公开(公告)号：US09850206B2

公开(公告)日：2017-12-26

申请号：US14443912

申请日：2013-11-20

Applicant: BIOGEN MA INC.

Inventor： Hairuo Peng ,  Edward Yin-Shiang Lin ,  Jianhua Chao ,  Zhili Xin ,  Bin Ma ,  Kevin Guckian ,  Timothy Chan ,  Gnanasambandam Kumaravel ,  Arthur G. Taveras

IPC: C07D211/22 ,  C07D213/74 ,  C07D401/12 ,  C07D237/22 ,  C07D239/47 ,  C07D207/08 ,  C07D211/56 ,  C07D211/62 ,  C07D295/15 ,  C07D295/155 ,  C07D211/70 ,  A61K31/451 ,  A61K31/4545 ,  A61K31/495 ,  A61K31/501 ,  A61K31/506 ,  A61K45/06 ,  C07D401/04 ,  C07D403/04

CPC classification number: C07D211/22 ,  A61K31/451 ,  A61K31/4545 ,  A61K31/495 ,  A61K31/501 ,  A61K31/506 ,  A61K45/06 ,  C07D207/08 ,  C07D211/56 ,  C07D211/62 ,  C07D211/70 ,  C07D213/74 ,  C07D237/22 ,  C07D239/47 ,  C07D295/15 ,  C07D295/155 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04

Abstract: Compounds of formula (I) wherein: X is —O—, —S(O)r—, —CH2—, or —NR—, wherein r is 0, 1, or 2; X1, X2, and X5 are each independently CR7 or N; one of X3 or X4 is C and is attached by a single bond to -L-, and the other is CR7 or N, provided that no more than three of X1, X2, X3, X or X5 are N; Ring A is monocyclic C5-6scycloalkyl or a 5- to 6-membered monocyclic heterocyclyl comprising from 1 to 5 heteroatoms independently selected from N, S, or O; wherein Ring A is further optionally substituted with from 1 to 3 R4; provided that Ring A is not morpholinyl, thiomorpholinyl or tetrahydro-2H-pyranyl; L is a bond, —O—, —NR—, —S(O)n—, —CH2—, or —C(O)—, wherein n is 0, 1, or 2; 1 2 L1 is an C1-8alkylene, C3-scycloalkylene, —CH2-L2-, or a 3- to 8-membered heterocyclylene comprising 1 to 5; R1 is C6-20alkyl or a monocyclic C3-8cycloalkyl; wherein said C3-8cycloalkyl is substituted with at least one R6 and may be optionally substituted with from 1 to 5 additional R6 substituents, wherein R6 for each occurrence is independently selected; and R2 is —C(O)OR3, —C(O)N(R3)—S(O)2R3, —S(O)2OR3, —C(O)NHC(O)R3, —Si(O)OH, —B(OH)2, —N(R3)S(O)2R3, —S(O)2N(R3)2, —O—P(O)(OR3)2, or —P(O)(OR3)2, —CN, —S(O)2NHC(O)R3, —C(O)NHS(O)2R3, —C(O)NHOH, —C(O)NHCN, —CH(CF3)OH, —C(CF3)2OH, or a selected heteroaryl or heterocyclyl; and pharmaceutically acceptable salts thereof, can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX).

公开(公告)号：US09808449B2

公开(公告)日：2017-11-07

申请号：US14757822

申请日：2015-12-23

Applicant: Biogen MA Inc.

Inventor： Jermaine Thomas ,  Sha Mi ,  Edward Yin-Shiang Lin ,  Guo Zhu Zheng ,  Bin Ma ,  Richard D. Caldwell ,  Kevin Guckian ,  Gnanasambandam Kumaravel

IPC: A61K31/445 ,  A61K38/21 ,  A61K31/225 ,  A61K39/395 ,  A61K31/517 ,  A61K31/695 ,  A61K31/4545 ,  C07K16/28 ,  A61K31/4709 ,  C07D215/20 ,  C07D405/12 ,  C07D211/34 ,  C07D211/60 ,  C07D211/62 ,  C07D401/06 ,  A61K31/498 ,  A61K31/55

CPC classification number: A61K31/445 ,  A61K31/225 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/498 ,  A61K31/517 ,  A61K31/55 ,  A61K31/695 ,  A61K38/21 ,  A61K39/3955 ,  C07D211/34 ,  C07D211/60 ,  C07D211/62 ,  C07D215/20 ,  C07D401/06 ,  C07D405/12 ,  C07K16/2842

Abstract: Compounds of formula (I) or (II) can modulate the activity of S1P receptors.

