http://rdf.ncbi.nlm.nih.gov/pubchem/patent/AR-111874-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_4bdd40041a585b2fbeb8bad59beb1449 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D239-42 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D403-10 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D403-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-505 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-506 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P35-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D413-10 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D409-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D409-14 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D409-04 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D405-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K45-06 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-506 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D403-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-519 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D405-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P35-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D239-42 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D409-04 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D409-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D409-14 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-505 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D403-10 |
| filingDate | 2018-05-17-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 2019-08-28-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | AR-111874-A1 |
| titleOfInvention | PIRIMIDINE DERIVATIVES |
| abstract | Its use in the treatment of cancer by modulating an immune response that comprises a reactivation of the immune system in the tumor. Its use as pharmaceutical products, its preparation, the salts acceptable for pharmaceutical use thereof, and its use as pharmaceutical products, pharmaceutical compositions, and especially its use as modulators of the EP2 and / or EP4 receptors of prostaglandin 2. Claim 1: A compound of formula (1) for use in the treatment of a cancer, wherein said cancer is treated by modulating an immune response comprising a reactivation of the immune system in the tumor; wherein said compound is optionally used in combination with one or more chemotherapy and / or radiotherapy and / or targeted therapy agents; wherein in the compounds of the formula (1) ring (A) in the fragment of formula (2) represents a 5 or 6-membered aromatic ring or a 5 or 6-membered non-aromatic ring, where the ring (A) is fused to the phenyl group, wherein said ring (A) independently contains optionally one or two heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein said fragment is optionally substituted with (R¹) ₙ; where (R¹) ₙ represents one, two, three, or four optional substituents, wherein said R¹ substituents are independently selected from C₁₋₃ alkyl, C₂₋₃ alkenyl, C₂₋₃ alkynyl, C₁₋₃ alkoxy, halogen, -S- C₁₋₃ alkyl, C₁₋₃ fluoroalkyl, C₁₋₃ fluoroalkoxy, cyano, oxo, or amino; R³ represents hydrogen, methyl or trifluoromethyl; R⁴ᵃ and R⁴ᵇ independently represent hydrogen, methyl, or R⁴ᵃ and R⁴ᵇ together with the carbon atom to which they are attached represent a cycloprop-1,1-diyl group; R⁵ᵃ and R⁵ᵇ independently represent hydrogen, methyl, or R⁵ᵃ and R⁵ᵇ together with the carbon atom to which they are attached represent a cycloprop-1,1-diyl group; Ar¹ represents or phenyl, or 5- or 6-membered heteroaryl; said 5 or 6 membered phenyl or heteroaryl is independently mono-, di-o, tri-substituted where the substituents are independently selected from C₁₋₆ alkyl; C₁₋₄ alkoxy; C₁₋₃ fluoroalkyl, wherein said C₁₋₃ fluoroalkyl is optionally substituted with hydroxy; C₁₋₃ fluoroalkoxy; halogen; cyano; C₃₋₆ cycloalkyl, wherein said C₃₋₆ cycloalkyl is unsubstituted or mono-substituted with amino; C₄₋₆ cycloalkyl containing a ring oxygen atom, wherein said C₄₋₆ cycloalkyl containing a ring oxygen atom is not substituted or is mono-substituted with hydroxy; C₃₋₆-oxy cycloalkyl; hydroxy; -X¹-CO-RO¹, where X¹ represents a direct bond, C₁₋₃ alkylene, -O-C₁₋₃- * alkylene, -NH-C₁₋₃- * alkylene, -S-CH₂- *, -CF₂-, -CH = CH-, -CHºCH-, -NH-CO- *, -CO-, or C₃₋₅ cycloalkylene; where the asterisks indicate the link that is attached to the -CO-RO¹ group; and RO¹ represents -OH; -O-C₁₋₄ alkyl; -NH-SO₂-RS³ where RS³ represents C₁₋₄ alkyl, C₃₋₆ cycloalkyl where the C₃₋₆ cycloalkyl optionally contains a ring oxygen atom, C₃₋₆-C₁₋₃ cycloalkyl where the C₃₋₆ cycloalkyl optionally contains a ring oxygen atom, C₁₋₃ fluoroalkyl, or -NH₂; -O-CH₂-CO-RO⁴, where RO⁴ represents hydroxy, or C₁₋₄ alkoxy, or -N [C₁₋₄ alkyl] ₂; -O-CH₂-O-CO-RO⁵, where RO⁵ represents C₁₋₄ alkyl or C₁₋₄ alkoxy; -O-CH₂-CH₂-N [C₁₋₄ alkyl] ₂; or (5-methyl-2-oxo- [1,3] dioxol-4-yl) -methyloxy-; -CO-CH₂-OH; the rest of formula (3); 2-hydroxy-3,4-dioxo-cyclobut-1-enyl; hydroxy-C₁₋₄ alkyl; dihydroxy-C₂₋₄ alkoxy; C₂₋₄ hydroxy-alkoxy; C₁₋₄ alkoxy-C₂₋₄ alkoxy; - (CH₂) ʳ-CO-NRN³RN⁴ where r represents the integer 0 or 1; and where RN³ and RN⁴ independently represent hydrogen, C₁₋₄ alkyl, hydroxy-C₂₋₄ alkyl, C₁₋₃ alkoxy-C₂₋₄ alkyl, or hydroxy; -X²-NRN¹RN², where X² represents - (CH₂) ₘ-, where m represents the integer 0 or 1; or X² represents -O-CH₂-CH₂- *, where the asterisk indicates the link that is attached to the group -NRN¹RN²; and where RN¹ and RN² independently represent hydrogen, C₁₋₄ cycloalkyl, C₁₋₄ alkoxy-C alquilo alkyl, C₃₋₆ cycloalkyl, or C₂₋₃ fluoroalkyl; or RN¹ independently represents hydrogen or C₁₋₄ alkyl, and RN² independently represents -CO-H, -CO-C₁₋₃ alkyl, -CO-C₁₋₃-alkylene, or -CO-O-C₁₋₃ alkyl; or RN¹ and RN² together with the nitrogen to which they are attached form a saturated ring of 4, 5 or 6 members optionally containing an oxygen atom of the ring or sulfur of the ring, where said ring is not substituted, or is mono-substituted with oxo in a carbon atom of the ring, or disubstituted with oxo in a sulfur atom of the ring; -NH-CO-NRN⁵RN⁶ where RN⁵ and RN⁶ independently represent hydrogen or C₁₋₄ alkyl; -SO₂-RS¹ where RS¹ represents hydroxy, C₁₋₄ alkyl, or -NRN⁷RN⁸ where RN⁷ and RN⁸ independently represent hydrogen or C₁₋₃ alkyl; -S-RS² where RS² represents C₁₋₄ alkyl, C₃₋₆ cycloalkyl optionally containing a ring oxygen atom; - (CH₂) q-HET¹, where q represents the integer 0, 1 or 2; and where HET¹ represents 5-oxo-4,5-dihydro- [1,2,4] oxadiazol-3-yl, 3-oxo-2,3-dihydro- [1,2,4] oxadiazol-5-yl, or 5-thioxo-4,5-dihydro- [1,2,4] oxadiazol-3-yl; - (CH₂) ₚ-HET, where p represents the integer 0 or 1; and where HET represents a 5 or 6 membered heteroaryl, wherein said 5 or 6 membered heteroaryl is not substituted, or is mono- or di-substituted, where the substituents are independently selected from C₁₋₄ alkyl, C₁₋₄ alkoxy, -COOH, hydroxy, hydroxy-C₁₋₃ alkyl, C₃₋₅ cycloalkyl optionally containing a ring oxygen atom, or -NRN⁹RN¹⁰ where RN⁹ and RN¹⁰ independently represent hydrogen, C₁₋₃ alkyl or hydroxy-C₂₋₄ alkyl; or Ar¹ represents bicyclic heteroaryl of 8 to 10 members; wherein said 8 to 10 membered bicyclic heteroaryl is independently unsubstituted, or is mono-, or di-substituted where the substituents are independently selected from C₁₋₄ alkyl; C₁₋₄ alkoxy; C₁₋₃ fluoroalkyl; C₁₋₃ fluoroalkoxy; halogen; cyano; hydroxy, or -C₀₋₃-COORO² alkylene where RO² represents hydrogen or C₁₋₄ alkyl; or Ar¹ represents a group of the structure of formula (4), where the ring (B) represents a 5 or 6-membered non-aromatic ring fused to the phenyl group, where the ring (B) comprises one or two