Tetrahydro-imidazo quinoline compositions as CBP / p300 inhibitors

Abstract

The present disclosure is directed to inhibitors of the CBP / p300 family of bromodomains. The compounds can be useful in the treatment of disease or disorders associated with the inhibition of the CBP / p300 family of bromodomains. For instance, the disclosure is concerned with compounds and compositions for inhibition of the CBP / p300 family of bromodomains, methods of treating, preventing, or ameliorating diseases or disorders associated with the inhibition of CBP / p300 family of bromodomains, and methods of synthesis of these compounds.

Description

TETRAHYDRO-IMIDAZO QUINOLINE COMPOSITIONS AS CBP / P300 INHIBITORS Cross-Reference to Related Applications

[0001] This application claims the benefit of priority of U.S. Provisional Application No. 62 / 559,436, filed September 15, 2017 and U.S. Provisional Application No. 62 / 692,593, filed June 29, 2018, Field of Disclosure

[0002] The present disclosure is directed to inhibitors of the CBP / p300 family of bromodomains useful in the treatment of disease or disorders associated with the inhibition of the CBP / p300 family of bromodomains. Specifically, the disclosure is concerned with compounds and compositions for inhibition of the CBP / p300 family of bromodomains, methods of treating, preventing, or ameliorating diseases or disorders associated with the inhibition of CBP / p300 family of bromodomains, and methods of synthesis of these compounds. Background of Disclosure

[0003] p300 (also known as EP300 and KAT3B) is a large protein with multiple domains that bind to diverse proteins including many DNA-binding transcription factors. The cyclic AMP- responsive element-binding protein (CREB) binding protein (CBP, also known as KAT3A) is a cellular paralog of p300. p300 and CBP share extensive sequence identity and functional similarity. As such, they are often referred to as CBP / p300 in the scientific literature. CBP / p300 are lysine acetyltransferases that catalyze the attachment of an acetyl group to a lysine side chain of histones and other protein substrates. As large proteins, CBP / p300 were proposed to activate transcription in part by bridging DNA-binding transcription factors to RNA polymerase machinery or by helping assemble the transcriptional pre-initiation complex (PIC). Importantly, CBP / p300- catalyzed acetylation of histones and other proteins is pivotal to gene activation. Heightened p300 expression and activities have been observed in advanced human cancers such as prostate and liver cancer and appear to be associated with poor prognosis of these cancer types. Compared to normal tissue counterparts, the expression levels of p300 are higher in human primary breast cancer specimens and in mouse mammary carcinomas induced by polyomavirus middle-T oncogene. Summary of Disclosure

[0004] Novel compounds useful for inhibiting CBP, including CBP Inhibitor Compounds and Selective CBP Inhibitor Compounds, are disclosed herein. A first aspect of the present disclosure relates to compounds of Formula (I): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I)<annotation encoding="application / x-tex">(I)< / annotation>< / semantics>< / com:Math>, or a pharmaceutically acceptable salt, enantiomer, hydrate, solvate, isomer, or tautomer thereof, wherein: <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkyl, <com:Math><semantics>−C4<annotation encoding="application / x-tex">-C_4< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkenyl, heterocyclyl, heteroaryl, aryl, <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(R5)2<annotation encoding="application / x-tex">-N(R^5)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−NHR5<annotation encoding="application / x-tex">-NHR^5< / annotation>< / semantics>< / com:Math>; [Image disponible dans le document PDF, Image available in the PDF document] C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math>; [Image disponible dans le document PDF, Image available in the PDF document] C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R4′<annotation encoding="application / x-tex">R^{4'}< / annotation>< / semantics>< / com:Math> are each independently –H, halogen, –OH, –CN, or –NH<com:Sub>2< / com:Sub>; each <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is independently <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>alkyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkyl, heterocyclyl, aryl, or heteroaryl; <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 each independently, at each occurrence, <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>alkyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkyl, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, –OH, halogen, oxo, <com:Math><semantics>−CN<annotation encoding="application / x-tex">-CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SR8<annotation encoding="application / x-tex">-SR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OR8<annotation encoding="application / x-tex">-OR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n<annotation encoding="application / x-tex">-(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>OR8<annotation encoding="application / x-tex">OR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHR8<annotation encoding="application / x-tex">-NHR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8R9<annotation encoding="application / x-tex">-NR^8R^9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2NR8R9<annotation encoding="application / x-tex">-S(O)_2NR^8R^9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2R8<annotation encoding="application / x-tex">-S(O)_2R^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)R8′<annotation encoding="application / x-tex">C(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)NR8R9<annotation encoding="application / x-tex">-C(O)NR^{8}R^{9}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8C(O)R9′<annotation encoding="application / x-tex">-NR^{8}C(O)R^{9'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8S(O)2R9′<annotation encoding="application / x-tex">-NR^{8}S(O)_{2}R^{9'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)R8′<annotation encoding="application / x-tex">-S(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)NR8R9<annotation encoding="application / x-tex">-S(O)NR^{8}R^{9}< / annotation>< / semantics>< / com:Math>, or -NR<com:Sup>8< / com:Sup>S(O)R<com:Sup>9< / com:Sup>, wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>; wherein any two <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> or any two <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math>, when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> or any two <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math>, when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are each independently, at each occurrence, -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, - C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; or R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> may combine with the atom to which they are both attached to form a -C<com:Sub>3< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; R<com:Sup>8'< / com:Sup> and R<com:Sup>9'< / com:Sup> are each independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>- C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; 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> may combine with the atom to which they are both attached to form a <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_{3}< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> are each independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>- C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, -CN, -NH<com:Sub>2< / com:Sub>, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, -Oaryl, -Oheteroaryl, -NHC<com:Sub>1< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2C1−C6<annotation encoding="application / x-tex">-S(O)_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)C1−C6alkyl,−C(O)NH2,−C(O)NH(C1−C6alkyl),−C(O)N(C1−C6alkyl)2,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O<annotation encoding="application / x-tex">C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(C1−C6alkyl)SO2C1−C6alkyl<annotation encoding="application / x-tex">N(C_1-C_6alkyl)SO_2C_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">-S(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−N(C1−C6alkyl)2<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math> C<com:Sub>6< / com:Sub>alkyl)S(O)(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>; wherein any two R<com:Sup>10< / com:Sup> or any two R<com:Sup>11< / com:Sup>, when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R<com:Sup>10< / com:Sup> or any two R<com:Sup>11< / com:Sup>, when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R<com:Sup>12< / com:Sup> is independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, - C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, - <com:Math><semantics>CN1<annotation encoding="application / x-tex">CN_{1}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NH2<annotation encoding="application / x-tex">-NH_{2}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC1<annotation encoding="application / x-tex">-OC_{1}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_{6}< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−NHC1<annotation encoding="application / x-tex">-NHC_{1}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_{6}< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1<annotation encoding="application / x-tex">-N(C_{1}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_{6}< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1<annotation encoding="application / x-tex">-S(O)_{2}NH(C_{1}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_{6}< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>S(O)2N(C1−C6alkyl)2,−S(O)2C1−C6alkyl,−C(O)C1−C6alkyl,−C(O)NH2,−C(O)NH(C1−C6alkyl),−C(O)NH(C1−C6alkyl)2<annotation encoding="application / x-tex">S(O)_2N(C_1-C_6alkyl)_2, -S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)NH(C_1-C_6alkyl), -C(O)NH(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">C(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OC1−C6alkyl<annotation encoding="application / x-tex">-C(O)OC_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(C1−C6alkyl)SO2C1−C6alkyl<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)SO_2C_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">-S(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−N(C1−C6alkyl)S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>; and n is an integer from 1 to 4. [0004a] Another aspect of the present disclosure relates to a compound of Formula (I-d): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−d)<annotation encoding="application / x-tex">(I-d)< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein: Ring B represents –C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, or heteroaryl; [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heterocyclyl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>7< / com:Sup>; R<com:Sup>4< / com:Sup> and R<com:Sup>4< / com:Sup> are each independently –H, halogen, –OH, –CN, or –NH<com:Sub>2< / com:Sub>; R<com:Sup>5< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, heterocyclyl, aryl, or heteroaryl; R<com:Sup>7< / com:Sup> is independently, at each occurrence, -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, -OH, halogen, oxo, -CN, -SR<com:Sup>8< / com:Sup>, -OR<com:Sup>8< / com:Sup>, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n< / com:Sub>-OR<com:Sup>8< / com:Sup>, -NHR<com:Sup>8< / com:Sup>, -NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, <com:Math><semantics>−S(O)2NR8R9<annotation encoding="application / x-tex">-S(O)_2NR^8R^9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2R8′<annotation encoding="application / x-tex">-S(O)_2R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)R8′<annotation encoding="application / x-tex">-C(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)NR8R9<annotation encoding="application / x-tex">-C(O)NR^8R^9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8C(O)R9′<annotation encoding="application / x-tex">-NR^8C(O)R^{9'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8S(O)2R9′<annotation encoding="application / x-tex">-NR^8S(O)_2R^{9'}< / annotation>< / semantics>< / com:Math>. -S(O)R<com:Sup>8< / com:Sup>, -S(O)NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, or -NR<com:Sup>8< / com:Sup>S(O)R<com:Sup>9< / com:Sup>, wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>; wherein any two R<com:Sup>7< / com:Sup>, when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R<com:Sup>7< / com:Sup>, when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are each independently, at each occurrence, -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>; or R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> may combine with the atom to which they are both attached to form a -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / 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 each independently, at each occurrence, <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>; 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> may combine with the atom to which they are both attached to form a <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_{3}< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or <com:Math><semantics>ℝ11<annotation encoding="application / x-tex">\mathbb{R}^{11}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math> are each independently, at each occurrence, <com:Math><semantics>−H<annotation encoding="application / x-tex">-H< / annotation>< / semantics>< / com:Math>, <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, [Image disponible dans le document PDF, Image available in the PDF document] -N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl)S(O)(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more -R<com:Sup>12< / com:Sup>; wherein any two R<com:Sup>10< / com:Sup> or any two R<com:Sup>11< / com:Sup>, when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or any two <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>, when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; [Image disponible dans le document PDF, Image available in the PDF document] [0004b] Another aspect of the present disclosure relates to a compound of Formula (I-e): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−e),<annotation encoding="application / x-tex">(I-e),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein: R<com:Sup>6< / com:Sup> and R<com:Sup>7< / com:Sup> are each independently, at each occurrence, -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, -OH, halogen, oxo, -CN, -SR<com:Sup>8< / com:Sup>, -OR<com:Sup>8< / com:Sup>, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n< / com:Sub>-OR<com:Sup>8< / com:Sup>, -NHR<com:Sup>8< / com:Sup>, -NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, [Image disponible dans le document PDF, Image available in the PDF document] -S(O)R<com:Sup>8< / com:Sup>, -S(O)NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, or -NR<com:Sup>8< / com:Sup>S(O)R<com:Sup>9< / com:Sup>, wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>, wherein any two R<com:Sup>6< / com:Sup> or any two R<com:Sup>7< / com:Sup>, when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R<com:Sup>6< / com:Sup> or any two R<com:Sup>7< / com:Sup>, when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are each independently, at each occurrence, -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>; 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> may combine with the atom to which they are both attached to form a <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / 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 each independently, at each occurrence, <com:Math><semantics>−C1<annotation encoding="application / x-tex">-C_1< / annotation>< / semantics>< / com:Math>-C<com:Sub>6< / com:Sub>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>; 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> may combine with the atom to which they are both attached to form a <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math> are each independently, at each occurrence, <com:Math><semantics>−H<annotation encoding="application / x-tex">-H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C1<annotation encoding="application / x-tex">-C_1< / annotation>< / semantics>< / com:Math>-C<com:Sub>6< / com:Sub>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, <com:Math><semantics>−NO2<annotation encoding="application / x-tex">-NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CN<annotation encoding="application / x-tex">-CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NH2<annotation encoding="application / x-tex">-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC1<annotation encoding="application / x-tex">-OC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−NHC1<annotation encoding="application / x-tex">-NHC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1<annotation encoding="application / x-tex">-N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6alkyl),−S(O)2N(C1−C6alkyl)2,−S(O)2C1−C6alkyl,−C(O)C1−C6alkyl,−C(O)NH2,<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6alkyl), -S(O)_2N(C_1-C_6alkyl)_2, -S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−C(O)NH(C1−C6alkyl),−C(O)N(C1−C6alkyl)2,−C(O)OC1−C6alkyl,<annotation encoding="application / x-tex">-C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−N(C1−C6alkyl)SO2C1−C6alkyl,−S(O)(C1−C6alkyl),−S(O)N(C1−C6alkyl)2,or<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)SO_2C_1-C_6alkyl, -S(O)(C_1-C_6alkyl), -S(O)N(C_1-C_6alkyl)_2, or< / annotation>< / semantics>< / com:Math> -N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl)S(O)(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more -R<com:Sup>12< / com:Sup>; wherein any two R<com:Sup>10< / com:Sup> or any two R<com:Sup>11< / com:Sup>, when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R<com:Sup>10< / com:Sup> or any two R<com:Sup>11< / com:Sup>, when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R<com:Sup>12< / com:Sup> is independently, at each occurrence, -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, <com:Math><semantics>−NO2<annotation encoding="application / x-tex">-NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CN<annotation encoding="application / x-tex">-CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NH2<annotation encoding="application / x-tex">-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC1<annotation encoding="application / x-tex">-OC_1< / annotation>< / semantics>< / com:Math>-C6alkyl, <com:Math><semantics>−NHC1<annotation encoding="application / x-tex">-NHC_1< / annotation>< / semantics>< / com:Math>-C6alkyl, <com:Math><semantics>−N(C1<annotation encoding="application / x-tex">-N(C_1< / annotation>< / semantics>< / com:Math>-C6alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6alkyl),−S(O)2N(C1−C6alkyl)2,−S(O)2C1−C6alkyl,−C(O)C1−C6alkyl,−C(O)NH2,<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6alkyl), -S(O)_2N(C_1-C_6alkyl)_2, -S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−C(O)NH(C1−C6alkyl),−C(O)N(C1−C6alkyl)2,−C(O)OC1−C6alkyl,<annotation encoding="application / x-tex">-C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−N(C1−C6alkyl)SO2C1−C6alkyl,−S(O)(C1−C6alkyl),−S(O)N(C1−C6alkyl)2,or<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)SO_2C_1-C_6alkyl, -S(O)(C_1-C_6alkyl), -S(O)N(C_1-C_6alkyl)_2, or< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−N(C1−C6alkyl)S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>; and p is 1 or 2. [0004c] Another aspect of the present disclosure relates to a pharmaceutical composition comprising the compound as defined herein and a pharmaceutically acceptable carrier.

[0005] Another aspect of the present disclosure relates to a pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier can further include an excipient, diluent, or surfactant. The pharmaceutical composition can be effective for treating a disease or disorder associated with CBP / p300 modulation in a subject in need thereof. The pharmaceutical compositions can comprise the compounds of the present disclosure for use in treating diseases described herein. The compositions can contain at least one compound of the disclosure and a pharmaceutically acceptable carrier.

