# US 9,006,275 B2 · Compounds as cannabinoid receptor ligands and uses thereof

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- Number: US 9,006,275 B2
- Document ID: US9006275B2
- Status: Granted
- Kind: B2
- Application number: 12/970,480
- Filed: 2010-12-16
- Published: 2011-04-14
- Granted: 2015-04-14
- Earliest claimed: 2006-05-31
- Assignees: AbbVie Inc.
- Applicants: Alan S. Florjancic; Michael J. Dart; Keith B. Ryther; Arturo Perez-Medrano; William A. Carroll; Meena V. Patel; Karin Rosemarie Tietje; Tongmei Li; Teodozyj Kolasa; Megan E. Gallagher; Sridhar Peddi; Jennifer M. Frost; Derek W. Nelson
- Inventors: Alan S. Florjancic; Michael J. Dart; Keith B. Ryther; Arturo Perez-Medrano; William A. Carroll; Meena V. Patel; Karin Rosemarie Tietje; Tongmei Li; Teodozyj Kolasa; Megan E. Gallagher; Sridhar Peddi; Jennifer M. Frost; Derek W. Nelson
- Web page: https://patentgrep.com/patent/US9006275B2

## CPC

- A61K 31/429: condensed with heterocyclic ring systems
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 277/46: by carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D 277/48: by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines
- C07D 277/82: Nitrogen atoms
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 493/08: Bridged systems
- C07D 513/04: Ortho-condensed systems
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and L2, are defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.

## Claims

### Claim 1

A method of treating inflammatory disorders in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of a compound having formula (I)
or a pharmaceutically acceptable salt, or a combination thereof, wherein
R1 is alkyl, alkenyl, alkoxyalkyl, alkoxyalkoxyalkyl, alkoxycarbonylalkyl, alkynyl, arylalkoxyalkyl, arylalkyl, aryloxyalkyl, carboxyalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkoxyalkyl, heteroarylalkyl, heteroaryloxyalkyl, heterocycle, heterocyclealkyl, heterocycleoxyalkyl, hydroxyalkyl, or RaRbN-alkylene-;
R2 and R3, together with the carbon atoms to which they are attached, form a 4-, 5-, 6-, or 7-membered monocyclic ring, optionally fused to a benzo or a monocyclic heteroaryl, said monocyclic ring contains zero or one additional double bonds, one oxygen atom, and zero or one nitrogen atom as ring atoms; two non-adjacent atoms of said monocyclic ring can be optionally linked by an alkenylene bridge of 2, 3, or 4 carbon atoms, or optionally linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms, said monocyclic ring is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of oxo, alkyl, alkylsulfonyl, halo, —OH, —O(alkyl), and haloalkyl; two substituents on the same carbon atom of said monocyclic ring, together with the carbon atom to which they are attached, optionally form a 3-, 4-, 5-, or 6-membered monocyclic cycloalkyl ring, wherein the monocyclic cycloalkyl ring is optionally substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of alkyl and haloalkyl;
R4 is a bridged cycloalkyl or a bridged heterocycle; optionally substituted with 1, 2, 3, 4, 5, or 6 substituents selected from the group consisting of alkyl, —ORp, —NRcRd, oxo, halo, haloalkyl, carboxy and ═CH2;
Ra and Rb are each independently hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylalkyl, arylcarbonyl, arylsulfonyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heteroarylsulfonyl, heterocycle, heterocyclealkyl, heterocyclecarbonyl or heterocyclesulfonyl;
Rc and Rd, at each occurrence, are each independently hydrogen, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl or arylalkyl;
L2 is a single bond, alkylene, —NRg- or —NRg-alkylene- wherein the alkylene moiety is attached to R4 of formula (I);
Rg is hydrogen or alkyl,
the aryl, cycloalkyl, cycloalkenyl, heterocycle, and heteroaryl moieties, as substituents or part of a substituent, represented by R1, R2, R3, Ra, Rb, Rc, and Rd, are each independently unsubstituted or substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkoxyalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylsulfinyl, alkylsulfinylalkyl, alkylsulfonyl, alkylsulfonylalkyl, alkylthio, alkylthioalkyl, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, formyl, formylalkyl, halo, haloalkyl, haloalkoxy, oxo, hydroxy, hydroxyalkyl, —SH, —NO2, —NZ1Z2, and (NZ3Z4)carbonyl;
Z1 and Z2 are each independently hydrogen, alkyl, haloalkyl, alkylcarbonyl, or formyl;
Z3 and Z4 are each independently hydrogen, alkyl, or haloalkyl; and
Rp, at each occurrence, is independently hydrogen, alkyl, or haloalkyl.

### Claim 2 (depends on 1)

The method of claim 1 wherein the compound is selected from the group consisting of
N-[(2Z)-3-(2-methoxyethyl)-4,6-dihydrofuro[3,4-d][1,3]thiazol-2(3H)-ylidene]adamantane-1-carboxamide;
N-[(2Z)-3-(2-methoxyethyl)-4,6-dihydrofuro[3,4-d][1,3]thiazol-2(3H)-ylidene]hexahydro-2,5-methanopentalene-3a(1H)-carboxamide;
N-[(2Z)-1-(2-methoxyethyl)-1,4,6,7-tetrahydro-2H-pyrano[4,3-d][1,3]thiazo-l-2 ylidene]hexahydro-2,5-methanopentalene-3a(1H)-carboxamide; and
N-[(2Z)-3-(2-methoxyethyl)-4,6-dihydrofuro[3,4-d][1,3]thiazol-2 (3H)-ylidene]-2-oxatricyclo[3.3.1.13,7]decane-1-carboxamide;
or a pharmaceutically acceptable salt thereof.