http://rdf.ncbi.nlm.nih.gov/pubchem/patent/AR-112822-A2
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_1a0c3e4b714908382e152c4ee0b8ed0b |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P37-02 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-519 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P43-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K9-0048 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P37-06 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61K31-437 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P29-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P27-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P27-04 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P27-02 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P27-02 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-519 |
| filingDate | 2018-09-19-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_7fc56963ced572aa67645b11bbfb2054 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_2d4f4bf75379af330bee2c6b908d82f5 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_5753288e8bd76a78f838c0589731e24e http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_28572e8d6357493ed07eb799ab3d6bb9 |
| publicationDate | 2019-12-18-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | AR-112822-A2 |
| titleOfInvention | JANUS KINASE INHIBITOR METHOD FOR THE TREATMENT OF DRY EYE AND OTHER EYE-RELATED DISEASES |
| abstract | Claim 1: A method for the treatment of a dry eye disorder in a patient in need thereof, characterized in that it comprises administering to said patient a therapeutically effective amount of an agent selected from: (a) compounds of formula (1), where : A¹ and A² are independently selected from C and N; T, U, and V are independently selected from O, S, N, CR⁵, and NR⁶; where the 5-membered ring formed by A¹, A², U, T, and V is aromatic; X is N or CR⁴; Y is C₁₋₈ alkylene, C₂₋₈ alkenylene, C₂₋₈ alkynylene, (CR¹¹R¹²) ₚ- (C₃₋₁₀ cycloalkylene) - (CR¹¹R¹²) q, (CR¹¹R¹²) ₚ- (arylene) - (CR¹¹R¹²) q, (CR¹¹R¹² ) ₚ- (C₁₋₁₀ heterocycloalkylene) - (CR¹¹R¹²) q, (CR¹¹R¹²) ₚ- (heteroarylene) - (CR¹¹R¹²) q, (CR¹¹R¹²) ₚO (CR¹¹R¹²) q, (CR¹¹R¹²) ₚS (CR¹¹R¹²) q, (CR¹¹R¹²) ₚC (O) (CR¹¹R¹²) q, (CR¹¹R¹²) ₚC (O) NRᶜ (CR¹¹R¹²) q, (CR¹¹R¹²) ₚC (O) O (CR¹¹R¹²) q, (CR¹¹R¹²) ₚOC (O) (CR¹¹R¹²) q, (CR¹¹R¹²) ₚOC (O) NRᶜ (CR¹¹R¹²) q, (CR¹¹R¹²) ₚNRᶜ (CR¹¹R¹²) q, (CR¹¹R¹²) ₚNRᶜC (O) NRᵈ (CR¹¹R¹²) q, (CR¹¹R¹²) ₚS (O) (CR¹¹R¹²) q, (CR¹¹R¹) ² ) NRᶜ (CR¹¹R¹²) q, (CR¹¹R¹²) ₚS (O) ₂ (CR¹¹R¹²) q, or (CR¹¹R¹²) ₚS (O) ₂NRᶜ (CR¹¹R¹²) q, where said C₁₋₈ alkylene, C₂₋₈ alkenylene, C₂₋₈ alkynylene , cycloalkylene, arylene, heterocycloalkylene, or heteroarylene, is optionally substituted with 1, 2, or 3 substituents independently selected from -D¹-D²-D³-D⁴; Z is H, halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₁₋₄ haloalkyl, halosulfanyl, C₁₋₄ hydroxyalkyl, C₁₋₄ cyanoalkyl, = C-Rⁱ, = N-Rⁱ, Cy¹, CN, NO₂, ORᵃ, SRᵃ, C (O) Rᵇ, C (O) NRᶜRᵈ, C (O) ORᵃ, OC (O) Rᵇ, OC (O) NRᶜRᵈ, NRᶜRᵈ, NRᶜC (O) Rᵇ, NRᶜC (O) NRᶜRᵈ, NRᶜC (O) ORᵃ, C (= NRⁱ) NRᶜRᵈ, NRᶜC (= NRⁱ) NRᶜRᵈ, S (O) Rᵇ, S (O) NRᶜRᵈ, S (O) ₂Rᵇ, NRᶜS (O) ₂Rᵇ, C (= NOH ) Rᵇ, C (= NO (C₁₋₆ alkyl)) Rᵇ, and S (O) ₂NRᶜRᵈ, where said C₁₋₈ alkyl, C₂₋₈ alkenyl, or C₂₋₈ alkynyl, is optionally substituted with 1, 2, 3 , 4, 5, or 6 substituents independently selected from halo, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₁₋₄ haloalkyl, halosulfanyl, C₁₋₄ hydroxyalkyl, C₁₋₄ cyanoalkyl, Cy¹, CN, NO₂ , ORᵃ, SRᵃ, C (O) Rᵇ, C (O) NRᶜRᵈ, C (O) ORᵃ, OC (O) Rᵇ, OC (O) NRᶜRᵈ, NRᶜRᵈ, NRᶜC (O) Rᵇ, NRᶜC (O) NRᶜRᵈ, NRᶜC (O) ORᵃ, C (= NRⁱ) NRᶜRᵈ, NRᶜC (= NRⁱ) NRᶜRᵈ, S (O) Rᵇ, S (O) NRᶜRᵈ, S (O) ₂Rᵇ, NRᶜS (O) ₂Rᵇ, C (= NOH) Rᵇ, C (= NO (C₁₋₆ alkyl)) Rᵇ, and S (O) ₂NRᶜRᵈ; where when Z is H, n is 1; or the - (Y) ₙ-Z portion is taken together with i) A² to which the portion is attached, ii) R⁵ or R⁶ of both T and V, and iii) the C or N atom to which the R⁵ or R⁶ of both T and V is linked to form a 4- to 20-membered aryl, cycloalkyl, heteroaryl, or heterocycloalkyl ring fused to the 5-membered ring formed by A¹, A², U, T, and V, where said aryl ring, 4- to 20-membered cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from - (W) ₘ-Q; W is C₁₋₈ alkylenyl, C₂₋₈ alkenylenyl, C₂₋₈ alkynylenyl, O, S, C (O), C (O) NRᶜ ', C (O) O, OC (O), OC (O) NRᶜ' , NRᶜ ', NRᶜ'C (O) NRᵈ', S (O), S (O) NRᶜ ', S (O) ₂, or S (O) ₂NRᶜ'; Q is H, halo, CN, NO₂, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₁₋₈ haloalkyl, halosulfanyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl, where said C₁₋₈ alkyl, C₂₋ ₈ alkenyl, C₂₋₈ alkynyl, C₁₋₈ haloalkyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋ ₄ alkynyl, C₁₋₄ haloalkyl, halosulfanyl, C₁₋₄ hydroxyalkyl, C₁₋₄ cyanoalkyl, Cy², CN, NO₂, ORᵃ ', SRᵃ', C (O) Rᵇ ', C (O) NRᶜ'Rᵈ', C ( O) ORᵃ ', OC (O) Rᵇ', OC (O) NRᶜ'Rᵈ ', NRᶜ'Rᵈ', NRᶜ'C (O) Rᵇ ', NRᶜ'C (O) NRᶜ'Rᵈ', NRᶜ'C ( O) ORᵃ ', S (O) Rᵇ', S (O) NRᶜ'Rᵈ ', S (O) ₂Rᵇ', NRᶜ'S (O) ₂Rᵇ ', and S (O) ₂NRᶜ'Rᵈ'; Cy¹ and Cy² are independently selected from aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl , C₁₋₄ haloalkyl, halosulfanyl, C₁₋₄ hydroxyalkyl, C₁₋₄ cyanoalkyl, CN, NO₂, ORᵃ '', SRᵃ '', C (O) Rᵇ '', C (O) NRᶜ''Rᵈ '', C (O) ORᵃ '', OC (O) Rᵇ '', OC (O) NRᶜ''Rᵈ '', NRᶜ''Rᵈ '', NRᶜ''C (O) Rᵇ '', NRᶜ''C (O ) ORᵃ '', NRᶜ''S (O) Rᵇ '', NRᶜ''S (O) ₂Rᵇ '', S (O) Rᵇ '', S (O) NRᶜ''Rᵈ '', S (O) ₂Rᵇ '', and S (O) ₂NRᶜ''Rᵈ ''; R¹, R², R³, and R⁴ are independently selected from H, halo, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₁₋₄ haloalkyl, halosulfanyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO₂, OR⁷, SR⁷, C (O) R⁸, C (O) NR⁹R¹⁰, C (O) OR⁷, OC (O) R⁸, OC (O) NR⁹R¹⁰, NR⁹R¹⁰, NR⁹C (O) R⁸, NRᶜC (O) OR⁷, S ( O) R⁸, S (O) NR⁹R¹⁰, S (O) ₂R⁸, NR⁹S (O) ₂R⁸, and S (O) ₂NR⁹R¹⁰; R⁵ is H, halo, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₁₋₄ haloalkyl, halosulfanyl, CN, NO₂, OR⁷, SR⁷, C (O) R⁸, C (O) NR⁹R¹⁰, C ( O) OR⁷, OC (O) R⁸, OC (O) NR⁹R¹⁰, NR⁹R¹⁰, NR⁹C (O) R⁸, NR⁹C (O) OR⁷, S (O) R⁸, S (O) NR⁹R¹⁰, S (O) ₂R⁸, NR⁹S ( O) ₂R⁸, or S (O) ₂NR⁹R¹⁰; R⁶ is H, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₁₋₄ haloalkyl, OR⁷, C (O) R⁸, C (O) NR⁹R¹⁰, C (O) OR⁷, S (O) R⁸, S (O) NR⁹R¹⁰, S (O) ₂R⁸, or S (O) ₂NR⁹R¹⁰; R⁷ is H, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl; R⁸ is H, C₁₋₆, alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl; R⁹ and R¹⁰ are independently selected from H, C₁₋₁₀ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆, alkylcarbonyl, arylcarbonyl, C₁₋₆ alkylsulfonyl, arylsulfonyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl; or R⁹ and R¹⁰ together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group; R¹¹ and R¹² are independently selected from H and -E¹-E²-E³-E⁴; D¹ and E¹ are independently absent or independently selected from C₁₋₆ alkylene, C₂₋₆ alkenylene, C₂₋₈ alkynylene, arylene, cycloalkylene, heteroarylene, and heterocycloalkylene, where each of C₁₋₆ alkylene, C₂₋₆, alkenylene , C₂₋₆ alkynylene, arylene, cycloalkylene, heteroarylene, and heterocycloalkylene is optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, NO₂, N₃, SCN, OH, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂ ₋₈ alkoxyalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, amino, C₁₋₆ alkylamino, and C₂₋₈ dialkylamino; D² and E² are independently absent or independently selected from C₁₋₆ alkylene, C₂₋₆ alkenylene, C₂₋₆ alkynylene, (C₁₋₆ alkylene) ʳ-O- (C₁₋₆ alkylene) ₛ, (C₁₋₆ alkylene ) ʳ-S- (C₁₋₆ alkylene) ₛ, (C₁₋₈ alkylene) ʳ-NRᵉ- (C₁₋₆ alkylene) ₛ, (C₁₋₆ alkylene) ʳ-CO- (C₁₋₆ alkylene) ₛ, ( C₁₋₆ alkylene) ʳ-COO- (C₁₋₆ alkylene) ₛ, (C₁₋₆ alkylene) ʳ-CONRᵉ- (C₁₋₆ alkylene) ₛ, (C₁₋₆ alkylene) ʳ-SO- (C₁₋₆ alkylene ) ₛ, (C₁₋₆ alkylene) ʳ-SO₂- (C₁₋₆ alkylene) ₛ, (C₁₋₆ alkylene) ʳ-SONRᵉ- (C₁₋₆ alkylene) ₛ, and (C₁₋₆ alkylene) ʳ-NRᵉCONRᶠ- (C₁₋₆ alkylene) ₛ, where each of C₁₋₆ alkylene, C₂₋₆ alkenylene, and C₂₋₆ alkynylene is optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, NO₂, N₃, SCN, OH, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋₈ alkoxyalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, amino, C₁₋₆ alkylamino, and C₂₋₈ dialkylamino; D³ and E³ are independently absent or independently selected from C₁₋₆ alkylene, C₂₋₆ alkenylene, C₂₋₆ alkynylene, arylene, cycloalkylene, heteroarylene, and heterocycloalkylene, where each of C₁₋₆ alkylene, C₂₋₆ alkenylene, C₂₋₆ alkynylene, arylene, cycloalkylene, heteroarylene, and heterocycloalkylene is optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, NO₂, N₃, SCN, OH, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋ ₈ alkoxyalkyl, C₁₋₈ alkoxy, C₁₋₆ haloalkoxy, amino, C₁₋₆ alkylamino, and C₂₋₈ dialkylamino; D⁴ and E⁴ are independently selected from H, halo, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₁₋₄ haloalkyl, halosulfanyl, C₁₋₄ hydroxyalkyl, C₁₋₄ cyanoalkyl, Cy¹, CN, NO₂, ORᵃ , SRᵃ, C (O) Rᵇ, C (O) NRᶜRᵈ, C (O) ORᵃ, OC (O) Rᵇ, OC (O) NRᶜRᵈ, NRᶜRᵈ, NRᶜC (O) Rᵇ, NRᶜC (O) NRᶜRᵈ, NRᶜC (O ) ORᵃ, C (= NRⁱ) NRᶜRᵈ, NRᶜC (= NRⁱ) NRᶜRᵈ, S (O) Rᵇ, S (O) NRᶜRᵈ, S (O) ₂Rᵇ, NRᶜS (O) ₂Rᵇ, C (= NOH) Rᵇ, C ( = NO (C₁₋₆ alkyl)) Rᵇ, and S (O) ₂NRᶜRᵈ, where said C₁₋₈ alkyl, C₂₋₆ alkenyl, or C₂₋₈ alkynyl, is optionally substituted with 1, 2, 3, 4, 5 or 6 substituents independently selected from halo, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₁₋₄ haloalkyl, halosulfanyl, C₁₋₄ hydroxyalkyl, C₁₋₄ cyanoalkyl, Cy¹, CN, NO₂, ORᵃ, SRᵃ, C (O) Rᵇ, C (O) NRᶜRᵈ, C (O) ORᵃ, OC (O) Rᵇ, OC (O) NRᶜRᵈ, NRᶜRᵈ, NRᶜC (O) Rᵇ, NRᶜC (O) NRᶜRᵈ, NRᶜC (O) ORᵃ, C (= NRⁱ) NRᶜRᵈ, NRᶜC (= NRⁱ) NRᶜRᵈ, S (O) Rᵇ, S (O) NRᶜRᵈ, S (O) ₂Rᵇ, NRᶜS (O) ₂Rᵇ, C (= NOH) Rᵇ, C (= NO (C₁ ₋₆ alkyl)) Rᵇ, and S (O) ₂NRᶜRᵈ; Rᵃ is H, Cy¹, - (C₁₋₆ alkyl) -Cy¹, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, where said C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋ ₆ alkenyl, or C₂₋₆ alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C₁₋₆ alkyl, C₁₋₆ haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl; Rᵇ is H, Cy¹, - (C₁₋₆ alkyl) -Cy¹, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, where said C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋ ₆ alkenyl, or C₂₋₆ alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ haloalkyl, halosulfanyl, aryl, arylalkyl , heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; Rᵃ 'and Rᵃ' 'are independently selected from H, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, where said C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH , CN, amino, halo, C₁₋₆ alkyl, C₁₋₆ haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl and heterocycloalkyl; Rᵇ 'and Rᵇ' 'are independently selected from H, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, where said C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH , CN, amino, halo, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; Rᶜ and Rᵈ are independently selected from H, Cy¹, - (C₁₋₆ alkyl) -Cy¹, C₁₋₁₀ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, wherein said C₁₋₁₀ alkyl, C₁₋ ₆ haloalkyl, C₂₋₆ alkenyl, or C₂₋₆ alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from Cy¹, - (C₁₋₆ alkyl) -Cy¹, OH, CN, amino, halo, C₁₋ ₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ haloalkyl, and halosulfanyl; or Rᶜ and Rᵈ together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from Cy¹, - (C₁₋₆ alkyl) -Cy¹, OH, CN, amino, halo, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ haloalkyl, and halosulfanyl; Rᶜ 'and Rᵈ' are independently selected from H, C₁₋₁₀ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C₁ ₋₁₀ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; or Rᶜ 'and Rᵈ' together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo , C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; Rᶜ "and Rᵈ" are independently selected from H, C₁₋₁₀ alkyl, C₁₋₆ haloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, where said C₁₋₁₀ alkyl, C₁₋₈ haloalkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C₁₋₆ alkyl, C₁₋₆ haloalkyl, halosulfanyl, C₁₋₆ haloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; or Rᶜ "and Rᵈ" together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino , halo, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ haloalkyl, halosulfanyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, and heterocycloalkyl; Rⁱ is H, CN, NO₂, or C₁₋₆ alkyl; Rᵉ and Rᶠ are independently selected from H and C₁₋₆ alkyl; Rⁱ is H, CN, or NO₂; m is 0 or 1; n is 0 or 1; p is 0, 1, 2, 3, 4, 5, or 6; q is 0, 1, 2, 3, 4, 5, or 6; r is 0 or 1; and s is 0 or 1; where when X is N, n is 1, and the portion formed by A¹, A², U, T, V, and - (Y) ₙ-Z has the formula (4); then Y is different from (CR¹¹R¹²) ₚC (O) NRᶜ (CR¹¹R¹²) q; (b) compounds of formula (2), where: Lᵃ is SO₂ or CO; R¹ᵃ is C₁₋₆ alkyl, C₃₋₇ cycloalkyl, phenyl, 5- or 6-membered heteroaryl, indolyl, NR²ᵃR³ᵃ, or OR⁴ᵃ, wherein said alkyl, cycloalkyl, phenyl, or heteroaryl is optionally substituted with 1, 2, or 3 selected substituents independently from F, CN, and C₁₋₄ alkyl; R²ᵃ and R³ᵃ are independently selected from H, C₁₋₄ alkyl, and phenyl; and R⁴ᵃ is C₁₋₆ alkyl, phenyl, or benzyl; (c) compounds of formula (3), where: R⁵ᵃ and R⁶ᵃ are independently selected from H, F, CN, OH, C₁₋₄ alkyl, benzyloxy, C₂₋₆ dialkylaminosulfonyl, and 5-membered heteroaryl, wherein said alkyl is substituted optionally with 1, 2, or 3 substituents selected from F, OH, CN, and C₁₋₄ alkoxy, and wherein said 5-membered heteroaryl is optionally substituted with C₁₋₄ alkyl; and pharmaceutically acceptable salts thereof; provided that the compound of formula (1) is not selected from 4- [5- (2-isopropyl-5-methylcyclohexyloxymethyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b ] pyridine; 4- [5- (4-tert-butylphenoxymethyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5-cyclopentylethyl-1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (2,6-Difluorophenyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (1-tert-butyl-3-methyl-1H-pyrazol-5-yl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (benzyloxymethyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (3-fluorophenyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (phenoxymethyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (4-methoxybenzyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (phenylthiomethyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (3-methylbutyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5-benzyl-1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (2,2-dimethylpropyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5-methyl-1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (formyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (furan-2-yl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (1-methyl-1H-pyrrol-2-yl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5- (sec-butyl) -1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; 4- [5-cyclopropyl-1,2-4-oxadiazol-3-yl] -1H-pyrrolo [2,3-b] pyridine; and pharmaceutically acceptable salts of any of the foregoing. Claim 18: A method according to claim 17, characterized in that said additional therapeutic agent is fluocinolone acetonide, rimexolone, cyclosporine, riaminolone, dexamethasone, fluocinolone, cortisone, prednisolone, flumetolone, civamide, testosterone, sodium ecabet, acid 15- (s) -hydroxyeicosatetraenoic, (2S, 3S, 4R, 5R) -3,4-dihydroxy-5- [6 - [(3-iodophenyl) methylamino] purin-9-yl] -N-methyl-oxolan-2- carboxamide, gefarnate, cevilemine, doxycline, minocycline, oxytetracycline, voclosporine, rivoglitazone, lacritin rebamipid, pilocarpine, tacrolimus, pimecrolimus ,lotprednol etabonate, rituximab, diquafosol tetrasizolanedrosodium, dehydrocepticine, tetrasizolanedrosodium, dehydro-ethaquine, ephydrosaline, dehydroquine, tetrasizolandrosterone sodium, Claim 51: A kit for the treatment of dry eye disorders, comprising an ophthalmic or pharmaceutical composition and instructions; characterized in that said composition comprises a therapeutically effective amount of an agent selected from: (a) compounds of formula (1), where: A¹ and A² are independently selected from C and N; T, U, and V are independently selected from O, S, N, CR⁵, and NR⁶; where the 5-membered ring formed by A¹, A², U, T, and V is aromatic; X is N or CR⁴; Y is C₁₋₈ alkylene, C₂₋₈ alkenylene, C₂₋₈ alkynylene, (CR¹¹R¹²) ₚ- (C₃₋₁₀ cycloalkylene) - (CR¹¹R¹²) q, (CR¹¹R¹²) ₚ- (arylene) - (CR¹¹R¹²) q, (CR¹¹R¹² ) ₚ- (C₁₋₁₀ heterocycloalkylene) - (CR¹¹R¹²) q, (CR¹¹R¹²) ₚ- (heteroarylene) - (CR¹¹R¹²) q, (CR¹¹R¹²) ₚO (CR¹¹R¹²) q, (CR¹¹R¹²) ₚS (CR¹¹R¹²) q, (CR¹¹R¹²) ₚC (O) (CR¹¹R¹²) q, (CR¹¹R¹²) ₚC (O) NRᶜ (CR¹¹R¹²) q, (CR¹¹R¹²) ₚC (O) O (CR¹¹R¹²) q, (CR¹¹R¹²) ₚOC (O) (CR¹¹R¹²) q, (CR¹¹R¹²) ₚOC (O) NRᶜ (CR¹¹R¹²) q, (CR¹¹R¹²) ₚNRᶜ (CR¹¹R¹²) q, (CR¹¹R¹²) ₚNRᶜC (O) NRᵈ (CR¹¹R¹²) q, (CR¹¹R¹²) ₚS (O) (CR¹¹R¹²) q, (CR¹¹R¹) ² ) NRᶜ (CR¹¹R¹²) q, (CR¹¹R¹²) ₚS (O) ₂ (CR¹¹R¹²) q, or (CR¹¹R¹²) ₚS (O) ₂NRᶜ (CR¹¹R¹²) q, where said C₁₋₈ alkylene, C₂₋₈ alkenylene, C₂₋₈ alkynylene , cycloalkylene, arylene, heterocycloalkylene, or heteroarylene, is optionally substituted with 1, 2, or 3 substituents independently selected from -D¹-D²-D³-D⁴; Z is H, halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₁₋₄ haloalkyl, halosulfanyl, C₁₋₄ hydroxyalkyl, C₁₋₄ cyanoalkyl, = C-Rⁱ, = N-Rⁱ, Cy¹, CN, NO₂, ORᵃ, SRᵃ, C (O) Rᵇ, C (O) NRᶜRᵈ, C (O) ORᵃ, OC (O) Rᵇ, OC (O) NRᶜRᵈ, NRᶜRᵈ, NRᶜC (O) Rᵇ, NRᶜC (O) NRᶜRᵈ, NRᶜC (O) ORᵃ, C (= NRⁱ) NRᶜRᵈ, NRᶜC (= NRⁱ) NRᶜRᵈ, S (O) Rᵇ, S (O) NRᶜRᵈ, S (O) ₂Rᵇ, NRᶜS (O) ₂Rᵇ, C (= NOH ) Rᵇ, C (= NO (C₁₋₆ alkyl)) Rᵇ, and S (O) ₂NRᶜRᵈ, where said C₁₋₈ alkyl, C₂₋₈ alkenyl, or C₂₋₈ alkynyl, is optionally substituted with 1, 2, 3 , 4, 5, or 6 substituents independently selected from halo, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₁₋₄ haloalkyl, halosulfanyl, C₁₋₄ hydroxyalkyl, C₁₋₄ cyanoalkyl, Cy¹, CN, NO₂ , ORᵃ, |
| priorityDate | 2008-10-02-04:00^^<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: 80.