[0006] In another aspect, the present disclosure relates to a method of modulating one or more of CBP / p300-family bromodomains. The method can comprise administering to a patient in need thereof a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. Another aspect of the present disclosure relates to a method of inhibiting one or more of CBP / p300-family bromodomains. The method can comprise administering to a patient in need thereof a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. In another aspect, the present disclosure relates to a method of inhibiting one or more of CBP / p300-family bromodomains. The method can comprise administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition described herein. [Image disponible dans le document PDF, Image available in the PDF document] /

[0007] Another aspect of the present disclosure relates to a method of treating, preventing, inhibiting, or eliminating a disease or condition in a patient associated with the inhibition of one or more of CBP / p300-family bromodomains. The method can comprise administering to a patient in need thereof a therapeutically effective amount of a compound disclosed herein, such as a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein said disease or condition is selected from the group consisting of cancer

[0008] The present disclosure further provides compounds and compositions with an improved efficacy and safety profile relative to known CBP / p300 domain inhibitors. The present disclosure also provides agents with novel mechanisms of action toward CBP / p300 proteins in the treatment of various types of diseases including cancers. The present disclosure can provide the medical community with a novel pharmacological strategy for the treatment of diseases and disorders associated with inhibition of CBP / p300 proteins, including the inhibition of CBP in the HTRF biochemical assay of Example 963 disclosed herein, with an IC<com:Sub>50< / com:Sub> value of 0.001-1 micromolar. Detailed Description of the Disclosure

[0009] The present disclosure relates to compounds and compositions that are capable of modulating the activity of the CBP / p300 family bromodomains. The disclosure features methods of treating, preventing or ameliorating a disease or disorder in which CBP / p300 bromodomains play a role by administering to a patient in need thereof a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof. The methods of the present disclosure can be used in the treatment of a variety of CBP / p300 bromodomain dependent diseases and disorders by inhibiting the activity of a CBP / p300 bromodomains. Inhibition of CBP / p300 bromodomains provides a novel approach to the treatment, prevention, or amelioration of diseases including, but not limited to, cancer, inflammatory diseases, diabetes and obesity, and to develop male contraceptives.

[0010] The details of the disclosure are set forth in the accompanying description below. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, illustrative methods and materials are now described. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Definitions

[0011] Unless otherwise indicated, "CBP Inhibitor Compound" as used herein refers to a compound having one or more of the following characteristics when tested according to the HTRF biochemical Assay Protocol of Example 963 below: (1) a CBP IC<com:Sub>50< / com:Sub> value of less than 1 μM; and (2) a CBP IC<com:Sub>50< / com:Sub> value of between 0.001 and 1 <com:Math><semantics>μ<annotation encoding="application / x-tex">\mu< / annotation>< / semantics>< / com:Math>M.

[0012] Unless otherwise indicated, a "Selective CBP Inhibitor Compound" as used herein refers to a CBP Inhibitor having a BRD4 IC<com:Sub>50< / com:Sub> value greater than that of its CBP IC<com:Sub>50< / com:Sub> value, preferably wherein its BRD4 IC<com:Sub>50< / com:Sub> value greater than 1 μM (e.g., 1 micromolar to 10 micromolar, or greater), wherein the <com:Math><semantics>IC50<annotation encoding="application / x-tex">IC_{50}< / annotation>< / semantics>< / com:Math> values are as determined in the procedures set forth in Example 963.

[0013] The articles "a" and "an" are used in this disclosure to refer to one or more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element.

[0014] The term "and / or" is used in this disclosure to mean either "and" or "or" unless indicated otherwise.

[0015] The term "optionally substituted" is understood to mean that a given chemical moiety (e.g. an alkyl group) can (but is not required to) be bonded other substituents (e.g. heteroatoms). For instance, an alkyl group that is optionally substituted can be a fully saturated alkyl chain (i.e. a pure hydrocarbon). Alternatively, the same optionally substituted alkyl group can have substituents different from hydrogen. For instance, it can, at any point along the chain be bonded to a halogen atom, a hydroxyl group, or any other substituent described herein. Thus the term "optionally substituted" means that a given chemical moiety has the potential to contain other functional groups, but does not necessarily have any further functional groups.

[0016] The term "aryl" refers to cyclic, aromatic hydrocarbon groups that have 1 to 2 aromatic rings, including monocyclic or bicyclic groups. In some embodiments, aryl groups have a total of 5 to 14 ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains three to seven ring members. Where containing two aromatic rings (bicyclic, etc.), the aromatic rings of the aryl group may be joined at a single point (e.g., biphenyl), or fused (e.g., naphthyl). The aryl group may be optionally substituted by one or more substituents, e.g., 1 to 5 substituents, at any point of attachment. Exemplary substituents include, but are not limited to, -H, -halogen, -O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -OC<com:Sub>2< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−OH<annotation encoding="application / x-tex">-OH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OP(O)(OH)2<annotation encoding="application / x-tex">-OP(O)(OH)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC(O)C1<annotation encoding="application / x-tex">-OC(O)C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1<annotation encoding="application / x-tex">-C(O)C_1< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−OC(O)OC1−C6<annotation encoding="application / x-tex">-OC(O)OC_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−NH2<annotation encoding="application / x-tex">-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NH(C1−C6<annotation encoding="application / x-tex">-NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2−C1−C6<annotation encoding="application / x-tex">-S(O)_2-C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)NHC1−C6<annotation encoding="application / x-tex">-S(O)NHC_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, and <com:Math><semantics>−S(O)N(C1−C6<annotation encoding="application / x-tex">-S(O)N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>. The substituents can themselves be optionally substituted. Furthermore when containing two fused rings the aryl groups herein defined may have an unsaturated or partially saturated ring fused with a fully saturated ring. Exemplary ring systems of these aryl groups include indanyl, indenyl, tetrahydronaphthalenyl, and tetrahydrobenzoannulenyl.

[0017] Unless otherwise specifically defined, "heteroaryl" means a monovalent monocyclic aromatic radical or a polycyclic aromatic radical of 5 to 24 ring atoms, containing one or more ring heteroatoms selected from N, S, P, and O, the remaining ring atoms being C. Heteroaryl as herein defined also means a bicyclic heteroaromatic group wherein the heteroatom is selected from N, S, P, and O. The aromatic radical is optionally substituted independently with one or more substituents described herein. Examples include, but are not limited to, furyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, pyrimidinyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazinyl, indolyl, thiophen-2-yl, quinolyl, benzopyranyl, isothiazolyl, thiazolyl, thiadiazole, indazole, benzimidazolyl, thieno[3,2-b]thiophene, triazolyl, triazinyl, imidazo[1,2-b]pyrazolyl, furo[2,3-c]pyridinyl, imidazo[1,2-a]pyridinyl, indazolyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2- c]pyridinyl, pyrazolo[3,4-c]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-c]py b]pyridinyl, benzothiazolyl, indolyl, indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, benzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, dihydrobenzoxanyl, quinolinyl, isoquinolinyl, 1,6-naphthyridinyl, benzo[de]isoquinolinyl, pyrido[4,3-b][1,6]naphthyridinyl, thieno[2,3-b]pyrazinyl, quinazolinyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, isoindolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,4-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl, pyrrolo[1,2- a]pyrimidinyl, tetrahydro pyrrolo[1,2-a]pyrimidinyl, 3,4-dihydro-2H-<com:Math><semantics>1λ2<annotation encoding="application / x-tex">1\lambda^2< / annotation>< / semantics>< / com:Math>-pyrrolo[2,1- b]pyrimidine, dibenzo[b,d] thiophene, pyridin-2-one, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, 1H-pyrido[3,4-b][1,4] thiazinyl, benzooxazolyl, benzoisoxazolyl, furo[2,3-b]pyridinyl, benzothiophenyl, 1,5-naphthyridinyl, furo[3,2-b]pyridine, [1,2,4]triazolo[1,5-a]pyridinyl, benzo [1,2,3]triazolyl, imidazo[1,2-a]pyrimidinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazole, 1,3-dihydro-2H-benzo[d]imidazol-2-one, 3,4-dihydro-2H-pyrazolo [1,5-b][1,2]oxazinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl, thiazolo[5,4-d]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, thieno[2,3-b]pyrrolyl, 3H-indolyl, and derivatives thereof. Furthermore when containing two fused rings the heteroaryl groups herein defined may have an unsaturated or partially saturated ring fused with a fully saturated ring. Exemplary ring systems of these heteroaryl groups include indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, 3,4-dihydro-1H-isoquinolinyl, 2,3-dihydrobenzofuran, indolinyl, indolyl, and dihydrobenzoxanyl. In some embodiments, "heteroaryl" refers to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math> electrons shared in a cyclic array; and / or having, in addition to carbon atoms, from one to five heteroatoms wherein the term "heteroatom" refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen.

[0018] "Alkyl" refers to a straight or branched chain saturated hydrocarbon containing 1-12 carbon atoms. <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>alkyl groups contain 1 to 6 carbon atoms. Examples of a <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>alkyl group include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, isopropyl, isobutyl, sec-butyl and tert-butyl, isopentyl and neopentyl.

[0019] "Alkenyl" refers to a straight or branched chain unsaturated hydrocarbon containing 2-12 carbon atoms. The "alkenyl" group contains at least one double bond in the chain. The double bond of an alkenyl group can be unconjugated or conjugated to another unsaturated group. Examples of alkenyl groups include ethenyl, propenyl, n-butenyl, iso-butenyl, pentenyl, or hexenyl. An alkenyl group can be unsubstituted or substituted. Alkenyl, as herein defined, may be straight or branched.

[0020] "Alkynyl" refers to a straight or branched chain unsaturated hydrocarbon containing 2-12 carbon atoms. The "alkynyl" group contains at least one triple bond in the chain. Examples of alkenyl groups include ethynyl, propanyl, n-butynyl, iso-butynyl, pentynyl, or hexynyl. An alkynyl group can be unsubstituted or substituted.

[0021] The term "cycloalkyl" means monocyclic or polycyclic saturated carbon rings containing 3-18 carbon atoms. Examples of cycloalkyl groups include, without limitations, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl, cyclooctanyl, norboranyl, norborenyl, bicyclo[2.2.2]octanyl, or bicyclo[2.2.2]octenyl. A C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub> cycloalkyl is a cycloalkyl group containing between 3 and 8 carbon atoms. A cycloalkyl group can be fused (e.g., decalin) or bridged (e.g., norbornane).

[0022] The term "cycloalkenyl" means monocyclic, non-aromatic unsaturated carbon rings containing 4-18 carbon atoms. Examples of cycloalkenyl groups include, without limitation, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, and norborenyl. A <com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math> cycloalkenyl is a cycloalkenyl group containing between 4 and 8 carbon atoms.

[0023] The terms "heterocyclyl" or "heterocycloalkyl" or "heterocycle" refer to monocyclic or polycyclic 3 to 24-membered rings containing carbon and heteroatoms taken from oxygen, phosphorous, nitrogen, or sulfur and wherein there is not delocalized <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math> electrons (aromaticity) shared among the ring carbon or heteroatoms. In some embodiments, "heterocyclyl" refers to a stable 5– to 7–membered monocyclic or 7–10–membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms selected from N, S, P, or O. Heterocyclyl rings can be fully saturated or partially unsaturated. Heterocyclyl rings include, but are not limited to, oxetanyl, azetadinyl, tetrahydrofuranyl, pyrrolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, thiopyranyl, tetrahydropyranyl, dioxalinyl, piperidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S-dioxide, piperazinyl, azepinyl, oxepinyl, diazepinyl, tropanyl, pyridonyl, and homotropanyl. A heteroycyclyl or heterocycloalkyl ring can also be fused or bridged, e.g., can be a bicyclic ring.

[0024] As used herein, the term "partially unsaturated" refers to a ring moiety that includes at least one double or triple bond. The term "partially unsaturated" is intended to encompass rings having multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties, as herein defined.

[0025] The term "spirocycle" is understood as a bicyclic ring system with both rings connected through a single atom. A spirocycle can be fully saturated or can be partially unsaturated.

[0026] The term "spirocycloalkyl" is understood to mean a fully carbogenic bicyclic ring systems with both rings connected through a single atom. The ring can be different in size and nature, or identical in size and nature. Examples include spiropentane, spirohexane, spirohexane, spirooctane, spirononane, or spirodecane. One or both of the rings in a spirocycloalkyl can be fused to another ring carbocyclic, heterocyclic, aromatic, or heteroaromatic ring. A (C<com:Sub>5< / com:Sub>-C<com:Sub>12< / com:Sub>) spirocycloalkyl is a spirocycle containing between 5 and 12 carbon atoms.

[0027] The term "spiroheterocycloalkyl" or "spiroheterocyclyl" is understood to mean a spirocycle as defined above wherein at least one of the rings is a heterocycle (e.g., at least one of the rings is furanyl, morpholinyl, or piperadinyl). Spiroheterocycloalkyl groups can be for instance, without limitation, azapiroheptanes; azaspirooctanes; azaspirononanes; azaspirodecanes; oxaspiroheptanes; oxaspirooctanes; octaspirononanes; or oxaspirodecanes.

[0028] As used herein, the term "halo" or "halogen" means a fluoro, chloro, bromo, or iodo group.

[0029] The term "carbonyl" refers to a functional group composing a carbon atom double-bonded to an oxygen atom. It can be abbreviated herein as <com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>, or as <com:Math><semantics>C=O<annotation encoding="application / x-tex">C=O< / annotation>< / semantics>< / com:Math>.

[0030] The term "oxo" refers to an oxygen atom that is double-bonded to another atom. An "oxo" group can be connected to a carbon atom (e.g., to form a carbonyl, as defined above) or can be connected to a heteroatom such as sulfur (e.g., to form a sulfoxide or a sulfone) or phosphorous (e.g., to form a phosphorous ylide).

[0031] The disclosure also includes pharmaceutical compositions comprising an effective amount of a disclosed compound and a pharmaceutically acceptable carrier. Representative "pharmaceutically acceptable salts" include, e.g., water-soluble and water-insoluble salts, such as the acetate, amsonate (4,4-diaminostilbene-2,2-disulfonate), benzenesulfonate, benzonate, bicarbonate, bisulfate, bitartrate, borate, bromide, butyrate, calcium, calcium edetate, camsylate, carbonate, chloride, citrate, clavulariate, dihydrochloride, edetate, edisylate, estolate, esylate, fiunarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexafluorophosphate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, sethionate, lactate, lactobionate, laurate, magnesium, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsylate, nitrate, N-methylglucamine ammonium salt, 3-hydroxy-2-naphthoate, oleate, oxalate, palmitate, pamoate (1,1-methene-bis-2- hydroxy-3-naphthoate, einbonate), pantothenate, phosphate / diphosphate, picrate, polygalacturonate, propionate, p-toluenesulfonate, salicylate, stearate, subacetate, succinate, sulfate, sulfosalicylate, suramate, tannate, tartrate, teoclate, tosylate, triethiodide, and valerate salts.

[0032] The term "tautomers" refers to a set of compounds that have the same number and type of atoms, but differ in bond connectivity and are in equilibrium with one another. A "tautomer" is a single member of this set of compounds. Typically a single tautomer is drawn but it is understood that this single structure is meant to represent all possible tautomers that might exist. Examples include enol-ketone tautomerism. When a ketone is drawn it is understood that both the enol and ketone forms are part of the disclosure.

