5-HT2a and / or 5-HT2c receptor agonists

Abstract

Provided herein are heterocyclic compounds, processes for their preparation, compositions comprising said compounds, and use of the compounds in therapy. More particularly, the present disclosure relates to a compound of Formula (I) [Image disponible dans le document PDF, Image available in the PDF document] or pharmaceutically acceptable salt or solvate thereof, useful in the treatment of diseases, disorders or conditions treatable by modulating the 5-HT2 receptor subtypes.

Description

5-HT2A AND / OR 5-HT2C RECEPTOR AGONISTS CROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 184,715, filed May 5, 2021. BACKGROUND

[0002] Provided herein are novel heterocyclic compounds, processes for their preparation, compositions comprising said compounds, and use in therapy. More particularly, the present disclosure relates to fluorinated and / or deuterated analog useful in the treatment of diseases, disorders or conditions treatable by modulating the 5-HT2 receptor subtypes. BRIEF SUMMARY OF THE INVENTION

[0003] Provided herein are heterocyclic 5-HT<com:Sub>2a< / com:Sub> and / or 5-HT<com:Sub>2c< / com:Sub> receptor agonists compounds, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.

[0004] One embodiment provides a compound, or pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (I) wherein, R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup> and R<com:Sup>3< / com:Sup> are independently selected from H or C1-C6 optionally substituted alkyl; and Ring A is an optionally substituted heteroaryl ring selected from [Image disponible dans le document PDF, Image available in the PDF document] Wherein * represents the points of attachment, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, CN, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl and OC1-4haloalkyl, NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup> R<com:Sup>6< / com:Sup> and R<com:Sup>7< / com:Sup> are independently selected from H or C1-C6 optionally substituted alkyl; and R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, C3-12heterocycloalkyl, optionally comprising one additional heteromoiety selected from NR10, O, S, S(O) and SO2, and optionally substituted with one or more substituents selected from halo, =O, OH, C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6heterocycloalkyl, C1-6alkyleneC3-6cycloalkyl, C1- 6alkylenearyl, C1-6alkyleneC5-6heteroaryl, C1-6alkyleneC3-6heterocycloalkyl, C(O)C1- 6alkyl, OC1-6alkyl, OC1-6alkyleneOC1-6alkyl, C(O)NH2, C(O)NH(C1-6alkyl), C(O)N(C1- 6alkyl)(C1-6alkyl), NHC(O)C1-6alkyl, N(C1-6alkyl)C(O)C1-6alkyl, NH2, NH(C1-6alkyl), N(C1-6alkyl)(C1-6alkyl), SC1-6alkyl, S(O)C1-6alkyl and SO2C1-6alkyl, wherein all alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups of the optional substituents on the C3-12heterocycloalkyl formed by R5 and R6 are also optionally substituted with one or more of halo, C1-6alkyl, OC1-6alkyl, C1-6haloalkyl and OC1-6haloalkyl; One embodiment provides a pharmaceutical composition comprising a compound of Formula (I), or pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient. In an aspect, the present disclosure provides a compound, or pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (I), wherein R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup> and R<com:Sup>3< / com:Sup> are each independently selected from H and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> optionally substituted alkyl; and [Image disponible dans le document PDF, Image available in the PDF document] ring A is an optionally substituted heteroaryl ring selected from [Image disponible dans le document PDF, Image available in the PDF document] wherein * represents the points of attachment; R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, CN, C<com:Sub>1< / com:Sub>-4alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math> are independently selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted alkyl; and R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a C<com:Sub>3-< / com:Sub> 12heterocycloalkyl, optionally comprising one additional heteromoiety selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math>, O, S, S(O) and SO<com:Sub>2< / com:Sub>, and optionally substituted with one or more substituents selected from halo, =O, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub> 6alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl)(C1-6alkyl), NHC(O)C<com:Sub>1-6< / com:Sub>alkyl, N(C<com:Sub>1-6< / com:Sub>alkyl)C(O)C<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl), N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), SC<com:Sub>1-6< / com:Sub>alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl, wherein R<com:Sup>10< / com:Sup> is selected from hydrogen, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub> 6alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-< / com:Sub> 6heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), <com:Math><semantics>C(O)N(C1−6alkyl)(C1−6alkyl)<annotation encoding="application / x-tex">C(O)N(C_{1-6}alkyl)(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>S(O)C1−6alkyl<annotation encoding="application / x-tex">S(O)C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>SO2C1−6alkyl<annotation encoding="application / x-tex">SO_2C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>; and all alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups of the optional substituents on the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>1-6< / com:Sub>haloalkyl, and OC<com:Sub>1-6< / com:Sub> 6haloalkyl.

[0007] In some embodiments, R1 is H. In some embodiments, R1 is H, and R2 is C1-6 alkyl. In some [Image disponible dans le document PDF, Image available in the PDF document] embodiments, R1 is H, and R2 is methyl. In some embodiments, ring A is <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> , R1 is H, [Image disponible dans le document PDF, Image available in the PDF document] and R2 is C1-6 alkyl. In some embodiments, ring A is , R1 is H, and R2 is methyl. In some embodiments, R3 is selected from H and C1-6 alkyl. In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>Γ5<annotation encoding="application / x-tex">\Gamma_5< / annotation>< / semantics>< / com:Math> , and R3 is H. In some embodiments, ring A is , and R3 is [Image disponible dans le document PDF, Image available in the PDF document] selected from H and C1-6 alkyl. In some embodiments, ring A is , and R3 is [Image disponible dans le document PDF, Image available in the PDF document] selected from H and methyl. In some embodiments, ring A is , and R3 is [Image disponible dans le document PDF, Image available in the PDF document] methyl. In some embodiments, ring A is selected from , and [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] . In some embodiments, ring A is selected from , [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] . In some embodiments, ring A is . In some [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] embodiments, ring A is . In some embodiments, ring A is . In [Image disponible dans le document PDF, Image available in the PDF document] some embodiments, ring A is . In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] . In some embodiments, ring A is . In some embodiments, R4 and R5 are independently selected from H, halo, CN, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl, OC1-4haloalkyl, and N(R8R9). In some embodiments, R4 and R5 are independently selected from H, halo, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl, OC1-4haloalkyl, and N(R8R9). In some embodiments, R4 and R5 are independently selected from H, halo, C1 alkyl, C1-4haloalkyl, OC1-4alkyl, OC1-4haloalkyl, and N(R8R9). In some embodiments, R4 and R5 are independently selected from H, halo, C1-4haloalkyl, OC1-4alkyl, OC1-4haloalkyl, and N(R8R9). In some embodiments, R4 and R5 are independently selected from H and N(R8R9). In some embodiments, exactly one of R4 and R5 is H, and exactly one of R4 and R5 is N(R8R9). In some embodiments, exactly one of R4 and R5 is H, and exactly one of R4 and R5 is N(R8R9). In some embodiments, R4 is H, and R5 is N(R8R9). In some embodiments, ring A [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] is - , R4 is H, and R5 is N(R8R9). In some embodiments, ring A is R<com:Sup>5< / com:Sup> ; and R4 and R5 are each independently selected from H, NO2, F, CN, C1-4alkyl, C1-4haloalkyl, [Image disponible dans le document PDF, Image available in the PDF document] OC1-4alkyl, OC1-4haloalkyl, and N(R8R9). In some embodiments, ring A is , and R4 and R5 are each independently selected from H, NO2, F, CN, C2-4alkyl, C1-4haloalkyl, OC2-4alkyl, O(optionally substituted C3-10 carbocycle), O(optionally substituted C3-10 aryl), O(3- to 10-membered heterocycle), O(3- to 10- membered heteroaryl), OC1-4haloalkyl, and N(R8R9). In some embodiments, R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, optionally comprising one additional heteromoiety selected from N(R10), O, and S. In some embodiments, R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, optionally comprising one additional heteromoiety selected from N(R10), and O. In some embodiments, R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, optionally comprising one WSGR Ref. No. 55554-710.601 additional oxygen atom. In some embodiments, the C3-12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from halo, =O, OH, C1- 6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C1-6 alkyleneC3- 6cycloalkyl, C1-6alkylenearyl, C1-6alkyleneC5-6heteroaryl, C1-6alkyleneC3- 6heterocycloalkyl, C(O)C1-6alkyl, OC1-6alkyl, OC1-6alkyleneOC1-6alkyl, C(O)NH2, C(O)NH(C1-6alkyl), C(O)N(C1-6alkyl)(C1-6alkyl), NHC(O)C1-6alkyl, N(C1-6alkyl)C(O)C1- 6alkyl, NH2, NH(C1-6alkyl), and N(C1-6alkyl)(C1-6alkyl). In some embodiments, the C3- 12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from halo, =O, OH, C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C1-6 alkyleneC3-6cycloalkyl, C1-6alkylenearyl, C1-6alkyleneC5- 6heteroaryl, C1-6alkyleneC3-6heterocycloalkyl, OC1-6alkyl, NH2, NH(C1-6alkyl), and N(C1- 6alkyl)(C1-6alkyl). In some embodiments, the C3-12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from halo, =O, OH, OC1-6alkyl, NH2, and NH(C1-6alkyl). In some embodiments, the C3-12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from halo, =O, OH, OC1alkyl, NH2, and NH(C1alkyl). In some embodiments, the C3-12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from halo, =O, OH, OC1alkyl, NH2, and NH(C1alkyl). In some embodiments, the C3-12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from fluoro, =O, OH, OC1alkyl, NH2, and NH(C1alkyl). In some embodiments, the C3-12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more fluoro substituents. In some embodiments, [Image disponible dans le document PDF, Image available in the PDF document] ring A is ; and the one additional heteromoiety of the C3-12heterocycloalkyl formed [Image disponible dans le document PDF, Image available in the PDF document] by R8 and R9 is NR10. In some embodiments, ring A is ; the one additional heteromoiety of the C3-12heterocycloalkyl formed by R8 and R9 is NR10; and the C3- 12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from halo, OH, NO2, C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C1-6 alkyleneC3-6cycloalkyl, C1-6alkylenearyl, C1-6alkyleneC5-6heteroaryl, C1-6alkyleneC3-6heterocycloalkyl, C(O)C1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, C(O)NH2, C(O)NH(C1-6alkyl), C(O)N(C1-6alkyl)(C1-6alkyl), NHC(O)C1-6alkyl, N(C1- 6alkyl)C(O)C1-6alkyl, NH2, NH(C1-6alkyl), N(C1-6alkyl)(C1-6alkyl), SC1-6alkyl, S(O)C1- WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document] 6alkyl, and SO2C1-6alkyl. In some embodiments, ring A is ; the one additional heteromoiety of the C3-12heterocycloalkyl formed by R8 and R9 is NR10; and the C3- 12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from halo, OH, NO2, C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 [Image disponible dans le document PDF, Image available in the PDF document] heterocycloalkyl, and OC1-6alkyl. In some embodiments, ring A is ; the one additional heteromoiety of the C3-12heterocycloalkyl formed by R8 and R9 is NR10; and R10 is selected from C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C1-6 alkyleneC3-6cycloalkyl, C1-6alkylenearyl, C1-6alkyleneC5-6heteroaryl, C1-6alkyleneC3- 6heterocycloalkyl, C(O)C1-6alkyl, C(O)NH2, C(O)NH(C1-6alkyl), C(O)N(C1-6alkyl)(C1- [Image disponible dans le document PDF, Image available in the PDF document] 6alkyl), S(O)C1-6alkyl, and SO2C1-6alkyl. In some embodiments, ring A is ; the one additional heteromoiety of the C3-12heterocycloalkyl formed by R8 and R9 is NR10; and R10 is selected from C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, and C3-6 [Image disponible dans le document PDF, Image available in the PDF document] heterocycloalkyl. In some embodiments, ring A is <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> ; the one additional heteromoiety of the C3-12heterocycloalkyl formed by R8 and R9 is NR10; and R10 is selected from C1- [Image disponible dans le document PDF, Image available in the PDF document] 6alkyl. In some embodiments, ring A is , and the C3-12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from halo, NO2, OH, C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C1-6 alkyleneC3- 6cycloalkyl, C1-6alkylenearyl, C1-6alkyleneC5-6heteroaryl, C1-6alkyleneC3- 6heterocycloalkyl, C(O)C1-6alkyl, OC1-6alkyl, OC1-6alkyleneOC1-6alkyl, C(O)NH2, C(O)NH(C1-6alkyl), C(O)N(C1-6alkyl)(C1-6alkyl), NHC(O)C1-6alkyl, N(C1-6alkyl)C(O)C1- 6alkyl, NH2, NH(C1-6alkyl), N(C1-6alkyl)(C1-6alkyl), SC1-6alkyl, S(O)C1-6alkyl, and WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document] SO2C1-6alkyl. In some embodiments, ring A is , and the C3- 12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from halo, NO2, OH, C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C1-6 alkyleneC3-6cycloalkyl, C1-6alkylenearyl, C1-6alkyleneC5-6heteroaryl, C1-6alkyleneC3-6heterocycloalkyl, C(O)C1-6alkyl, OC1-6alkyl, NH2, and NH(C1-6alkyl). In [Image disponible dans le document PDF, Image available in the PDF document] some embodiments, ring A is , and the C3-12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from halo, NO2, OH, C1- 6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C(O)C1-6alkyl, OC1- [Image disponible dans le document PDF, Image available in the PDF document] 6alkyl, NH2, and NH(C1-6alkyl). In some embodiments, ring A is , and the C3- 12heterocycloalkyl formed by R8 and R9 is optionally substituted with one or more substituents selected from halo, NO2, OH, C1-6alkyl, OC1-6alkyl, NH2, and NH(C1-6alkyl). In some embodiments, R10 is selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C1-6 alkyleneC3-6cycloalkyl, C1-6alkylenearyl, C1-6alkyleneC5- 6heteroaryl, and C1-6alkyleneC3-6heterocycloalkyl. In some embodiments, R10 is selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, and C3-6 heterocycloalkyl. In some embodiments, R10 is selected from hydrogen, and C1-6alkyl. In some embodiments, the [Image disponible dans le document PDF, Image available in the PDF document] heterocycle formed by R8 and R9 is selected from [Image disponible dans le document PDF, Image available in the PDF document] . In some embodiments, R8 and R9 are methyl. In some embodiments, R1 and R2 [Image disponible dans le document PDF, Image available in the PDF document] are H; R3 is selected from H and C1-C6 optionally substituted alkyl; ring A is and R5 are each independently selected from H, C1-4haloalkyl, OC1-4alkyl, OC1-4haloalkyl, O(optionally substituted C3-10 carbocycle), O(optionally substituted C3-10 aryl), and N(R8R9); R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, and optionally substituted with one or more substituents selected from halo, OH, NO2, C1- 6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C1-6 alkyleneC3- 6cycloalkyl, C1-6alkylenearyl, C1-6alkyleneC5-6heteroaryl, C1-6alkyleneC3- 6heterocycloalkyl, C(O)C1-6alkyl, OC1-6alkyl, OC1-6alkyleneOC1-6alkyl, C(O)NH2, C(O)NH(C1-6alkyl), C(O)N(C1-6alkyl)(C1-6alkyl), NHC(O)C1-6alkyl, N(C1-6alkyl)C(O)C1- 6alkyl, NH2, NH(C1-6alkyl), N(C1-6alkyl)(C1-6alkyl), SC1-6alkyl, S(O)C1-6alkyl, and SO2C1-6alkyl, wherein R10 is selected from C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C1-6 alkyleneC3-6cycloalkyl, C1-6alkylenearyl, C1-6alkyleneC5- 6heteroaryl, C1-6alkyleneC3-6heterocycloalkyl, C(O)C1-6alkyl, C(O)NH2, C(O)NH(C1- 6alkyl), C(O)N(C1-6alkyl)(C1-6alkyl), S(O)C1-6alkyl, and SO2C1-6alkyl. In some embodiments, R1 and R2 are H; R3 is selected from H and C1-C6 optionally substituted alkyl; [Image disponible dans le document PDF, Image available in the PDF document] ring A is ; R4 and R5 are each independently selected from H, C1-4haloalkyl, OC1- 4alkyl, OC1-4haloalkyl, O(optionally substituted C3-10 carbocycle), O(optionally substituted C3-10 aryl), and N(R8R9); R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, optionally comprising one additional heteromoiety selected from N(R10) and O and optionally substituted with one or more substituents selected from halo, OH, NO2, C1-6alkyl, C3- 6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C(O)C1-6alkyl, OC1-6alkyl, NH2, and NH(C1-6alkyl), wherein R10 is selected from C1-6alkyl, C3-6cycloalkyl, aryl, C5- 6heteroaryl, C3-6 heterocycloalkyl, C(O)C1-6alkyl, C(O)NH2, and C(O)NH(C1-6alkyl). In some embodiments, R1 and R2 are H; R3 is selected from H and C1-C6 optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> ; R4 and R5 are each independently selected from H, C1-4haloalkyl, OC1-4alkyl, and N(R8R9); R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, WSGR Ref. No. 55554-710.601 optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO2, C1-6alkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, OC1-6alkyl, NH2, and NH(C1-6alkyl). In some embodiments, R1 and R2 are [Image disponible dans le document PDF, Image available in the PDF document] H; R3 is selected from H and C1-C6 optionally substituted alkyl; ring A is ; R4 and R5 are each independently selected from H, C1-4haloalkyl, OC1-4alkyl, and N(R8R9); R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO2, C1-6alkyl, aryl, and C5-6heteroaryl. In some embodiments, R1 and R2 are H; R3 is selected from H and C1-C6 optionally substituted alkyl; ring A is [Image disponible dans le document PDF, Image available in the PDF document] ; R4 and R5 are each independently selected from H and N(R8R9); R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO2, C1-6alkyl, aryl, and C5-6heteroaryl. In some embodiments, R1 and R2 are H; R3 is selected from H and C1-C6 optionally substituted alkyl; [Image disponible dans le document PDF, Image available in the PDF document] ring A is R4 and R5 are each independently selected from H and N(R8R9); R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, and C1-6alkyl. In some embodiments, R1 and R2 are H; R3 is selected [Image disponible dans le document PDF, Image available in the PDF document] from H and C1-C6 optionally substituted alkyl; ring A is ; R4 and R5 are each independently selected from H and N(R8R9); R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, and OH. In some embodiments, R1 and R2 are H; R3 is selected WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document] from H and C1-C6 optionally substituted alkyl; ring A is ; R4 and R5 are each independently selected from H and N(R8R9); R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more halo substituents. In some embodiments, R1 and R2 [Image disponible dans le document PDF, Image available in the PDF document] are H; R3 is selected from H and C1-C6 optionally substituted alkyl; ring A is R4 and R5 are each independently selected from H and N(R8R9); R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more fluoro substituents. In some embodiments, R1 and R2 are H; R3 is selected from H and C1-C6 [Image disponible dans le document PDF, Image available in the PDF document] optionally substituted alkyl; ring A is R4 and R5 are each independently selected from H, C1-4haloalkyl, OC1-4alkyl, OC1-4haloalkyl, O(optionally substituted C3-10 carbocycle), O(optionally substituted C3-10 aryl), and N(R8R9); R8 and R9 are joined to form, together with the atom therebetween, a C3-12heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO2, C1-6alkyl, C3-6cycloalkyl, aryl, C5-6heteroaryl, C3-6 heterocycloalkyl, C(O)C1-6alkyl, OC1-6alkyl, OC1-6alkyleneOC1-6alkyl, NH2, and NH(C1-6alkyl). In an aspect, the present disclosure provides a compound, or pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (I), wherein R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup> and R<com:Sup>3< / com:Sup> are each independently selected from H and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> optionally substituted alkyl; and [Image disponible dans le document PDF, Image available in the PDF document] ring A is an optionally substituted heteroaryl ring selected from , [Image disponible dans le document PDF, Image available in the PDF document] wherein * represents the points of attachment; R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, halo, CN, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-< / com:Sub> 4haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), O(3- to 10-membered heterocycle), O(3- to 10- membered heteroaryl), OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>), wherein each OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>3-10< / com:Sub>aryl, and O(3- to 10-membered heteroaryl), of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is independently optionally substituted with one or more substituents selected from C<com:Sub>3-6< / com:Sub> carbocycle, C<com:Sub>3-6< / com:Sub> aryl, 3- to 10- membered heterocycle, and 3- to 10- membered heteroaryl,, wherein each C<com:Sub>3-6< / com:Sub> carbocycle, C<com:Sub>3-6< / com:Sub> aryl, 3- to 10- membered heterocycle, and 3- to 10- membered heteroaryl of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup>, is optionally substituted wih one or more substituents selected from halogen, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub>aminoalkyl, CN, <com:Math><semantics>NO2<annotation encoding="application / x-tex">NO_2< / annotation>< / semantics>< / com:Math>, OH, and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; [Image disponible dans le document PDF, Image available in the PDF document] when ring A is 24 and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, F, CN, C<com:Sub>1< / com:Sub>-4alkyl, C<com:Sub>1< / com:Sub>-4haloalkyl, OC<com:Sub>1< / com:Sub>-4alkyl, OC<com:Sub>1< / com:Sub>-4haloalkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), O(3- to 10-membered heterocycle), O(3- to 10- membered heteroaryl), and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; and [Image disponible dans le document PDF, Image available in the PDF document] when ring A is ; R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, F, CN, C<com:Sub>2-4< / com:Sub>alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>2-4< / com:Sub>alkyl, O(optionally substituted carbocycle), O(optionally substituted heterocycle), OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>); R<com:Sup>6< / com:Sup> and R<com:Sup>7< / com:Sup> are each independently selected from H and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> optionally substituted alkyl; and R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are each independently selected from hydrogen; <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> optionally substituted alkyl, <com:Math><semantics>C(O)(C1−6<annotation encoding="application / x-tex">C(O)(C_{1-6}< / annotation>< / semantics>< / com:Math> optionally substituted alkyl), <com:Math><semantics>C(O)N(C1−6)<annotation encoding="application / x-tex">C(O)N(C_{1-6})< / annotation>< / semantics>< / com:Math> optionally substituted alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>C(O)O(C1−6)<annotation encoding="application / x-tex">C(O)O(C_{1-6})< / annotation>< / semantics>< / com:Math> optionally substituted alkyl), S(O)(C<com:Sub>1-6< / com:Sub> optionally substituted alkyl), and S(O)<com:Sub>2< / com:Sub>(C<com:Sub>1-6< / com:Sub> optionally substituted alkyl), wherein [Image disponible dans le document PDF, Image available in the PDF document] when ring A is , and R<com:Sup>8< / com:Sup> is H; R<com:Sup>9< / com:Sup> is selected from <com:Math><semantics>C(O)N(C1−6)<annotation encoding="application / x-tex">C(O)N(C_{1-6})< / annotation>< / semantics>< / com:Math> optionally substituted alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>C(O)O(C1−6)<annotation encoding="application / x-tex">C(O)O(C_{1-6})< / annotation>< / semantics>< / com:Math> optionally substituted alkyl), <com:Math><semantics>S(O)(C1−6)<annotation encoding="application / x-tex">S(O)(C_{1-6})< / annotation>< / semantics>< / com:Math> optionally substituted alkyl), and <com:Math><semantics>S(O)2(C1−6)<annotation encoding="application / x-tex">S(O)_2(C_{1-6})< / annotation>< / semantics>< / com:Math> optionally substituted alkyl); and C<com:Sub>3-10< / com:Sub> carbocycle, C<com:Sub>3-10< / com:Sub> aryl, 3- to 10-membered heteroaryl, and 3- to 10- membered heterocycle, optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>1-6< / com:Sub>haloalkyl, and <com:Math><semantics>OC1−6<annotation encoding="application / x-tex">OC_{1-6}< / annotation>< / semantics>< / com:Math>haloalkyl; and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>1-6< / com:Sub>haloalkyl, and OC<com:Sub>1-6< / com:Sub>haloalkyl; andC<com:Sub>3-10< / com:Sub> carbocycle, C<com:Sub>3-10< / com:Sub> aryl, 3- to 10-membered heteroaryl, and 3- to 10-membered heterocycle, optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>1-6< / com:Sub>haloalkyl, and OC<com:Sub>1-6< / com:Sub>haloalkyl; or R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a C<com:Sub>3-< / com:Sub> <com:Sub>12< / com:Sub>heterocycloalkyl, optionally substituted with one or more substituents selected from NO<com:Sub>2< / com:Sub>, CN, halo, =O, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub> 6alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-< / com:Sub> 6heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, <com:Math><semantics>C(O)NH2<annotation encoding="application / x-tex">C(O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NH(C1−6alkyl)<annotation encoding="application / x-tex">C(O)NH(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(C1−6alkyl)<annotation encoding="application / x-tex">C(O)N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>(<com:Math><semantics>C1−6alkyl<annotation encoding="application / x-tex">C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>NHC(O)C1−6alkyl<annotation encoding="application / x-tex">NHC(O)C_{1-6}alkyl< / annotation>< / semantics>< / com:Math> 6alkyl, N(C<com:Sub>1-6< / com:Sub>alkyl)C(O)C<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl), SC<com:Sub>1-6< / com:Sub>alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl, wherein R<com:Sup>10< / com:Sup> is selected from hydrogen, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub> 6alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-< / com:Sub> 6heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), <com:Math><semantics>C(O)N(C1−6alkyl)(C1−6alkyl)<annotation encoding="application / x-tex">C(O)N(C_{1-6}alkyl)(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>S(O)C1−6alkyl<annotation encoding="application / x-tex">S(O)C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>SO2C1−6alkyl<annotation encoding="application / x-tex">SO_2C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>; all alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups of the optional substituents on the C<com:Sub>3< / com:Sub>- <com:Sub>12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub> 6alkyl, C<com:Sub>1-6< / com:Sub>haloalkyl, and OC<com:Sub>1-6< / com:Sub>haloalkyl; [Image disponible dans le document PDF, Image available in the PDF document] when ring A is , and the one additional heteromoiety of the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is NR<com:Sup>10< / com:Sup>; the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-< / com:Sub> 6cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-< / com:Sub> 6alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub> 6alkyl), C(O)N(C1-6alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), NHC(O)C<com:Sub>1-6< / com:Sub>alkyl, <com:Math><semantics>N(C1−6alkyl)C(O)C1−6alkyl,NH2,NH(C1−6alkyl),N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)C(O)C_{1-6}alkyl, NH_2, NH(C_{1-6}alkyl), N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math> 6alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), SC<com:Sub>1-6< / com:Sub>alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-< / com:Sub> 6alkyl; and R<com:Sup>10< / com:Sup> is selected from C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-< / com:Sub> 6cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, <com:Math><semantics>C(O)NH2<annotation encoding="application / x-tex">C(O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NH(C1−6alkyl)<annotation encoding="application / x-tex">C(O)NH(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(C1−6alkyl)(C1−6alkyl)<annotation encoding="application / x-tex">C(O)N(C_{1-6}alkyl)(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math> 6alkyl), S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl; and [Image disponible dans le document PDF, Image available in the PDF document] when ring A is , the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, NO<com:Sub>2< / com:Sub>, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-< / com:Sub> 6cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-< / com:Sub> 6alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub> 6alkyl), C(O)N(C1-6alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), NHC(O)C<com:Sub>1-6< / com:Sub>alkyl, <com:Math><semantics>N(C1−6alkyl)C(O)C1−6alkyl<annotation encoding="application / x-tex">N(C_{1-6}alkyl)C(O)C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NH2<annotation encoding="application / x-tex">NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NH(C1−6alkyl)<annotation encoding="application / x-tex">NH(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math> 6alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), SC<com:Sub>1-6< / com:Sub>alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-< / com:Sub> 6alkyl.

