BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS
3 Assignments
0 Petitions
Accused Products
Abstract
Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.
10 Citations
41 Claims
-
1-31. -31. (canceled)
-
32. A method for prevention or treatment of multiple sclerosis in a mammal comprising administering to said mammal an effective amount of a compound of formula (IIa):
- View Dependent Claims (33, 34, 35, 40, 41)
-
33. The method of claim 32, wherein T1 is —
- C(O)(ORf), —
C(O)N(Rf)S(O2Rf), —
O—
P(O)(ORf)ORf, —
P(O2)(ORf), tetrazolyl or —
S(O)2ORf.
- C(O)(ORf), —
-
34. The method of claim 32, wherein R1a and R2a are both hydrogen, and R1b is fluoro, chloro, bromo, iodo, methyl, trifluromethyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, t-butyl, n-pentyl, isopentyl, 1,1-dimethylpropyl, neopentyl, cyclopentyl, n-hexyl, cyclohexyl, methoxy, trifluoromethoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, t-butoxy, n-pentyloxy, i-pentyloxy, 1,1-dimethylpropoxy, neopentyloxy, cyclopentyloxy, n-hexyloxy, or cyclohexyloxy.
-
35. The method of claim 32, or a pharmaceutically acceptable salt thereof, wherein:
J is
-
40. The method of claim 32, wherein the compound is selected from the group consisting of:
-
3-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methylamino)-N-(phenylsulfonyl)propanamide; 3-((6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)methylamino)-N-(phenylsulfonyl)propanamide; 2-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methylamino)propanoic acid; 3-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methylamino)butanoic acid; 2-(((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methyl)(methyl)amino) acetic acid; 3-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methylamino)propanoic acid; 3-(((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methyl)(methyl)amino) propanoic acid; 1-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methyl)azetidine-3-carboxylic acid; 1-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methyl)pyrrolidine-3-carboxylic acid; 1-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid; 1-((6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)methyl)azetidine-3-carboxylic acid; 3-((6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)methylamino)propanoic acid; 3-((6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methylamino)-2,2-difluoropropanoic acid; 2,2-difluoro-3-((6-(spiro[5.5]undecan-3-yloxy)naphthalen-2-yl)methylamino)propanoic acid; 2-(((2-(trans-4-tert-butylcyclohexyloxy)naphthalen-6-yl)methyl)amino)acetic acid; 4-(((2-(trans-4-tert-butylcyclohexyloxy)naphthalen-6-yl)methyl)amino)butyric acid; 4-(((2-(trans-4-tert-butylcyclohexyloxy)naphthalen-6-yl)methyl)amino)butyric acid; (R)-1-((2-(trans-4-tert-butylcyclohexyloxy)naphthalen-6-yl)methyl)piperidine-3-carboxylic acid; (S)-1-((2-(trans-4-tert-butylcyclohexyloxy)naphthalen-6-yl)methyl)piperidine-3-carboxylic acid; 4-((2-(trans-4-tert-butylcyclohexyloxy)naphthalen-6-yl)methyl)butyric acid; 5-((2-(trans-4-tert-butylcyclohexyloxy)naphthalen-6-yl)methyl)pentanoic acid; 6-((2-(trans-4-tert-butylcyclohexyloxy)naphthalen-6-yl)methyl)hexanoic acid; 4-(6-(trans-4-tert-butylcyclohexyloxy)-3,4-dihydroisoquinolin-2(1H)-yl)butanoic acid; 4-(6-(cis-4-tert-butylcyclohexyloxy)-3,4-dihydroisoquinolin-2(1H)-yl)butanoic acid; 2-(((2-(trans-4-tert-butylcyclohexyloxy)naphthalen-6-yl)methyl)amino)ethylphosphonic acid; 2-(2-(5-(trans-4-tert-butylcyclohexyloxy)indolin-1-yl)-2-oxoethylamino)ethylphosphonic acid; 3-amino-4-(5-(trans-4-tert-butylcyclohexyloxy)indolin-1-yl)-4-oxo-butanoic acid; 3-{[6-(4-tert-butyl-cyclohexyloxy)-8-methyl-naphthalen-2-ylmethyl]-amino}-propionic acid; {[6-(4-tert-butyl-cyclohexyloxy)-8-methyl-naphthalen-2-ylmethyl]-amino}-acetic acid; 4-{[6-(4-tert-butyl-cyclohexyloxy)-8-methyl-naphthalen-2-ylmethyl]-amino}-butyric acid; 1-[6-(4-tert-butyl-cyclohexyloxy)-8-methyl-naphthalen-2-ylmethyl]-azetidine-3-carboxylic acid; and 1-[6-(4-tert-butyl-cyclohexyloxy)-8-methyl-naphthalen-2-ylmethyl]-pyrrolidine-3-carboxylate; or a pharmaceutically acceptable salt thereof.