[0033] The term "prodrug," as used in this disclosure, means a compound which is convertible in vivo by metabolic means (e.g., by hydrolysis) to a disclosed compound. Furthermore, as used herein a prodrug is a drug which is inactive in the body, but is transformed in the body typically either during absorption or after absorption from the gastrointestinal tract into the active compound. The conversion of the prodrug into the active compound in the body may be done chemically or biologically (i.e., using an enzyme).

[0034] The term "solvate" refers to a complex of variable stoichiometry formed by a solute and solvent. Such solvents for the purpose of the disclosure may not interfere with the biological activity of the solute. Examples of suitable solvents include, but are not limited to, water, MeOH, EtOH, and AcOH. Solvates wherein water is the solvent molecule are typically referred to as hydrates. Hydrates include compositions containing stoichiometric amounts of water, as well as compositions containing variable amounts of water.

[0035] The term "isomer" refers to compounds that have the same composition and molecular weight but differ in physical and / or chemical properties. The structural difference may be in constitution (geometric isomers) or in the ability to rotate the plane of polarized light (stereoisomers). With regard to stereoisomers, the compounds of Formula (I) may have one or more asymmetric carbon atom and may occur as racemates, racemic mixtures and as individual enantiomers or diastereomers.

[0036] The term "stereoisomers" refers to the set of compounds which have the same number and type of atoms and share the same bond connectivity between those atoms, but differ in three dimensional structure. The term "stereoisomer" refers to any member of this set of compounds. For instance, a stereoisomer may be an enantiomer or a diastereomer.

[0037] The term "enantiomers" refers to a pair of stereoisomers which are non-superimposable mirror images of one another. The term "enantiomer" refers to a single member of this pair of stereoisomers. The term "racemic" refers to a 1:1 mixture of a pair of enantiomers.

[0038] The term "diastereomers" refers to the set of stereoisomers which cannot be made superimposable by rotation around single bonds. Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more (but not all) of the equivalent (related) stereocenters and are not mirror images of each other. Compounds containing multiple stereogenic centers with different relative configurations are considered to be diastereomers. The term "diastereomer" refers to any member of this set of compounds. In some examples presented, the synthetic route may produce a single diastereomer or a mixture of diastereomers. In some cases these diastereomers were separated and in other cases a wavy bond is used to indicate the structural element where configuration is variable.

[0039] An "effective amount" when used in connection with a compound is an amount effective for treating or preventing a disease in a subject as described herein.

[0040] The term "carrier", as used in this disclosure, encompasses carriers, excipients, and diluents and means a material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting a pharmaceutical agent from one organ, or portion of the body, to another organ, or portion of the body of a subject.

[0041] The term "treating" with regard to a subject, refers to improving at least one symptom of the subject's disorder. Treating includes curing, improving, or at least partially ameliorating the disorder.

[0042] The term "disorder" is used in this disclosure to mean, and is used interchangeably with, the terms disease, condition, or illness, unless otherwise indicated.

[0043] The term "administer", "administering", or "administration" as used in this disclosure refers to either directly administering a disclosed compound or pharmaceutically acceptable salt of the disclosed compound or a composition to a subject, or administering a prodrug derivative or analog of the compound or pharmaceutically acceptable salt of the compound or composition to the subject, which can form an equivalent amount of active compound within the subject's body.

[0044] A "patient" or "subject" is a mammal, e.g., a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or non-human primate, such as a monkey, chimpanzee, baboon or rhesus.

[0045] It should be understood that all isomeric forms are included within the present disclosure, including mixtures thereof. If the compound contains a double bond, the substituent may be in the E or Z configuration. If the compound contains a disubstituted cycloalkyl, the cycloalkyl substituent may have a cis- or trans configuration. All tautomeric forms are also intended to be included.

[0046] Compounds of Formula (I), and salts, solvates, esters and prodrugs thereof, may exist in their tautomeric form (for example, as an amide or imino ether). All such tautomeric forms are contemplated herein as part of the present disclosure.

[0047] The compounds of Formula (I), may contain asymmetric or chiral centers, and, therefore, exist in different stereoisomeric forms. It is intended that all stereoisomeric forms of the compounds of Formula (I) as well as mixtures thereof, including racemic mixtures, form part of the present disclosure. In addition, the present disclosure embraces all geometric and positional isomers. For example, if a compound of Formula (I), incorporates a double bond or a fused ring, both the cis- and trans-forms, as well as mixtures, are embraced within the scope of the disclosure. Each compound herein disclosed includes all the enantiomers that conform to the general structure of the compound. The compounds may be in a racemic or enantiomerically pure form, or any other form in terms of stereochemistry. The assay results may reflect the data collected for the racemic form, the enantiomerically pure form, or any other form in terms of stereochemistry.

[0048] Diastereomeric mixtures can be separated into their individual diastereomers on the basis of their physical chemical differences by methods well known to those skilled in the art, such as, for example, by chromatography and / or fractional crystallization. Enantiomers can be separated by converting the enantiomeric mixture into a diastereomeric mixture by reaction with an appropriate optically active compound (e.g., chiral auxiliary such as a chiral alcohol or Mosher's acid chloride), separating the diastereomers and converting (e.g., hydrolyzing) the individual diastereomers to the corresponding pure enantiomers. Also, some of the compounds of Formula (I) may be atropisomers (e.g., substituted biaryls) and are considered as part of this disclosure. Enantiomers can also be separated by use of a chiral HPLC column.

[0049] It is also possible that the compounds of Formula (I), may exist in different tautomeric forms, and all such forms are embraced within the scope of the disclosure. Also, for example, all keto-enol and imine-enamine forms of the compounds are included in the disclosure.

[0050] All stereoisomers (for example, geometric isomers, optical isomers and the like) of the present compounds (including those of the salts, solvates, esters and prodrugs of the compounds as well as the salts, solvates and esters of the prodrugs), such as those which may exist due to asymmetric carbons on various substituents, including enantiomeric forms (which may exist even in the absence of asymmetric carbons), rotameric forms, atropisomers, and diastereomeric forms, are contemplated within the scope of this disclosure, as are positional isomers (such as, for example, 4-pyridyl and 3-pyridyl). (For example, if a compound of Formula (I) incorporates a double bond or a fused ring, both the cis- and trans-forms, as well as mixtures, are embraced within the scope of the disclosure. Also, for example, all keto-enol and imine-enamine forms of the compounds are included in the disclosure.) Individual stereoisomers of the compounds of the disclosure may, for example, be substantially free of other isomers, or may be admixed, for example, as racemates or with all other, or other selected, stereoisomers. The chiral centers of the present disclosure can have the S or R configuration as defined by the IUPAC 1974 Recommendations. The use of the terms "salt", "solvate", "ester," "prodrug" and the like, is intended to equally apply to the salt, solvate, ester and prodrug of enantiomers, stereoisomers, rotamers, tautomers, positional isomers, racemates or prodrugs of the inventive compounds.

[0051] The present disclosure also embraces isotopically-labelled compounds of the present disclosure which are identical to those recited herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds of the disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, such as <com:Sup>2< / com:Sup>H (or D), <com:Sup>3< / com:Sup>H, <com:Sup>13< / com:Sup>C, <com:Sup>14< / com:Sup>C, <com:Sup>15< / com:Sup>N, <com:Sup>18< / com:Sup>O, <com:Sup>17< / com:Sup>O, <com:Sup>31< / com:Sup>P, <com:Sup>32< / com:Sup>P, <com:Sup>35< / com:Sup>S, <com:Sup>18< / com:Sup>F, and <com:Sup>36< / com:Sup>Cl, respectively.

[0052] Certain isotopically-labelled compounds of Formula (I) (e.g., those labeled with <com:Sup>3< / com:Sup>H and <com:Sup>14< / com:Sup>C) are useful in compound and / or substrate tissue distribution assays. Tritiated (i.e., <com:Sup>3< / com:Sup>H) and carbon-14 (i.e., <com:Sup>14< / com:Sup>C) isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium (i.e., <com:Sup>2< / com:Sup>H) may afford certain therapeutic advantages resulting from greater metabolic stability (e.g., increased in vivo half-life or reduced dosage requirements) and hence may be preferred in some circumstances. Isotopically labelled compounds of Formula (I) can generally be prepared by following procedures analogous to those disclosed in the Schemes and / or in the Examples herein below, by substituting an appropriate isotopically labelled reagent for a non-isotopically labelled reagent.

[0053] The compounds of Formula (I) may form salts which are also within the scope of this disclosure. Reference to a compound of the Formula (I) herein is understood to include reference to salts thereof, unless otherwise indicated.

[0054] The present disclosure relates to compounds which are modulators of one or more bromodomains of the CBP / p300 family. In one embodiment, the compounds of the present disclosure are inhibitors of one or more bromodomains of the CBP / p300 family. Compounds of the Disclosure

[0055] The present disclosure relates to compounds, or pharmaceutically acceptable salts or isomers thereof, capable of modulating CBP / p300 family bromodomains which are useful for the treatment of diseases and disorders associated with modulation of CBP / p300 family bromodomains. The disclosure further relates to compounds, or pharmaceutically acceptable salts or isomers thereof, which are useful for inhibiting CBP / p300 family bromodomains.

[0056] One aspect of the present disclosure describes compounds of Formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (I) or a pharmaceutically acceptable salt, enantiomer, hydrate, solvate, isomer, or tautomer thereof, wherein: R<com:Sup>1< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(R5)2<annotation encoding="application / x-tex">-N(R^5)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−NHR5<annotation encoding="application / x-tex">-NHR^5< / annotation>< / semantics>< / com:Math>; [Image disponible dans le document PDF, Image available in the PDF document] C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math>; [Image disponible dans le document PDF, Image available in the PDF document] C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>; R<com:Sup>4< / com:Sup> and R<com:Sup>4< / com:Sup> are each independently –H, halogen, –OH, –CN, or –NH<com:Sub>2< / com:Sub>; each <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is independently <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>alkyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkyl, heterocyclyl, aryl, or heteroaryl; R<com:Sup>6< / com:Sup> and R<com:Sup>7< / com:Sup> are each independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, - C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, –OH, halogen, oxo, <com:Math><semantics>−CN<annotation encoding="application / x-tex">-CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SR8<annotation encoding="application / x-tex">-SR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OR8<annotation encoding="application / x-tex">-OR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n<annotation encoding="application / x-tex">-(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>OR8<annotation encoding="application / x-tex">OR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHR8<annotation encoding="application / x-tex">-NHR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8R9<annotation encoding="application / x-tex">-NR^8R^9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2NR8R9<annotation encoding="application / x-tex">-S(O)_2NR^8R^9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2R8′<annotation encoding="application / x-tex">-S(O)_2R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)R8′<annotation encoding="application / x-tex">C(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)NR8R9<annotation encoding="application / x-tex">-C(O)NR^{8}R^{9}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8C(O)R9′<annotation encoding="application / x-tex">-NR^{8}C(O)R^{9'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8S(O)2R9′<annotation encoding="application / x-tex">-NR^{8}S(O)_{2}R^{9'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)R8′<annotation encoding="application / x-tex">-S(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)NR8R9<annotation encoding="application / x-tex">-S(O)NR^{8}R^{9}< / annotation>< / semantics>< / com:Math>, or -NR<com:Sup>8< / com:Sup>S(O)R<com:Sup>9< / com:Sup>, wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup>; wherein any two <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> or any two <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math>, when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R<com:Sup>6< / com:Sup> or any two R<com:Sup>7< / com:Sup>, when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are each independently, at each occurrence, -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, - C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; 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> may combine with the atom to which they are both attached to form a <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are each independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>- C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; 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> may combine with the atom to which they are both attached to form a <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heterocyclyl, or aryl, wherein the formed -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> are each independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>- C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, -CN, -NH<com:Sub>2< / com:Sub>, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, -Oaryl, -Oheteroaryl, -NHC<com:Sub>1< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2C1−C6<annotation encoding="application / x-tex">-S(O)_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)2N(C1−C6)<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)C1−C6alkyl,−C(O)NH2,−C(O)NH(C1−C6alkyl),−C(O)N(C1−C6alkyl)2,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O<annotation encoding="application / x-tex">C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(C1−C6alkyl)SO2C1−C6alkyl<annotation encoding="application / x-tex">N(C_1-C_6alkyl)SO_2C_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">-S(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−N(C1−C6alkyl)2<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math> C<com:Sub>6< / com:Sub>alkyl)S(O)(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more -R<com:Sup>12< / com:Sup>; wherein any two R<com:Sup>10< / com:Sup> or any two R<com:Sup>11< / com:Sup>, when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or any two <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>, when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R<com:Sup>12< / com:Sup> is independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, - C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, - <com:Math><semantics>CN<annotation encoding="application / x-tex">CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NH2<annotation encoding="application / x-tex">-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC1<annotation encoding="application / x-tex">-OC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−NHC1<annotation encoding="application / x-tex">-NHC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1<annotation encoding="application / x-tex">-N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1<annotation encoding="application / x-tex">-S(O)_2NH(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>S(O)2N(C1−C6alkyl)2<annotation encoding="application / x-tex">S(O)_2N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2C1−C6alkyl<annotation encoding="application / x-tex">-S(O)_2C_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)C1−C6alkyl<annotation encoding="application / x-tex">-C(O)C_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <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−C6alkyl)<annotation encoding="application / x-tex">-C(O)NH(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>< / com:Math>, <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<annotation encoding="application / x-tex">-C(O)NH< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">C(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OC1−C6alkyl<annotation encoding="application / x-tex">-C(O)OC_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(C1−C6alkyl)SO2C1−C6alkyl<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)SO_2C_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">-S(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−N(C1−C6alkyl)S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>; and n is an integer from 1 to 4.

[0057] Another aspect of the present disclosure is the provision of pharmaceutical compositions comprising therapeutically effective amounts of at least one compound of Formula (I).

[0058] An aspect of the present disclosure concerns compounds which are, or can be, inhibitors of one or more bromodomains of the CBP / p300 family (e.g., compounds of Formula (I)).

[0059] An aspect of the present disclosure concerns the use of an inhibitor of CBP / p300 family bromodomains (e.g., a compound of Formula (I)) for the preparation of a medicament used in the treatment, prevention, inhibition or elimination of tumors (e.g., solid tumors).

[0060] An aspect of the present disclosure concerns the use of an inhibitor of CBP / p300 family bromodomains (e.g., a compound of Formula (I)) for the preparation of a medicament used in the treatment, prevention, inhibition or elimination of cancer. In some embodiments, the cancer is a hematological cancer such as leukemia (e.g., acute myeloid leukemia).

[0061] An aspect of the present disclosure concerns the use of an inhibitor of CBP / p300 family bromodomains (e.g., a compound of Formula (I)) for use in the treatment, prevention, inhibition or elimination of cancer.