[0009] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is H. In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some [Image disponible dans le document PDF, Image available in the PDF document] embodiments, R<com:Sup>1< / com:Sup> is H, and R<com:Sup>2< / com:Sup> is methyl. In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> allkyl. In some embodiments, ring A is is H, and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is methyl. In some embodiments, <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some embodiments, <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected [Image disponible dans le document PDF, Image available in the PDF document] from H. In some embodiments, ring A is , and R<com:Sup>3< / com:Sup> is H. In some embodiments, ring [Image disponible dans le document PDF, Image available in the PDF document] A is , and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some embodiments, ring A [Image disponible dans le document PDF, Image available in the PDF document] is , and R<com:Sup>3< / com:Sup> is selected from H and methyl. In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , and R<com:Sup>3< / com:Sup> is methyl. In some embodiments, ring A is selected from WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document] . In some embodiments, ring A is selected from , [Image disponible dans le document PDF, Image available in the PDF document] . In some embodiments, [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] ring A is K<com:Sub>5< / com:Sub> . In some embodiments, ring A is . In some [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] embodiments, ring A is . In some embodiments, ring A is . In [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] some embodiments, ring A is . In some embodiments, ring A is In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, CN, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-1< / com:Sub> 4haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), O(3- to 10-membered heterocycle), O(3- to 10- membered heteroaryl), OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>), In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, CN, C<com:Sub>1< / com:Sub>- 4 alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is H, and exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is H, and exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>. In some embodiments, ring A is , <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>. In some embodiments, ring A is ; and R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, halo, CN, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), O(3- to 10-membered heterocycle), O(3- to 10- membered heteroaryl), OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] ; and R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, halo, CN, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), and <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>. In some embodiments, ring A is ; and R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, halo, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), and OC<com:Sub>1-< / com:Sub> [Image disponible dans le document PDF, Image available in the PDF document] 4haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, ring A is R<com:Sup>5< / com:Sup> ; and R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, halo, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), and <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>. In some embodiments, R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a C<com:Sub>3< / com:Sub>- <com:Sub>12< / com:Sub>heterocycloalkyl, optionally comprising one additional heteromoiety selected from N(R<com:Sup>10< / com:Sup>), O, and S. In some embodiments, R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a C<com:Sub>3-12< / com:Sub>heterocycloalkyl, optionally comprising one additional heteromoiety selected from N(R<com:Sup>10< / com:Sup>), and O. In some embodiments, R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional oxygen atom. In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from NO<com:Sub>2< / com:Sub>, CN, halo, =O, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-< / com:Sub> 6cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-< / com:Sub> 6alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub> 6alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C<com:Sub>1-6< / com:Sub>alkyl)(C1-6alkyl), NHC(O)C<com:Sub>1-6< / com:Sub>alkyl, N(C<com:Sub>1-6< / com:Sub>alkyl)C(O)C<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), and N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl). In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted WSGR Ref. No. 55554-710.601 with one or more substituents selected from NO<com:Sub>2< / com:Sub>, CN, halo, =O, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-< / com:Sub> 6alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, OC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), and <com:Math><semantics>N(C1−6alkyl)(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>. In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from NO<com:Sub>2< / com:Sub>, CN, halo, =O, OH, OC<com:Sub>1< / com:Sub>- 6alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1-6< / com:Sub>alkyl). In some embodiments, the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from NO<com:Sub>2< / com:Sub>, CN, halo, =O, OH, OC<com:Sub>1< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1< / com:Sub>alkyl). In some embodiments, the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from NO<com:Sub>2< / com:Sub>, CN, halo, =O, OH, OC<com:Sub>1< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1< / com:Sub>alkyl). In some embodiments, the C<com:Sub>3< / com:Sub>- <com:Math><semantics>12<annotation encoding="application / x-tex">_{12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from NO<com:Sub>2< / com:Sub>, CN, fluoro, =O, OH, OC<com:Sub>1< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1< / com:Sub>alkyl). In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from fluoro, =O, OH, OC<com:Sub>1< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1< / com:Sub>alkyl). In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one [Image disponible dans le document PDF, Image available in the PDF document] or more fluoro substituents. In some embodiments, ring A is ; and the one additional heteromoiety of the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is NR<com:Sup>10< / com:Sup>. In some embodiments, [Image disponible dans le document PDF, Image available in the PDF document] ring A is the one additional heteromoiety of the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and R<com:Sup>9< / com:Sup> is NR<com:Sup>10< / com:Sup>; and the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-< / com:Sub> 6alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), NHC(O)C<com:Sub>1-6< / com:Sub>alkyl, N(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl)C(O)C<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), SC<com:Sub>1-6< / com:Sub>alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, [Image disponible dans le document PDF, Image available in the PDF document] and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl. In some embodiments, ring A is ; the one additional heteromoiety of the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is NR<com:Sup>10< / com:Sup>; and the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, and OC<com:Sub>1-6< / com:Sub>alkyl. In WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document] some embodiments, ring A is ; the one additional heteromoiety of the <com:Math><semantics>C3−<annotation encoding="application / x-tex">C_{3-}< / annotation>< / semantics>< / com:Math> <com:Sub>12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is NR<com:Sup>10< / com:Sup>; and R<com:Sup>10< / com:Sup> is selected from C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-< / com:Sub> 6cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-8< / com:Sub> 6alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, <com:Math><semantics>C(O)NH2<annotation encoding="application / x-tex">C(O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NH(C1−6alkyl)<annotation encoding="application / x-tex">C(O)NH(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(C1−6alkyl)<annotation encoding="application / x-tex">C(O)N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>(C1-6alkyl), <com:Math><semantics>S(O)C1−6alkyl<annotation encoding="application / x-tex">S(O)C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>SO2C1−6alkyl<annotation encoding="application / x-tex">SO_2C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>.In [Image disponible dans le document PDF, Image available in the PDF document] some embodiments, ring A is ; the one additional heteromoiety of the <com:Math><semantics>C3−<annotation encoding="application / x-tex">C_{3-}< / annotation>< / semantics>< / com:Math> <com:Sub>12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is NR<com:Sup>10< / com:Sup>; and R<com:Sup>10< / com:Sup> is selected from C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-< / com:Sub> 6cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, and C<com:Sub>3-6< / com:Sub> heterocycloalkyl. In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] ; the one additional heteromoiety of the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>NR10<annotation encoding="application / x-tex">NR^{10}< / annotation>< / semantics>< / com:Math>; and <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl. In some embodiments, ring A is , and the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from halo, NO<com:Sub>2< / com:Sub>, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub> 6alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, <com:Math><semantics>C(O)NH(C1−6alkyl),C(O)N(C1−6alkyl)(C1−6alkyl),NHC(O)C1−6alkyl,N(C1−6alkyl)C(O)C1−6alkyl,<annotation encoding="application / x-tex">C(O)NH(C_{1-6}alkyl), C(O)N(C_{1-6}alkyl)(C_{1-6}alkyl), NHC(O)C_{1-6}alkyl, N(C_{1-6}alkyl)C(O)C_{1-6}alkyl,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>NH2<annotation encoding="application / x-tex">NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NH(C1−6alkyl)<annotation encoding="application / x-tex">NH(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(<annotation encoding="application / x-tex">N(< / annotation>< / semantics>< / com:Math> [Image disponible dans le document PDF, Image available in the PDF document] some embodiments, ring A is , and the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, NO<com:Sub>2< / com:Sub>, OH, C<com:Sub>1-< / com:Sub> 6alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>OC1−6<annotation encoding="application / x-tex">OC_{1-6}< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>NH2<annotation encoding="application / x-tex">NH_2< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>NH(C1−6<annotation encoding="application / x-tex">NH(C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl). In some embodiments, ring A is , and the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, NO<com:Sub>2< / com:Sub>, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1-6< / com:Sub>alkyl). In some embodiments, [Image disponible dans le document PDF, Image available in the PDF document] ring A is , and the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from halo, NO<com:Sub>2< / com:Sub>, OH, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1-6< / com:Sub>alkyl). In some embodiments, R<com:Sup>10< / com:Sup> is selected from hydrogen, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-< / com:Sub> 6cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-8< / com:Sub> 6alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, and C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl. In some embodiments, R<com:Sup>10< / com:Sup> is selected from hydrogen, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, and <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> heterocycloalkyl. In some embodiments, <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> is selected from hydrogen, and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In [Image disponible dans le document PDF, Image available in the PDF document] some embodiments, the heterocycle formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is selected from , [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , and . In some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are methyl. In some embodiments, R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup> are H; R<com:Sup>3< / com:Sup> is selected from H and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> are each independently selected from H, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>1-4< / com:Sub>haloalkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional heteromoiety selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math>, O, S, S(O) and SO<com:Sub>2< / com:Sub>, and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, WSGR Ref. No. 55554-710.601 C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub> 6alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub> 6alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C1-6alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), NHC(O)C<com:Sub>1-6< / com:Sub>alkyl, N(C<com:Sub>1-6< / com:Sub>alkyl)C(O)C<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), SC<com:Sub>1-6< / com:Sub> 6alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl, wherein R<com:Sup>10< / com:Sup> is selected from C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub> 6alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, <com:Math><semantics>C(O)NH(C1−6alkyl),C(O)N(C1−6alkyl)(C1−6alkyl),S(O)C1−6alkyl,andSO2C1−6alkyl.<annotation encoding="application / x-tex">C(O)NH(C_{1-6}alkyl), C(O)N(C_{1-6}alkyl)(C_{1-6}alkyl), S(O)C_{1-6}alkyl, and SO_2C_{1-6}alkyl.< / annotation>< / semantics>< / com:Math> In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted alkyl; [Image disponible dans le document PDF, Image available in the PDF document] ring A is and R<com:Sup>5< / com:Sup> are each independently selected from H, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-< / com:Sub> 4alkyl, OC<com:Sub>1-4< / com:Sub>haloalkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a C<com:Sub>3-12< / com:Sub>heterocycloalkyl, optionally comprising one additional heteromoiety selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math> and O and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1-6< / com:Sub>alkyl), wherein R<com:Sup>10< / com:Sup> is selected from C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, <com:Math><semantics>C(O)C1−6<annotation encoding="application / x-tex">C(O)C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>C(O)NH2<annotation encoding="application / x-tex">C(O)NH_2< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>C(O)NH(C1−6<annotation encoding="application / x-tex">C(O)NH(C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl). In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted alkyl; ring A is [Image disponible dans le document PDF, Image available in the PDF document] ; R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, and <com:Math><semantics>N(R8R9);<annotation encoding="application / x-tex">N(R^8R^9);< / annotation>< / semantics>< / com:Math> R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a C<com:Sub>3-12< / com:Sub>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, <com:Math><semantics>OC1−6<annotation encoding="application / x-tex">OC_{1-6}< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>NH2<annotation encoding="application / x-tex">NH_2< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>NH(C1−6<annotation encoding="application / x-tex">NH(C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl). In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected [Image disponible dans le document PDF, Image available in the PDF document] from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted alkyl; ring A is <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> are each independently selected from H, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>); <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, aryl, and C<com:Sub>5-6< / com:Sub>heteroaryl. In some embodiments, R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup> are H; R<com:Sup>3< / com:Sup> is selected from H and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> are each independently selected from H and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, aryl, and C<com:Sub>5-6< / com:Sub>heteroaryl. In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted alkyl; [Image disponible dans le document PDF, Image available in the PDF document] ring A is and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> are each independently selected from H and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl. In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted alkyl; ring A is [Image disponible dans le document PDF, Image available in the PDF document] ; <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> are each independently selected from H and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, and OH. In some embodiments, R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup> are H; R<com:Sup>3< / com:Sup> is selected [Image disponible dans le document PDF, Image available in the PDF document] from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted alkyl; ring A is and R<com:Sup>5< / com:Sup> are each independently selected from H and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more halo substituents. In some embodiments, R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup> are H; R<com:Sup>3< / com:Sup> is selected from H and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> [Image disponible dans le document PDF, Image available in the PDF document] optionally substituted alkyl; ring A is and R<com:Sup>5< / com:Sup> are each independently selected from H and N(<com:Math><semantics>R8R9<annotation encoding="application / x-tex">R^8R^9< / annotation>< / semantics>< / com:Math>); <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−<annotation encoding="application / x-tex">C_{3-}< / annotation>< / semantics>< / com:Math> 12heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more fluoro substituents. In some embodiments, R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup> are H; R<com:Sup>3< / com:Sup> is selected [Image disponible dans le document PDF, Image available in the PDF document] from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted alkyl; ring A is and R<com:Sup>5< / com:Sup> are each independently selected from H, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>1-4< / com:Sub>haloalkyl, O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>); R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a C<com:Sub>3-12< / com:Sub>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1-6< / com:Sub>alkyl). In some embodiments, the compound, pharmaceutically acceptable salt or solvate thereof, has NH the struc . In some embodiments, the compound, pharmaceutically [Image disponible dans le document PDF, Image available in the PDF document] acceptable salt or solvate thereof, has the structure: In some embodiments, the compound, pharmaceutically acceptable salt or solvate thereof, has the NH structure . In some embodiments, the compound, pharmaceutically [Image disponible dans le document PDF, Image available in the PDF document] acceptable salt or solvate thereof, has the structure:

[0010] In an aspect, the present disclosure provides a compound, or pharmaceutically acceptable salt or solvate thereof, as provided in Table 1.

[0011] In an aspect, the present disclosure provides a compound, or pharmaceutically acceptable salt or [Image disponible dans le document PDF, Image available in the PDF document] , WSGR Ref. No. 55554-710.601 In an aspect, the present disclosure provides a pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt or solvate thereof, as described in any of the embodiments disclosed herein and a pharmaceutically acceptable excipient. In an aspect, the present disclosure provides a pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt or solvate thereof, as described in any of the embodiments disclosed herein and a pharmaceutically acceptable excipient. In an aspect, the present disclosure provides use of the composition of any of the embodiments disclosed herein in the treatment of a disease or disorder mediated by the 5-HT2 receptor. In an aspect, the present disclosure provides use of the compound, salt, or solvate of any of the embodiments disclosed herein in the treatment of a disease or disorder mediated by the 5-HT2 receptor. In an aspect, the present disclosure provides the use of any of the embodiments disclosed herein according to any of the embodiments disclosed herein, wherein the disease or disorder is a 5-HT2A and / or 5-HT<com:Sub>2c< / com:Sub> receptor-mediated disorder. The use according to any of the embodiments disclosed herein, wherein the disease or disorder is depressive disorder, an anxiety disorder, panic attack, agoraphobia, specific phobia, social phobia, bipolar disorder, post-traumatic stress, an eating disorder, obesity, a gastro-intestinal disorder, alcoholism, drug addiction, schizophrenia, a psychotic disorder, a sleep disorder, sleep apnea, migraine, sexual dysfunction, a central nervous system disorder, trauma, stroke, spinal cord injury, a cardio-vascular disorder, diabetes insipidus, or obsessive disorder. In an aspect, the present disclosure provides a use of the composition of any of the embodiments disclosed herein to ameliorate at least one symptom of a brain disorder, stress, anxiety, addiction, depression, compulsive behavior, or by promoting weight loss, or by improving mood, or by treating or preventing a psychological disorder, or by enhancing performance. In an aspect, the present disclose provides a method of treating at least one symptom of a brain disorder, stress, anxiety, addiction, depression, or compulsive behavior comprising administering to a patient in need thereof the compound, salt, or solvate of any of the embodiments disclosed herein. In an aspect, the present disclosure provides a method of promoting weight loss comprising administering to a patient in need thereof the compound, salt, or solvate of any of the embodiments disclosed herein. In an aspect, the present disclosure provides a method of improving mood comprising administering to a patient in need thereof the compound, salt, or solvate of any of the embodiments disclosed herein.

[0015] In an aspect, the present disclosure provides a method of preventing a psychological disorder comprising administering to a patient in need thereof the compound, salt, or solvate of any of the embodiments disclosed herein. WSGR Ref. No. 55554-710.601

[0016] In an aspect, the present disclosure provides a method of enhancing performance comprising administering to a patient in need thereof the compound, salt, or solvate of any of the embodiments disclosed herein.

[0017] In an aspect, the present disclosure provides a method of treating depressive disorder, an anxiety disorder, panic attack, agoraphobia, specific phobia, social phobia, bipolar disorder, post- traumatic stress, an eating disorder, obesity, a gastro-intestinal disorder, alcoholism, drug addiction, schizophrenia, a psychotic disorder, a sleep disorder, sleep apnea, migraine, sexual dysfunction, a central nervous system disorder, trauma, stroke, spinal cord injury, a cardio- vascular disorder, diabetes insipidus, or obsessive disorder comprising administering to a patient in need thereof the compound, salt, or solvate of any of the embodiments disclosed herein.

[0018] In an aspect, the present disclosure provides a method of preparing the compound [Image disponible dans le document PDF, Image available in the PDF document]

[0019] In an aspect, the present disclosure provides a method of preparing the compound [Image disponible dans le document PDF, Image available in the PDF document] •

[0020] In an aspect, the present disclosure provides a method of preparing the compound [Image disponible dans le document PDF, Image available in the PDF document] , the method comprising: (a) a chlorination of an aminopyrazine, optionally comprising treatment of the aminopyrizine with tBuONO or TiCl<com:Sub>4< / com:Sub> to form a chloropyrazine; (b) a nucleophilic aromatic substitution of the chloropyrazine, optionally comprising treatment with a primary or secondary amine and optionally comprising treatment with a base, to form an aminopyrazine.

[0021] In an aspect, the present disclosure provides method of preparing the compound [Image disponible dans le document PDF, Image available in the PDF document] , the method comprising: (a) a chlorination of an aminopyrazine, optionally comprising treatment of the aminopyrizine with tBuONO or TiCl<com:Sub>4< / com:Sub> to form a chloropyrazine; (b) a nucleophilic aromatic substitution of the chloropyrazine, optionally comprising treatment with a primary or secondary amine and optionally comprising treatment WSGR Ref. No. 55554-710.601 with a base, to form an aminopyrazine; and further comprising (c) a deprotection of a protected amine, optionally comprising an N-dealkylation compsising treatment with 1-chloroethyl chloroformate. DETAILED DESCRIPTION OF THE INVENTION

[0022] As used herein and in the appended claims, the singular forms "a," "and," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an agent" includes a plurality of such agents, and reference to "the cell" includes reference to one or more cells (or to a plurality of cells) and equivalents thereof known to those skilled in the art, and so forth. When ranges are used herein for physical properties, such as molecular weight, or chemical properties, such as chemical formulae, all combinations and subcombinations of ranges and specific embodiments therein are intended to be included. The term "about" when referring to a number or a numerical range means that the number or numerical range referred to is an approximation within experimental variability (or within statistical experimental error), and thus the number or numerical range, in some instances, will vary between 1% and 15% of the stated number or numerical range. The term "comprising" (and related terms such as "comprise" or "comprises" or "having" or "including") is not intended to exclude that in other certain embodiments, for example, an embodiment of any composition of matter, composition, method, or process, or the like, described herein, "consist of" or "consist essentially of" the described features. Definitions

[0023] As used in the specification and appended claims, unless specified to the contrary, the following terms have the meaning indicated below.

[0024] "Amino" refers to the –NH<com:Sub>2< / com:Sub> radical.

[0025] "Cyano" refers to the -CN radical.

[0026] "Nitro" refers to the -NO<com:Sub>2< / com:Sub> radical.

[0027] "Oxa" refers to the -O- radical.

[0028] "Oxo" refers to the =O radical.

[0029] "Thioxo" refers to the =S radical.

[0030] "Imino" refers to the =N-H radical.

[0031] "Oximo" refers to the =N-OH radical.

[0032] "Hydrazino" refers to the =N-NH<com:Sub>2< / com:Sub> radical.

[0033] "Alkyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to fifteen carbon atoms (e.g., WSGR Ref. No. 55554-710.601 <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C15<annotation encoding="application / x-tex">C_{15}< / annotation>< / semantics>< / com:Math> alkyl). In certain embodiments, an alkyl comprises one to thirteen carbon atoms (e.g., <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C13<annotation encoding="application / x-tex">C_{13}< / annotation>< / semantics>< / com:Math> alkyl). In certain embodiments, an alkyl comprises one to eight carbon atoms (e.g., <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math> alkyl). In other embodiments, an alkyl comprises one to five carbon atoms (e.g., <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C5<annotation encoding="application / x-tex">C_5< / annotation>< / semantics>< / com:Math> alkyl). In other embodiments, an alkyl comprises one to four carbon atoms (e.g., C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub> alkyl). In other embodiments, an alkyl comprises one to three carbon atoms (e.g., C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl). In other embodiments, an alkyl comprises one to two carbon atoms (e.g., C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub> alkyl). In other embodiments, an alkyl comprises one carbon atom (<com:Math><semantics>e.g.<annotation encoding="application / x-tex">e.g.< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math> alkyl). In other embodiments, an alkyl comprises five to fifteen carbon atoms (e.g., C<com:Sub>5< / com:Sub>-C<com:Sub>15< / com:Sub> alkyl). In other embodiments, an alkyl comprises five to eight carbon atoms (e.g., C<com:Sub>5< / com:Sub>-C<com:Sub>8< / com:Sub> alkyl). In other embodiments, an alkyl comprises two to five carbon atoms (e.g., C<com:Sub>2< / com:Sub>-C<com:Sub>5< / com:Sub> alkyl). In other embodiments, an alkyl comprises three to five carbon atoms (e.g., C<com:Sub>3< / com:Sub>-C<com:Sub>5< / com:Sub> alkyl). In other embodiments, the alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl). The alkyl is attached to the rest of the molecule by a single bond. Unless stated otherwise specifically in the specification, an alkyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR<com:Sup>a< / com:Sup>, -SR<com:Sup>a< / com:Sup>, -OC(O)-R<com:Sup>a< / com:Sup>, -N(R<com:Sup>a< / com:Sup>)<com:Sub>2< / com:Sub>, -C(O)R<com:Sup>a< / com:Sup>, -C(O)OR<com:Sup>a< / com:Sup>, -C(O)N(R<com:Sup>a< / com:Sup>)<com:Sub>2< / com:Sub>, - <com:Math><semantics>N(Ra)C(O)ORa<annotation encoding="application / x-tex">N(R^{a})C(O)OR^{a}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(O)−N(Ra)2<annotation encoding="application / x-tex">-OC(O)-N(R^{a})_{2}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)C(O)Ra<annotation encoding="application / x-tex">-N(R^{a})C(O)R^{a}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)S(O)tRa<annotation encoding="application / x-tex">-N(R^{a})S(O)_{t}R^{a}< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tORa<annotation encoding="application / x-tex">-S(O)_{t}OR^{a}< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tRa<annotation encoding="application / x-tex">-S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) and <com:Math><semantics>−S(O)tN(Ra)2<annotation encoding="application / x-tex">-S(O)_tN(R^a)_2< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) where each R<com:Sup>a< / com:Sup> is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl).

