US 10,793,515 B2Granted

Compounds advantageous in the treatment of central nervous system diseases and disorders

AssigneeAurimmed Pharma, Inc.

InventorsAmir Pesyan, Manuel F. Balandrin

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Abstract

A series of novel amides showing broad pharmaceutical activity. Compounds described herein are effective as anticonvulsants, chemical countermeasures, and analgesics. Such compounds also show, neuroprotective/neuroreparative effects and activity against spinal muscular atrophy. Such pharmaceutically active compounds show utility in the treatment of central nervous system (“CNS”) diseases and disorders, such as anxiety, depression, insomnia, migraine headaches, schizophrenia, neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's, ALS, and Huntington's disease) spasticity, and bipolar disorder. Furthermore, such compounds may additionally find utility as analgesics (e.g., for the treatment of chronic or neuropathic pain) and as neuroprotective agents useful in the treatment of stroke(s), and/or traumatic brain and/or spinal cord injuries.

Claims14

Dependent claims

A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of Formula II admixed with at least one of a pharmaceutically acceptable carrier or an excipient, wherein Formula II is represented by

wherein:
R1 is one of H, CH3, C2H5, (CH2)2SO3H, or CHZCOOH, wherein Z is one of H, CH3, CH(CH3)2, CH2C6H5, CH2CH(CH3)2, or CH(CH3)CH2CH3;
R2 is one of H, C1-C5 alkyl, (CH2)2OCH3, (CH2)3OCH3;
R3 is one of CH3, CH2CH3, CH(CH3)2, cyclopropyl or together with R5 (—CH2-)2, (—CH2-)3, (—CH2-)4, or (—CH2-)5,
R5 is one of H, CH3 when R3 is CH3, or together with R3 (—CH2-)2, (—CH2-)3, (—CH2-)4, or (—CH2-)5,
each R4 is independently one of Cl, F, CF3, C1-C5 alkyl, C1-C5 alkoxy, OCF3, or CONR1R2, or R4 is
where X is CH2, (CH2)2, or CF2;
and
n=1-4, wherein:
when R1 is H, R2 is H, R3 is CH3, R5 is H, and n=1, then R4 is one of F, CF3, C2-C5 alkyl, C2-C5 alkoxy, OCF3, CONR1R2, or
where X is CH2, (CH2)2, or CF2;
when R1 is H, R2 is H, R3 is CH3, R5 is H, and n=2, then each R4 is independently one of F, CF3, C1-C5 alkyl, C2-C5 alkoxy, OCF3, or CONR1R2, or
R4 is
where X is CH2, (CH2)2, or CF2;
when R1 is H, R2 is H, R3 is CH3, R5 is CH3, and n=1, then R4 is one of F, CF3, C2-C5 alkyl, C3-C5 alkoxy, OCF3, CONR1R2,
where X is CH2, (CH2)2, or CF2;
when R1 is H, R2 is H, R3 is CH3, R5 is CH3, and n=2, then each R4 is independently one of Cl, F, CF3, C2-C5 alkyl, C2-C5 alkoxy, OCF3, or CONR1R2, or R4 is
where X is CH2, (CH2)2, or CF2;
when R1 is CH3 or C2H5, R2 is CH3 or C2H5, R3 is CH3, R5 is H, and n=1, then R4 is one of C1, CF3, C1-C5 alkyl, C2-C5 alkoxy, OCF3, CONR1R2,
where X is CH2, (CH2)2, or CF2;
when R1 is H, R2 is C1-C5 alkyl, R3 is CH3, R5 is H, and n=1, then R4 is one of F, CF3, C1-C5 alkyl, OCF3, or CONR1R2, or R4 is
where X is CH2, (CH2)2, or CF2;
and
when R1 is H, R2 is H, R3 is together with R5 (—CH2-)4, and n=2, then each R4 is independently one of Cl, F, CF3, C1-C5 alkyl, OCF3, or CONR1R2, or
R4 is
where X is CH2, (CH2)2, or CF2.

23 more elements

A pharmaceutical composition comprising at least one compound represented by Formula II admixed with at least one of a pharmaceutically acceptable carrier or an excipient:

wherein
R1 is one of H, CH3, C2H5, (CH2)2SO3H, or CHZCOOH, wherein Z is one of H, CH3, CH(CH3)2, CH2C6H5, CH2CH(CH3)2, or CH(CH3)CH2CH3;
R2 is one of H, C1-C5 alkyl, (CH2)2OCH3, (CH2)3OCH3;
R3 is one of CH3, CH2CH3, CH(CH3)2, cyclopropyl or together with R5 (—CH2-)2, (—CH2-)3, (—CH2-)4, or (—CH2-)5,
R5 is one of H, CH3 when R3 is CH3, or together with R3 (—CH2-)2, (—CH2-)3, (—CH2-)4, or (—CH2-)5,
each R4 is independently one of Cl, F, CF3, C1-C5 alkyl, C1-C5 alkoxy, OCF3, or CONR1R2, or R4 is
where X is CH2, (CH2)2, or CF2;
and
n=1-4,
wherein:
when R1 is H, R2 is H, R3 is CH3, R5 is H, and n=1, then R4 is one of F, CF3, C2-C5 alkyl, C2-C5 alkoxy, OCF3, CONR1R2, or
where X is CH2, (CH2)2, or CF2;
when R1 is H, R2 is H, R3 is CH3, R5 is H, and n=2, then each R4 is independently one of F, CF3, C1-C5 alkyl, C2-C5 alkoxy, OCF3, or CONR1R2, or
R4 is
where X is CH2, (CH2)2, or CF2;
when R1 is H, R2 is H, R3 is CH3, R5 is CH3, and n=1, then R4 is one of Cl, F, CF3, C1-C5 alkyl, C3-C5 alkoxy, OCF3, CONR1R2,
where X is CH2, (CH2)2, or CF2;
when R1 is H, R2 is H, R3 is CH3, R5 is CH3, and n=2, then each R4 is independently one of Cl, F, CF3, C2-C5 alkyl, C2-C5 alkoxy, OCF3, or CONR1R2, or R4 is
where X is CH2, (CH2)2, or CF2;
and
when R1 is CH3 or C2H5, R2 is CH3 or C2H5, R3 is CH3, R5 is H, and n=1, then R4 is one of C1, CF3, C1-C5 alkyl, C2-C5 alkoxy, OCF3, CONR1R2,
where X is CH2, (CH2)2, or CF2.