[0062] In some embodiments, compounds of the disclosure are of Formula (I), or a pharmaceutically acceptable salt, enantiomer, hydrate, solvate, isomer, or tautomer thereof thereof, wherein: [Image disponible dans le document PDF, Image available in the PDF document] heterocyclyl, heteroaryl, aryl, or -OR<com:Sup>5< / com:Sup>; [Image disponible dans le document PDF, Image available in the PDF document] C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math>, and wherein a <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>alkyl group may have one or more methylene units replaced by - <com:Math><semantics>NR6<annotation encoding="application / x-tex">NR^6< / annotation>< / semantics>< / com:Math>-, -O- or -S-; [Image disponible dans le document PDF, Image available in the PDF document] C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>; R<com:Sup>4< / com:Sup> and R<com:Sup>4< / com:Sup> are each independently –H, halogen, –OH, –CN, or –NH<com:Sub>2< / com:Sub>; [Image disponible dans le document PDF, Image available in the PDF document] <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 each independently, at each occurrence, <com:Math><semantics>−H<annotation encoding="application / x-tex">-H< / annotation>< / semantics>< / com:Math>, <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>alkyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, -OH, halogen, oxo, -CN, -SR<com:Sup>8< / com:Sup>, -OR<com:Sup>8< / com:Sup>, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n< / com:Sub>-OR<com:Sup>8< / com:Sup>, -NHR<com:Sup>8< / com:Sup>, -NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, - [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <Formule mathématique disponible dans le document PDF, Math available in the PDF document>${\bf R}^{10}$; wherein any two R<com:Sup>6< / com:Sup> or any two R<com:Sup>7< / com:Sup>, when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> or any two <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math>, when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are each independently, at each occurrence, -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, - C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; or R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> may combine with the atom to which they are both attached to form a -C<com:Sub>3< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; R<com:Sup>8'< / com:Sup> and R<com:Sup>9'< / com:Sup> are each independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>- C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; 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> may combine with the atom to which they are both attached to form a <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_{3}< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; R<com:Sup>10< / com:Sup> and R<com:Sup>11< / com:Sup> are each independently, at each occurrence, -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, <com:Math><semantics>−NO2<annotation encoding="application / x-tex">-NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CN<annotation encoding="application / x-tex">-CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NH2<annotation encoding="application / x-tex">-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC1<annotation encoding="application / x-tex">-OC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−NHC1<annotation encoding="application / x-tex">-NHC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1<annotation encoding="application / x-tex">-N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>S(O)2NH(C1−C6alkyl),−S(O)2N(C1−C6alkyl)2,−S(O)2C1−C6alkyl,−C(O)C1−C6alkyl,−C(O)NH2,−<annotation encoding="application / x-tex">S(O)_2NH(C_1-C_6alkyl), -S(O)_2N(C_1-C_6alkyl)_2, -S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2, -< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)NH(C1−C6alkyl),−C(O)N(C1−C6alkyl)2,−C(O)OC1−C6alkyl,−N(C1−C6alkyl)SO2C1−C6alkyl,<annotation encoding="application / x-tex">C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl, -N(C_1-C_6alkyl)SO_2C_1-C_6alkyl,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−S(O)(C1−C6alkyl),−S(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">-S(O)(C_1-C_6alkyl), -S(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−N(C1−C6alkyl)S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>; wherein any two R<com:Sup>10< / com:Sup> or any two R<com:Sup>11< / com:Sup>, when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R<com:Sup>10< / com:Sup> or any two R<com:Sup>11< / com:Sup>, when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; [Image disponible dans le document PDF, Image available in the PDF document] n is an integer from 1 to 4.

[0063] In some embodiments, compounds of the disclosure have the Formula (I-a): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−a),<annotation encoding="application / x-tex">(I-a),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein Ring A represents a -C<com:Sub>3< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl and wherein each of R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>4< / com:Sup>, and R<com:Sup>7< / com:Sup> is as defined with respect to Formula (I) above and described in classes and subclasses herein, both singly and in combination.

[0064] In some embodiments, compounds of the disclosure have the Formula (I-b): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−b),<annotation encoding="application / x-tex">(I-b),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein Ring B represents a -C<com:Sub>3< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, or aryl and wherein each of R<com:Sup>1< / com:Sup>, R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>4< / com:Sup>, and R<com:Sup>6< / com:Sup> is as defined with respect to Formula (I) above and described in classes and subclasses herein, both singly and in combination.

[0065] In some embodiments, compounds of the disclosure have the Formula (I-c): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−c),<annotation encoding="application / x-tex">(I-c),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein m is an integer from 1 to 4 and wherein each of R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>4< / com:Sup>, and R<com:Sup>7< / com:Sup> is as defined with respect to Formula (I) above and described in classes and subclasses herein, both singly and in combination.

[0066] In some embodiments, compounds of the disclosure have the Formula (I-d): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−d),<annotation encoding="application / x-tex">(I-d),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein Ring B represents –C<com:Sub>3< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, or heteroaryl, and wherein p is an integer from 1 to 2 and wherein each of R<com:Sup>1< / com:Sup>, R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>4< / com:Sup>, and R<com:Sup>10< / com:Sup> is as defined with respect to Formula (I) above and described in classes and subclasses herein, both singly and in combination. In some embodiments, Ring B is -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl. In some embodiments, Ring B is -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl. In some embodiments, Ring B is aryl. In some embodiments, Ring B is heterocyclyl. In some embodiments, Ring B is heteroaryl.

[0067] In some embodiments, compounds of the disclosure have the Formula (I-e): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−e),<annotation encoding="application / x-tex">(I-e),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein p is 1 or 2 and wherein each of R<com:Sup>6< / com:Sup> and R<com:Sup>7< / com:Sup> is as defined with respect to Formula (I) above and described in classes and subclasses herein, both singly and in combination.

[0068] In some embodiments (e.g., embodiments of Formula I-e), p is 1. In some embodiments (e.g., embodiments of Formula I-e), p is 2. In some embodiments (e.g., embodiments of Formula I-e), R<com:Sup>7< / com:Sup> is -S(O)<com:Sub>2< / com:Sub>NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, -C(O)OR<com:Sup>8< / com:Sup>, -C(O)NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, or -S(O)NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>. In some embodiments (e.g., embodiments of Formula I-e), R<com:Sup>7< / com:Sup> is -S(O)<com:Sub>2< / com:Sub>NH<com:Sub>2< / com:Sub>, -C(O)OH, -C(O)NH<com:Sub>2< / com:Sub>, or -S(O)NH<com:Sub>2< / com:Sub>. In some embodiments (e.g., embodiments of Formula I-e), R<com:Sup>7< / com:Sup> is -C(O)OH. In some embodiments (e.g., embodiments of Formula I-e), R<com:Sup>7< / com:Sup> is -S(O)<com:Sub>2< / com:Sub>NH<com:Sub>2< / com:Sub>. In some embodiments (e.g., embodiments of Formula I-e), R<com:Sup>7< / com:Sup> is -C(O)NH<com:Sub>2< / com:Sub>. In some embodiments (e.g., embodiments of Formula I-e), R<com:Sup>7< / com:Sup> is - S(O)NH<com:Sub>2< / com:Sub>. In some embodiments (e.g., embodiments of Formula I-e), R<com:Sup>6< / com:Sup> is aryl or heteroaryl, wherein each aryl or heteroaryl is optionally substituted with one or more <com:Math><semantics>ℝ10<annotation encoding="application / x-tex">\mathbb{R}^{10}< / annotation>< / semantics>< / com:Math>.

[0069] In some embodiments, compounds of the disclosure have the Formula (I-f): [Image disponible dans le document PDF, Image available in the PDF document] (I-f), or pharmaceutically acceptable salt thereof, wherein Ring B is -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, or heteroaryl; and L is a <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> alkylene chain optionally substituted with one or more <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> or L is a <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> alkylene chain optionally substituted with one or more R<com:Sup>6< / com:Sup>, and wherein at least one methylene unit of L is replaced by -NR<com:Sup>6< / com:Sup>-, -O- or -S-; and wherein each of R<com:Sup>1< / com:Sup>, R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>6< / com:Sup> and R<com:Sup>10< / com:Sup> is as defined with respect to Formula (I) above and described in classes and subclasses herein, both singly and in combination. In some embodiments, Ring B is -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl. In some embodiments, Ring B is -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl. In some emodiments, Ring B is aryl. In some embodiments, Ring B is heterocyclyl. In some embodiments Ring B is heteroaryl. In some embodiments, L is a C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkylene chain optionally substituted with one or more <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math>. In some embodiments, L is a <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math> alkylene chain optionally substituted with one or more <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math>. In some embodiments, L is a <com:Math><semantics>ℂ1<annotation encoding="application / x-tex">\mathbb{C}_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ6<annotation encoding="application / x-tex">\mathbb{C}_6< / annotation>< / semantics>< / com:Math> alkylene chain optionally substituted with one or more R<com:Sup>6< / com:Sup>, and wherein at least one methylene unit is replaced by <com:Math><semantics>−NR6<annotation encoding="application / x-tex">-NR^6< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−O<annotation encoding="application / x-tex">-O< / annotation>< / semantics>< / com:Math>- or <com:Math><semantics>−S<annotation encoding="application / x-tex">-S< / annotation>< / semantics>< / com:Math>-. In some embodiments, L is a <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> alkylene chain optionally substituted with one or more R<com:Sup>6< / com:Sup>, and wherein at least one methylene unit of L is replaced by -NR<com:Sup>6< / com:Sup>. In some embodiments, L is a C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkylene chain optionally substituted with one or more R<com:Sup>6< / com:Sup>, and wherein at least one methylene unit of L is replaced by -O-. In some embodiments, L is a C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkylene chain optionally substituted with one or more R<com:Sup>6< / com:Sup>, and wherein at least one methylene unit of L is replaced by -S-. In some embodiments (e.g., embodiments of Formula I-f), L is a C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub> alkylene chain optionally substituted with R<com:Sup>6< / com:Sup> wherein R<com:Sup>6< / com:Sup> is -CH<com:Sub>3< / com:Sub>, -S(O)<com:Sub>2< / com:Sub>NH<com:Sub>2< / com:Sub>, -C(O)OH, -C(O)NH<com:Sub>2< / com:Sub>, or -S(O)NH<com:Sub>2< / com:Sub>. In some embodiments (e.g., embodiments of Formula I-f), L is a C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub> alkylene chain optionally substituted with R<com:Sup>6< / com:Sup> wherein R<com:Sup>6< / com:Sup> is -CH<com:Sub>3< / com:Sub>. In some embodiments (e.g., embodiments of Formula I-f), L is a C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub> alkylene chain optionally substituted with R<com:Sup>6< / com:Sup> wherein R<com:Sup>6< / com:Sup> is -S(O)<com:Sub>2< / com:Sub>NH<com:Sub>2< / com:Sub>. In some embodiments (e.g., embodiments of Formula I-f), L is a <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math> alkylene chain optionally substituted with <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> wherein <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−ℂ(O)OH<annotation encoding="application / x-tex">-\mathbb{C}(O)OH< / annotation>< / semantics>< / com:Math>. In some embodiments (e.g., embodiments of Formula I-f), L is a <com:Math><semantics>ℂ1<annotation encoding="application / x-tex">\mathbb{C}_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ2<annotation encoding="application / x-tex">\mathbb{C}_2< / annotation>< / semantics>< / com:Math> alkylene chain optionally substituted with <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> wherein <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>< / com:Math>. In some embodiments (e.g., embodiments of Formula I-f), L is a C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub> alkylene chain optionally substituted with R<com:Sup>6< / com:Sup> wherein R<com:Sup>6< / com:Sup> is -S(O)NH<com:Sub>2< / com:Sub>. In some embodiments (e.g., embodiments of Formula I-f), L is - CH<com:Sub>2< / com:Sub>CH(C(O)OH)-*, wherein "*" denotes the point of attachment to Ring B. In some embodiments, R<com:Sup>1< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, or -OR<com:Sup>5< / com:Sup>; L is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, where L is optionally substituted with one or more R<com:Sup>6< / com:Sup>; Ring B is -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, heterocyclyl, heteroaryl, or aryl; and R<com:Sup>3< / com:Sup> is -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, or -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, wherein each alkyl or cycloalkyl, is optionally substituted with one or more R<com:Sup>7< / com:Sup>; R<com:Sup>5< / com:Sup> is methyl; R<com:Sup>7< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, -CN, -OR<com:Sup>8< / com:Sup>, -NHR<com:Sup>8< / com:Sup>, -NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, -C(O)OH, - C(O)NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, -S(O)CH<com:Sub>3< / com:Sub>, or -S(O)NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>; and R<com:Sup>8< / com:Sup> or R<com:Sup>9< / com:Sup> is -H or -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl. In some embodiments R<com:Sup>6< / com:Sup> is -C(O)OH. In some embodiments, R<com:Sup>3< / com:Sup> is -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, or heteroaryl. In some embodiments, R<com:Sup>3< / com:Sup> is cyclopentyl, cyclohexyl, 3-pyranyl, or 4-pyranyl. In some embodiments, R<com:Sup>3< / com:Sup> is cyclopentyl, cyclohexyl or 3- pyranyl. In some embodiments, L is an C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkylene chain optionally substituted with one or more R<com:Sup>6< / com:Sup>, and wherein at least one methylene unit is replaced by -NR<com:Sup>6< / com:Sup>-, -O- or -S-; and R<com:Sup>3< / com:Sup> is -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, or heteroaryl, wherein each -C<com:Sub>3< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>7< / com:Sup>; and R<com:Sup>6< / com:Sup> is independently, at each occurrence, -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, -OH, halogen, oxo, <com:Math><semantics>−CN<annotation encoding="application / x-tex">-CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SR8<annotation encoding="application / x-tex">-SR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OR8<annotation encoding="application / x-tex">-OR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n<annotation encoding="application / x-tex">-(CH_2)_n< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>OR8<annotation encoding="application / x-tex">OR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHR8<annotation encoding="application / x-tex">-NHR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8R9<annotation encoding="application / x-tex">-NR^8R^9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2NR8R9<annotation encoding="application / x-tex">-S(O)_2NR^8R^9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2R8′<annotation encoding="application / x-tex">-S(O)_2R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)R8′<annotation encoding="application / x-tex">C(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)NR8R9<annotation encoding="application / x-tex">-C(O)NR^{8}R^{9}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8C(O)R9′<annotation encoding="application / x-tex">-NR^{8}C(O)R^{9'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8S(O)2R9′<annotation encoding="application / x-tex">-NR^{8}S(O)_{2}R^{9'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)R8′<annotation encoding="application / x-tex">-S(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)NR8R9<annotation encoding="application / x-tex">-S(O)NR^{8}R^{9}< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−NR8S(O)R9′<annotation encoding="application / x-tex">-NR^{8}S(O)R^{9'}< / annotation>< / semantics>< / com:Math>, wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup>, wherein R<com:Sup>10< / com:Sup> is -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>- C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, halogen, <com:Math><semantics>−NO2<annotation encoding="application / x-tex">-NO_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−CN<annotation encoding="application / x-tex">-CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NH2<annotation encoding="application / x-tex">-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC1<annotation encoding="application / x-tex">-OC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−NHC1<annotation encoding="application / x-tex">-NHC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1<annotation encoding="application / x-tex">-N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1<annotation encoding="application / x-tex">-S(O)_2NH(C_1< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2C1−C6<annotation encoding="application / x-tex">-S(O)_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_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>, <com:Math><semantics>−C(O)NH(C1−C6)<annotation encoding="application / x-tex">-C(O)NH(C_1-C_6)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−C(O)N(C1−C6<annotation encoding="application / x-tex">-C(O)N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−C(O)OC1−C6<annotation encoding="application / x-tex">-C(O)OC_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>SO2C1−C6<annotation encoding="application / x-tex">SO_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)(C1−C6)<annotation encoding="application / x-tex">-S(O)(C_1-C_6)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)N(C1−C6<annotation encoding="application / x-tex">-S(O)N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, or <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>S(O)(C1−C6<annotation encoding="application / x-tex">S(O)(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>. In some embodiments, L is a <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> alkylene chain, <com:Math><semantics>−OCH2<annotation encoding="application / x-tex">-OCH_2< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−CH2O<annotation encoding="application / x-tex">-CH_2O< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> NR<com:Sup>6< / com:Sup>CH<com:Sub>2< / com:Sub>-, or -CH<com:Sub>2< / com:Sub>NR<com:Sup>6< / com:Sup>-; and R<com:Sup>6< / com:Sup> is H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl or -C(O)NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is cyclopentyl or cyclohexyl, wherein each cyclopentyl or cyclohexyl is optionally substituted with <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In some embodidments, <com:Math><semantics>ℝ3<annotation encoding="application / x-tex">\mathbb{R}^3< / annotation>< / semantics>< / com:Math> is cyclopentyl or cyclohexyl, wherein each cyclopentyl or cyclohexyl is optionally substituted with <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math> is -OH, halogen, oxo, <com:Math><semantics>−CN<annotation encoding="application / x-tex">-CN< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−SH<annotation encoding="application / x-tex">-SH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OH<annotation encoding="application / x-tex">-OH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NH2<annotation encoding="application / x-tex">-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2NH2<annotation encoding="application / x-tex">-S(O)_2NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OH<annotation encoding="application / x-tex">-C(O)OH< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−C(O)NH2<annotation encoding="application / x-tex">-C(O)NH_2< / annotation>< / semantics>< / com:Math>.