[0034] "Alkoxy" refers to a radical bonded through an oxygen atom of the formula –O-alkyl, where alkyl is an alkyl chain as defined above.

[0035] "Alkenyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and having from two to twelve carbon atoms. In certain embodiments, an alkenyl comprises two to eight carbon atoms. In other embodiments, an alkenyl comprises two to four carbon atoms. The LEGAL_1:87302383 WSGR Ref. No. 55554-710.601 alkenyl is attached to the rest of the molecule by a single bond, for example, ethenyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like. Unless stated otherwise specifically in the specification, an alkenyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, <com:Math><semantics>−ORa<annotation encoding="application / x-tex">-OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SRa<annotation encoding="application / x-tex">-SR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(O)−Ra<annotation encoding="application / x-tex">-OC(O)-R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)2<annotation encoding="application / x-tex">-N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)Ra<annotation encoding="application / x-tex">-C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)ORa<annotation encoding="application / x-tex">-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)N(Ra)2<annotation encoding="application / x-tex">-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(Ra)C(O)ORa<annotation encoding="application / x-tex">N(R^{a})C(O)OR^{a}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(O)−N(Ra)2<annotation encoding="application / x-tex">-OC(O)-N(R^{a})_{2}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)C(O)Ra<annotation encoding="application / x-tex">-N(R^{a})C(O)R^{a}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)S(O)tRa<annotation encoding="application / x-tex">-N(R^{a})S(O)_{t}R^{a}< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tORa<annotation encoding="application / x-tex">-S(O)_{t}OR^{a}< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tRa<annotation encoding="application / x-tex">-S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) and <com:Math><semantics>−S(O)tN(Ra)2<annotation encoding="application / x-tex">-S(O)_tN(R^a)_2< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) where each R<com:Sup>a< / com:Sup> is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl). "Alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, having from two to twelve carbon atoms. In certain embodiments, an alkynyl comprises two to eight carbon atoms. In other embodiments, an alkynyl comprises two to six carbon atoms. In other embodiments, an alkynyl comprises two to four carbon atoms. The alkynyl is attached to the rest of the molecule by a single bond, for example, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Unless stated otherwise specifically in the specification, an alkynyl group is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -ORa, -SRa, -OC(O)-Ra, -N(Ra)2, -C(O)Ra, -C(O)ORa, - <com:Math><semantics>C(O)N(Ra)2<annotation encoding="application / x-tex">C(O)N(R^{a})_{2}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)C(O)ORa<annotation encoding="application / x-tex">-N(R^{a})C(O)OR^{a}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(O)−N(Ra)2<annotation encoding="application / x-tex">-OC(O)-N(R^{a})_{2}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)C(O)Ra<annotation encoding="application / x-tex">-N(R^{a})C(O)R^{a}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)S(O)tRa<annotation encoding="application / x-tex">-N(R^{a})S(O)_{t}R^{a}< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tORa<annotation encoding="application / x-tex">-S(O)_tOR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tRa<annotation encoding="application / x-tex">-S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) and <com:Math><semantics>−S(O)tN(Ra)2<annotation encoding="application / x-tex">-S(O)_tN(R^a)_2< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) where each R<com:Sup>a< / com:Sup> is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or WSGR Ref. No. 55554-710.601 trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl).

[0037] "Alkylene" or "alkylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing no unsaturation and having from one to twelve carbon atoms, for example, methylene, ethylene, propylene, n-butylene, and the like. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group are through one carbon in the alkylene chain or through any two carbons within the chain. In certain embodiments, an alkylene comprises one to eight carbon atoms (e.g., C<com:Sub>1< / com:Sub>-C<com:Sub>8< / com:Sub> alkylene). In other embodiments, an alkylene comprises one to five carbon atoms (e.g., C<com:Sub>1< / com:Sub>-C<com:Sub>5< / com:Sub> alkylene). In other embodiments, an alkylene comprises one to four carbon atoms (e.g., C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub> alkylene). In other embodiments, an alkylene comprises one to three carbon atoms (e.g., C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkylene). In other embodiments, an alkylene comprises one to two carbon atoms (e.g., C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub> alkylene). In other embodiments, an alkylene comprises one carbon atom (<com:Math><semantics>e.g.<annotation encoding="application / x-tex">e.g.< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math> alkylene). In other embodiments, an alkylene comprises five to eight carbon atoms (e.g., C5-C8 alkylene). In other embodiments, an alkylene comprises two to five carbon atoms (e.g., C2-C5 alkylene). In other embodiments, an alkylene comprises three to five carbon atoms (e.g., C<com:Sub>3< / com:Sub>-C<com:Sub>5< / com:Sub> alkylene). Unless stated otherwise specifically in the specification, an alkylene chain is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR<com:Sup>a< / com:Sup>, - <com:Math><semantics>SRa<annotation encoding="application / x-tex">SR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(O)−Ra<annotation encoding="application / x-tex">-OC(O)-R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)2<annotation encoding="application / x-tex">-N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)Ra<annotation encoding="application / x-tex">-C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)ORa<annotation encoding="application / x-tex">-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)N(Ra)2<annotation encoding="application / x-tex">-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)C(O)ORa<annotation encoding="application / x-tex">-N(R^a)C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(O)−N(Ra)2<annotation encoding="application / x-tex">-OC(O)-N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(Ra)C(O)Ra<annotation encoding="application / x-tex">N(R^a)C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)S(O)tRa<annotation encoding="application / x-tex">-N(R^a)S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tORa<annotation encoding="application / x-tex">-S(O)_tOR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tRa<annotation encoding="application / x-tex">-S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) and -S(O)<com:Sub>t< / com:Sub>N(R<com:Sup>a< / com:Sup>)<com:Sub>2< / com:Sub> (where t is 1 or 2) where each R<com:Sup>a< / com:Sup> is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl).

[0038] "Alkenylene" or "alkenylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, WSGR Ref. No. 55554-710.601 containing at least one carbon-carbon double bond, and having from two to twelve carbon atoms. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. In certain embodiments, an alkenylene comprises two to eight carbon atoms (e.g., C<com:Sub>2< / com:Sub>-C<com:Sub>8< / com:Sub> alkenylene). In other embodiments, an alkenylene comprises two to five carbon atoms (e.g., C<com:Sub>2< / com:Sub>-C<com:Sub>5< / com:Sub> alkenylene). In other embodiments, an alkenylene comprises two to four carbon atoms (e.g., C<com:Sub>2< / com:Sub>-C<com:Sub>4< / com:Sub> alkenylene). In other embodiments, an alkenylene comprises two to three carbon atoms (e.g., C2-C3 alkenylene). In other embodiments, an alkenylene comprises two carbon atoms (e.g., C2 alkenylene). In other embodiments, an alkenylene comprises five to eight carbon atoms (e.g., C<com:Sub>5< / com:Sub>-C<com:Sub>8< / com:Sub> alkenylene). In other embodiments, an alkenylene comprises three to five carbon atoms (e.g., C<com:Sub>3< / com:Sub>-C<com:Sub>5< / com:Sub> alkenylene). Unless stated otherwise specifically in the specification, an alkenylene chain is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR<com:Sup>a< / com:Sup>, -SR<com:Sup>a< / com:Sup>, -OC(O)-R<com:Sup>a< / com:Sup>, -N(R<com:Sup>a< / com:Sup>)<com:Sub>2< / com:Sub>, -C(O)R<com:Sup>a< / com:Sup>, -C(O)OR<com:Sup>a< / com:Sup>, -C(O)N(R<com:Sup>a< / com:Sup>)<com:Sub>2< / com:Sub>, - <com:Math><semantics>N(Ra)C(O)ORa<annotation encoding="application / x-tex">N(R^a)C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(O)−N(Ra)2<annotation encoding="application / x-tex">-OC(O)-N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)C(O)Ra<annotation encoding="application / x-tex">-N(R^a)C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)S(O)tRa<annotation encoding="application / x-tex">-N(R^a)S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tORa<annotation encoding="application / x-tex">-S(O)_tOR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tRa<annotation encoding="application / x-tex">-S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) and <com:Math><semantics>−S(O)tN(Ra)2<annotation encoding="application / x-tex">-S(O)_tN(R^a)_2< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) where each R<com:Sup>a< / com:Sup> is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl).

[0039] "Alkynylene" or "alkynylene chain" refers to a straight or branched divalent hydrocarbon chain linking the rest of the molecule to a radical group, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and having from two to twelve carbon atoms. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. In certain embodiments, an alkynylene comprises two to eight carbon atoms (e.g., C<com:Sub>2< / com:Sub>-C<com:Sub>8< / com:Sub> alkynylene). In other embodiments, an alkynylene comprises two to five carbon atoms (e.g., C<com:Sub>2< / com:Sub>-C<com:Sub>5< / com:Sub> alkynylene). In other embodiments, an alkynylene comprises two to four carbon atoms (<com:Math><semantics>e.g.<annotation encoding="application / x-tex">e.g.< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math> alkynylene). In other embodiments, an alkynylene comprises two to three carbon atoms (e.g., C<com:Sub>2< / com:Sub>-C<com:Sub>3< / com:Sub> alkynylene). In other embodiments, an alkynylene comprises two carbon atoms (e.g., C2 alkynylene). In other embodiments, an WSGR Ref. No. 55554-710.601 alkynylene comprises five to eight carbon atoms (e.g., C<com:Sub>5< / com:Sub>-C<com:Sub>8< / com:Sub> alkynylene). In other embodiments, an alkynylene comprises three to five carbon atoms (e.g., C<com:Sub>3< / com:Sub>-C<com:Sub>5< / com:Sub> alkynylene). Unless stated otherwise specifically in the specification, an alkynylene chain is optionally substituted by one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, <com:Math><semantics>−ORa<annotation encoding="application / x-tex">-OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SRa<annotation encoding="application / x-tex">-SR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(O)−Ra<annotation encoding="application / x-tex">-OC(O)-R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)2<annotation encoding="application / x-tex">-N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)Ra<annotation encoding="application / x-tex">-C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)ORa<annotation encoding="application / x-tex">-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)N(Ra)2<annotation encoding="application / x-tex">-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(Ra)C(O)ORa<annotation encoding="application / x-tex">N(R^a)C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(O)−N(Ra)2<annotation encoding="application / x-tex">-OC(O)-N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)C(O)Ra<annotation encoding="application / x-tex">-N(R^a)C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(Ra)S(O)tRa<annotation encoding="application / x-tex">-N(R^a)S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tORa<annotation encoding="application / x-tex">-S(O)_tOR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−S(O)tRa<annotation encoding="application / x-tex">-S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) and <com:Math><semantics>−S(O)tN(Ra)2<annotation encoding="application / x-tex">-S(O)_tN(R^a)_2< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) where each R<com:Sup>a< / com:Sup> is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl).

[0040] "Aryl" refers to a radical derived from an aromatic monocyclic or multicyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or multicyclic hydrocarbon ring system contains only hydrogen and carbon from five to eighteen carbon atoms, where at least one of the rings in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized <com:Math><semantics>(4n+2)<annotation encoding="application / x-tex">(4n+2)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system in accordance with the Hückel theory. The ring system from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin and naphthalene. Unless stated otherwise specifically in the specification, the term "aryl" or the prefix "ar-" (such as in "aralkyl") is meant to include aryl radicals optionally substituted by one or more substituents independently selected from alkyl, alkenyl, alkynyl, halo, fluoroalkyl, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted carbocyclyl, optionally substituted carbocyclylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R<com:Sup>b< / com:Sup>-OR<com:Sup>a< / com:Sup>, -R<com:Sup>b< / com:Sup>-OC(O)-R<com:Sup>a< / com:Sup>, -R<com:Sup>b< / com:Sup>-OC(O)-OR<com:Sup>a< / com:Sup>, -R<com:Sup>b< / com:Sup>-OC(O)- <com:Math><semantics>N(Ra)2<annotation encoding="application / x-tex">N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−N(Ra)2<annotation encoding="application / x-tex">-R^b-N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)Ra<annotation encoding="application / x-tex">-R^b-C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)ORa<annotation encoding="application / x-tex">-R^b-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−O−Rc−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-O-R^c-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−<annotation encoding="application / x-tex">-R^b-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(Ra)C(O)ORa<annotation encoding="application / x-tex">N(R^a)C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−N(Ra)C(O)Ra<annotation encoding="application / x-tex">-R^b-N(R^a)C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−N(Ra)S(O)tRa<annotation encoding="application / x-tex">-R^b-N(R^a)S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−Rb−S(O)tRa<annotation encoding="application / x-tex">-R^b-S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−Rb−S(O)tORa<annotation encoding="application / x-tex">-R^b-S(O)_tOR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) and <com:Math><semantics>−Rb−S(O)tN(Ra)2<annotation encoding="application / x-tex">-R^b-S(O)_tN(R^a)_2< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), where each <com:Math><semantics>Ra<annotation encoding="application / x-tex">R^a< / annotation>< / semantics>< / com:Math> is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R<com:Sup>b< / com:Sup> is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R<com:Sup>c< / com:Sup> is a straight or branched alkylene or alkenylene chain, and where each of the above substituents is unsubstituted unless otherwise indicated.

[0041] "Aralkyl" refers to a radical of the formula -R<com:Sup>c< / com:Sup>-aryl where R<com:Sup>c< / com:Sup> is an alkylene chain as defined above, for example, methylene, ethylene, and the like. The alkylene chain part of the aralkyl radical is optionally substituted as described above for an alkylene chain. The aryl part of the aralkyl radical is optionally substituted as described above for an aryl group.

[0042] "Aralkenyl" refers to a radical of the formula –R<com:Sup>d< / com:Sup>-aryl where R<com:Sup>d< / com:Sup> is an alkenylene chain as defined above. The aryl part of the aralkenyl radical is optionally substituted as described above for an aryl group. The alkenylene chain part of the aralkenyl radical is optionally substituted as defined above for an alkenylene group.

[0043] "Aralkynyl" refers to a radical of the formula -R<com:Sup>e< / com:Sup>-aryl, where R<com:Sup>e< / com:Sup> is an alkynylene chain as defined above. The aryl part of the aralkynyl radical is optionally substituted as described above for an aryl group. The alkynylene chain part of the aralkynyl radical is optionally substituted as defined above for an alkynylene chain.

[0044] "Aralkoxy" refers to a radical bonded through an oxygen atom of the formula -O-R<com:Sup>c< / com:Sup>-aryl where R<com:Sup>c< / com:Sup> is an alkylene chain as defined above, for example, methylene, ethylene, and the like. The alkylene chain part of the aralkyl radical is optionally substituted as described above for an alkylene chain. The aryl part of the aralkyl radical is optionally substituted as described above for an aryl group.