-
-
41. The method of claim 32, further comprising administering to said mammal an effective amount of one or more drugs selected from the group consisting of:
- a corticosteroid, a bronchodilator, an antiasthmatic, an antiinflammatory, an antirheumatic, an immunosuppressant, an antimetabolite, an immunomodulator, an antipsoriatic, and an antidiabetic.
-
33. The method of claim 32, wherein T1 is —
-
36. A method for prevention or treatment of multiple sclerosis in a mammal comprising administering to said mammal an effective amount of a compound of formula (IIa), (IIIa) or (IIIb):
- View Dependent Claims (37, 38, 39)
-
37. The method of claim 36, wherein T1 is —
- C(O)(ORf), —
C(O)N(Rf)S(O2Rf), —
O—
P(O)(ORf)ORf, —
P(O2)(ORf), tetrazolyl or —
S(O)2ORf.
- C(O)(ORf), —
-
38. The method of claim 36, wherein R1a and R2a are both hydrogen, and R1b is fluoro, chloro, bromo, iodo, methyl, trifluromethyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, t-butyl, n-pentyl, isopentyl, 1,1-dimethylpropyl, neopentyl, cyclopentyl, n-hexyl, cyclohexyl, methoxy, trifluoromethoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, t-butoxy, n-pentyloxy, i-pentyloxy, 1,1-dimethylpropoxy, neopentyloxy, cyclopentyloxy, n-hexyloxy, or cyclohexyloxy.
-
39. The method of claim 36, or a pharmaceutically acceptable salt thereof, wherein:
J is
-
37. The method of claim 36, wherein T1 is —
Specification
- Resources
Thank you for your request. You will receive a custom alert email when the Litigation Campaign Assessment is available.
×
-
Current AssigneeBiogen MA Inc. (Biogen, Inc.)
-
Original AssigneeBiogen MA Inc. (Biogen, Inc.)
-
InventorsThomas, Jermaine, Liu, Xiaogao, Lin, Edward Yin-Shiang, Zheng, Guo Zhu, Ma, Bin, Caldwell, Richard D., Guckian, Kevin M., Kumaravel, Gnanasambandam, Taveras, Arthur G.