[0070] In some embodiments, compounds of the disclosure have the Formula (I-g) [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−g),<annotation encoding="application / x-tex">(I-g),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein each of R<com:Sup>1< / com:Sup>, R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>6< / com:Sup>, Ring B and R<com:Sup>10< / com:Sup> is as defined with respect to Formula (I) above and described in classes and subclasses herein, both singly and in combination.

[0071] In some embodiments, compounds of the disclosure have the Formula (I-h) [Image disponible dans le document PDF, Image available in the PDF document] (I-h), or a pharmaceutically acceptable salt thereof, wherein each of R<com:Sup>1< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>6< / com:Sup>, and R<com:Sup>7< / com:Sup> is as defined with respect to Formula (I) above and described in classes and subclasses herein, both singly and in combination.

[0072] In some embodiments, compounds of the disclosure have the Formula (I-h') [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−h′),<annotation encoding="application / x-tex">(I-h'),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein each of R<com:Sup>1< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>6< / com:Sup>, and R<com:Sup>7< / com:Sup> is as defined with respect to Formula (I) above and described in classes and subclasses herein, both singly and in combination.

[0073] In some embodiments, compounds of the disclosure have the Formula (I-h'') [Image disponible dans le document PDF, Image available in the PDF document] (I-h''), or a pharmaceutically acceptable salt thereof, wherein each of R<com:Sup>1< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>6< / com:Sup>, and R<com:Sup>7< / com:Sup> is as defined with respect to Formula (I) above and described in classes and subclasses herein, both singly and in combination.

[0074] In some embodiments, compounds of the disclosure have the Formula (I-i): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−i),<annotation encoding="application / x-tex">(I-i),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein, R<com:Sup>1< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(R5)2<annotation encoding="application / x-tex">-N(R^5)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−NHR5<annotation encoding="application / x-tex">-NHR^5< / annotation>< / semantics>< / com:Math>; R<com:Sup>5< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, heterocyclyl, aryl, or heteroaryl; each <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is -OH, halogen, oxo, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, -NO<com:Sub>2< / com:Sub>, -CN, -NH<com:Sub>2< / com:Sub>, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n< / com:Sub>- <com:Math><semantics>OR8<annotation encoding="application / x-tex">OR^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)R8′<annotation encoding="application / x-tex">-C(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^8< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−C(O)NR8R9<annotation encoding="application / x-tex">-C(O)NR^8R^9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHC1−C6<annotation encoding="application / x-tex">-NHC_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6)<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2C1−C6<annotation encoding="application / x-tex">-S(O)_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>SO2C1−C6<annotation encoding="application / x-tex">SO_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)(C1−C6)<annotation encoding="application / x-tex">-S(O)(C_1-C_6)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)N(C1−C6<annotation encoding="application / x-tex">-S(O)N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, or <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>S(O)(C1−C6<annotation encoding="application / x-tex">S(O)(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R6′<annotation encoding="application / x-tex">R^{6'}< / annotation>< / semantics>< / com:Math> is H or <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>alkyl; R<com:Sup>7< / com:Sup> is independently, at each occurrence, –H, halogen, –OH, –CN, –OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, –NH<com:Sub>2< / com:Sub>, – <com:Math><semantics>NHC1−C6<annotation encoding="application / x-tex">NHC_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2C1−C6<annotation encoding="application / x-tex">-S(O)_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl) <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)2OH<annotation encoding="application / x-tex">-S(O)_2OH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_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>, <com:Math><semantics>−C(O)NH(C1−C6<annotation encoding="application / x-tex">-C(O)NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−C(O)N(C1−C6<annotation encoding="application / x-tex">-C(O)N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−C(O)OH<annotation encoding="application / x-tex">-C(O)OH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OC1<annotation encoding="application / x-tex">-C(O)OC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1<annotation encoding="application / x-tex">-N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>SO2C1<annotation encoding="application / x-tex">SO_2C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)(C1<annotation encoding="application / x-tex">-S(O)(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)N(C1<annotation encoding="application / x-tex">-S(O)N(C_1< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH2<annotation encoding="application / x-tex">-S(O)_2NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>S(O)(C1−C6<annotation encoding="application / x-tex">S(O)(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl) or tetrazole; <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 each independently, at each occurrence, <com:Math><semantics>−H<annotation encoding="application / x-tex">-H< / annotation>< / semantics>< / com:Math>, <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup>; or R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> may combine with the atom to which they are both attached to form a spiroheterocyclyl, heterocyclyl, or heteroaryl, wherein the formed spiroheterocyclyl, heterocyclyl, or heteroaryl is optionally substituted with one or more <com:Math><semantics>ℝ10<annotation encoding="application / x-tex">\mathbb{R}^{10}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R8′<annotation encoding="application / x-tex">R^{8'}< / annotation>< / semantics>< / com:Math> is each independently, at each occurrence, <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>; or R<com:Sup>10< / com:Sup> is independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, –OH, halogen, oxo, –NO<com:Sub>2< / com:Sub>, –CN, -NH<com:Sub>2< / com:Sub>, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, -Oaryl, -Oheteroaryl, -NHC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6alkyl),−S(O)2N(C1−C6alkyl)2,−S(O)2C1−C6alkyl,−C(O)C1−C6alkyl,−C(O)NH2,−C(O)C1−C6alkyl)2<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6alkyl), -S(O)_2N(C_1-C_6alkyl)_2, -S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)NH(C1−C6alkyl),−NHC(O)C1−C6alkyl,−C(O)N(C1−C6alkyl)2,−C(O)OC1−C6alkyl,−N(C1−C6alkyl)2<annotation encoding="application / x-tex">C(O)NH(C_1-C_6alkyl), -NHC(O)C_1-C_6alkyl, -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl, -N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>SO2C1<annotation encoding="application / x-tex">SO_2C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)(C1<annotation encoding="application / x-tex">-S(O)(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)N(C1<annotation encoding="application / x-tex">-S(O)N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>S(O)(C1<annotation encoding="application / x-tex">S(O)(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>S(O)(C1<annotation encoding="application / x-tex">S(O)(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>S(O)(C1<annotation encoding="application / x-tex">S(O)(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>S(O)(C1<annotation encoding="application / x-tex">S(O)(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>S(O)(C1<annotation encoding="application / x-tex">S(O)(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>S(O)(C1<annotation encoding="application / x-tex">S(O)(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>S(O)(C<annotation encoding="application / x-tex">S(O)(C< / annotation>< / semantics>< / com:Math> C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>; wherein any two R<com:Sup>10< / com:Sup> when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R<com:Sup>10< / com:Sup> when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R<com:Sup>12< / com:Sup> is independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, - C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, - <com:Math><semantics>CN,−NH2,−OC1−C6<annotation encoding="application / x-tex">CN, -NH_2, -OC_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−NHC1−C6<annotation encoding="application / x-tex">-NHC_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>S(O)2N(C1−C6alkyl)2,−S(O)2C1−C6alkyl,−C(O)C1−C6alkyl,−C(O)NH2,−C(O)NH(C1−C6alkyl),−C(O)NH2,−C(O)NH2,−C(O)NH2,−C(O)NH2,−C(O)NH2,−C(O)NH2,−C(O)NH2,−C(O)NH2,−C(O)NH2,−C(O)NH2,−C(O)NH2,<annotation encoding="application / x-tex">S(O)_2N(C_1-C_6alkyl)_2, -S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)NH(C_1-C_6alkyl), -C(O)NH_2, -C(O)NH_2, -C(O)NH_2, -C(O)NH_2, -C(O)NH_2, -C(O)NH_2, -C(O)NH_2, -C(O)NH_2, -C(O)NH_2, -C(O)NH_2, -C(O)NH_2,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">C(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OC1−C6alkyl<annotation encoding="application / x-tex">-C(O)OC_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(C1−C6alkyl)SO2C1−C6alkyl<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)SO_2C_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">-S(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−N(C1−C6alkyl)S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>; and m is an integer from 0 to 5; n is an integer from 1 to 4; and q is an integer from 0 to 4.

[075] In some embodiments, compounds of the disclosure have the Formula (I-j): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−j),<annotation encoding="application / x-tex">(I-j),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein: R<com:Sup>1< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(R5)2<annotation encoding="application / x-tex">-N(R^5)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−NHR5<annotation encoding="application / x-tex">-NHR^5< / annotation>< / semantics>< / com:Math>; R<com:Sup>5< / com:Sup> is independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, heterocyclyl, aryl, or heteroaryl; [Image disponible dans le document PDF, Image available in the PDF document] spirocycloalkyl, spiroheterocyclyl, heteroaryl, halogen, oxo, –(CH<com:Sub>2< / com:Sub>)<com:Sub>n< / com:Sub>-OR<com:Sup>8< / com:Sup>, –C(O)R<com:Sup>8< / com:Sup>, –C(O)OR<com:Sup>8< / com:Sup>, or –C(O)NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>; R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are each independently, at each occurrence, –H, –C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, –C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, – C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, –C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; or R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> may combine with the atom to which they are both attached to form a spiroheterocyclyl, heterocyclyl, or heteroaryl, wherein the formed spiroheterocyclyl, heterocyclyl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^{8}< / annotation>< / semantics>< / com:Math> is each independently, at each occurrence, <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>- C<com:Sub>6< / com:Sub>alkynyl, –C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>; R<com:Sup>10< / com:Sup> is each independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>- C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, -CN, -NH<com:Sub>2< / com:Sub>, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, -Oaryl, -Oheteroaryl, -NHC<com:Sub>1< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2C1−C6<annotation encoding="application / x-tex">-S(O)_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)2N(C1−C6)<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)C1−C6alkyl,−C(O)NH2,−C(O)NH(C1−C6alkyl),−C(O)N(C1−C6alkyl)2,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O<annotation encoding="application / x-tex">C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O< / annotation>< / semantics>< / com:Math> [Image disponible dans le document PDF, Image available in the PDF document] C<com:Sub>6< / com:Sub>alkyl)S(O)(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>; wherein any two R<com:Sup>10< / com:Sup> when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R<com:Sup>10< / com:Sup> when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; [Image disponible dans le document PDF, Image available in the PDF document] n is an integer from 1 to 4.

[076] In some embodiments, for compounds of Formula (I-j) or a pharmaceutically acceptable salt thereof: R<com:Sup>1< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(R5)2<annotation encoding="application / x-tex">-N(R^5)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−NHR5<annotation encoding="application / x-tex">-NHR^5< / annotation>< / semantics>< / com:Math>; [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] spirocycloalkyl, spiroheterocyclyl, heteroaryl, halogen, oxo, –(CH<com:Sub>2< / com:Sub>)<com:Sub>n< / com:Sub>-OR<com:Sup>8< / com:Sup>, –C(O)R<com:Sup>8< / com:Sup>′, –C(O)OR<com:Sup>8< / com:Sup>, or –C(O)NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>; R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> are each independently, at each occurrence, -H, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, - C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, –C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; or R<com:Sup>8< / com:Sup> and R<com:Sup>9< / com:Sup> may combine with the atom to which they are both attached to form a spiroheterocyclyl, heterocyclyl, or heteroaryl, wherein the formed spiroheterocyclyl, heterocyclyl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; <com:Math><semantics>R8<annotation encoding="application / x-tex">R^{8}< / annotation>< / semantics>< / com:Math> is each independently, at each occurrence, <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>- C<com:Sub>6< / com:Sub>alkynyl, –C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>; or R<com:Sup>10< / com:Sup> is each independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>- C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, -CN, -NH<com:Sub>2< / com:Sub>, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, -Oaryl, -Oheteroaryl, -NHC<com:Sub>1< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2C1−C6<annotation encoding="application / x-tex">-S(O)_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)2N(C1−C6)<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)C1−C6alkyl,−C(O)NH2,−C(O)NH(C1−C6alkyl),−C(O)N(C1−C6alkyl)2,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O<annotation encoding="application / x-tex">C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(C1−C6alkyl)SO2C1−C6alkyl,−S(O)(C1−C6alkyl),−S(O)N(C1−C6alkyl)2,or−N(C1−C6alkyl)2<annotation encoding="application / x-tex">N(C_1-C_6alkyl)SO_2C_1-C_6alkyl, -S(O)(C_1-C_6alkyl), -S(O)N(C_1-C_6alkyl)_2, or -N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math> C<com:Sub>6< / com:Sub>alkyl)S(O)(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>; wherein any two R<com:Sup>10< / com:Sup> when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R<com:Sup>10< / com:Sup> when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> is independently, at each occurrence, <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, - <com:Math><semantics>CN,−NH2,−OC1−C6<annotation encoding="application / x-tex">CN, -NH_2, -OC_1-C_6< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−NHC1−C6<annotation encoding="application / x-tex">-NHC_1-C_6< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math> alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math> alkyl), <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>S(O)2N(C1−C6alkyl)2,−S(O)2C1−C6alkyl,−C(O)C1−C6alkyl,−C(O)NH2,−C(O)NH(C1−C6alkyl),−C(O)NH(C1−C6alkyl)2<annotation encoding="application / x-tex">S(O)_2N(C_1-C_6alkyl)_2, -S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)NH(C_1-C_6alkyl), -C(O)NH(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)N(C1−C6alkyl)2,−C(O)OC1−C6alkyl,−N(C1−C6alkyl)SO2C1−C6alkyl,−S(O)(C1−C6alkyl),<annotation encoding="application / x-tex">C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl, -N(C_1-C_6alkyl)SO_2C_1-C_6alkyl, -S(O)(C_1-C_6alkyl),< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−S(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">-S(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−N(C1−C6alkyl)S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>; and n is an integer from 1 to 4.