[0045] "Carbocyclyl" refers to a stable non-aromatic monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, which includes fused or bridged ring systems, having from three to fifteen carbon atoms. In certain embodiments, a carbocyclyl comprises three to ten carbon atoms. In other embodiments, a carbocyclyl comprises five to seven carbon atoms. The carbocyclyl is attached to the rest of the molecule by a single bond. Carbocyclyl is saturated (i.e., containing single C-C bonds only) or unsaturated (i.e., containing one or more double bonds or triple bonds). A fully saturated carbocyclyl radical is also referred to as WSGR Ref. No. 55554-710.601 "cycloalkyl." Examples of monocyclic cycloalkyls include, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. An unsaturated carbocyclyl is also referred to as "cycloalkenyl." Examples of monocyclic cycloalkenyls include, e.g., cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Polycyclic carbocyclyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornenyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. Unless otherwise stated specifically in the specification, the term "carbocyclyl" is meant to include carbocyclyl radicals that are optionally substituted by one or more substituents independently selected from alkyl, alkenyl, alkynyl, halo, fluoroalkyl, oxo, thioxo, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted carbocyclyl, optionally substituted carbocyclylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R<com:Sup>b< / com:Sup>-OR<com:Sup>a< / com:Sup>, -R<com:Sup>b< / com:Sup>-OC(O)-R<com:Sup>a< / com:Sup>, -R<com:Sup>b< / com:Sup>-OC(O)-OR<com:Sup>a< / com:Sup>, -R<com:Sup>b< / com:Sup>-OC(O)- <com:Math><semantics>N(Ra)2<annotation encoding="application / x-tex">N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−N(Ra)2<annotation encoding="application / x-tex">-R^b-N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)Ra<annotation encoding="application / x-tex">-R^b-C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)ORa<annotation encoding="application / x-tex">-R^b-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−O−Rc−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-O-R^c-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−<annotation encoding="application / x-tex">-R^b-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(Ra)C(O)ORa<annotation encoding="application / x-tex">N(R^a)C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−N(Ra)C(O)Ra<annotation encoding="application / x-tex">-R^b-N(R^a)C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−N(Ra)S(O)tRa<annotation encoding="application / x-tex">-R^b-N(R^a)S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−Rb−S(O)tRa<annotation encoding="application / x-tex">-R^b-S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−Rb−S(O)tORa<annotation encoding="application / x-tex">-R^b-S(O)_tOR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) and <com:Math><semantics>−Rb−S(O)tN(Ra)2<annotation encoding="application / x-tex">-R^b-S(O)_tN(R^a)_2< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), where each <com:Math><semantics>Ra<annotation encoding="application / x-tex">R^a< / annotation>< / semantics>< / com:Math> is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R<com:Sup>b< / com:Sup> is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R<com:Sup>c< / com:Sup> is a straight or branched alkylene or alkenylene chain, and where each of the above substituents is unsubstituted unless otherwise indicated.

[0046] "Carbocyclylalkyl" refers to a radical of the formula –R<com:Sup>c< / com:Sup>-carbocyclyl where R<com:Sup>c< / com:Sup> is an alkylene chain as defined above. The alkylene chain and the carbocyclyl radical is optionally substituted as defined above.

[0047] "Carbocyclylalkynyl" refers to a radical of the formula –R<com:Sup>c< / com:Sup>-carbocyclyl where R<com:Sup>c< / com:Sup> is an alkynylene chain as defined above. The alkynylene chain and the carbocyclyl radical is optionally substituted as defined above.

[0048] "Carbocyclylalkoxy" refers to a radical bonded through an oxygen atom of the formula –O- R<com:Sup>c< / com:Sup>-carbocyclyl where R<com:Sup>c< / com:Sup> is an alkylene chain as defined above. The alkylene chain and the carbocyclyl radical is optionally substituted as defined above.

[0049] As used herein, "carboxylic acid bioisostere" refers to a functional group or moiety that exhibits similar physical, biological and / or chemical properties as a carboxylic acid moiety. Examples of carboxylic acid bioisosteres include, but are not limited to, [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]

[0050] "Halo" or "halogen" refers to bromo, chloro, fluoro or iodo substituents.

[0051] "Fluoroalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more fluoro radicals, as defined above, for example, trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like. In some embodiments, the alkyl part of the fluoroalkyl radical is optionally substituted as defined above for an alkyl group.

[0052] "Heterocyclyl" refers to a stable 3- to 18-membered non-aromatic ring radical that comprises two to twelve carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen and sulfur. Unless stated otherwise specifically in the specification, the heterocyclyl radical is a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which optionally includes fused or bridged ring systems. The heteroatoms in the heterocyclyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heterocyclyl radical is partially or fully saturated. The heterocyclyl is attached to the rest of the molecule through any atom of the ring(s). Examples of such heterocyclyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Unless stated otherwise specifically in the specification, the term "heterocyclyl" is meant to include heterocyclyl radicals as defined above that are optionally substituted by one or more substituents selected from alkyl, alkenyl, alkynyl, halo, fluoroalkyl, oxo, thioxo, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted carbocyclyl, WSGR Ref. No. 55554-710.601 optionally substituted carbocyclylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -R<com:Sup>b< / com:Sup>-OR<com:Sup>a< / com:Sup>, -R<com:Sup>b< / com:Sup>-OC(O)-R<com:Sup>a< / com:Sup>, -R<com:Sup>b< / com:Sup>-OC(O)-OR<com:Sup>a< / com:Sup>, -R<com:Sup>b< / com:Sup>-OC(O)-N(R<com:Sup>a< / com:Sup>)<com:Sub>2< / com:Sub>, -R<com:Sup>b< / com:Sup>-N(R<com:Sup>a< / com:Sup>)<com:Sub>2< / com:Sub>, -R<com:Sup>b< / com:Sup>- <com:Math><semantics>C(O)Ra<annotation encoding="application / x-tex">C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)ORa<annotation encoding="application / x-tex">-R^b-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−O−Rc−C(O)N(Ra)2<annotation encoding="application / x-tex">-R^b-O-R^c-C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−N(Ra)C(O)ORa<annotation encoding="application / x-tex">-R^b-N(R^a)C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)ORa<annotation encoding="application / x-tex">-R^b-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)ORa<annotation encoding="application / x-tex">-R^b-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)ORa<annotation encoding="application / x-tex">-R^b-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)ORa<annotation encoding="application / x-tex">-R^b-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)ORa<annotation encoding="application / x-tex">-R^b-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)ORa<annotation encoding="application / x-tex">-R^b-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−C(O)ORa<annotation encoding="application / x-tex">-R^b-C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−R<annotation encoding="application / x-tex">-R< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(Ra)C(O)Ra<annotation encoding="application / x-tex">N(R^{a})C(O)R^{a}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−N(Ra)S(O)tRa<annotation encoding="application / x-tex">-R^{b}-N(R^{a})S(O)_{t}R^{a}< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−Rb−S(O)tRa<annotation encoding="application / x-tex">-R^{b}-S(O)_{t}R^{a}< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−Rb−S(O)tRa<annotation encoding="application / x-tex">-R^{b}-S(O)_{t}R^{a}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>S(O)tORa<annotation encoding="application / x-tex">S(O)_tOR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) and <com:Math><semantics>−Rb−S(O)tN(Ra)2<annotation encoding="application / x-tex">-R^b-S(O)_tN(R^a)_2< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), where each <com:Math><semantics>Ra<annotation encoding="application / x-tex">R^a< / annotation>< / semantics>< / com:Math> is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R<com:Sup>b< / com:Sup> is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R<com:Sup>c< / com:Sup> is a straight or branched alkylene or alkenylene chain, and where each of the above substituents is unsubstituted unless otherwise indicated.

[0053] "N-heterocyclyl" or "N-attached heterocyclyl" refers to a heterocyclyl radical as defined above containing at least one nitrogen and where the point of attachment of the heterocyclyl radical to the rest of the molecule is through a nitrogen atom in the heterocyclyl radical. An N-heterocyclyl radical is optionally substituted as described above for heterocyclyl radicals. Examples of such N-heterocyclyl radicals include, but are not limited to, 1-morpholinyl, 1- piperidinyl, 1-piperazinyl, 1-pyrrolidinyl, pyrazolidinyl, imidazolinyl, and imidazolidinyl.

[0054] "C-heterocyclyl" or "C-attached heterocyclyl" refers to a heterocyclyl radical as defined above containing at least one heteroatom and where the point of attachment of the heterocyclyl radical to the rest of the molecule is through a carbon atom in the heterocyclyl radical. A C-heterocyclyl radical is optionally substituted as described above for heterocyclyl radicals. Examples of such C-heterocyclyl radicals include, but are not limited to, 2-morpholinyl, 2- or 3- or 4-piperidinyl, 2-piperazinyl, 2- or 3-pyrrolidinyl, and the like.

[0055] "Heterocyclylalkyl" refers to a radical of the formula –R<com:Sup>c< / com:Sup>-heterocyclyl where R<com:Sup>c< / com:Sup> is an alkylene chain as defined above. If the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heterocyclylalkyl radical is optionally substituted as defined above for an alkylene chain. WSGR Ref. No. 55554-710.601 The heterocyclyl part of the heterocyclylalkyl radical is optionally substituted as defined above for a heterocyclyl group. "Heterocyclylalkoxy" refers to a radical bonded through an oxygen atom of the formula –O- R<com:Sup>c< / com:Sup>-heterocyclyl where R<com:Sup>c< / com:Sup> is an alkylene chain as defined above. If the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heterocyclylalkoxy radical is optionally substituted as defined above for an alkylene chain. The heterocyclyl part of the heterocyclylalkoxy radical is optionally substituted as defined above for a heterocyclyl group. "Heteroaryl" refers to a radical derived from a 3- to 18-membered aromatic ring radical that comprises two to seventeen carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen and sulfur. As used herein, the heteroaryl radical is a monocyclic, bicyclic, tricyclic or tetracyclic ring system, wherein at least one of the rings in the ring system is fully unsaturated, i.e., it contains a cyclic, delocalized (4n+2) <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system in accordance with the Hückel theory. Heteroaryl includes fused or bridged ring systems. The heteroatom(s) in the heteroaryl radical is optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl is attached to the rest of the molecule through any atom of the ring(s). Examples of heteroaryls include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzimdolyl, 1,3-benzodioxolyl, benzofuranyl, benzooxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, benzo[b][1,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzothieno[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H- benzo[6,7]cyclohepta[1,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, furo[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridazinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indazolyl, isoindolyl, isoindolyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, 5,8-methano-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyridinonyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, WSGR Ref. No. 55554-710.601 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, triazolyl, triazolyl, triazolyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]pridinyl, and thiophenyl (i.e. thienyl). Unless stated otherwise specifically in the specification, the term "heteroaryl" is meant to include heteroaryl radicals as defined above which are optionally substituted by one or more substituents selected from alkyl, alkenyl, alkynyl, halo, fluoroalkyl, haloalkenyl, haloalkynyl, oxo, thioxo, cyano, nitro, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted aralkynyl, optionally substituted carbocyclyl, optionally substituted carbocyclylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, <com:Math><semantics>−Rb<annotation encoding="application / x-tex">-R^b< / annotation>< / semantics>< / com:Math>-OR<com:Sup>a< / com:Sup>, <com:Math><semantics>−Rb<annotation encoding="application / x-tex">-R^b< / annotation>< / semantics>< / com:Math>-OC(O)-R<com:Sup>a< / com:Sup>, <com:Math><semantics>−Rb<annotation encoding="application / x-tex">-R^b< / annotation>< / semantics>< / com:Math>-OC(O)-OR<com:Sup>a< / com:Sup>, <com:Math><semantics>−Rb<annotation encoding="application / x-tex">-R^b< / annotation>< / semantics>< / com:Math>-OC(O)-N(R<com:Sup>a< / com:Sup>)<com:Sub>2< / com:Sub>, <com:Math><semantics>−Rb<annotation encoding="application / x-tex">-R^b< / annotation>< / semantics>< / com:Math>-N(R<com:Sup>a< / com:Sup>)<com:Sub>2< / com:Sub>, <com:Math><semantics>−Rb<annotation encoding="application / x-tex">-R^b< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C(O)Ra<annotation encoding="application / x-tex">C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb<annotation encoding="application / x-tex">-R^b< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(O)ORa<annotation encoding="application / x-tex">C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb<annotation encoding="application / x-tex">-R^b< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(O)N(Ra)2<annotation encoding="application / x-tex">C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb<annotation encoding="application / x-tex">-R^b< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>O<annotation encoding="application / x-tex">O< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>Rc<annotation encoding="application / x-tex">R^c< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(O)N(Ra)2<annotation encoding="application / x-tex">C(O)N(R^a)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb<annotation encoding="application / x-tex">-R^b< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>N(Ra)C(O)ORa<annotation encoding="application / x-tex">N(R^a)C(O)OR^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb<annotation encoding="application / x-tex">-R^b< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>N(Ra)C(O)Ra<annotation encoding="application / x-tex">N(R^a)C(O)R^a< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−Rb−N(Ra)S(O)tRa<annotation encoding="application / x-tex">-R^b-N(R^a)S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−Rb−S(O)tRa<annotation encoding="application / x-tex">-R^b-S(O)_tR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), <com:Math><semantics>−Rb−S(O)tRa<annotation encoding="application / x-tex">-R^b-S(O)_tR^a< / annotation>< / semantics>< / com:Math> <com:Math><semantics>S(O)tORa<annotation encoding="application / x-tex">S(O)_tOR^a< / annotation>< / semantics>< / com:Math> (where t is 1 or 2) and <com:Math><semantics>−Rb−S(O)tN(Ra)2<annotation encoding="application / x-tex">-R^b-S(O)_tN(R^a)_2< / annotation>< / semantics>< / com:Math> (where t is 1 or 2), where each <com:Math><semantics>Ra<annotation encoding="application / x-tex">R^a< / annotation>< / semantics>< / com:Math> is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, or trifluoromethyl), each R<com:Sup>b< / com:Sup> is independently a direct bond or a straight or branched alkylene or alkenylene chain, and R<com:Sup>c< / com:Sup> is a straight or branched alkylene or alkenylene chain, and where each of the above substituents is unsubstituted unless otherwise indicated.

[0058] "N-heteroaryl" refers to a heteroaryl radical as defined above containing at least one nitrogen and where the point of attachment of the heteroaryl radical to the rest of the molecule is through a nitrogen atom in the heteroaryl radical. An N-heteroaryl radical is optionally substituted as described above for heteroaryl radicals.

[0059] "C-heteroaryl" refers to a heteroaryl radical as defined above and where the point of attachment of the heteroaryl radical to the rest of the molecule is through a carbon atom in the heteroaryl radical. A C-heteroaryl radical is optionally substituted as described above for heteroaryl radicals. WSGR Ref. No. 55554-710.601

[0060] "Heteroarylalkyl" refers to a radical of the formula <com:Math><semantics>−Rc<annotation encoding="application / x-tex">-R^c< / annotation>< / semantics>< / com:Math>-heteroaryl, where <com:Math><semantics>Rc<annotation encoding="application / x-tex">R^c< / annotation>< / semantics>< / com:Math> is an alkylene chain as defined above. If the heteroaryl is a nitrogen-containing heteroaryl, the heteroaryl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heteroarylalkyl radical is optionally substituted as defined above for an alkylene chain. The heteroaryl part of the heteroarylalkyl radical is optionally substituted as defined above for a heteroaryl group.

[0061] "Heteroarylalkoxy" refers to a radical bonded through an oxygen atom of the formula –O- R<com:Sup>c< / com:Sup>-heteroaryl, where R<com:Sup>c< / com:Sup> is an alkylene chain as defined above. If the heteroaryl is a nitrogen-containing heteroaryl, the heteroaryl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heteroarylalkoxy radical is optionally substituted as defined above for an alkylene chain. The heteroaryl part of the heteroarylalkoxy radical is optionally substituted as defined above for a heteroaryl group.

[0062] The compounds disclosed herein, in some embodiments, contain one or more asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that are defined, in terms of absolute stereochemistry, as <com:Math><semantics>(R)<annotation encoding="application / x-tex">(R)< / annotation>< / semantics>< / com:Math>- or <com:Math><semantics>(S)<annotation encoding="application / x-tex">(S)< / annotation>< / semantics>< / com:Math>-. Unless stated otherwise, it is intended that all stereoisomeric forms of the compounds disclosed herein are contemplated by this disclosure. When the compounds described herein contain alkene double bonds, and unless specified otherwise, it is intended that this disclosure includes both E and Z geometric isomers (e.g., cis or trans.) Likewise, all possible isomers, as well as their racemic and optically pure forms, and all tautomeric forms are also intended to be included. The term "geometric isomer" refers to E or Z geometric isomers (e.g., cis or trans) of an alkene double bond. The term "positional isomer" refers to structural isomers around a central ring, such as ortho-, meta-, and para- isomers around a benzene ring.