heteroatoms independently selected from nitrogen and oxygen; wherein said ring (B) is independently unsubstituted, or is mono-, or di-substituted, wherein the substituents are independently selected from oxo, C₁₋₆ alkyl and -C₀₋₃-COORO³ alkylene where RO³ represents hydrogen or C₁₋ alkyl ₃; or a salt acceptable for pharmaceutical use thereof. Claim 5: A compound of formula (5), wherein in compounds of formula (5), ring (A) in the fragment of formula (2) represents an aromatic ring of 5 or 6 members or a non-aromatic ring of 5 or 6 members, where the ring (A) is fused to the phenyl group, where independently said ring (A) optionally contains one or two heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein said fragment is optionally substituted with (R¹) ₙ; where (R¹) ₙ represents one, two, three, or four optional substituents, wherein said R¹ substituents are independently selected from C₁₋₃ alkyl, C₂₋₃ alkenyl, C₂₋₃ alkynyl, C₁₋₃ alkoxy, halogen, -S- C₁₋₃ alkyl, C₁₋₃ fluoroalkyl, C₁₋₃ fluoroalkoxy, cyano, oxo, or amino; and Ar¹ represents a phenyl group of the structure of formula (6), where Rᵖ represents -X¹-CO-RO¹, where X¹ represents a direct bond, C₁₋₃ alkylene, -O-C₁₋₃- * alkylene, -NH -C₁₋₃- * alkylene, CH = CH-, -NH-CO- *, or C₃₋₅ cycloalkylene; where the asterisks indicate the link that is attached to the -CO-RO¹ group; and RO¹ represents -OH; -O-C₁₋₄ alkyl; -NH-SO₂-RS³ where RS³ represents C₁₋₄ alkyl, C₃₋₆ cycloalkyl where the C₃₋₆ cycloalkyl optionally contains a ring oxygen atom, C₃₋₆-C₁₋₃ cycloalkyl where the C₃₋₆ cycloalkyl optionally contains a ring oxygen atom, C₁₋₃ fluoroalkyl, or -NH₂; HET¹, where HET¹ represents 5-oxo-4,5-dihydro- [1,2,4] oxadiazol-3-yl, or 3-oxo-2,3-dihydro- [1,2,4] oxadiazol-5- ilo; HET, where HET represents a group selected from 1H-tetrazol-5-yl, 3-hydroxy-isoxazol-5-yl, 2-hydroxy- [1,3,4] oxadiazol-4-yl, 3-amino-isoxazol- 5-yl, 2-amino-oxazol-5-yl, 5-amino- [1,3,4] thiadiazol-2-yl, 5-methylamino- [1,3,4] thiadiazol-2-yl, 5- amino- [1,2,4] oxadiazol-3-yl; Rᵐ¹ represents C₁₋₆ alkyl; C₁₋₄ alkoxy; C₁₋₃ fluoroalkyl; C₁₋₃ fluoroalkoxy; halogen; C₃₋₆ cycloalkyl; C₃₋₆-oxy cycloalkyl; C₂₋₄ hydroxy-alkoxy; or -S-RS² where RS² represents C₁₋₄ alkyl or C₃₋₆ cycloalkyl optionally containing an oxygen atom of a ring; R² represents hydrogen, methyl, fluoro, or chloro; and Rᵒ¹ represents hydrogen; or Ar¹ represents a 5-membered heteroaryl group of the structure of formula (7), where Y represents CH or N; R⁷ represents -X¹-CO-RO¹, where X¹ represents a direct bond, C₁₋₃ alkylene, -O-C₁₋₃- * alkylene-, -CH = CH-, -NH- CO- *, or C₃₋₅ cycloalkylene; where the asterisks indicate the link that is attached to the -CO-RO¹ group; and RO¹ represents -OH; -O-C₁₋₄ alkyl (especially ethoxy, methoxy); -NH-SO₂-RS³ where RS³ represents C₁₋₄ alkyl, C₃₋₆ cycloalkyl where the C₃₋₆ cycloalkyl optionally contains a ring oxygen atom, C₃₋₆-C₁₋₃ cycloalkyl where the C₃₋₆ cycloalkyl optionally contains a ring oxygen atom, C₁₋₃ fluoroalkyl, or -NH₂; HET¹, where HET¹ represents 5-oxo-4,5-dihydro- [1,2,4] oxadiazol-3-lid, or 3-oxo-2,3-dihydro- [1,2,4] oxadiazol-5- ilo; or HET, where HET represents a group selected from 1H-tetrazol-5-yl, 3-hydroxy-isoxazol-5-yl, 2-hydroxy- [1,3,4] oxadiazol-4-yl, 3-amino-isoxazole -5-yl, 2-amino-oxazol-5-yl, 5-amino- [1,3,4] thiadiazol-2-yl, 5-methylamino- [1,3,4] thiadiazol-2-yl, 5 -amino- [1,2,4] oxadiazol-3-yl; R⁶ represents C₁₋₆ alkyl; C₁₋₄ alkoxy; C₁₋₃ fluoroalkyl; C₁₋₃ fluoroalkoxy; halogen; C₃₋₆ cycloalkyl; C₃₋₆-oxy cycloalkyl; C₂₋₄ hydroxy-alkoxy; or -S-RS² where RS² represents C₁₋₄ alkyl or C₃₋₆ cycloalkyl optionally containing an oxygen atom of a ring; or a salt acceptable for pharmaceutical use thereof. |
| priorityDate | 2017-05-18-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
Total number of triples: 53.