[077] In some embodiments, compounds of the disclosure have the Formula (I-k): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−k),<annotation encoding="application / x-tex">(I-k),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <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>alkyl; R<com:Sup>6< / com:Sup> is -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, wherein each cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R10<annotation encoding="application / x-tex">-R^{10}< / annotation>< / semantics>< / com:Math>; [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> is independently, at each occurrence, <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, - CN, -NH<com:Sub>2< / com:Sub>, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, -Oaryl, -Oheteroaryl, -NHC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -N(C<com:Sub>1< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2C1−C6<annotation encoding="application / x-tex">-S(O)_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_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>, <com:Math><semantics>−C(O)NH(C1−C6alkyl)<annotation encoding="application / x-tex">-C(O)NH(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHC(O)C1−C6alkyl<annotation encoding="application / x-tex">-NHC(O)C_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">-C(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OC1−C6alkyl<annotation encoding="application / x-tex">-C(O)OC_1-C_6alkyl< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>SO2C1−C6<annotation encoding="application / x-tex">SO_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)(C1−C6<annotation encoding="application / x-tex">-S(O)(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)N(C1−C6<annotation encoding="application / x-tex">-S(O)N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, or <com:Math><semantics>−N(C1−C6)<annotation encoding="application / x-tex">-N(C_1-C_6)< / annotation>< / semantics>< / com:Math> C<com:Sub>6< / com:Sub>alkyl)S(O)(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>; each R<com:Sup>12< / com:Sup> is independently halogen; m is an integer from 0 to 5.

[078] In some embodiments, compounds of the disclosure have the Formula (I-1): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−1),<annotation encoding="application / x-tex">(I-1),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <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>alkyl; R<com:Sup>6< / com:Sup> is –OH, halogen, oxo, –NO<com:Sub>2< / com:Sub>, –CN, –NH<com:Sub>2< / com:Sub>, –OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, -Oaryl, - Oheteroaryl, <com:Math><semantics>−NHC1<annotation encoding="application / x-tex">-NHC_1< / annotation>< / semantics>< / com:Math>-C6alkyl, <com:Math><semantics>−N(C1<annotation encoding="application / x-tex">-N(C_1< / annotation>< / semantics>< / com:Math>-C6alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1<annotation encoding="application / x-tex">-S(O)_2NH(C_1< / annotation>< / semantics>< / com:Math>-C6alkyl), <com:Math><semantics>−S(O)2N(C1<annotation encoding="application / x-tex">-S(O)_2N(C_1< / annotation>< / semantics>< / com:Math>-C6alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1<annotation encoding="application / x-tex">-S(O)_2NH(C_1< / annotation>< / semantics>< / com:Math>-C6alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1<annotation encoding="application / x-tex">-S(O)_2NH(C_1< / annotation>< / semantics>< / com:Math>-C6alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1<annotation encoding="application / x-tex">-S(O)_2NH(C_1< / annotation>< / semantics>< / com:Math>-C6alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1<annotation encoding="application / x-tex">-S(O)_2NH(C_1< / annotation>< / semantics>< / com:Math>-C6alkyl)<com:Sub>2< / com:Sub> <com:Math><semantics>S(O)2C1−C6alkyl,−C(O)C1−C6alkyl,−C(O)NH2,−C(O)NH(C1−C6alkyl),−C(O)N(C1−C6alkyl)2,−C(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)OC1<annotation encoding="application / x-tex">C(O)OC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1<annotation encoding="application / x-tex">-N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>SO2C1<annotation encoding="application / x-tex">SO_2C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)(C1<annotation encoding="application / x-tex">-S(O)(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)N(C1<annotation encoding="application / x-tex">-S(O)N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, or -N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl)S(O)(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R10<annotation encoding="application / x-tex">-R^{10}< / annotation>< / semantics>< / com:Math>; R<com:Sup>7< / com:Sup> is independently, at each occurrence, -H, halogen, -OH, -CN, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -NH<com:Sub>2< / com:Sub>, - <com:Math><semantics>NHC1−C6alkyl<annotation encoding="application / x-tex">NHC_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(C1−C6alkyl)2<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2NH(C1−C6alkyl)<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2N(C1−C6alkyl)2<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2C1−C6alkyl<annotation encoding="application / x-tex">-S(O)_2C_1-C_6alkyl< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)2OH<annotation encoding="application / x-tex">-S(O)_2OH< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)C1<annotation encoding="application / x-tex">-C(O)C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_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>, <com:Math><semantics>−C(O)NH(C1<annotation encoding="application / x-tex">-C(O)NH(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−C(O)N(C1<annotation encoding="application / x-tex">-C(O)N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−C(O)OH,−C(O)OC1−C6<annotation encoding="application / x-tex">-C(O)OH, -C(O)OC_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>SO2C1−C6<annotation encoding="application / x-tex">SO_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)(C1−C6<annotation encoding="application / x-tex">-S(O)(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)N(C1−C6)<annotation encoding="application / x-tex">-S(O)N(C_1-C_6)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH2<annotation encoding="application / x-tex">-S(O)_2NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>S(O)(C1−C6<annotation encoding="application / x-tex">S(O)(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl) or tetrazole; R<com:Sup>10< / com:Sup> is independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, - CN, -NH<com:Sub>2< / com:Sub>, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, -Oaryl, -Oheteroaryl, -NHC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -N(C<com:Sub>1< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2C1−C6<annotation encoding="application / x-tex">-S(O)_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1−C6<annotation encoding="application / x-tex">-C(O)C_1-C_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>, <com:Math><semantics>−C(O)NH(C1−C6alkyl)<annotation encoding="application / x-tex">-C(O)NH(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHC(O)C1−C6alkyl<annotation encoding="application / x-tex">-NHC(O)C_1-C_6alkyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">-C(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OC1−C6alkyl<annotation encoding="application / x-tex">-C(O)OC_1-C_6alkyl< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>SO2C1−C6<annotation encoding="application / x-tex">SO_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)(C1−C6<annotation encoding="application / x-tex">-S(O)(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)N(C1−C6<annotation encoding="application / x-tex">-S(O)N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)2, or <com:Math><semantics>−N(C1−C6)<annotation encoding="application / x-tex">-N(C_1-C_6)< / annotation>< / semantics>< / com:Math> C<com:Sub>6< / com:Sub>alkyl)S(O)(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>; each R<com:Sup>12< / com:Sup> is independently halogen; m is an integer from 0 to 5; and r is an integer from 0 to 5.

[079] In some embodiments, compounds of the disclosure have the Formula (I-m) [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−m),<annotation encoding="application / x-tex">(I-m),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt, thereof, wherein: <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>; [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is phenyl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>; R<com:Sup>10< / com:Sup> is each independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>- C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, -CN, -NH<com:Sub>2< / com:Sub>, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, -Oaryl, -Oheteroaryl, -NHC<com:Sub>1< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2C1−C6<annotation encoding="application / x-tex">-S(O)_2C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)2N(C1−C6)<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)C1−C6alkyl,−C(O)NH2,−C(O)NH(C1−C6alkyl),−C(O)N(C1−C6alkyl)2,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O)OC1−C6alkyl,−C(O<annotation encoding="application / x-tex">C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O)OC_1-C_6alkyl, -C(O< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(C1−C6alkyl)SO2C1−C6alkyl,−S(O)(C1−C6alkyl),−S(O)N(C1−C6alkyl)2,or−N(C1−C6alkyl)2<annotation encoding="application / x-tex">N(C_1-C_6alkyl)SO_2C_1-C_6alkyl, -S(O)(C_1-C_6alkyl), -S(O)N(C_1-C_6alkyl)_2, or -N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math> C<com:Sub>6< / com:Sub>alkyl)S(O)(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>; wherein any two R<com:Sup>10< / com:Sup> when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R<com:Sup>10< / com:Sup> when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; [Image disponible dans le document PDF, Image available in the PDF document] n is an integer from 1 to 4.

[080] In some embodiments, compounds of the disclosure have the Formula (I-n) [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−n),<annotation encoding="application / x-tex">(I-n),< / annotation>< / semantics>< / com:Math> or a pharmaceutically acceptable salt thereof, wherein: <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−C1<annotation encoding="application / x-tex">-C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkyl; <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is phenyl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>; R<com:Sup>10< / com:Sup> is independently, at each occurrence halogen, –OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, - Oaryl, or -Oheteroaryl, wherein each alkyl, cycloalkyl, aryl or heteroaryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>; R<com:Sup>12< / com:Sup> is independently halogen.

[081] In some embodiments, for compounds of Formula (I-n), or a pharmaceutically acceptable salt thereof: [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>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is phenyl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>; R<com:Sup>10< / com:Sup> is independently, at each occurrence halogen, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, - Oaryl, or -Oheteroaryl, wherein each alkyl, cycloalkyl, aryl or heteroaryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>; R<com:Sup>12< / com:Sup> is halogen.

[082] It will be appreciated that throughout the present disclosure, unless otherwise indicated, reference to a compound of Formula (I) is intended to also include formulae (I-a), (I-b), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), (I-c), d), (I-e), (I-f), (I-g), (I-h), (I-h'), (I-h''), (I-i), (I-j), (I-k), (I-l), (I-m), and (I-n) and compound species of such formulae disclosed herein.

[083] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OCR5<annotation encoding="application / x-tex">-OCR^5< / annotation>< / semantics>< / com:Math>.

[084] Compounds of the present disclosure can be compounds wherein <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>- C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, - OR<com:Sup>5< / com:Sup>, -N(R<com:Sup>5< / com:Sup>)<com:Sub>2< / com:Sub>, or -NHR<com:Sup>5< / com:Sup>. Compounds of the present disclosure can be compounds wherein R<com:Sup>1< / com:Sup> is -OR<com:Sup>5< / com:Sup>. Compounds of the present disclosure can be compounds wherein R<com:Sup>1< / com:Sup> is -OR<com:Sup>5< / com:Sup> and R<com:Sup>5< / com:Sup> is methyl.

[085] Compounds of the present disclosure can be compounds wherein R<com:Sup>5< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkyl, heterocyclyl, aryl, or heteroaryl. Compounds of the present disclosure can be compounds wherein R<com:Sup>5< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl. Compounds of the present disclosure can be compounds wherein R<com:Sup>5< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl. Compounds of the present disclosure can be compounds wherein R<com:Sup>5< / com:Sup> is methyl.

[086] Compounds of the present disclosure can be compounds wherein R<com:Sup>6< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, halogen, oxo, <com:Math><semantics>−(CH2)n<annotation encoding="application / x-tex">-(CH_2)_n< / annotation>< / semantics>< / com:Math>-OR<com:Sup>8< / com:Sup>, <com:Math><semantics>−C(O)R8<annotation encoding="application / x-tex">-C(O)R^8< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^8< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−C(O)NR8R9<annotation encoding="application / x-tex">-C(O)NR^8R^9< / annotation>< / semantics>< / com:Math>, wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup>. Compounds of the present disclosure can be compounds wherein R<com:Sup>6< / com:Sup> is -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup>. Compounds of the present disclosure can be compounds wherein <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is any optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>. Compounds of the present disclosure can be compounds wherein R<com:Sup>6< / com:Sup> is phenyl optionally substituted with one or more R<com:Sup>10< / com:Sup>. Compounds of the present disclosure can be compounds wherein R<com:Sup>6< / com:Sup> is phenyl substituted with one <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>. Compounds of the present disclosure can be compounds wherein <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is phenyl substituted with two <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>.

[087] Compounds of the present disclosure can be compounds wherein R<com:Sup>10< / com:Sup> is independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, –OH, halogen, oxo, –NO<com:Sub>2< / com:Sub>, –CN, –NH<com:Sub>2< / com:Sub>, –OC<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, -Oaryl, -Oheteroaryl, -NHC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl)<com:Sub>2< / com:Sub>, - <com:Math><semantics>S(O)2NH(C1−C6alkyl),−S(O)2N(C1−C6alkyl)2,−S(O)2C1−C6alkyl,−C(O)C1−C6alkyl,−C(O)NH2,−C(O)C1−C6alkyl)2<annotation encoding="application / x-tex">S(O)_2NH(C_1-C_6alkyl), -S(O)_2N(C_1-C_6alkyl)_2, -S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)NH(C1−C6alkyl),−C(O)N(C1−C6alkyl)2,−C(O)OC1−C6alkyl,−N(C1−C6alkyl)SO2C1−C6alkyl,<annotation encoding="application / x-tex">C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl, -N(C_1-C_6alkyl)SO_2C_1-C_6alkyl,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">-S(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−N(C1−C6alkyl)S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>. Compounds of the present disclosure can be compounds wherein R<com:Sup>10< / com:Sup> is independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, CN, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, or -NHC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl)<com:Sub>2< / com:Sub> wherein each alkyl, cycloalkyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>. Compounds of the present disclosure can be compounds wherein R<com:Sup>10< / com:Sup> is independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, or halogen wherein each alkyl, or cycloalkyl, is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>. Compounds of the present disclosure can be compounds wherein R<com:Sup>10< / com:Sup> is independently, at each occurrence, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, or halogen wherein each alkyl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math>.

[088] Compounds of the present disclosure can be compounds wherein R<com:Sup>12< / com:Sup> is independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, –OH, halogen, oxo, –NO<com:Sub>2< / com:Sub>, –CN, –NH<com:Sub>2< / com:Sub>, –OC<com:Sub>1< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−NHC1−C6<annotation encoding="application / x-tex">-NHC_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6)<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>S(O)2C1−C6alkyl,−C(O)C1−C6alkyl,−C(O)NH2,−C(O)NH(C1−C6alkyl),−C(O)N(C1−C6alkyl)2,−C(O)N(C1−C6alkyl)2<annotation encoding="application / x-tex">S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)N(C_1-C_6alkyl)_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)OC1<annotation encoding="application / x-tex">C(O)OC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1<annotation encoding="application / x-tex">-N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>SO2C1<annotation encoding="application / x-tex">SO_2C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)(C1<annotation encoding="application / x-tex">-S(O)(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)N(C1<annotation encoding="application / x-tex">-S(O)N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, or <com:Math><semantics>−N(C1−C6alkyl)S(O)(C1−C6alkyl)<annotation encoding="application / x-tex">-N(C_1-C_6alkyl)S(O)(C_1-C_6alkyl)< / annotation>< / semantics>< / com:Math>. Compounds of the present disclosure can be compounds wherein R<com:Sup>12< / com:Sup> is independently, at each occurrence, halogen. Compounds of the present disclosure can be compounds wherein <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> is fluoro. Compounds of the present disclosure can be compounds wherein <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> is chloro.