[0063] A "tautomer" refers to a molecule wherein a proton shift from one atom of a molecule to another atom of the same molecule is possible. The compounds presented herein, in certain embodiments, exist as tautomers. In circumstances where tautomerization is possible, a chemical equilibrium of the tautomers will exist. The exact ratio of the tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some examples of tautomeric equilibria include: WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document]

[0064] The compounds disclosed herein, in some embodiments, are used in different enriched isotopic forms, e.g., enriched in the content of <com:Sup>2< / com:Sup>H, <com:Sup>3< / com:Sup>H, <com:Sup>11< / com:Sup>C, <com:Sup>13< / com:Sup>C and / or <com:Sup>14< / com:Sup>C. In one particular embodiment, the compound is deuterated in at least one position. Such deuterated forms can be made by the procedure described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve the metabolic stability and or efficacy, thus increasing the duration of action of drugs.

[0065] Unless otherwise stated, structures depicted herein are intended to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by <com:Sup>13< / com:Sup>C- or <com:Sup>14< / com:Sup>C-enriched carbon are within the scope of the present disclosure.

[0066] The compounds of the present disclosure optionally contain unnatural proportions of atomic isotopes at one or more atoms that constitute such compounds. For example, the compounds may be labeled with isotopes, such as for example, deuterium (<com:Sup>2< / com:Sup>H), tritium (<com:Sup>3< / com:Sup>H), iodine-125 (125I) or carbon-14 (14C). Isotopic substitution with <com:Sup>2< / com:Sup>H, <com:Sup>11< / com:Sup>C, <com:Sup>13< / com:Sup>C, <com:Sup>14< / com:Sup>C, <com:Sup>15< / com:Sup>C, <com:Sup>12< / com:Sup>N, <com:Sup>13< / com:Sup>N, <com:Sup>15< / com:Sup>N, <com:Sup>16< / com:Sup>N, <com:Sup>16< / com:Sup>O, <com:Sup>17< / com:Sup>O, <com:Sup>14< / com:Sup>F, <com:Sup>15< / com:Sup>F, <com:Sup>16< / com:Sup>F, <com:Sup>17< / com:Sup>F, <com:Sup>18< / com:Sup>F, <com:Sup>33< / com:Sup>S, <com:Sup>34< / com:Sup>S, <com:Sup>35< / com:Sup>S, <com:Sup>36< / com:Sup>S, <com:Sup>35< / com:Sup>Cl, <com:Sup>37< / com:Sup>Cl, <com:Sup>79< / com:Sup>Br, <com:Sup>81< / com:Sup>Br, <com:Sup>125< / com:Sup>I are all contemplated. In some embodiments, isotopic substitution with <com:Sup>18< / com:Sup>F is contemplated. All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.

[0067] In certain embodiments, the compounds disclosed herein have some or all of the <com:Sup>1< / com:Sup>H atoms replaced with <com:Sup>2< / com:Sup>H atoms. The methods of synthesis for deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthetic methods.

[0068] Deuterium substituted compounds are synthesized using various methods such as described in: Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0069] Deuterated starting materials are readily available and are subjected to the synthetic methods described herein to provide for the synthesis of deuterium-containing compounds. Large numbers of deuterium-containing reagents and building blocks are available commercially from chemical vendors, such as Aldrich Chemical Co.

[0070] Deuterium-transfer reagents suitable for use in nucleophilic substitution reactions, such as iodomethane-d<com:Sub>3< / com:Sub> (CD<com:Sub>3< / com:Sub>I), are readily available and may be employed to transfer a deuterium- substituted carbon atom under nucleophilic substitution reaction conditions to the reaction substrate. The use of CD<com:Sub>3< / com:Sub>I is illustrated, by way of example only, in the reaction schemes below. [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]

[0071] Deuterium-transfer reagents, such as lithium aluminum deuteride (LiAlD<com:Sub>4< / com:Sub>), are employed to transfer deuterium under reducing conditions to the reaction substrate. The use of LiAlD<com:Sub>4< / com:Sub> is illustrated, by way of example only, in the reaction schemes below. [Image disponible dans le document PDF, Image available in the PDF document]

[0072] Deuterium gas and palladium catalyst are employed to reduce unsaturated carbon-carbon linkages and to perform a reductive substitution of aryl carbon-halogen bonds as illustrated, by way of example only, in the reaction schemes below. [Image disponible dans le document PDF, Image available in the PDF document] In one embodiment, the compounds disclosed herein contain one deuterium atom. In another embodiment, the compounds disclosed herein contain two deuterium atoms. In another embodiment, the compounds disclosed herein contain three deuterium atoms. In another embodiment, the compounds disclosed herein contain four deuterium atoms. In another embodiment, the compounds disclosed herein contain five deuterium atoms. In another embodiment, the compounds disclosed herein contain six deuterium atoms. In another embodiment, the compounds disclosed herein contain more than six deuterium atoms. In another embodiment, the compound disclosed herein is fully substituted with deuterium atoms and contains no non-exchangeable <com:Sup>1< / com:Sup>H hydrogen atoms. In one embodiment, the level of deuterium incorporation is determined by synthetic methods in which a deuterated synthetic building block is used as a starting material. "Pharmaceutically acceptable salt" includes both acid and base addition salts. A pharmaceutically acceptable salt of any one of the heterocyclic 5-HT<com:Sub>2a< / com:Sub> and / or 5-HT<com:Sub>2c< / com:Sub> receptor agonists compounds described herein is intended to encompass any and all pharmaceutically suitable salt forms. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0075] "Pharmaceutically acceptable acid addition salt" refers to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, and the like. Also included are salts that are formed with organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, aliphatic and. aromatic sulfonic acids, etc. and include, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Exemplary salts thus include sulfates, pyrosulfates, bisulfates, bisulfites, nitrates, phosphates, monohydrogenphosphates, dihydrogenphosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, acetates, trifluoroacetates, propionates, caprylates, isobutyrates, oxalates, malonates, succinate suberates, sebacates, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, phthalates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, malates, tartrates, methanesulfonates, and the like. Also contemplated are salts of amino acids, such as arginates, gluconates, and galacturonates (see, for example, Berge S.M. et al., "Pharmaceutical Salts," Journal of Pharmaceutical Science, 66:1- WSGR Ref. No. 55554-710.601 19 (1997). Acid addition salts of basic compounds are, in some embodiments, prepared by contacting the free base forms with a sufficient amount of the desired acid to produce the salt according to methods and techniques with which a skilled artisan is familiar. "Pharmaceutically acceptable base addition salt" refers to those salts that retain the biological effectiveness and properties of the free acids, which are not biologically or otherwise undesirable. These salts are prepared from addition of an inorganic base or an organic base to the free acid. Pharmaceutically acceptable base addition salts are, in some embodiments, formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, for example, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N,N- dibenzylethylenediamine, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenedianiline, N-methylglucamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins and the like. See Berge et al., supra. "Pharmaceutically acceptable solvate" refers to a composition of matter that is the solvent addition form. In some embodiments, solvates contain either stoichiometric or non- stoichiometric amounts of a solvent, and are formed during the process of making with pharmaceutically acceptable solvents such as water, ethanol, and the like. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of compounds described herein are conveniently prepared or formed during the processes described herein. The compounds provided herein optionally exist in either unsolvated as well as solvated forms. The term "subject" or "patient" encompasses mammals. Examples of mammals include, but are not limited to, any member of the Mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice and guinea pigs, and the like. In one aspect, the mammal is a human. As used herein, "treatment" or "treating," or "palliating" or "ameliorating" are used interchangeably. These terms refer to an approach for obtaining beneficial or desired results including but not limited to therapeutic benefit and / or a prophylactic benefit. By "therapeutic benefit" is meant eradication or amelioration of the underlying disorder being treated. Also, a WSGR Ref. No. 55554-710.601 therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the patient, notwithstanding that the patient is still afflicted with the underlying disorder. For prophylactic benefit, the compositions are, in some embodiments, administered to a patient at risk of developing a particular disease, or to a patient reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease has not been made. Heterocyclic 5-HT<com:Sub>2a< / com:Sub> and / or 5-HT<com:Sub>2c< / com:Sub> Receptor Agonists Compounds Neuropsychiatric diseases, including mood and anxiety disorders, are some of the leading causes of disability worldwide and place an enormous economic burden on society. Approximately one third of patients will not respond to current antidepressant drugs, and those who do will usually require at least two to four weeks of treatment before they experience any beneficial effects. Evidence from a combination of human imaging, postmortem studies, and animal models suggest that atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. These structural changes, such as the retraction of neurites and loss of dendritic spines, can potentially be counteracted by compounds capable of promoting structural and functional neural plasticity. Recently the nonclassical psychedelics has shown remarkable clinical potential as a fast-acting antidepressant and anxiolytic, exhibiting efficacy in treatment-resistant populations. Animal models suggest that its therapeutic effects stem from its ability to promote the growth of dendritic spines, increase the synthesis of synaptic proteins, and strengthen synaptic responses. Clinical studies have demonstrated the potential for using classical psychedelics to treat a variety of neuropsychiatric disorders including depression, anxiety, addiction, and post-traumatic disorders. However, their therapeutic mechanism of action remains poorly understood, and concerns about safety have severely limited their clinical usefulness. Psychedelic compounds have the potential to meet the therapeutic needs for a number of indications without the addictiveness and overdose risk of other mind-altering drugs, such as cocaine, heroin, alcohol, methamphetamine, and so forth. The need for new therapies is urgent because addiction, overdose, and suicide deaths have risen throughout the North America and around the world. The problem is further exacerbated by the lack of significant advances in psychiatric drug development, as current treatments are plagued with limited efficacy, significant side effects, and dependency on long time use, which may lead some patients to develop treatment-resistance. Recent academic research effort along with anecdotal reports suggest that psychedelics have promising therapeutic potential (BMC Psychiatry 2018, 18, 245). Psychedelic compound research has previously been stymied as a result of governmental regulation and societal taboo which has left many unanswered questions regarding the WSGR Ref. No. 55554-710.601 pharmacology and toxicology of psychedelics. There has been renewed interest in the therapeutic potential of psychedelics. For example, psilocybin-assisted psychotherapy has been effective in the treatment of depression and anxiety in cancer patients and also in the treatment of resistant depression (J. Psychopharmacol. 2016, 30, 1181).

[0083] Therefore, the future of therapeutic psychedelics research in general holds enormous potential to save lives and meet unmet medical needs throughout the world.

[0084] The molecular features that could confer good metabolic and pharmacokinetic characteristic are unpredictable. We have identified key structural feature in compounds of Formula I that offer improved metabolic properties for the treatment of diseases, disorders or conditions treatable by activating the 5HT<com:Sub>2A< / com:Sub> and / or 5-HT<com:Sub>2c< / com:Sub> signaling axis.

[0085] In one aspect, provided herein is a heterocyclic 5-HT<com:Sub>2a< / com:Sub> and / or 5-HT<com:Sub>2c< / com:Sub> receptor agonist compound.

[0086] One embodiment provides a compound, or pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (I) wherein, R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup> and R<com:Sup>3< / com:Sup> are independently selected from H or C1-C6 optionally substituted alkyl; and Ring A is an optionally substituted heteroaryl ring selected from [Image disponible dans le document PDF, Image available in the PDF document] wherein * represents the points of attachment, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, CN, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl and OC1-4haloalkyl, NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup> WSGR Ref. No. 55554-710.601 R<com:Sup>6< / com:Sup> and R<com:Sup>7< / com:Sup> are independently selected from H or C1-C6 optionally substituted alkyl; and R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, C3-12heterocycloalkyl, optionally comprising one additional heteromoiety selected from NR<com:Sup>10< / com:Sup>, O, S, S(O) and SO2, and optionally substituted with one or more substituents selected from halo, =O, OH, C1-6alkyl, C3- 6cycloalkyl, aryl, C5-6heteroaryl, C3-6heterocycloalkyl, C1-6alkyleneC3-6cycloalkyl, C1- 6alkylenearyl, C1-6alkyleneC5-6heteroaryl, C1-6alkyleneC3-6heterocycloalkyl, C(O)C1- 6alkyl, OC1-6alkyl, OC1-6alkyleneOC1-6alkyl, C(O)NH2, C(O)NH(C1-6alkyl), C(O)N(C1- 6alkyl)(C1-6alkyl), NHC(O)C1-6alkyl, N(C1-6alkyl)C(O)C1-6alkyl, NH2, NH(C1-6alkyl), N(C1-6alkyl)(C1-6alkyl), SC1-6alkyl, S(O)C1-6alkyl and SO2C1-6alkyl, wherein all alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups of the optional substituents on the C3-12heterocycloalkyl formed by R5 and R6 are also optionally substituted with one or more of halo, C1-6alkyl, OC1-6alkyl, C1-6haloalkyl and OC1-6haloalkyl. In an aspect, ring A can be attached to the core (e.g., azepane core, e.g., tetrahydroazepine core) of formula (I) in a first possible orientation or a second possible orienation. For example, in [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] some embodiments, ring A is <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> , the first possible orientation is , [Image disponible dans le document PDF, Image available in the PDF document] and the second possible orientation is . In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , the first possible orientation is , and the second [Image disponible dans le document PDF, Image available in the PDF document] possible orientation is . In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , the first possible orientation is , and the second WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] possible orientation is . In some embodiments, ring A is , [Image disponible dans le document PDF, Image available in the PDF document] the first possible orientation is , and the second possible orientation is [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] . In some embodiments, ring A is , the first possible [Image disponible dans le document PDF, Image available in the PDF document] orientation is , and the second possible orientation is [Image disponible dans le document PDF, Image available in the PDF document] •

[0088] In some embodiments, the heterocyclic 5-HT<com:Sub>2a< / com:Sub> and / or 5-HT<com:Sub>2c< / com:Sub> receptor agonist compound as described herein has a structure and / or compound name provided in Table 1. Table 1 [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]

[0089] In an aspect, the present disclosure provides a compound, or pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (I), wherein, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> are each independently selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted alkyl; and [Image disponible dans le document PDF, Image available in the PDF document] ring A is an optionally substituted heteroaryl ring selected from , [Image disponible dans le document PDF, Image available in the PDF document] wherein * represents the points of attachment; R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, CN, C<com:Sub>1< / com:Sub>-4alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math> are independently selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted alkyl; and <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional heteromoiety selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math>, O, S, S(O) and SO<com:Sub>2< / com:Sub>, and optionally substituted with one or more substituents selected from halo, =O, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub> 6alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub> 6alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C<com:Sub>1-6< / com:Sub>alkyl)(C1-6alkyl), NHC(O)C<com:Sub>1-6< / com:Sub>alkyl, N(C<com:Sub>1-6< / com:Sub>alkyl)C(O)C<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), SC<com:Sub>1-6< / com:Sub> 6alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl, wherein R<com:Sup>10< / com:Sup> is selected from hydrogen, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub> 6alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl)(C1-6alkyl), S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl; and all alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups of the optional substituents on the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are optionally substituted with WSGR Ref. No. 55554-710.601 one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>1-6< / com:Sub>haloalkyl, and OC<com:Sub>1-6< / com:Sub> 6haloalkyl.

[0090] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is H. In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some [Image disponible dans le document PDF, Image available in the PDF document] embodiments, R<com:Sup>1< / com:Sup> is H, and R<com:Sup>2< / com:Sup> is methyl. In some embodiments, ring A is <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is H, [Image disponible dans le document PDF, Image available in the PDF document] and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some embodiments, ring A is , <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is methyl.

[0091] In some embodiments, <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , and R<com:Sup>3< / com:Sup> is H. In some embodiments, ring A is , and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected [Image disponible dans le document PDF, Image available in the PDF document] from H and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some embodiments, ring A is , and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected [Image disponible dans le document PDF, Image available in the PDF document] from H and methyl. In some embodiments, ring A is , and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is methyl.

[0092] In some embodiments, ring A is an optionally substituted 3- to 10-membered heterocycle, C<com:Sub>3-10< / com:Sub> carbocycle, 3- to 10-membered heteroaryl, or C<com:Sub>3-10< / com:Sub> aryl. In some embodiments, ring A is an optionally substituted 3- to 10-membered heterocycle. In some embodiments, ring A is an optionally substituted 3- to 10-membered heteroarene. In some embodiments, ring A is selected [Image disponible dans le document PDF, Image available in the PDF document] , wherein * represents the points of WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document] attachment. In some embodiments, ring A is selected from [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] . In some embodiments, ring A is . In some [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] embodiments, ring A is . In some embodiments, ring A is . In [Image disponible dans le document PDF, Image available in the PDF document] some embodiments, ring A is . In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] . In some embodiments, ring A is ٠ In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, CN, C<com:Sub>1< / com:Sub>-4alkyl, C<com:Sub>1< / com:Sub>- 4haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, C<com:Sub>1< / com:Sub>-4alkyl, C<com:Sub>1< / com:Sub>-4haloalkyl, OC<com:Sub>1< / com:Sub>-4alkyl, OC<com:Sub>1< / com:Sub>-4haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, C<com:Sub>1< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is H, and exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is H, and exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>. WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document]

[0095] In some embodiments, ring A is <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> , <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>. In some embodiments, [Image disponible dans le document PDF, Image available in the PDF document] ring A is ; and R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, F, CN, C<com:Sub>1< / com:Sub>- 4alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). [Image disponible dans le document PDF, Image available in the PDF document]

[0096] In some embodiments, ring A is ; and R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, F, CN, C<com:Sub>2-4< / com:Sub>alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>2-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), O(3- to 10-membered heterocycle), O(3- to 10- membered heteroaryl), <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>.