19 more elements

A pharmaceutical composition comprising at least one compound represented by Formula II admixed with at least one of a pharmaceutically acceptable carrier or an excipient:

wherein:
R1 is one of H, CH3, C2H5, (CH2)2SO3H, or CHZCOOH, wherein Z is one of H, CH3, CH(CH3)2, CH2C6H5, CH2CH(CH3)2, or CH(CH3)CH2CH3;
R2 is one of H, C1-C5 alkyl, (CH2)2OCH3, (CH2)3OCH3;
R3 is one of CH3, CH2CH3, CH(CH3)2, cyclopropyl or together with R5 (—CH2-)2, (—CH2-)3, (—CH2-)4, or (—CH2-)5,
R5 is one of H, CH3 when R3 is CH3, or together with R3 (—CH2-)2, (—CH2-)3, (—CH2-)4, or (—CH2-)5,
each R4 is independently one of Cl, F, CF3, C1-C5 alkyl, C1-C5 alkoxy, OCF3, or CONR1R2, or R4 is
where X is CH2, (CH2)2, or CF2;
and
n=1-4, wherein:
when R1 is H, R2 is H, R3 is CH3, R5 is H, and n=1, then R4 is one of F, C2-C5 alkyl, C2-C5 alkoxy, OCF3, CONR1R2, or
where X is CH2, (CH2)2, or CF2;
when R1 is H, R2 is H, R3 is CH3, R5 is H, and n=2, then each R4 is independently one of F, CF3, C1-C5 alkyl, C2-C5 alkoxy, OCF3, or CONR1R2, or
R4 is
where X is CH2, (CH2)2, or CF2;
when R1 is H, R2 is H, R3 is CH3, R5 is CH3, and n=1, then R4 is one of Cl, F, CF3, C1-C5 alkyl, C3-C5 alkoxy, OCF3, CONR1R2,
where X is CH2, (CH2)2, or CF2;
when R1 is H, R2 is H, R3 is CH3, R5 is CH3, and n=2, then each R4 is independently one of Cl, F, CF3, C2-C5 alkyl, C2-C5 alkoxy, OCF3, or CONR1R2, or R4 is
where X is CH2, (CH2)2, or CF2;
when R1 is CH3 or C2H5, R2 is CH3 or C2H5, R3 is CH3, R5 is H, and n=1, then R4 is one of C1, CF3, C1-C5 alkyl, C2-C5 alkoxy, OCF3, CONR1R2,
where X is CH2, (CH2)2, or CF2;
and
when one of R1 or R2 is H, one of R1 or R2 is CH3, R3 is CH3, R5 is H, and n=2, then each R4 is independently one of CF3, C1-C5 alkyl, C2-C5 alkoxy, OCF3, or CONR1R2, or R4 is
where X is CH2, (CH2)2, or CF2.

20 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/938,341Filed 11 Nov 2015 · continuation in part
Priority: 19 Mar 2008
Published: US 2016/0137592 A119 May 2016
Granted: 6 Oct 2020
Term ends: Not estimatedThe source records don’t support an estimate.

Classification34 codes

C07C 233/08
Having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals: with carbon atoms of…
A61K 31/165
Amides, e.g. hydroxamic acids: having aromatic rings, e.g. colchicine, atenolol, progabide
A61K 31/353
Condensed with carbocyclic rings, e.g. methantheline: 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
A61K 31/36
Having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel: compounds containing methylenedioxyphenyl groups, e.g. sesamin

Family

Application61/037,987Us provisional application · filed 19 Mar 2008
PCT/US2009/037558Parent of this continuation-in-part · filed 18 Mar 2009
Application61/243,110Us provisional application · filed 16 Sep 2009
Application61/334,356Us provisional application · filed 13 May 2010
Application12/881,068Parent of this continuation-in-part · filed 13 Sep 2010
Application62/242,807Us provisional application · filed 16 Oct 2015
US 2016/0137592 A1Pre-grant publication · published 19 May 2016
US 9,212,155 B2Parent of this continuation-in-part
Application12/922,068Parent of this continuation-in-part
US 9,206,143 B2Parent of this continuation-in-part
US 2011/0046128 A1Published application
US 2011/0046138 A1Published application
US 10,793,515 B2This patent

From the US filing history. Foreign family members aren’t listed.