公开(公告)号：US09186367B2

公开(公告)日：2015-11-17

申请号：US14306231

申请日：2014-06-17

Applicant: Biogen MA Inc.

Inventor： Jermaine Thomas ,  Xiaogao Liu ,  Edward Yin-Shiang Lin ,  Guo Zhu Zheng ,  Ma Bin ,  Richard D. Caldwell ,  Kevin M. Guckian ,  Gnanasambandam Kumaravel ,  Arthur G. Taveras

IPC: A61K31/695 ,  A61K31/085 ,  A61K31/11 ,  A61K31/18 ,  A61K31/197 ,  A61K31/216 ,  A61K31/277 ,  A61K31/337 ,  A61K31/397 ,  A61K31/40 ,  A61K31/404 ,  A61K31/41 ,  A61K31/428 ,  A61K31/445 ,  A61K31/4709 ,  A61K31/472 ,  A61K31/517 ,  A61K31/662 ,  A61K31/683 ,  A61K31/06 ,  C07C229/14 ,  C07C229/22 ,  C07C229/46 ,  C07C229/48 ,  C07C237/08 ,  C07C237/52 ,  C07C309/14 ,  C07C311/51 ,  C07D205/04 ,  C07D207/16 ,  C07D209/08 ,  C07D211/60 ,  C07D211/62 ,  C07D215/20 ,  C07D217/24 ,  C07D257/04 ,  C07D305/08 ,  C07D403/06 ,  C07D417/06 ,  C07F9/38 ,  C07F9/40 ,  A61K31/47 ,  A61K45/06 ,  C07C43/247 ,  C07C47/575 ,  C07C255/54 ,  C07D215/227 ,  C07D217/04 ,  C07D239/74 ,  C07D277/64 ,  C07D401/06 ,  C07F7/08

CPC classification number: A61K31/695 ,  A61K31/085 ,  A61K31/11 ,  A61K31/137 ,  A61K31/165 ,  A61K31/18 ,  A61K31/185 ,  A61K31/197 ,  A61K31/198 ,  A61K31/216 ,  A61K31/222 ,  A61K31/223 ,  A61K31/235 ,  A61K31/277 ,  A61K31/337 ,  A61K31/397 ,  A61K31/40 ,  A61K31/401 ,  A61K31/404 ,  A61K31/41 ,  A61K31/428 ,  A61K31/445 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/472 ,  A61K31/517 ,  A61K31/662 ,  A61K31/683 ,  A61K45/06 ,  C07C43/247 ,  C07C47/575 ,  C07C229/14 ,  C07C229/22 ,  C07C229/46 ,  C07C229/48 ,  C07C237/08 ,  C07C237/52 ,  C07C255/54 ,  C07C309/14 ,  C07C311/51 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2601/16 ,  C07D205/04 ,  C07D207/16 ,  C07D209/08 ,  C07D211/60 ,  C07D211/62 ,  C07D215/20 ,  C07D215/227 ,  C07D217/04 ,  C07D217/24 ,  C07D239/74 ,  C07D257/04 ,  C07D277/64 ,  C07D305/08 ,  C07D401/06 ,  C07D403/06 ,  C07D417/06 ,  C07F7/081 ,  C07F9/3808 ,  C07F9/3834 ,  C07F9/4006

Abstract: Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphin-gosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.

Abstract translation: 提供了在一种或多种S1P受体上具有激动剂活性的化合物。 化合物是肌氨酸 - 甙类似物，磷酸化后，可以作为S1P受体的激动剂。