Methods and materials for inhibiting CB1 activity
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsBeibei Chen, Toren Finkel, Yuan Liu
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Abstract
This document provides compounds that can inhibit CB1 activity within a mammal (e.g., a human), as well as the methods of using such compounds for treating diseases, disorders, and conditions such as obesity, fear, metabolic-related disorders, diabetes, dyslipidaemia, and atherosclerosis.
Claims8
A method of inhibiting CB-1 activity within a mammal, wherein said method comprises administering, to said mammal, an effective amount of a compound of Formula (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- X1 is selected from O;
- X2 is NR4;
- X3 is C(═O),
- n is 0 or 1;
- R2 is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein each of C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from R9;
- each R3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R9;
- each R4 is each independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, S(O)2Rb1, and S(O)2NRc1Rd1;
- wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R9;
- R5 is H or halo,
- R6 is halo or C1-C6 alkyl,
- R7 a group of formula (i):
- and R8 is H;
- or R8 is a group of formula (i):
- and R7 is H;
- R11 is selected from C1-3 alkyl and ring A, wherein C1-3 alkyl is optionally substituted with C6 aryl;
- RN is selected from H, or
- R11 and RN, together with the N atom to which they are attached, for a 5-6 membered heterocycloalkyl, optionally substituted with 1, 2, or 3 substituents independently selected from R9;
- each R9 is independently selected from H, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, NO2, ORa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1S(O)2Rb1, S(O)2Rb1, and S(O)2NRc1Rd1,
- ring A is selected from C6-10 aryl, C3-10 cycloalkyl, each of which is substituted with 1-10 substituents independently selected from RA;
- each RA is independently selected from halo, CN, ORa1, and C(O)Rb1,
- each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-4 haloalkyl.
A method of inhibiting CB-1 activity within a mammal, wherein said method comprises administering, to said mammal, an effective amount of a compound selected from:
- or a pharmaceutically acceptable salt thereof, wherein
- R2 is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein each of C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from R9:
- each R3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R9;
- each R4 is each independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, S(O)2Rb1, and S(O)2NRc1Rd1, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R9;
- R5 is H or halo,
- R6 is halo or C1-C6 alkyl
- R7 is a group of formula (i):
- and R8 is H;
- or R8 is a group of formula (i):
- and R7 is H;
- R11 is selected from C1-3 alkyl and ring A, wherein C1-3 alkyl is optionally substituted with C6 aryl;
- RN is selected from H, or
- R11 and RN, together with the N atom to which they are attached, for a 5-6 membered heterocycloalkyl, optionally substituted with 1, 2, or 3 substituents independently selected from R9;
- each R9 is independently selected from H, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, NO2, ORa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1S(O)2Rb1, S(O)2Rb1, and S(O)2NRc1Rd1;
- ring A is selected from C6-10 aryl, C3-10 cycloalkyl, each of which is substituted with 1-10 substituents independently selected from RA;
- each RA is independently selected from halo, CN, ORa1, C(O)Rb1 and each Ra1 and Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-4 haloalkyl.
A method of inhibiting CB-1 activity within a mammal, wherein said method comprises administering, to said mammal, an effective amount of a compound selected from any one of the following compounds:
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.