[0097] In some embodiments, R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a C<com:Sub>3< / com:Sub>- 12 heterocycloalkyl. In some embodiments, the C<com:Sub>3-12< / com:Sub> heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> contains additional heteromoieties. In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math> heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> contains multiple additional heteromoieties selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math>, O, S, S(O) and SO<com:Sub>2< / com:Sub>. In some embodiments, the C<com:Sub>3-12< / com:Sub> heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> contains one, two, three, four, or five additional heteromoieties selected from N(R<com:Sup>10< / com:Sup>), O, S, S(O) and SO<com:Sub>2< / com:Sub>. In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math> heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> contains one additional heteromoiety selected from N(R<com:Sup>10< / com:Sup>), O, S, S(O) and SO<com:Sub>2< / com:Sub>. In some embodiments, the C<com:Sub>3-12< / com:Sub> heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> contains one additional heteromoiety selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math>, O, and S. In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math> heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> contains one additional heteromoiety selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math>, and O. In some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a C<com:Sub>3-12< / com:Sub>heterocycloalkyl. In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math> heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> contains one additional oxygen atom.

[0098] In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math> heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from halo, =O, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-< / com:Sub> 6alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C<com:Sub>1-6< / com:Sub>alkyl)(C1-6alkyl), NHC(O)C<com:Sub>1-6< / com:Sub>alkyl, N(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl)C(O)C<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), and N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl). In some embodiments, WSGR Ref. No. 55554-710.601 the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from halo, =O, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub> 6alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, OC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), and N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl). In some embodiments, the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, =O, OH, OC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1-6< / com:Sub>alkyl). In some embodiments, the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, =O, OH, OC<com:Sub>1< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1< / com:Sub>alkyl). In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from halo, =O, OH, OC<com:Sub>1< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1< / com:Sub>alkyl). In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from fluoro, =O, OH, OC<com:Sub>1< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1< / com:Sub>alkyl). In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more fluoro substituents. [Image disponible dans le document PDF, Image available in the PDF document]

[0099] In some embodiments, ring A is ; and the one additional heteromoiety of the <com:Math><semantics>C3−<annotation encoding="application / x-tex">C_{3-}< / annotation>< / semantics>< / com:Math> [Image disponible dans le document PDF, Image available in the PDF document] <com:Sub>12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is NR<com:Sup>10< / com:Sup>. In some embodiments, ring A is the one additional heteromoiety of the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is NR<com:Sup>10< / com:Sup>; and the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub> 6alkyleneC3-6heterocycloalkyl, C(O)C1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alkyl, OC1-6alk <com:Math><semantics>C(O)NH(C1−6alkyl),C(O)N(C1−6alkyl)(C1−6alkyl),NHC(O)C1−6alkyl,N(C1−6alkyl)C(O)C1−6alkyl,<annotation encoding="application / x-tex">C(O)NH(C_{1-6}alkyl), C(O)N(C_{1-6}alkyl)(C_{1-6}alkyl), NHC(O)C_{1-6}alkyl, N(C_{1-6}alkyl)C(O)C_{1-6}alkyl,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>NH2<annotation encoding="application / x-tex">NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>NH(C1−6alkyl)<annotation encoding="application / x-tex">NH(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>N(C1−6alkyl)<annotation encoding="application / x-tex">N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math> (<com:Math><semantics>C1−6alkyl<annotation encoding="application / x-tex">C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>SC1−6alkyl<annotation encoding="application / x-tex">SC_{1-6}alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>S(O)C1−6alkyl<annotation encoding="application / x-tex">S(O)C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>SO2C1−6alkyl<annotation encoding="application / x-tex">SO_2C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>. In [Image disponible dans le document PDF, Image available in the PDF document] some embodiments, ring A is ; the one additional heteromoiety of the <com:Math><semantics>C3−<annotation encoding="application / x-tex">C_{3-}< / annotation>< / semantics>< / com:Math> <com:Sub>12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is NR<com:Sup>10< / com:Sup>; and the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1< / com:Sub>- 6alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, and OC<com:Sub>1-6< / com:Sub>alkyl. In some WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document] embodiments, ring A is ; the one additional heteromoiety of the <com:Math><semantics>C3−<annotation encoding="application / x-tex">C_{3-}< / annotation>< / semantics>< / com:Math> <com:Sub>12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is NR<com:Sup>10< / com:Sup>; and R<com:Sup>10< / com:Sup> is selected from C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-< / com:Sub> 6cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-8< / com:Sub> 6alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, <com:Math><semantics>C(O)NH2<annotation encoding="application / x-tex">C(O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NH(C1−6alkyl)<annotation encoding="application / x-tex">C(O)NH(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(C1−6alkyl)<annotation encoding="application / x-tex">C(O)N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>(C1-6alkyl), <com:Math><semantics>S(O)C1−6alkyl<annotation encoding="application / x-tex">S(O)C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>SO2C1−6alkyl<annotation encoding="application / x-tex">SO_2C_{1-6}alkyl< / annotation>< / semantics>< / com:Math>.In [Image disponible dans le document PDF, Image available in the PDF document] some embodiments, ring A is ; the one additional heteromoiety of the <com:Math><semantics>C3−<annotation encoding="application / x-tex">C_{3-}< / annotation>< / semantics>< / com:Math> <com:Sub>12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is NR<com:Sup>10< / com:Sup>; and R<com:Sup>10< / com:Sup> is selected from C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-< / com:Sub> 6cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, and C<com:Sub>3-6< / com:Sub> heterocycloalkyl. In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] ; the one additional heteromoiety of the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>NR10<annotation encoding="application / x-tex">NR^{10}< / annotation>< / semantics>< / com:Math>; and <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> is selected from <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl. [Image disponible dans le document PDF, Image available in the PDF document]

[00100] In some embodiments, ring A is , and the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, NO<com:Sub>2< / com:Sub>, OH, C<com:Sub>1< / com:Sub>- 6alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C1-6alkyl)(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl), NHC(O)C<com:Sub>1-6< / com:Sub>alkyl, N(C<com:Sub>1-6< / com:Sub>alkyl)C(O)C<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl), SC<com:Sub>1-6< / com:Sub>alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl. In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] , and the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from halo, NO<com:Sub>2< / com:Sub>, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>) WSGR Ref. No. 55554-710.601 [Image disponible dans le document PDF, Image available in the PDF document] 6alkyl). In some embodiments, ring A is , and the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, NO<com:Sub>2< / com:Sub>, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-< / com:Sub> [Image disponible dans le document PDF, Image available in the PDF document] 6alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1-6< / com:Sub>alkyl). In some embodiments, ring A is , and the <com:Math><semantics>C3−<annotation encoding="application / x-tex">C_{3-}< / annotation>< / semantics>< / com:Math> <com:Sub>12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is optionally substituted with one or more substituents selected from halo, NO<com:Sub>2< / com:Sub>, OH, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1-6< / com:Sub>alkyl). In some embodiments, R<com:Sup>10< / com:Sup> is selected from hydrogen, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, and C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl.

[00101] In some embodiments, R<com:Sup>10< / com:Sup> is selected from hydrogen, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-< / com:Sub> 6heteroaryl, and C<com:Sub>3-6< / com:Sub> heterocycloalkyl. In some embodiments, R<com:Sup>10< / com:Sup> is selected from hydrogen, and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl. [Image disponible dans le document PDF, Image available in the PDF document]

[00102] In some embodiments, the heterocycle formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> is selected from , [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , and . In some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are methyl. In , some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> is methyl, and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is ethyl.

[00103] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> are each independently selected from H, <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>1-4< / com:Sub>haloalkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl. In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl comprises one additional WSGR Ref. No. 55554-710.601 heteromoiety selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math>, O, S, S(O) and SO<com:Sub>2< / com:Sub>, and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, <com:Math><semantics>C(O)NH2<annotation encoding="application / x-tex">C(O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)NH(C1−6alkyl)<annotation encoding="application / x-tex">C(O)NH(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(O)N(C1−6alkyl)<annotation encoding="application / x-tex">C(O)N(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(C1−6alkyl)<annotation encoding="application / x-tex">C(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(C1−6alkyl)<annotation encoding="application / x-tex">C(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(C1−6alkyl)<annotation encoding="application / x-tex">C(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(C1−6alkyl)<annotation encoding="application / x-tex">C(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C(C1−6alkyl)<annotation encoding="application / x-tex">C(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math> 6alkyl)C(O)C<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), SC<com:Sub>1-6< / com:Sub>alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl, wherein R<com:Sup>10< / com:Sup> is selected from C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-< / com:Sub> 6 heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub> 6alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl)(C1-6alkyl), S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl.

[00104] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> ; R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>1-4< / com:Sub>haloalkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional heteromoiety selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math> and O and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-< / com:Sub> 6alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1-6< / com:Sub>alkyl), wherein R<com:Sup>10< / com:Sup> is selected from C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, and C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl).

[00105] In some embodiments, R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup> are H; R<com:Sup>3< / com:Sup> is selected from H and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is <com:Math><semantics>ℝ5<annotation encoding="application / x-tex">\mathbb{R}^5< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>ℝ4<annotation encoding="application / x-tex">\mathbb{R}^4< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>ℝ5<annotation encoding="application / x-tex">\mathbb{R}^5< / annotation>< / semantics>< / com:Math> are each independently selected from H, <com:Math><semantics>ℂ1−4<annotation encoding="application / x-tex">\mathbb{C}_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>alkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a C<com:Sub>3-12< / com:Sub>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, aryl, C<com:Sub>5-< / com:Sub> 6heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, OC<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, and NH(C<com:Sub>1-6< / com:Sub>alkyl).

[00106] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> are each independently selected from H, <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>alkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a WSGR Ref. No. 55554-710.601 C<com:Sub>3-12< / com:Sub>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, aryl, and C<com:Sub>5-< / com:Sub> 6heteroaryl.

[00107] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is ; <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> are each independently selected from H and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, aryl, and C<com:Sub>5-6< / com:Sub>heteroaryl.

[00108] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is <com:Sup>1< / com:Sup> and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> are each independently selected from H and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, and C<com:Sub>1-6< / com:Sub>alkyl.

[00109] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is and R<com:Sup>5< / com:Sup> are each independently selected from H and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>); R<com:Sup>8< / com:Sup> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, and OH.

[00110] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> are each independently selected from H and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more halo substituents.

[00111] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is ; R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>); R<com:Sup>8< / com:Sup> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more fluoro substituents.

[00112] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> are H; <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] alkyl; ring A is and R<com:Sup>5< / com:Sup> are each independently selected from H, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>1-4< / com:Sub>haloalkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a C<com:Sub>3-12< / com:Sub>heterocycloalkyl, optionally comprising one additional oxygen atom and optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, <com:Math><semantics>NH2<annotation encoding="application / x-tex">NH_2< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>NH(C1−6alkyl)<annotation encoding="application / x-tex">NH(C_{1-6}alkyl)< / annotation>< / semantics>< / com:Math>.

[00113] In an aspect, the present disclosure provides a compound, or pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (I): [Image disponible dans le document PDF, Image available in the PDF document] wherein <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> are each independently selected from H and <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> optionally substituted alkyl; and [Image disponible dans le document PDF, Image available in the PDF document] ring A is an optionally substituted heteroaryl ring selected from , [Image disponible dans le document PDF, Image available in the PDF document] wherein * represents the points of attachment; R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, halo, CN, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>alkyl, O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), O(3- to 10-membered heterocycle), O(3- to 10- membered heteroaryl), <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>, wherein each OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>3-10< / com:Sub>aryl, and O(3- to 10-membered heteroaryl), of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is independently optionally substituted with one or more substituents selected from C<com:Sub>3-6< / com:Sub> carbocycle, C<com:Sub>3-6< / com:Sub> aryl, 3- to 10- membered heterocycle, and 3- to 10- membered heteroaryl, wherein each C<com:Sub>3-6< / com:Sub> carbocycle, C<com:Sub>3-6< / com:Sub> aryl, 3- to 10- membered heterocycle, and 3- to 10- membered heteroaryl of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup>, is optionally substituted with one or more substituents selected from halogen, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub>aminoalkyl, CN, NO<com:Sub>2< / com:Sub>, OH, and C<com:Sub>1-6< / com:Sub> alkoxy; [Image disponible dans le document PDF, Image available in the PDF document] when ring A is R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, F, CN, C<com:Sub>1< / com:Sub>- 4alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, OC<com:Sub>1-4< / com:Sub>haloalkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), O(3- to 10-membered heterocycle), O(3- to 10- membered heteroaryl), and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; and [Image disponible dans le document PDF, Image available in the PDF document] when ring A is ; R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, F, CN, C<com:Sub>2-4< / com:Sub>alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>2-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), O(3- to 10-membered heterocycle), O(3- to 10- membered heteroaryl), <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>; R<com:Sup>6< / com:Sup> and R<com:Sup>7< / com:Sup> are each independently selected from H and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> optionally substituted alkyl; and R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are each independently selected from hydrogen, NO<com:Sub>2< / com:Sub>, C(O)(C<com:Sub>1-6< / com:Sub> optionally substituted alkyl), C(O)N(C<com:Sub>1-6< / com:Sub> optionally substituted alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>C(O)O(C1−6<annotation encoding="application / x-tex">C(O)O(C_{1-6}< / annotation>< / semantics>< / com:Math> optionally substituted alkyl), <com:Math><semantics>S(O)(C1−6<annotation encoding="application / x-tex">S(O)(C_{1-6}< / annotation>< / semantics>< / com:Math> optionally substituted alkyl), and <com:Math><semantics>S(O)2(C1−6)<annotation encoding="application / x-tex">S(O)_2(C_{1-6})< / annotation>< / semantics>< / com:Math> optionally substituted alkyl), wherein [Image disponible dans le document PDF, Image available in the PDF document] when ring A is , and R<com:Sup>8< / com:Sup> is H; R<com:Sup>9< / com:Sup> is selected from <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C(O)N(C1−6<annotation encoding="application / x-tex">C(O)N(C_{1-6}< / annotation>< / semantics>< / com:Math> optionally substituted alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>C(O)O(C1−6<annotation encoding="application / x-tex">C(O)O(C_{1-6}< / annotation>< / semantics>< / com:Math> optionally substituted alkyl), <com:Math><semantics>S(O)(C1−6)<annotation encoding="application / x-tex">S(O)(C_{1-6})< / annotation>< / semantics>< / com:Math> optionally substituted alkyl), and <com:Math><semantics>S(O)2(C1−6)<annotation encoding="application / x-tex">S(O)_2(C_{1-6})< / annotation>< / semantics>< / com:Math> optionally substituted alkyl); and C<com:Sub>3-10< / com:Sub> carbocycle, C<com:Sub>3-10< / com:Sub> aryl, 3- to 10-membered heteroaryl, and 3- to 10-membered heterocycle, optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>1-6< / com:Sub>haloalkyl, and OC<com:Sub>1-6< / com:Sub>haloalkyl; and C<com:Sub>1-6< / com:Sub> alkyl, optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>1-6< / com:Sub>haloalkyl, and OC<com:Sub>1-6< / com:Sub>haloalkyl; and C<com:Sub>3-< / com:Sub> <com:Sub>10< / com:Sub> carbocycle, C<com:Sub>3-10< / com:Sub> aryl, 3- to 10-membered heteroaryl, and 3- to 10-membered heterocycle, optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>1-6< / com:Sub>haloalkyl, and OC<com:Sub>1-6< / com:Sub>haloalkyl; or <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> are joined to form, together with the atom therebetween, a <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl, optionally substituted with one or more substituents selected from NO<com:Sub>2< / com:Sub>, CN, halo, =O, OH, C<com:Sub>1< / com:Sub>- 6alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl), NHC(O)C<com:Sub>1-6< / com:Sub>alkyl, N(C<com:Sub>1-6< / com:Sub>alkyl)C(O)C<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl), SC<com:Sub>1-6< / com:Sub>alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl, wherein R<com:Sup>10< / com:Sup> is selected from hydrogen, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub> 6alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C<com:Sub>1-6< / com:Sub>alkyl) 6alkyl)(C1-6alkyl), S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl; all alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups of the optional substituents on the C<com:Sub>3-12< / com:Sub>heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are optionally substituted with one or more substituents selected from halo, C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>1-6< / com:Sub>haloalkyl, and OC<com:Sub>1-6< / com:Sub> 6haloalkyl; [Image disponible dans le document PDF, Image available in the PDF document] when ring A is , and the one additional heteromoiety of the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>NR10<annotation encoding="application / x-tex">NR^{10}< / annotation>< / semantics>< / com:Math>; WSGR Ref. No. 55554-710.601 the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from halo, OH, NO<com:Sub>2< / com:Sub>, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub> 6alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, <com:Math><semantics>C(O)NH(C1−6alkyl),C(O)N(C1−6alkyl)(C1−6alkyl),NHC(O)C1−6alkyl,N(C1−6alkyl)C(O)C1−6alkyl,<annotation encoding="application / x-tex">C(O)NH(C_{1-6}alkyl), C(O)N(C_{1-6}alkyl)(C_{1-6}alkyl), NHC(O)C_{1-6}alkyl, N(C_{1-6}alkyl)C(O)C_{1-6}alkyl,< / annotation>< / semantics>< / com:Math> NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), N(C<com:Sub>1-6< / com:Sub>alkyl)(C<com:Sub>1-6< / com:Sub>alkyl), SC<com:Sub>1-6< / com:Sub>alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl; and R<com:Sup>10< / com:Sup> is selected from C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-< / com:Sub> 6heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C<com:Sub>1-6< / com:Sub>alkyl)(C1-6alkyl), S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl; and [Image disponible dans le document PDF, Image available in the PDF document] when ring A is , the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from halo, NO<com:Sub>2< / com:Sub>, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub> 6alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, <com:Math><semantics>C(O)NH(C1−6alkyl),C(O)N(C1−6alkyl)(C1−6alkyl),NHC(O)C1−6alkyl,N(C1−6alkyl)C(O)C1−6alkyl,<annotation encoding="application / x-tex">C(O)NH(C_{1-6}alkyl), C(O)N(C_{1-6}alkyl)(C_{1-6}alkyl), NHC(O)C_{1-6}alkyl, N(C_{1-6}alkyl)C(O)C_{1-6}alkyl,< / annotation>< / semantics>< / com:Math> NH<com:Sub>2< / com:Sub>, NH(<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl), N(<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl)(<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl), SC<com:Sub>1-6< / com:Sub>alkyl, S(O)C<com:Sub>1-6< / com:Sub>alkyl, and SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub>alkyl.