-
Granted Patent
-
Time in Patent OfficeDays
-
Field of Search
-
US Class Current
-
CPC Class CodesA61K 31/085 having an ether linkage to ...A61K 31/11 AldehydesA61K 31/137 Arylalkylamines, e.g. amphe...A61K 31/165 having aromatic rings, e.g....A61K 31/18 Sulfonamides compounds cont...A61K 31/185 Acids; Anhydrides, halides ...A61K 31/197 the amino and the carboxyl ...A61K 31/198 Alpha-amino acids, e.g. ala...A61K 31/216 of acids having aromatic ri...A61K 31/222 with compounds having aroma...A61K 31/223 of alpha-aminoacidsA61K 31/235 having an aromatic ring att...A61K 31/277 having a ring, e.g. verapamilA61K 31/337 having four-membered rings,...A61K 31/397 having four-membered rings,...A61K 31/40 having five-membered rings ...A61K 31/401 Proline; Derivatives thereo...A61K 31/404 Indoles, e.g. pindololA61K 31/41 having five-membered rings ...A61K 31/428 condensed with carbocyclic ...A61K 31/445 : Non condensed piperidines, ...A61K 31/47 : Quinolines; IsoquinolinesA61K 31/4709 : Non-condensed quinolines an...A61K 31/472 : Non-condensed isoquinolines...A61K 31/517 : ortho- or peri-condensed wi...A61K 31/662 : Phosphorus acids or esters ...A61K 31/683 : Diesters of a phosphorus ac...A61K 31/695 : Silicon compoundsA61K 45/06 : Mixtures of active ingredie...A61P 1/00 : Drugs for disorders of the ...A61P 1/04 : for ulcers, gastritis or re...A61P 11/00 : Drugs for disorders of the ...A61P 11/06 : AntiasthmaticsA61P 11/08 : BronchodilatorsA61P 17/06 : AntipsoriaticsA61P 19/02 : for joint disorders, e.g. a...A61P 25/00 : Drugs for disorders of the ...A61P 25/02 : for peripheral neuropathiesA61P 25/04 : Centrally acting analgesics...A61P 25/28 : for treating neurodegenerat...A61P 27/02 : Ophthalmic agentsA61P 29/00 : Non-central analgesic, anti...A61P 3/00 : Drugs for disorders of the ...A61P 3/10 : for hyperglycaemia, e.g. an...A61P 31/12 : AntiviralsA61P 35/00 : Antineoplastic agentsA61P 35/04 : specific for metastasisA61P 37/00 : Drugs for immunological or ...A61P 37/02 : ImmunomodulatorsA61P 37/04 : ImmunostimulantsA61P 37/06 : Immunosuppressants, e.g. dr...A61P 43/00 : Drugs for specific purposes...A61P 5/48 : of the pancreatic hormonesA61P 9/00 : Drugs for disorders of the ...A61P 9/10 : for treating ischaemic or a...A61P 9/14 : Vasoprotectives; Antihaemor...C07C 229/14 : to carbon atoms of carbon s...C07C 229/22 : the carbon skeleton being f...C07C 229/46 : having amino or carboxyl gr...C07C 229/48 : with amino groups and carbo...C07C 237/08 : having the nitrogen atom of...C07C 237/52 : having the nitrogen atom of...C07C 255/54 : containing cyano groups and...C07C 2601/02 : with a three-membered ringC07C 2601/04 : with a four-membered ringC07C 2601/08 : the ring being saturatedC07C 2601/14 : The ring being saturatedC07C 2601/16 : the ring being unsaturatedC07C 309/14 : containing amino groups bou...C07C 311/51 : Y being a hydrogen or a car...C07C 43/247 : containing halogenC07C 47/575 : containing ether groups, g...C07D 205/04 : having no double bonds betw...C07D 207/16 : Carbon atoms having three b...C07D 209/08 : with only hydrogen atoms or...C07D 211/60 : Carbon atoms having three b...C07D 211/62 : attached in position 4C07D 215/20 : Oxygen atomsC07D 215/227 : only one oxygen atom which ...C07D 217/04 : with hydrocarbon or substit...C07D 217/24 : Oxygen atomsC07D 239/74 : with only hydrogen atoms, h...C07D 257/04 : Five-membered ringsC07D 277/64 : with only hydrocarbon or su...C07D 305/08 : with hetero atoms or with c...C07D 401/06 : linked by a carbon chain co...C07D 403/06 : linked by a carbon chain co...C07D 417/06 : linked by a carbon chain co...C07F 7/081 : comprising at least one ato...C07F 9/3808 : Acyclic saturated acids whi...C07F 9/3834 : Aromatic acids (P-C aromati...C07F 9/4006 : Esters of acyclic acids whi...