Substituted bicyclic compounds
AssigneeBristol-Myers Squibb Company
InventorsAlaric J. Dyckman, T.G. Murali Dhar, Hai-Yun Xiao, John L. Gilmore, Michael G. Yang, Zili Xiao, David Marcoux
Life of this patent
Estimating the term…
Abstract
Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R1 is —OH or —OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
Claims12
1-16. (canceled)
A compound of Formula (II):
- or a salt thereof, wherein:
- R1 is —OH or —OP(O)(OH)2;
- X1 is CH2 or O;
- X2 is CH2 or 0;
- X3 is CH2 or O, provided that X2 is O only if both X1 and X3 are each CH2;
- R2a is —(CH2)3-6CH3, —(CH2)1-4CH═CRxRx, —(CH2)1-4CH═CRx(CH2CH3), —CH═CH(CH2)1-3C(Rx)3, —CH═CH(CH2)1-3OCH3, —(CH2)1-3CH═CHCH═CRxRx, —CH═CH(CH2)1-3CH═CRxRx, —CH═CHRz, —(CH2)1-3Rz, —(CH2)1-3O(CH2)0-3Rz, —(CH2)1-3S(CH2)0-3Rz, —CH2S(O)Rz, —CH2S(O)2Rz, —O(CH2)1-2Rz, —O(CH2)1-2O(CH2)0-2Rz, —OC(O)Rz, —(CH2)1-4O(CH2)0-9C(Rx)3, —(CH2)1-4O(CH2)0-9CF3, —(CH2)1-4CRxRxO(CH2)0-4C(Rx)3, —(CH2)1-3O(CH2)1-4CH═CRx(CH2)0-3CH3, —(CH2)1-3O(CH2)1-4CH═CRxRx, —(CH2)1-3O(CH2)1-4C(OH)RxRx, —(CH2)1-3O(CH2)1-4O(CH2)0-3CH3, —(CH2)1-3S(CH2)0-4C(Rx)3, —(CH2)0-3O(CH2)1-4S(CH2)0-3C(Rx)3, —(CH2)1-3S(CH2)1-4Si(CH3)3, —(CH2)1-3S(O)(CH2)0-4C(Rx)3, —(CH2)1-3 S(O)2(CH2)0-4C(Rx)3, —(CH2)1-5NRxRx, —O(CH2)1-7C(Rx)3, —O(CH2)1-4O(CH2)0-4C(Rx)3, —O(CH2)1-4CH═CRx(CH2)0-3CH3, —O(CH2)1-4O(CH2)0-3C(Rx)3, —O(CH2)1-4O(CH2)1-3CH═CRxRx, —O(CH2)1-4O(CH2)1-3C≡CRx, —C(O)(CH2)0-4C(Rx)3, —OC(O)(CH2)0-4C(Rx)3, —OC(O)CRxRx(CH2)0-4C(Rx)3, —OC(O)NRx(CH2)0-5C(Rx)3, —NRxC(O)NRx(CH2)0-5C(Rx)3, —C(CH3)═N—O(CH2)0-5C(Rx)3, —C(CH3)═N—O(CH2)1-2(phenyl), —C(CH3)═N—O(CH2)1-2(fluorophenyl), —C(CH3)═N—O(CH2)1-2(methoxyphenyl), phenyl, or pyridinyl;
- each Rx is independently H or —CH3;
- and
- Rz is phenyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, quinolinyl, thiophenyl, thiazolyl, oxetanyl, C3-6 cycloalkyl, adamantanyl, or tetrahydropyranyl, each substituted with zero to 4 substituents independently selected from F, Cl, I, C1-4 alkyl, —O(C1-3 alkyl), —CF3, —OCF3, —(CH2)1-6OCH3, —CH2NRxRx, —C(O)NRxRx, —C(O)NRx(C1-4 alkyl), and —CH2C(O)NRxRx.
The compound according to claim 1, wherein said compound is:
- (1-amino-3-((R)-2-((pentyloxy)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl) cyclopentyl)methanol (1-6);
- (1-amino-3-(2-hexylchroman-6-yl)cyclopentyl)methanol (15-18);
- ((1R,3S)-1-amino-3-(3-hexylisochroman-7-yl)cyclopentyl)methanol (19);
- (1-amino-3-(3-hexylchroman-7-yl)cyclopentyl)methanol (20-23);
- ((1R,3S)-1-amino-3-((S)-3-hexylisochroman-7-yl)cyclopentyl)methanol (24);
- ((1R,3S)-1-amino-3-((R)-3-hexylisochroman-7-yl)cyclopentyl)methanol (25);
- or
- ((1R,3S)-1-amino-3-((S)-3-heptylisochroman-7-yl)cyclopentyl)methanol (26-27);
Dependencies are inferred from the claim text.