http://rdf.ncbi.nlm.nih.gov/pubchem/patent/AR-113820-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_42e94091a4fc81b8d0237117707cc7ee |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-496 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P13-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D261-08 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-429 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P29-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-428 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-4245 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P1-18 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P1-16 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-422 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-4709 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D471-04 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-4439 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D417-14 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P35-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D417-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D413-14 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D413-04 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D413-14 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D417-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P29-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D417-14 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P3-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D471-04 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P35-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D261-08 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-422 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-4245 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-429 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-428 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D413-04 |
| filingDate | 2018-10-31-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_0bf6779923973f46744ab46a46fe97ee http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_967ddfaf028b2b587db80668c724dff4 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_2584a92d398cd910920e8a4b13662caa http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_d3e0cba99a13c09580ffbb8699a1fe81 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_a7807edc130742fb331f146df8fe1fbd http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_084d523d3265e0dc82b8ac8515d78302 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_e2f27cfb74bc741f81b75d29e2810e6b http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_02f0e0a2b73161d14b75486124232a23 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_42cae86da327596a4153c8fe09971a31 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_3b479fd85dc4a4c205861fc17652f16c http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_abc386c64d9bcc92156c199bb95d9037 |
| publicationDate | 2020-06-17-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | AR-113820-A1 |
| titleOfInvention | BRIDGE BICYCLIC COMPOUNDS AS MODULATORS OF THE X FARNESOID RECEIVER |
| abstract | Compounds of formula (1), or stereoisomers, tautomers, or salts or solvates of those pharmaceutically acceptable, wherein all variables are as defined herein. These compounds modulate the activity of the farnesoid X receptor (FXR), for example, as agonists. Also pharmaceutical compositions comprising these compounds and methods for treating a disease, disorder or condition associated with the dysregulation of FXR, such as pathological fibrosis, transplant rejection, cancer, osteoporosis and inflammatory disorder, through the use of compounds and pharmaceutical compositions. Claim 1: A compound characterized by formula (1), or a pharmaceutically acceptable stereoisomer, tautomer, salt or solvate thereof; wherein: Ring B is a 5- to 8-membered bridged cycloheteroalkyl or cycloalkyl; and the point of attachment to L¹ or Z is a carbon atom; X¹ and X⁴ are each independently C or N; X² and X³ are each independently CR³, N, NR⁴, O or S; E¹ and E³ are each independently a covalent bond, O, S, N, NR⁶, CR⁵, or CR⁵ᵃR⁵ᵇ; E² is O, S, N, NR⁸, CR⁷ or CR⁷ᵃR⁷ᵇ; wherein (E¹ and E²) or (E³ and E²) form a single bond or a double bond; provided that [1] the bonds between (E¹ and E²) and (E³ and E²) are not both double bonds; and [2] no more than one of E¹, E² and E³ is O, S, N or NR⁸; L¹ is a covalent bond, O, S, NR¹⁶, -C (S) NH-, C₁₋₃ alkylene, C₁₋₃ heteroalkylene, C₂₋₄ alkenylene, C₂₋₄ alkynylene, aryl, or a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms independently selected from N, O, and S; wherein the alkylene, heteroalkylene, aryl, and heteroaryl are each independently substituted with 0 to 3 R⁹; Z is 6 to 10 membered aryl, 5 to 10 membered heteroaryl, 3 to 10 membered carbocyclyl, or 4 to 10 membered heterocyclyl, wherein aryl, heteroaryl, carbocyclyl, and heterocyclyl are independently substituted with 0 to 5 R 5 ; L² are each independently a covalent bond, O, S, NR¹⁷, C₁₋₃ alkylene or C₁₋₃ heteroalkylene, wherein the alkylene and heteroalkylene are substituted, independently, with 0 to 3 R¹¹; RX is - (CR¹²ᵃR¹²ᵇ) ₑ-RZ or -O (CR¹²ᵃR¹²ᵇ) ₑ-RZ; e is 0 or 1; RZ is selected from -CN, -OH, -O (O) OR¹³, -C (O) NR¹⁴ᵃR¹⁴ᵇ, or a residue from the group of formulas (2); Rᵉ is C₁₋₆ alkyl, C₃₋₆ cycloalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, or phenyl; R¹ is C₁₋₆ alkyl, C₃₋₅ cycloalkyl, or C₄₋₆ heterocyclyl, wherein alkyl, cycloalkyl, and heterocyclyl are each independently substituted with 0 to 3 R¹⁵; R² is 6 to 10 membered aryl, 5 to 10 membered heteroaryl, 3 to 10 membered carbocyclyl, or 4 to 10 membered heterocyclyl, wherein aryl, heteroaryl, carbocyclyl and heterocyclyl are independently substituted with 0 to 5 R¹⁶ ; R³ and R⁷ are each independently hydrogen, halo, cyano, hydroxyl, amino, C₁₋₆ alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy or haloalkoxy; R⁴, R⁶, R⁸, R¹⁶ and R¹⁷ are each independently hydrogen, C₁₋₆ alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl or haloalkoxyalkyl; R⁵ is hydrogen, C₁₋₆ alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl; R⁵ᵃ, R⁵ᵇ, R⁷ᵃ, and R⁷ᵇ are each independently hydrogen, halo, cyano, hydroxyl, amino, C₁₋₆ alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R⁹ and R¹¹ are each independently halo, oxo, cyano, hydroxyl, amino, C₁₋₆ alkyl, C₃₋₆ cycloalkyl, C₄₋₆ heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy or haloalkoxy; a is an integer of 0, 1, 2, or 3; R¹⁰ and R¹⁶ are each independently halo, cyano, hydroxyl, amino, oxo, -ORᵃ, -SRᵃ, = S, -NRᶜRᶜ, = NH, = N-OH, = NRᵃ, = N-ORᵃ, -NO₂, -S (O) ₂Rᵃ, -S (O) ₂NHRᵇ, -S (O) ₂NRᶜRᶜ, -S (O) ₂ORᵇ, -OS (O) ₂Rᵇ, -OS (O) ₂ORᵇ, -P (O) (ORᵇ) (ORᵇ), -C (O) Rᵇ, -C (NRᵇ) Rᵇ, -C (O) ORᵇ, -C (O) NRᶜRᶜ, -C (NRᵇ) NRᶜRᶜ, -OC (O) Rᵇ, -NRᵇC (O ) Rᵇ, -OC (O) ORᵇ, -NRᵇC (O) ORᵇ, -OC (O) NRᶜRᶜ, -NRᵇC (O) NRᶜRᶜ, -NRᵇC (NRᵇ) Rᵇ, -NRᵇC (NRᵇ) NRᶜRᶜ, C₁₋₆ alkyl, C₁₋₆ haloalkyl, aryl, arylalkyl, heteroaryl, carbocyclyl, or heterocyclyl; wherein alkyl, aryl, heteroaryl, carbocyclyl, and heterocyclyl, by themselves or as part of another group, are each independently substituted with 0 to 5 Rᵈ; Rᵃ is selected from C₁₋₆ alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, carbocyclyl, carbocyclylalkyl, heterocyclyl, and heterocyclylalkyl; Rᵇ is, each independently, hydrogen or Rᵃ; Rᶜ is each independently Rᵇ or, alternatively, the two Rᶜ are taken together with the nitrogen atom to which they are attached to form a 4-, 5-, 6-, or 7-membered heterocyclyl; Rᵈ are each independently selected from Rᵃ, alkoxy, haloalkoxy, alkylamino, cycloalkylamino, heterocyclylamino, haloalkyl, hydroxyalkyl, aminoalkyl, cycloalkoxy, heterocyclyloxy, haloalkoxy, alkoxyalkoxy, haloalkylamino, alkoxyalkylamino, haloalkoxyalkylamino, arylaminoaryl heteroalkoxyalkylamino, arylaminoaryl heteroxy, arylaminoaryl, heterocyclyloxy, arylaminoaryl , alkylthio, halo, cyano, hydroxyl, amino, oxo, -ORᵃ, -SRᵃ, = S, -NRᶜRᶜ, = NH, = N-OH, = NRᵃ, = N-ORᵃ, -NO₂, -S (O) ₂Rᵃ , -S (O) ₂NHRᵇ, -S (O) ₂NRᶜRᶜ, -S (O) ₂ORᵇ, -OS (O) ₂Rᵇ, -OS (O) ₂ORᵇ, -P (O) (ORᵇ) (ORᵇ), -C (O) Rᵇ, -C (NRᵇ) Rᵇ, -C (O) ORᵇ, -C (O) NRᶜRᶜ, -C (NRᵇ) NRᶜRᶜ, -OC (O) Rᵇ, -NRᵇC (O) Rᵇ, -OC ( O) ORᵇ, -NRᵇC (O) ORᵇ, -NRᵇC (O) NRᶜRᶜ, -NRᵇC (NRᵇ) Rᵇ and -NRᵇC (NRᵇ) NRᶜRᶜ; R¹²ᵃ and R¹²ᵇ are each independently hydrogen, halo, cyano, hydroxyl, amino, C₁₋₆ alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy or haloalkoxy; or, alternatively, R¹²ᵃ and R¹²ᵇ, together with the atoms to which they are attached, form a 3- or 4-membered carbocyclic or heterocyclic ring; R¹³ is hydrogen, C₁₋₁₀ alkyl, or glucosyl; R¹⁴ᵃ and R¹⁴ᵇ are each independently hydrogen, C₁₋₆ alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; and R¹⁵ is hydrogen, halo, cyano, hydroxyl, amino, C₁₋₆ alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy. |
| priorityDate | 2017-11-01-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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Total number of triples: 67.