide, amino-carbonyl, and alkylamine-carbonyl.

### Claim 18 (depends on 1)

The method of claim 1, wherein R2 has a structure represented by a formula:
wherein Y is selected from O and S;
wherein R5a and R5b together comprise ═O or ═S, or wherein each of R5a and R5b is independently selected from hydrogen and optionally substituted C1-C6 alkyl;
wherein R6 is selected from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, and optionally substituted benzyl.

### Claim 19 (depends on 12)

The method of claim 12, wherein R3 is hydrogen.

### Claim 20 (depends on 12)

The method of claim 12, wherein the compound has a structure represented by a formula:
wherein R1 is optionally substituted C1-C6 alkyl;
wherein R2 is selected from nitrile, formyl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted alkoxyl, optionally substituted thioalkyl, optionally substituted alkylsulfonyl, thioamido, carboxamide, amino-carbonyl and alkylamine-carbonyl;
or a pharmaceutically acceptable salt thereof.

### Claim 21 (depends on 12)

The method of claim 12, wherein the compound is selected from:

### Claim 22 (depends on 12)

The method of claim 12, wherein the compound has a structure represented by a formula:

### Claim 23

A method for treating a disorder in a mammal, the method comprising the step of administering to the mammal an effective amount of least one compound having a structure represented by a formula:
wherein Z is selected from O and S;
wherein R2 is selected from nitrile, formyl, optionally substituted heteroaryl, optionally substituted heterocycloalkyl, optionally substituted alkoxyl, optionally substituted thioalkyl, optionally substituted alkyl sulfonyl, thioamido, alkoxycarbonyl, amino-carbonyl, and alkylamine-carbonyl;
or a pharmaceutically acceptable salt thereof,
wherein the disorder is asthma.

### Claim 24 (depends on 23)

The method of claim 23, wherein R2 is —CH2OH.