[089] Compounds of the present disclosure can be compounds wherein <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−C1<annotation encoding="application / x-tex">-C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>6< / com:Sub>alkyl; R<com:Sup>6< / com:Sup> is -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup>; R<com:Sup>10< / com:Sup> is independently, at each occurrence, – C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, –OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, or halogen wherein each alkyl, or cycloalkyl, is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math> is halogen.

[090] Compounds of the present disclosure can be compounds wherein <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−C1<annotation encoding="application / x-tex">-C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>3< / com:Sub>alkyl; R<com:Sup>6< / com:Sup> is aryl optionally substituted with one or more R<com:Sup>10< / com:Sup>; R<com:Sup>10< / com:Sup> is independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, or halogen wherein each alkyl, or cycloalkyl, is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math> is halogen.

[091] Compounds of the present disclosure can be compounds wherein <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−C1<annotation encoding="application / x-tex">-C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>3< / com:Sub>alkyl; R<com:Sup>6< / com:Sup> is aryl substituted with one R<com:Sup>10< / com:Sup>; R<com:Sup>10< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -OC<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, or halogen wherein each alkyl, or cycloalkyl, is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math> and –R<com:Sup>12< / com:Sup> is halogen.

[092] Compounds of the present disclosure can be compounds wherein <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−C1<annotation encoding="application / x-tex">-C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>3< / com:Sub>alkyl; <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is aryl substituted with two <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> is independently, at each occurrence, <com:Math><semantics>−OC1<annotation encoding="application / x-tex">-OC_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>6< / com:Sub>alkyl or halogen wherein each alkyl is optionally substituted with one or more –R<com:Sup>12< / com:Sup> and –R<com:Sup>12< / com:Sup> is halogen.

[093] Compounds of the present disclosure can be compounds wherein <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is methyl; R<com:Sup>6< / com:Sup> is phenyl substituted with two R<com:Sup>10< / com:Sup>; R<com:Sup>10< / com:Sup> is independently, at each occurrence, –OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl or halogen wherein each alkyl is optionally substituted with one or more <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>−R12<annotation encoding="application / x-tex">-R^{12}< / annotation>< / semantics>< / com:Math> is halogen.

[094] Compounds of the present disclosure can be compounds wherein <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is methyl; and <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is phenyl.

[095] Compounds of the present disclosure can be compounds wherein R<com:Sup>6< / com:Sup> is aryl, optionally substituted with one or two R<com:Sup>10< / com:Sup>, wherein R<com:Sup>10< / com:Sup> is independently, at each occurrence, halogen or – OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, wherein -OC<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl is optionally substituted with halogen.

[096] Compounds of the present disclosure can comprise aryl, wherein aryl can be ring systems having a total of five to fourteen ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains 3 to 7 ring members. For example, aryl can include, but is not limited to, phenyl.

[097] Compounds of the present disclosure can comprise heteroaryl, wherein heteroaryl is a group having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math> electrons shared in a cyclic array; and / or having, in addition to carbon atoms, from one to five heteroatoms wherein the term "heteroatom" refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. For example, heteroaryl can include, but are is not limited to, pyridine, indole, benzapyrazole, benzoxale, furopyridine, or isoquinoline.

[098] Compounds of the present disclosure can comprise heterocyclyl, wherein heterocyclyl is a stable 5– to 7–membered monocyclic or 7–10–membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above. For example, heterocyclyl can include, but are is not limited to, dihydrofuran, dihydrofuropyrine or dihydroisofuran.

[099] In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−OR5<annotation encoding="application / x-tex">-OR^5< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−N(R5)2<annotation encoding="application / x-tex">-N(R^5)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHR5<annotation encoding="application / x-tex">-NHR^5< / annotation>< / semantics>< / com:Math>, or <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>alkyl. In some embodiments, R<com:Sup>1< / com:Sup> is –OR<com:Sup>5< / com:Sup> or –C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl. In some embodiments, R<com:Sup>5< / com:Sup> of R<com:Sup>1< / com:Sup> is –C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl. In some embodiments, R<com:Sup>1< / com:Sup> is -OCH<com:Sub>3< / com:Sub>. In some embodiments, R<com:Sup>1< / com:Sup> is -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, or aryl. In some embodiments, R<com:Sup>1< / com:Sup> is – C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl. In some embodiments, R<com:Sup>1< / com:Sup> is methyl, ethyl or propyl. In some embodiments, R<com:Sup>1< / com:Sup> is methyl. In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl. In some embodiments, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> is aryl.

[0100] In some embodiments, <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−H<annotation encoding="application / x-tex">-H< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <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>alkyl optionally substituted with one or more <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is any optionally substituted with one or more <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkyl optionally substituted with one or more <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>alkyl substituted with anyl or heteroaryl, wherein each aryl or heteroaryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>. In some embodiments <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is methyl optionally substituted with one or more <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math>. In some embodiments <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is ethyl optionally substituted with one or more <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>alkyl substituted with aryl or heteroaryl, wherein each aryl or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup>, and wherein <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is cyclohexyl optionally substituted with one or more <com:Math><semantics>−C(O)OH<annotation encoding="application / x-tex">-C(O)OH< / annotation>< / semantics>< / com:Math>.

[0101] In some embodiments, <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> or R<com:Sup>3< / com:Sup> is -H. In some embodiments, R<com:Sup>3< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl. In some embodiments, R<com:Sup>3< / com:Sup> is heterocyclyl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is heteroaryl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is spirocycloalkyl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is spiroheterocyclyl optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>ℝ3<annotation encoding="application / x-tex">\mathbb{R}^3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>ℂ3<annotation encoding="application / x-tex">\mathbb{C}_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is aryl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is cyclohexyl optionally substituted with one or more <com:Math><semantics>−ℝ7<annotation encoding="application / x-tex">-\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>ℝ3<annotation encoding="application / x-tex">\mathbb{R}^3< / annotation>< / semantics>< / com:Math> is cyclohexyl optionally substituted with one or more <com:Math><semantics>−C(O)OH<annotation encoding="application / x-tex">-C(O)OH< / annotation>< / semantics>< / com:Math>.

[0102] In some embodiments, <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is –H. In some embodiments, R<com:Sup>3< / com:Sup> is –C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl. In some embodiments, R<com:Sup>3< / com:Sup> is heterocyclyl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is cyclopropyl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is cyclobutyl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is cyclopentyl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is cyclohexyl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is heteroaryl optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>ℝ3<annotation encoding="application / x-tex">\mathbb{R}^3< / annotation>< / semantics>< / com:Math> is spirocycloalkyl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is spiroheterocyclyl optionally substituted with one or more R<com:Sup>7< / com:Sup>. In some embodiments, R<com:Sup>3< / com:Sup> is C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>ℝ3<annotation encoding="application / x-tex">\mathbb{R}^3< / annotation>< / semantics>< / com:Math> is any optionally substituted with one or more <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is cyclohexyl optionally substituted with one or more <com:Math><semantics>−R7<annotation encoding="application / x-tex">-R^7< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is cyclohexyl optionally substituted with one or more – <com:Math><semantics>C(O)OH<annotation encoding="application / x-tex">C(O)OH< / annotation>< / semantics>< / com:Math>.

[0103] In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>4< / com:Sup> are independently hydrogen, halogen, -OH, -CN, or - NH<com:Sub>2< / com:Sub>. In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>4< / com:Sup> are –H. In some embodiments, R<com:Sup>4< / com:Sup> and R<com:Sup>4< / com:Sup> are halogen.

[0104] In some embodiments, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkyl, heterocyclyl, aryl, or heteroaryl. In some embodiments, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <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>alkyl. In some embodiments, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−C1<annotation encoding="application / x-tex">-C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkyl. In some embodiments, R<com:Sup>5< / com:Sup> is methyl. In some embodiments, R<com:Sup>5< / com:Sup> is ethyl.

[0105] In some embodiments, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkyl, <com:Math><semantics>−C4<annotation encoding="application / x-tex">-C_4< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, –OH, halogen, oxo, –CN, –SR<com:Sup>8< / com:Sup>, <com:Math><semantics>−OR8<annotation encoding="application / x-tex">-OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n−OR8<annotation encoding="application / x-tex">-(CH_{2})_{n}-OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHR8<annotation encoding="application / x-tex">-NHR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8R9<annotation encoding="application / x-tex">-NR^{8}R^{9}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2NR8R9<annotation encoding="application / x-tex">-S(O)_{2}NR^{8}R^{9}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2R8′<annotation encoding="application / x-tex">-S(O)_{2}R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)R8′<annotation encoding="application / x-tex">-C(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <Formule mathématique disponible dans le document PDF, Math available in the PDF document>-C(O)OR^{ <com:Math><semantics>C(O)NR8R9<annotation encoding="application / x-tex">C(O)NR^8R^9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8C(O)R9′<annotation encoding="application / x-tex">-NR^8C(O)R^{9'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8S(O)2R9′<annotation encoding="application / x-tex">-NR^8S(O)_2R^{9'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)R8′<annotation encoding="application / x-tex">-S(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)NR8R9<annotation encoding="application / x-tex">-S(O)NR^8R^9< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−NR8S(O)R9<annotation encoding="application / x-tex">-NR^8S(O)R^9< / annotation>< / semantics>< / com:Math>, wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkyl, <com:Math><semantics>−C4<annotation encoding="application / x-tex">-C_4< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkenyl, heterocyclyl, or aryl. In some embodiments, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is <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>alkyl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is any optionally substituted with one or more R<com:Sup>10< / com:Sup>. In some embodiments, R<com:Sup>6< / com:Sup> is heteroaryl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−C(O)OH<annotation encoding="application / x-tex">-C(O)OH< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is halogen. In some embodiments, R<com:Sup>6< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, halogen, oxo, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n< / com:Sub>-OR<com:Sup>8< / com:Sup>, -C(O)R<com:Sup>8< / com:Sup>, - C(O)OR<com:Sup>8< / com:Sup>, or -C(O)NR<com:Sup>8< / com:Sup>R<com:Sup>9< / com:Sup>, wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R<com:Sup>10< / com:Sup>.

[0106] In some embodiments, <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkyl, <com:Math><semantics>−C4<annotation encoding="application / x-tex">-C_4< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, –OH, halogen, oxo, –CN, –SR<com:Sup>8< / com:Sup>, <com:Math><semantics>−OR8<annotation encoding="application / x-tex">-OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)n−OR8<annotation encoding="application / x-tex">-(CH_{2})_{n}-OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NHR8<annotation encoding="application / x-tex">-NHR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8R9<annotation encoding="application / x-tex">-NR^{8}R^{9}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2NR8R9<annotation encoding="application / x-tex">-S(O)_{2}NR^{8}R^{9}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)2R8′<annotation encoding="application / x-tex">-S(O)_{2}R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)R8′<annotation encoding="application / x-tex">-C(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)OR8<annotation encoding="application / x-tex">-C(O)OR^{8}< / annotation>< / semantics>< / com:Math>, <Formule mathématique disponible dans le document PDF, Math available in the PDF document>-C(O)OR^{ <com:Math><semantics>C(O)NR8R9<annotation encoding="application / x-tex">C(O)NR^8R^9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8C(O)R9′<annotation encoding="application / x-tex">-NR^8C(O)R^{9'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NR8S(O)2R9′<annotation encoding="application / x-tex">-NR^8S(O)_2R^{9'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)R8′<annotation encoding="application / x-tex">-S(O)R^{8'}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−S(O)NR8R9<annotation encoding="application / x-tex">-S(O)NR^8R^9< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−NR8S(O)R9′<annotation encoding="application / x-tex">-NR^8S(O)R^{9'}< / annotation>< / semantics>< / com:Math>, wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, or aryl. In some embodiments R<com:Sup>7< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math> is any optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math> is heteroaryl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>−C(O)OH<annotation encoding="application / x-tex">-C(O)OH< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R7<annotation encoding="application / x-tex">R^7< / annotation>< / semantics>< / com:Math> is halogen.

[0107] In some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, –C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^{8}< / annotation>< / semantics>< / com:Math> is –H. In some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^{8}< / annotation>< / semantics>< / com:Math> is –C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, or aryl, wherein R<com:Sup>8< / com:Sup> is optionally substituted with <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^{8}< / annotation>< / semantics>< / com:Math> is <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>alkyl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^{8}< / annotation>< / semantics>< / com:Math> is any optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^8< / annotation>< / semantics>< / com:Math> is heteroaryl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>.

[0108] In some embodiments, <com:Math><semantics>R8′<annotation encoding="application / x-tex">R^{8'}< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R8′<annotation encoding="application / x-tex">R^{8'}< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkyl, <com:Math><semantics>−C4<annotation encoding="application / x-tex">-C_4< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, or aryl, wherein R<com:Sup>8< / com:Sup> is optionally substituted with R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>. In some embodiments, <com:Math><semantics>R8′<annotation encoding="application / x-tex">R^{8'}< / annotation>< / semantics>< / com:Math> is <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>alkyl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>. In some embodiments, R<com:Sup>8< / com:Sup> is anyloptionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>. In some embodiments, <com:Math><semantics>R8<annotation encoding="application / x-tex">R^{8}< / annotation>< / semantics>< / com:Math> is heteroaryl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>.

[0109] In some embodiments, <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>. In some embodiments, R<com:Sup>9< / com:Sup> is –H. In some embodiments, R<com:Sup>9< / com:Sup> is –C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, or aryl, wherein R<com:Sup>9< / com:Sup> is optionally substituted with <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is <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>alkyl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is any optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R9<annotation encoding="application / x-tex">R^9< / annotation>< / semantics>< / com:Math> is heteroaryl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>.

[0110] In some embodiments, <com:Math><semantics>R9<annotation encoding="application / x-tex">R^{9}< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R9<annotation encoding="application / x-tex">R^{9}< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkyl, <com:Math><semantics>−C4<annotation encoding="application / x-tex">-C_4< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, or aryl, wherein R<com:Sup>9< / com:Sup> is optionally substituted with R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>. In some embodiments, <com:Math><semantics>R9<annotation encoding="application / x-tex">R^{9}< / annotation>< / semantics>< / com:Math> is <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>alkyl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>. In some embodiments, R<com:Sup>9< / com:Sup> is anyloptionally substituted with one or more R<com:Sup>10< / com:Sup> or R<com:Sup>11< / com:Sup>. In some embodiments, <com:Math><semantics>R9<annotation encoding="application / x-tex">R^{9}< / annotation>< / semantics>< / com:Math>' is heteroaryl optionally substituted with one or more <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>.

