Bicyclic aryl sphingosine 1-phosphate analogs
First Claim
Patent Images
1. A method for treatment of multiple sclerosis in a mammal comprising administering to said mammal an effective amount of a compound of formula (IIa):
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 sphin-gosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.
24 Citations
10 Claims
-
1. A method for treatment of multiple sclerosis in a mammal comprising administering to said mammal an effective amount of a compound of formula (IIa):
- View Dependent Claims (2, 3, 4, 9, 10)
-
2. The method of claim 1, 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), —
-
3. The method of claim 1, wherein R1a and R2a are both hydrogen, and R1b is fluoro, chloro, bromo, iodo, methyl, triflurormethyl, 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.
-
4. The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
J is
-
9. The method of claim 1, 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.
-
-
10. The method of claim 1, 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.
-
2. The method of claim 1, wherein T1 is —
-
5. A method for 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 (6, 7, 8)
-
6. The method of claim 5, 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), —
-
7. The method of claim 5, wherein R1a and R2a are both hydrogen, and R1b is fluoro, chloro, bromo, iodo, methyl, triflurormethyl, 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.
-
8. The method of claim 5, or a pharmaceutically acceptable salt thereof, wherein:
J is
-
6. The method of claim 5, 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.
-
Primary Examiner(s)Rozof, Timothy R
-
Application NumberUS15/397,421Publication NumberTime in Patent Office329 DaysField of SearchUS Class CurrentCPC 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...