Alkoxy aryl &bgr;2 adrenergic receptor agonists

Details Alkoxy aryl &bgr;2 adrenergic receptor agonists Alkoxy aryl &bgr;2 adrenergic receptor agonists

2003-05-27

2004-06-08

Davis, Zinna Northington (Department: 1625)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C514S613000, C514S646000, C546S157000, C564S123000, C564S305000

Reexamination Certificate

active

06747043

ABSTRACT:

FIELD OF THE INVENTION
The invention is directed to novel &bgr;
2
adrenergic receptor agonists. The invention is also directed to pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with &bgr;
2
adrenergic receptor activity, and processes and intermediates useful for preparing such compounds.
BACKGROUND OF THE INVENTION
&bgr;
2
adrenergic receptor agonists are recognized as effective drugs for the treatment of pulmonary diseases such as asthma and chronic obstructive pulmonary disease (including chronic bronchitis and emphysema). &bgr;
2
adrenergic receptor agonists are also useful for treating pre-term labor, and are potentially useful for treating neurological disorders and cardiac disorders. In spite of the success that has been achieved with certain &bgr;
2
adrenergic receptor agonists, current agents possess less than desirable potency, selectivity, onset, and/or duration of action. Thus, there is a need for additional &bgr;
2
adrenergic receptor agonists having improved properties. Preferred agents may possess, among other properties, improved potency, selectivity, onset, and/or duration of action.
SUMMARY OF THE INVENTION
The invention provides novel compounds that possess &bgr;
2
adrenergic receptor agonist activity. Accordingly, there is provided a compound of the invention which is a compound of formula (I):
wherein:
R
1
is —CH
2
OH or —NHCHO, and R
2
is hydrogen; or R
1
and R
2
taken together are —NHC(═O)CH═CH—;
R
3
, R
4
, and R
5
are each independently hydrogen, halo, alkyl, alkoxy, or aryl, wherein each alkyl and alkoxy is optionally substituted with one or more halo; or R
3
and R
4
together form a fused benzo ring; or R
4
and R
5
together form a fused benzo ring; and
R
6
is hydrogen or hydroxy;
or a pharmaceutically-acceptable salt or solvate or stereoisomer thereof.
The invention also provides a pharmaceutical composition comprising a compound of the invention and a pharmaceutically-acceptable carrier. The invention further provides combinations comprising a compound of the invention and one or more other therapeutic agents and pharmaceutical compositions comprising such combinations.
The invention also provides a method of treating a disease or condition associated with &bgr;
2
adrenergic receptor activity (e.g. a pulmonary disease, such as asthma or chronic obstructive pulmonary disease, pre-term labor, a neurological disorder, a cardiac disorder, or inflammation) in a mammal, comprising administering to the mammal, a therapeutically effective amount of a compound of the invention. The invention further provides a method of treatment comprising administering a therapeutically effective amount of a combination of a compound of the invention together with one or more other therapeutic agents.
The invention also provides a method of treating a disease or condition associated with &bgr;
2
adrenergic receptor activity (e.g. a pulmonary disease, such as asthma or chronic obstructive pulmonary disease, pre-term labor, a neurological disorder, a cardiac disorder, or inflammation) in a mammal, comprising administering to the mammal, a therapeutically effective amount of a pharmaceutical composition of the invention.
This invention also provides a method of modulating a &bgr;
2
adrenergic receptor, the method comprising stimulating a &bgr;
2
adrenergic receptor with a modulatory amount of a compound of the invention.
In separate and distinct aspects, the invention also provides synthetic processes and intermediates described herein, which are useful for preparing compounds of the invention.
The invention also provides a compound of the invention as described herein for use in medical therapy, as well as the use of a compound of the invention in the manufacture of a formulation or medicament for treating a disease or condition associated with &bgr;
2
adrenergic receptor activity (e.g. a pulmonary disease, such as asthma or chronic obstructive pulmonary disease, pre-term labor, a neurological disorder, a cardiac disorder, or inflammation) in a mammal.
DETAILED DESCRIPTION OF THE INVENTION
When describing the compounds, compositions and methods of the invention, the following terms have the following meanings, unless otherwise indicated.
The term “alkyl” refers to a monovalent saturated hydrocarbon group which may be linear or branched or combinations thereof. Such alkyl groups preferably contain from 1 to 20 carbon atoms; more preferably, from 1 to 8 carbon atoms; and still more preferably, from 1 to 4 carbon atoms. Representative alkyl groups include, by way of example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl and the like.
The term “alkoxy” refers to a group of the formula —OR, where R is an alkyl group as defined herein. Representative alkoxy groups include, by way of example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, n-pentoxy, n-hexoxy and the like.
The term “aryl” refers to a monovalent carbocyclic group which may be monocyclic or multicyclic (i.e., fused) wherein at least one ring is aromatic. Such aryl groups preferably contain from 6 to 20 carbon atoms, more preferably, from 6 to 10 carbon atoms. This term includes multicyclic carbocyclic ring systems wherein one or more rings are not aromatic, provided the point of attachment is on an aromatic ring. Representative aryl groups include, by way of example, phenyl, napthyl, azulenyl, indan-5-yl, 1,2,3,4-tetrahydronaphth-6-yl, and the like.
The term “halo” refers to a fluoro, chloro, bromo or iodo.
The term “therapeutically effective amount” refers to an amount sufficient to effect treatment when administered to a patient in need of treatment.
The term “treatment” as used herein refers to the treatment of a disease or medical condition in a patient, such as a mammal (particularly a human) which includes:
(a) preventing the disease or medical condition from occurring, i.e., prophylactic treatment of a patient;
(b) ameliorating the disease or medical condition, i.e., eliminating or causing regression of the disease or medical condition in a patient;
(c) suppressing the disease or medical condition, i.e., slowing or arresting the development of the disease or medical condition in a patient; or
(d) alleviating the symptoms of the disease or medical condition in a patient.
The phrase “disease or condition associated with &bgr;
2
adrenergic receptor activity” includes all disease states and/or conditions that are acknowledged now, or that are found in the future, to be associated with &bgr;
2
adrenergic receptor activity. Such disease states include, but are not limited to, pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (including chronic bronchitis and emphysema), as well as neurological disorders and cardiac disorders. &bgr;
2
adrenergic receptor activity is also known to be associated with pre-term labor (see U.S. Pat. No. 5,872,126) and some types of inflammation (see International Patent Application Publication Number WO 99/30703 and U.S. Pat. No. 5,290,815).
The term “pharmaceutically-acceptable salt” refers to a salt prepared from a base or acid which is acceptable for administration to a patient, such as a mammal. Such salts can be derived from pharmaceutically-acceptable inorganic or organic bases and from pharmaceutically-acceptable inorganic or organic acids.
Salts derived from pharmaceutically-acceptable acids include acetic, benzenesulfonic, benzoic, camphosulfonic, citric, ethanesulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, lactic, maleic, malic, mandelic, methanesulfonic, mucic, nitric, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic, xinafoic (1-hydroxy-2-naphthoic acid) and the like. Particularly preferred are salts derived from fumaric, hydrobromic, hydrochloric, acetic, sulfuric, methanesulfonic, xinafoic, and tartaric acids.
Salts derived from pharmaceutically-acceptable inorganic bases include a

Affiliated with

Also associated with

Rating

Alkoxy aryl &bgr;2 adrenergic receptor agonists does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Alkoxy aryl &bgr;2 adrenergic receptor agonists, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Alkoxy aryl &bgr;2 adrenergic receptor agonists will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3345622