[00114] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is H. In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some [Image disponible dans le document PDF, Image available in the PDF document] embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is methyl. In some embodiments, ring A is is H, [Image disponible dans le document PDF, Image available in the PDF document] and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some embodiments, ring A is , <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is methyl.

[00115] In some embodiments, <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected from H and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , and R<com:Sup>3< / com:Sup> is H. In some embodiments, ring A is , and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected [Image disponible dans le document PDF, Image available in the PDF document] from H and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. In some embodiments, ring A is , and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is selected [Image disponible dans le document PDF, Image available in the PDF document] from H and methyl. In some embodiments, ring A is , and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is methyl.

[00116] In some embodiments, ring A is an optionally substituted 3- to 10-membered heterocycle, C<com:Sub>3-10< / com:Sub> carbocycle, 3- to 10-membered heteroaryl, or C<com:Sub>3-10< / com:Sub> aryl. In some embodiments, ring A is an optionally substituted 3- to 10-membered heterocycle. In some embodiments, ring A is an optionally substituted 3- to 10-membered heteroarene. In some embodiments, ring A is selected [Image disponible dans le document PDF, Image available in the PDF document] from . In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] selected from . In some [Image disponible dans le document PDF, Image available in the PDF document] embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document]

[00117] In some embodiments, ring A is . In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] . In some embodiments, ring A is . In some embodiments, ring [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] . In some embodiments, ring A is ٠

[00118] WSGR Ref. No. 55554-710.601

[00119] In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, CN, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-1< / com:Sub> 4haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), O(3- to 10-membered heterocycle), O(3- to 10- membered heteroaryl), OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, CN, C<com:Sub>1< / com:Sub>- 4 alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), OC<com:Sub>1-4< / com:Sub>haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H, halo, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>. In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are independently selected from H and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is H, and exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is H, and exactly one of R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> is N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>. In some embodiments, ring A is , <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> is H, and <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>. [Image disponible dans le document PDF, Image available in the PDF document]

[00120] In some embodiments, ring A is ; and R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, halo, CN, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), O(3- to 10-membered heterocycle), O(3- to 10- membered heteroaryl), <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>. In some embodiments, ring A is [Image disponible dans le document PDF, Image available in the PDF document] ; and R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, NO<com:Sub>2< / com:Sub>, halo, CN, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), and <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>. In some embodiments, ring A is ; and R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each independently selected from H, halo, C<com:Sub>1-4< / com:Sub> alkyl, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted C<com:Sub>3-10< / com:Sub> aryl), and OC<com:Sub>1-< / com:Sub> [Image disponible dans le document PDF, Image available in the PDF document] 4haloalkyl, and N(R<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>). In some embodiments, ring A is R<com:Sup>5< / com:Sup> ; and R<com:Sup>4< / com:Sup> and R<com:Sup>5< / com:Sup> are each WSGR Ref. No. 55554-710.601 independently selected from H, halo, C<com:Sub>1-4< / com:Sub>haloalkyl, OC<com:Sub>1-4< / com:Sub>alkyl, O(optionally substituted C<com:Sub>3-10< / com:Sub> carbocycle), O(optionally substituted <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> aryl), and <com:Math><semantics>OC1−4<annotation encoding="application / x-tex">OC_{1-4}< / annotation>< / semantics>< / com:Math>haloalkyl, and <com:Math><semantics>N(R8R9)<annotation encoding="application / x-tex">N(R^8R^9)< / annotation>< / semantics>< / com:Math>.

[00121]

[00122] In some embodiments, R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a C<com:Sub>3-< / com:Sub> <com:Sub>12< / com:Sub>heterocycloalkyl. In some embodiments, the C<com:Sub>3-12< / com:Sub> heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> contains additional heteromoieties. In some embodiments, the C<com:Sub>3-12< / com:Sub> heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> contains multiple additional heteromoieties selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math>, O, S, S(O) and SO<com:Sub>2< / com:Sub>. In some embodiments, the C<com:Sub>3-12< / com:Sub> heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> contains one, two, three, four, or five additional heteromoieties selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math>, O, S, S(O) and SO<com:Sub>2< / com:Sub>. In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math> heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> contains one additional heteromoiety selected from N(R<com:Sup>10< / com:Sup>), O, S, S(O) and SO<com:Sub>2< / com:Sub>. In some embodiments, the C<com:Sub>3-12< / com:Sub> heterocycloalkyl formed by R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> contains one additional heteromoiety selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math>, O, and S. In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math> heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> contains one additional heteromoiety selected from <com:Math><semantics>N(R10)<annotation encoding="application / x-tex">N(R^{10})< / annotation>< / semantics>< / com:Math>, and O. In some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and R<com:Sup>9< / com:Sup> are joined to form, together with the atom therebetween, a C<com:Sub>3-12< / com:Sub>heterocycloalkyl. In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math> heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> contains one additional oxygen atom.

[00123] In some embodiments, the <com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math>heterocycloalkyl formed by <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is optionally substituted with one or more substituents selected from NO<com:Sub>2< / com:Sub>, CN, halo, =O, OH, C<com:Sub>1-6< / com:Sub>alkyl, C<com:Sub>3-6< / com:Sub>cycloalkyl, aryl, C<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>3-6< / com:Sub> heterocycloalkyl, C<com:Sub>1-6< / com:Sub> alkyleneC<com:Sub>3-6< / com:Sub>cycloalkyl, C<com:Sub>1-6< / com:Sub>alkylenearyl, C<com:Sub>1-6< / com:Sub> 6alkyleneC<com:Sub>5-6< / com:Sub>heteroaryl, C<com:Sub>1-6< / com:Sub>alkyleneC<com:Sub>3-6< / com:Sub>heterocycloalkyl, C(O)C<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub>alkyl, OC<com:Sub>1-6< / com:Sub> 6alkyleneOC<com:Sub>1-6< / com:Sub>alkyl, C(O)NH<com:Sub>2< / com:Sub>, C(O)NH(C<com:Sub>1-6< / com:Sub>alkyl), C(O)N(C<com:Sub>1-6< / com:Sub>alkyl)(C1-6alkyl), NHC(O)C<com:Sub>1-6< / com:Sub> 6alkyl, N(C<com:Sub>1-6< / com:Sub>alkyl)C(O)C<com:Sub>1-6< / com:Sub>alkyl, NH<com:Sub>2< / com:Sub>, NH(C<com:Sub>1-6< / com:Sub>alkyl), and N(C<com:Sub>1-6< / c...

Claims

1. A compound, or pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (I): [Image disponible dans le document PDF, Image available in the PDF document] ( I ) (I) , wherein R 1 , R 2 and R 3 are each independently selected from H and C 1 -C 6 optionally substituted alkyl; and [Image disponible dans le document PDF, Image available in the PDF document] ring A is an optionally substituted heteroaryl ring having the structure of wherein * represents the points of attachment; R 4 and R 5 are independently selected from H, halo, CN, C 1 -4alkyl, C 1 - 4haloalkyl, OC 1 -4alkyl, OC 1 -4haloalkyl, O(optionally substituted C 3-10 carbocycle), O(optionally substituted C 3-10 aryl), and N(R 8 R 9 ); and R 8 and R 9 are joined to form, together with the atom therebetween, a C 3 - 12heterocycloalkyl, optionally comprising one additional heteromoiety selected from N ( R 10 ) N(R^{10}) , O, S, S(O) and SO 2 , and optionally substituted with one or more substituents selected from halo, OH, C 1-6 alkyl, C 3-6 cycloalkyl, aryl, C 5- 6heteroaryl, C 3-6 heterocycloalkyl, C 1-6 alkyleneC 3-6 cycloalkyl, C 1- 6alkylenearyl, C 1 -6alkyleneC 5 -6heteroaryl, C 1 -6alkyleneC 3 -6heterocycloalkyl, C(O)C 1 -6alkyl, OC 1 -6alkyl, OC 1 -6alkyleneOC 1 -6alkyl, C(O)NH 2 , C(O)NH(C 1 - 6alkyl), C(O)N(C 1 -6alkyl)(C 1 -6alkyl), NHC(O)C 1 -6alkyl, N(C 1 -6alkyl)C(O)C 1 - 6alkyl, NH2, NH(C1-6alkyl), N(C1-6alkyl)(C1-6alkyl), SC1-6alkyl, S(O)C1-6alkyl, and SO 2 C 1-6 alkyl, wherein R 10 is selected from hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, aryl, C 5- 6heteroaryl, C 3-6 heterocycloalkyl, C 1-6 alkyleneC 3-6 cycloalkyl, C 1-7 6alkylenearyl, C 1 -6alkyleneC 5 -6heteroaryl, C 1 -6alkyleneC 3 - 6heterocycloalkyl, C(O)C 1 -6alkyl, C(O)NH 2 , C(O)NH(C 1 -6alkyl), C(O)N(C 1 -6alkyl)(C 1 -6alkyl), S(O)C 1 -6alkyl, and SO 2 C 1 -6alkyl; and all alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl groups of the optional substituents on the C 3-12 heterocycloalkyl formed by R 8 and R 9 are optionally substituted with one or more substituents selected from halo, C 1-6 alkyl, OC 1-6 alkyl, C 1-6 haloalkyl, and OC 1- 6haloalkyl, with the proviso that: when R 1 R^1 , R 2 R^2 and R 4 R^4 are H then (i) R 3 is not a substituted ethyl when R 5 is -OCH 3 , and (ii) R 3 is not -CH 2 CH 3 when R 5 is halo or piperazinyl.

2. The compound, salt, or solvate of claim 1, wherein R 10 R^{10} is selected from hydrogen, and C 1-6 alkyl.

3. The compound, salt, or solvate of claim 1 or 2, wherein R 1 R^1 and R 2 R^2 are H; R 3 is selected from H and C 1 -C 6 optionally substituted alkyl; [Image disponible dans le document PDF, Image available in the PDF document] R 4 and R 5 are each independently selected from H, C 1 - 4haloalkyl, OC 1 -4alkyl, OC 1 -4haloalkyl, O(optionally substituted C 3-10 carbocycle), O(optionally substituted C 3-10 aryl), and N ( R 8 R 9 ) ; N(R^8R^9); R 8 and R 9 are joined to form, together with the atom therebetween, a C 3-12 heterocycloalkyl, and optionally substituted with one or more substituents selected from halo, OH, NO 2 , C 1-6 alkyl, C 3-6 cycloalkyl, aryl, C 5-6 heteroaryl, C 3-6 heterocycloalkyl, C 1-6 alkyleneC 3-6 cycloalkyl, C 1-6 alkylenearyl, C 1 -6alkyleneC 5 -6heteroaryl, C 1 -6alkyleneC 3 -6heterocycloalkyl, C(O)C 1 -6alkyl, OC 1 -6alkyl, OC 1 -6alkyleneOC 1 -6alkyl, C(O)NH 2 , C ( O ) N H ( C 1 − 6 a l k y l ) , C ( O ) N ( C 1 − 6 a l k y l ) ( C 1 − 6 a l k y l ) , N H C ( O ) C 1 − 6 a l k y l ) C(O)NH(C_{1-6}alkyl), C(O)N(C_{1-6}alkyl)(C_{1-6}alkyl), NHC(O)C_{1-6}alkyl) 6alkyl, N(C 1 -6alkyl)C(O)C 1 -6alkyl, NH 2 , NH(C 1 -6alkyl), N(C 1 - 6alkyl)(C 1 -6alkyl), SC 1 -6alkyl, S(O)C 1 -6alkyl, and SO 2 C 1 -6alkyl.

4. The compound, salt, or solvate of claim 1 or 2, wherein: (a) R 1 R^1 is H, and R 2 R^2 is C 1 − 6 C_{1-6} alkyl; or (b) R 1 R^1 is H, and R 2 R^2 is methyl.

5. The compound, salt, or solvate of any one of claims 1 to 4, wherein R 3 is H or C 1-6 alkyl.

6. The compound, salt, or solvate of any one of claims 1 to 5, wherein R 3 R^3 is H.

7. The compound, salt, or solvate of any one of claims 1 to 6, wherein the heterocycle [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]8. A compound of claim 1, or pharmaceutically acceptable salt or solvate thereof, having [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]9. A compound, or pharmaceutically acceptable salt or solvate thereof, selected from [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]10. A pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt or solvate thereof, according to any one of claims 1 to 9 and a pharmaceutically acceptable excipient.

11. Use of the compound according to any one of claims 1 to 9 or the composition according to claim 10 for treatment of a disease or disorder mediated by the 5-HT2 receptor.

12. The compound, salt, or solvate of any one of claims 1 to 9 for use in treatment of a disease or disorder mediated by the 5-HT2 receptor.

13. The compound for use according to claim 12, wherein the disease or disorder is a 5- HT2A and / or 5-HT2c receptor-mediated disorder.

14. The compound, salt, or solvate for use according to claim 12 or 13, wherein the disease or disorder is depressive disorder, an anxiety disorder, panic attack, agoraphobia, specific phobia, social phobia, bipolar disorder, post-traumatic stress, an eating disorder, obesity, a gastro-intestinal disorder, alcoholism, drug addiction, schizophrenia, a psychotic disorder, a sleep disorder, sleep apnea, migraine, sexual dysfunction, a central nervous system disorder, trauma, stroke, spinal cord injury, a cardio-vascular disorder, diabetes insipidus, or obsessive disorder.

15. The compound, salt, or solvate according to any one of claims 1 to 9 for use in: amelioration of at least one symptom of a brain disorder, stress, anxiety, addiction, depression, or compulsive behavior; promotion of weight loss; improvement of mood; treatment or prevention of a psychological disorder; or performance enhancement.