[0111] In some embodiments, <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> is <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>alkyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkenyl, <com:Math><semantics>−C2<annotation encoding="application / x-tex">-C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkynyl, <com:Math><semantics>−C3<annotation encoding="application / x-tex">-C_3< / annotation>< / semantics>< / com:Math>- C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, -NO<com:Sub>2< / com:Sub>, -CN, <com:Math><semantics>−NH2<annotation encoding="application / x-tex">-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−OC1−C6<annotation encoding="application / x-tex">-OC_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−NHC1−C6<annotation encoding="application / x-tex">-NHC_1-C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1−C6<annotation encoding="application / x-tex">-N(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2NH(C1−C6<annotation encoding="application / x-tex">-S(O)_2NH(C_1-C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)2N(C1−C6)<annotation encoding="application / x-tex">-S(O)_2N(C_1-C_6)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−S(O)2C1<annotation encoding="application / x-tex">-S(O)_2C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)C1<annotation encoding="application / x-tex">-C(O)C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_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>, <com:Math><semantics>−C(O)NH(C1<annotation encoding="application / x-tex">-C(O)NH(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−C(O)N(C1<annotation encoding="application / x-tex">-C(O)N(C_1< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>−C(O)OC1<annotation encoding="application / x-tex">-C(O)OC_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−N(C1<annotation encoding="application / x-tex">-N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl)<com:Math><semantics>SO2C1<annotation encoding="application / x-tex">SO_2C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−S(O)(C1<annotation encoding="application / x-tex">-S(O)(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl), <com:Math><semantics>−S(O)N(C1<annotation encoding="application / x-tex">-S(O)N(C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>6< / com:Sub>alkyl)<com:Sub>2< / com:Sub>, or -N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl)S(O)(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more <com:Math><semantics>−ℝ12<annotation encoding="application / x-tex">-\mathbb{R}^{12}< / annotation>< / semantics>< / com:Math>. In some embodiments, R<com:Sup>10< / com:Sup> is -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>- <com:Math><semantics>C8<annotation encoding="application / x-tex">C_8< / annotation>< / semantics>< / com:Math>cycloalkenyl, heterocyclyl, heteroaryl, aryl, wherein <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> is substituted with <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math>. In some embodiments, <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> is halogen. In some embodiments, <com:Math><semantics>R10<annotation encoding="application / x-tex">R^{10}< / annotation>< / semantics>< / com:Math> is each independently, at each occurrence, -C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, -C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, -C<com:Sub>3< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkyl, -C<com:Sub>4< / com:Sub>-C<com:Sub>8< / com:Sub>cycloalkenyl, heterocyclyl, heteroa...

Claims

1. A compound of Formula (I-d): [Image disponible dans le document PDF, Image available in the PDF document] ( I − d ) (I-d) or a pharmaceutically acceptable salt thereof, wherein: Ring B represents –C 3 -C 8 cycloalkyl, –C 4 -C 8 cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, or heteroaryl; R 1 R^1 is- O R 5 OR^5 or − C 1 -C_1 - C 6 C_6 alkyl; [Image disponible dans le document PDF, Image available in the PDF document] C8cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R 7 ; R 4 and R 4 are each independently –H, halogen, –OH, –CN, or –NH 2 ; R 5 is -C 1 -C 6 alkyl, -C 3 -C 8 cycloalkyl, heterocyclyl, aryl, or heteroaryl; R 7 is independently, at each occurrence, −H, −C 1 -C 6 alkyl, -C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, − O H -OH , halogen, oxo, − C N -CN , − S R 8 -SR^8 , − O R 8 -OR^8 , − ( C H 2 ) n − O R 8 -(CH_2)_n-OR^8 , − N H R 8 -NHR^8 , − N R 8 R 9 -NR^8R^9 , [Image disponible dans le document PDF, Image available in the PDF document] − S ( O ) R 8 ′ -S(O)R^{8'} , − S ( O ) N R 8 R 9 -S(O)NR^{8}R^{9} , or − N R 8 S ( O ) R 9 ′ -NR^{8}S(O)R^{9'} , wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with ( R 10 ) m (R^{10})_m ; wherein any two R 7 , when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R 7 , when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R 8 and R 9 are each independently, at each occurrence, –H, –C 1 -C 6 alkyl, –C 2 -C 6 alkenyl, -C 2 -C 6 alkynyl, -C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R 10 R^{10} or R 11 R^{11} ; or R 8 and R 9 may combine with the atom to which they are both attached to form a -C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed − C 3 -C_3 - C 8 C_8 cycloalkyl, − C 4 -C_4 - C 8 C_8 cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R 10 R^{10} or R 11 R^{11} ; R 8' and R 9' are each independently, at each occurrence, -C 1 -C 6 alkyl, -C 2 -C 6 alkenyl, -C 2 -C 6 alkynyl, -C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R 10 or R 11 ; or R 8 and R 9 may combine with the atom to which they are both attached to form a – C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed -C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R 10 R^{10} or R 11 R^{11} ; R 10 and R 11 are each independently, at each occurrence, –H, –C 1 -C 6 alkyl, –C 2 - C6alkenyl, -C2-C6alkynyl, -C3-C8cycloalkyl, -C4-C8cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, − N O 2 -NO_2 , − C N -CN , − N H 2 -NH_2 , − O C 1 -OC_1 - C 6 C_6 alkyl, − N H C 1 -NHC_1 - C 6 C_6 alkyl, − N ( C 1 -N(C_1 - C 6 C_6 alkyl) 2 , − S ( O ) 2 N H ( C 1 − C 6 a l k y l ) , − S ( O ) 2 N ( C 1 − C 6 a l k y l ) 2 , − S ( O ) 2 C 1 − C 6 a l k y l , − C ( O ) C 1 − C 6 a l k y l , − C ( O ) N H 2 , − C ( O ) 2 N H ( C 1 − C 6 a l k y l ) 2 -S(O)_2NH(C_1-C_6alkyl), -S(O)_2N(C_1-C_6alkyl)_2, -S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2, -C(O)_2NH(C_1-C_6alkyl)_2 C ( O ) N H ( C 1 − C 6 a l k y l ) , − C ( O ) N ( C 1 − C 6 a l k y l ) 2 , − C ( O ) O C 1 − C 6 a l k y l , C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl, − N ( C 1 − C 6 a l k y l ) S O 2 C 1 − C 6 a l k y l , − S ( O ) ( C 1 − C 6 a l k y l ) , − S ( O ) N ( C 1 − C 6 a l k y l ) 2 , o r -N(C_1-C_6alkyl)SO_2C_1-C_6alkyl, -S(O)(C_1-C_6alkyl), -S(O)N(C_1-C_6alkyl)_2, or -N(C 1 -C 6 alkyl)S(O)(C 1 -C 6 alkyl), wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more - R 12 R^{12} : wherein any two R 10 R^{10} or any two R 11 R^{11} , when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R 10 R^{10} or any two R 11 R^{11} , when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R 12 R^{12} is independently, at each occurrence, − H -H , − C 1 -C_1 - C 6 C_6 alkyl, − C 2 -C_2 - C 6 C_6 alkenyl, -C 2 -C 6 alkynyl, -C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, − N O 2 -NO_2 , − C N -CN , − N H 2 -NH_2 , − O C 1 -OC_1 - C 6 C_6 alkyl, − N H C 1 -NHC_1 - C 6 C_6 alkyl, − N ( C 1 -N(C_1 - C 6 C_6 alkyl) 2 , − S ( O ) 2 N H ( C 1 − C 6 a l k y l ) , − S ( O ) 2 N ( C 1 − C 6 a l k y l ) 2 , − S ( O ) 2 C 1 − C 6 a l k y l , − C ( O ) C 1 − C 6 a l k y l , − C ( O ) N H 2 , -S(O)_2NH(C_1-C_6alkyl), -S(O)_2N(C_1-C_6alkyl)_2, -S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2, − C ( 0 ) N H ( C 1 − C 6 a l k y l ) , − C ( 0 ) N ( C 1 − C 6 a l k y l ) 2 , − C ( 0 ) O C 1 − C 6 a l k y l , -C(0)NH(C_1-C_6alkyl), -C(0)N(C_1-C_6alkyl)_2, -C(0)OC_1-C_6alkyl, − N ( C 1 − C 6 a l k y l ) S O 2 C 1 − C 6 a l k y l , − S ( O ) ( C 1 − C 6 a l k y l ) , − S ( O ) N ( C 1 − C 6 a l k y l ) 2 -N(C_1-C_6alkyl)SO_2C_1-C_6alkyl, -S(O)(C_1-C_6alkyl), -S(O)N(C_1-C_6alkyl)_2 , or − N ( C 1 − C 6 a l k y l ) S ( O ) ( C 1 − C 6 a l k y l ) ; -N(C_1-C_6alkyl)S(O)(C_1-C_6alkyl); m is an integer from 1 to 4; n is an integer from 1 to 4; and p is an integer from 1 to 2.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 5 is -C 1 -C 6 alkyl.

3. The compound of claim 1 or claim 2 or a pharmaceutically acceptable salt thereof, wherein R 1 is –OCH 3 .

4. The compound of any one of claims 1-3 or pharmaceutically acceptable salt thereof, wherein R 3 is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl optionally substituted with one or more − R 7 -R^7 .

5. The compound of any one of claims 1-4 or a pharmaceutically acceptable salt thereof, wherein R 3 R^3 is cyclohexyl optionally substituted with one or more − R 7 -R^7 .

6. The compound of any one of claims 1-5 or a pharmaceutically acceptable salt thereof, wherein Ring B is aryl.

7. A compound which 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] [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] [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] [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] [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] [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] [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] [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] [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] [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] or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 which 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] [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt thereof.

9. A compound of Formula (I-e): [Image disponible dans le document PDF, Image available in the PDF document] (I-e), or a pharmaceutically acceptable salt thereof, wherein: R 6 and R 7 are each independently, at each occurrence, –H, –C 1 -C 6 alkyl, -C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, heterocyclyl, aryl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, − O H -OH , halogen, oxo, − C N -CN , − S R 8 -SR^8 , − O R 8 -OR^8 , − ( C H 2 ) n − O R 8 -(CH_2)_n-OR^8 , − N H R 8 -NHR^8 , − N R 8 R 9 -NR^8R^9 , − S ( O ) 2 N R 8 R 9 -S(O)_2NR^8R^9 , − S ( O ) 2 R 8 -S(O)_2R^8 , − C ( O ) R 8 -C(O)R^8 , − C ( O ) O R 8 -C(O)OR^8 , − C ( O ) N R 8 R 9 -C(O)NR^8R^9 , − N R 8 C ( O ) R 9 -NR^8C(O)R^9 , − N R 8 S ( O ) 2 R 9 -NR^8S(O)_2R^9 , − S ( O ) R 8 ′ -S(O)R^{8'} , − S ( O ) N R 8 R 9 -S(O)NR^{8}R^{9} , or − N R 8 S ( O ) R 9 ′ -NR^{8}S(O)R^{9'} , wherein each alkyl, cycloalkyl, heterocyclyl, spirocycloalkyl, spiroheterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R 10 ; wherein any two R 6 or any two R 7 , when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R 6 or any two R 7 , when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R 8 R^8 and R 9 R^9 are each independently, at each occurrence, − H -H , − C 1 -C_1 - C 6 C_6 alkyl, − C 2 -C_2 - C 6 C_6 alkenyl, -C 2 -C 6 alkynyl, -C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R 10 or R 11 ; or R 8 R^8 and R 9 R^9 may combine with the atom to which they are both attached to form a − C 3 -C_3 - C8cycloalkyl, -C4-C8cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed − C 3 -C_3 - C 8 C_8 cycloalkyl, − C 4 -C_4 - C 8 C_8 cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R 10 R^{10} or R 11 R^{11} ; R 8' and R 9' are each independently, at each occurrence, -C 1 -C 6 alkyl, -C 2 -C 6 alkenyl, -C2-C6alkynyl, -C3-C8cycloalkyl, -C4-C8cycloalkenyl, heterocyclyl, aryl, heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more R 10 or R 11 ; or R 8 and R 9 may combine with the atom to which they are both attached to form a – C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl, wherein the formed -C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, spirocycloalkyl, spiroheterocyclyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more R 10 R^{10} or R 11 R^{11} ; R 10 and R 11 are each independently, at each occurrence, –H, –C 1 -C 6 alkyl, –C 2 - C6alkenyl, -C2-C6alkynyl, -C3-C8cycloalkyl, -C4-C8cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, halogen, oxo, − N O 2 -NO_2 , − C N -CN , − N H 2 -NH_2 , − O C 1 -OC_1 - C 6 C_6 alkyl, − N H C 1 -NHC_1 - C 6 C_6 alkyl, − N ( C 1 -N(C_1 - C 6 C_6 alkyl) 2 , − S ( O ) 2 N H ( C 1 − C 6 a l k y l ) , − S ( O ) 2 N ( C 1 − C 6 a l k y l ) 2 , − S ( O ) 2 C 1 − C 6 a l k y l , − C ( O ) C 1 − C 6 a l k y l , − C ( O ) N H 2 , − -S(O)_2NH(C_1-C_6alkyl), -S(O)_2N(C_1-C_6alkyl)_2, -S(O)_2C_1-C_6alkyl, -C(O)C_1-C_6alkyl, -C(O)NH_2, - C ( O ) N H ( C 1 − C 6 a l k y l ) , − C ( O ) N ( C 1 − C 6 a l k y l ) 2 , − C ( O ) O C 1 − C 6 a l k y l , C(O)NH(C_1-C_6alkyl), -C(O)N(C_1-C_6alkyl)_2, -C(O)OC_1-C_6alkyl, − N ( C 1 − C 6 a l k y l ) S O 2 C 1 − C 6 a l k y l , − S ( O ) ( C 1 − C 6 a l k y l ) , − S ( O ) N ( C 1 − C 6 a l k y l ) 2 , o r -N(C_1-C_6alkyl)SO_2C_1-C_6alkyl, -S(O)(C_1-C_6alkyl), -S(O)N(C_1-C_6alkyl)_2, or − N ( C 1 − C 6 a l k y l ) S ( O ) ( C 1 − C 6 a l k y l ) -N(C_1-C_6alkyl)S(O)(C_1-C_6alkyl) , wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, heteroaryl, or aryl is optionally substituted with one or more - R 12 R^{12} : wherein any two R 10 R^{10} or any two R 11 R^{11} , when on non-adjacent atoms, can combine to form a bridging cycloalkyl or heterocyclyl; wherein any two R 10 R^{10} or any two R 11 R^{11} , when on adjacent atoms, can combine to form a cycloalkyl, heterocyclyl, aryl or heteroaryl; R 12 R^{12} is independently, at each occurrence, -H, -C 1 -C 6 alkyl, -C 2 -C 6 alkenyl, -C 2 -C 6 alkynyl, -C 3 -C 8 cycloalkyl, -C 4 -C 8 cycloalkenyl, heterocyclyl, heteroaryl, aryl, -OH, [Image disponible dans le document PDF, Image available in the PDF document] n is an integer from 1 to 4.

10. The compound of claim 9, wherein p is 1.

11. The compound of claim 9, wherein R 7 R^7 is − C ( 0 ) O H -C(0)OH .

12. A compound which 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] [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] [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] [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] [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] or a pharmaceutically acceptable salt thereof.

13. A compound which 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] or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 of the chemical formula: [Image disponible dans le document PDF, Image available in the PDF document] 215. The compound of claim 1 of the chemical formula: [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt thereof.

16. The compound of claim 9 of the chemical formula: [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt thereof.

17. A compound which 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] [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] [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] [Image disponible dans le document PDF, Image available in the PDF document] 0 . . . . . . [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] [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] [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] 4 0 .

18. A pharmaceutical composition comprising the compound of any one of claims 1-17 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.